Radiation
NRG-GU005 NCT03367702
ForLocalized favorable intermediate-risk prostate, T1-T2b, GG1-2, PSA <20
88.6% vs 92.1%
SBRT not superior; adjusted HR 1.40 (0.91-2.13), P=.12
TL;DR3yr DFS 88.6% SBRT vs 92.1% MH-IMRT, superiority rejected (adjusted HR 1.40, 0.91-2.13); bowel and GU toxicity favored SBRT.
The number that should move practice is biochemical failure: 7.8% vs 4.2% at 3yr (adj HR 1.82, 1.01-3.27), while local failure was flat at 1.2% vs 1.0%. The SBRT prescription was deliberately modest, 36.25 Gy/5 fx with dose uniformity prioritized and urethral max held to 38.78 Gy, so this reads as a dose and margin question, not a verdict on 5 fractions.
In favorable intermediate-risk localized prostate cancer choosing between 5-fraction SBRT and moderate hypofractionation, this supports the toxicity and convenience case for SBRT while flagging a 3-year PSA-failure gap; it does not speak to unfavorable intermediate or high-risk disease, or to dose-escalated SBRT regimens.
Biochemical failure, not DFS, carries the read: 7.8% vs 4.2% at 3yr (adj HR 1.82, 1.01-3.27) with local failure flat at 1.2% vs 1.0%. The prescription was deliberately uniform, 36.25 Gy/5 fx with urethral max 38.78 Gy and no focal boost, so this argues about dose and margin rather than about 5 fractions.
Also covered Jul 8
13 details 5 trials watching
Phase 3, international, open-label, 1:1 randomized superiority trial across 136 centers, accruing November 2017 to June 2022 with last follow-up October 2024. N=698 randomized (353 SBRT, 345 MH-IMRT), median follow-up 3.2 years. Two coprimary end points, patient-reported QoL and DFS, each tested at 2-sided alpha .05 with no study-wise correction, so both had to be positive for a positive trial.
Localized cT1-T2b, either Gleason 3+4 (GG2) with PSA <20 ng/mL or Gleason 3+3 (GG1) with PSA 10-20 ng/mL. Median age 68 (range 42-84); 80% White, 13% Black, 3% Asian; 81.7% T1c and 88.1% Zubrod 0. Stratified by risk group and by rectal manipulation, of whom 55.6% used spacer alone and 40.3% no device.
SBRT 36.25 Gy in 5 fractions (7.25 Gy per fraction), delivered as prescribed in 96.6%; MH-IMRT 70 Gy/28 fx in 70.6% or 60 Gy/20 fx in 26.6%. Rectal constraints were max 38 Gy to 0.03 mL and 18 Gy to 50%; bladder 39 Gy and 15 Gy. Where PTV max exceeded 38.78 Gy the urethra had to be contoured and capped at 38.78 Gy, a deliberately uniform, non-escalated prescription. Protocol-compliant or acceptable variation in 97.7% and 97.2% of arms.
Coprimary: MCID frequency in EPIC-26 urinary irritative/obstructive and bowel domains at 24 months, and DFS at 3 years (powered for HR 0.62). Secondary: the other EPIC-26 domains at 12 and 24 months, overall survival, biochemical DFS, regional and distant failure. EPIC-26 adherence was 82% at 1yr and 84% at 2yr.
Urinary irritative/obstructive MCID was flat (35.4% vs 33.7%, P=.68); bowel MCID favored SBRT (34.9% vs 43.8%, P=.03). DFS superiority was rejected at a 91-event interim (HR 1.38, 0.91-2.09), with 3yr rates 88.6% vs 92.1% and no adjusted difference (HR 1.40, P=.12).
| Endpoint | SBRT | MH-IMRT | Effect |
|---|---|---|---|
| Biochemical failure | 7.8% | 4.2% | adj HR 1.82 (1.01-3.27), P=.046 |
| Local failure | 1.2% | 1.0% | P=.97 |
| Overall survival | n/a | n/a | P=.65; adj HR 1.15 (0.55-2.41), P=.70 |
Grade 3+4 GU adverse events were lower with SBRT (0.6% vs 2.5%, P=.04), as were any-grade rectal hemorrhage (10.5% vs 17.3%, P=.01) and fatigue (39.2% vs 50.8%, P=.002). Longitudinal bowel scores favored SBRT (LS mean 2.68 [1.02-4.34], P=.002) and urinary incontinence scores likewise (LS mean 2.91 [0.85-4.97], P=.006).
PACE-B and HYPO-RT-PC established that 5-fraction prostate SBRT is tolerable and non-inferior on biochemical control; this trial asked the harder superiority question and lost it, and adds a rectal-manipulation stratification neither predecessor used, which balanced spacer use across arms rather than leaving it a center-level confounder.
The biochemical failure signal, the one result that argues against SBRT, sits on 3-year rates with a CI whose lower bound touches unity (adj HR 1.82, 1.01-3.27) and cannot be separated from the higher benign PSA bounce rate after SBRT, which the trial was not designed to distinguish from true failure. Local, regional and distant failure events were too few to analyze (8 vs 7, 4 vs 2, 4 vs 4), so the mechanism behind the PSA gap is unobserved.
The authors attribute the PSA-control gap to a possible lower biologically effective dose and smaller SBRT margins, the same two choices that plausibly produced the bowel benefit. If that trade is real, it is tunable: focal boost to the dominant intraprostatic lesion was explicitly excluded here and is where the next version of this question belongs.
CONSORT flow
Randomised phase 3, prespecified coprimary endpoints, ITT: the DFS superiority hypothesis was rejected and biochemical failure ran higher with SBRT, contesting the assumption 5 fractions cost nothing.
- Whether benign PSA bounce explains the biochemical failure gap
- Does focal boost to the dominant intraprostatic lesion close it recruiting Image-guided Focal Dose Escalation- Primary pc Treated With Primary External Beam Hypofract.Stereotactic rt Phase NAn=374 · primary completion 2025-08 · randomised focal dose escalation, SBRT vs IMRT/IGRTn=186 · primary completion 2032-08 · randomised DIL boost vs whole-gland boost in SBRTrecruiting Phase III Adaptive Adaptive Stereostactic Body Radiotherapy (SBRT) With Dose Escalation for High-Risk Prostate Cancer Phase NAn=390 · primary completion 2033-04 · DIL dose-escalated SBRT vs mod hypofx, high risk
- Late GI/GU toxicity and QoL beyond 2 years n=68 · primary completion 2025-10 · 5y cumulative GI/GU/sexual toxicity, MR-linac SBRTactive Germline DNA-Based Radiosensitivity Biomarker Influence on Toxicity Following Prostate Radiotherapy, GARUDA Trial Phase NAn=208 · primary completion 2027-12 · long-term physician-scored GU toxicity after SBRT
📚 Sources · 📄 1 paper
Abstract
Moderately hypofractionated partial breast reirradiation
ForIsolated IBTR after BCS + WBI, T1-2, unifocal, ≥48mo interval, age ≥50
TL;DR40Gy/15fx PBI re-RT after second lumpectomy: 3yr LR-FS, DR-FS and OS all 86%, no grade 3+ late events (N=11).
The transferable read is the fractionation, not the outcome: 40 Gy / 2.67 Gy daily PBI met every OAR objective with heart Dmean 1.44 Gy and ipsilateral lung V16Gy 7.74%, so a once-daily 15-fraction re-RT can be planned inside standard constraints. That removes the BID-visit burden that limits RTOG 1014 uptake, though no plan sum with the first WBI course was possible.
For the woman with an isolated T1-2 IBTR ≥4 years after BCS plus WBI who wants to keep her breast, this supports offering once-daily hypofractionated PBI re-RT rather than only BID schedules; it says nothing about multifocal, T4, or short-interval recurrence, where mastectomy remains the comparator.
The transferable detail is the plan, not the outcome: 40 Gy / 2.67 Gy daily PBI with direct-planning IMRT achieved heart Dmean 1.44 Gy and ipsilateral lung V16Gy 7.74%, well inside objectives, in previously whole-breast-irradiated tissue. That makes a once-daily 15-fraction re-RT schedule planable without the BID burden, though no plan sum with the first course was possible.
Repeat lumpectomy rather than salvage mastectomy held in 9 of 11 at 3 years, with recurrences at 11 and 15 months. Selection was tight: unifocal T1-2 on triple imaging, ≥48 months from primary treatment. SLNB was attempted in 8 and failed to identify a node in 2, which is worth flagging when planning axillary staging at second conservation.
16 details 2 trials watching
Retrospective review of a departmental re-RT database, single institution (Porto), treated 2017-2021. Thirteen identified, two excluded (different fractionation; T4 treated with WBI), leaving N = 11. Median follow-up 41 months (27-62), Kaplan-Meier estimates with two-sided log-rank comparisons.
Isolated ipsilateral breast tumor recurrence after BCS plus whole-breast irradiation, all T1-2, clinically node negative, no metastatic disease before second BCS. Inclusion required age ≥ 50, unifocal disease on ultrasound, mammography and MRI, size < 2-3 cm, and an interval of ≥ 48 months from primary treatment. Median age at recurrence 63 (41-81), ECOG 0-1 in all.
Initial course was whole-breast irradiation at 2 Gy/fraction in all 11, with a 10 Gy / 5 fraction boost in 2. Re-RT was partial breast, 40 Gy at 2.67 Gy daily, direct-planning IMRT, supine, without DIBH. Median interval between courses 107 months (27-239).
No registered primary. LR-FS, DR-FS and OS by Kaplan-Meier from the day of re-RT completion, with adverse events graded by CTCAE v5.0 (acute < 90 days, late > 90 days) and cosmesis by the Harris scale.
At 3 years, 9/11 free from local recurrence, 10/11 from distant recurrence, 9/11 alive, each 86%. Two local recurrences, at 11 and 15 months. TAM-stratified LR-FS was 100% low risk, 80% intermediate, 100% in the single high-risk patient; the OS difference between low and intermediate risk was not significant (p = 0.75).
| Parameter | Objective | Achieved mean (range) |
|---|---|---|
| PTV V95% | > 98% | 98.36 (98-99.45) |
| PTV V107% | < 2% | 0 (0) |
| Ipsi lung V16Gy | < 15% | 7.74 (1.41-14.98) |
| Ipsi lung V8Gy | < 35% | 13.22 (2.78-34.58) |
| Heart Dmean | < 3.2 Gy | 1.44 (0.48-3.09) |
| Heart V16Gy | < 5% | 1.53 (0-4.89) |
| Contra lung V4Gy | < 10% | 1.09 (0-8.74) |
No grade 3 or higher late reactions. Acute events were skin-limited, most commonly grade 1-2 dermatitis (8 grade 1 erythema, 2 grade 1 pigmentation, 1 pruritus). At 1 year, grade 1 fibrosis in 9 and grade 1-2 oedema in 5, breast pain grade 1 in 2. No cardiopulmonary events, no rib fractures. Cosmesis good in 6, fair in 2, poor in 3.
RTOG 1014 (45 Gy / 1.5 Gy BID, 3D-CRT, n = 66) reported 7% late grade 3 and no grade 4-5 at 5.5 years; Janssen 2018 (n = 83, 45 Gy / 1.8 Gy daily) reported a 15% LR rate at 35 months. Brachytherapy series sit at 94-100% third-IBTR-free survival with 8-11% grade 3-4 complications. This cohort's toxicity is at or below all of them, on a fraction of the patient numbers and follow-up.
The first course's dose distribution was unavailable, so no composite plan sum could be produced and cumulative OAR dose stays uncharacterized, which is the number that actually gates re-RT safety. Cosmesis was scored unblinded by the treating radiation oncologist, and the reported confidence intervals (46-62%, 52-65%, 47-63%) do not contain their own 86% point estimates as printed.
The contribution is schedule feasibility, not efficacy: a once-daily 15-fraction re-RT plan met every published constraint with wide margin, which is what a department needs before abandoning BID. Whether 40 Gy in 15 fractions matches 45 Gy BID for in-breast control remains untested; two events in 11 patients cannot answer it.
Retrospective single-arm series, N=11, 2 events, median f/u 41 months. No comparator vs mastectomy or vs the established BID re-RT schedules.
- Does 40 Gy/15fx match 45 Gy BID for in-breast control? n=30 · primary completion 2025-08 · same 40Gy/15fx re-RT schedule, skin toxicityn=171 · primary completion 2027-06 · rPBI 5fx after prior WBI, in-breast recurrence
- Late fibrosis beyond 4 years in the overlap volume
- Cumulative OAR dose without a first-course plan sum
📚 Sources · 📄 1 paper
Cardiac Risk After Heart-Sparing Breast Radiotherapy
ForLeft-sided breast cancer, 3D-CRT or IMRT, 2008-2018
TL;DRMax LAD ≥12 Gy EQD2: sHR 1.81 (1.04-3.16) for cardiac events; mean heart dose ≥2 Gy null (P=.99), 2223 left-sided pts.
The number that reaches the planning system is the physical-dose translation: 12 Gy EQD2 max LAD is about 10.5 Gy at 42.5 Gy/16 fx and 7 Gy at 26 Gy/5 fx. Discrimination was weak for both metrics (C index 0.58 vs 0.53), so this argues for adding an LAD max objective and motion management, not for retiring mean heart dose.
In left-sided breast cancer planned with 3D-CRT or IMRT, this supports carrying an LAD max objective alongside the usual heart constraint; it does not extend to right-sided disease, which sat outside the primary analysis.
The actionable number is the physical-dose translation: 12 Gy EQD2 max LAD is about 10.5 Gy at 42.5 Gy/16 fx and 7 Gy at 26 Gy/5 fx, both checkable at the workstation. Discrimination was weak for both metrics (C index 0.58 vs 0.53), so this adds an LAD max objective and breath-hold rather than retiring the heart constraint.
9 details 4 trials watching
Cross-sectional cohort of 4908 breast cancer pts treated with 3D-CRT or IMRT from 2008 to 2018 at one Canadian tertiary center, 2223 left-sided in the primary analysis. Median follow-up 10.8 years (IQR 8.4-13.1). Dosimetry auto-segmented from planning CT, converted to EQD2; competing-risks (Fine and Gray) regression adjusted for cardiovascular risk factors.
Breast cancer treated with 3-dimensional conformal or intensity-modulated RT, 2008 to 2018, with the primary analysis restricted to left-sided disease. Systemic cardiotoxic exposure (anthracycline, trastuzumab) is not reported in source.
3D-CRT or IMRT across the heart-sparing era; LAD and heart automatically segmented and dose converted to EQD2. The threshold is a max point dose to the LAD, not a mean, and the reference schedules are moderate hypofractionation (42.5 Gy in 16 fx) and ultrahypofractionation (26 Gy in 5 fx).
Adverse cardiac events: MI, or admission / ED visit for unstable angina, arrhythmia, heart failure, pericarditis, myocarditis. Coronary angiography and revascularization captured separately as CAD. Discrimination compared by ROC C index, adjusted association by competing-risks regression.
10-year cumulative incidence of cardiac event or CAD was 5.0% (95% CI 4.1-6.0). Metric-by-metric comparison is in the table above.
| Metric | Max LAD dose | Mean heart dose |
|---|---|---|
| Discrimination (C index) | 0.58 (95% CI 0.52-0.64) | 0.53 (95% CI 0.47-0.60) |
| Adjusted association | ≥12 Gy EQD2: sHR 1.81 (1.04-3.16), P=.04 | ≥2 Gy: not associated, P=.99 |
| Schedule | Physical max LAD dose |
|---|---|
| 42.5 Gy / 16 fx | approx 10.5 Gy |
| 26 Gy / 5 fx | approx 7 Gy |
Current whole-heart constraints descend from population dose-response work on cohorts irradiated when incidental cardiac exposure was far higher (Darby, NEJM 2013), the era in which mean heart dose had usable spread. This is the modern counterpart of those series, and the reversal it reports is what you would expect if heart-sparing planning compressed mean heart dose below its discriminating range. The referenced schedules, 42.5 Gy in 16 fractions and 26 Gy in 5 fractions (FAST-Forward), are current practice, so the dosimetric translation transfers.
The mean heart dose null is hard to separate from restricted range: a 2 Gy dichotomy inside a heart-sparing cohort may not span enough exposure for a gradient to show. The endpoint counts coronary angiography and revascularization, which track ascertainment and access as well as biology. Systemic cardiotoxic exposure is not reported in source, leaving an obvious confounder unaddressed.
The asymmetry that matters is cost: an LAD max objective plus breath-hold usually costs optimization time, not target coverage, so a weak association is enough to justify it, while it would not justify trading away chest wall or nodal coverage. The measurement problem cuts the other way, since a max point dose to a small mobile auto-segmented vessel is among the least reproducible quantities to write into a protocol. Motion management carries the least methodological baggage of the two recommendations: it lowers LAD dose and heart dose together.
Cross-sectional single-center cohort with a cut point derived in the same data; C index 0.58 barely above chance and its interval overlaps mean heart dose's.
- External validation of the 12 Gy EQD2 LAD cut point
- Whether LAD-directed planning prospectively lowers cardiac events n=400 · primary completion 2026-04 · DIBH vs free-breathing cardiac dose, paired plansn=750 · primary completion 2027-12 · IMPT vs IMRT/VMAT, cardiac toxicity endpoint
- Generalizability to regional nodal irradiation and 5-fraction schedules active Postmastecomy Internal Mammary Nodal Irradiation for High-risk Breast Cancer Patients Phase 3n=2400 · primary completion 2025-11 · phase 3 IMN irradiation vs none, n=2400recruiting Ultra-Hypofractionated vs. Hypofractionated Radiation for Node-Positive Breast Cancer Phase 2n=220 · primary completion 2034-04 · randomised ultra-hypofx vs hypofx with nodal RT
📚 Sources · 📄 1 paper
Abstract
Organs at Risk Radiation Dose Constraints: 2025 Update
TL;DRSFRO 2025 OAR dose-constraint update: normofractionated, moderate hypofractionated and ablative tables across skull base, H&N, lung, breast, oesophagus, liver.
START BFAST-FORWARDRTCMIENDOMETRE
The practical shift is coverage of ablative regimens per fraction number (1, 3, 4, 5, 8) alongside normofractionation, plus cardiac substructures (LAD, left ventricle) and a proposed dorsal vagal complex OAR. Numbers are tiered optimal vs mandatory, so a plan that exceeds an optimal value is a documented conversation, not a violation.
Practical shift is the per-fraction-number ablative columns (1, 3, 4, 5, 8) sitting alongside normofractionation in one grid, plus cardiac substructures (LAD, left ventricle) as constrained organs. The optimal versus mandatory tiering is what changes planning behaviour: it names which values are negotiable against target coverage.
12 details
SFRO consensus update, part of the RecoRad 4th edition, covering adult external beam radiotherapy and brachytherapy practice. Constraints were compiled from international consensus guidelines and clinical trial data, then validated by national reference experts rather than derived from a new dataset.
Tables are indexed by tumour site and by fractionation: normofractionation, moderate hypofractionation, accelerated hyperfractionation (lung), and ablative regimens split by fraction number (1, 3, 4, 5, 8). Dmax is approximated by D2 % in normofractionation and D0.035 cm3 in stereotactic plans; several hypofractionated entries are given as EQD2.
No clinical endpoint. The deliverable is a set of dose-volume objectives intended for direct implementation into treatment planning systems as standardized clinical objectives.
Constraints are tiered as optimal versus mandatory, with ALARA used where no numeric threshold is offered (parotid in the brain table, lacrymal gland under moderate hypofractionation). The authors require that pts be informed of the risk when a constraint is exceeded.
Breast constraints are anchored to the schedules of START B (40 Gy in 15) and FAST-FORWARD (26 Gy in 5); liver constraints are built on the ASTRO clinical practice guideline across 3, 5 and ≥ 20 fractions. This is a national harmonization layer over those sources, not a competing evidence synthesis.
The authors state most constraints still rest on 3D conformal-era data, which sits awkwardly with IMRT's larger low-dose bath and with ablative dose gradients. Biological modifiers of risk (individual radiosensitivity, genomic profile, concurrent immunotherapy) are not accounted for, and dose to immune organs at risk is named as unresolved.
The value here is harmonization, not novelty: the stated problem is the multiplicity of circulating constraint sets and the absence of a single reference. The optimal/mandatory tiering is the part that changes daily behaviour, because it tells a planner which values are negotiable against target coverage and which are not.
- Validity of 3D conformal-derived constraints under IMRT and SBRT
- Dose thresholds for immune organs at risk with concurrent immunotherapy
- Dorsal vagal complex as an OAR for radiation-induced nausea
📚 Sources · 📄 1 paper
Dose-Escalated RT for Muscle-Invasive Bladder Cancer
ForMIBC (T2-T3, N0-N1) post-TURBT, curative-intent trimodality or RT alone
TL;DR2yr invasive local recurrence 5.5% vs 27.5% with SIB dose escalation, adjusted SHR 0.20 (0.05-0.89), p=0.035; no OS or MFS difference.
The boost was a simultaneous integrated boost to the primary lesion, 60Gy/20fx or 70Gy/32fx, deliverable on daily CBCT without an elective-volume change, and G2+ GU toxicity did not rise (17.9% vs 22.1%). Half the cohort got no chemotherapy, so this speaks directly to the chemo-ineligible pt where RT intensity is the only lever left.
In an MIBC pt going to bladder preservation who cannot take concurrent chemotherapy, this supports discussing a boost to the primary lesion as the available intensification; it says nothing about pts with multifocal disease, who were entirely absent from the escalated cohort.
The boost was simultaneous integrated, 60Gy/20fx or 70Gy/32fx to the primary lesion, elective volume unchanged, on daily CBCT with MRI/PET fusion for delineation, and G2+ GU toxicity did not rise (17.9% vs 22.1%). That combination makes the escalation technically transferable today, and moves the dose decision for the chemo-ineligible pt.
Half the cohort (51%) received no concurrent chemotherapy, mostly for performance status, and absence of chemo carried worse OS (HR 2.83 [1.42, 5.63], p<0.01). Chemo showed no association with invasive local recurrence on univariable analysis, so this frames RT dose, not the radiosensitiser, as the intensification available when a pt cannot take cisplatin.
Salvage cystectomy was performed in only 2 standard-dose and 1 escalated pt, because most pts with invasive relapse were judged unfit for surgery at recurrence. Bladder preservation rates here therefore reflect operability as much as disease control, which matters when counselling a marginal-fitness pt that salvage is a real fallback.
10 details
Multicentre retrospective cohort across three centres, March 2015 to May 2025, chosen to capture the daily-CBCT image-guidance era. N=107 (39 dose-escalated, 68 standard), median follow-up 23 months (range 3 to 104).
MIBC after TURBT treated with curative intent, with or without concurrent chemotherapy; node-positive pts eligible if non-metastatic. Metastatic or palliative-intent pts excluded. T2 86%, ECOG 2-3 in half the cohort, hypofractionation in 91%.
Standard cohort received 55Gy/20fx or 64Gy/32fx to the whole bladder. Escalated cohort received a simultaneous integrated boost to the primary lesion, up to 60Gy/20fx or 70Gy/32fx. CT simulation with empty bladder; MRI and FDG PET fused for target delineation in selected pts; daily CBCT in all but one pt.
2-year local control for invasive and non-invasive disease, metastasis-free survival, overall survival, bladder preservation, and toxicity. Local control analysed by Fine-Gray competing-risk models, univariable then multivariable adjusted for T stage.
Dose escalation was associated with lower invasive local recurrence; non-invasive recurrence, metastasis, and survival did not differ. Numbers are in the outcomes table above.
| Endpoint | Dose escalation | Standard dose | Effect |
|---|---|---|---|
| 2yr invasive local recurrence (CI) | 5.5% | 27.5% | SHR 0.20 (0.05, 0.89), p=0.035 (adj T stage) |
| 2yr non-invasive recurrence (CI) | 6.7% | 9.9% | SHR 0.88 (0.23-3.33), p=0.98 |
| 2yr metastasis (CI) | 21.1% | 32.3% | p=0.79 univariable |
| 2yr overall survival | 71.1% | 64.4% | p=0.5 |
| G2+ GU toxicity | 17.9% (7) | 22.1% (15) | p=0.8 |
| G2+ GI toxicity | 5.1% (2) | 7.4% (5) | p=0.9 |
No difference in G2+ GU (17.9% vs 22.1%, p=0.8) or G2+ GI toxicity (5.1% vs 7.4%, p=0.9). Grade 3 toxicity in 2 pts (2.9%), both in the standard-dose arm. No pt required early cessation of treatment for toxicity.
The direction matches BC2001 and BCON, which established chemoradiation and hypoxic modification as ways to improve local control within bladder preservation but never randomised the RT dose itself. The open question these left, whether escalating the primary lesion adds control on top of a modern image-guided plan, is what this cohort probes, at retrospective strength rather than randomised.
The escalated cohort was systematically more favourable: 100% single-focus disease vs 65%, hydronephrosis in 10% vs 28%, T3 in 8% vs 16%. Only T stage entered the multivariable model, and with 18 invasive events total the model could not have supported more. Recurrence ascertainment differed by arm: 3 standard-dose recurrences were presumed invasive on CT and MDT consensus while every escalated-cohort recurrence was confirmed cystoscopically.
The local-control signal is real in this dataset but its magnitude is not transferable: an SHR of 0.20 resting on 2 events versus 16, in cohorts that differ on tumour focality, is an effect size that would be expected to shrink under randomisation. What survives the caveats is a tolerability finding, that an integrated boost to the primary did not raise G2+ GU or GI toxicity.
Retrospective, N=107, 18 total invasive events driving the SHR; boost cohort had single-focus disease and less hydronephrosis, with only T stage adjusted.
- Does the local-control benefit survive randomisation and balanced tumour focality?
- Can multifocal MIBC be boosted at all, or only unifocal disease?
- Late GU toxicity beyond 23 months with an integrated boost
📚 Sources · 📄 1 paper
Proactive Immune Cell Sparing SBRT (NCT04273893) NCT04273893
PREPRINTnot peer-reviewed
ForEarly-stage NSCLC (cT1-T2 N0) medically inoperable, treated with 5-fraction SBRT
13.4% (5.3%)
95% CI 2.8 to 24.0, p = 0.014
TL;DRALC reduction 13.4% (5.3%) less with immune-sparing planning across all timepoints (95% CI 2.8-24.0, p=0.01) in early-stage lung SBRT.
The dosimetric recipe is the transferable part: adding heart, great vessels, thoracic spine and lymph-node-stations as OARs down to 40 cGy/fx cut LN-station V5 by 58% and spine V5 by 87% without loosening RTOG 0813/0915 constraints or lung sparing (total lung-PTV V10 unchanged, 0%). The benefit concentrated in central tumors and peripheral PTV >20cc, which is where a planner would spend the effort.
In a medically inoperable early-stage NSCLC patient with a central or larger peripheral (PTV >20cc) tumor being planned for 5-fraction SBRT, this supports adding immune-rich structures as secondary optimization objectives; it does not inform peripheral PTV <20cc cases, where no ALC difference was seen.
The transferable part is the planning recipe: adding heart, great vessels, thoracic spine and lymph-node-stations as OARs down to 40 cGy/fx cut LN-station V5 by 58% and spine V5 by 87% with RTOG 0813/0915 constraints intact and total lung-PTV V10 unchanged (0%). The gain concentrated in central tumors and peripheral PTV >20cc, which is where the planning effort is worth spending.
12 details 3 trials watching
Phase II randomized trial, 1:1, unmasked, single institution, accrual February 2020 to April 2023, database lock June 2024. 55 randomized, 4 withdrew or were ineligible, 51 analyzed (25 optimized, 26 standard). Randomization used permuted blocks of 2 and 4, stratified by tumor location.
Early-stage NSCLC, pathologically or imaging-confirmed, unable or unwilling to undergo surgery; ECOG 0-2; pre-RT ALC > 0.5 x 10^9 cells/L. Prior-recurrence pts eligible. Excluded prior thoracic RT within 2 years and systemic therapy within the prior year or planned within 6 months post-SBRT. Median age 74 both arms; cT1 in 100% optimized vs 88.5% standard.
SBRT 45-60 Gy in 5 fractions (BED 85.5-132 Gy) by IMRT or VMAT, 6X-FFF, 4DCT-based ITV, PTV margin 5mm radial and 8mm superior-inferior, daily CBCT. Both arms met RTOG 0813/0915 constraints; the optimized arm added heart, great vessels, thoracic spine and lymph-node-stations (Chapet atlas) contoured to a 40 cGy per fraction threshold as competing OARs.
Primary: in vivo lymphocyte depletion (ALC change) at end-of-treatment, 4 weeks and 6 months, plus safety/toxicity comparison. OS and EFS were unplanned subgroup analyses, descriptive only.
Two grade 3 events (lung infection) in the optimized arm vs four in the standard arm (dyspnea, hypoxia, lung infection); all recovered. Grade 2 events in 6 (24%) optimized vs 9 (35%) standard. No grade 2+ pneumonitis and no grade 4+ toxicity in either arm.
The premise rests on the observed link between post-RT lymphopenia and worse outcomes rather than on any prior trial that randomized immune-organ sparing, so there is no comparator trial to place this against. The authors cite lung SBRT plus immunotherapy improving 4-year EFS from 53% to 77% as the alternative route to the same immune endpoint, which is an add-a-drug strategy rather than a planning one.
Chance imbalance runs against the optimized arm on some axes (fewer treatment-naive: 64.0% vs 88.5%) and toward it on others (more central tumors: 36.0% vs 23.1%), and with 51 pts neither is correctable by adjustment. The LN V5 35.4cc OS split is a post-hoc median dichotomy on the same small cohort, so it cannot be read as an independent confirmation of the ALC result. Only 15 central tumors carried the largest effect estimate.
The trial establishes that the dose can be moved, and that ALC follows it, in a setting where the target dose was held fixed. What it does not establish is that the lymphocyte curve translates into disease control, and the OS and EFS signals here are explicitly underpowered and unplanned.
| Organ | Integral dose | V5 | V10 |
|---|---|---|---|
| Aorta | 35% | 48% | 69% |
| Heart | 21% | 43% | 68% |
| Vena cava | 37% | 58% | 75% |
| Thoracic spine | 57% | 87% | 92% |
| Lymph-node-stations | 37% | 58% | 68% |
| Total lung - PTV | 5% | 8% | 0% |
| Timepoint | Optimized | Standard | Between-group diff |
|---|---|---|---|
| Immediately post | -16% | -31% | 15.1% (95% CI 3.7-26.5), p=0.01 |
| 4 weeks | -22% | -34% | 12.3% (95% CI 0.2-24.5), p=0.05 |
| 6 months | -16% | -26% | 10.4% (95% CI -4.7-25.5), p=0.17 |
CONSORT flow
Preprint, single-institution phase II, N=51, endpoint is a lymphocyte surrogate not a clinical outcome; survival analyses unplanned and underpowered.
- Does reduced RIIS translate into disease control or survival benefit n=212 · primary completion 2026-11 · lymphocyte-sparing vs conventional RT, randomised
- Whether immune-organ sparing adds anything when SBRT is combined with immunotherapy active Testing the Addition of the Drug Atezolizumab to the Usual Radiation Treatment for Patients With Early Non-small Cell Lung Cancer Phase 3n=415 · primary completion 2024-08 · phase 3 SBRT +/- atezolizumab, stage I-IIA NSCLC
- Which immune-rich organ dominates RIIS when multiple OARs compete active Thymus Dosimetric and Morphologic Predictors of Radiation-Induced Lymphopenia in Stage III NSCLCn=450 · primary completion 2027-12 · thymus dose vs lymphopenia in thoracic RT
📚 Sources · 📄 1 paper
Abstract
IROCK Contouring Guidelines (RCC SABR)
ForLocalized RCC considered for SABR, including IVC thrombus, post-RN or post-RFA recurrence
TL;DRFirst international consensus contouring atlas for RCC SABR: median DSC 0.85 across 16 experts, 4 scenario-specific iGTV statements.
The two hardest scenarios are named and quantified: Case 1 (IVC thrombus) and Case 4 (post-RFA cavity) carried the worst agreement (DSC 0.85 and 0.75, HD 64.60 and 9.00 mm), driven by how far superiorly thrombus was covered and how much cavity was included. Both statements push toward larger volumes, so OAR priority and a 5 mm PTV are the gates on whether that transfers.
In a patient with post-RFA residual RCC or an IVC tumor thrombus being planned for SABR, this defines the target as the whole ablation cavity or the full thrombus rather than the visible nodule alone; it does not address dose selection or whether SABR beats nephrectomy.
Case 1 (IVC thrombus) and Case 4 (post-RFA cavity) carried the worst agreement, DSC 0.85 and 0.75 with HD 64.60 and 9.00 mm, and both consensus statements push toward the larger volume: full thrombus, entire ablation cavity. OAR constraints outrank coverage, and the 5 mm PTV assumes 4D-CT with daily CBCT.
12 details
International contouring consensus under IROCK, convened at ASTRO 2023. 16 radiation oncologists contoured 4** RCC SABR scenarios on CT alone via EduCase; a STAPLE algorithm generated the 95% consensus contour, refined across 2 online meetings in May and June 2024. Statements were revised to uniform (100%) agreement**.
Panelists, not patients: inclusion required ≥10 prior RCC SABR cases, with 14 of 16 having treated ≥10 in the preceding 12 months. Cases were a >10 cm RCC with IVC tumor thrombus, a central tumor abutting the hilum, a local recurrence post-nephrectomy, and a post-RFA cavity recurrence.
Target is the iGTV (GTV incorporating internal motion); no participant added a microscopic-spread margin, so no separate ITV is recommended. The most common PTV expansion was a uniform 5 mm, predicated on supine vacuum-cushion setup, 4D-CT sim, IV contrast and daily CBCT. Dose objectives and OAR constraints for 1, 3, or 5 fractions are tabulated from FASTRACK-II and AQuOS-II.
Overall median DSC 0.85 (range 0.40-0.95), median MDA 2.17 mm (0.71-10.82), median HD 9.00 mm (4.00-89.31), with DSC above 0.70 in every case. Two-way ANOVA showed all three metrics differed by case (P < .05); only MDA differed by participant (P = .03).
| Case | DSC | MDA (mm) | HD (mm) |
|---|---|---|---|
| 1: >10 cm RCC + IVC thrombus | 0.85, 0.79-0.85 | 6.69, 5.88-8.79 | 64.60, 64.44-86.40 |
| 2: central tumor at hilum | 0.90, 0.84-0.93 | 1.55, 1.00-2.09 | 7.92, 5.35-9.98 |
| 3: local recurrence post-RN | 0.91, 0.88-0.93 | 1.42, 1.18-1.89 | 6.18, 6.00-7.12 |
| 4: post-RFA cavity recurrence | 0.75, 0.60-0.79 | 2.50, 2.12-2.99 | 9.00, 9.00-12.39 |
IROCK previously supplied the outcome evidence (its pooled international analyses and the FASTRACK-II phase 2), and both showed heterogeneous dose, fractionation and planning conventions across contributing centers. This fills the delineation gap those datasets left open, and it borrows its constraint table from FASTRACK-II and the ongoing AQuOS-II rather than deriving new dose-response thresholds.
The renal substructure question is left deliberately unsettled: cortex is defined for use, hilum is explicitly not a dose-limiting OAR, on the reasoning that sparing an unvalidated structure would redistribute dose into parenchyma that does correlate with renal function. AQuOS-II is the trial that may resolve it.
CT-only images were supplied on purpose, for international accessibility, so measured variation likely overstates what an MRI-equipped center would see. Participants never recontoured post-consensus, so the guideline's own effect on agreement is unmeasured, and adoption assumes urology, radiology and nephrology collaboration plus advanced planning technology.
Expert consensus atlas, not an outcome study: 16-panel STAPLE contours with unanimous statements, no efficacy or toxicity endpoint, unvalidated prospectively.
- Does renal hilum sparing reduce artery stenosis or ureteric stricture?
- Does guideline adherence improve local control or reduce toxicity?
- Would MRI-based simulation narrow contour variability?
📚 Sources · 📄 1 paper
DBCG Skagen Trial 1
ForHigh-risk breast cancer with an indication for locoregional (nodal) radiotherapy
8.0% vs 9.4%
OR 0.84 (95% CI 0.62-1.14), P=.27; within +5pp NI margin
TL;DR3yr lymphedema 8.0% (40Gy/15fx) vs 9.4% (50Gy/25fx), OR 0.84 (0.62-1.14), noninferior; no recurrence or mortality differences at 8yr.
The lymphedema signal that kept 50Gy/25fx alive for nodal volumes does not appear: 8.0% vs 9.4% at 3yr, OR 0.84 (0.62-1.14). Locoregional recurrence HR 0.96 (0.62-1.51) says the shorter course does not trade control for convenience, so 15 fractions becomes defensible when the nodes are in the field.
In high-risk breast cancer needing nodal irradiation, this supports 40Gy/15fx over 50Gy/25fx on both arm morbidity and locoregional control; it does not speak to pts needing a boost regimen or reconstruction subgroups the abstract does not break out.
The morbidity objection to nodal hypofractionation does not hold: lymphedema 8.0% vs 9.4% at 3yr, OR 0.84 (0.62-1.14), with locoregional recurrence HR 0.96 (0.62-1.51). 40Gy/15fx to the full locoregional volume becomes the defensible default, with SIB and reconstruction still untested here.
Lymphedema is the shared surgical and radiation morbidity after axillary management, and fraction size is now off the list of drivers: 8.0% with 40Gy/15fx vs 9.4% with 50Gy/25fx at 3yr. Counseling about arm morbidity after nodal surgery plus RT should not attribute risk to the shorter course.
8 details 5 trials watching
Phase III noninferiority RCT, 17 centers, accrual 2015-2021. ITT cohort n=2,908 (1,444 at 50Gy, 1,464 at 40Gy). Accrual continued until 3-year lymphedema estimates were reported in 1,012 patients.
High-risk breast cancer with an indication for locoregional radiotherapy, the population where nodal coverage has kept 25 fractions standard in Denmark. Median age 57 (range 23-86).
Standard arm 50Gy/25fx, experimental arm 40Gy/15fx, both delivered to the locoregional volume rather than breast or chest wall alone. That target volume is the whole point: it is where the morbidity concern lives.
Primary: arm lymphedema at 3 years, with an assumed 10% incidence under 50Gy/25fx and noninferiority predefined as maximum 5 percentage points excess. Cancer endpoints (locoregional recurrence, distant recurrence, breast cancer mortality, all-cause mortality) were assessed within 8 years.
Lymphedema 8.0% vs 9.4%, OR 0.84 (0.62-1.14), P=.27, comfortably inside the margin. Cancer-outcome HRs are tabulated above and show no difference by random assignment.
| Endpoint | HR | 95% CI |
|---|---|---|
| Locoregional recurrence | 0.96 | 0.62 to 1.51 |
| Distant recurrence | 1.10 | 0.89 to 1.37 |
| BC mortality | 1.25 | 0.93 to 1.66 |
| All-cause mortality | 1.08 | 0.85 to 1.36 |
The UK hypofractionation programme (START A/B, then FAST-Forward) established 40Gy/15fx and shorter for breast and chest wall, but node-positive patients receiving comprehensive regional coverage were a small fraction, which left the nodal question open. Skagen 1 tests exactly that gap prospectively with morbidity as the primary endpoint.
Median lymphedema follow-up of 4.1 years captures the 3-year endpoint but not the later plateau, and the abstract reports no brachial plexopathy, shoulder, cardiac, or pulmonary late toxicity. The BC mortality HR 1.25 (0.93-1.66) runs the wrong way with a CI that does not exclude harm; the trial was sized for lymphedema, not survival.
The trial removes the specific objection that blocked hypofractionated nodal RT rather than merely adding another positive fractionation result. It does not settle very-long-term arm and shoulder function, nor whether the same holds with a simultaneous integrated boost or in reconstructed chest walls.
CONSORT flow
Phase III, prespecified noninferiority margin met on the morbidity endpoint that blocked nodal hypofractionation, with 8yr recurrence and mortality HRs showing no difference.
- Does 40Gy/15fx hold with a simultaneous integrated boost? active Hypofractionation With Simultaneous Integrated Boost vs. Standard Fractionation in Early Breast Cancer Phase NAn=2324 · primary completion 2019-01 · phase 3 hypofx SIB vs standard fx, n=2324n=132 · primary completion 2026-03 · 40.05Gy/15fx + SIB, 4y fibrosis endpointrecruiting 5 fr Ultrahypofractionated WBI and SIB for Breast Cancer With Unfavorable Characteristics Phase NAn=458 · primary completion 2029-06 · randomised vs 40.05Gy/15fx + 48Gy SIB control arm
- Lymphedema and shoulder function beyond 5 years
- Safety in immediate breast reconstruction n=20 · primary completion 2025-12 · post-surgical complications after RT then immediate reconactive Hypofractionated Regional Nodal Irradiation Clinical Trial for Women With Breast Cancer Phase NAn=137 · primary completion 2026-04 · hypofx RNI cohort stratified by post-mastectomy recon
📚 Sources · 📄 1 paper
Abstract
PACE-B
ForLow-/intermediate-risk localised prostate cancer, definitive RT
64% vs 69% leak-free
diff +5.51% (95% CI -2.70 to +13.72), p=0.19
TL;DR5-yr PROMs: leak-free 64% (164/258) SBRT vs 69% (172/249) CRT, p=0.19; no domain differed significantly.
The transient 2-yr urinary leakage excess after SBRT converged by 5 yr, which is the number that settles the fractionation conversation: 36.25 Gy/5 fx carried no durable continence penalty against 78 Gy/39 fx or 62 Gy/20 fx. Note the irritative/obstructive domain was not collected, so the symptom cluster patients complain of most after SBRT is unmeasured here.
In low-/intermediate-risk localised prostate cancer choosing between five-fraction SBRT and conventional or moderately hypofractionated RT, these 5-yr PROMs support fractionation choice on convenience rather than late continence, sexual, or bowel risk; they do not extend to high-risk disease, nodal treatment, or randomised comparison with prostatectomy.
The 2-yr urinary leakage excess after 36.25 Gy/5 fx converged by 5 yr, removing the late-toxicity argument for holding a low-/intermediate-risk patient on 78 Gy/39 fx or 62 Gy/20 fx. Caveat for consent: the EPIC-26 irritative/obstructive domain was not collected, so the urgency and flow symptoms patients ask about are unmeasured here.
11 details 4 trials watching
Phase 3 international randomised trial, 1:1 central allocation by ICR-CTSU with permuted blocks, stratified by centre and NCCN risk group. Treatment allocation was open-label. Of 874 randomised, 844 formed the analysis population (SBRT=414, CRT=430), median follow-up 85.7 and 85.6 mo.
Men with low-/intermediate-risk localised prostate cancer. Baseline characteristics balanced; baseline PROM data pooled across arms given equivalent pretreatment function.
SBRT 36.25 Gy in five fractions versus CRT 78 Gy in 39 fractions or 62 Gy in 20 fractions. Image-guidance method was not analysed as a variable, and rectal spacer use is not reported in this analysis.
Primary comparison: SBRT vs CRT at 5 yr for each PROM endpoint, using EPIC-26 urinary incontinence, sexual and bowel domains plus the Vaizey faecal incontinence score at baseline, 1, 2 and 5 yr. Binary outcomes by chi-squared with Wilson 95% CIs; continuous by Mann-Whitney.
All predefined between-group differences were nonsignificant. Sexual domain median score fell from 48.7 (IQR 22.2-77.8) to 26.3 (IQR 16.7-57) for SBRT and 54.2 (IQR 27.8-75.0) to 24.3 (IQR 16.7-52.8) for CRT, p=0.89.
Moderate or big urinary leakage problems reached 6% (15/250) SBRT and 4% (9/244) CRT; bowel problems 5% in both arms. Solid stool incontinence never/rarely in 94% (232/248) SBRT and 90% (217/241) CRT; liquid stool 92% in both.
PACE-B previously showed SBRT non-inferior to conventional and moderately hypofractionated RT for efficacy but with higher cumulative GU adverse events; these PROMs argue that excess did not persist to 5 yr. Against TrueNTH's robotic prostatectomy benchmark at 1 yr (42% leak- and pad-free, 6% of baseline-potent men retaining intercourse-adequate erections), the RT curves sit far better, and PACE-A reported pad use of 4.6% after SBRT versus 46.9% after prostatectomy.
The EPIC-26 irritative/obstructive domain was not included, removing the symptom cluster most often attributed to SBRT, though the authors note no 5-yr difference was seen in prior reporting. There is no untreated control arm, so age-related decline is unseparated from treatment effect, and no analysis by image-guidance method.
The clinically useful claim is narrow and real: five fractions buys convenience without a late functional cost relative to 20 or 39 fractions. The cross-modality framing against surgery is the weaker half, comparing separate cohorts at different timepoints with a shared instrument rather than a randomised contrast.
CONSORT flow
Prespecified 5-yr PROM analysis of a phase 3 RCT; all between-group differences nonsignificant, supporting five-fraction SBRT already in guideline use. Attrition to ~60% limits precision.
- Irritative/obstructive symptom trajectory at 5 yr after prostate SBRT active Stereotactic Body Radiation Therapy or Intensity-Modulated Radiation Therapy in Treating Patients With Stage IIA-B Prostate Cancer Phase 3n=692 · primary completion 2027-12 · phase 3 SBRT vs IMRT with QoL questionnaire endpointrecruiting Is Adaptive SBRT for Prostate vs Image-guided Radiotherapy a True Evolution (ASPIRE) Phase 3n=320 · primary completion 2030-02 · adaptive vs image-guided SBRT, urinary outcomes
- Whether rectal spacer or image-guidance method alters 5-yr PROMs n=179 · primary completion 2027-04 · phase 3 CT- vs MRI-guided SBRT, questionnaire PROMsn=500 · primary completion 2027-12 · SpaceOAR Vue for late GI toxicity in SBRT pts, n=500
- 5-yr PROMs for the TrueNTH prostatectomy cohort
📚 Sources · 📄 1 paper
Abstract
ESTRO Prostate SBRT Consensus Recommendations
TL;DRDelphi: 36.25 Gy/5 fx standard, 100% vote against elective pelvic nodal RT with prostate SBRT outside trial.
PACE-BPACE-CHYPO-RT-PCNRG-GU005hypo-FLAMEMIRAGEPARTIQoL
Two operational lines move practice: elective pelvic nodal RT alongside prostate SBRT is rejected 100% (12 votes) outside a trial, and intra-fraction tracking is only carried by 71% (10 votes) once PTV margin drops below 5 mm, no consensus. Prior BPH surgery is permitted with a median 6-month wait (range 2-12).
In ISUP 2-3, cT1c-cT2c, PSA <20 ng/mL localised prostate cancer, this supports five-fraction SBRT as a standard option without elective pelvic nodal coverage or a rectal spacer; it does not extend to cT3b, ISUP 5, or pts needing nodal irradiation.
The actionable lines are operational: no elective pelvic nodal RT with prostate SBRT outside a trial (100%, 12 votes), no routine rectal spacer (85%, 11 votes), and intra-fraction tracking only at 71% (10 votes) once PTV margin falls under 5 mm. Standard is 36.25 Gy/5 fx to 95% PTV with 40 Gy to 95% CTV.
15 details 5 trials watching
ESTRO task force literature review, then two Delphi survey rounds with a purposively selected expert panel, refined at ESTRO 2025 in Vienna. Ten multiple-choice questions covered areas of controversy. Consensus was predefined at ≥75% agreement, strong consensus at ≥90%, thresholds borrowed from APCCC.
Panel: eleven radiation oncologists, three medical physicists, one RTT from nine European countries. Voting counts per question ran 12 to 14. Target patient population is localised prostate cancer, with ISUP 2-3, cT1c-cT2c, PSA <20 ng/mL carrying strong consensus for SBRT as standard treatment outside a trial.
Standard is 36.25 Gy in five fractions of 7.25 Gy to 95% of the PTV, with 40 Gy to 95% of the prostate CTV (PACE-B), or 42.7 Gy in seven fractions of 6.1 Gy (HYPO-RT-PC). Prostate is contoured on T2-weighted planning MRI registered to CT; seminal vesicles omitted in low risk, proximal 1 cm included for all in PACE, proximal 2 cm to 30 Gy/5 fx in Gleason 4+3 or NCCN high risk. Rectal, bladder, femoral head, bowel and optional urethra PRV / penile bulb / crura constraints are given for five-fraction schedules only.
ADT per existing international guidelines, independent of the radiation schedule (100%, 13 votes). Intermediate risk: short-term ADT with conventional fractionation improves overall and cancer-specific survival by 7%, with no added benefit beyond roughly four months. High risk: long-term ADT plus RT improves overall and disease-specific survival irrespective of dose escalation.
No efficacy endpoint. The output is a set of recommendations plus per-question panel agreement percentages, so every "result" here is opinion measured against opinion.
The dose recommendation tracks PACE-B rather than splitting the difference with HYPO-RT-PC, whose lower biologically effective dose was still non-inferior, which the authors read as evidence 40 Gy in five fractions may not be needed for everyone. The unresolved counterweight is NRG-GU005, presented in preliminary form at ASTRO 2025: 36.25 Gy in five fractions gave lower side effects but a slightly higher three-year biochemical relapse rate, cause not yet determined. On protons, PARTIQoL found no difference in outcomes or QoL versus IMRT, with pencil beam scanning in only 48% of cases.
High-risk practice is running ahead of its evidence: HYPO-RT-PC is the only phase III reporting oncologic outcomes in high-risk pts and they were 11% of participants, while PACE-C has published toxicity but not oncological outcomes. Urethral sparing is recommended on mechanistic and single-study grounds while a post hoc PACE-B analysis found no significant association between urinary substructure dose and late urinary toxicity, and the panel itself flags the PACE-B urethra V42 <50% constraint as possibly too permissive.
The document's real contribution is the negative recommendations: no elective pelvic nodal RT with prostate SBRT outside a trial (100%, 12 votes) and no routine rectal spacer (85%, 11 votes), both areas where practice has drifted ahead of randomised data. It does not settle prostate volume cut-off, prophylactic medication, or whether intra-fraction tracking is required below a 5 mm margin, all of which returned no consensus.
| Category | Recommend SBRT (% of votes) |
|---|---|
| ISUP 2 | 100% (13 votes) |
| ISUP 3 | 100% (13 votes) |
| ISUP 4 | 38% (5 votes) |
| ISUP 5 | 0% (0 votes) |
| cT1c-cT2a | 100% (13 votes) |
| cT2b-cT2c | 100% (13 votes) |
| cT3a | 38% (5 votes) |
| cT3b | 0% (0 votes) |
| cT4 | 0% (0 votes) |
| PSA <20 ng/mL | 100% (13 votes) |
| PSA 20-40 ng/mL | 8% (1 vote) |
| PSA >40 ng/mL | 0% (0 votes) |
| Question | Vote | Level |
|---|---|---|
| Elective pelvic nodal RT with prostate SBRT (Q6) | No 100% (12 votes) | Strong consensus against |
| Bladder/bowel prep protocol (Q8) | Yes 100% (14 votes) | Strong consensus |
| ADT per existing guidelines, fractionation-independent (Q7) | Yes 100% (13 votes) | Strong consensus |
| Rectal spacer (Q9) | No 85% (11 votes) | Consensus against |
| Max IPSS cut-off (Q3) | Yes 85% (11 votes) | Consensus; median 17, range 10-20 |
| Max prostate volume cut-off (Q2) | Yes 62% (8 votes) | No consensus; median 90 cc, range 70-150 |
| Prophylactic meds (α1-blockers etc, Q4) | No 46% (6 votes) | No consensus |
| SBRT after BPH surgery (Q5) | Selected pts with waiting period 100% (13 votes) | Strong consensus; median wait 6 mo, range 2-12 |
- Cause of higher 3y biochemical relapse with 36.25 Gy in NRG-GU005
- Whether focal GTV dose escalation improves outcome in high-risk SBRT recruiting Image-guided Focal Dose Escalation- Primary pc Treated With Primary External Beam Hypofract.Stereotactic rt Phase NAn=374 · primary completion 2025-08 · randomised focal dose escalation vs no boost, cN0n=54 · primary completion 2027-06 · SBRT + mpMRI focal boost, unfavourable/high-risk
- Whether online adaptive RT improves toxicity over non-adaptive SBRT recruiting Adaptive Radiation Therapy (ART) Stereotactic Ablative Body Radiotherapy (SABR) for Primary Localized Prostate Cancer Phase NAn=164 · primary completion 2026-08 · margin-less adaptive 2 fx vs standard 5 fx SABR QoLrecruiting Is Adaptive SBRT for Prostate vs Image-guided Radiotherapy a True Evolution (ASPIRE) Phase 3n=320 · primary completion 2030-02 · phase 3 adaptive vs image-guided SBRT, urinary EPrecruiting Image-Guidance and Online Adaptation With Stereotactic Body Radiation Therapy for the Treatment of Localized Prostate Cancer, MANTICORE Trial Phase NAn=186 · primary completion 2031-12 · online adaptation vs IGRT SBRT, toxicity endpoint
📚 Sources · 📄 1 paper
TROG 08.03 RAVES QOL Substudy
ForPost-RP prostate cancer with adverse pathology (margins, EPE, or SVI)
Severe urinary leakage 16% vs 2%
aRT vs no RT at 5 yr, p = 0.01
TL;DRSevere urinary leakage 16% vs 2% at 5yr with aRT vs no RT; timing of salvage RT unrelated to QOL.
The QOL benefit of a salvage approach is avoidance, not delay: 52% of the sRT arm never needed RT, and among men who did get RT, severe urinary leakage at 5 yr was the same whether early or late (16% vs 13%, p = 0.7), with no coefficient linking RP-to-RT interval to any domain. Dose was 64 Gy/32 fx fossa-only, no ADT, no nodes.
For a man with adverse pathology after RP and an undetectable PSA, this supports PSA surveillance with early salvage rather than adjuvant RT on functional grounds; it does not speak to men needing ADT, pelvic nodal RT, or Gleason 9 disease, who were sparse or excluded here.
Delay buys nothing functionally: among men who received RT, severe urinary leakage at 5 yr was 16% aRT vs 13% sRT (p = 0.7) and no RP-to-RT interval coefficient reached significance. The advantage of a salvage policy is that 52% of that arm never needed RT. Dose was 64 Gy/32 fx fossa-only, 3D-CRT era, no ADT or nodes.
For counselling after RP with adverse pathology, the functional cost quoted to a man should be conditional on recurring: irradiated men reported severe urinary leakage of 16% at 5 yr against 2% in those never irradiated, but that no-RT group is defined by not recurring, not by randomization. Continence counselling is unchanged by RT timing.
11 details
Protocol-planned secondary analysis of the TROG 08.03 RAVES phase 3 noninferiority RCT, 166 aRT vs 167 sRT. Median follow-up 6 yr (IQR 4 to 7.1) in both arms. Complete-case analysis, no imputation, chi-square per timepoint.
High-risk features after RP: positive margins, extraprostatic extension, or seminal vesicle invasion. 82% Gleason 7, 3% Gleason 8, 12% Gleason 9. Median age 63.8 vs 63.9 yr (p = 0.9).
64 Gy in 32 fractions to the prostate fossa in both arms, mostly 3D-CRT rather than IMRT. aRT within 6 mo of RP; sRT triggered at PSA 0.20 ng/ml and delivered within 4 mo. Concurrent ADT and pelvic nodal treatment were not permitted.
Primary: proportion with a minimal clinically important change, defined as a >0.5 SD decline from baseline on each QLQ-PR25 domain. MCIC thresholds were 7 points urinary, 2 points bowel, 14 sexual activity, 12 sexual functioning. Global QOL by QLQ-C30.
The RP-to-RT interval regression is the cleanest read: no coefficient approached significance at 3, 4, or 5 yr in any domain, with the largest estimate 0.20 (95% CI -0.29 to 0.70, p = 0.4).
| Endpoint at 5 yr | Adjuvant RT | No RT | p |
|---|---|---|---|
| MCIC bowel symptoms | 37% (40/109) | 12% (6/50) | not reported in source |
| Severe urinary leakage | 18/111 (16) | 1/50 (2) | 0.01 |
| Severe urinary leakage at 4 yr | 15/124 (12) | 1/59 (1.7) | 0.02 |
| Urinary urgency | 18/110 (16) | 3/50 (6) | 0.072 |
GETUG-AFU 17 and RADICALS reported the same directional late GU penalty for adjuvant RT, though cross-trial comparison is blocked by differing urinary grading. Prior clinician-rated series put CTCAE grade 2 incontinence at 10 to 20%, bracketing the 16% seen here.
The aRT versus never-irradiated comparison is not randomized: those 87 men were selected by not recurring, so comorbidity and baseline continence are unbalanced by construction. The sRT-received group's worse sexual activity at 3 and 4 yr is confounded by higher-risk disease and likely more ADT off-protocol, and the 5-yr sexual functioning cells are as small as n = 10.
The patient-reported bowel signal is invisible on CTCAE (RAVES showed no clinician-rated GI difference), and the patient-reported urinary trend never reached consistent significance despite a 70% vs 54% clinician-rated G2+ GU gap. The two instruments are measuring different things, and neither alone describes what a man experiences.
CONSORT flow
Protocol-planned secondary analysis of a randomized trial; supports the established early-salvage standard. Exploratory, unadjusted for multiple testing, 3D-CRT era.
- Long-term patient-reported QOL with hypofractionated postprostatectomy RT
- QOL impact of adding short-course ADT and pelvic nodal RT post-RP
- Whether IMRT eliminates the patient-reported bowel signal
📚 Sources · 📄 1 paper
EANO Consensus Statement on Radiation Necrosis
ForPost-cranial-RT pts with a new enhancing lesion, glioma or brain metastases
TL;DRDelphi consensus: 53/57 statements reached ≥80% agreement across 20 experts; perfusion MRI + amino acid PET preferred, bevacizumab for steroid-refractory RN.
The dose-volume numbers are the transferable part: V12Gy ~10 cm³ carrying 5-10% symptomatic necrosis in single-fraction SRS, and hypofractionated brain+target V20Gy (3fx) or V24Gy (5fx) <20 cm³ holding RN needing resection under 4%. That is a planning constraint, and it gates the single-session vs hypofractionated choice for larger or eloquent-region metastases.
For a patient 6-24 months out from SRS or cranial RT with a new enhancing lesion, this supports going to perfusion MRI plus amino acid PET before calling progression; it does not settle mixed lesions, where the panel still points to tissue.
The planning-relevant numbers: V12Gy ~10 cm³ carries 5-10% symptomatic necrosis after single-fraction SRS, while hypofractionated brain+target V20Gy (3fx) or V24Gy (5fx) <20 cm³ keeps RN requiring resection under 4%. Re-irradiation risk climbs to 25% above cumulative EQD2 130 Gy, which constrains repeat SRS for lesions over 2.0-3.0 cm.
Bevacizumab moves from rescue to a triggered step at steroid dependence >4 weeks or dexamethasone 8 mg/day, with four accepted dosing schemes and no evidence favouring one. The panel also flags added RN risk when SRS is combined with dual checkpoint blockade or antibody-drug conjugates, which bears on sequencing brain RT against systemic therapy.
Resection carries the lowest accepted agreement in the management table (80.0%) yet is positioned as giving diagnosis and definitive treatment in one step for accessible lesions. LITT reached 100% agreement as the option for treatment-resistant RN unsuitable for resection, which gives a documented pathway for the steroid-dependent or bevacizumab-cycling patient.
11 details 5 trials watching
Three-round Delphi. 57 statements drafted after literature review across epidemiology-pathophysiology (n=8), causes (n=10), imaging (n=10), histopathology (n=9), management (n=20), plus an exploratory research set of 8. Consensus prespecified at ≥80% agreement on a 5-point Likert scale.
The voting panel, not patients: 15 volunteers (2 radiation/clinical oncologists, 4 neuro-oncologists, 4 medical oncologists, 2 neurosurgeons, 1 neuropathologist, 1 neuroradiologist, 1 nuclear medicine physician), expanded by 5 more in round 1 (4 neuro-oncologists, 1 radiation/clinical oncologist) to 20 total. Clinically the scope is RN after RT for primary glial or metastatic brain tumors.
RN is called uncommon below EQD2 ~40 Gy (α/β 2 Gy), rising with dose per fraction, total dose and irradiated volume. V12Gy ~10 cm³ carries a 5-10% symptomatic necrosis risk after single-session SRS; for hypofractionated SRT, brain-plus-target V20Gy (3fx) or V24Gy (5fx) <20 cm³ associates with <10% any necrosis and <4% RN requiring resection. Re-irradiation risk stays under 10% at cumulative EQD2 100-110 Gy and reaches up to 25% above 130 Gy.
Consensus reached on 53 of 57 statements after three rounds. Diagnostic and management statements are tabulated separately in the details; the four that failed to reach 80% are not identified in the available text.
| Modality | Setting | Sensitivity | Specificity |
|---|---|---|---|
| T1 contrast-enhanced MRI alone | WHO grade 3-4 glioma | 68% | 77% |
| T1 contrast-enhanced MRI alone | Brain metastases | 79% | 76% |
| DSC rCBV | Grade 3-4 glioma | 87-90% | 86-88% |
| DSC rCBV | Brain metastases (418 lesions) | 83% | 78% |
| MR spectroscopy Cho/NAA | Glioma (455 pts) | 88% | 86% |
| Amino acid PET | Brain metastases (~400 pts) | 82% | 84% |
The document's practical contribution is a decision sequence rather than a new treatment: advanced MRI first, amino acid PET to add confidence, tissue when doubt persists, and treatment triggered only by symptoms of >7 days with increasing severity. Its most consequential position is moving bevacizumab from rescue to an expected next step at a defined steroid threshold (dependence >4 weeks or dexamethasone 8 mg/day), which is a lower bar than many centres apply.
Agreement percentages measure how a self-selected 20-person European panel voted, and the panel skews neuro-oncology (8 of 20) over radiation oncology (3 of 20) for a complication defined by dose and volume. FET and F-DOPA availability is largely European, so the imaging algorithm's top tier is not reproducible in most centres worldwide. The 4 non-consensus statements are not enumerated in the accessible text, so the reader cannot see where the panel actually split.
Delphi expert-opinion document, no efficacy endpoint. Agreement measured against opinion, not outcomes; authors state absence of Level 1 evidence and call for randomised trials.
- Optimal bevacizumab dose, interval and duration for symptomatic RN n=408 · primary completion 2028-07 · phase 3 bevacizumab vs dexamethasone, 1L sCRNrecruiting Corticodependent or Corticoresistant Brain Radionecrosis After Radiotherapy for Brain Metastases Phase 3n=84 · primary completion 2028-08 · randomised bev vs placebo in steroid-refractory RN
- Single-session SRS vs hypofractionated SRT for RN risk active Comparing Single vs Multiple Dose Radiation for Cancer Patients With Brain Metastasis and Receiving Immunotherapy Phase NAn=58 · primary completion 2028-03 · single vs fractionated SRS toxicity on ICIn=54 · primary completion 2029-02 · staged SRS vs FSRT, 2-5 cm mets, safety endpointn=504 · primary completion 2030-01 · phase 3 3x10 Gy SRT vs 1x20-25 Gy SRS
- Predictors of bevacizumab response and recurrence rate after treatment
📚 Sources · 📄 1 paper
Abstract
SUPREMO
ForPost-mastectomy breast, node-negative high-risk or 1-3 positive nodes
TL;DREditorial critique: chest-wall-only RT cut 10yr CW recurrence 1.1% vs 2.5% (HR 0.45) but RNI was prohibited.
The RT-relevant number is buried in SUPREMO's supplement: node-positive LRR 3.3% vs 4.8%, HR 0.51 (0.27-0.96), significant even with chest-wall-only fields and RNI prohibited. With supraclavicular coverage in 12% and IMN in under 2%, this trial never tested comprehensive PMRT, so it cannot settle the elective nodal decision.
In a post-mastectomy patient with 1-3 positive nodes staged by SLNB alone, this argues SUPREMO does not license PMRT omission; it says nothing about node-negative pts without adverse features, where EBCTCG also found no benefit.
The supplement carries the number the headline drops: node-positive LRR 3.3% vs 4.8%, HR 0.51 (0.27-0.96), achieved even with RNI prohibited, supraclavicular coverage in 12% and IMN in under 2%. SUPREMO therefore constrains chest-wall-only treatment, not the elective nodal volume decision.
Axillary staging gates how far SUPREMO travels: only 14% had SLNB alone, and roughly 30% of SLNB pts with 1-3 positive nodes harbour further nodes at completion ALND. Choosing ALND to justify skipping PMRT trades a 8% five-year lymphedema risk with SLNB alone for 25% with ALND alone.
Also covered Jul 7
9 details
ASO Perspectives editorial in Annals of Surgical Oncology, not new trial data. Two radiation oncologists re-read SUPREMO against the PMRT and RNI evidence base. PMRT after neoadjuvant therapy is explicitly out of scope.
The central claim is that SUPREMO tested chest wall alone, not PMRT: RNI was prohibited, supraclavicular nodes were covered in 12% of PMRT-arm pts (n=97), and internal mammary irradiation occurred in fewer than 2% across both arms. Non-UK centres could give RNI in the observation arm, and 12 control pts received supraclavicular RNI.
Only 25% were truly node-negative and would not be offered PMRT under current guidelines; the majority had N1 disease (1-3 nodes). 65% were hormone-receptor positive, TNBC was 10%, and only 14% had SLNB alone with the majority undergoing ALND.
SUPREMO's 10-year chest-wall recurrence fell from 2.5% to 1.1% (HR 0.45) with no gain in overall LRR, DFS or OS. The supplement carries the signal the headline drops: LRR 4.8% to 3.3%, HR 0.51 (95% CI 0.27-0.96) in node-positive pts, not in node-negative.
| Approach | 5yr lymphedema risk |
|---|---|
| SLNB alone | 8% |
| SLNB + RNI | 11% |
| ALND alone | 25% |
| ALND + RNI | 30% |
EBCTCG 2014 found PMRT cut 10-year LRR by 17.9% and 20-year breast cancer mortality by 8% in 1-3 node-positive women, persisting with a single positive node, with no node-negative benefit. MA-20 and EORTC 22922 both showed RNI benefit in 1-3 node-positive disease despite near-universal ALND, and a later EBCTCG RNI meta-analysis showed gains at 15 years including in contemporary systemic-therapy trials.
This is a single-perspective editorial from two radiation oncologists, so the framing selects evidence favouring comprehensive RNI, and the reader gets no independent re-analysis of SUPREMO's data. Its strongest number, the node-positive LRR HR 0.51, comes from a supplementary subgroup the trial did not power for.
The authors leave the genuinely open questions to trials in progress: MA.39 (Tailor-RT) for RNI omission at low recurrence score, T-Rex for RNI omission in hormone-sensitive disease with one to two macrometastatic SLNs. They also note the surgical corollary, that ALND should not be chosen to earn a PMRT omission, since ALND is the dominant lymphedema driver.
Editorial, no new data; contests the omission reading of SUPREMO on field design and population grounds, aligning with ASTRO 2025 and NCCN rather than the trial's public messaging.
- RNI omission in 1-3 node-positive pts staged by SLNB alone
- Whether low Oncotype score permits comprehensive RNI omission
- PMRT effect in triple-negative disease after mastectomy
📚 Sources · 📄 1 paper
ASTRO 2024: SBRT for Unfavorable Intermediate-Risk Prostate Cancer
TL;DRConference education session on SBRT for UIR prostate: 5 fractions over 1-2wks, 1-2% bothersome toxicity vs 10-30% with 45-fraction 2D era.
Reported via UroToday →
RTOG 9408PACE BHYPO-RT-PCFLAME 2.0FORT
The actionable detail is the urethral-constraint critique of PACE-B: contouring was optional and constrained only "if visualized" (V44Gy <20%), so hotspots ≥120% put ~48Gy (≈121Gy EQD2) on the urethra. That reframes the 5.4% vs 3.7% G2+ GU gap as a planning artifact, not an SBRT property, and argues for contouring and constraining the urethra in 5-fraction prostate plans.
Contour and constrain the urethra in 5-fraction prostate plans: PACE-B made it optional ("if visualized", V44Gy <20%), and plausible ≥120% hotspots mean ~48Gy (≈121Gy EQD2) there, which reframes the 5.4% vs 3.7% G2+ GU gap as planning, not modality. Separately, RTOG 9408 keeps 4mo ADT tied to UIR, not FIR.
14 details 4 trials watching
ASTRO 2024 education session (EDU 16), not a trial report. Dr Daniel Spratt reviews risk stratification, fractionation history, and the SBRT evidence base for unfavorable intermediate-risk prostate cancer.
Unfavorable intermediate-risk disease, defined since 2013 by Gleason grade group 3 (HR 3.49 for distant mets) or ≥2 intermediate risk factors (HR 2.40). FIR and UIR also separate on cumulative PCSM incidence (p=0.013).
Options span brachytherapy and EBRT (protons or photons/IGRT) across conventional (~40fx), moderate hypofractionation (~20fx), and ultra-hypofractionation (~5fx). Era contrast: 1980s 2D delivered 45 fractions over 9 weeks with 10-30% bothersome GU/GI toxicity; modern SBRT is 5 fractions over 1-2 weeks with 1-2%.
RTOG 9408 secondary analysis anchors the ADT question: in UIR, 4mo ADT improved distant metastasis (HR 0.48, 0.28-0.83, P=.008) and PCSM (HR 0.40, 0.26-0.60, P<.001), with no benefit in FIR. PACE-B 5yr showed no significant EFS difference for SBRT vs conventional/moderate hypofractionation.
| Question | Endpoint | Result |
|---|---|---|
| UIR vs FIR prognosis | Distant metastasis | HR 2.36 (95% CI 1.44-3.89), P=.001 |
| UIR vs FIR prognosis | PCSM | HR 1.84 (95% CI 1.29-2.62), P=.001 |
| ADT benefit in UIR | Distant metastasis | HR 0.48 (95% CI 0.28-0.83), P=.008 |
| ADT benefit in UIR | PCSM | HR 0.40 (95% CI 0.26-0.60), P<.001 |
| ADT benefit in FIR | DM / PCSM | No improvement |
PACE-B G2+ GU 5.4% SBRT vs 3.7% control (p=0.28), no significant bowel difference. Pooled SBRT series: late grade ≥3 GU 2.0% (1.4-2.8%) and GI 1.1% (0.6-2.0%), with dose associated with both better biochemical control (P=.018) and worse late G3+ GU (P=.014).
The session's argument is that SBRT toxicity is a planning problem, not a modality problem: PACE-B did not require urethral contouring, so likely hotspots of ≥120% (≥48Gy, ~121Gy EQD2 to urethra) can explain the GU excess. Focal-boost work (36.25Gy/5fx + DIL to 45-50Gy; Loblaw's 35Gy prostate / 25Gy pelvis / 50Gy DIL) points the field toward whole-gland de-escalation with a boost.
Single-speaker synthesis with the speaker's own interpretive framing rather than a systematic review; the urethral-hotspot explanation for PACE-B GU toxicity is inference, not a reported dosimetric analysis. The captured excerpt truncates mid-FLAME 2.0 and never reaches the FORT trial named in the keywords.
- Does mandatory urethral constraint erase SBRT's GU excess? recruiting Daily Adaptive Radiation Therapy Using an Individualized Approach for Prostate Cancer Phase NAn=132 · primary completion 2026-07 · urethral-sparing adaptive SBRT, EPIC-26 acute GU 1° EPn=42 · primary completion 2028-01 · SUPR-SABR urethra sparing vs historical GU tox rates
- Does whole-gland de-escalation with DIL boost preserve biochemical control? n=58 · primary completion 2028-01 · microboost SBRT with whole gland dropped to 30-35 Gy
- Optimal DIL boost dose in 5 fractions n=132 · primary completion 2025-02 · 5-fraction MR-guided SBRT with SIB to the DIL
📚 Sources · 📄 1 paper
Abstract
HYDRA
ForLocalised prostate cancer, definitive external-beam RT
TL;DRNo PFS difference for either isodose (HR 0.92) or dose-escalated MHFRT (HR 0.94), but escalation raises late G2+ GI (OR 1.48).
The split that matters is isodose vs dose-escalated MHFRT, not hypofractionation itself: escalation adds no PFS (HR 0.94, 0.82-1.09) and costs bowel on both physician grading (OR 1.48) and patient report (OR 1.68). GU was unchanged in both strata. The schedule decision lands on 60 Gy in 20 fractions.
In a man with localised prostate cancer starting definitive prostate-only EBRT, this supports an isodose moderately hypofractionated schedule over a dose-escalated one; it does not extend to five-fraction ultrahypofractionation, post-prostatectomy salvage, or whole-pelvis treatment.
The decision this moves is schedule selection, not modality: escalated MHFRT shows no PFS gain (HR 0.94, 0.82-1.09) and raises late G2+ GI (OR 1.48) plus patient-reported bowel decrement (OR 1.68), while isodose shows neither. 60 Gy in 20 fractions is the defensible default for prostate-only volumes.
7 details 5 trials watching
IPD meta-analysis of randomised phase 3 CFRT vs MHFRT trials via the MARCAP consortium. Searches on Dec 15, 2023 and re-run Jan 8, 2025 screened 1696 records down to 7 eligible trials. Three separate analyses: efficacy, physician-scored late toxicity, and patient-reported outcomes.
Localised prostate cancer on trials that published patient-level efficacy AND late toxicity data. 3454 pts across three isodose trials, 2426 pts across four dose-escalated trials. Trials whose CFRT arm fell below modern dose were excluded.
The intervention split is the whole point: isodose MHFRT (same equivalent dose in fewer fractions, eg 60 Gy in 20 fractions) versus dose-escalated MHFRT. The CFRT comparator had to deliver ≥70 Gy in 2 Gy equivalents.
Primary (efficacy): progression-free survival. Co-primary toxicity endpoints: late grade 2 or higher GU and GI. Co-primary PRO endpoints: clinically-significant decrement in urinary or bowel quality of life.
The GI signal sits entirely in the dose-escalated stratum and shows up on both physician grading and patient report; the isodose stratum carries neither. GU odds ran above 1 in both comparisons with intervals crossing unity.
CHHiP and PROFIT established 60 Gy in 20 fractions as non-inferior to conventional fractionation. The escalated schedules were built on the premise that a higher equivalent dose in fewer fractions would improve control; pooled here that premise fails on PFS while adding bowel toxicity.
Toxicity scales and PRO instruments were not uniform across the seven trials, and the dose-escalated stratum pools four schedules that are not interchangeable, so the OR describes escalation as a class, not one regimen. Follow-up also differs between strata (5.4 vs 7.1 yrs).
With efficacy answered as a null, the schedule decision turns entirely on toxicity, and the toxicity difference runs one way. Escalating per-fraction dose beyond isodose buys no measurable PFS while adding bowel morbidity that pts themselves report, which leaves little argument for an escalated MHFRT schedule in intact localised disease.
Pooled IPD from seven randomised phase 3 trials, aligned with existing moderate-hypofractionation practice; refines which regimen rather than establishing a new modality or population.
- Does the escalation bowel signal extend to five-fraction ultrahypofractionation? recruiting Comparing Moderately Ultra Hypofractionated Radiation Treatments for Prostate Cancer Phase 2n=204 · primary completion 2030-11 · randomised 20fx vs 5fx post-op bed +/- pelvisrecruiting Salvage Moderate Hypofractionated Versus Ultrahypofractionated Radiotherapy for Biochemical Recurrence After Radical Prostatectomy in Prostate Cancer Phase 3n=270 · primary completion 2034-12 · phase 3 moderate vs ultrahypo salvage, toxicity EP
- Do rectal spacers and daily IGRT narrow the dose-escalated GI gap? n=500 · primary completion 2027-12 · SpaceOAR Vue for late GI toxicity under SBRTn=84 · primary completion 2027-12 · Barrigel anterior rectal sparing in post-op RT
- Same toxicity read when MHFRT covers whole-pelvis nodal volumes? n=18 · primary completion 2026-08 · 20/16/12fx pelvic nodal RT with prostate SIB
📚 Sources · 📄 1 paper
Abstract
ESTRO OCSCC Post-op CTV Delineation Guidelines
ForResected oral cavity SCC proceeding to post-operative radiotherapy
TL;DRFirst ESTRO guideline for post-op CTV delineation in oral cavity SCC: GTV-P pre-op + 10 mm composited with surgical defect/flap + 5 mm.
The margin recipe is asymmetric and that is the operative detail: 10 mm around the re-created pre-op GTV-P but only 5 mm around the surgical defect or flap, composited rather than either alone. Fig 3.1/3.2 shows why, the re-created GTV-P extended superiorly beyond the defect into infratemporal fossa, a geographical miss if you contour the defect alone.
In resected OCSCC going to PORT, this supports re-creating the pre-op GTV-P from diagnostic MRI alongside the defect or flap rather than contouring the operative bed alone; it does not extend to R2 resections or other head and neck subsites.
The margin recipe is asymmetric: 10 mm around the re-created pre-op GTV-P but 5 mm around the surgical defect or flap, composited rather than either alone. Nodal margin is pENE-gated at 5 mm versus 10 mm on GTV-N pre-op. Fig 3.1/3.2 shows the pre-op GTV extending past the defect into infratemporal fossa, a geographical miss if you contour the bed alone.
11 details 5 trials watching
ESTRO-convened multi-disciplinary expert group developing delineation guidelines through discussion and review of current evidence and international practice. Drafts were reviewed by HNSCC experts from countries outside the authorship (Japan, Hong Kong, Australia, Brazil, Mexico, Canada, Denmark, France, Spain, Poland, Ireland, UK) and modified on their feedback. No efficacy endpoint, no patient cohort.
Patients with oral cavity squamous cell carcinoma requiring post-operative radiotherapy, regardless of margin status and other histological risk factors. R2 resection (macroscopic residual disease) is explicitly out of scope. Companion background manuscript from the same group covers indications for PORT.
Planning CT 2.0 mm slices (range 1-3 mm), skull base to below sterno-clavicular joint, IV contrast mandatory, rigid co-registration with pre-op contrast-enhanced CT and/or MRI matched to C1-C3 vertebral bodies or nearby bone, not to soft tissue. CTV-P is the composite of GTV-P pre-op + 10 mm and surgical defect/flap + 5 mm, edited for bone, fascia, air, teeth and any intra-oral prosthesis. Nodal margin is 5 mm on GTV-N pre-op without pENE, 10 mm with pENE.
None. The stated aim is consistency of delineation to enable multi-institutional audit, clinical trials and RTQA. Authors position prospective audits of practice and outcomes as the route to establishing these volumes as standard of care.
Extends the 2018 international CTV-P consensus for definitive HNSCC RT, whose 5+5 mm geometric expansion supplies the 10 mm used here around GTV-P pre-op. Cites the DAHANCA finding that geometric expansion is more conformal than anatomical margins, a post-hoc De-ESCALaTE analysis correlating the anatomical-to-geometric protocol change with lower late dysphagia, and non-randomised Dutch series where reducing the high-risk margin 10 mm to 6 mm cut salivary and constrictor dose. GORTEC's 2020 flap delineation guidance is named as an adjunct.
The 5 mm and 10 mm margins are imported from definitive-setting geometry and one surgical pathology series (>95 % of microscopic infiltration within 5 mm of GTV-P edge), not from post-operative recurrence mapping. The dose to dissected but uninvolved levels rests on a 1993 MD Anderson observation never tested prospectively, and is left to clinician discretion (EQD2 50-60 Gy). The whole method assumes accurate pre-op to planning CT co-registration, and the fallback where it fails is to treat the entire involved level, a larger volume.
The novel move is refusing to pick between the two available surrogates for a resected tumour: re-created pre-op GTV and operative bed are contoured independently and unioned, because each fails in a different direction. Fig 3.1 shows a GTV-P pre-op extending superiorly past the defect toward the infratemporal fossa, and Fig 8.1 a pectoralis major pedicled flap whose composite volume extends outside the oral cavity and is trimmed back. What is left unsettled is dose de-escalation to central flap tissue, where the guideline offers a flap avoidance structure for standardisation while stating there is a lack of data and consequently a lack of consensus.
| Volume | Indication | EQD2 dose |
|---|---|---|
| CTV-P post-op | PTV associated with post-op primary CTV | 60 Gy |
| CTV-P high-risk | Positive (<1 mm) margin, whole CTV-P or localised strip | over 60 Gy, e.g. 64-66 Gy |
| CTV-N1 | Involved nodal levels | 60 Gy |
| CTV-N2 | Undissected at-risk levels | 50 Gy |
| CTV-N2, dissected at-risk levels | Optimal dose unknown | 50 Gy to 60 Gy, clinician discretion |
| CTV-N high-risk | Pathological extranodal extension | over 60 Gy, e.g. 64-66 Gy |
ESTRO expert guideline, no efficacy endpoint. Fills a documented gap (no prior post-op HNSCC CTV consensus); authors themselves position prospective audit as the validation step.
- Optimal dose to dissected but uninvolved nodal levels recruiting Preservation of Swallowing in Respected Oral Cavity Squamous Cell Carcinoma: Examining Radiation Volume Effects (PRESERVE): A Randomized Trial Phase 2n=90 · primary completion 2026-09 · OCSCC RCT: omit RT to dissected pN0 hemi-neckn=50 · primary completion 2029-01 · compartment-based post-op volume reduction in HNSCCrecruiting De-Intensification of Postoperative Radiotherapy in Patients With Squamous Cell Carcinoma of the Head and Neck Phase 2/3n=508 · primary completion 2031-12 · omits elective neck RT after neck dissection
- Whether flap dose de-escalation is safe not yet Lipiodal Injection Technique for Free Flap Sparing Adjuvant RT Planning in HNC Phase Early 1n=10 · primary completion 2026-03 · lipiodol marks flap borders for sparing plansn=348 · primary completion 2031-03 · phase 3 RCT: flap-sparing vs standard post-op RT
- Whether 10 mm post-op primary margin can be reduced as in definitive setting
📚 Sources · 📄 1 paper
NRG-GU005 (quality of life)
ForLocalized intermediate-risk prostate cancer, median age 68, no ADT specified
Bowel 33% vs 46% at 1 yr
p=0.002; 2yr bowel/UIO primary PRO endpoint not reported in source
TL;DRFewer MCID declines with SBRT at 1yr bowel (33% vs 46%, p=0.002) and sexual (34% vs 44%, p=0.026).
Reported via UroToday →
The QoL separation is domain-specific, not global: bowel and sexual at 1yr, urinary incontinence at 2yr, with no longitudinal effect in sexual or hormonal. Rectal manipulation (SpaceOAR 55%) and the 38.78 Gy PTV max cap gate transfer, since the bowel and GU signals came from a spacer-heavy, urethra-constrained delivery.
In localized intermediate-risk prostate cancer choosing between 5-fraction SBRT and moderate hypofractionation, this supports SBRT on patient-reported bowel, sexual, and continence grounds; it does not speak to high-risk disease, nodal coverage, or oncologic non-inferiority, which the trial's primary endpoint carries.
Domain-specific, not global: bowel and sexual at 1yr, incontinence at 2yr, with no longitudinal sexual or hormonal effect. The 38.78 Gy PTV max cap and 55% SpaceOAR use gate transfer, since the favorable GU and bowel profile came from a urethra-constrained, spacer-heavy delivery, not from five fractions alone.
Also covered Aug 14
11 details
Randomized, non-blinded phase III, 1:1, N=698 (MH-IMRT 345, SBRT 353), stratified by Gleason score, PSA, and rectal manipulation. The trial's oncologic primary endpoint sits elsewhere; this analysis reports the patient-reported secondary endpoints.
Localized intermediate-risk prostate cancer, median age 68 (IMRT) and 69 (SBRT). Two patients were ineligible (one high-risk, one PSA out of window). Baseline EPIC domains were balanced across arms, all p≥0.093.
SBRT 36.25 Gy in 5 fractions delivered 2-3 per week, PTV expansion 5mm except 3mm posteriorly and anteriorly, PTV max capped at 38.78 Gy unless the urethra was visualized and contoured (acceptable variation 43.5 Gy). MH-IMRT 70 Gy/28 fx or 60 Gy/20 fx, PTV expansion 8mm except 5mm posteriorly. CTV was prostate ± 1cm proximal seminal vesicles. Rectal manipulation was common: SpaceOAR in 55% overall.
EPIC-26 at baseline, 12 and 24 months. MCID thresholds: >5 points urinary irritative/obstructive, >6 urinary incontinence, >10 sexual, >4 bowel and hormonal. Individual MCID rather than group mean scores was the analytic unit, with an exploratory longitudinal linear model adjusted for baseline score, arm, stratification factors, T-stage, age, and race.
The arm-level MCID and toxicity comparisons are tabulated above. Longitudinal modeling of urinary incontinence gave a least square mean difference of 2.91 (95% CI 0.85-4.97, p=0.0058) favoring SBRT, while sexual and hormonal domains showed no significant treatment effect.
| Domain / timepoint | SBRT | MH-IMRT | p |
|---|---|---|---|
| Bowel, 1 yr | 33% | 46% | 0.002 |
| Sexual, 1 yr | 34% | 44% | 0.026 |
| Urinary incontinence, 2 yr | 26% | 35% | 0.023 |
| Event | SBRT | MH-IMRT | p |
|---|---|---|---|
| Treatment-related G≥3 GU | 0.6% | 2.5% | 0.04 |
| Rectal hemorrhage, any grade | 10.5% | 17.3% | 0.01 |
| Fatigue, any grade | 39.2% | 50.8% | 0.0025 |
Investigator-reported toxicity favored SBRT across the board: grade ≥3 GU 0.6% vs 2.5% (p=0.04), any-grade rectal hemorrhage 10.5% vs 17.3% (p=0.01), any-grade fatigue 39.2% vs 50.8% (p=0.0025). The GU finding is the one that most often runs the other way in ultrahypofractionation series, so it is worth reading as the trial's own answer to the pre-trial toxicity concern.
PACE-B is the other large randomized SBRT vs moderate hypofractionation comparison, and both trials show lower urinary incontinence decline with SBRT despite differing MCID definitions. Prior patient-level meta-analysis had suggested less clinically meaningful bowel and urinary irritative/obstructive decline at two years with SBRT, and the 1-year bowel result here is directionally consistent.
Differential attrition ran against the IMRT arm: 22 IMRT patients (6.4%) died or withdrew before year 1 versus 4 SBRT patients (1.1%), and 22 IMRT patients never received the assigned RT after withdrawal versus 1 in the SBRT arm. Completion was 79.9% (IMRT) and 84.0% (SBRT) at year 1. The domain-by-timepoint pattern (bowel and sexual at 1yr, incontinence at 2yr) is the kind of scattered significance that multiplicity should temper.
The trial was designed when the open question was whether five fractions cost the patient something. The PRO answer is that it does not, and the investigator-reported toxicity answer is that it may cost less. What the QoL data cannot do is settle whether SBRT is oncologically non-inferior, which is the primary endpoint and is not reported in this source.
CONSORT flow
Prespecified PRO secondary analysis of a phase III trial, non-blinded with patient-reported endpoints; aligns with PACE-B rather than establishing a new position. Oncologic primary endpoint not reported here.
- Oncologic non-inferiority of SBRT vs MH-IMRT in this trial
- Whether bowel benefit holds without rectal spacer
- Durability of QoL separation beyond 2 years
📚 Sources · 📄 1 paper
Abstract
10-yr SBRT Survival/Toxicity (Meier et al.)
ForLocalised low- or intermediate-risk prostate, no ADT, prostate volume up to 100 cc
TL;DR10-yr RFS 90% overall (94% LR, 86% IR) with 40 Gy/5 fx; grade 3 late toxicity 1.4-1.5%, no grade 4-5.
Two-thirds of relapses fell between 5 and 10 yr, so the reassurance PACE-B gives at 5 yr is provisional. The unfavorable IR subgroup sits at 77% (60-93) vs 92% for favorable IR (p=0.002), which is where the ADT-with-SBRT question actually lives, not in the pooled 86% IR number.
In unfavorable intermediate-risk prostate considered for 40 Gy/5 fx monotherapy, the 77% 10-yr RFS (vs 92% favorable IR) is the number that informs an ADT discussion; the favorable IR and low-risk data do not carry that concern.
Two-thirds of relapses fell between 5 and 10 yr, so PACE-B's 5-yr reassurance is provisional. Within IR, unfavorable pts sat at 77% (60-93) vs 92% favorable (p=0.002) with 40 Gy/5 fx and no ADT, which is where the ADT-addition question lives, not in the pooled 86%.
11 details 4 trials watching
Investigator-initiated phase 2 nonrandomized trial across 21 centers (community, regional, academic), enrolling Jan 2008 to Apr 2010. 310 evaluable pts, median age 68, median follow-up 9 yr. Kaplan-Meier estimation with log-rank comparison of LR vs IR.
172 low-risk (T1b-T2a, Gleason 6, PSA under 10) and 138 intermediate-risk (T1b-T2b, Gleason 7 or Gleason 6 with PSA 10-20), all confirmed by central pathologic review. IR pts subclassified favorable vs unfavorable by MSK criteria. Prostate volume up to 100 cc allowed; prior TURP and baseline AUA score were not exclusions.
40 Gy in 5 fractions (8 Gy x 5, equivalent to ~100 Gy at 2 Gy/fx assuming a/b = 2) on a noncoplanar robotic platform. Fiducial tracking with translational and rotational intrafractional motion correction was mandatory. Androgen suppression was not allowed, so the outcomes are RT-attributable.
Relapse defined as biochemical failure (nadir + 2), clinical failure, or administration of any salvage, antiandrogen, or systemic therapy. Late toxicity was physician-reported, CTCAE v3, events beyond 3 mo. Day 0 was the last day of treatment.
10-yr OS 84% (76-91). Freedom from local failure 96% (93-99) overall. The separation that matters is within IR: favorable 92% vs unfavorable 77%, p = 0.002, whereas LR vs IR overall was not significant (p = 0.19).
| Group | 10-yr RFS (95% CI) | p |
|---|---|---|
| Whole group | 92% (87-96) | n/a |
| Low risk | 94% (89-99) | 0.19 (LR vs IR) |
| Intermediate risk | 86% (77-94) | 0.19 (LR vs IR) |
| MSK favorable IR | 92% (90-100) | 0.002 (fav vs unfav) |
| MSK unfavorable IR | 77% (60-93) | 0.002 (fav vs unfav) |
Four pts had five grade 3 events, all GU, and no grade 4-5 events occurred. Cumulative 10-yr grade 3 rates were 1.4% LR and 1.5% IR, far below the 10% rate the trial deemed acceptable. Grade 2+ GU 14% exceeds grade 2+ GI 2.1% by roughly sevenfold; no new late grade 3+ events after year 5.
IR relapse-free survival (86%) sits above the 74-78% 10-yr RFS of dose-escalated EBRT in RTOG 0126, and the authors note an updated HYPO-RT-PC now shows superior 10-yr RFS in the 6.1 Gy x 7 arm. Toxicity matched Fuller's CyberKnife trial but was lower than the PACE-B SBRT arm and PATRIOT, both of which treated substantial fractions on a conventional linac.
The toxicity advantage over PACE-B and PATRIOT is confounded by platform, and the sponsor makes that platform, so the comparison cannot separate tracking from delivery-era and case-mix differences. Toxicity is physician-reported CTCAE only, with no patient-reported instrument, which understates GU bother relative to the EPIC-based comparators. Comparator EBRT series (RTOG 0126) predate modern IGRT.
The durability question, not the toxicity question, is what 10 yr answers here: two-thirds of relapses occurred between 5 and 10 yr, in this trial and in Fuller's. That timing means a 5-yr non-inferiority readout is structurally optimistic for both arms, and it reframes what PACE-B's 5-yr result can and cannot settle.
Single-arm nonrandomized phase 2, no concurrent comparator; sponsor-funded with device-specific delivery. Extends existing 5-yr SBRT data rather than testing a new question.
- Whether ADT improves outcomes for unfavorable intermediate-risk pts receiving SBRT n=310 · primary completion 2025-12 · phase 3 prostate SRT +/- short-term ADT, bDFSn=222 · primary completion 2027-12 · SBRT without ADT in UIR, Decipher-gatedn=392 · primary completion 2030-04 · SBRT + 6-mo ADT vs SBRT alone, NCCN UIR cohort
- Whether intrafractional tracking, not platform, drives the toxicity difference recruiting Is Adaptive SBRT for Prostate vs Image-guided Radiotherapy a True Evolution (ASPIRE) Phase 3n=320 · primary completion 2030-02 · adaptive vs image-guided SBRT, urinary endpoint
- 10-yr PACE-B relapse rates vs conventional fractionation
📚 Sources · 📄 1 paper
American Radium Society AUC: Local Intraprostatic Recurrence
ForIsolated intraprostatic recurrence after definitive prostate RT
TL;DRSevere GU toxicity 20% after salvage RP vs 5.6% SBRT, 9.6% HDR: panel prefers biopsy-confirmed reirradiation.
The modality recommendation is a toxicity argument, not an efficacy one: MASTER found adjusted 5-yr recurrence-free survival of 50% to 60% across modalities with no survival difference vs RP, so reirradiation wins on severe GU toxicity (5.6% SBRT, 9.6% HDR vs 20% RP). Target volume then follows concordance, focal when mpMRI and systematic biopsy agree, whole-gland when they do not.
In a man with rising PSA after conventionally fractionated definitive prostate EBRT whose PSMA PET and mpMRI show isolated intraprostatic recurrence, this supports biopsy confirmation before reirradiation rather than ADT alone; it does not extend to recurrence after primary brachytherapy or to nodal or distant failure.
Every accepted schema fits in six or fewer fractions (34 Gy or 40 Gy in 5 fractions, 36 Gy in 6 fractions per GETUG-AFU 31, HDR 27 Gy in 2 fractions), and focal CTV is mpMRI plus choline PET GTV with a 5-7 mm margin bound by the capsule. None of it was validated after hypofractionated primary RT.
ADT alone is recommended against for confirmed local recurrence. Only a short 4-6 mo LHRH agonist is endorsed, as a radiosensitizer with salvage SBRT, and the panel reached no agreement on relugolix (HERO's cardiac benefit was an unplanned secondary, PRONOUNCE did not replicate). Classic ADT is preferred over novel hormonal agents.
Salvage RP holds equivalent adjusted 5-yr recurrence-free survival in MASTER (50% to 60% across modalities, no survival difference vs RP), so the case against it is toxicity: severe GU 20% vs 5.6% after SBRT. Biopsy and ablation should not be combined in one procedure, since histologic confirmation must precede salvage.
9 details 4 trials watching
PRISMA systematic review of PubMed and Embase (searched 28 June 2022) across four topics, excluding conference abstracts, non-English publications and series of fewer than five patients. A 12-member multidisciplinary panel of radiation oncologists, urologists and medical oncologists voted in two rounds by modified Delphi, with RAND methodology defining disagreement.
Scope is tier A disease, local-only intraprostatic radiorecurrence after definitive RT, with BCR defined as PSA 2.0 ng/ml above nadir. Evidence was restricted to men whose primary treatment was conventionally fractionated EBRT, and prior brachytherapy patients were excluded from the synthesis. Every variant presumes the patient wants curative-intent local salvage.
All accepted salvage schemas fit in six or fewer fractions. For focal salvage, GETUG-AFU 31 defines GTV by mpMRI plus choline PET with a 5-7 mm margin bound by the prostatic capsule; whole-gland salvage SBRT has prospective support from the Fuller series. Dose constraints and IGRT method are out of scope.
Long hormone courses are recommended against across all salvage scenarios. A short 4-6 mo LHRH agonist carries moderate consensus as a radiosensitizer with salvage SBRT in patients without cardiac history, weaker consensus with cardiac comorbidity, and classic ADT is preferred over novel hormonal agents.
The toxicity read that drives the reirradiation preference comes from pooled retrospective data that could not evaluate sexual toxicity and included no PSMA PET selection. Approaches that combine biopsy and ablation in one procedure are discouraged, since histologic confirmation must precede salvage.
No prior consensus guideline addressed intraprostatic radiorecurrence exclusively. The hormone-only comparators being displaced (Crook intermittent vs continuous ADT, TOAD immediate vs delayed, EMBARK enzalutamide MFS benefit) all enrolled before PET-based selection and none isolated a biopsy-confirmed, local-only cohort. RTOG 0526 reported after MASTER closed, adding prospective LDR support.
The search closed 28 June 2022 with an acknowledged lag to publication. MASTER carries between-study heterogeneity and follow-up asymmetry favoring older modalities, so its flat efficacy comparison is not a randomised one. The hormone recommendation rests on no qualifying study and is extrapolated from de novo intermediate-risk data.
Settled: image, biopsy with both systematic and targeted cores, then prefer reirradiation over hormones alone. Not settled: the modality for a second salvage, for castrate-resistant local recurrence, for short PSA doubling time, or after prior grade 3 toxicity, all of which drew panel disagreement.
| Variant | Panel position |
|---|---|
| Variant 1: isolated intraprostatic recurrence | Reirradiation usually appropriate; cryotherapy or HIFU may be appropriate; ADT alone not recommended |
| Variant 2: short PSA doubling time, short interval to failure | HIFU may be appropriate, but disagreement across all interventions; ADT alone not recommended |
| Variant 3: castrate-resistant local recurrence | Disagreement on intervention; androgen suppression uniformly not recommended |
| Variant 4: second local salvage | Disagreement on which modality to select |
| Variant 5: prior grade ≥3 toxicity | Disagreement; active surveillance may be appropriate; ADT can be considered |
| Modality | Severe GU | Severe GI |
|---|---|---|
| Salvage RP (reference) | 20% | 1.8% |
| SBRT | 5.6% | not reported in source |
| HDR brachytherapy | 9.6% | 0.0%, p < 0.01 vs RP |
| LDR brachytherapy | 9.1% | not reported in source |
| Scenario | Target volume |
|---|---|
| mpMRI and systematic biopsy agree on lesion location | Focal favored |
| History of grade ≥3 toxicity from initial RT course | Focal favored |
| Lesion occult on mpMRI, localised by PET plus systematic biopsy | Focal or whole-gland both appropriate |
| mpMRI and systematic biopsy disagree on lesion location | Whole-gland preferred |
| Recurrent lesion in a different location to the index lesion | Whole-gland preferred, focal appropriate in selected cases |
Appropriate use criteria from a 12-member Delphi panel; the output is a recommendation grid, not an efficacy result. No trial endpoint, so efficacy verdicts do not apply.
- Salvage outcomes after primary hypofractionated RT or prior brachytherapy n=60 · primary completion 2024-11 · RO-PIP: salvage ultra-hypofx EBRT vs HDR, pt-reported toxrecruiting Stereotactic Re-irradiation of Local Recurrences of Prostate Cancer After Radiotherapy Phase 2n=55 · primary completion 2029-12 · focal SBRT reRT, G2/G3 GU-GI tox 1° EPn=30 · primary completion 2032-01 · salvage HDR after prior EBRT or LDR brachytherapy
- Whether short ADT adds oncologic benefit to salvage reirradiation
- Optimal modality for castrate-resistant or second local salvage n=50 · primary completion 2025-03 · focal salvage HDR, biopsy/MRI-guided local recurrence
📚 Sources · 📄 1 paper
SUPREMO
ForPost-mastectomy pT1-2N1, pT3N0, or pT2N0 grade 3/LVI+ breast cancer
81.4% vs 81.9%
HR 1.04, 95% CI 0.82-1.30, P=0.80; primary endpoint not met
TL;DR10yr OS 81.4% vs 81.9% (HR 1.04, 0.82-1.30, p=0.80): PMRT omission safe in intermediate-risk pN0-pN1 post-mastectomy.
The RT read is the local-control trade: 1.1% vs 2.5% chest-wall recurrence, 29 events total, bought with 40-50 Gy to the chest wall in a population where OS was flat at 10 years. Nodal volumes were not routinely treated (SCF 97/808), so this speaks to chest wall alone, not to regional nodal irradiation.
In a pT2N1 or pT3N0 mastectomy patient who has completed modern adjuvant systemic therapy, this supports discussing PMRT omission with an absolute chest-wall recurrence trade under 2 points; it does not address regional nodal irradiation or pN2-N3 disease.
The trade is 1.1% vs 2.5% chest-wall recurrence from 40-50 Gy, with 10yr OS flat (HR 1.04). Nodal volumes were not routinely treated (SCF 97/808, IMC 12/808), so this licenses chest-wall omission specifically, not regional nodal omission, and moves PMRT here into a morbidity-versus-local-control discussion.
The systemic backbone (85% chemo, 79% endocrine, 19% trastuzumab) is what makes the null interpretable: with modern adjuvant therapy the residual chest-wall event rate is 2.5% untreated, leaving no room for RT to alter survival. Referral for PMRT in this band becomes optional rather than expected.
After mastectomy plus an axillary procedure in pT1-2N1, pT3N0, or pT2N0 grade 3/LVI disease, expected PMRT no longer carries a survival argument (HR 1.04), which changes the reconstruction conversation at the time of surgery since a planned reconstruction need not be sequenced around anticipated chest-wall irradiation.
Also covered Jul 9
9 details
International phase 3 randomized trial (BIG 2-04 MRC/EORTC SUPREMO), 125 UK sites plus 27 European and 21 international sites. N=1607 ITT (808 CWI, 799 no CWI), randomized August 2006 to April 2013, database lock June 2024. Median follow-up 9.6 years.
"Intermediate-risk" post-mastectomy disease: pT1N1, pT2N1, pT3N0, or pT2N0 with grade 3 and/or LVI. All had mastectomy, an axillary procedure, and systemic therapy. Baseline systemic exposure: 85% chemotherapy, 79% endocrine, 19% trastuzumab.
Chest wall 40 to 50 Gy in the irradiation arm. Nodal volumes were not part of the randomized question: supraclavicular fossa treated in only 97/808 irradiated patients, internal mammary chain in 12/808. Twelve patients in the no-irradiation arm received SCF treatment.
Primary: overall survival at 10 years. Secondary: chest-wall recurrence, regional recurrence, disease-free survival, distant metastasis-free survival, cause of death, radiation-related adverse events.
The historic case for postmastectomy RT in node-positive disease rests on the EBCTCG overview, where the locoregional-control gain translated into a mortality benefit. SUPREMO tests that inheritance in the 1-3 node and high-risk node-negative band under contemporary systemic therapy and finds the recurrence signal preserved (HR 0.45) but the survival signal absent (HR 1.04).
The chest-wall recurrence benefit rests on 29 events total with a CI upper bound of 0.99, so the point estimate is unstable. Accrual ran 2006-2013, predating routine dual HER2 blockade, extended adjuvant CDK4/6 inhibition, and current genomic risk stratification, all of which lower the baseline recurrence rate this trial was powered against.
A flat OS with a halved chest-wall recurrence is the signature of a locoregional intervention operating below the threshold where local control converts into survival. At 1.1% vs 2.5%, the absolute chest-wall event rate in both arms is low enough that no plausible salvage-to-mortality pathway could move a 10-year OS curve. The result reframes PMRT in this band as a local-control decision to be weighed against RT morbidity, not as a survival decision.
| Endpoint | CWI | No CWI | HR (95% CI) |
|---|---|---|---|
| Overall survival (1°) | 81.4% | 81.9% | 1.04 (0.82-1.30), p=0.80 |
| Disease-free survival | 76.2% | 75.5% | 0.97 (0.79-1.18) |
| Distant MFS | 78.2% | 79.2% | 1.06 (0.86-1.31) |
| Chest-wall recurrence | 9 (1.1%) | 20 (2.5%) | 0.45 (0.20-0.99) |
CONSORT flow
Adequately powered phase 3, prespecified OS primary, 9.6yr median follow-up, modern systemic backbone. Supports omitting PMRT in a population where guidelines still often recommend it.
- Does regional nodal irradiation carry the same null in pN1 disease
- Which biomarker or genomic subgroup still benefits from chest-wall RT
- Late cardiac and second-malignancy burden of the irradiated arm
📚 Sources · 📄 1 paper
Abstract
ReCOG HNSCC Reirradiation Consensus
TL;DRInternational consensus: 24 of 31 statements reached ≥85% agreement; elective nodal irradiation not recommended (100%), definitive CTV = GTV + 5 mm.
RTOG 9610RTOG 9911GORTEC 2008-01GORTEC 98-03GORTEC-GETTEC
Two statements change planning immediately: elective nodal irradiation is off (100% agreement, no locoregional-failure or OS gain in the 505-pt Caudell cohort, more acute toxicity), and volume, not phase preference, picks the technique at 25 cc. Below 25 cc IMRT and SBRT are called equivalent (88%); above it IMRT is preferred (88%).
In a previously irradiated HNSCC recurrence being contoured this week, this supports omitting elective nodal volumes and using GTV + 5 mm for definitive CTV; it does not cover nasopharyngeal recurrence or rare histologies, which were excluded.
Two statements change planning immediately: elective nodal irradiation is off (100% agreement, no locoregional-failure or OS gain in the 505-pt Caudell cohort, more acute toxicity), and volume picks the technique at 25 cc, IMRT and SBRT equivalent below (88%), IMRT preferred above (88%). Definitive CTV is GTV + 5 mm (94%).
The panel decouples the reirradiation decision from final margin status: reirradiation can be considered when R0 is unlikely on preoperative imaging or surgical assessment even if pathology does not report positive margins (82%), because recurrent tumour sits as small islets in fibrotic tissue. RPA class I (resected, >2 yr interval) with R1 or extracapsular extension is the clearest postoperative indication (100%).
10 details 2 trials watching
Expert-driven clinical practice statement. A core group of six radiation oncologists, three physicists, and one research fellow drafted statements from the literature, then an international panel of 17 radiation oncologists voted once on 31 statements (agree / disagree / no opinion, no-opinion retained in the denominator). No second round.
Recurrent or second-primary HNSCC within a previously irradiated region, definitive or postoperative reirradiation. Nasopharyngeal cancers and rare histologies are excluded, the former covered by separate 2021 international recommendations.
Definitive: CTV = GTV + 5 mm (94%), IMRT to ~66 Gy for GTV >25 cc, IMRT or SBRT below 25 cc, SBRT at an equivalent ~40 Gy in five fractions. Postoperative: normofractionated IMRT ~60 Gy (94%), SBRT discouraged for lack of data. Elective nodal irradiation is not recommended in either setting (100%).
The output is agreement, not an outcome. Each statement carries an observed agreement percentage against predefined thresholds (high ≥85%, moderate 70-84%, low <70%) plus an Oxford-adapted evidence level 1 to 4.
24 of 31 (77%) statements reached high consensus. The seven moderate statements cluster on R0-unlikely postoperative indications (82%), RPA class III exclusion (76%), postoperative CTV rules (82%), the 66 Gy reference dose (82%), hyperfractionation (76%), SBRT dose (76%), and cord/brainstem cumulative limits (70%, the lowest).
| Scenario | Recommendation | Consensus | Evidence level |
|---|---|---|---|
| Definitive, GTV >25 cc | IMRT preferred, superior to SBRT | 88% | 3 |
| Definitive, GTV ≤25 cc (cT1-T2) | IMRT or SBRT, similar outcomes | 88% | 3 |
| Definitive IMRT dose | 66 Gy commonly used | 82% | 4 |
| Definitive CTV | GTV + 5 mm margin | 94% | 4 |
| Postoperative technique | Normofractionated IMRT over SBRT | 94% | 3 |
| Postoperative dose | 60 Gy commonly used | 94% | 3 |
| SBRT dose | ~40 Gy in five fractions | 76% | 3 |
| Elective nodal irradiation | Not recommended | 100% | 3 |
| Scenario | Statement | Consensus | Evidence level |
|---|---|---|---|
| Recurrence <6 mo | Reirradiation generally not advised | 100% | 2 |
| Recurrence 6-12 mo | Highly selected cases only | 88% | 2 |
| RPA class I, R1 or ECE | Postoperative reirradiation considered | 100% | 2 |
| R0 unlikely, margins negative | Reirradiation can still be considered | 82% | 4 |
| RPA class III | Generally no curative-intent reirradiation | 76% | 3 |
| Previous plan review | Distinguish in-field vs marginal failure | 100% | 3 |
The supporting literature reports pooled grade 3 or higher acute toxicity of 32% and late toxicity of 29% across 39 studies (3766 pts). Carotid blowout occurred in 41 (2.6%) of 1554 reirradiated pts with carotid involvement, with mortality in 29 (76%) of 38 with data. Mandibular osteoradionecrosis rates ranged 2% to 18%.
The technique statements track Vargo's multi-institutional comparison: in RPA class II, IMRT gave 2-yr OS 35.4% vs 18.6% for SBRT (p<0.001), but the difference vanished for ≥35 Gy in five fractions to ≤25 cc or T1-T2 targets. The 66 Gy threshold comes from Caudell's 505-pt cohort (2-yr OS 49.3% with ≥66 Gy vs 34.2% at 60.0-65.9 Gy vs 30.4% below 60 Gy), the same cohort that found no locoregional-control or OS gain from elective nodal irradiation.
Agreement was computed with no-opinion votes left in the denominator, so a statement can read as moderate because panellists abstained rather than objected, and the text does not report how often that happened. Evidence levels are also assigned to the highest available direct evidence, so a level 3 label does not mean the specific dose corridor or margin was tested at that level.
The moderate-agreement statements are the informative ones: they mark where the field genuinely splits (cord and brainstem cumulative limits, hyperfractionation, SBRT dose), and the authors read that split as clinical uncertainty rather than process failure. Sequencing against first-line immune checkpoint inhibitors is explicitly left open, with no randomised data on whether to treat locally first or defer.
- Optimal sequencing of reirradiation vs first-line immune checkpoint inhibitors active SBRT +/- Pembrolizumab in Patients With Local-Regionally Recurrent or Second Primary Head and Neck Carcinoma Phase 2n=86 · primary completion 2027-07 · SBRT reirradiation +/- pembrolizumab, PFS 1° EPrecruiting Re-Radiochemotherapy and Pembrolizumab vs. Immuno(Chemo)Therapy for Locoregionally Recurrent PD-L1 Positive (CPS≥1) HNSCC Phase 3n=214 · primary completion 2032-12 · phase 3 re-CRT + sequential pembro vs pembro alone
- Validated tissue recovery factor for cord and brainstem cumulative dose
- Whether hyperfractionated reirradiation improves outcomes outside nasopharynx
📚 Sources · 📄 1 paper
BART
ForPost-cystectomy MIBC, pT3-4 / pN+ / R+, chemo-treated, no adjuvant IO
87.1% vs 76.0%
HR 0.43, 95% CI 0.20-0.96, p=0.04
TL;DR2yr LRFFS 87.1% vs 76.0% with adjuvant pelvic RT after cystectomy, HR 0.43 (0.20-0.96), p=0.04; OS unchanged.
Reported via UroToday →
The RT read is the per-protocol and subgroup magnitude: LRFFS HR 0.27 (0.10-0.71) among those actually irradiated, and HR 0.22 (0.06-0.75) in pN+. Target was cystectomy bed plus full pelvic nodes to 50.4Gy/28fx with stoma-sparing IMRT, a plan deliverable in standard practice, and late G3+ toxicity was 8.4% vs 10.5%. That moves the offer-RT decision for pN+ disease.
In pN+ or pT3-4 urothelial MIBC after cystectomy and cisplatin-based chemotherapy, this supports discussing adjuvant pelvic RT for locoregional control; it does not inform pts receiving adjuvant nivolumab, who were unrepresented here.
The deliverable read is technique plus magnitude: 50.4Gy/28fx to cystectomy bed and full pelvic nodes with stoma-sparing IMRT and daily IGRT, late G3+ 8.4% vs 10.5%, LRFFS HR 0.22 (0.06-0.75) in pN+. This moves the offer-adjuvant-RT decision for pN+ or margin-positive disease.
Chemotherapy was neoadjuvant in 71% and adjuvant in 20%, and no pt received immunotherapy, so this speaks to a failure mode the chemo backbone did not cover: 26% locoregional recurrence under observation. It does not change regimen choice, but it questions whether adjuvant nivolumab alone addresses pelvic failure.
With a median 20 nodes dissected and a 4.6% positive margin rate, locoregional recurrence still reached 26% without RT, so this is not attributable to inadequate surgery. For pT3-4, pN+, or R+ specimens, it argues for referral for adjuvant RT discussion rather than surveillance alone.
12 details 2 trials watching
Phase III multicenter RCT, 1:1 adjuvant radiotherapy versus observation, N=153 accrued 2016-2024 (RT 77, observation 76). Stratified by nodal stage (N0 vs N+) and chemotherapy timing. Median follow-up 47 months; per-protocol comparison by log rank, with Fine-Gray competing-risk subdistribution HRs for LRFFS (competing risks distant metastases, non-cancer death) and DFS.
High-risk non-metastatic urothelial MIBC post radical cystectomy: T3-4, N1-3, or R+. 62% pT3-T4, 41% pN+, variant histology component in 28%. Median age 57, median nodes dissected 20, positive margin rate 4.6%, neobladder in 2.6%.
Chemotherapy was neoadjuvant in 71% and adjuvant in 20%; 9.2% received none. No patient received immunotherapy in either arm.
50.4Gy in 28 fractions to the cystectomy bed and pelvic nodes. CTV covered common iliac, internal and external iliac, presacral and obturator nodes plus the cystectomy bed. Stoma and bowel sparing IMRT with daily onboard image guidance. 63 of 77 allocated received planned RT.
Primary: 2-year locoregional failure-free survival. Secondary: bladder cancer-specific survival, disease-free survival, overall survival.
Primary endpoint met. Overall 37% recurred, 18% locoregionally (8% RT vs 26% observation, p=0.006), and there were no isolated locoregional recurrences in the RT arm. Survival endpoints all favored RT numerically without reaching significance.
| Endpoint | Adjuvant RT | Observation | Effect size |
|---|---|---|---|
| LRFFS (primary) | 87.1% | 76.0% | HR 0.43 (0.20-0.96), p=0.04 |
| LRFFS per protocol | 93.2% | 75.0% | HR 0.27 (0.10-0.71), p=0.008 |
| DFS | 71.6% | 58.7% | HR 0.62 (0.36-1.05), p=0.07 |
| Bladder cancer-specific survival | 79.6% | 65.0% | HR 0.59 (0.33-1.10), p=0.09 |
| Overall survival | 70.4% | 57.4% | HR 0.78 (0.49-1.26), p=0.31 |
Grade 3 GI events were low and no higher with RT (1.6% vs 4.1%); the cost was grade 2 GI (17.5% vs 1.4%) with no toxicity-related discontinuation. Late grade 3+ toxicity was similar (8.4% vs 10.5%, p=0.60).
The comparator that defines current adjuvant practice is CheckMate 274 (adjuvant nivolumab), which no BART patient received, so this addresses a locoregional failure mode nivolumab was never shown to control. Prior adjuvant RT evidence in this space is the smaller Egyptian NCI randomised experience; BART is described as the largest RCT here.
Accrual over eight years fell short of target, so the survival endpoints are underpowered rather than negative: the OS CI (0.49-1.26) is compatible with both a substantial benefit and modest harm. 14 of 77 allocated to RT never received it and were analyzed with observation (n=90), which is the per-protocol comparison the headline HR 0.27 comes from.
This establishes that pelvic RT after cystectomy does what RT does elsewhere: it controls the field it treats, at an acceptable late-toxicity cost. What it does not establish is whether preventing a locoregional recurrence in a disease this systemically aggressive translates into survival, which the planned MERCY IPD meta-analysis is meant to answer.
CONSORT flow
Randomised, primary endpoint met, prespecified stratification. Adjuvant RT is not standard post-cystectomy; this is the first positive phase III. Underpowered for OS, no IO backbone.
- Does locoregional control translate into an overall survival benefit active Adjuvant Radiotherapy in Patients With Pathological High-risk Bladder Cancer (GETUG-AFU 30) Phase NAn=81 · primary completion 2027-12 · randomised adjuvant pelvic RT post-RC + PLND
- Adjuvant radiotherapy combined with adjuvant immunotherapy recruiting Adjuvant Concurrent Immunotherapy and Radiotherapy for the Treatment of Bladder Cancer Phase 1n=10 · primary completion 2027-04 · phase 1 concurrent adjuvant IO + RT safety
- Generalizability to older pts with limited lymphadenectomy
📚 Sources · 📄 1 paper
Abstract
DOREMY NCT02106312
ForLocalized translocation-confirmed myxoid liposarcoma, trunk or extremity, resectable
TL;DR5yr LRFS 97.4% after 36Gy/18fx preop RT in myxoid liposarcoma, wound complications 21%, median f/u 66.4mo.
The number that moves the dose decision is 97.4% 5yr LRFS at 36 Gy, matched to a 21% wound complication rate, with only 3% late G3. Dose is 2 Gy daily to 36 Gy preop, standard fractionation, so it transfers directly. This is a de-escalation read confined to translocation-confirmed MLS.
In localized translocation-confirmed myxoid liposarcoma of trunk or extremity going to resection, this supports 36 Gy preop as a discussed option in place of 50 Gy; it does not extend to other soft tissue sarcoma histologies, which were not enrolled.
36 Gy in 2 Gy daily fractions preop yielded 97.4% 5yr LRFS (95% CI 93.9-100%) at median 66.4 mo, with late G3 in only 3%. Standard fractionation, no special technique required, so the de-escalation from 50 Gy transfers directly in translocation-confirmed MLS.
The surgical read is the wound complication rate: 21% overall, 16% needing intervention, after preop RT at the reduced dose. Whether that beats 50 Gy is untested here (no comparator arm), but it is the number to weigh against reconstruction planning in trunk and extremity resections.
10 details 1 trial watching
Prospective, single-group, phase 2 nonrandomized trial across 9 tertiary sarcoma centers in Europe and the US. Enrollment ran November 2010 to May 2020; data analyzed January to December 2025. Median follow-up 66.4 months (IQR 48.8-87.5).
Adults with biopsy-proven and translocation-confirmed localized myxoid liposarcoma of the trunk or extremity. N=90, mean age 47 (SD 13.1), 50 (56%) male.
Preoperative RT to a reduced dose of 36 Gy in once-daily 2-Gy fractions, followed by resection. Delivered per protocol in all patients. Three pts (3%) did not proceed to surgery because of intercurrent metastatic disease.
Long-term local recurrence-free survival, progression-free survival, disease-specific survival, overall survival, and late toxic effects. No single stated primary endpoint for this long-term analysis.
Wound complications in 18 pts (21%), with 14 (16%) requiring intervention. Late toxic effects were grade 2 in 13 pts (15%) and grade 3 in 3 pts (3%).
The authors argue the long-term data support adopting 36 Gy as an option through shared decision-making, explicitly on the grounds that a phase 3 trial is impractical in a rare cancer. That is an argument about feasibility, not about evidence level, and the reader should price it as such.
Fourteen-year accrual window spans changing surgical and imaging practice, so the wound complication rate reflects a long era rather than current technique. Late toxicity is reported only as pooled grade counts, without organ or site attribution, which limits comparison against 50 Gy series.
| Endpoint | 5yr rate | 95% CI |
|---|---|---|
| Local recurrence-free survival | 97.4% | 93.9-100% |
| Progression-free survival | 81.0% | 72.6-89.4% |
| Disease-specific survival | 89.5% | 82.6-96.4% |
| Overall survival | 88.5% | 81.2-95.8% |
Single-arm phase 2, no randomised 50 Gy comparator; authors concede phase 3 impractical in a rare histology. Long f/u strengthens but does not replace randomisation.
- Wound complication rate vs 50 Gy in a randomised comparison n=300 · primary completion 2031-01 · prospective MLS registry, 36Gy vs 50Gy preop arms
- Whether dose reduction extends to other translocation-driven sarcoma subtypes
- Local control beyond 10 years
📚 Sources · 📄 1 paper
Abstract
GEC-ESTRO Breast Cancer Working Group APBI patient selection recommendations
TL;DRUpdated APBI selection criteria collapse to two groups (low-risk eligible, high-risk contraindicated), widening eligibility to pT1-2 ≤30mm, pN1mi, any histology.
The eligibility boundary moved, not the technique: pN1mi and multifocal disease within 2 cm are now inside the low-risk group, and the ceiling is 30 mm across all histologies. The 2010 intermediate tier is gone, so the contralateral question at consent is binary. BRCA 1-2 carriers are contraindicated regardless of age.
In a woman over 40 post-lumpectomy with a 25 mm pT2 pN1mi tumor and clear margins, this supports offering APBI where the 2010 criteria would not have; it does not extend to triple negative, BRCA carriers, or an unstaged axilla.
The eligibility boundary moved, not the technique: pN1mi and multifocal disease within 2 cm are now inside the low-risk group, with a 30 mm ceiling across all histologies. The intermediate tier is gone, so the APBI-vs-whole-breast conversation is binary. No dose, fractionation or target volume is specified in source.
Margin status is the surgical lever: a negative invasive margin qualifies, but DCIS requires ≥ 2 mm, so a close DCIS margin decides re-excision vs losing APBI eligibility. Unknown axillary status (pNx) is a contraindication, so skipping staging forecloses the option; pN1mi does not.
9 details
Evidence-based recommendation update from the GEC-ESTRO Breast Cancer Working Group. Systematic search 2010 to 2024 across PubMed, Medline, Scopus and Cochrane returned 618 articles, supplemented by reference lists, conference abstracts and book chapters. Ten prospective randomized trials and seven retrospective comparative studies with ≥ 5 yr median follow-up formed the evidence base.
Applies to pts after breast-conserving surgery being considered for partial breast irradiation. The low-risk group is age > 40 yr, unifocal or multifocal within 2 cm, pTis or T1-2 (≤ 30 mm), pN0 or pN1mi, all histology types, no EIC, no extensive LVI, negative invasive margins (≥ 2 mm for DCIS).
The document addresses who gets APBI, not how. No dose, fractionation, technique (brachytherapy vs external beam) or target-volume recommendation is given in the source text.
Two categories replace the prior scheme: low-risk good candidates and high-risk contraindicated. Contraindications are BRCA 1-2 mutation, age < 40 yr, positive invasive margins (< 2 mm for DCIS), multicentric or > 30 mm disease, triple negative, EIC positive, extensive LVI, and ≥ pN1a or pNx.
| Criterion | Low risk (APBI suitable) | High risk (APBI contraindicated) |
|---|---|---|
| Age | > 40 years | < 40 years |
| Germline | not specified | BRCA 1-2 mutation |
| T stage / size | pTis, T1-2 (≤ 30 mm) | > 30 mm |
| Focality | unifocal or multifocal within 2 cm | multicentric |
| Nodal status | pN0 or pN1mi | ≥ pN1a, or unknown axilla (pNx) |
| Histology | all histology types | triple negative |
| EIC | absent | EIC positive |
| LVI | no extensive LVI | extensive LVI |
| Margins | negative for invasive (≥ 2 mm for DCIS) | positive for invasive (< 2 mm for DCIS) |
Recommendation strength per criterion is not reported in the source text, so a reader cannot tell which thresholds rest on randomized data and which on panel opinion. The evidence base mixes ten randomized trials with seven retrospective comparative series without stated weighting.
The direction of travel is eligibility expansion: the authors state the 2010 criteria can be significantly expanded so more pts may receive APBI in routine practice. What the document does not settle is whether the widened boundary holds at the margins it moved most, node-micrometastatic and multifocal disease, where the randomized APBI trials enrolled few pts.
- IBTR outcomes for APBI in pN1mi disease
- Whether multifocal disease within 2 cm carries equivalent in-field control
- Whether triple negative warrants blanket APBI exclusion
📚 Sources · 📄 1 paper
Abstract
WOLVERINE
ForOligometastatic prostate cancer, up to 5 mets, mostly castration-sensitive
TL;DRIPD meta-analysis of 6 randomised phase 2 trials, 472 pts: MDT improved PFS (HR 0.44, 0.35-0.56), OS non-significant (HR 0.63, 0.39-1.00, p=0.051).
Surfaced from a review's discussed trials
The endpoint that survives every sensitivity cut is PFS (HR 0.44, and 0.46 excluding the observation-SOC trials), while OS stops at HR 0.63 (0.39-1.00, p=0.051). CRFS 0.58 in CSPC is the more decision-relevant signal, since delaying castration resistance is what MDT is being asked to buy. Nothing here resolves dose, target, or which oligo burden benefits.
In castration-sensitive oligometastatic prostate cancer with up to five lesions and a treated primary, this supports adding MDT for progression-free and castration resistance-free benefit; it does not establish an OS benefit, and the CRPC-only and untreated-primary populations are thinly represented.
The endpoint that survives every sensitivity cut is PFS (HR 0.44, and 0.46 excluding the observation-SOC trials), and CRFS 0.58 in CSPC is what MDT is being asked to buy. None of the constituent trials' dose, fractionation or target-selection choices are resolved by pooling, and rPFS carried I²=50% heterogeneity, so how to deliver MDT stays a local decision.
MDT deferred castration resistance (CRFS HR 0.58) in the castration-sensitive subset (n=257), which is the sequencing-relevant read: the question is whether local therapy buys time before ARPI escalation. Note the SOC arm actually got MORE second-generation ARPI (59.8% vs 50.4%), so the systemic backbone was not favouring MDT.
10 details 5 trials watching
Systematic review and individual patient data meta-analysis (X-MET collaboration), PROSPERO CRD42023479078. Searched Embase, PubMed, CENTRAL, MEDLINE and ClinicalTrials.gov to Nov 3 2023, updated May 4 2025; dual independent screening in Covidence, Cochrane RoB 2.0. Of 2975 studies screened, 7 phase 2 trials randomising 574 men were included.
Published randomised prospective trials in oligometastatic (up to five metastases) prostate cancer with data sufficient for PFS and OS. Most patients were castration-sensitive (n=375, 65%); ARTO enrolled entirely CRPC and the two EXTEND baskets a CRPC subset. The primary tumour had received prior definitive local therapy in 491 patients (85.5%), required in every trial except the EXTEND baskets and ARTO.
Co-primary: progression-free survival and overall survival. Secondary: radiographic PFS and castration resistance-free survival. Primary analysis restricted to the six trials randomising MDT plus SOC versus SOC, with both a random-effects trial-level analysis and a patient-level analysis stratified by trial.
Effect sizes are in the endpoint table. Trial- and patient-level estimates agreed closely on all four endpoints, and OS showed HR<1 in every individual trial without reaching significance in aggregate.
The constituent trials are the ones that currently drive MDT practice: STOMP and ORIOLE (small randomised phase 2, ADT-free intervals and progression), ARTO (MDT added to abiraterone in CRPC), the two EXTEND hormone baskets, and the prostate subgroup of SABR-COMET (16 men). Pooling them raises precision on PFS but cannot add the phase 3 evidence none of them supply, and the ongoing randomised phase 3 programmes remain the gate.
The SOC arm was not one thing: observation in all or part of STOMP, ORIOLE and COMET-SABR, and second-generation ARPI use differed between arms (59.8%, n=134 in SOC vs 50.4%, n=125 in MDT), which cuts against MDT rather than for it. Four abstract-only randomised primary analyses could not supply IPD and were excluded, and the prostate contribution from SABR-COMET is 16 men.
PFS is where the estimate is tight and consistent; OS is where the question stays open, and at p=0.051 the honest read is an underpowered signal, not a negative result. The endpoint most likely to matter to practice is CRFS (HR 0.58) in castration-sensitive disease, because deferring castration resistance is the outcome MDT is being asked to deliver.
Pools only phase 2 trials with non-blinded randomisation and mixed SOC; co-primary OS missed (p=0.051). Supports existing MDT practice rather than establishing level 1 evidence.
- Does MDT extend overall survival in a phase 3 population active Prostate-cancer Treatment Using Stereotactic Radiotherapy for Oligometastases Ablation in Hormone-sensitive Patients Phase 3n=550 · primary completion 2026-06 · phase 3 SBRT to all oligomets, 550 pts, mHSPCrecruiting Veterans Affairs Seamless Phase II/III Randomized Trial of STAndard Systemic theRapy With or Without PET-directed Local Therapy for Oligometastatic pRosTate Cancer Phase 2/3n=464 · primary completion 2026-09 · seamless ph2/3, CRPC-free survival, PET-directedrecruiting Metastasis Directed Stereotactic Body Radiotherapy for Oligo Metastatic Hormone Sensitive Prostate Cancer Phase NAn=118 · primary completion 2031-12 · randomised ph3 MD-SBRT vs standard tx, 1-3 mets
- Optimal dose, fractionation and target selection for prostate MDT recruiting OligoCare TwiCs (Trials Within Cohorts) Trial Comparing Acute Toxicity in Single-fraction vs Multiple-fraction SBRT for Metastasis-directed Treatment (SPRINT) Phase NAn=302 · primary completion 2029-02 · single- vs multi-fraction SBRT, acute toxicity 1° EPrecruiting SBRT Versus Hypofractionated Radiotherapy for Biochemically Recurrent or Oligometastatic Prostate Adenocarcinoma Phase 3n=118 · primary completion 2030-01 · ph3 SBRT vs hypofx RT in oligomet/BCR prostate
- Upper bound on metastasis number that still benefits
📚 Sources · 📄 1 paper
Abstract
ORIOLE NCT02680587
ForHormone-sensitive oligorecurrent prostate ca, 1-3 mets on conventional imaging, ADT-free
19% vs 61%
7/36 vs 11/18, P=.005
TL;DR6-mo composite progression 19% vs 61% with SABR (P=.005); mPFS not reached vs 5.8 mo, HR 0.30.
Surfaced from a review's discussed trials
The actionable RT parameter is target selection, not dose: 16 of 36 SABR pts had PSMA-avid lesions left untreated because planning was blinded to PET, and those men progressed at 38% vs 5% by 6mo (distant MFS 6.0 vs 29.0mo, HR 0.19). That argues total consolidation of PET-avid disease, so PSMA-PET-based planning is the decision this moves.
In hormone-sensitive oligorecurrent prostate cancer with 1-3 conventionally imaged mets and no recent ADT, this supports deferring ADT with SABR to all PET-avid sites; it does not speak to de novo synchronous oligometastatic or castration-resistant disease.
Target selection, not dose, is the transferable parameter: planning was blinded to PSMA-PET, so 16/36 SABR pts had avid lesions untreated, and they progressed 38% vs 5% at 6mo with distant MFS 6.0 vs 29.0mo (HR 0.19). That argues for PET-based planning and total consolidation of avid disease. Dose and fractionation are not reported in source text.
The comparator here is observation with ADT deferral, not a systemic regimen, so the read is about sequencing: SABR pushed median PFS from 5.8 months to not reached in men deliberately kept off ADT. Whether that delay costs anything downstream is untested at 18.8 months median follow-up.
11 details 5 trials watching
Phase 2, 2-arm randomized trial across 3 US radiation facilities affiliated with one university hospital. 80 men screened, 54 randomized 2:1 to SABR or observation, accrual May 2016 to March 2018, data cutoff May 20 2019. Median follow-up 18.8 months (range 5.8-35.0).
Recurrent hormone-sensitive prostate cancer with 1 to 3 metastases detected on conventional imaging (CT, MRI, or bone scan), asymptomatic, arisen within the prior 6 months, no larger than 5.0 cm. Prior definitive treatment of the primary required; salvage prostate-bed or pelvic RT allowed. No ADT within 6 months of enrollment or 3 or more years total. Median age 68 in both arms; Gleason grade ran higher in the observation arm (mean 8 vs 7).
SABR to metastatic sites, with treatment planning blinded to PSMA-PET, so PET-avid lesions outside the conventional-imaging map were left untreated in 16 of 36 SABR pts. Dose and fractionation are not reported in the source text. Local control 98.9% at 6 months.
Primary: progression at 6 months, a composite of PSA rise, radiographic progression on conventional imaging, symptomatic progression, ADT initiation for any reason, or death. Secondary: SABR toxicity, 6-month local control, PFS, Brief Pain Inventory QoL, and concordance between conventional imaging and PSMA-PET.
No grade 3 or higher adverse events in either arm. No differences in Brief Pain Inventory scores between arms or within either arm over time.
Sits alongside STOMP, the other randomized trial of metastasis-directed therapy versus surveillance in oligorecurrent hormone-sensitive disease, and reaches the same directional conclusion from an independent population. What ORIOLE adds is the PSMA-PET consolidation question, which STOMP's choline-PET-selected design could not isolate.
The composite primary is driven partly by ADT initiation for any reason, a clinician decision made without blinding in an open trial, so the treating team's knowledge of arm allocation can move the endpoint directly. The PET-untreated-lesion comparison is a within-arm post-randomization subgroup (19 vs 16 men), not a randomized contrast, and the men whose conventional imaging missed more disease plausibly had more disease to begin with.
The trial makes two distinct claims and they carry different weight. That SABR beats observation on a 6-month composite in a 54-man phase 2 is a signal, not a standard; that leaving PSMA-avid disease untreated tracks with earlier and more distant failure is the finding that changed how the field plans these treatments, even though it rests on an observational contrast inside one arm.
CONSORT flow
Phase 2, N=54, 6-month composite primary including ADT initiation, median f/u 18.8mo. Hypothesis-generating for MDT; no OS or definitive endpoint.
- Does deferring ADT via SABR change overall survival n=162 · primary completion 2031-04 · randomises RDT alone vs RDT + ADT, PFS primary
- Optimal SABR dose and fractionation for prostate oligometastases recruiting OligoCare TwiCs (Trials Within Cohorts) Trial Comparing Acute Toxicity in Single-fraction vs Multiple-fraction SBRT for Metastasis-directed Treatment (SPRINT) Phase NAn=302 · primary completion 2029-02 · single- vs multi-fraction SBRT, acute toxicity primary
- Does PSMA-PET-guided total consolidation improve outcomes prospectively recruiting Treatment With Darolutamide +/- Radiation Therapy for Patients With a Castration Resistant Cancer and Metastases Detected by Functional Imaging Phase 3n=336 · primary completion 2029-10 · phase 3 darolutamide +/- SBRT to functional-imaging metsn=1000 · primary completion 2030-12 · prospective registry, PSMA PET-guided directed RTrecruiting Metastasis Directed Stereotactic Body Radiotherapy for Oligo Metastatic Hormone Sensitive Prostate Cancer Phase NAn=118 · primary completion 2031-12 · randomised MD-SBRT vs SOC, PSMA-PET-defined 1-3 mets
📚 Sources · 📄 1 paper
Abstract
EAU 2026: What Evidence Do We Have from Intensification with SBRT?
TL;DRSession review of MDT in oligometastatic prostate: ARTO the only randomised OS signal; no effect sizes reported in source.
Reported via UroToday →
Selection is the weak point, not delivery: eligibility still rests on a lesion count of up to five, while the PSMA PET burden analysis cited suggests imaging-derived burden stratifies more finely. Adding Ra-223 to MDT (RAVENS) gained neither PFS nor MFS, so intensifying the radiation side has no support yet; the live decision is whether to ablate at all outside metachronous oligorecurrence.
In metachronous oligorecurrent hormone-sensitive disease with a low lesion burden, this supports MDT to delay progression and defer systemic therapy; it does not extend to de novo synchronous presentation, where STAMPEDE2, PLATON, TERPS and OLIGOPRESTO are still accruing.
MDT is being asked to earn its place on selection, not technique: the up-to-five lesion cutoff is the enrolment gate across these trials, and RAVENS found no PFS or MFS gain from adding Ra-223 to ablation. Outside metachronous oligorecurrence the RT case is unproven, with STAMPEDE2, PLATON, TERPS and OLIGOPRESTO still accruing.
The systemic read is de-escalation, not addition: SOLAR (21 pts) asked whether testosterone can recover with PSA suppressed after MDT, and WOLVERINE delayed castration resistance without a significant OS gain. ARTO's OS and PCSS signal sits in castration-resistant disease, so it does not license dropping systemic therapy in hormone-sensitive pts.
9 details 3 trials watching
- 🔍 EAU 2026 thematic session talk (Fonteyne, Ghent), a round-up of prior trials, not a new dataset
- 🔍 De novo synchronous evidence is thin; STAMPEDE2, PLATON, TERPS and OLIGOPRESTO still accruing
- 🔍 SOLAR (21 pts) asked whether testosterone can recover with PSA suppressed after MDT
- 🔍 Eligibility still keys on a lesion count of up to five; PSMA PET burden proposed as a finer stratifier
- 📊 MDT evidence by setting, as characterised in the session (no effect sizes reported in source)
Trial Setting Reported signal STOMP / ORIOLE Metachronous oligorecurrent HSPC Local control, delayed progression, minimal toxicity RADIOSA Oligorecurrent HSPC ADT + MDT improved PFS vs MDT alone WOLVERINE Oligometastatic PCa PFS and rPFS improved, CRPC delayed, OS not significant ARTO Castration-resistant oligometastatic PFS plus OS and PCSS improved vs SOC alone RAVENS Oligometastatic PCa Ra-223 added to MDT: no PFS or MFS gain - 📊 ARTO framed as the first randomised trial suggesting an OS and PCSS benefit from adding MDT
- ⚠️ That OS signal is one trial, in castration-resistant disease, and unreplicated in this evidence base
- ⚠️ WOLVERINE gained PFS, rPFS and delayed CRPC, but no significant OS difference
- ⚠️ SOLAR vs SATURN (synchronous vs metachronous) is a cross-trial comparison, hypothesis-generating only
- Does MDT benefit de novo synchronous oligometastatic HSPC? not yet Radiotherapy for Prostate and Oligo-metastatic Lesions in Patients With Low-burden Oligo-metastatic Prostate Cancer Phase NAn=30 · primary completion 2025-09 · prospective prostate + oligomet RT in low-burden OMPCrecruiting Prostate Radiotherapy and Metastasis-Directed Therapy in Synchronous Oligometastatic Prostate Cancern=700 · primary completion 2028-12 · 700-pt registry, MDT SBRT in de novo synchronous
- Can systemic therapy be safely de-escalated after MDT?
- Which imaging or biomarker metric selects MDT candidates? not yet Maximal Cytoreductive Therapies on Post-treatment Metastases in Pts With mHSPC During Apalutamide Plus ADT Treatment Phase 2n=47 · primary completion 2025-12 · post-ADT PSMA PET oligopersistence gates MDT
📚 Sources · 📄 1 paper
Abstract
NRG Oncology RTOG 0539 NCT00895622
ForWHO grade 1-3 meningioma, newly diagnosed or recurrent, any resection extent
TL;DR10-yr PFS 85.2% observed low-risk, 72.2% intermediate-risk at 54 Gy, 42.5% high-risk at 60 Gy.
The transferable RT read is the target: 54 Gy/30 fx for intermediate-risk and 60 Gy/30 fx for high-risk, with grade 3+ RT-attributed toxicity 9.6% and 15.1%. Recurrent grade 1 salvaged with RT reached only 67.0% 10-yr OS, worse than upfront grade 2 post-GTR at 91.0%, which argues against deferring RT in a grade 1 you expect to recur.
In newly diagnosed WHO grade 2 meningioma after GTR, this supports upfront 54 Gy while NRG BN003 and ROAM read out; it does not speak to observation in that group, since no untreated grade 2 arm was enrolled.
The transferable parameters are 54 Gy/30 fx intermediate-risk and 60 Gy/30 fx high-risk, with grade 3+ RT-attributed toxicity of 9.6% and 15.1%. Recurrent grade 1 salvaged with RT reached only 67.0% 10-yr OS vs 91.0% for upfront grade 2 post-GTR, which argues against deferring RT in a grade 1 likely to recur.
Extent of resection carried more weight than histology: STR vs GTR gave PFS HR 2.58 (1.09-6.11) and OS HR 3.38 (1.28-8.91) on multivariable analysis. Even in observed low-risk grade 1 disease, 10-yr PFS was 88.0% after GTR vs 72.7% after STR, so a Simpson-grade decision at the first operation still shows at 10 years.
10 details 4 trials watching
Multi-arm prospective phase 2 trial (NCT00895622) of risk-adapted management, not randomised: each risk group followed its own assigned strategy. 244 consented, 165 eligible and treated per protocol. Original primary endpoint was 3-yr PFS, previously reported; this is the mature analysis with data cutoff 8/15/2023 and median follow-up 12.1, 12.0 and 11.1 years across the three cohorts.
Adults ≥18 with Zubrod 0-1 and histologically confirmed unifocal WHO grade 1-3 meningioma, newly diagnosed or recurrent, any resection extent, with centrally confirmed pathology. Median age 56, 62 in the high-risk group; 65.5% female overall. Recurrent disease made up 30.8% of the intermediate and 47.2% of the high-risk cohorts.
Group 1 (grade 1 post-GTR/STR) was observed only. Group 2 (recurrent grade 1, or newly diagnosed grade 2 post-GTR) received 54 Gy in 30 fractions. Group 3 (newly diagnosed grade 2 post-STR, newly diagnosed grade 3, or recurrent grade 2/3) received 60 Gy in 30 fractions.
The gradient tracks risk assignment cleanly at 10 years, and the two Cox covariates that survive adjustment are recurrent disease and subtotal resection, both for PFS and OS. See the cohort and covariate tables above.
| Cohort | Management | 10-yr PFS | 10-yr OS | 10-yr cum. incidence progression |
|---|---|---|---|---|
| Low (grp 1, n=60) | Observation | 85.2% (75.7-94.8) | 94.1% (87.6-100) | 8.9% (3.2-18.2) |
| Intermediate (grp 2, n=52) | RT 54 Gy | 72.2% (59.2-85.1) | 84.7% (74.2-95.2) | 21.2% (10.8-33.9) |
| High (grp 3, n=53) | RT 60 Gy | 42.5% (28.7-56.3) | 51.1% (37.0-65.2) | 39.3% (25.8-52.5) |
| Covariate | PFS HR (95% CI), p | OS HR (95% CI), p |
|---|---|---|
| Recurrent vs initial | 2.5 (1.01-6.18), p=0.047 | 2.86 (1.06-7.70), p=0.038 |
| STR vs GTR | 2.58 (1.09-6.11), p=0.031 | 3.38 (1.28-8.91), p=0.014 |
Grade 3+ AEs attributed to radiotherapy occurred in 5 pts (9.6%) of the intermediate-risk and 8 pts (15.1%) of the high-risk cohorts. Newly reported late events in the intermediate group were auditory and neurologic grade 3 plus one grade 4 hemorrhage. Zubrod, MMSE and neurologic function score were stable over time.
This is the mature counterpart to the trial's own 3-yr landmark reports and now sits as the benchmark alongside the ongoing de-escalation questions in NRG BN003 (NCT03180268) and ROAM/EORTC 1308, both of which test whether grade 2 post-GTR needs RT at all. Until those read out, the 10-yr PFS 72.2% and OS 84.7% here are the reference numbers for treating that group.
Pathology was graded under the WHO criteria of the enrolment era, so some group 1 tumors would likely be reclassified today, which is the trial's own proposed explanation for the poor recurrent grade 1 outcomes. Subgroup estimates rest on very small denominators, with intervals such as 15.0% (0-42.0%) for recurrent grade 2 PFS that cannot support a practice decision on their own.
The trial settles the low-risk question (observe after GTR, 10-yr PFS 88.0%) and confirms that high-risk disease is not controlled by 60 Gy, with 10-yr PFS 42.5%. What it cannot settle is whether the intermediate-risk result reflects RT or favorable biology, since no group 2 patient went untreated.
Non-randomised risk-adapted phase 2 with mature 10+ yr follow-up; supports existing consensus (observe post-GTR grade 1, RT otherwise) rather than testing it against a control.
- Does grade 2 meningioma post-GTR need adjuvant RT at all recruiting Observation or Radiation Therapy in Treating Patients With Newly Diagnosed Grade II Meningioma That Has Been Completely Removed by Surgery Phase 3n=163 · primary completion 2027-06 · randomised RT vs observation, GTR grade II
- Whether molecular classification reassigns recurrent grade 1 tumors n=210 · primary completion 2026-03 · methylation + histone PTM signature for recurrence
- How to improve first-line treatment for high-risk meningioma recruiting Vismodegib, FAK Inhibitor GSK2256098, Capivasertib, and Abemaciclib in Treating Patients With Progressive Meningiomas Phase 2n=124 · primary completion 2027-01 · mutation-matched targeted arms, progressive tumorsactive A Trial of Increased Dose Intensity Modulated Proton Therapy (IMPT) for High-Grade Meningiomas Phase NAn=21 · primary completion 2027-08 · dose-escalated IMPT, STR grade II / grade III
📚 Sources · 📄 1 paper
Abstract
FIRESTORM
ForHigh-risk meningioma (WHO gr 2 post-STR, recurrent gr 2, any gr 3), postop RT
HR 0.40
95% CI 0.24-0.69, P = .001 (MVA); IPTW HR 0.45 (0.24-0.83)
TL;DR5-yr PFS 65.8% vs 38.8% with dose-escalated postop RT (BED ≥79.2 Gy) in high-risk meningioma; MVA HR 0.40.
The benefit survives the obvious confounders: excluding the 35 single-fraction SRS cases from SD-RT, DE-RT still gave 5-yr PFS 65.8% vs 41.7% (HR 0.56, 0.36-0.86), and photon-alone escalation matched carbon on PFS (68.3% vs 61.1%) with 0% grade ≥3 radionecrosis. That makes 66-70 Gy conventionally fractionated photons the practical escalation route, not particle referral.
In a subtotally resected WHO grade 2 or any grade 3 meningioma being planned for postoperative RT, this supports considering escalation beyond 60 Gy/30 fx rather than defaulting to it; it does not speak to gross-totally resected grade 1 disease.
Photon-alone escalation to 70 Gy/35 fx or 66 Gy/33 fx matched carbon on 5-yr PFS (68.3% vs 61.1%) with zero grade ≥3 radionecrosis, versus 9.1% in the carbon subgroup. Boost PTV margins were 0.5 to 2 mm off cavity and residual tumor. That makes escalation a standard photon department decision, not a particle referral.
14 details
Individual patient-level meta-analysis pooling 248 patients from 7 international institutions, all retrospective except one prospective trial. Median follow-up 67.1 months (range 2.13-178). PFS was the primary outcome, analyzed by Kaplan-Meier, Cox MVA, and IPTW propensity weighting.
High-risk meningioma per RTOG 0539: newly diagnosed WHO grade 2 after STR/biopsy, any recurrent grade 2, or any grade 3. 188 (75.8%) were grade 2, 103 (41.5%) recurrent, and 182 (75.2%) had Simpson grade 4/STR. Median age 60; 55 (22.2%) had prior RT.
DE-RT was defined by biologically effective dose ≥79.2 Gy (equivalent to 66 Gy in 33 fractions) or receipt of a carbon-ion boost; anything below that threshold counted as SD-RT. Photon DE-RT used a sequential or simultaneous integrated boost with a 0.5 to 2 mm PTV margin, versus 1-2 cm CTV margins in the SD-RT arm. Carbon DE-RT boosted 16 Gy/8 fx after 50 Gy/25 fx photons with a 6 mm CTV margin.
Whole-cohort 3- and 5-yr PFS were 62.8% and 45.0%. DE-RT improved 3-yr (86.4% vs 55.6%) and 5-yr PFS (65.8% vs 38.8%), P = .0022, holding on stratified Cox by grade (HR 0.40, 0.22-0.73) and after IPTW (3-yr 84.7% vs 55.8%). OS was not improved on MVA or IPTW.
| Subgroup | 3-yr PFS DE-RT vs SD-RT | 5-yr PFS DE-RT vs SD-RT | MVA HR (95% CI) | P |
|---|---|---|---|---|
| Simpson 1-3 | 87.5% vs 55.9% | 70.0% vs 40.0% | 0.31 (0.08-1.14) | .08 |
| Simpson 4-5 | 86.3% vs 55.4% | 63.3% vs 38.4% | 0.55 (0.36-0.84) | .006 |
| Cohort | Any-grade RN | Grade ≥3 RN |
|---|---|---|
| DE-RT overall | 20 of 59 (33.9%) | 3 of 59 (5.1%) |
| DE-RT mixed carbon/photon | 15 of 33 (45%) | 3 of 33 (9.1%) |
| DE-RT photon-alone | 5 of 26 (19.2%) | 0% |
| SD-RT | 25 of 189 (13.2%) | 6 of 189 (3.2%) |
Any-grade radionecrosis was 33.9% with DE-RT vs 13.2% with SD-RT (P = .001), but grade ≥3 RN did not differ (5.1% vs 3.2%, P = .47). All 3 grade ≥3 events in the DE-RT arm occurred in the mixed carbon-photon cohort; the photon-alone DE-RT cohort had none, and its any-grade RN rate was not significantly higher than SD-RT (P = .41). One grade 5 event occurred in each arm.
Published series anchored on RTOG 0539 report 5-yr PFS of roughly 40% to 60% with 60 Gy/30 fx, which is what the SD-RT arm reproduces (45.0% overall). The escalation signal draws on MARCIE (carbon boost) and the Zeng et al. photon series, both contributors to this pool, so the comparison is partly internal rather than independent.
DE-RT was delivered at only 2 of 7 institutions, one carbon-only and one photon-only, so treatment arm is nearly collinear with center, and unmeasured practice differences (DOTATATE PET planning, response assessment, supportive care) travel with it. Molecular classification was unavailable, and P values were not adjusted for multiple testing across the subgroup analyses.
The Simpson 1-3 subgroup showed absolute separation as large as Simpson 4-5 (5-yr PFS 70.0% vs 40.0%) without reaching significance (P = .08 on MVA), which the authors attribute to a smaller GTR subset and fewer events rather than an absent effect. Whether escalation belongs in fully resected disease is the open question, and the PFS-only benefit means the case rests on avoiding local progression and its neurologic morbidity, not on survival.
Retrospective IPD pooling, DE-RT confined to 2 centers, no randomization; IPTW cannot remove selection. Direction consistent across every sensitivity analysis, but prospective randomization still needed.
- Benefit of dose escalation after gross total resection
- Whether molecular subgroups predict DE-RT benefit
- Prospective randomized confirmation of the PFS signal
📚 Sources · 📄 1 paper
Abstract
RAPCHEM (BOOG 2010-03) NCT01872975
ForcT1-2 (<5cm) cN1 breast cancer, post-neoadjuvant chemo and surgery
2.9% (24/838)
Low 2.4%, intermediate 3.2%, high 2.8%
TL;DR10yr locoregional recurrence 2.9% (24/838) with response-adapted RT after neoadjuvant chemo; 2.4% in the RT-omission-eligible low-risk group.
Reported via The ASCO Post →
The allocation rule, not the recurrence rate, is the transferable part: ypN0 after mastectomy received no RT at all and still ran 2.4% at 10yr, and ypN1 pts had regional nodes omitted entirely. Dose, fractionation and target-volume detail are not reported in source, which limits direct transfer.
In cT1-2 cN1 pts who convert to ypN0 after neoadjuvant chemotherapy, this supports the safety of a de-escalated RT volume over 10 years; it does not extend to cN2-3 disease, and the randomised comparison remains open.
The transferable content is the allocation rule: ypN0 after mastectomy got no RT and ran 2.4% at 10yr, ypN1 had regional nodes omitted at 3.2%. Dose, fractionation and target volumes are not reported in source, so the volume decision transfers but the technique does not.
The de-escalation is entirely downstream of chemotherapy response: nodal clearance after neoadjuvant treatment is what unlocks the smaller RT volume, which raises the stakes on regimen choice and on documenting response. It does not change drug selection or sequencing itself.
8 details 3 trials watching
Prospective multicentre cohort, N=848 across 17 Dutch centres, accrued 2011-2015, presented at EBCC15 with 10-year follow-up; 838 completed follow-up. Not randomised: every patient received the RT volume their risk group assigned.
Breast tumour under 5 cm with 1 to 3 involved lymph nodes at presentation, treated with neoadjuvant chemotherapy then surgery (BCS or mastectomy). Most underwent axillary lymph node dissection.
Volume was set by post-chemotherapy nodal status. ypN0: breast RT after BCS, none after mastectomy. ypN1: breast or chest wall only, regional nodes omitted. ypN2+: breast or chest wall plus regional nodal irradiation. Dose and fractionation are not reported in source.
24 of 838 (2.9%) had a locoregional recurrence without distant spread at 10 years. Per-group counts appear in the detail table; the rates do not separate across strata.
The randomised test of this exact question is NSABP B-51/RTOG 1304 (NCT01872975), which the investigators expect in about 3 years; until then no trial has randomised ypN0 pts to nodal RT versus omission. Prior nodal-RT evidence (MA.20, EORTC 22922) was built in upfront-surgery populations, so it cannot arbitrate a post-chemotherapy response-adapted rule.
The 2.9% rate is uninterpretable without a comparator: a low event count in a de-escalated cohort is equally consistent with the omitted RT having been unnecessary and with the cohort being low-risk to begin with. ALND staging also means the ypN0 label carries more information than a modern sentinel-node ypN0 does.
The finding that recurrence is flat at 2.4% / 3.2% / 2.8% across escalating risk is the intended signal: the added RT in the higher strata may be doing the work that keeps them level with the low-risk group. It does not settle whether the low-risk group needed any RT, only that the allocation rule did not produce a visible failure.
Single-arm prospective cohort with no randomised comparator; allocation used ALND-era nodal staging. Confirmatory randomised answer (NSABP B-51) still pending.
- Does response-adapted RT omission hold under sentinel-node-only staging?
- Late toxicity avoided by omitting regional nodal irradiation n=827 · primary completion 2029-12 · randomised WBI alone vs WB+RNI in pN1 post-BCSnot yet A Study of Postoperative Regional Nodal Radiotherapy in Intermediate-risk Breast Cancer Phase 3n=3142 · primary completion 2032-12 · phase 3 RNI vs no RNI, toxicity evaluated
- Distant recurrence and survival in the de-escalated groups not yet A Study of Postoperative Regional Nodal Radiotherapy in Intermediate-risk Breast Cancer Phase 3n=3142 · primary completion 2032-12 · tumor-free survival non-inferiority without RNI
📚 Sources · 📄 1 paper
Abstract
AREST
ForpT1-2N0 oral SCC post adequate resection, ≥1 intermediate-risk feature
HR 0.52
95% CI 0.30-0.91, p=0.02; 3yr LRFS 89.2% vs 80.9%
TL;DR3yr LRFS 89.2% vs 80.9% with adjuvant RT after adequate resection of intermediate-risk pT1-2N0 OSCC; HR 0.52, no OS gain.
Transfer hinges on the surgery: benefit was shown only after margins ≥5mm and a ≥16-node level I-III dissection, so a lesser neck operation is not the population studied. Per-protocol the effect strengthens (HR 0.43, 91.1% vs 80.9%), and competing-risk LRF ran 10.6% vs 18.9%. Dose was 60Gy/30fx to bed plus at-risk nodes.
In an intermediate-risk pT1-2N0 oral tongue resection, this is the first randomised evidence supporting adjuvant RT for loco-regional control, with no survival gain shown; buccal mucosa benefit looked smaller and stays exploratory, and node-positive or close-margin disease sits outside the trial.
The target was the resected bed plus at-risk neck at 60Gy/30fx, so this transfers directly to standard post-op practice with no unusual technique requirement. Per-protocol the estimate strengthens to HR 0.43 (91.1% vs 80.9%), so the ITT figure likely understates a completed course. No toxicity data to set against it.
RT was only tested after margins ≥5mm and a ≥16-node level I-III dissection, so the referral question sits downstream of node yield and margin width. A neck below that bar is outside the evidence entirely, and the features driving the referral (DOI ≥5 to ≤10mm, PNI, LVE, poor differentiation) come off the specimen.
| Arm | 3yr LRFS (95% CI) | HR (95% CI) | p |
|---|---|---|---|
| Adjuvant RT | 89.2% (84.3-93.3) | 0.52 (0.30-0.91) | 0.02 |
| Observation | 80.9% (74.6-86.1) | reference | n/a |
8 details 3 trials watching
Multicentre open-label phase III RCT from India, 1:1 randomisation, N=392 (191 adjuvant RT, 201 observation), stratified by oral cavity subsite, PNI/LVE and differentiation. Median follow-up 47.2 months (IQR 30-59.4).
pT1-2, pN0 OSCC after adequate surgery, defined as clear margins ≥5mm plus at least ipsilateral level I-III neck dissection yielding ≥16 nodes. At least one intermediate risk factor required: DOI ≥5 to ≤10mm, PNI, LVE, or poor differentiation. Baseline characteristics reported as balanced.
60Gy in 30 fractions over 6 weeks to the resected tumour bed and the at-risk neck nodal region. Technique, target volume detail and dose constraints are not reported in the source.
Primary: loco-regional recurrence-free survival, from randomisation to first documented local and/or regional recurrence of the index cancer. Kaplan-Meier 3-year point estimates with log-rank comparison; DFS and OS secondary.
Primary endpoint met on both ITT and per-protocol analysis, and reproduced in the competing-risk analysis. DFS and OS did not differ between arms.
| Analysis | Adjuvant RT | Observation | HR (95% CI), p |
|---|---|---|---|
| 3yr LRFS, per-protocol | 91.1% | 80.9% | 0.43 (0.23-0.80), p=0.01 |
| Cumulative LRF, ITT | 10.6% | 18.9% | 0.52 (0.30-0.91), p=0.021 |
| Cumulative LRF, per-protocol | 8.7% | 18.9% | 0.43 (0.23-0.79), p=0.007 |
The randomised adjuvant evidence in resected head and neck cancer (EORTC 22931, RTOG 9501) tested chemoradiation against radiation in high-risk disease defined by positive margins and extranodal extension, leaving the intermediate-risk indication to retrospective series, which the abstract itself names as the basis for the debate. This is the first randomised test of that indication in an adequately resected node-negative cohort.
The observation arm reached 80.9% 3-year LRFS against the 70% the sample size assumed, so the trial ran event-poor and the DFS and OS comparisons are underpowered rather than reassuring. No toxicity, xerostomia or quality-of-life data appear in the source, so the price of the local control gain is unquantified. The subsite effect is exploratory.
The whole content of the result is loco-regional control at a median 47.2 months, with no survival separation, so the decision turns on how the reader values preventing a recurrence in a cohort whose failures are visible and often salvageable. The exploratory oral tongue over buccal mucosa split, if it replicates, would narrow the indication rather than extend adjuvant RT to every intermediate-risk resection.
CONSORT flow
First randomised test of an indication previously grounded in retrospective data; primary endpoint met, but open-label and the gain is loco-regional only, no DFS or OS.
- Does the oral tongue vs buccal mucosa subsite effect replicate? recruiting A Study of Radiation Therapy After Surgery in People With Oral Tongue Squamous Cell Carcinoma Phase 2n=24 · primary completion 2027-06 · pT1-2 pN0-2b oral tongue only, post-op IMRT
- Toxicity and QoL cost of the loco-regional control gain recruiting A Study of Radiation Therapy After Surgery in People With Oral Tongue Squamous Cell Carcinoma Phase 2n=24 · primary completion 2027-06 · post-op IMRT sparing tongue site; QoL questionnairesnot yet A Study Evaluating the Contribution of Non-Coplanar Beam Arrangement in Reducing Toxicity in Radiotherapy for Upper Aerodigestive Tract Cancers Phase NAn=70 · primary completion 2028-02 · non-coplanar vs coplanar EBRT, OAR dose + xerostomia
- Whether longer follow-up reveals any survival difference
📚 Sources · 🐦 1 tweet · 📄 1 paper
#ASCO26
— Dr Rishabh Jain (@DrRishabhOnco) May 27, 2026
🗣️ The AREST trial tackles one of the biggest gray zones in oral cavity cancer.
After adequate surgery in pT1-2N0 OSCC with intermediate-risk features:
✅ Adjuvant RT improved loco-regional control
❌ No OS benefit observed
3-year LRFS:
🔹 89.2% vs 80.9%
🔹 HR 0.52… https://t.co/qsALPFX032 pic.twitter.com/F4XzTMETih
Abstract
COMPPARE
ForDe novo localized prostate cancer, excluding very high risk and metastatic
5.7% vs 6%
P=0.28, hypothesized 7% vs 15%
TL;DRProton vs IMRT: no difference in bowel urgency (5.7% vs 6%), ≥G2 GI toxicity (5.2% vs 5.6%), or 3yr disease control.
The spacer table is the actionable finding, not the modality comparison: 2yr GI G2+ fell to 4.4% (IMRT) and 4.7% (proton) with a spacer vs 7.2% and 8.7% without, P=0.009. Rectal separation, available at any IMRT center, delivered what particle therapy did not.
In de novo localized prostate cancer outside very high risk, this argues the rectal-sparing decision sits with spacer placement rather than referral to a proton center; it says nothing about late GU endpoints or very high risk disease.
The spacer stratum, not the modality arm, is where the toxicity separated: 2yr GI G2+ 4.4% (IMRT, spacer) and 4.7% (proton, spacer) vs 7.2% and 8.7% without, P=0.009. That moves the rectal-sparing decision toward spacer placement at your own center rather than proton referral.
| Outcome | Hypothesized IMRT | Hypothesized PT | Actual IMRT | Actual PT | P-value |
|---|---|---|---|---|---|
| Bowel urgency | 15% | 7% | 6% | 5.7% | 0.28 |
| Bowel frequency | 10% | 4% | 4% | 3.5% | 0.43 |
| GI toxicity CTCAEv5 ≥2 | 29% | 20% | 5.6% | 5.2% | 0.60 |
| Freedom from progression 3yr | 89% | 91% | 97.9% | 98.0% | 0.90 |
+2 more figures
| Group | 2yr cumulative CTCAE v5 GI G2+ | P |
|---|---|---|
| IMRT, no spacer | 7.2% (5.0%, 9.9%) | 0.009 |
| Proton, no spacer | 8.7% (5.0%, 14%) | |
| IMRT, spacer | 4.4% (2.8%, 6.4%) | |
| Proton, spacer | 4.7% (3.6%, 6.0%) |
8 details 4 trials watching
Prospective nonrandomised comparative-effectiveness cohort study funded by PCORI, comparing proton therapy and IMRT across 51 centers. Accrual 2524 pts from July 2018 to October 2022, allocated to a proton cohort (1500) and a photon cohort (1000).
All de novo prostate cancer except very high risk and metastatic. The exclusion is the boundary that matters: the pts in whom elective nodal coverage and integral dose arguments are strongest were never enrolled.
Primary: patient-reported bowel urgency and bowel frequency (EPIC) and CTCAE v5 ≥G2 GI toxicity, each powered at 90%. Freedom from disease progression at 3 years (PSA) was exploratory, not powered.
Every prespecified comparison was null. The more telling result is that observed rates undershot the design assumptions in both arms: ≥G2 GI toxicity 5.6% IMRT and 5.2% proton against 29% and 20% hypothesized.
Rectal spacer use separated the toxicity curves where modality did not. 2yr cumulative ≥G2 GI toxicity was 4.4% (2.8%, 6.4%) IMRT with spacer and 4.7% (3.6%, 6.0%) proton with spacer, vs 7.2% (5.0%, 9.9%) and 8.7% (5.0%, 14%) without, P=0.009 by Gray's test.
The ≥G2 GI rates here are far below the toxicity burden that motivated the proton hypothesis, and align with the modern IMRT plus spacer experience rather than the older photon series the 29% assumption was drawn from.
Cohort allocation, not randomisation, so the arms differ by referral pattern, geography, and insurance in ways baseline adjustment cannot fully absorb. The unequal cohort sizes (1500 vs 1000) reflect enrollment at proton-capable centers, not a design ratio.
A null comparative-effectiveness result in a low-event setting is weak evidence of equivalence and strong evidence that the toxicity target moved. The question the field now needs answered is late toxicity and second malignancy, which 3 years cannot address.
Nonrandomised prospective cohort comparison; residual confounding unaddressable. Null on every prespecified endpoint, but 3yr follow-up cannot capture the late toxicity protons are argued to prevent.
- Late GI and GU toxicity beyond 3 years n=303 · primary completion 2026-12 · proton vs IMRT hypofx registry, f/u to 2026n=400 · primary completion 2027-03 · randomised proton vs photon, late GI primary EPrecruiting Reduction of Gastrointestinal Toxicity in Prostate Cancer by Proton Spot Placement Phase NAn=500 · primary completion 2030-01 · proton LET vs rectal/bladder toxicity, n=500
- Second malignancy risk from integral dose
- Whether protons add anything once a spacer is placed n=50 · primary completion 2025-09 · 2-arm spacer trial in pts planned for proton
📚 Sources · 🐦 1 tweet
#COMPPARE early results: in localized #ProstateCancer, #proton therapy vs #IMRT showed no sig difference in pt-reported bowel urgency/frequency, ≥G2 GI toxicity, or 3-year biochemical control. Longer follow-up needed for late toxicity/long term outcomes #ASCO2026 pic.twitter.com/yli4l8nEOY
— QianJanieQin (@QianJanieQin) May 31, 2026
ROADS
ForResected brain metastasis >2 cm, post-op cavity radiation candidates
NR vs 17 mo
GammaTile vs SRS; no HR, CI, or p reported in source
TL;DRSurgical bed recurrence 1% with GammaTile brachytherapy vs 12% post-op SRS in resected brain mets >2cm, N=230.
The RT read is the bed-control mechanism: GammaTile puts dose in the cavity at resection, closing the gap where post-op SRS fails in cavities >2 cm, with median time to bed recurrence not reached vs 17 mo. LMD was 10% GT vs 3% SRS, so the trade is bed control against meningeal seeding when picking the cavity strategy.
In a resected brain metastasis larger than 2 cm being planned for cavity radiation, this questions post-op SRS as the default bed strategy; it does not extend to intact metastases, cavities under 2 cm, or pts already carrying leptomeningeal disease.
Bed control is the read: median time to bed recurrence not reached vs 17 mo with post-op SRS, in cavities >2 cm where SRS control is weakest, with radiation necrosis flat at 8% GT vs 7% SRS. LMD 10% GT vs 3% SRS is the counterweight when choosing the cavity strategy.
The cavity radiation decision moves into the operation itself: GammaTile is implanted at resection, so a met >2 cm being taken out becomes a pre-op discussion about tile placement rather than a post-op SRS referral. The 10% vs 3% LMD signal is the intraoperative trade to weigh.
| Endpoint | GammaTile | SRS |
|---|---|---|
| Time to surg bed recur | NR | 17 mo |
| Surg bed recur FS | NR | 11 mo |
| 2 yr OS | 62% | 36% |
10 details
Randomized trial of GammaTile brachytherapy vs post-op SRS after resection of a brain metastasis, N=230, reported as final results at ASCO 2026 (Weinberg). Randomization ratio, number of sites, and follow-up duration not reported in source.
Resected brain metastasis >2 cm, the size band where post-op cavity SRS control is weakest. Histology mix, number of brain metastases allowed, systemic disease status, and performance status not reported in source.
Experimental arm is GammaTile, a Cs-131 collagen tile implanted in the cavity at the time of resection, so dose starts without the post-op delay. SRS dose, fractionation, cavity margin, and time from surgery to SRS are not reported in source, and those are exactly the parameters that decide whether the control arm reflects the reader's own practice.
Primary I: time to surgical bed recurrence. Primary II: surgical bed recurrence-free survival. 2 yr OS is reported alongside them; the source does not state whether OS was a prespecified secondary.
Both primaries favor GammaTile with medians not reached vs 17 mo and 11 mo. No HR, confidence interval, or p-value appears in the source.
Radiation necrosis 7% SRS vs 8% GT, essentially flat. Leptomeningeal disease 3% SRS vs 10% GT is the signal that cuts against the arm winning on bed control; timing and denominators not reported in source.
Post-op cavity SRS became standard on N107C/CEC.3 and the MDACC randomized trial, both of which traded whole-brain neurocognitive toxicity for weaker bed control, with failure concentrated in larger cavities. ROADS attacks that residual failure directly rather than re-litigating whole-brain RT.
The 2 yr OS separation, 62% vs 36%, is far larger than bed recurrence alone (12% vs 1%) would mechanistically support, which points at arm imbalance, differential salvage, or systemic therapy that the source does not report. The trial is also inherently unblinded, and the LMD excess in the GammaTile arm has no reported timing to judge whether it is procedure-related seeding.
If the bed-control numbers hold in the full report, the cavity strategy for a large resected met becomes a surgical-planning decision made before the operation rather than a radiation-planning decision made after it. The OS claim should wait for the manuscript.
Randomized, both primaries reported, final analysis. Verdict held below practice-changing: conference-slide source with no HR, CI, or p-value, and unexplained LMD excess.
- Is the 2yr OS separation confirmed with hazard ratios and cause of death?
- Does the leptomeningeal excess with GammaTile reflect seeding or longer survival?
- Does the benefit hold against fractionated post-op SRS rather than single fraction?
📚 Sources · 🐦 1 tweet
🚨🚨 ASCO 2026 Final Results Randomized trial resected brain met Brachytherapy vs Post-Op SRS🚨
— PDBrown (@PDBrownOnc) May 30, 2026
- Incredible Surg Bed Control with Brachy (↑↑OS as well)
- Surg bed recurrence 12% SRS vs 1% GammaTile pic.twitter.com/PCTsCluyUd
SPIN Score (Celiac Plexus Radiosurgery) NCT03323489
ForPancreatic cancer with retroperitoneal pain considered for celiac plexus SRS
TL;DRPost-hoc predictors of pain response after celiac SRS: response 32% / 53% / 89% by 0 / 1 / 2 SPIN points.
The actionable RT read is timing, not technique: neurotoxic chemo exposure carried OR 5.1 (p=0.009) against response, so the referral decision moves earlier in the disease course, before oxaliplatin or taxane neuropathy. Celiac SRS is NCCN-listed and single-fraction, so the gate is who you irradiate and when, not dose.
In pancreatic cancer pts with retroperitoneal pain scoring above 6 and no prior neurotoxic chemo, this supports considering celiac SRS earlier rather than after systemic lines; it does not tell you what to do for the chemo-exposed, low-pain pt, where response was 32%.
The gate on celiac SRS is patient selection and timing, not plan quality: neurotoxic chemo exposure carried OR 5.1 (p=0.009) against pain response, and 2-point pts responded 89% vs 32% at 0 points. Argues for taking the referral early rather than as last-line salvage.
The variable that mattered is one med onc controls: prior neurotoxic chemotherapy predicted failure of celiac SRS (OR 5.1, p=0.009). For a pt with severe retroperitoneal pain, this argues for a celiac SRS referral alongside, not after, an oxaliplatin or taxane backbone.
| SPIN score | n | Pain response |
|---|---|---|
| 0 | 31 | 32% |
| 1 | 40 | 53% |
| 2 | 19 | 89% |
10 details
Post-hoc analysis of the pivotal single-arm phase 2 celiac plexus radiosurgery trial (NCT03323489), n=90 evaluable. Candidate baseline predictors screened by univariate then multivariate logistic regression, with only multivariate-significant variables carried into the score. Internal validation by bootstrap resampling, 500 iterations, for an optimism-corrected AUC.
Pain response per parent protocol: a ≥2-point reduction in average pain on the Brief Pain Inventory-Short Form, baseline to three weeks. Parent-trial response was 53% (95% CI 42-64%).
Only neurotoxic chemotherapy exposure (OR 5.1, p=0.009) and baseline pain intensity (OR 1.8, p=0.003) survived multivariate analysis; age and therapy line dropped out to collinearity. The resulting 2-point score separated response into 32% / 53% / 89%, with AUC 0.716 apparent, 0.714 optimism-corrected.
| Predictor | Univariate | Multivariate |
|---|---|---|
| Neurotoxic chemo exposure | OR 5.33 (2.13-13.4), p<0.001 | OR 5.1, p=0.009 |
| Baseline pain intensity | OR 1.73, p=0.003 | OR 1.8, p=0.003 |
| Age | OR 1.06, p=0.014 | lost significance |
| Therapy line | OR 0.65, p=0.04 | lost significance |
The score was derived and internally validated in the same 90 pts, so the bootstrap corrects optimism from resampling but not from the variable-selection step that preceded it. The 2-point stratum is n=19, and the dichotomy at pain >6 was picked from the same data that shows steeper response above 7 and 8.
The neurotoxic-chemo term is the interesting one because it is a timing variable a clinician controls, not a fixed patient trait: it implies referral for celiac SRS competes with the systemic sequence rather than following it. Whether that reflects true nerve injury blunting an ablative pain response, or confounding by later-line disease biology, the post-hoc design cannot separate.
Post-hoc derivation on the parent trial's own 90 pts; internal bootstrap only, no external cohort. Design dominates the read regardless of effect size.
- External validation of the SPIN score in an independent cohort
- Is neurotoxic chemo effect causal or a proxy for later-line disease
- Durability of pain response beyond the 3-week endpoint
📚 Sources · 🐦 1 tweet
Celiac SRS = convenient, effective tx for intractable pain, but who benefits most?
— Dr. Nina Niu Sanford (@NiuSanford) May 30, 2026
Post-hoc Ph2 analysis identified 2 response predictors (SPIN score): severe baseline pain & no prior neurotoxic chemo.
Supports earlier use before potential chemo neuropathy. #ASCO26 @OncoAlert pic.twitter.com/3qFYU6N1iD
Wait or Treat (NCT05236946) NCT05236946
ForMetastatic EGFR/ALK+ NSCLC, asymptomatic measurable brain mets, ECOG 0-2
sub-HR 0.35
95% CI 0.21-0.59, p<0.001; 2y icPD 21.7% vs 50%
TL;DRUpfront cranial RT cut intracranial progression (sub-HR 0.35, 0.21-0.59, p<0.001) but 2y OS favored delayed RT, 48% vs 60%.
The intracranial win is real (2y progression 21.7% vs 50%, sub-HR 0.35) yet does not convert: 2y OS 48% upfront vs 60% delayed, HR 1.45. With necrosis reported ~6% upfront vs none delayed, and RT dose/technique unstated in source, this moves the timing decision toward deferral with MRI q3m surveillance.
In treatment-naive EGFR or ALK-driven metastatic NSCLC with asymptomatic measurable brain mets starting a TKI, this supports deferring cranial RT with q3m MRI rather than treating reflexively; it says nothing about symptomatic mets, large or dominant lesions, or oncogene-negative disease.
This is a timing question, not an omission question: both arms got cranial RT, and deferring cost 2y intracranial progression of 50% vs 21.7% while sparing necrosis (~6% upfront vs none delayed). Dose, fractionation, and WBRT-vs-SRS are absent from source, which is what gates transferring the toxicity read to your own technique.
The delayed arm's 1y intracranial progression of 25.7% on TKI plus chemotherapy is the number that makes upfront RT deferrable: most asymptomatic brain mets did not declare themselves in the first year. Deferral is contingent on q3m MRI surveillance, not on the TKI alone.
+2 more figures
10 details
Phase III open-label RCT, single-centre (Tata Memorial, Mumbai), N=208 randomised 1:1 to upfront (n=105) vs delayed cranial RT, both on TKI plus chemotherapy. Stratified by GPA (0-2 vs >2) and synchronous vs metachronous BM. Median follow-up 30.6 mo (28.7, 36).
Metastatic NSCLC with an EGFR or ALK alteration, ECOG PS 0-2, radiologically measurable brain metastases that were completely asymptomatic. Number, size, and location of lesions are not reported in source.
Upfront arm received cranial RT at diagnosis; the delayed arm received it at intracranial progression or patient's wish, so both arms are RT-exposed and the question is timing, not omission. Dose, fractionation, and technique (WBRT vs SRS) are not reported in source, which is the main barrier to transferring this result.
Primary: intracranial PFS. Secondary: OS, PFS, toxicity, ORR, neurocognition, PROM. Surveillance was MRI brain q3m for the first year, then q6m, which is what makes a delayed strategy safe to run.
Primary endpoint met. Survival ran the other way: 2y OS 48% upfront vs 60% delayed, OS HR 1.45, reported by attendees rather than captured in the slide OCR.
| Timepoint | Upfront RT (n=105) | Delayed RT (n=103) |
|---|---|---|
| 1-year | 8.7% (2.9%, 14.5%) | 25.7% (16.8%, 34.7%) |
| 2-years | 21.7% (12.6%, 30.8%) | 50% (39.2%, 60.9%) |
| Sub-HR (95% CI) | 0.35 (0.21, 0.59), p<0.001 | ref |
Radiation necrosis ~6% in the upfront arm and none in the delayed arm per attendee reports, and described as less severe when delayed. Full toxicity tables, neurocognition, and PROM were secondary endpoints not reported in the source.
The intracranial magnitude sits alongside the older WBRT-era data (QUARTZ, and the historic SRS-vs-WBRT trials) in showing that cranial RT controls the brain without buying survival. What is new is testing it where a CNS-penetrant TKI is the competing intracranial therapy, a setting those trials predate entirely.
Single-centre and open-label, and the RT prescription is absent from the source, so a reader cannot tell whether the necrosis signal reflects WBRT, SRS technique, or concurrent TKI exposure. Median follow-up of 30.6 mo is short relative to expected survival in this population, and the OS comparison was a secondary endpoint, not powered.
The result splits the two things RT is usually credited with: it clearly buys intracranial control, and it clearly does not buy time. Whether the OS direction is a real cost of upfront RT or noise in an underpowered secondary is the open question, and it decides whether deferral is merely non-inferior or actually preferred.
CONSORT flow
Randomised phase 3, prespecified intracranial PFS met, but the survival signal runs opposite the intracranial win. Directly contests reflex upfront cranial RT.
- Does the OS direction hold with longer follow-up?
- Was cranial RT whole-brain or stereotactic, at what dose?
- Neurocognition and PROM outcomes by RT timing
📚 Sources · 🐦 3 tweets
#ASCO26 | Wait or Treat? Brain RT in EGFR/ALK+ NSCLC
— OncLive.com (@OncLive) May 29, 2026
Presented by Dr Anil Ramakant Tibdewal.
A landmark Phase III randomized trial from @TataMemorial addressed a long-standing question: should asymptomatic brain metastases in oncogene-driven NSCLC receive upfront cranial RT or… pic.twitter.com/lRy9CfyQ8r
Should asymptomatic brain mets await systemic response in front line within EGFR/ALK context? I think yes. Despite reducing icPD, delayed brain RT OS looked better and radiation necrosis didn’t occur vs 6% #ASCO26 pic.twitter.com/O6d7GrvtU4
— Dr Riyaz Shah (@DrRiyazShah) May 29, 2026
No improvement in survival with up front radiation. OS favored delayed radiation with 2y OS 48% with early radiation vs 60% in late (OS HR 1.45). Also, radiation necrosis less common and less severe in delayed arm. Each case unique but delayed approach appealing #ASCO26 pic.twitter.com/wIhjqxhSaq
— Stephen V Liu, MD (@StephenVLiu) May 29, 2026
EORTC Cutaneous Lymphoma Tumour Group RT Recommendations
TL;DRExpert-opinion dose recommendations consolidating reduced-dose RT (4-12 Gy) across cutaneous lymphoma subtypes; no randomised trials underpin any of it.
The operative number for an RT reader is the dose floor, not the ceiling: 8-12 Gy in two or three fractions holds ≥92% 1-yr local control in MF, while 4 Gy underperforms there but suffices for CD4+ small/medium T-LPD (100% remission, no relapses). That split is the prescribing decision, and it argues against one ultra-low-dose default across subtypes.
In a patient with a symptomatic MF plaque or an indolent pcMZL/pcFCL lesion, this supports prescribing 8-12 Gy rather than a 30-40 Gy course; it does not extend to advanced MF, Sézary syndrome, or DLBCL leg type, where the authors concede combined-modality room for improvement.
The prescribing decision is where the floor sits by subtype: 8-12 Gy in two or three fractions holds ≥92% 1-yr local control in MF, while 4 Gy underperforms there yet suffices for CD4+ small/medium T-LPD. Pair a 4 Gy start in indolent B-cell disease with a four-month response assessment and escalation to 24 Gy.
11 details 1 trial watching
Expert opinion from the EORTC cutaneous lymphoma tumour group, tabulating published retrospective and small prospective series (Tables 1 and 2) into a dose algorithm (Figs 2A/2B). No pooled estimate, no protocol-registered synthesis.
Covers MF, Sézary syndrome, pcALCL, CD4+ small/medium T-LPD, pcMZL, pcFCL, and DLBCL leg type. Explicitly excludes the aggressive CTCL variants (subcutaneous panniculitis-like, gamma/delta, CD8+ epidermotropic, NK/T), where the authors say low-dose RT has a limited role.
MF plaques/tumours 8-12 Gy in two or three fractions; low-dose TSEBT 8-12 Gy for palliation and up to 24 Gy pre-autologous transplant; pcALCL few relapses at 20 Gy, palliative 2×4 Gy; CD4+ T-LPD 4 Gy in two fractions; DLBCL leg type consolidation reduced to 30 Gy, with 20 Gy reported post-systemic. Modalities named: electrons, photons, kilovoltage X-ray, brachytherapy.
The efficacy signal is uniformly high ORR across the tabulated series, but the discriminating result is dose-dependent local control: ≥92% 1-yr local control after low-dose MF RT versus an inferior rate at 4 Gy, and 28% vs 5% local relapse for 4 Gy vs 8-50 Gy in the ILROG registry series (p < 0.001).
Grade 3/4 toxicity is absent across most tabulated low-dose series. The one clear dose-toxicity signal in MF local RT is 27% grade 3/4 following 12 Gy versus 0% after 4-8 Gy; a prospective DLBCL leg-type cohort reported 14%.
The reference frame is the 30-40 Gy conventional standard that governed cutaneous lymphoma until roughly two decades ago. This document formalises the retreat from it, but does so on a base the authors concede is retrospective, so it codifies practice already in motion rather than establishing it.
The dose tables mix single-lesion and per-patient denominators and span decades of technique, so a 4 Gy series and a 40 Gy series are not comparing like populations. Several tabulated rows report dose comparisons as n.s. in cohorts far too small to exclude a real difference, which is not the same as equivalence.
The unresolved question is not whether reduced dose works but where its floor sits, and the answer looks subtype-specific rather than universal. The authors' own response-adapted proposal (escalate to a cumulative 24 Gy for residual disease or failure after 4 Gy) concedes that 4 Gy alone is a starting position, not a definitive prescription.
- Dose floor for ultra-low-dose RT in indolent cutaneous B-cell lymphoma n=52 · primary completion 2025-12 · 4 Gy/2 fx in early-stage PCBCL, n=52
- Whether low-dose TSEBT plus immunotherapy prolongs remission in advanced MF/SS
- RT dose after systemic therapy in DLBCL leg type
📚 Sources · 📄 1 paper
DBCG IMN2 NCT06549920
ForNode-positive breast cancer, macrometastatic, adjuvant taxane/trastuzumab/AI era
HR 0.85
95% CI 0.76-0.94, p=0.0016; 15y OS 65.0% vs 60.8%
TL;DRIMNI cut 15y mortality: OS 65.0% vs 60.8%, adjusted HR 0.85 (0.76-0.94), p=0.0016, in 4541 node-positive pts.
The 1-3 node group (n=3100, HR 0.85, 0.73-0.97) is the whole point: that is exactly where guidelines allow IMNI omission, and no measured factor identified a safe-omission subgroup. Right-sided IMN CTV V90% coverage was 94.6% with 25% under 64.8%, so a modern gated VMAT plan should exceed the dose separation that produced this 4.2% 15y OS gain.
In macrometastatic node-positive breast cancer with 1-3 involved axillary nodes going to locoregional RT, this supports including the internal mammary chain rather than omitting it; it does not speak to pts treated with neoadjuvant systemic therapy, who were excluded.
The 1-3 node subgroup (n=3100, HR 0.85, 0.73-0.97) removes the usual reason to skip the IMN chain, and no measured factor found a safe-omission group. Right-sided IMN CTV V90% was 94.6% with a quarter under 64.8%, so gated VMAT should beat the dose separation that produced this 4.2% 15y OS gain.
Benefit persisted on a modern backbone: 96.2% of chemo pts got a taxane, 13.5% trastuzumab, aromatase inhibitors postmenopausal, and the absolute 15y OS gain of 4.2% matched IMN1's 4.7% from the pre-taxane era. Effective systemic therapy did not absorb the regional RT effect, so this argues against dropping locoregional RT as drugs improve.
12 details
Nationwide population-based prospective cohort across six Danish RT centres, 2007-14, allocating IMNI by tumour laterality (right yes, left no) under national guideline. N=4541 of 5206 assessed. Median follow-up 13.7 years for OS, 13.2 for distant metastasis; analysis was intention-to-treat by side.
Macrometastatic node-positive breast cancer receiving locoregional RT; median age 59; 68.3% had 1-3 positive nodes. Excluded: prior malignancy, bilateral disease, neoadjuvant systemic therapy, recurrence before RT, non-standard RT. Axillary surgery was always axillary dissection.
Chemotherapy was three cycles EC (epirubicin 900 mg/m2, cyclophosphamide 600 mg/m2) then three cycles docetaxel 100 mg/m2; 96.2% of chemo pts received a taxane. Tamoxifen premenopausal, aromatase inhibitor postmenopausal; trastuzumab concurrent with chemo and RT in HER2+ (13.5% overall).
48 Gy/24 Fx before Jan 2009 (26.2%), 50 Gy/25 Fx after (73.2%), 3D conformal wide tangents in free-breathing. IMN target was intercostal space 1-4; all pts had axilla level II-III plus interpectoral and level IV, with level I added for ≥6 positive nodes or <10 nodes removed. QA showed IMN CTV V90% 94.6% right vs 20.4% left.
Primary: overall survival. Secondary: breast cancer mortality and distant metastasis, both with non-breast-cancer death as a competing event. Cox models adjusted for age, menopausal status, histology, tumour size, and nodal count, stratified by IHC subtype and grade.
The OS point estimate sits on top of the EBCTCG regional-node meta-analysis rate ratio 0.90 (0.84-0.96) and of KROG 08-06's HR 0.87 (0.57-1.31), the only other 3D-based IMNI study, which was underpowered at n=735 and read as negative. It also reproduces DBCG IMN1's absolute OS gain of 4.7%, arguing the taxane/trastuzumab/AI era did not absorb the benefit.
Contamination runs both ways: 10.1% of left-sided pts (n=238) got IMNI and a quarter of right-sided pts had under 64.8% IMN coverage, so the observed gain likely understates a fully delivered one. Cardiac and lung toxicity were captured only as death, with no smoking, comorbidity, or cardiac-event data, and the era predates PET-CT staging and respiratory gating.
The ER-/HER2+ signal (HR 1.49, 0.98-2.25, interaction p=0.021) echoes Kyndi's DBCG 82b&c finding but conflicts with NSABP B-51, and the analysis was explorative without multiplicity correction, so it should not gate treatment. The medial/central plus ≥4 node cell (HR 0.98, 0.79-1.21) is the one group where benefit looks absent, matching IMN1's 0.91 (0.73-1.15).
| Endpoint | IMNI | No IMNI | Adjusted HR (95% CI), p |
|---|---|---|---|
| OS at 15y | 65.0% | 60.8% | 0.85 (0.76-0.94), p=0.0016 |
| BC mortality at 15y | 21.4% | 23.6% | 0.84 (0.74-0.95), p=0.0077 |
| Distant mets at 15y | 25.1% | 26.9% | 0.87 (0.78-0.98), p=0.026 |
CONSORT flow
Prospective nationwide cohort, prespecified primary endpoint, 13.7y follow-up; contradicts guidelines withholding IMNI at 1-3 nodes. Non-randomised laterality allocation keeps it below practice-changing.
- Effect of IMNI alongside immunotherapy and antibody-drug conjugates
- Is ER-/HER2+ a genuine predictive subtype for IMNI harm
- Safe RT omission in cN+ pts with pCR after neoadjuvant therapy
📚 Sources · 📄 1 paper
PEACE V-STORM NCT03569241
ForPelvic nodal oligorecurrence (≤5 nodes) on PET after radical local therapy
63% vs 76% at 4yr
HR 0·62 (80% CI 0·44-0·86), p=0·063; α set at 0·20
TL;DR4yr MFS 76% vs 63% with elective pelvic nodal RT over MDT, HR 0·62 (80% CI 0·44-0·86), p=0·063.
The clean radiation read is locoregional control, not MFS: 85% vs 62% at 4 years, HR 0·45 (80% CI 0·31-0·65), and pelvic nodal relapse fell from 29% to 8%. Toxicity did not follow the field: grade 2+ GI 9% vs 7%. Prostate bed inclusion, not pelvic volume, drove GI events (OR 4·6 [95% CI 1·5-15·8]).
In a man with ≤5 PET-positive pelvic nodes after prostatectomy or definitive RT, this supports treating the whole pelvis with a nodal boost rather than nodes alone when 6 months of ADT is being given; it says nothing about node-negative biochemical relapse or extrapelvic disease.
Field size is the whole question and locoregional control is the clean answer: 85% vs 62% at 4 years, HR 0·45, with pelvic nodal relapse 8% vs 29%. The deliverable is 45 Gy/25 fx whole pelvis to L4-L5 with a 65 Gy SIB, and the added pelvic volume cost nothing in GI toxicity (9% vs 7%); the prostate bed did (OR 4·6).
Both arms received an identical 6 months of ADT, so nothing here changes systemic choice, but ADT-free survival was 77% vs 60% at 4 years (HR 0·60) with median time off ADT beyond 48 months. For men who would otherwise be considered for ADT intensification on PSA doubling time, local therapy is competing for the same population.
8 details
Phase 2, open-label, randomised 1:1, investigator-initiated, 21 hospitals across Australia, Belgium, Italy, Norway, Spain and Switzerland. Recruited June 11, 2018 to April 30, 2021; median follow-up 50 months (IQR 42-58). Stratified by PET tracer (choline vs PSMA) and MDT type (sLND vs SBRT); participants and investigators unmasked.
Biochemical relapse after radical prostatectomy, postoperative RT, or definitive RT, with up to five PET-detected pelvic nodes (pelvis defined up to the aortic bifurcation, common iliac included). Bone, visceral, or above-bifurcation nodal disease excluded, as was previous RT overlapping current fields. Median age 70-71, median PSA at inclusion 1·00 vs 0·85 ng/mL, 91% and 86% EAU high-risk BCR, and 55-62% had a single positive node.
MDT arm: SBRT 30 Gy in 3 fractions every other day to 90% of the PTV with a 3 mm margin, or salvage lymph node dissection. ENRT arm: 45 Gy in 25 fractions to the whole pelvis on a modified RTOG 2009 template (upper limit L4-L5) with a simultaneous integrated boost to 65 Gy on PET-positive nodes; IMRT or rotational technique mandatory, with a benchmark-case QA programme. Prostate bed RT (≥66 Gy/33 fx) was advised for pT3-4, Gleason ≥8, or positive margins and given to 25% of MDT and 41% of ENRT pts.
Both groups received 6 months of LHRH agonist or antagonist, started no later than the first fraction (or day 1-10 postoperatively after sLND). Every patient who started intended local therapy plus ADT completed it. Physicians were instructed not to restart ADT absent clinical progression.
Primary: metastasis-free survival (any M1 on PET or death), with local or pelvic nodal relapse explicitly NOT counted as an event. Secondary: biochemical RFS, locoregional RFS, ADT-free survival, and late grade 2+ GU/GI toxicity to 48 months. OS, prostate cancer-specific survival, and time to castration resistance had insufficient events and are deferred.
Grade 2+ GU events above baseline at 4 years were 28% MDT vs 31% ENRT (absolute difference 3%, p=0·73) and grade 2+ GI 7% vs 9% (difference 2%, p=0·93). Most common grade 3 events were urinary incontinence (6% vs 10%) and diarrhoea (1% vs 2%). In post-hoc analysis the driver of toxicity was the prostate bed, not the pelvic volume: GI OR 4·6 (95% CI 1·5-15·8), p=0·0085 and GU OR 1·85 (0·95-3·60), p=0·068 with bed inclusion. No treatment-related deaths.
The single-arm GETUG-P07 OLIGOPELVIS reported 3-year bRFS of 45% for ENRT against 57% at 4 years here, though its median PSA was 3-4 ng/mL and staging was choline-based, so the populations differ. Against the ADT-intensification trials, EMBARK and PRESTO enrolled the PSA-doubling-time population that simulations put at up to 40% pelvic nodal relapse on PET, and this trial's median time off ADT exceeded 48 months in MDT and was not reached in ENRT, versus 13-18 months with RT alone and 16-17 months with ADT alone across earlier series.
No central PET review at baseline or follow-up, so the primary endpoint depends on local reads (authors cite κ 0·74 for pelvic nodes). Curves did not separate in year 1 because of the shared 6 months of ADT, which strains the proportional hazards assumption the HR summarises. The open-label design plausibly biased adverse-event attribution in both directions, and prostate bed RT was left to physician discretion, so a treatment that materially changed both toxicity and local recurrence was not randomised.
The result reads as a field-size question answered on pattern of failure rather than on distant control: relapse after MDT was predominantly locoregional, meaning PSMA PET missed nodal disease in at least half of pts treated to visible targets only. That reframes ENRT less as escalation than as compensation for imaging sensitivity that has not caught up with the treatment paradigm it enabled.
| Endpoint | MDT | ENRT | HR (80% CI) | p |
|---|---|---|---|---|
| MFS (1°) | 63% (56-69) | 76% (69-81) | 0·62 (0·44-0·86) | 0·063 |
| Biochemical RFS | 41% (34-47) | 57% (50-64) | 0·62 (0·48-0·80) | 0·014 |
| Locoregional RFS | 62% (55-69) | 85% (80-90) | 0·45 (0·31-0·65) | 0·0047 |
| ADT-free survival | 60% (53-67) | 77% (70-82) | 0·60 (0·43-0·83) | 0·049 |
CONSORT flow
Phase 2 powered at α=0·20; primary MFS p=0·063 would not clear conventional significance, and the authors themselves await a phase 3 (POINTER-PC).
- Does the MFS benefit hold at conventional significance in phase 3
- Is ENRT plus ADT better than intermittent ADT alone
- Should prostate bed RT be omitted when PSMA PET is bed-negative
📚 Sources · 📄 1 paper
SWOG S1007
ForHR+/ERBB2- breast, 1-3 positive nodes, Oncotype RS ≤25
TL;DR5yr LRR 0.85% with RNI vs 0.55% without after BCS+RT in RS≤25 N1 disease; IDFS unchanged by RNI.
The number that moves the RNI decision is 0.55% 5yr LRR after BCS+RT without RNI, and equally low LRR in the endocrine-alone arm. Chemotherapy omission on a low RS does not by itself justify adding supraclavicular coverage. Target-volume detail beyond supraclavicular is not reported in source.
In HR+/ERBB2- N1 disease with RS ≤25 treated with BCS and whole-breast RT, this argues low RS alone does not compel nodal irradiation; it does not speak to RS >25, higher nodal burden, or ERBB2+ disease.
The actionable number is 0.55% 5yr LRR after BCS+RT without RNI in RS ≤25 N1 disease, against 0.85% with RNI. That floor leaves little absolute room for regional coverage, and IDFS did not move (premenopausal HR 1.03, postmenopausal HR 0.85). This informs the elective supraclavicular decision.
LRR stayed similarly low in the endocrine-therapy-alone group, so omitting chemotherapy on a low Recurrence Score did not raise locoregional risk. The conclusion is explicit: chemo omission is not an independent indication for RNI, which removes a reason to hedge a de-escalation decision.
9 details
Secondary analysis of the randomized SWOG S1007 trial (endocrine therapy alone vs chemotherapy then endocrine therapy). Radiotherapy data were prospectively collected across diverse practice settings, but RNI receipt itself was not randomized. Data analyzed June 2022 to April 2023.
Hormone receptor-positive, ERBB2-negative breast cancer with 1 to 3 involved nodes and Oncotype DX 21-gene Recurrence Score ≤25. 4871 female patients had radiotherapy forms; median age 57 (range 18-87).
RNI defined as targeting at least the supraclavicular region. 3947 (81.0%) reported radiotherapy receipt; of 3852 with complete target information, 2274 (59.0%) received RNI. Dose, fractionation, and internal mammary coverage are not reported in source.
Cumulative incidence of locoregional recurrence by locoregional treatment received, plus association between invasive disease-free survival and locoregional therapy, adjusted for menopausal status, treatment group, recurrence score, tumor size, nodes involved, and axillary surgery.
Median follow-up 6.1 years. See the LRR and IDFS tables above; IDFS did not differ by RNI receipt in either menopausal stratum.
| Locoregional treatment | 5yr LRR |
|---|---|
| BCS + RT with RNI | 0.85% |
| BCS + RT without RNI | 0.55% |
| Mastectomy + PMRT | 0.11% |
| Mastectomy, no RT | 1.7% |
| Group | HR (95% CI) | P |
|---|---|---|
| Premenopausal | 1.03 (0.74-1.43) | .87 |
| Postmenopausal | 0.85 (0.68-1.07) | .16 |
MA.20 and EORTC 22922 established the regional irradiation question in node-positive disease, both without an overall survival gain, in cohorts assembled before genomic risk stratification. This analysis reads that question in the population those trials could not define, biologically favorable N1, and finds an LRR floor low enough that a relative benefit has little absolute room to operate.
Radiotherapy information was recorded only in the first year after randomization, forcing a 1-year landmark that excludes the earliest events. Target detail stops at supraclavicular coverage, so internal mammary treatment cannot be separated, and the low absolute event count leaves the IDFS confidence intervals wide enough to accommodate a small effect in either direction.
The finding that matters is the floor, not the comparison: with 5yr LRR at or below 1.7% in every locoregional strategy examined, the population has too few events for regional irradiation to demonstrate meaningful absolute benefit. The explicit conclusion is that omission of chemotherapy is not an independent indication for RNI, which addresses a specific compensatory reflex rather than the general RNI question.
Prospectively collected RT data in a large trial cohort, but RNI receipt was not randomized; observational comparison, so an unmeasured-confounding read is unavoidable.
- Does any favorable N1 subgroup (3 nodes, RS near 25) still warrant RNI?
- Internal mammary coverage contribution, unseparable in this dataset
- Longer follow-up for late locoregional events in HR+ disease
📚 Sources · 📄 1 paper
Abstract
EORTC 22922/10925
ForStage I-III breast, central/medial tumor or involved axilla, post-ALND
61.0% vs 61.8% at 20yr
HR 1.00, p=.967; primary endpoint not met
TL;DR20yr OS 61.0% vs 61.8% (HR 1.00, p=.967): IM-MS nodal RT cut breast cancer mortality but added non-cancer deaths.
The breast cancer mortality gain (22.4% vs 18.6%, HR 0.82) is real and was fully offset by non-breast-cancer deaths (15.8% vs 20.4%, HR 1.26) that only emerged after 15 years. Cardiac disease ran 15.2% vs 11.7%. In a 1996-2004 planning era, that trade gates IM-MS coverage on achievable heart dose, not on nodal risk alone.
In a woman with a medial or central stage I-III tumor being considered for IM chain coverage, this supports treating the cardiac dose constraint as co-equal with nodal risk; it does not speak to modern DIBH or proton delivery, where the competing-mortality arm may not hold.
Breast cancer mortality fell (HR 0.82) and non-cancer death rose (HR 1.26), netting OS HR 1.00, with cardiac disease 15.2% vs 11.7% and lung fibrosis 6.3% vs 3.2%. Planning ran in the 2D era, so the decision this moves is achievable heart dose, not whether to cover the IM chain.
Systemic therapy was per institutional preference across 1996-2004 accrual, so the disease-specific gain (HR 0.82) sits on a backbone that predates current regimens. For a med onc the read is competing mortality: the excess non-cancer deaths after 15 years reframes how long-term cardiac surveillance should run in irradiated survivors.
9 details
Prospective multicenter randomized phase 3 trial, accrual 1996-2004, 4004 pts, with an RT quality-assurance program built in. The last analysis was planned at 20 years on the assumption that any survival effect of IM-MS-RT would be delayed. Median follow-up 22.2 years.
Women ≤75 yrs, unilateral histologically confirmed breast adenocarcinoma, stage I-III. Gate was tumor location or nodal status: centrally or medially located primary irrespective of axillary involvement, or any quadrant with axillary involvement. Median age 54.
Randomization was to internal mammary and medial supraclavicular (levels 3-4) nodal irradiation or not, layered on standard breast or chest wall treatment. Dose and fractionation are not given in the source excerpt. Planning ran in the two-dimensional and early-conformal era, when IM coverage at least doubled heart dose.
Primary: overall survival. Secondary: disease-free survival, distant metastases-free survival, breast cancer mortality, any breast recurrence.
Lung fibrosis 6.3% vs 3.2%, cardiac fibrosis 2.7% vs 1.7%, cardiac disease 15.2% vs 11.7% with IM-MS-RT. Severe (grade 3-4) events were uncommon and near-equal: cardiac 1.9% vs 1.7%, lung 0.3% vs 0.0%, so the excess sits in lower-grade, chronic morbidity rather than catastrophic events.
MA.20 and DBCG-IMN both read regional nodal RT positively at roughly ten-year horizons, and DBCG-IMN reported an OS gain. This trial covers the same anatomic question at twice that follow-up and shows the disease-specific gain surviving while the survival gain does not, which is the read those trials were too short to produce.
Systemic therapy was left to physician and institutional preference across an eight-year accrual, so the systemic backbone is heterogeneous and predates current regimens. The competing-mortality signal is a cause-of-death attribution over two decades in a population whose baseline cardiovascular risk rises independently, and the source does not report a cardiac-specific mortality breakdown separating RT-attributable from age-attributable death.
The two effects are both real and point opposite ways: HR 0.82 on breast cancer mortality, HR 1.26 on other deaths, netting HR 1.00 on OS. That arithmetic is the finding, and it argues the relevant question is not whether IM-MS coverage works but whether its cost can be engineered down.
| Endpoint | Control | IM-MS-RT | Effect size |
|---|---|---|---|
| Overall survival | 61.8% | 61.0% | HR 1.00, p=.967 |
| Disease-free survival | 49.0% | 48.2% | HR 0.97 (0.89-1.06), p=.5148 |
| Distant metastasis-free survival | 59.8% | 58.9% | HR 0.97 (0.88-1.08), p=.578 |
| Breast cancer mortality | 22.4% | 18.6% | HR 0.82 (0.72-0.95), p=.006 |
| Death not from breast cancer/unknown | 15.8% | 20.4% | HR 1.26, p=.002 |
Randomised, prespecified 20yr primary analysis, adequate power, endpoint reported honestly. Divergence from the 10yr-era read of nodal RT is internally valid, not a design artifact.
- Does modern heart-sparing delivery erase the excess non-cancer mortality?
- Which subgroups have enough breast cancer risk to justify the trade?
- Cardiac surveillance interval for irradiated long-term survivors
📚 Sources · 📄 1 paper
Abstract
Bladder Adjuvant Radiotherapy
ForPost-cystectomy MIBC, pT3-4 / pN+ / margin+ / ≤10 nodes dissected
87.1% v 76.0%
HR 0.43 (95% CI, 0.20 to 0.96), P = .04
TL;DR2yr LRFS 87.1% vs 76.0% with adjuvant pelvic IMRT after RC, HR 0.43 (0.20-0.96), P=.04; DFS/BCSS/OS not significant.
The RT read is the target volume and the technique: stoma-sparing IG-IMRT, 50.4Gy/28fx to cystectomy bed plus pelvic nodes, with no additional severe toxicity reported. That combination is deliverable in a standard department today, so this moves the offer-vs-observe decision for a pT3-4 or pN+ postcystectomy patient rather than leaving adjuvant pelvic RT as a historical toxicity concern.
In a postcystectomy MIBC patient with pT3-4, pN+, positive margin, or ≤10 nodes dissected who has completed perioperative chemotherapy, this supports discussing adjuvant pelvic RT for locoregional control; it does not address patients who received adjuvant immunotherapy.
The transferable detail is the technique: stoma-sparing IG-IMRT, 50.4Gy/28fx to cystectomy bed plus pelvic nodes, with no additional severe toxicity reported. Elective nodal coverage was standard in the treated volume. This moves the offer-versus-observe decision for pT3-4 or pN+ postcystectomy patients.
Over 90% of patients received perioperative chemotherapy (71% neoadjuvant), so the RT benefit sits on top of a modern systemic backbone rather than substituting for it. No patient received immunotherapy, so how adjuvant RT interacts with adjuvant checkpoint blockade in this same high-risk group is untested here.
Surgical adequacy is embedded in eligibility: ≤10 nodes dissected and positive margin were qualifying high-risk features alongside T3-4 and N1-3. That reframes a limited lymphadenectomy or a close margin as a trigger for adjuvant RT referral rather than observation.
10 details
Multicenter phase III RCT, 1:1 adjuvant RT versus observation after radical cystectomy. 153 patients randomly assigned June 2016 to May 2024 (Obs 76, RT 77), stratified by nodal involvement and chemotherapy timing. Median follow-up 47 months.
Nonmetastatic urothelial MIBC, high risk after RC by any one of T3-4, N1-3, positive margin, or ≤10 nodes dissected. Baseline load was heavy: 62% pT3-T4 and 41% pN+.
Over 90% received systemic chemotherapy (71% neoadjuvant, 20% adjuvant). None received immunotherapy in either arm.
Stoma-sparing IG-IMRT, 50.4Gy in 28 fractions, prescribed to the cystectomy bed and pelvic nodes. Elective nodal coverage was part of the treated volume, not an optional add-on.
Primary: 2-year locoregional recurrence-free survival. Secondary: disease-free survival, bladder cancer-specific survival, overall survival.
The primary endpoint was met; secondary endpoints all favored RT numerically without reaching significance. See the endpoint table for arm-level rates and hazard ratios.
| Endpoint | RT | Obs | HR (95% CI) |
|---|---|---|---|
| LRFS (1°) | 87.1% | 76.0% | 0.43 (0.20-0.96), P=.04 |
| DFS | 71.6% | 58.7% | 0.62 (0.36-1.05) |
| BCSS | 79.6% | 65.0% | 0.59 (0.33-1.10) |
| OS | 70.4% | 57.4% | 0.78 (0.49-1.26) |
The authors report no additional severe toxicity with adjuvant pelvic IMRT. Grade-level AE breakdown is not reported in the source abstract.
The primary endpoint is a 2-year locoregional readout under a 47-month median follow-up, so the headline reports early control rather than durability. Accrual spanned eight years, during which adjuvant immunotherapy entered practice in this exact population, and the control arm reflects none of it.
Adjuvant pelvic RT after cystectomy has been an open question since the older Egyptian NCI randomized experience, which used larger fields and conventional technique. This is the modern IMRT-era answer, and it lands positive on local control only, not survival.
A HR of 0.43 on locoregional control with an upper CI bound of 0.96 is a real but fragile signal in 153 patients. The consistent numeric direction across DFS (HR 0.62), BCSS (HR 0.59), and OS (HR 0.78) is reassuring but underpowered, and none of it settles whether locoregional control converts to survival.
CONSORT flow
Randomised, prespecified 2yr LRFS primary endpoint met in a setting where adjuvant RT is not standard. Small N and borderline CI limit confidence, not internal validity.
- Does locoregional benefit persist alongside adjuvant immunotherapy
- Does 2yr LRFS gain translate to survival with longer follow-up
- Which high-risk feature drives the benefit: pN+, margin, or nodal yield
📚 Sources · 📄 1 paper
Abstract
Proton vs Photon PMRT Capsular Contracture
ForPost-mastectomy breast cancer, implant-based reconstruction (TE/I or DTI), receiving PMRT
TL;DR2yr CC 50% with proton+DTI vs 12% photon+TE/I; proton HR 2.3 univariate, 1.76 (0.93-3.32) multivariable, ns.
The actionable variable is reconstruction type, not beam: DTI carried HR 3.0 (1.7-5.5) for CC independent of modality, and proton+DTI was the worst cell at 50% at 2 years vs 12% for photon+TE/I. That reframes the pre-RT conversation with plastic surgery toward staged TE/I when protons are planned, rather than toward declining protons outright.
In a woman heading to PMRT after mastectomy with implant reconstruction, this informs the timing and type of reconstruction discussed with plastic surgery when proton is on the table; it says nothing about autologous reconstruction or prepectoral placement, neither of which was studied.
The proton CC signal did not survive adjustment (HR 1.76, 0.93-3.32, P=.083), so this is not on its own grounds to decline protons where cardiac sparing is the indication. It is grounds to know the reconstruction plan before simulation: proton with DTI hit 50% CC at 2 years, and every TE/I patient here was irradiated with the expander in place.
Reconstruction type outweighed beam modality: DTI carried HR 3.0 (1.7-5.5) for CC versus staged TE/I on multivariable analysis. When PMRT is planned, particularly proton PMRT, that argues for staging the reconstruction rather than direct-to-implant, in subpectoral placement at least, which is all this cohort covers.
9 details
IRB-approved retrospective cohort at 2 centers within one institution, PMRT delivered 2017-2023. N=175 (89 PBS proton, 86 IMRT photon). CC estimated by Kaplan-Meier, with Cox proportional hazards for covariates and a binary logistic model as verification.
Breast cancer pts who underwent subpectoral 2-stage TE/I or DTI reconstruction and then PMRT. Median age 49 (range 24-78), 63% Hispanic. Groups were balanced except on tumor laterality (P < .001) and reconstruction type (P < .001), the two axes the analysis turns on.
Pencil beam scanning proton PMRT vs IMRT photon PMRT. All TE/I pts had the tissue expander in place and irradiated, so this cohort speaks to expander-in-situ RT, not to post-exchange irradiation of a permanent implant. Dose and fractionation are not reported in source.
Proton was associated with CC on univariate analysis (HR 2.3, 1.26-4.30, P=.007) but the association did not hold after adjustment (HR 1.76, 0.93-3.32, P=.083). DTI vs TE/I carried HR 3.0 (1.7-5.5), P < .001 in the multivariable model. No other factor was significantly associated with CC.
| Group | n | 2yr CC rate |
|---|---|---|
| Proton + DTI | 36 | 50% |
| Photon + DTI | 15 | 35% |
| Proton + TE/I | 53 | 23% |
| Photon + TE/I | 71 | 12% |
Modality was assigned by practice pattern, not randomized, so the residual proton association could be confounding the model did not capture. CC is clinician-graded on unblinded chart review, and the DTI cells are thin (36 proton, 15 photon), which is where the widest rate gap sits.
The paper set out to test a prespecified suspicion that protons increase CC and returned a trend that did not clear significance once reconstruction type entered the model. What it does establish is the interaction cell worth counseling on: proton + DTI at 50% CC at 2 years.
Retrospective, non-randomized modality assignment with baseline imbalance in reconstruction type and laterality; the proton signal loses significance once adjusted.
- Does prepectoral placement change the proton CC signal?
- Expander-in-situ vs post-exchange RT sequencing for implant reconstruction
- Proton PMRT reconstruction toxicity in a prospective randomized comparison
📚 Sources · 📄 2 papers
Abstract
Single-fraction SABR pooled analysis, 1687 pts
ForPrimary NSCLC or pulmonary oligomets selected for single-fraction SABR
TL;DRLocal control 90-93% at 2yr and G3+ AEs 2.9% across 1687 single-fraction SABR pts at 3 centres.
The oligomet read is the gap between local control and PFS: 90-93% LC at 2yr against median PFS 11 mo, so distant failure, not the treated lesion, drives the course. For primary NSCLC the same LC sits with median PFS 30 mo, which is the split that should decide whether one-visit ablation is offered as definitive treatment or as a break from systemic therapy.
In early-stage primary NSCLC where visit burden drives the fractionation choice, this supports single fraction as a durable local option (LC 90-93% at 2yr, G3+ 2.9%); tumour location and operability are not reported, so who it represents stays open.
Local control holds at 90-93% at 2yr for a primary and for a metastasis alike, so the single fraction is not the variable separating outcomes; median PFS is (30 vs 11 mo). Tumour size and location go unreported, so the target selection behind that number is unmeasured.
For a pt with pulmonary oligometastases, one-visit ablation gave 90-93% local control at 2yr but median PFS of 11 mo, so it clears the treated lesion without changing the systemic course. That frames referral as a local step between systemic lines, not a substitute for one.
| Cohort | n | Median PFS | Median OS |
|---|---|---|---|
| Primary NSCLC | 1200 | 30 mo | 3.5 yrs |
| Pulmonary oligometastases | 487 | 11 mo | >4 yrs |
+2 more figures
| Endpoint | Primary NSCLC | Oligometastases |
|---|---|---|
| 1yr OS | 84% (95% CI 82, 86) | 90% (95% CI 86, 92) |
| 2yr OS | 67% (95% CI 64, 69) | 75% (95% CI 71, 79) |
| Median OS | 40 mo (36, 43) | 51 mo (42, 58) |
| Adverse event (n=789) | n (%) |
|---|---|
| Any AE | 215 (27%) |
| Grade 2+ | 124 (15.7%) |
| Grade 3+ | 23 (2.9%) |
| Chest wall pain | 114 (14%) |
| Pneumonitis | 52 (7%) |
| Fatigue | 29 (4%) |
| Dyspnea | 13 (2%) |
6 details
Pooled analysis of 1687 pts treated with single-fraction SABR at three centres (Peter MacCallum, Cleveland Clinic, Roswell Park): 1200 primary NSCLC and 487 pulmonary oligometastases. Whether the contributing cohorts were prospective or retrospective is not stated in source.
Eligibility, operability, tumour size and central vs peripheral location are not reported in source. Cohort mix differs sharply by centre: Roswell Park supplied 401 of the NSCLC pts but only 34 oligomet pts, while Peter Mac supplied 283 of 487 oligomet pts.
Single fraction throughout, but the prescribed dose is not reported in source. Without it the outcome cannot be mapped onto a schedule a reader could write, which is the one parameter that would carry this into planning.
No primary endpoint is stated in the source. Reported outcomes are local control, freedom from local failure, PFS, OS and adverse events, each descriptive rather than tested against a comparator.
Local control 90-93% at 2 years across both cohorts, with isolated local or locoregional failure described as very uncommon. Survival separates by cohort while local outcome does not.
| Centre | Primary NSCLC | Pulmonary oligomets |
|---|---|---|
| Cleveland Clinic | 576 | 170 |
| Peter MacCallum | 223 | 283 |
| Roswell Park | 401 | 34 |
AE reporting covers 789 primary NSCLC pts only, with no Roswell Park data and no oligometastasis toxicity in source. Within that subset chest wall pain and pneumonitis dominate and G3+ events stay at 2.9%.
Single-fraction SABR already carries randomised support: RTOG 0915 in peripheral early-stage NSCLC and SAFRON II in pulmonary oligometastases, both randomised single against multi-fraction schedules. This series adds scale and follow-up at three high-volume centres, which is what a non-randomised dataset can contribute, and no comparator.
Toxicity rests on 789 of 1687 pts, with one centre absent from the AE table and the oligometastatic cohort not represented in it at all. Centre mix is uneven, so pooled rates carry each centre's own selection rather than a common one.
The question the thread raises, whether one-stop SABR should be used more often, is not the question this dataset answers. What it does show is that local control near 90-93% and G3+ toxicity near 3% hold at scale outside a protocol, which is the usual worry about a schedule with no second chance. The unreported dose sits between that reassurance and a prescription.
Pooled uncontrolled series across three centres, no multi-fraction comparator and no stated design; dose unreported, so outcomes cannot be tied to a prescription.
- Whether single-fraction outcomes hold for central tumours
- Durability of single-fraction ablation for pulmonary oligometastases beyond first progression
- Toxicity of single-fraction SABR in the oligometastatic cohort
📚 Sources · 🐦 1 tweet
👏🏽👏🏽👏🏽@neildwallaceie at #ESTRO26 - 1687 patients receiving single fraction SABR for #lungcancer and pulmonary oligomets, @PeterMacRadOnc / @ClevelandClinic / @RoswellPark. Fantastic local control, and low adverse rates. Should we be using “one stop” SABR more often #radonc ? pic.twitter.com/w2IlGKRU5o
— Shankar Siva (@_ShankarSiva) May 18, 2026
HEAT NCT01794403
ForLocalized low- to intermediate-risk prostate, IPSS <12, gland <80 cc
7% vs 7.4%
p-non-inferiority = 0.007 at 4.25y, margin 12%
TL;DRInterim: BF 7% vs 7.4% at 4.25y, p-non-inferiority 0.007, 5-fx SBRT non-inferior to 26-fx IMRT with ADT allowed.
The design detail that transfers is the SIB: 36.25 Gy/5 fx with GTV boost to 40 Gy, against a 70.2 Gy/26 fx IMRT comparator rather than conventional fractionation, with ≤6 months ADT permitted in both arms. That combination is closer to what most departments now offer than HYPO-RT-PC or PACE-B, so it addresses whether 5 fractions holds up when the control arm is already moderately hypofractionated.
In localized low- to intermediate-risk disease with IPSS <12 and gland under 80 cc, including men receiving short-course ADT, this supports 5-fraction SBRT as an option against moderate hypofractionation; it does not speak to high-risk disease or nodal coverage.
The transferable parameters are 36.25 Gy/5 fx with GTV SIB to 40 Gy against a 70.2 Gy/26 fx IMRT comparator, with ≤6 months ADT permitted in both arms. Acute G2+ GI favored 5 fractions and late G2+ GI and GU were comparable at median 59.7 months, so this moves the fractionation choice in low- to intermediate-risk disease.
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| Arm | Dose | Fractions | Dose per fraction |
|---|---|---|---|
| AHRT | 36.25 Gy (+ GTV SIB to 40 Gy) | 5 | 7.25 Gy |
| EHRT | 70.2 Gy | 26 | 2.7 Gy |
9 details 5 trials watching
International phase III randomized non-inferiority trial, 1:1, comparing accelerated (AHRT) vs extended (EHRT) hypofractionation. Interim analysis presented; accrual goal n = 456 with 420 evaluable, and 142 analyzed so far. Median follow-up 59.7 months.
Localized low- to intermediate-risk prostate cancer with IPSS <12. Stratified by risk group, prostate volume (<60 cc vs 60-80 cc) and ADT administration. 82.4% intermediate-risk; 28% received ADT.
AHRT: 36.25 Gy in 5 fractions (7.25 Gy per fraction) with GTV SIB to 40 Gy. EHRT: 70.2 Gy in 26 fractions (2.7 Gy per fraction), IMRT in all patients. ADT permitted in both arms, ≤6 months.
Primary: biochemical failure, Phoenix definition, with a non-inferiority margin of 12%. Clinician-reported acute and late GI and GU toxicity reported alongside.
BF 7% vs 7.4%, p-non-inferiority = 0.007 at 4.25y, meeting the non-inferiority criterion.
Acute G2+ GI toxicity lower with AHRT. No significant difference in late G2+ GI or in acute or late G2+ GU. Note that use of supportive medication (laxatives, psyllium) was scored as G2.
The presenters position HEAT against HYPO-RT-PC (limited IMRT use), PACE-B and NRG-GU005 (heterogeneous control arms), all of which allowed no ADT. HEAT is framed as the first trial comparing AHRT and EHRT 1:1 with modern technique plus ADT.
Event counts are low (7% vs 7.4%) against a 12% margin, so the interval around the difference is wide relative to the difference being excluded. The comparator is itself hypofractionated, so this does not test 5 fractions against conventional fractionation.
The question HEAT answers is narrower than 'does SBRT work': it asks whether 5 fractions holds when the control arm is already 26 fractions of IMRT and short ADT is on the table. A positive interim read supports 5 fractions as a default offer in this risk band, but the final prespecified analysis is what settles it.
Interim analysis at 142 of a planned 420 evaluable; prespecified final primary analysis is the gate. Wide 12% margin relative to observed event rates.
- Does non-inferiority hold at the final prespecified analysis
- Effect of concurrent ADT on the fractionation comparison n=60 · primary completion 2028-02 · randomises SBRT +/- relugolix in cFIR/cgUIRn=130 · primary completion 2028-11 · adds ultra-short ADT to single-fraction SBRT
- Late GU outcomes beyond 5 years with 7.25 Gy fractions n=100 · primary completion 2027-10 · 36.25 Gy/5 fx, 1-2mm PTV, late urethra toxicityn=175 · primary completion 2028-12 · 3 fx vs 5 fx benchmark, late GU grade 2+ 1° EPrecruiting Erectile Dysfunction in Good Prognosis Prostate Cancer : Comparison Between Brachytherapy and Stereotactic Body Radiotherapy Phase NAn=240 · primary completion 2030-04 · 7.25 Gy x5 vs I-125 brachy, f/u to 2030
📚 Sources · 🐦 2 tweets
Day FOUR of #ESTRO26 Coverage by OncoAlert 🚨
— OncoAlert (@OncoAlert) May 18, 2026
Results of a Randomized Non-Inferiority Trial of Hypofractionation via Extended versus Accelerated Therapy (HEAT) for Prostate Cancer Presented by Matthew C. Abramowitz🇺🇸 #RadOnc ☢️ #ProstateCancer
HEAT is an international phase… pic.twitter.com/IkSTgQHwXK
The HEAT trial is another randomized demonstration of the safety & efficacy of SBRT compared to hypofractionted RT in #prostatecancer at #ESTRO26 pic.twitter.com/c9sNb3KOqo
— Pierre Blanchard, MD (@PBlanchardMD) May 18, 2026
TORPEdO
ForOropharyngeal SCC requiring concurrent chemo-RT with bilateral neck treatment
No difference vs IMRT
Mean scores similar at 3/12/24 mo post RT; no effect size reported in source
TL;DRNo mean UW-QoL physical composite difference IMPT vs IMRT at 3/12/24 mo post RT, 205 pts.
Both arms were prescribed the same 70 Gy / 56 Gy in 33 fractions under identical constraints, so this tests IMPT under photon-derived objectives, not its dosimetric ceiling. The physical composite (saliva, taste, chewing, swallowing) separates at no timepoint from week 6, weakening the QoL case for referring unselected bilateral-neck OPSCC pts to protons.
In oropharyngeal SCC needing bilateral-neck chemoradiotherapy, patient-reported QoL alone does not support a proton referral; it does not speak to unilateral-neck, RT-alone, or reirradiation pts, where the sparing case differs.
The referral decision is what moves: with identical prescriptions (70 Gy / 56 Gy in 33 fractions) and matched constraints, IMPT showed no mean UW-QoL physical composite advantage at any timepoint from week 6. That argues for model-based selection of individual patients over categorical proton referral in bilateral-neck OPSCC.
+1 more figure
9 details
Multicentre phase 3 RCT, 2:1 randomisation to IMPT vs IMRT, 205 pts recruited. Stratified by T-stage, N-stage, p16 status and smoking history. This ESTRO 2026 presentation reports the longitudinal HR-QoL analysis only.
Oropharyngeal SCC requiring concurrent chemo-radiotherapy including bilateral neck treatment. p16 status was a stratification factor, not an exclusion, so both HPV-driven and HPV-negative disease are represented.
70 Gy / 56 Gy in 33 fractions over 6.5 weeks in both arms, IMPT vs IMRT. Same dose, same schedule, same constraints, so delivery technique is the only variable.
Concurrent cisplatin 100mg/m2 on D1 and D22, identical in both arms. The systemic backbone is fixed, so nothing here reads on regimen choice.
Co-primary (clinician): CTCAE grade 3 weight loss (≥20% decrease from baseline) or gastrostomy dependence at 12 months post RT. Co-primary (patient): UW-QoL physical composite of saliva, taste, chewing, swallowing, appearance and speech at 12 months post CRT.
No difference in mean UW-QoL physical composite between arms at 3, 12 and 24 months post RT, with similar trajectories from week 6 post CRT and similar results across multiple PRO instruments. Scores fell at end of treatment then recovered, most stabilising from 12 months. No effect sizes given in source.
Non-randomised proton series in oropharynx have reported lower gastrostomy dependence and xerostomia than photon comparators, and that expectation is what this trial was built to test. The randomised patient-reported comparison does not reproduce a separation. No cross-trial numbers are in the source.
A composite of six domains dilutes a benefit confined to one, xerostomia being the obvious candidate. 90% CIs and no stated non-inferiority margin mean this is an absence of difference, not demonstrated equivalence. The commentary point that UK proton centres are early on the learning curve is untestable from the source.
The clean part of this design, matched dose and matched constraints, is also what bounds the answer: IMPT was planned to objectives written for photons, so the trial measures what protons deliver under photon rules rather than what they can achieve when pushed. It supports selecting patients by individual sparing benefit rather than referring bilateral-neck OPSCC to protons as a class.
Randomised phase 3 PRO co-primary shows no arm difference, supporting IMRT as standard. Clinician-reported co-primary and effect sizes absent from source.
- Clinician co-primary (weight loss / gastrostomy) result not yet reported
- Whether proton-experienced centres would show a QoL difference
- HR-QoL beyond 2 years; follow-up ongoing to 5 years
📚 Sources · 🐦 2 tweets · 📄 1 paper
Day FOUR of #ESTRO26 Coverage by OncoAlert 🚨
— OncoAlert (@OncoAlert) May 18, 2026
Health-related quality of life in the phase III trial of Toxicity Reduction using Proton Beam Therapy for Oropharyngeal Cancer (TORPEdO;CRUK/18/010) Presented by Matthew Tyler🇬🇧 #RadOnc ☢️
TORPEdO, a multicentre phase 3… pic.twitter.com/ZP6yK7RThL
TORPEdO. Misma planificación + constraints idénticas y centros UK noveles probablemente limitaron el potencial de #IMPT.
— Amadeo Wals (@AmadeoWals) May 18, 2026
Centros con alta experiencia se siguen viendo ventajas clínicas . La QA rigurosa del UK es una fortaleza, pero no maximiza la diferencia.#ESTRO26 #HNCSM https://t.co/rASp3QDIk1
INRT-AIR & DARTBOARD pooled analysis
ForHNSCC oropharynx/larynx/hypopharynx, stage I-IVB, excluding T1-2N0 larynx
TL;DR5yr solitary elective nodal recurrence 0% with ENI omission in HNSCC; 5yr OS 87%, PFS 74%, n=117.
The number that matters is 0% solitary elective nodal recurrence at 5 yrs: elective volumes are where the parotid, constrictor and pharyngeal dose lives, and this is the first pooled long-term read that omitting them does not trade nodal control. MDADI 84.9 at 12 mo with no significant decline is the swallowing correlate. No dose or CTV detail in source, so the contouring approach cannot be replicated from this abstract.
In stage I-IVB oropharynx, larynx or hypopharynx SCC being planned for definitive chemoRT, this supports enrolling on an INRT protocol rather than adopting nodal omission off-trial; it does not extend to T1-2N0 larynx, which was excluded.
This is the elective-volume decision, the one de-escalation lever definitive chemoRT has never randomised. 0% solitary elective nodal recurrence at 5 yrs with MDADI 84.9 at 12 mo says the trade is not nodal control, but the nodal selection ran through an AI model on staging PET/CT, so the transferable piece may be the selection step, not the omission.
+1 more figure
11 details 2 trials watching
Patient-level pooled analysis of 2 prospective trials, INRT-AIR and DARTBOARD, both testing involved nodal radiotherapy. N=117, median follow-up 3.4 years. No randomised comparator arm receiving standard elective nodal irradiation.
HNSCC of oropharynx, larynx, and hypopharynx, stage I-IVB, explicitly excluding T1-2N0 larynx. Completed PET/CT and neck CT were required for eligibility, which is also the imaging substrate the nodal-selection step depends on.
Definitive chemoradiotherapy with omission of elective nodal irradiation (ENI), treating involved nodes only (INRT). Suspicious node identification was assisted by an artificial-intelligence model reading the staging PET/CT and neck CT. Dose, fractionation and margin expansions are not reported in the source.
5-yr solitary elective nodal recurrence 0%. 3-yr cumulative incidence: local 9.5%, regional 4.3%, distant 11%. 5-yr OS 87%, PFS 74%. Mean composite MDADI 84.9 at 12 months with no significant decline after treatment.
Pooling two protocols with different designs into one patient-level cohort assumes their INRT definitions were interchangeable, which the source does not establish. Median follow-up of 3.4 years supports a 5-year estimate on a shrinking risk set, and HPV status, which drives OS in an oropharynx-weighted cohort, is not reported.
The zero solitary elective nodal failures make the mechanistic case that undissected, PET-negative elective levels rarely harbour disease that only ENI would sterilise. What the pooled cohort cannot settle is whether the result survives outside two experienced centres using an AI-assisted nodal-selection step, which is precisely the component a general department would have to reproduce.
Pooled single-arm prospective cohorts, n=117, no randomised comparator against standard elective nodal RT. Presenters state randomised evidence needed before non-trial use.
- Randomised INRT vs elective nodal irradiation in definitive chemoRT recruiting Dose De-escalation and Sentinel LN Mapping Driven Radiotherapy of Contralateral Neck in Ipsilateral Node Positive HNSCC Phase NAn=147 · primary completion 2027-01 · sentinel node mapping tailors contralateral neck volumerecruiting Invert-Prospective Phase II Randomized Trial of Involved Nodal Versus Elective Neck RadioTherapy Phase 2n=80 · primary completion 2028-07 · randomised INRT vs ENI, solitary elective recurrence
- Does AI-assisted nodal selection outperform physician contouring
- Whether INRT toxicity benefit is measurable against standard elective volumes
📚 Sources · 🐦 1 tweet
Day FOUR of #ESTRO26 Coverage by OncoAlert 🚨
— OncoAlert (@OncoAlert) May 18, 2026
Omission of elective nodal irradiation in HNSCC: long-term results and patient-level pooled analysis from 2 prospective trials (INRT-AIR & DARTBOARD)
Presenter Sympascho Young 🇺🇸
A patient-level pooled analysis of 117 patients… pic.twitter.com/KaaT70nSNH
NRG/RTOG 1005 NCT01349322
ForHigh-risk early breast cancer post-lumpectomy + axillary surgery, boost indicated
HR 1.31
90% CI 0.84-2.04, P=.037 (noninferiority met)
TL;DR7yr IBR 2.6% concurrent vs 2.2% sequential, HR 1.31 (90% CI 0.84-2.04), noninferior, one shorter course.
The concurrent arm is 15 fractions total, 40 Gy/15F whole breast with an 8 Gy SIB at 0.53 Gy/day, versus 21-32 fractions sequentially. Cosmesis was noninferior on patient BCTOS, physician rating, and blinded photo review, so the usual objection to a simultaneous integrated boost in a high-risk, 16.7% close-margin population does not hold at 3 years.
In a post-lumpectomy patient with grade 3, ER-negative, close-margin, or node-positive disease where you would add a boost, this supports a 15-fraction SIB course instead of sequential; it does not address partial-breast, regional nodal irradiation, or ultrahypofractionated 5-fraction boost.
The concurrent arm is 15 fractions total, 40 Gy/15F whole breast with an 8 Gy SIB at 0.53 Gy/day, against 21-32 fractions sequentially. Cosmesis was noninferior on patient BCTOS, physician rating, and blinded photo review, so the usual SIB objection does not hold at 3 years in a cohort with 16.7% close margins.
10 details 5 trials watching
Randomized, unblinded phase 3 noninferiority trial run by NRG Oncology, 278 sites across North America and 6 other countries, accrual May 2011 to June 2014. 2,354 randomly assigned, 2,255 eligible (sequential 1,118, concurrent 1,137). Median follow-up 7.3 years.
Post-lumpectomy and axillary surgery, selected for higher risk of ipsilateral breast recurrence. Median age 55 (IQR 47-64), 35.6% under 50; 96.8% invasive, 52.7% grade 3, 29.6% ER-negative, 16.7% LVI, 16.7% close (<2 mm) or focally positive margins, 16.3% node-positive, 61.8% received chemotherapy.
Sequential arm: WBI 50 Gy/25F or 42.7 Gy/16F, then boost 12 Gy/6F (84.9%) or 14 Gy/7F. Concurrent arm: WBI 40 Gy/15F with an 8 Gy/15F integrated boost at 0.53 Gy per day. 3DCRT in 1,290 (59%), photons in 1,614 (73.8%). QART scored contours and plans per protocol or acceptable variation in 92.8% and 91.9%.
Primary: IBR as first recurrence, noninferiority margin an HR upper 90% CI limit of 2.12, powered at 80% off an assumed 1.59% 5-year sequential-arm IBR. Secondary: DFS, OS, adverse events, and cosmesis (patient BCTOS, physician global cosmetic score, blinded central digital photo review).
56 IBR events, 24 sequential and 32 concurrent. Cause-specific hazards and Fine-Gray gave the same HR 1.31, and noninferiority held against each sequential WBI fractionation separately. The protocol-specified superiority test was not significant, and post-hoc analyses by stratification variable showed no treatment interactions.
| Arm | WBI | Boost |
|---|---|---|
| Sequential | 50 Gy/25F (575, 52.4%) or 42.7 Gy/16F (523, 47.6%) | 12 Gy/6F (932, 84.9%) or 14 Gy/7F, after WBI |
| Concurrent | 40 Gy/15F | 8 Gy/15F at 0.53 Gy/day, during WBI |
Grade >2 treatment-related toxicity was uncommon with no difference in grade 3-4 events (p=0.81); radiation dermatitis, fatigue, and breast pain were the most prevalent events. Physician-rated excellent/good cosmesis at 3 years was 85.9% sequential vs 82.4% concurrent (p=0.34), photo review 64.2% vs 72.0% (p=0.11).
The boost itself was established by EORTC 22881-10882, where 16 Gy sequential cut IBR but added treatment time and worsened fibrosis. IMPORT HIGH tested integrated boosts on a 40 Gy/15F backbone and found 48 Gy acceptable while its 53 Gy arm carried more induration. NRG 1005 answers the delivery question at scale rather than the dose question.
Cosmetic assessment thinned badly over time: blinded photo review response fell from 79.7% at baseline to 47.1% at 3 years, and physician rating from 90.3% to 50.5%, so the cosmesis conclusions rest on roughly half the cohort with unblinded delivery. The QoL substudy also had imbalances, more stage II sequentially (39.7% vs 32.5%) and more IMRT concurrently (27.1% vs 18.5%).
The point estimate favors sequential (HR 1.31) even as the confidence bound clears the margin, so this is a noninferiority conclusion in the honest sense, not equivalence. With 7-year IBR at 2.2% and 2.6%, the absolute difference is under a percentage point in a deliberately high-risk cohort, which is the frame in which trading 6 to 7 fractions is reasonable.
CONSORT flow
Adequately powered phase III, prespecified noninferiority margin met at 7.3yr median f/u, with cosmesis and toxicity co-endpoints also noninferior. Removes 6-7 fractions.
- Late cosmesis and fibrosis beyond 3 years with an integrated boost n=132 · primary completion 2026-03 · 1° EP RT fibrosis at 4y with hypofx tumor bed boostn=50 · primary completion 2028-09 · cosmesis + PROMs to 60mo after ultra-short WBI/SIB
- Does noninferiority hold at 10-year IBR follow-up
- Integrated boost on ultrahypofractionated 5-fraction whole-breast RT recruiting Ultra Hypo-fractionated Adjuvant Whole Breast Radiation Therapy With Simultaneous Integrated Boost for Early-Stage Breast Cancer (H-ASSIST) Phase 2n=90 · primary completion 2028-02 · 5fx WBI + SIB, toxicity and QoL endpointsrecruiting 5 fr Ultrahypofractionated WBI and SIB for Breast Cancer With Unfavorable Characteristics Phase NAn=458 · primary completion 2029-06 · randomised 26Gy/5fx + SIB 30Gy vs 40.05Gy/15fx + SIBn=400 · primary completion 2030-12 · phase 3 FAST-Forward 1wk vs 2wk concomitant boost
📚 Sources · 📄 1 paper
Abstract
Multinational HCC EBRT IPD Cohort
ForVery early / early-stage HCC (BCLC-0 or A), incl. treatment-naive
TL;DRMedian OS 6.8y BCLC-0 and 4.6y BCLC-A across 4,913 EBRT-treated HCC pts, comparable to resection and ablation.
The modifiable RT variable in the Cox model is ablative dose, which was associated with reduced mortality, so the transferable read is that dose, not simply delivering EBRT, tracks with the outcome. Fractionation and dose thresholds are not given in the abstract. This is the citation for putting EBRT on the BCLC-0/A allocation discussion.
In BCLC-0 or A HCC where resection, transplant, or ablation is not feasible or is declined, this supports discussing ablative-dose EBRT as a locoregional option; it does not establish EBRT over resection or ablation in a pt eligible for either.
Ablative dose was the modifiable variable associated with reduced mortality, so the transferable read is dose, not simply offering EBRT. Dose thresholds, fractionation, and modality mix are not given in the source abstract. This is the citation for putting EBRT into the BCLC-0/A allocation discussion at tumor board.
Child-Pugh B or C, performance status, and tumor burden drove mortality in the multivariable model, which is the gating frame for who gets locoregional therapy at all. For the med onc coordinating a BCLC-0/A pt, EBRT enters the locoregional menu alongside ablation rather than as a last resort.
Median OS of 6.8 y (BCLC-0) and 4.6 y (BCLC-A) in EBRT-treated pts is a cross-literature benchmark against resection and ablation, not a head-to-head. It bears on referral for the medically inoperable or anatomically difficult pt, and does not establish EBRT over resection in a fully resectable candidate.
9 details 2 trials watching
Systematic review of EBRT publications meeting prespecified HCC technical standards (search date December 15, 2022), with corresponding authors invited to contribute individual patient data. Kaplan-Meier OS and RMST stratified by BCLC stage and treatment status; random-effects Cox for covariates. No comparator arm.
4,913 pts treated with EBRT, median follow-up 5.0 years, multinational. Analyses split by BCLC stage and by treatment-naive vs treatment-experienced; the headline read sits in BCLC-0 and BCLC-A.
EBRT delivered per each contributing series, gated by the prespecified technical standards rather than one protocol. Ablative dose was associated with a reduced risk of death; specific dose levels, fractionation, and modality mix are not given in the source abstract.
Overall survival by Kaplan-Meier and restricted mean survival time, stratified by BCLC stage and treatment status. Covariate associations from multivariable random-effects Cox modeling.
Median OS 6.8 y (95% CI 5.7-8.7) for BCLC-0 and 4.6 y (95% CI 4.1-5.1) for BCLC-A. Treatment-naive: not reached (95% CI 8.6-NR) for BCLC-0, 5.4 y (95% CI 4.5-6.7) for BCLC-A.
| Cohort | BCLC-0 | BCLC-A |
|---|---|---|
| All pts | 6.8 y (95% CI 5.7-8.7) | 4.6 y (95% CI 4.1-5.1) |
| Treatment-naive | NR (95% CI 8.6-NR) | 5.4 y (95% CI 4.5-6.7) |
The authors frame these medians as comparable with resection, thermal ablation, and other ablative locoregional therapies, a cross-study benchmark rather than a randomised comparison. EBRT's exclusion from BCLC has rested on the absence of OS evidence, which is the gap this cohort is built to fill.
IPD came only from authors who published and agreed to share, so contributing centers are self-selected and unmeasured selection at the patient level (who was routed to EBRT rather than resection) is unrecoverable. More recent year of treatment predicting survival mixes technique gains with stage migration and modern systemic salvage over a multi-decade accrual window.
The claim is an allocation claim, not an efficacy claim: EBRT belongs in the BCLC decision tree as an option to be weighed. It does not settle sequencing against ablation in a pt eligible for both, and the ablative-dose signal makes the quality of the RT, not its mere availability, the operative variable.
Largest EBRT IPD cohort argues for a BCLC allocation change, but it is pooled non-randomised data with no head-to-head comparator against resection or ablation.
- Ablative dose threshold and fractionation driving the survival association
- EBRT vs thermal ablation head-to-head in early HCC recruiting Stereotactic Radiosurgery Versus Radiofrequency Ablation for Primary Liver Cancer Phase 2n=130 · primary completion 2025-01 · phase 2 SBRT vs RFA, inoperable primary liver caactive Stereotactic Body Radiotherapy Versus Radiofrequency Ablation for Unresectable, Small (≤ 3 cm) HCC Phase NAn=178 · primary completion 2026-12 · randomised SBRT vs RFA, unresectable HCC <=3cm
- Selection differences between EBRT-treated and resected early-stage pts
📚 Sources · 📄 1 paper
Abstract
EXTEND
ForOligometastatic solid tumors, 1-5 metastases, on standard systemic therapy
HR 0.54
95% CI 0.41-0.72, p<0.001
TL;DRPFS HR 0.54 (0.41-0.72), p<0.001 for MDT added to SOC across 6 oligometastatic baskets; RT delivered 98% of MDT.
The prostate-excluded HR 0.60 (0.40-0.89) is the number that matters for an RT reader: the benefit survives removal of the two prostate baskets, where MDT is already routine. RT delivered 98% of MDT (370/379), so this is a radiotherapy result, though dose and fractionation are not reported in source.
In a patient with 1-5 metastases from pancreas or a non-breast, non-kidney histology already on standard systemic therapy, this supports discussing MDT as an addition rather than a deferral; it does not resolve the breast or kidney question, where the baskets were inconclusive.
RT delivered 98% of MDT (370/379 metastases), so the all-basket HR 0.54 and the prostate-excluded HR 0.60 (0.40-0.89) are radiotherapy effect sizes. The prostate-excluded analysis is the one that moves practice beyond the population where MDT is already routine, though dose, fractionation and target volume are not reported in source.
MDT was added on top of standard systemic therapy rather than substituted for it, so nothing here supports deferring or de-escalating systemic treatment. The ctDNA findings (detectable at enrollment with shorter PFS, clearance at 3 months with better survival) are the medonc-relevant signal, pointing toward a molecular rather than lesion-count definition of who to refer.
13 details 5 trials watching
Multicenter randomized phase II basket trial, 6 histology baskets with basket-specific stratification and powering. Accrual 2018 to 2023, median follow-up 53 months.
Patients with 1-5 metastases on standard-of-care systemic therapy, allocated to breast, pancreas, kidney, two prostate baskets, or an "Other" basket. 521 screened, 350 randomized, 334 analyzed per protocol (MDT+SOC n=166; SOC n=168).
Radiotherapy delivered 98% of MDT (370/379 metastases), so this is effectively a radiotherapy trial. Dose, fractionation, technique and target-volume definition are not reported in source.
Primary: PFS, pre-specified in the per-protocol set at three levels (within each basket, across all baskets, and across all baskets excluding the prostate baskets). Exploratory: ctDNA and immune profiling.
All-basket PFS HR 0.54 (95% CI 0.41-0.72), p<0.001; excluding prostate, HR 0.60 (95% CI 0.40-0.89). Superiority in pancreas, prostate and "Other"; breast and kidney inconclusive. No per-basket effect sizes reported in source.
SABR-COMET randomized 99 patients across mixed histologies; STOMP and ORIOLE were prostate-only and smaller. EXTEND's contribution is scale plus histology resolution: it keeps a benefit when the prostate baskets are removed, which the prostate-only trials could not address.
The primary analysis is per-protocol rather than ITT, and an unblinded PFS endpoint in a trial that ablates the very lesions being measured favors the intervention arm. The "Other" basket is a mixed-histology pool, so its superiority signal is the hardest of the three to carry into a single phase III.
The prostate-excluded HR 0.60 is the trial's most load-bearing number, since it shows the pooled result is not simply the prostate literature reasserting itself. The ctDNA correlations (detectable at enrollment with worse PFS and survival; clearance at 3 months with better survival) point at a biological rather than anatomic definition of oligometastasis, which is the more interesting question EXTEND raises without settling.
CONSORT flow
Randomized phase II, per-protocol primary, histology-specific signals explicitly framed as hypothesis-generating for phase III. Consistent with SABR-COMET / STOMP / ORIOLE direction.
- Does MDT-driven PFS benefit translate to overall survival n=340 · primary completion 2026-11 · OLIGAMI: randomised MDT after 12wk systemic, breastactive Stereotactic Ablative Radiotherapy for Comprehensive Treatment of Oligometastatic (1-3 Metastases) Cancer Phase NAn=330 · primary completion 2030-11 · SABR-COMET-style RCT with OS as primary, 1-3 mets
- Can ctDNA select oligometastatic patients for MDT n=60 · primary completion 2027-12 · SABR cohort tracking ctDNA dynamics as biomarker
- Confirmatory phase III in pancreas oligometastatic disease recruiting Stereotactic Body Radiotherapy in Patients With Rare Oligometastatic Cancers (OligoRARE) Phase NAn=200 · primary completion 2028-08 · phase III SBRT+SOC, OS endpoint, pancreas among sitesactive SENECA: First Line metaStatic pancrEatic caNcer Primary and Distant (if Oligometastatic) lEsion direCted rAdiotherapy Phase 3n=108 · primary completion 2030-01 · randomised phase 3 SBRT vs chemo alone, 1L met pancreas
📚 Sources · 📄 1 paper
Abstract
FASTRACK II NCT02613819
ForPrimary RCC ≤10cm, T1b-dominant, medically inoperable or declined surgery
100% at 36, 60, 84 mo
ITT population, RECIST-assessed, median f/u 62 mo
TL;DR100% freedom from local progression at 36, 60, and 84mo after single-fraction 26Gy or 42Gy/3fx SABR in inoperable primary RCC.
The transferable detail is the size-adapted prescription: 26Gy in one fraction under 4cm, 42Gy/3fx above it, with median tumour 46mm and 65% T1b or higher. That is a larger-tumour cohort than most ablation series, and zero local failures out to 84mo supports offering SABR when a 77-year-old is turned down for nephrectomy.
In a medically inoperable or surgery-declining patient with a primary RCC up to 10cm, including T1b and larger where thermal ablation is a poor fit, this supports SABR as a durable local option; it does not speak to the operable patient, where nephrectomy remains untested against it.
The transferable detail is the size-adapted prescription: 26Gy single fraction under 4cm, 42Gy/3fx above it, in a cohort with median tumour 46mm and 65% at least T1b. Zero local failures to 84mo supports offering SABR when the patient is turned down for nephrectomy; bowel toxicity (two colonic obstructions) sets the technical ceiling.
This is the non-surgical arm of the small-renal-mass conversation getting real prospective follow-up, at a median tumour of 46mm where thermal ablation performs worst. It changes what you can tell a high-risk or surgery-declining patient at referral; it does not test SABR against partial nephrectomy in an operable patient, which remains unstudied.
10 details
Non-randomised phase 2, eight hospitals in Australia and the Netherlands, run by TROG and ANZUP. Enrolment July 28 2016 to Feb 27 2020; 71 enrolled, one withdrew consent before treatment. This report is the pre-planned final follow-up at a median of 62 months (IQR 60-72).
Histologically confirmed primary RCC, medically inoperable, high risk, or declined surgery, ECOG ≤2, tumours ≤10 cm, N0-N1. Median age 77 years (70-82), 49 (70%) male. Median tumour size 46 mm (37-55), with 39 (56%) T1b, six (9%) T2a and one (1%) T3a.
Size-adapted prescription: 26 Gy in a single fraction for tumours ≤4 cm, 42 Gy in three fractions 48 h apart for tumours >4 cm. Histological confirmation was required before treatment, so this is a biopsy-proven cohort rather than a radiographic-diagnosis one.
Primary: freedom from local progression by RECIST, assessed in the intention-to-treat population, as was safety.
100% local control at 36, 60 and 84 months, with no local recurrences and no cancer-related deaths reported in the cohort.
Seven (10%) patients had at least one treatment-related grade 3 event within 9 months: pain in four (6%), nausea and vomiting in three (4%), colonic obstruction in two (3%), diarrhoea in one (1%). No grade 4 events and no treatment-related deaths; no new long-term safety signals emerged with extended follow-up.
A 100% point estimate in 70 pts carries a wide confidence bound that the headline hides, and RECIST is an imperfect local-control instrument after ablative RT, where a treated mass commonly persists without viable tumour. Renal function trajectory, the endpoint that actually competes with nephrectomy, is not reported in this source.
Prior SABR evidence in primary RCC was retrospective and pooled, so a prospective multicentre dataset at 84 months is the new contribution rather than the effect size itself. Comparison to partial nephrectomy and thermal ablation remains indirect: no randomised trial has run, and this cohort was selected against surgery by definition.
The finding that transfers is durability at a tumour size where thermal ablation performs worst, with a median of 46 mm and 65% at least T1b. What it does not settle is whether SABR is a choice rather than a fallback, which needs a randomised or matched comparison in operable pts, with renal function as a co-primary.
Single-arm phase 2, N=70, inoperable or surgery-declining pts only. No randomised comparator vs partial nephrectomy or thermal ablation. Maturity gate holds despite 62mo f/u.
- SABR vs partial nephrectomy in operable pts
- Renal function trajectory after SABR vs nephrectomy
- SABR vs thermal ablation in T1b tumours
📚 Sources · 📄 1 paper
Abstract
POP-RT vs PEACE-2
TL;DRWPRT bFFS HR 0.50 (POP-RT) vs bPFS HR 0.97 (PEACE-2); pelvic RT benefit vanishes with 3yr ADT, PSMA staging.
POP-RTPEACE-2
The reversal tracks four coupled changes, and the one an RT reader controls is target volume: with 36 months ADT, 78 Gy EQD2 and PSMA staging, WPRT bought nothing biochemically (HR 0.97, p=0.73) where it halved biochemical failure at 24 months ADT and 74-76 Gy (HR 0.50). This moves elective nodal coverage toward optional in PSMA-staged very-high-risk N0M0 on 3 years of ADT, not in conventionally staged pts.
In very-high-risk N0M0 prostate staged by PSMA PET and planned for 36 months ADT with dose-escalated RT, this questions routine whole-pelvis coverage; it does not extend to conventionally staged pts or shorter ADT, where POP-RT still supports it.
Target volume is the variable you own here. WPRT halved biochemical failure at 24 months ADT and 74-76 Gy EQD2 (HR 0.50) but returned HR 0.97 (p=0.73) at 36 months ADT, 78 Gy and PSMA staging, with no toxicity penalty either way. Elective nodal coverage becomes conditional on staging and ADT length, not automatic.
ADT duration is the confounder doing the heavy lifting: 24 vs 36 months separates the two trials as much as the RT volume does. If 3 years of ADT is what erases the nodal-RT signal, then shortening ADT for tolerability reopens the case for pelvic coverage, so the systemic and RT decisions cannot be made independently in very-high-risk N0M0.
| Endpoint | POP-RT HR (95% CI), p | PEACE-2 HR (95% CI), p |
|---|---|---|
| bFFS / bPFS | 0.50 (0.42-0.61), p<0.001 | 0.97 (0.81-1.16), p=0.73 |
| cFFS / cPFS | 0.74 (0.61-0.90), p=0.002 | 0.81 (0.63-1.03), p=0.09 |
| MFS | 0.72 (0.58-0.89), p=0.002 | 0.93 (0.74-1.17), p=0.54 |
8 details 4 trials watching
Two independent phase III, open-label, randomized trials of whole-pelvis RT vs prostate-only RT, set side by side in a curator comparison graphic. POP-RT accrued 2011-2016 (median f/u 6.3-7.2 yr, updated); PEACE-2 accrued 2018-2023 and reads out at ~5.5 yr median f/u as an interim analysis (ESTRO 2026).
POP-RT enrolled high / very-high-risk localized N0M0 disease staged by conventional CT and bone scan. PEACE-2 restricted to very-high-risk N0M0 with PSMA PET/CT widely used, so its N0 is a cleaner, node-negative-by-molecular-imaging population.
Both delivered IMRT to whole pelvis plus prostate boost against prostate-only IMRT. Prostate dose was 74-76 Gy EQD2 in POP-RT and 78 Gy EQD2 in PEACE-2, so the control arm in the newer trial is the better-treated prostate.
ADT was a GnRH analog plus antiandrogen in both, but 24 months in POP-RT vs 36 months in PEACE-2. The extra year of systemic control is the single most plausible eraser of a nodal-RT effect.
Primary: bFFS in POP-RT, biochemical PFS in PEACE-2. Secondaries overlap (clinical failure/progression, MFS, OS, toxicity), with PEACE-2 adding CSS. The endpoints are close analogues but not identically defined, which limits how tightly the HRs can be compared.
Both trials reported comparable Grade ≥2 late GU toxicity between arms, with no significant increase in toxicity from WPRT in either. Toxicity is therefore not the lever in this decision; efficacy is.
POP-RT remains the only randomized trial to show a clear elective pelvic RT benefit (bFFS HR 0.50, MFS HR 0.72). PEACE-2's null biochemical result (HR 0.97) at interim is the first randomized read to contradict it, and it does so with a systemic and staging backbone POP-RT never had.
The two trials differ simultaneously in ADT duration, prostate dose, staging modality, risk band and accrual era, so no single factor can be assigned the loss of effect. PEACE-2's read is also interim with shorter follow-up than POP-RT's, and biochemical endpoints mature earliest, so the later endpoints are the least settled.
The graphic's own reading is that longer ADT, modern staging and intensified local therapy may reduce the incremental benefit of elective pelvic RT in very-high-risk disease. That is a hypothesis this comparison cannot test: it settles nothing about which of the four changes did the work, and a reader who shortens ADT while omitting pelvic RT is borrowing from both trials at once.
| Endpoint | POP-RT | PEACE-2 |
|---|---|---|
| Biochemical (bFFS / bPFS) | HR 0.50 (0.42-0.61), p<0.001 | HR 0.97 (0.81-1.16), p=0.73 |
| Clinical (cFFS / cPFS) | HR 0.74 (0.61-0.90), p=0.002 | HR 0.81 (0.63-1.03), p=0.09 |
| MFS | HR 0.72 (0.58-0.89), p=0.002 | HR 0.93 (0.74-1.17), p=0.54 |
- Does PEACE-2's cPFS signal mature into benefit at final analysis?
- Is longer ADT or PSMA staging the reason pelvic RT stopped working? n=250 · primary completion 2031-05 · PSMA-N0M0 randomised to PORT vs prostate+WPRTrecruiting Abi/Pred + ADT vs ADT in PSMA-Positive, Conventionally Node-Negative Prostate Cancer Phase 2n=140 · primary completion 2033-04 · PSMA+ cN0 nodes: ADT vs abi/pred intensification
- Does elective pelvic RT still help pts on shorter ADT? recruiting Phase II Trial of PSA Response-based Androgen Deprivation Therapy and Nodal Coverage for Prostate Cancer Early Salvage Radiotherapy (RANGER) Phase 2n=68 · primary completion 2030-11 · adds pelvic nodal RT + 4mo ADT in PSA nonrespondersn=250 · primary completion 2031-05 · prostate-only vs whole-pelvis RT, high-risk N0
📚 Sources · 🐦 1 tweet
POP RT Vs PEACE II
— Rohit Malde (@roxboxfix) May 18, 2026
2 years ADT + WPRT
Vs 3 years ADT + Prostate Only RT
Tough to choose or you already have a choice ?? pic.twitter.com/42kdSKQYKW
PRIME NCT03561961
ForHigh-risk, very high-risk or node-positive non-metastatic prostate; ECOG 0-2
TL;DRInterim: acute grade ≥2 GU ~5.4% vs ~4.0% (p=0.59) for 5-fx SBRT vs 25-fx, both with whole-pelvis RT; BFFS immature.
The transferable parameter is the nodal dose: 25 Gy in 5 fractions to elective pelvis in both arms, with SIB to involved nodes permitted only in the SBRT arm. Late grade ≥2 GU ran ~10-12% vs ~9-11% at 1-2 yr, so the 5-fraction schedule carried no toxicity penalty over 25 fractions in a node-covered field.
In high-risk or node-positive non-metastatic prostate cancer where whole-pelvis RT and ~2 years of ADT are already planned, this supports 5-fraction delivery on toxicity grounds; it does not yet inform biochemical control, and does not extend to pts treated to prostate alone.
The gate is the elective nodal dose: 25 Gy in 5 fractions to whole pelvis in both arms, SIB to involved nodes only in the SBRT arm. Grade 3+ GU/GI stayed <1% either way, so the decision this moves is whether pelvic coverage can be compressed to 5 fractions, not whether it controls nodes.
+1 more figure
| Feature | HYPO-RT-PC | PRIME |
|---|---|---|
| Fractionation | 42.7 Gy/7 fx vs 78 Gy/39 fx | 36.25 Gy/5 fx vs 68 Gy/25 fx |
| Pelvic RT | None (prostate + SV) | Whole pelvis, 25 Gy/5 fx, both arms |
| ADT | Not permitted | Long course (~2 years), both arms |
| Nodal status | Node-negative only | Includes node-positive |
| Primary result | 10-yr FFS 72% vs 65%, adj HR 0.84 (95% CI 0.69-1.03) | BFFS not yet mature |
9 details 3 trials watching
Phase III, open-label, randomized non-inferiority trial from Tata Memorial Centre and collaborating Indian centres. Accrual 2018 to 2023, completed at ~434 pts, 1:1, stratified by risk group and nodal status. Interim analysis with follow-up of 1 to 2 years.
High-risk, very high-risk and/or node-positive non-metastatic prostate cancer, ECOG 0-2, life expectancy 10 years. PSMA PET/CT staging was permitted, so nodal staging is not uniform across the cohort.
Arm A 36.25 Gy in 5 fractions (7.25 Gy/fx), every other day. Arm B ~68 Gy in 25 fractions (2.7 Gy/fx) over ~5 weeks. Both arms received whole-pelvis elective nodal RT at 25 Gy in 5 fractions or equivalent, with SIB to positive nodes allowed in the SBRT arm; delivery was modern IMRT/VMAT with daily IGRT.
Long-course ADT (~2 years) in both arms, so the randomised variable is fractionation alone, not systemic intensity.
Primary: biochemical failure-free survival (Phoenix, nadir + 2 ng/mL). Secondary: acute and late toxicity (RTOG/CTCAE v4.0/5.0), OS, MFS, cFFS, QoL (EORTC QLQ-C30, QLQ-PR25, IPSS) and cost-effectiveness.
No BFFS, MFS or OS estimate is reported in the source. The interim efficacy statement is only no signal of inferiority for the SBRT arm, with mature 4 to 5 year data awaited.
| Toxicity | SBRT 5 fx | Mod hypo 25 fx | p |
|---|---|---|---|
| Acute GU (≤90 days) | ~5.4% | ~4.0% | 0.59 |
| Acute GI (≤90 days) | ~2.2% | ~3.7% | 0.20 |
| Late GU (1-2 yr) | ~10-12% | ~9-11% | NS |
| Late GI (1-2 yr) | ~5-7% | ~4-6% | NS |
| Grade 3+ GU/GI | <1% | <1% | not reported |
QoL by EORTC QLQ-C30, QLQ-PR25 and IPSS showed urinary and bowel domains stable and comparable between arms, with transient declines during and soon after treatment then recovery. ADT-related sexual and hormonal effects were similar, as expected with a fixed 2-year backbone in both arms.
HYPO-RT-PC gave level-1 support for ultra-hypofractionation (10-yr FFS 72% vs 65%, adjusted HR 0.84, 95% CI 0.69-1.03), but in node-negative pts with no pelvic RT and no ADT, mostly on 3D-CRT. PRIME asks the fractionation question where the target includes the pelvis and the backbone is 2 years of ADT, so its toxicity read is not inherited from that trial.
Toxicity reaches the reader as approximate values on a third-party summary graphic rather than a published table, and late follow-up of 1 to 2 years is short for the GU and GI events that separate fractionation schedules. Open-label design also leaves the QoL and IPSS readouts unblinded.
If BFFS holds at 4 to 5 years, the practical claim is that elective pelvic coverage can be delivered in 5 fractions instead of 25, compressing a 5-week course to 1 to 2 weeks where linac time rations access. Toxicity is the necessary first gate and it clears; non-inferiority is an efficacy claim and nothing here tests it yet.
Interim toxicity and QoL readout at 1-2 yr; primary BFFS not reported and 4-5 yr efficacy pending. Safety comparability cannot establish non-inferiority of 5-fraction SBRT.
- Adequacy of 25 Gy/5 fx elective nodal dose for microscopic disease recruiting A Trial of 5 Fraction Prostate SBRT Versus 5 Fraction Prostate and Pelvic Nodal SBRT Phase 3n=1128 · primary completion 2028-06 · phase 3, 5-fx prostate vs prostate+pelvic nodal SBRTrecruiting PRO-BOOST-N: Prostate-First Versus Combined Prostate and Nodal Dose Escalation in PSMA PET-Staged Node-Positive Prostate Cancer Phase 2/3n=600 · primary completion 2033-12 · randomises nodal dose escalation over UHF whole-pelvis
- Late GU/GI toxicity beyond 2 years with 5-fraction whole-pelvis RT
- Mature BFFS non-inferiority at 4-5 years recruiting Comparing Moderately Ultra Hypofractionated Radiation Treatments for Prostate Cancer Phase 2n=204 · primary completion 2030-11 · non-inferiority: 25 Gy/5 fx vs 44 Gy/20 fx pelvic nodes
📚 Sources · 🐦 1 tweet
PRIME trial
— Rohit Malde (@roxboxfix) May 18, 2026
Can we safely deliver ultra-short SBRT including pelvic nodal irradiation in biologically aggressive disease treated with ADT?
With Pelvic RT
Moderate hypofractionation:
~68 Gy/25#/5w
Vs
Extreme hypofractionation/SBRT:
36.25 Gy / 5 # /1-2w
Compare HYPO RT PC pic.twitter.com/7NABknLsD5
PIVOTALboost
ForHigh-risk localised prostate, 20-fraction IMRT candidates
TL;DRAdding pelvic nodal IMRT to a focal prostate boost in 20fx raised early bowel toxicity only; 2yr G2+ rates similar across arms.
The 2-year cumulative G2+ rates run in the wrong direction for a toxicity argument against nodal RT: bowel 6.5% (4.5-9.5) and bladder 16.5% (13.1-20.6) in the nodes+boost arm, below both prostate-only arms. Whatever excess bowel toxicity nodal RT causes lives inside 18 weeks. That removes late toxicity as the reason to omit pelvic nodes in 20fx, and leaves the decision resting entirely on the unreported efficacy endpoint.
In high-risk localised prostate planned for 20-fraction IMRT, this supports that adding a focal boost with or without pelvic nodal coverage does not raise 2-year G2+ bowel or bladder toxicity; it says nothing about whether either improves biochemical control.
At 2 years, the nodes-plus-boost arm sat at 6.5% G2+ bowel (4.5-9.5) and 16.5% bladder (13.1-20.6), below both prostate-only arms, so the excess bowel toxicity from pelvic coverage is confined to the first 18 weeks. In a 20-fraction schedule, late morbidity is no longer the argument for omitting elective nodal RT or a focal boost.
| Arm | Bowel G2+ (95% CI) | Bladder G2+ (95% CI) |
|---|---|---|
| Prostate (n=281) | 8.2% (5.7-11.7) | 19.5% (15.5-24.4) |
| Prostate+Boost (n=345) | 8.7% (6.3-12.1) | 24.1% (20.2-28.7) |
| Prostate+Nodes+Boost (n=347) | 6.5% (4.5-9.5) | 16.5% (13.1-20.6) |
+1 more figure
8 details 5 trials watching
Phase 3 RCT, N=1465 randomised at 39 UK centres. Primary endpoint is biochemical/clinical failure; the side-effect endpoints presented here are secondary. Early toxicity assessed to 18 weeks, late toxicity at 2 years.
Localised prostate cancer, with the slides naming the high-risk localised group as most likely to benefit from the interventions under test. Full eligibility criteria not stated in the source.
20-fraction moderately hypofractionated IMRT in all arms. Randomisation is to prostate alone (388), prostate + focal boost (464), or prostate + pelvic nodes + focal boost (462), so the trial separates the boost question from the nodal question. Prescription dose and boost dose level not stated in the source slides.
Primary: biochemical/clinical failure, not reported at this presentation. Secondary (reported here): early bowel and bladder side effects to 18 weeks and late G2+ events at 2 years.
Nodal RT increased early bowel side effects, resolving by 18 weeks. Late cumulative rates were reported for the 973 (74%) patients with at least 2 years' follow-up.
The nodal question in prostate RT is currently split: POP-RT favoured whole-pelvis RT on biochemical failure-free survival while PEACE-2 was null on its nodal comparison, and both used conventional or near-conventional fractionation. PIVOTALboost is the first randomised test of pelvic nodal coverage in a 20-fraction schedule, so its eventual efficacy readout is the one that transfers to how most UK and increasingly non-UK practice actually delivers prostate RT.
The late analysis rests on the 74% with 2 years of follow-up, so a differential drop-out by arm would bias the comparison, and cumulative-incidence estimates at 2 years cannot address the fibrotic and stricture toxicity that appears at 5 to 10 years. The source does not state the grading instrument, and a clinician-graded versus patient-reported difference materially changes the size of a G2+ bowel signal.
A safety readout without its efficacy partner cannot move the nodal decision on its own, but it does close off one of the two arguments against nodal coverage in the hypofractionated era. The remaining argument is whether pelvic nodal RT does anything for disease control, which this trial is powered to answer and has not yet reported.
CONSORT flow
Randomised phase 3, but this is the secondary toxicity readout only; the biochemical/clinical failure primary endpoint is unreported, so it settles safety, not benefit.
- Does pelvic nodal RT improve biochemical/clinical failure at 20 fractions? n=18 · primary completion 2026-08 · 20fx pelvic nodal RT with prostate SIBrecruiting Phase III Adaptive Adaptive Stereostactic Body Radiotherapy (SBRT) With Dose Escalation for High-Risk Prostate Cancer Phase NAn=390 · primary completion 2033-04 · WPRT + DIL boost vs standard RT, high risk
- Does the focal intraprostatic boost add control over prostate IMRT alone? recruiting Image-guided Focal Dose Escalation- Primary pc Treated With Primary External Beam Hypofract.Stereotactic rt Phase NAn=374 · primary completion 2025-08 · arm A focal dose escalation vs arm B IMRTactive Standard Moderately Hypofractionated RT vs. Ultra-hypofractionated Focal Lesion Ablative Microboost in Prostate Cancer Phase NAn=484 · primary completion 2032-01 · Hypo-FLAME microboost vs standard 20fx RTrecruiting Addition of Focal Boost to Primary Radiotherapy for Prostate Cancer in 12 or 20 Fractions Phase NAn=1016 · primary completion 2040-10 · randomises focal boost vs none at 20fx
- Do G2+ rates diverge beyond 2 years as late fibrotic toxicity matures?
📚 Sources · 🐦 1 tweet
Day THREE of #ESTRO26 Coverage by OncoAlert 🚨
— OncoAlert (@OncoAlert) May 17, 2026
Moderately fractionated prostate radiotherapy with a focal boost: acute and preliminary late side effects from the phase 3 PIVOTALboost trial Presented by Isabel Syndikus 🇬🇧 #RadOnc ☢️
In the PIVOTALboost trial, we treated 1314… pic.twitter.com/cGuR1j2Qos
PACE-NODES
ForHigh-risk localised prostate (T3a-T4, Gleason 8-10, or PSA>20), on 12-36mo ADT
28% vs 21%
PPN-SBRT vs P-SBRT; no effect size or p-value reported in source
TL;DRCTCAE G2+ GI toxicity 28% vs 21% with added pelvic nodal SBRT; no GU difference, symptoms resolved by 12wk.
Nodal SBRT at 25Gy/5f costs 7 points of acute G2+ GI (28% vs 21%) and nothing in GU, with the EPIC-26 bowel signal at 4 weeks resolving by 12. That makes acute tolerability a weak argument against 5f elective nodal coverage; the decision now waits on late effects and the immature failure endpoint.
In high-risk localised prostate already planned for 5f prostate SBRT plus 12-36mo ADT, this supports the feasibility of extending to pelvic nodes without a GU penalty; it says nothing yet about whether nodal coverage improves control.
The cost of adding 25Gy/5f to the pelvis is 7 points of acute G2+ GI (28% vs 21%), transient by 12 weeks, with no GU penalty. The gating practical fact is deliverability: 11% of PPN-SBRT patients never received allocation on unmet constraints.
| Endpoint | PPN-SBRT | P-SBRT |
|---|---|---|
| CTCAE G2+ GI, 12wk | 28% | 21% |
| Did not receive allocation | 11% | 4% |
+1 more figure
10 details 3 trials watching
Phase 3 randomised 1:1 multicentre trial, target n=1128, 1166 randomised. This presentation reports the acute toxicity analysis only; the efficacy primary is time to biochemical or clinical failure and is not yet mature.
High-risk localised prostate cancer: T3a-T4 and/or Gleason 8-10 and/or PSA>20ng/ml, all planned for 12-36 months ADT.
Both arms 36.25Gy in 5 fractions to the prostate on alternate days. PPN-SBRT adds 25Gy in 5 fractions to the pelvic nodes; P-SBRT is prostate-only.
Primary for this analysis: CTCAE grade ≥2 GI and grade ≥2 GU toxicity up to 12 weeks. Patient-reported EPIC-26 domain scores collected at 4 weeks.
GI was the only separating domain; GU did not differ by clinician or patient report, and the GI gap had closed by 12 weeks.
11% of PPN-SBRT and 4% of P-SBRT patients did not receive their allocated treatment, mostly because planning constraints were not met, which is itself a deliverability signal for 5f nodal treatment.
Patient-reported outcomes were captured at 4 weeks only, so the 12-week convergence rests on clinician CTCAE grading. No effect size, confidence interval or p-value for the GI difference appears in the source, and late GI toxicity is the endpoint that historically decides elective nodal coverage.
The trial's answer so far is about deliverability rather than benefit: 5f nodal SBRT can be given across multiple centres at an acute cost confined to transient bowel symptoms. Whether that cost is worth paying depends entirely on the failure endpoint still to read out.
Acute-toxicity readout only; the efficacy primary (time to biochemical or clinical failure) is immature, so the nodal-coverage question stays open.
- Late GI toxicity beyond the 12-week acute window n=100 · primary completion 2027-10 · 1-2mm PTV margins to cut late rectal toxicityn=500 · primary completion 2027-12 · late GI toxicity as primary endpoint after prostate SBRT
- Whether 5f nodal SBRT improves biochemical or clinical failure recruiting PRO-BOOST-N: Prostate-First Versus Combined Prostate and Nodal Dose Escalation in PSMA PET-Staged Node-Positive Prostate Cancer Phase 2/3n=600 · primary completion 2033-12 · randomises nodal dose in cN1 ultrahypofx pelvic RT
- Which anatomy or constraints drove the 11% non-delivery rate
📚 Sources · 🐦 1 tweet
Day THREE of #ESTRO26 Coverage by OncoAlert 🚨
— OncoAlert (@OncoAlert) May 17, 2026
Acute toxicity in PACE-NODES: A randomised trial of 5 fraction (f) prostate stereotactic body radiotherapy (SBRT) vs 5f prostate and pelvic nodal SBRT
Presented by Angela Pathmanathan 🇬🇧 #RadOnc ☢️ #ProstateCancer
PACE-NODES is a… pic.twitter.com/z9bAOiKSIy
PEACE-2
ForVery-high-risk localized prostate, N0M0, ≥2 of Gleason ≥8 / T3-T4 / PSA ≥20
HR 0.81
95% CI 0.63-1.03, p=0.088, primary endpoint not met
TL;DRcPFS HR 0.81 (0.63-1.03), p=0.088: pelvic RT over prostate-only missed its primary endpoint in very-high-risk N0M0.
The target-volume decision is the whole trial: ADT × 3 years and the systemic backbone were fixed, so the 4.2-point 7yr cPFS gap (67.1% vs 62.9%, p=0.088) is what elective pelvic coverage buys in conventionally-staged N0M0 disease. No dose or fractionation appears in the source slides, and staging used conventional imaging or choline PET, not PSMA.
In very-high-risk localized prostate cancer staged N0M0 on conventional imaging or choline PET, this questions routine elective pelvic nodal coverage added to 3 years of ADT; it does not address PSMA-staged or node-positive disease.
Target volume is the randomized variable with the systemic backbone fixed, so the 7yr cPFS gap of 67.1% vs 62.9% (HR 0.81, p=0.088) is the entire return on elective pelvic coverage in conventionally-staged N0M0. Dose and fractionation are absent from source, blocking a technique-level transfer.
ADT × 3 years ran in every arm and cabazitaxel × 4 cycles was the second randomization, so nothing here moves systemic choice. The relevant read is prognostic: fewer than 1 in 10 men died of prostate cancer in a decade, which questions intensification in this clinicopathologically-defined very-high-risk group.
| Arm | 7yr cPFS | HR (95% CI) | p |
|---|---|---|---|
| Pelvic RT | 67.1% [61.6; 72.2] | 0.81 [0.63; 1.03] | 0.088 |
| Prostate only RT | 62.9% [57.4; 68.1] | n/a | n/a |
+2 more figures
9 details 5 trials watching
International multicenter randomized trial with four arms crossing two questions: RT target volume (prostate only vs pelvis) and cabazitaxel × 4 cycles vs none. Primary: cPFS. The target-volume comparison reads out at 7 years.
Very-high-risk localized prostate cancer defined as ≥2 risk factors among Gleason ≥8, T3-T4, and PSA ≥20 ng/mL. N0M0 by conventional imaging or choline PET/CT.
Androgen deprivation therapy × 3 years in every arm, with cabazitaxel × 4 cycles as the second randomization. The systemic backbone is held constant across the target-volume comparison.
The randomized variable is target volume alone: prostate-only RT versus pelvic RT. Dose, fractionation, and nodal CTV definition are not reported in the source slides.
Primary: cPFS. Secondary: PSA response at 3 months, bPFS, metastasis-free survival, prostate-cancer-specific survival, OS, acute and long-term tolerance, QoL, and biopsy biomarkers.
cPFS HR 0.81 (0.63-1.03), p=0.088 on multivariable analysis, so the primary endpoint was not met. 7yr cPFS 67.1% pelvic versus 62.9% prostate-only. Toxicity and secondary endpoints are not reported in these slides.
POP-RT, a single-center randomized trial of roughly 224 men, reported a whole-pelvis benefit that made elective nodal coverage common practice in high-risk disease. PEACE-2 is larger and multicenter and does not reproduce a comparable signal on its own primary endpoint.
Staging predates routine PSMA PET, so occult nodal disease sits in both arms and dilutes a target-volume comparison. The RT dose, fractionation, and pelvic CTV definition are absent from the source, which blocks a transfer judgment to any specific technique.
The plenary's own conclusion turned on prognosis rather than the RT question: with fewer than 1 in 10 men dying of prostate cancer in the first decade, the "very high-risk" definition itself is what the investigators challenged. A cohort with that little cancer-specific mortality has little room for a target-volume difference to show up in cPFS.
CONSORT flow
Randomized, prespecified cPFS primary, adequate accrual (380 vs 381) and 7yr readout. Negative result contests routine elective pelvic coverage in N0M0 very-high-risk disease.
- Does PSMA PET staging identify a subgroup where pelvic RT helps n=250 · primary completion 2031-05 · PSMA-N0M0 high-risk randomised to PORT vs whole-pelvis RTrecruiting PRO-BOOST-N: Prostate-First Versus Combined Prostate and Nodal Dose Escalation in PSMA PET-Staged Node-Positive Prostate Cancer Phase 2/3n=600 · primary completion 2033-12 · PSMA PET-staged cN1M0: nodal dose escalation vs…
- Biomarkers to guide intensification vs de-intensification in very-high-risk disease
- Pelvic RT toxicity and QoL tradeoff not reported in source n=700 · primary completion 2021-12 · longitudinal GI/heme/GU toxicity + HRQoL after WPRTactive Hypofractionated Whole-Pelvis Radiotherapy (WPRT) vs Conventionally-Fractionated WPRT in Prostate Cancer Phase 2n=58 · primary completion 2026-09 · QoL of 5-fraction vs 25-fraction WPRTn=400 · primary completion 2027-03 · late GI toxicity, protons vs photons, whole-pelvis RT
📚 Sources · 🐦 1 tweet
📣@PBlanchardMD shows #ESTRO26 that pelvic #radiotherapy in high risk #prostatecancer does not have a large improve in outcomes.
— Shankar Siva (@_ShankarSiva) May 17, 2026
- With only 1 in 10 dying of prostate cancer in 10 years, are these patients truly “high risk”? #pcsm #radonc pic.twitter.com/D0XrGD6iNX
OLIGOMA NCT04495309
ForMetastatic breast cancer, ≤5 lesions, any treatment line; mostly ER+/HER2- first-line
35.8 vs 20.4 mo
HR 0.48 (95%-CI 0.25-0.91), p=0.021
TL;DRmPFS 35.8 vs 20.4mo, HR 0.48 (0.25-0.91) p=0.021 with ablative RT to all lesions in oligometastatic breast.
The RT question here is whether ALL lesions must be treated: eligibility required ablative RT to every metastasis, and pts needing palliative RT to all sites were excluded, so this is comprehensive ablation, not selective consolidation. With 2/3 bone lesions and >80% carrying 1-3 mets, the transferable case is the low-burden bone-dominant pt. No dose or fractionation reported in source.
In ER+/HER2- metastatic breast with 1-3 mostly bone lesions starting first-line systemic therapy, this supports discussing ablative RT to all sites; it does not extend to pts with >5 lesions or those needing palliative RT to every site.
The transferable detail is the eligibility rule, not the HR: RT went to ALL metastatic lesions, and pts needing palliative RT to every site were excluded. With >80% carrying 1-3 mets and 2/3 bone, this is comprehensive ablation of low-burden disease. Dose and fractionation not reported in source.
The systemic regimen was fixed by tumor board BEFORE randomisation, so the PFS separation is attributable to RT rather than to differential drug management. Nearly three-quarters were on first-line endocrine or chemotherapy, so the question this moves is whether to pause and refer for ablation at diagnosis of oligometastatic disease, not which regimen to pick.
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| Arm | QLQ-C30 summary, mean (95%-CI) | Between-group change (ANCOVA) |
|---|---|---|
| Experimental | 72.2 (67.2-77.2) | -2.1 (-9.2-5.1) |
| Control | 74.3 (69.3-79.3) | n/a |
9 details 5 trials watching
Randomised trial (ARO-2021-09), systemic therapy alone vs systemic therapy plus local ablative radiotherapy to all metastatic lesions. Stratified by type of systemic therapy and treatment line. Systemic regimen was set by multidisciplinary tumor board before randomisation, so the only variable is RT.
Metastatic breast cancer, any treatment line, maximum 5 lesions. Median age 58 (experimental) vs 59 (control); ER positive 76.7% vs 81.8%, HER2 positive 7.5% vs 15.0%. Nearly three-quarters were on first-line endocrine or chemotherapy. >80% had 1-3 metastases and 2/3 of lesions were bone.
Local ablative RT was delivered to all metastatic lesions, not a selected subset. Palliative RT to symptomatic metastases was permitted, but pts requiring palliative RT to all metastases were not eligible. Dose, fractionation and technique not reported in source.
Co-primary: PFS and quality of life (EORTC QLQ-C30) at 12 weeks post-randomisation. Secondary: overall survival, toxicity, compliance, QLQ-C30 and QLQ-BR23, and patient satisfaction with cancer care (EORTC PATSAT C33).
Both co-primary endpoints read out in the trial's favour: PFS separated, and the 12-week QoL difference stayed inside the prespecified non-inferiority margin of -10 points with baseline adjustment. OS not reported in source.
Beyond the accrual shortfall, the QoL co-primary rested on n=64 of 87 randomised, and 12 weeks is too early to capture late RT toxicity in a population with a 35.8-month median PFS. Toxicity and compliance were secondary and are not reported in source.
This is the first RCT to show a PFS benefit from MDT in oligometastatic breast cancer specifically, a histology under-represented in the earlier mixed-tumour MDT randomised experience. Eight trials in the same question (TAORMINA, STEREO-SEIN, LARA, CLEAR, COSMO, ARCHER, ISTMET, OLIGAMI) are still recruiting, so the field will not settle on 87 pts.
The result establishes direction, not magnitude: an HR of 0.48 from an early-terminated trial is the estimate most likely to regress. What it does settle is the tolerability question, since short-term QoL was not degraded by treating every lesion. Which pts benefit most, by lesion count, site and systemic line, remains open.
CONSORT flow
Recruitment stopped at <20% of initial target; 87 pts, PFS CI 0.25-0.91. Positive and randomised, but underpowered against eight ongoing confirmatory trials.
- Which oligometastatic breast subgroups benefit most from MDT n=340 · primary completion 2026-11 · phase 3 MDT with subtype-specific systemic therapynot yet Adding Surgery and Radiation to the Usual Treatment for HER2-Positive Breast Cancer That Had Already Spread at Diagnosis Phase 3n=562 · primary completion 2032-05 · HER2+ de novo, 1-5 mets, SBRT added to SOC
- Does the PFS benefit translate to overall survival n=150 · primary completion 2025-08 · randomised SABR vs SOC in de novo oligomet BCn=345 · primary completion 2025-12 · TAORMINA: randomised SABR + systemic, 1-5 mets
- Optimal dose and fractionation for bone-dominant ablation recruiting OligoCare TwiCs (Trials Within Cohorts) Trial Comparing Acute Toxicity in Single-fraction vs Multiple-fraction SBRT for Metastasis-directed Treatment (SPRINT) Phase NAn=302 · primary completion 2029-02 · SPRINT: single- vs multi-fraction SBRT randomised
📚 Sources · 🐦 3 tweets
📌 Metastases-directed treatment in Patients with Oligometastatic Breast Cancer: Results from the OLIGOMA-trial (ARO-2021-09, NCT04495309) @DavidKrugMD 👏🏻 #ESTRO26 @ESTRO_RT @OncoAlert #OncoAlertAF pic.twitter.com/YDMef0fXRm
— Elisabetta Bonzano MD, PhD (@to_be_elizabeth) May 17, 2026
❗️ The OLIGOMA trial results just dropped at #ESTRO26 and they are massive. A 15-month improvement in median PFS for OMD breast cancer (HR = 0.48). This adds to the growing mountain of evidence that MDT (Metastasis-Directed Therapy) works. Lets’s go 🧵 1/n pic.twitter.com/5uiEVSYtdH
— NonsparseOncologist (@5_utr) May 17, 2026
Here are some details!
— Jeff Ryckman (@jryckman3) May 17, 2026
On OLIGOMA, nearly 3/4 were first line endocrine or chemotherapy. #ESTRO26 #OncTwitter@CJTsaiMDPhD pic.twitter.com/r3kJzNNsyK
APBI-IMRT Florence NCT02104895
ForEarly breast cancer post-BCS, pT <25 mm, margins ≥5 mm, age >40
7.7% vs 4.2%
HR 1.57 (95% CI 0.82-3.04), p=0.17
TL;DR15-yr IBTR 7.7% APBI vs 4.2% WBI, HR 1.57 (0.82-3.04) p=0.17; excess driven by new ipsilateral primaries, not true local relapse.
The 5-fraction 30Gy IMRT schedule is what transfers: this is the longest follow-up for that specific PBI regimen, and the 15-yr excess sits in new ipsilateral primaries (5.9% vs 2.7%, p=0.09) rather than local relapse (2.1% vs 1.6%, p=0.75). That distinction is the whole case for keeping PBI in Florence-eligible pts, and it rests on adjudication, not on a powered endpoint.
In a woman over 40 after breast-conserving surgery with a tumour under 25 mm and margins of at least 5 mm, this supports offering 5-fraction PBI as a durable option; it does not extend to node-positive disease, close margins, or younger patients.
The transferable parameter is 30Gy in 5 fractions by IMRT, now with 15-yr follow-up. The excess ipsilateral events are new primaries (5.9% vs 2.7%, p=0.09), not local relapse (2.1% vs 1.6%, p=0.75), which is the distinction that justifies continuing PBI in Florence-eligible pts.
Nothing here moves systemic therapy: distant metastasis 2.7% vs 4.6% and breast-cancer deaths 2.3% vs 3.1% are indistinguishable at 15 years. What matters downstream is the new-primary rate of 5.9% with PBI, which shapes how much ipsilateral surveillance a de-escalated local approach earns.
+2 more figures
10 details
Phase III equivalence trial, 1:1 randomisation, n=520, accrued 2005-2013, median follow-up 15 years. Powered at 80% against a 5-year estimated IBTR of 3% with a 5% equivalence margin. Survival outcomes analysed ITT; toxicity and cosmesis per protocol after 14 withdrawals.
Post-breast-conserving-surgery early breast cancer: pT <25 mm, final surgical margins ≥5 mm, age >40 years. A selected, low-risk population by design.
PBI arm: 30Gy in 5 fractions delivered by IMRT (n=260). WBI arm: 50Gy in 25 fractions plus a 10Gy in 5-fraction tumour-bed boost (n=260).
No endpoint separated the arms at 15 years. The IBTR point estimate favours WBI (HR 1.57, 95% CI 0.82-3.04, p=0.17) but the confidence interval spans unity.
Florence remains the only randomised test of a 5-fraction IMRT PBI schedule with follow-up this long; other external-beam PBI randomisations used different dose and fractionation, so their recurrence rates are not directly interchangeable with this one. The direction here, a numerically higher IBTR concentrated in new primaries, is the pattern PBI trials have consistently reported when they separate the two.
The trial was sized for 5-year equivalence, so the 15-year IBTR comparison is a long-term description rather than a powered test, and the upper CI bound of 3.04 leaves room for a real excess. The relapse-versus-new-primary split is an adjudicated distinction, not a molecularly confirmed one, and it carries the entire reassurance.
The result supports continuing PBI in Florence-eligible pts rather than expanding the indication. It does not settle whether the new-primary excess is a genuine consequence of leaving untreated breast tissue unirradiated, which is biologically the expected cost of the approach and would not be captured by any local-control endpoint.
CONSORT flow
Randomised phase III with mature 15-yr follow-up; no significant difference on any oncological endpoint. Supports an already guideline-listed de-escalation rather than establishing a new one.
- Whether the new-primary excess reflects untreated ipsilateral breast tissue
- Ipsilateral surveillance intensity after partial-breast irradiation
- Applicability of 5-fraction PBI below age 40
📚 Sources · 🐦 1 tweet
📌 Fifteen-year outcomes of the randomised APBI-IMRT Florence phase Ill trial of partial versus whole-breast irradiation in early breast cancer ✨
— Elisabetta Bonzano MD, PhD (@to_be_elizabeth) May 17, 2026
Excellent presentation led by @CarlottaB 👏🏻#ESTRO26 @Icro_Meattini @ESTRO_RT @OncoAlert #OncoAlertAF pic.twitter.com/1j4bIA2nyC
EORTC IM-MS (22922/10925)
ForStage I-III breast cancer considering internal mammary / medial supraclavicular nodal RT
61.0% vs 61.8%
HR=1.00, 95% CI 0.90-1.10, P=0.967 (1° EP not met)
TL;DR20yr OS 61.0% vs 61.8%, HR 1.00 (0.90-1.10), P=0.967: the 15yr breast-cancer mortality benefit is erased by non-BCM.
The 20yr null OS is a competing-risk cancellation, not absent efficacy: BCM 18.6% vs 22.4% (HR 0.82) offset by non-BCM 20.4% vs 15.8% (HR 1.26), with cardiac disease 15.2% vs 11.7% and lung fibrosis 6.3% vs 3.2%. Whether IM coverage survives depends entirely on your heart dose, and DBCG IMN2 ran 4-9x lower.
In stage I-III breast cancer where IM-MS coverage is on the table, this supports the anti-cancer effect of IM irradiation while showing the 20yr survival gain is forfeited at 1990s-era heart doses; it does not describe outcomes at modern DIBH/IMRT cardiac exposures.
This is a planning-constraint result, not a target-volume result. IM coverage delivered BCM 18.6% vs 22.4% (HR 0.82) and gave it all back as non-BCM (HR 1.26), with cardiac disease 15.2% vs 11.7%. The benefit survives only if your mean heart dose looks like DBCG IMN2's 1.2-2.3 Gy, not this trial's.
The 20yr OS null (61.0% vs 61.8%) should not be read as breast-cancer control being unimproved: BCM fell to 18.6% from 22.4%. The excess deaths are cardiopulmonary, which is a comorbidity and cardiac-surveillance consideration in long survivors treated in older RT eras rather than a systemic-therapy signal.
| Endpoint | IM-MS RT | No IM-MS RT | HR | P |
|---|---|---|---|---|
| BCM rate | 18.6% | 22.4% | 0.82 (0.72-0.95) | 0.006 |
| non-BCM rate | 20.4% | 15.8% | 1.26 (1.09-1.46) | 0.002 |
+3 more figures
| Endpoint | IM-MS RT | No IM-MS RT | HR (95% CI) | P |
|---|---|---|---|---|
| Overall survival (ITT), 20yr | 61.0% | 61.8% | 1.00 (0.90-1.10) | 0.967 |
| RT-related side effect | IM-MS RT | No IM-MS RT |
|---|---|---|
| Lung fibrosis | 6.3% | 3.2% |
| Cardiac fibrosis | 2.7% | 1.7% |
| Cardiac diseases | 15.2% | 11.7% |
| Endpoint (pN0) | IM-MS RT | No IM-MS RT | HR | P |
|---|---|---|---|---|
| DFS rate | 53.9% | 53.6% | 0.93 (0.81-1.07) | 0.318 |
| DMFS rate | 67.2% | 67.4% | 0.93 (0.78-1.10) | 0.397 |
9 details
Randomised EORTC trial 22922/10925, stage I-III breast cancer, internal mammary + medial supraclavicular irradiation versus no IM-MS irradiation. This is the 20-year readout, presented as a plenary at ESTRO 2026, including a dedicated pN0 analysis.
The intervention is the IM-MS target volume itself, added to otherwise standard locoregional treatment. Per-arm dose and fractionation are not reported in source; what the presenters did quantify is the dosimetric era gap, with DBCG IMN2 mean heart doses 4-9 times lower (MHD 1.2 Gy right-sided, 2.3 Gy left-sided, treated 2007-2014).
Primary: overall survival (ITT). Secondary readouts presented at 20 years include DFS and DMFS under DATECAN definitions (DFS counts all deaths and all breast events including DCIS and contralateral; DMFS counts all deaths and distant metastases), breast-cancer mortality, non-breast-cancer mortality, second cancers, and RT-related late effects.
OS 61.0% vs 61.8%, HR=1.00 (0.90-1.10), P=0.967. DFS and DMFS are likewise flat (HR 0.97 each), and the pN0 subgroup shows no separation. The signal lives entirely in the cause-specific split.
No statistical difference in secondary cancers or second breast cancers between arms. Absolute RT-related late effects favour the control arm: cardiac disease 15.2% vs 11.7%, lung fibrosis 6.3% vs 3.2%, cardiac fibrosis 2.7% vs 1.7%.
The Danish DBCG IMN2 cohort (Nielsen, Lancet Reg Health Eur 2024) reported that IM-MS irradiation reduced distant metastasis and BCM and improved OS in node-positive pts at 15 years. The presenters attribute the divergence to technique, since IMN2 heart doses were 4-9x lower.
The pN0 result is a subgroup read on endpoints that were flat overall, so it cannot exclude a small benefit in that group. The competing-risk interpretation also rests on comparing this trial's toxicity against a non-randomised cohort treated a decade later, which is a dosimetric argument, not a trial result.
This is the cleanest available demonstration that an oncologically real nodal-RT benefit can be spent entirely on late cardiopulmonary mortality. It settles that IM-MS irradiation reduces breast cancer death; it does not settle whether the survival benefit is recoverable, which is now a planning question rather than a target-volume question.
Randomised, prespecified 1° OS, 20yr follow-up, null. Divergence from DBCG IMN2 is confounded by an old-technique heart dose (4-9x higher), not by design flaw.
- Does IM-MS survival benefit re-emerge at modern cardiac-sparing doses?
- Which nodal subgroups justify IM coverage given competing cardiac mortality?
📚 Sources · 🐦 2 tweets
📌 Internal Mammary and Medial Supraclavicular irradiation in stage I-III breast cancer: 20 years results of the randomised EORTC trial 22922/10925, including in pNo patients
— Elisabetta Bonzano MD, PhD (@to_be_elizabeth) May 17, 2026
Special Joint Presentation Led by Prof. Philip Poortmans and Orit Kaidar-Person ✨ at #ESTRO26 @ESTRO_RT… pic.twitter.com/KIoJtdhEzp
20-year outcomes of @EORTC internal mammary #radiotherapy trial.
— Shankar Siva (@_ShankarSiva) May 17, 2026
➡️internal mammary improved control
➡️ survival counterbalanced by late adverse events #radiotherapy #bcsm
Great to see the long term data at #ESTRO26, and discussing Charlotte Cole suggests with modern RT, long… pic.twitter.com/yPtlfrLcri
DBCG RT Natural
For≥60y, pT1N0, grade 1-2, ER≥10%, HER2 normal, margin ≥2mm, post-BCS
1.5% vs 9.8%
+RT 2/236, 1.5% (0.3-5.1); -RT 19/272, 9.8% (5.9-14.9)
TL;DR5yr invasive LR 1.5% with PBI vs 9.8% randomised no-PBI vs 8.2% self-selected no-PBI at 4yr median f/u.
The 2x2 by treatment received is the actionable read, not the arm comparison: -RT +ET reached 3.7% (7/213) while -RT -ET hit 12.2% (32/352), so ET adherence is what holds the omission strategy together, and it was suboptimal. PBI was 40Gy/15fr, not a 5-fraction schedule.
In a woman ≥60 with pT1N0 grade 1-2 ER-positive HER2-normal disease post-lumpectomy, this argues against dropping both PBI and endocrine therapy, and it does not address node-positive, lobular, grade 3, or ER-low disease, which were excluded.
PBI 40Gy/15fr drove LR to 1.5% (2/236) vs 9.8% randomised omission, and the -RT arm crossed the prespecified 4% ceiling. The +RT -ET cell at 3.0% (2/132) means RT alone holds local control without endocrine therapy, which moves the omission conversation for a patient who will not take or tolerate ET.
The -RT +ET cell reached 3.7% (7/213) versus 12.2% (32/352) with neither, so endocrine therapy alone is close to RT alone for local control here. But the ET grouping is by treatment received (≥4.5y vs <4.5y or low-risk), so that 3.7% describes completers and adherence is the load-bearing assumption in an ET-only strategy.
+3 more figures
| Study arm | Events/Total | CIF % (95% CI) |
|---|---|---|
| +RT | 2/236 | 1.5 (0.3-5.1%) |
| -RT | 19/272 | 9.8 (5.9-14.9%) |
| S-RT | 18/278 | 8.2 (4.5-13.3%) |
9 details 3 trials watching
Phase III randomized trial, PBI 40Gy/15fr vs no PBI, stratified by institution and endocrine therapy yes/no, with a third non-randomised self-selecting no-PBI cohort. Planned accrual 926 randomised with an interim analysis at 200 patients with 2 year follow-up. Median follow-up 4 years at this reading.
≥60 years, breast cancer treated with breast conservation, pT1N0, unilateral, unifocal, non-lobular, ER ≥10%, HER2 normal, grade 1-2, limited DCIS, margin ≥2mm. Endocrine therapy given per DBCG guideline, which recommends ET for pT1c and/or grade 2.
Partial breast irradiation, 40Gy in 15 fractions. This is a moderately hypofractionated PBI schedule, not the 5-fraction regimens now in wide use, which matters for how the toxicity and convenience side of the omission trade transfers.
Primary: 5 year invasive local recurrence, with a design assumption of 2% and a prespecified maximum acceptable 4%. Secondary: loco-regional side effects and quality of life. Follow-up yearly mammography plus loco-regional side effect assessment to 10 years.
All 41 recurrences were invasive and 39 of 41 arose in patients who received no PBI. Distant failure was rare across the whole trial at 4 events, 2 in each of the +RT and no-PBI groups.
Loco-regional side effects and QoL were prespecified secondary endpoints but no toxicity or QoL figures were reported in the source. The omission-versus-PBI toxicity trade that drives this decision is therefore unquantified here.
PRIME II and CALGB 9343 established that RT omission in older low-risk women is tolerable because absolute local recurrence stays low. Here the randomised no-RT arm reached 9.8% and crossed the trial's own 4% ceiling, which is the opposite result, and the discussant framed surgery alone as carrying high local recurrence even in low risk.
Median follow-up is 4 years against a 5 year primary endpoint, so the reported cumulative incidences are read before the timepoint the trial was designed around. The third arm is self-selected, not randomised, so its 8.2% carries confounding by whatever drove refusal, and the endocrine therapy split is by treatment received rather than assignment.
The trial's contribution is that it isolates the floor: a group with no adjuvant treatment at all, which the modern omission trials do not have because endocrine therapy is universal in their omission arms. 12.2% at that floor reframes the published omission literature as measuring RT omission on an endocrine backbone, not omission of local therapy. It does not settle whether PBI or ET is the better single agent, since 3.0% and 3.7% overlap widely.
CONSORT flow
Randomised, prespecified LR endpoint, stopped early by independent monitoring for exceeding the 4% threshold. Cuts against the de-escalation direction PRIME II and CALGB 9343 set.
- Does 5-fraction PBI match 40Gy/15fr local control in this population n=910 · primary completion 2029-11 · phase 3 PBI vs WBI, 1 week each, LR endpoint
- Toxicity and QoL trade between PBI and endocrine monotherapy n=30 · primary completion 2023-11 · SBRT added to endocrine tx, unoperated pts 75+n=168 · primary completion 2030-07 · randomised 30Gy vs 26Gy/5fr PBI, PRO endpoint
- Whether 4yr separation holds at the 5yr primary timepoint
📚 Sources · 🐦 2 tweets
Another trial showing even for lR optimal local control with RT and ET and suboptimal adherence to ET. In era of 5 fraction decision making is easier # Estro2026 pic.twitter.com/nkvYl3iuTn
— Sushil (@Sushilberiwal) May 17, 2026
Danish #breastcancer partial breast #radiotherapy “natural” trial.
— Shankar Siva (@_ShankarSiva) May 17, 2026
➡️ No postoperative treatment had highest risk of recurrence
➡️either tamoxifen or #radonc reduced recurrence
➡️combined tamoxifen + RT had no recurrences
In context of EUROPA trial, RT has best QoL vs endocrine… pic.twitter.com/bDVmbDKRNb
IMPORT HIGH
ForInvasive early breast, pT1-3 pN0-pN3a M0, post-BCS, requiring tumour bed boost
3.7% vs 3.5% 10yr IBTR (48Gy SIB vs 40+16Gy)
95% CI 2.6-5.3 vs 2.4-5.0; 53Gy/15F 5.5% (4.1, 7.3)
TL;DR10yr IBTR 3.7% with 48Gy/15F SIB vs 3.5% with 40Gy/15F + 16Gy/8F sequential; 53Gy/15F higher at 5.5%.
The decision this hardens is delivery, not dose: 48Gy/15F SIB holds at 3.7% (2.6, 5.3) IBTR at 10 years against 3.5% (2.4, 5.0) for a sequential 16Gy/8F phase, in a higher risk group. 53Gy/15F sits at 5.5% (4.1, 7.3), so escalation buys nothing.
For a woman after breast conserving surgery for pT1-3 pN0-pN3a invasive disease who needs a tumour bed boost, the 10-year data support the integrated 48Gy/15F arm over a separate sequential boost; they do not speak to boost omission or to 5-fraction whole-breast schedules.
Three weeks, one plan: the boost is integrated into 15 fractions with a modest dose reduction to whole breast distant from tumour, and IBTR at 10 years matches the sequential 16Gy/8F phase. Escalating the integrated boost to 53Gy/15F does not improve local control.
| Dose group | 10yr IBTR (95% CI) | 10yr OS abs. diff vs 40Gy/15F |
|---|---|---|
| 40Gy/15F + 16Gy/8F | 3.5% (2.4, 5.0) | reference |
| 48Gy/15F (3.2Gy/F) | 3.7% (2.6, 5.3) | -0.5 (-3.0, 2.8) |
| 53Gy/15F (3.5Gy/F) | 5.5% (4.1, 7.3) | 1.5 (-1.4, 5.1) |
+1 more figure
8 details 4 trials watching
Three-arm randomised multicentre trial, 1:1:1, N=2617 across 76 UK hospitals, recruited 2009-2015. Annual clinical follow-up to 10 years; PRO and photographic assessment collected only to 5 years.
Women ≥18 after breast conserving surgery for invasive early breast cancer, pT1-3, pN0-pN3a, M0, all requiring a tumour bed boost. Described as a higher-than-average risk group.
40Gy/15F + 16Gy/8F sequential boost (N=871), 48Gy/15F SIB at 3.2Gy/F (N=874), 53Gy/15F SIB at 3.5Gy/F (N=872). The SIB arms escalate to the regions at highest risk with a modest dose reduction to whole breast distant from tumour, all delivered in 3 weeks.
Endpoint reported here: ipsilateral breast tumour relapse at 10 years. The original sample size calculation assumed a 5% control rate at 5 years. Absolute OS difference and clinician-assessed normal tissue effects also reported.
The 5-year ordering holds at 10 years: the two lower-dose groups sit close together and 53Gy/15F stays highest. Both absolute OS differences vs 40Gy/15F have intervals containing zero.
Moderate/marked effects at 10 years were given as bounds across all randomised groups: <18% breast distortion or shrinkage, <10% induration, <2% telangiectasia, <2% breast oedema. No per-arm split reported in source.
EORTC 22881-10882 established the tumour bed boost itself; IMPORT HIGH asks how to deliver it and whether more dose helps. At 10 years, integration works and escalation does not, the same ranking the 5-year publication (Coles et al. Lancet 2023;401:2124-37) reported.
PRO and photographic assessment stopped at 5 years, so the 10-year toxicity comparison rests on clinician scoring reported as all-group bounds, not per-arm rates. Observed IBTR also ran below the 5% control rate the sample size calculation assumed.
The practical read is fraction count, not dose: a boost folded into 15 fractions removes the separate 16Gy/8F phase with no 10-year IBTR cost, while 53Gy/15F returns nothing. What the trial does not settle is whether the same integration transfers to 5-fraction whole-breast schedules.
CONSORT flow
Mature 10yr follow-up of a 2617-pt randomised trial; extends the 5-year Lancet 2023 read rather than changing it. No formal 10yr non-inferiority margin stated in source.
- Simultaneous integrated boost within 5-fraction whole-breast schedules recruiting Ultra-hypofractioNated Adjuvant Radiotherapy ± sImultaneous Integrated Boost for Low-risk Breast Cancer Patients Phase 2n=65 · primary completion 2025-10 · ultra-hypofx WBI +/- SIB, low-risk, phase 2recruiting Ultra Hypo-fractionated Adjuvant Whole Breast Radiation Therapy With Simultaneous Integrated Boost for Early-Stage Breast Cancer (H-ASSIST) Phase 2n=90 · primary completion 2028-02 · 5-fraction WBI with SIB tumor bed boost, phase 2
- Patient-reported cosmesis beyond 5 years, unmeasured after photographic follow-up ended n=139 · primary completion 2025-12 · 10y registry with cosmesis + QoL assessmentsn=50 · primary completion 2028-09 · cosmesis + PROMs to 60mo after ultra-short WBI/SIB
📚 Sources · 🐦 1 tweet
Day THREE of #ESTRO26 Coverage by OncoAlert 🚨
— OncoAlert (@OncoAlert) May 17, 2026
Ten-year results of the IMPORT HIGH trial (ISRCTN47437448): Dose escalated simultaneous integrated boost radiotherapy in early breast cancer Presented by Charlotte Coles 🇬🇧 #RadOnc ☢️
Ten-year IMPORT HIGH trial data show that a… pic.twitter.com/7RqVy2SrQm
DBCG HYPO
ForNode-negative early breast cancer or DCIS, post-BCS whole-breast RT
24.7% vs 19.5% at 10 yr
HR 0.76 (95% CI 0.62-0.92), p=0.005, favouring 40 Gy/15 fr
TL;DR10yr grade 2-3 breast induration 24.7% (50Gy) vs 19.5% (40Gy), HR 0.76 (0.62-0.92), p=0.005, no recurrence penalty.
The fibrosis separation persists at a decade, 24.7% vs 19.5%, HR 0.76 (0.62-0.92): 40 Gy/15 fr is not merely non-inferior on late morbidity, it is better, with OS numerically higher (93.0% vs 92.1%, p=0.10). For a node-negative or DCIS patient, the residual argument for 25 fractions is gone.
For node-negative invasive breast cancer or DCIS after breast conservation, this supports 40 Gy/15 fr over 50 Gy/25 fr on late induration with no recurrence cost; node-positive and regional nodal irradiation populations were not enrolled and are not addressed.
The fibrosis separation persists at a decade, 24.7% vs 19.5%, HR 0.76 (0.62-0.92), so 40 Gy/15 fr is superior on late induration rather than merely non-inferior. In node-negative disease or DCIS, whole-breast only, the late-tissue argument for 25 fractions has no support here.
| Endpoint (10-yr) | 50 Gy/25 fr | 40 Gy/15 fr | HR (95% CI), p |
|---|---|---|---|
| Grade 2-3 breast induration | 24.7% | 19.5% | 0.76 (0.62-0.92), p=0.005 |
| Overall survival | 92.1% | 93.0% | 0.81 (0.63-1.04), p=0.10 |
+1 more figure
8 details 5 trials watching
Phase III randomised non-inferiority trial, 1:1, run across Denmark, Norway and Germany from 2009-2014. These are the prespecified 10-year analyses of toxicity, recurrence and survival, at a median follow-up of 12.8 years.
1,882 women with node-negative breast cancer or DCIS. After exclusions (13 and 16), 933 and 936 women were analysed in the two arms, with 917 carried into the morbidity analysis of one arm.
Whole-breast irradiation only: 50 Gy in 25 fractions versus 40 Gy in 15 fractions. No regional nodal irradiation question is posed, and boost details are not reported in the source slides.
Primary: grade ≥2 breast induration at 3 years, requiring two consecutive visits or the final follow-up. Morbidity was scored at years 0, 1, 2, 3, 4, 5 and 10; recurrence and survival are the co-reported 10-year outcomes.
The toxicity endpoint is the positive result here: 10-year grade 2-3 induration 24.7% with 50 Gy vs 19.5% with 40 Gy, HR 0.76 (0.62-0.92), p=0.005. The fibrosis advantage of hypofractionation is durable, not an early-follow-up artefact.
START-B and the UK 10-year hypofractionation data established 40 Gy/15 fr as at least equivalent for control with less normal-tissue effect; DBCG HYPO reproduces that direction in a contemporary node-negative and DCIS population treated 2009-2014, in an era of CT planning and modern systemic therapy rather than the 1990s cohorts.
Breast induration is a clinician-scored endpoint and the source does not state whether assessment was blinded, which matters when the two arms are trivially distinguishable by treatment duration. Locoregional recurrence, distant failure and breast cancer mortality are reported only as 'no significant difference' with no event counts or confidence intervals in the source, so the precision of the non-inferiority claim cannot be judged from these slides.
A 5.2-percentage-point absolute reduction in decade-level grade 2-3 induration is a real cosmetic and symptomatic difference in a population most of whom will never recur. The OS HR of 0.81 (0.63-1.04) is directionally in favour of the shorter schedule but is not significant and should not be read as a survival benefit of hypofractionation.
Randomised phase III, prespecified 10-yr analysis, 12.8-yr median follow-up, primary toxicity endpoint favours 40 Gy/15 fr. Reinforces already-standard moderate hypofractionation rather than changing it.
- How does 40 Gy/15 fr compare with five-fraction schedules on 10-yr fibrosis? n=2100 · primary completion 2029-03 · randomised 1 wk vs 3 wk adjuvant WBI, non-inferiorityrecruiting 5 fr Ultrahypofractionated WBI and SIB for Breast Cancer With Unfavorable Characteristics Phase NAn=458 · primary completion 2029-06 · 26 Gy/5 fr + SIB vs 40.05 Gy/15 fr + SIB, randomisedrecruiting Ultra-Hypofractionated vs Moderate Hypofractionated Radiotherapy for Regional Lymph Nodes in High Risk Breast Cancer Phase NAn=1950 · primary completion 2034-03 · 26 Gy/5 fr vs 40-42.5 Gy/15-16 fr nodal RT
- Does the induration benefit hold with regional nodal irradiation? recruiting Hypofractionated Irradiation At Regional Nodal Area for Breast Cancer Vs Existed Standard Treatment Phase 3n=801 · primary completion 2022-12 · phase 3 hypofx vs conventional RNI, safety endpointactive Hypofractionated vs. Conventional Regional Nodal Radiation Therapy for Patients With Invasive Breast Cancer Phase 2n=805 · primary completion 2030-02 · 3 wk vs 5 wk nodal RT, arm edema and recurrence
- Locoregional recurrence event counts and confidence intervals
📚 Sources · 🐦 1 tweet
Day TWO of #ESTRO26 Coverage by OncoAlert 🚨
— OncoAlert (@OncoAlert) May 17, 2026
10-year Follow-Up of the DBCG HYPO Trial: Breast Induration, Recurrence and Survival After Hypofractionated Whole Breast Irradiation Presented by Hanna Forsberg 🇩🇰 @BOffersen #RadOnc ☢️ #BreastCancer
The DBCG HYPO trial reports… pic.twitter.com/4qf9R3HZwT
HypoG-01
ForBreast cancer receiving adjuvant RT incl. nodal volumes, ESTRO-contoured
118 events / 1260 pts
Median f/u 4.8 yrs; LRR 20/118, iLRR sites in-volume 20/30 (67%)
TL;DR118 first events over 4.8yr median f/u; 67% of LRR sites in-volume, patterns comparable across 40Gy/15fx and 50Gy/25fx.
The actionable number is 20/30 iLRR sites in-volume, with 19/30 nodal and concentrated in levels 1 and 2: failures are happening inside correctly contoured CTVs, not at their edges, so this argues against widening nodal volumes and supports ESTRO contouring as drawn. Per-arm event counts not reported in source.
In node-involved breast cancer planned for adjuvant regional nodal RT, this supports keeping ESTRO-guideline CTVs rather than expanding level 1 to 2 coverage for geographic-miss concern; it does not address volume choice in pts contoured outside those guidelines.
20/30 iLRR sites were in-volume and 19/30 nodal, mainly levels 1 and 2. Recurrences are inside correctly drawn CTVs, so the fix is not a wider nodal volume, and ESTRO contouring holds under 40 Gy/15 fx. Per-arm counts not reported in source.
19/30 recurrence sites were nodal, concentrated in levels 1 and 2, the levels most affected when axillary dissection is replaced by sentinel-node-only management. Relevant to how much residual nodal risk surgical de-escalation leaves for RT to absorb; the analysis does not stratify by axillary surgery type.
| Event / site | n |
|---|---|
| Isolated distant recurrence | 61 |
| Second malignancy | 37 |
| Isolated locoregional recurrence | 19 |
| Concomitant locoregional recurrence | 1 |
| LRR as first event | 20 / 118 |
| iLRR sites in-volume | 20 / 30 (67%) |
| iLRR sites nodal | 19 / 30 |
+1 more figure
9 details 5 trials watching
Pre-planned secondary analysis of the HypoG-01 phase III trial, analysed ITT. N=1,260, median follow-up 4.8 years. Reported as a patterns-of-failure and dosimetric mapping study, not a re-test of the parent efficacy endpoint.
Randomisation was 40 Gy/15 fractions over 3 weeks vs 50 Gy/25 fractions over 5 weeks, each with a tumour-bed boost. Contouring followed ESTRO guidelines, which is what makes the in-volume/marginal classification interpretable rather than institution-specific.
Primary event was the first oncological event: locoregional recurrence, distant recurrence, or second malignancy. LRR was classified against the CTV as in-volume (within CTV), marginal (outside CTV but ≥50% prescribed dose), or out-of-volume (<50%). Planned dose at each recurrence site was re-estimated on the original planning CT.
118 first events. Distant recurrence and second malignancy dominated (61 and 37); LRR was the least common first event at 20/118. Among 30 iLRR sites, 20 (67%) were in-volume and 19/30 were nodal, mainly levels 1 and 2.
The dosimetric read is retrospective by construction: dose at the recurrence site is estimated on the initial plan CT, so anatomic change and registration error over a median 4.8 years both push sites toward an in-volume label. The event count also caps what can be concluded, since 30 sites split across two arms leaves the "not obviously different" claim underpowered rather than negative.
START-B and FAST-Forward established that moderate and ultra-hypofractionation do not cost local control, but neither mapped recurrence sites against the CTV. The contribution here is geographic rather than actuarial: it tests whether the *volume*, not the *dose per fraction*, is where hypofractionated regional treatment could fail.
A 67% in-volume rate reframes residual LRR as a biology problem, not a coverage problem: pts recurred where dose was delivered. The nodal concentration in levels 1 and 2 is the one signal worth watching, since those are the levels most variably treated when surgical axillary management is de-escalated.
Pre-planned secondary analysis, descriptive only. No per-arm effect size or statistical comparison in source; 30 iLRR sites cannot exclude an arm difference.
- Per-arm LRR site distribution, 40 Gy/15 fx vs 50 Gy/25 fx recruiting Hypofractionated Irradiation At Regional Nodal Area for Breast Cancer Vs Existed Standard Treatment Phase 3n=801 · primary completion 2022-12 · phase 3 hypofx vs conventional RNI, node-positiverecruiting Conventionally Fractionated vs. Hypofractionated Comprehensive Nodal Irradiation for Breast Cancer Using Pencil Beam Scanning Proton Therapy Phase 3n=276 · primary completion 2038-02 · phase 3 3wk vs 5wk comprehensive nodal RT, protons
- Does ultra-hypofractionation shift nodal failure geography? n=768 · primary completion 2029-01 · randomised ultrahypo vs moderate hypo RNI, 4 cohortsrecruiting Ultra-Hypofractionated vs Moderate Hypofractionated Radiotherapy for Regional Lymph Nodes in High Risk Breast Cancer Phase NAn=1950 · primary completion 2034-03 · 26Gy/5fx vs 40Gy/15fx RNI, n=1950, recurrence f/u
- Level 1-2 coverage after sentinel-node-only axillary management n=205 · primary completion 2027-12 · RNI volume tailored to SLND-alone vs SLND+ALND
📚 Sources · 🐦 1 tweet
Day TWO of #ESTRO26 Coverage by OncoAlert 🚨
— OncoAlert (@OncoAlert) May 16, 2026
Patterns of locoregional and distant recurrence and dosimetric analysis in the HypoG-01 phase III trial Presented by Louis Munschi 🇫🇷 #RadOnc ☢️
In the HypoG-01 phase III trial (1260 patients, median follow-up 4.8 years), 118… pic.twitter.com/ogARInu0fB
Tumour bed boost after BCS+WBRT (Dutch cohort)
ForPost-BCS invasive breast cancer receiving WBRT, boost decision pending
TL;DR10yr IBTR 1.2% with 0-2 risk factors regardless of boost, supporting boost omission in the modern systemic era.
The decision this moves is boost omission, and the number that moves it is 10yr IBTR 1.2% in the 0-2 risk-factor group whether or not a boost was given, on 15,085 vs 13,845 pts. Note the ≥3 group ran higher WITH boost (3.3% vs 2.7%), which is allocation bias, not boost harm. Boost dose and fractionation are not in the source.
In a post-BCS patient over 40 with grade 1-2, hormone-receptor-positive disease receiving guideline-concordant systemic therapy, this supports omitting the tumour bed boost; it does not resolve the boost question for pts carrying three or more risk factors.
The omission decision rests on 10yr IBTR of 1.2% in the 0-2 risk-factor group with and without boost (15,085 vs 13,845 pts). The ≥3 stratum ran higher WITH boost (3.3% vs 2.7%), a signature of risk-based allocation rather than boost harm. Boost dose and fractionation are absent from the source.
| Risk factors | N no boost | N boost | 5yr no boost | 5yr boost | 10yr no boost | 10yr boost |
|---|---|---|---|---|---|---|
| 0-2 | 15,085 | 13,845 | 0.6% | 0.7% | 1.2% | 1.2% |
| ≥ 3 | 149 | 733 | 1.3% | 2.9% | 2.7% | 3.3% |
| Uncertain | 592 | 944 | 0.8% | 3.3% | 1.4% | 3.6% |
+2 more figures
9 details
Population-based Dutch cohort from the Netherlands Cancer Registry linked to pathology, on behalf of the DBRT group. Treatment years 2012-2016, follow-up to 10 years. Observational, no randomisation and no adjusted comparison reported in source.
Breast-conserving treatment with or without an RT boost, N=31,348 across the three risk strata. Stratification is by a count of five risk factors: age ≤40, grade 3, triple-negative, guideline-indicated systemic therapy not adequately given, and no pCR after neoadjuvant chemo in TNBC or HER2+.
Whole-breast RT with or without a tumour bed boost. Boost dose, fractionation, technique (photon vs electron vs SIB) and the WBRT schedule are not reported in the source slides, which limits transfer to a specific departmental protocol.
Primary: ipsilateral breast tumour recurrence (IBTR), histologically confirmed, identified by an algorithm over pathology report codes and free text. Reported as cumulative incidence at 5 and 10 years by risk-factor count. Benchmarked against the Assisi thresholds: omission acceptable at <3% 10yr IBTR with boost, <6% without.
IBTR was low in every stratum. The only cell crossing an Assisi threshold was ≥3 risk factors treated with a boost at 10 years, and even there the no-boost value in the same stratum was lower.
EORTC 22881-10882 established that a boost roughly halves IBTR, and that trial's control-arm event rates were an order of magnitude above these. IMPORT HIGH and the 2024 Assisi think tank both moved the field toward de-escalating or restricting the boost; this cohort supplies the contemporary absolute rates those recommendations assumed but could not show.
Boost was allocated by guideline-based risk, so the boost groups are adversely selected and the raw contrast understates any boost effect; the higher rate in the ≥3 boost group is the visible signature of that confounding. The ≥3 no-boost cell holds only 149 pts, and the 'uncertain' stratum (592 / 944) shows a boost-no-boost gap wide enough to suggest unmeasured risk is driving allocation there too.
The finding is about absolute rather than relative benefit: a preserved 50% relative reduction applied to a 1.2% 10-year event rate is not worth five extra fractions and a fibrosis penalty. What the cohort cannot say is whether the boost is the reason those low-risk rates are low, since roughly half the low-risk group received one.
Registry cohort, no randomisation and no adjusted effect estimate; boost allocation confounded by risk. Supports the direction already set by IMPORT HIGH and Assisi thresholds.
- Which ≥3 risk-factor subgroups actually benefit from a boost
- Whether boost omission holds under randomised testing in low-risk pts
- Boost dose and technique used across this cohort
📚 Sources · 🐦 1 tweet
Day TWO of #ESTRO26 Coverage by OncoAlert 🚨
— OncoAlert (@OncoAlert) May 16, 2026
Is a boost to the tumour bed still indicated after breast-conserving surgery and whole-breast radiotherapy in the era of modern systemic therapy? Presented by Femke Froklage 🇳🇱 #RadOnc ☢️
We aimed to identify a subgroup of breast… pic.twitter.com/RqK5r9XPqW
OligoCare
ForOligometastatic solid tumors treated with SABR, mixed primaries and lesion sites
TL;DRReal-world SABR local failure 5.0% at 1yr, 11.4% at 3yr across 2447 pts / 3533 lesions; CRC worst at 19.6%.
The actionable RT signal is minimum PTV dose, called the single most critical technical factor, and the de novo vs repeat OMD gap the authors attribute to higher delivered dose. CRC failed most (19.6% at 3yr) despite the highest median dose per fraction, which argues for escalation or combination rather than coverage alone. No dose thresholds are reported in source.
For a prostate or NSCLC oligomet being planned for SABR, this real-world cohort supports expecting durable in-field control (8.1% and 9.8% failure at 3yr); it does not support the same expectation for a colorectal met, where 3yr failure reached 19.6%.
Minimum PTV dose is named the most critical technical factor, so coverage of the low-dose region, not the prescription isodose, is where the planning attention goes. CRC failed worst (19.6% at 3yr) despite the highest median dose per fraction, so escalation alone may not close that gap. No dose thresholds reported in source.
SABR delivers 88.6% in-field control at 3yr in routine practice, so local failure is not the dominant driver of progression in most oligometastatic primaries. The exception is colorectal, at 19.6% failure by 3yr, where the authors suggest combination systemic approaches alongside local therapy rather than dose escalation alone.
| Primary | Total | 1 year | 3 years |
|---|---|---|---|
| Colorectal | 518 | 9.3% | 19.6% |
| Breast | 378 | 4.1% | 11.3% |
| NSCLC | 530 | 6.0% | 9.8% |
| Prostate | 1021 | 2.7% | 8.1% |
+2 more figures
10 details 4 trials watching
Prospective EORTC OligoCare registry cohort, interim analysis. 57 institutions, enrolment July 2019 to July 2025. No randomisation and no comparator arm; technique and dose were chosen by the treating institution.
2447 eligible pts with 3533 lesions. Median age 69 (range 28-94), 69% male. Primaries reported for the local-control breakdown were prostate (1021), NSCLC (530), colorectal (518) and breast (378).
SABR to oligometastatic lesions across bone (869 non-vertebral, 515 spine), lung (807), non-regional nodes (558), liver (306), brain (231) and other (247) sites. Minimum PTV dose was the technical factor most associated with outcome; specific dose and fractionation schedules are not reported in source.
Local in-field progression, reported as cumulative incidence with 99% CI, at 1 and 3 years. Median follow-up 31 months, minimum 6 months.
Overall local in-field progression 5.0% at 1yr and 11.4% at 3yr, ie 88.6% local control at 3yr. By primary, colorectal was the outlier and prostate the best.
Randomised oligometastatic SABR trials (SABR-COMET, STOMP, ORIOLE) were built on much smaller, more selected cohorts and reported survival or progression endpoints rather than lesion-level in-field control at this scale. This registry does not test the SABR question those trials asked; it reports what in-field control looks like once SABR is delivered in routine multi-institutional practice.
Dose and fractionation were institution-chosen, so the minimum-PTV-dose association is confounded by target site, prior irradiation and case selection. No PTV dose threshold, no per-primary dose data and no toxicity are reported in source, so the technical conclusion cannot be translated into a planning constraint.
The CRC finding is the one that changes a plan: worst local control despite the highest median dose per fraction points at intrinsic radioresistance rather than underdosing, and the authors call for escalation or combination strategies. The de novo versus repeat OMD gap is reported as a dose effect, which is plausible but is exactly the kind of comparison a registry cannot separate from the reasons a lesion is being re-treated.
Prospective multi-site registry, no randomised comparator, institution-chosen technique. Large real-world cohort supports existing SABR practice in OMD rather than testing it.
- Minimum PTV dose threshold that predicts local control
- Combination or dose-escalation strategies for colorectal oligomets recruiting Fruquintinib Combined With Sintilimab ± Radiotherapy for Third-line Treatment of Colorectal Cancer With Liver Metastases Phase 2n=62 · primary completion 2026-10 · SBRT+LDRT with sintilimab/fruquintinib, MSS CRC liverrecruiting Low and Intermediate Risk OliGometastatic ColoREctal CancEr PatieNts Treated with Stereotactic ABlative Radiotherapy Phase NAn=204 · primary completion 2031-04 · randomised SABR + chemo in 1-3 CRC oligomets
- Whether repeat OMD failure reflects dose or disease biology active Bony M - Stereotactic Ablative Radiotherapy (SABR) of Bony Metastases in Patients With Oligometastatic Disease Phase NAn=67 · primary completion 2023-01 · SABR in de novo vs recurrent OMD bone lesionsn=397 · primary completion 2028-06 · MR-guided adaptive SBRT, tumor control by site
📚 Sources · 🐦 1 tweet
📣 #ESTRO26 - @UmbertoRicardo e2irradiate @EORTC prospective OLIGOCARE registry of SABR for oligomets. ~2500 patients, ~3500 mets.
— Shankar Siva (@_ShankarSiva) May 17, 2026
➡️ local failure 5% at 1 year and 11% at 3 years
➡️ Colorectal cancer has higher risk of progression
➡️ minimum PTV dose correlated with outcome… pic.twitter.com/cx4zERqHhK
RCC SBRT (5-year local control)
ForPrimary RCC treated with SBRT; stage and operability not stated in source
TL;DR100% local control at 5 years for RCC treated with SBRT, per a conference slide; no N, dose, or CI in source.
7 details
Not reported in source. The tweet gives a 5-year local control figure with no study type, N, institution, or registry identifier, so design cannot be inferred.
SBRT to primary RCC; dose, fractionation, number of fractions, and target definition are not reported in source. These are the parameters that gate transfer to practice, and none are available here.
100% local control at 5 years as stated in the source tweet. No confidence interval, no n-at-risk, and no statement of whether this is a Kaplan-Meier estimate or a crude proportion.
Beyond the missing design, the specific risk is effective follow-up: a medically inoperable RCC cohort loses pts to non-cancer death well before 5y, so a 100% figure can rest on very few pts at risk. Local control definition (RECIST-style size change vs absence of growth vs biopsy) is also unstated and swings the estimate.
Single tweet with one number, no N, design, dose, or LC definition. Cannot judge whether the 100% figure reflects efficacy or short effective follow-up.
- Dose and fractionation behind the reported 5-year local control
- Local control definition and n-at-risk at 5 years
- SBRT vs partial nephrectomy in operable primary RCC
📚 Sources · 🐦 1 tweet
These results are so impressive!! 💯 local control at 5 years for RCC treated with SBRT@DrRanaMcKay @AdityaBagrodia @DrTylerStewart @DrYukselUrun @OncoAlert https://t.co/fUB3airM5g
— Tyler Seibert MD PhD (@TylerSbrt) May 17, 2026
DIREKHT
ForResected HNSCC referred for post-operative RT
TL;DRDe-escalated post-op HNSCC RT: contralateral neck sparing and primary CTV to 56 Gy in selected pts; no outcome numbers in source tweet.
The two levers named are the ones that gate post-op HNSCC RT morbidity: contralateral neck omission and a 56 Gy primary CTV rather than standard higher-dose coverage. Which pts qualified is the whole question, and the source text does not give the selection criteria or any control or toxicity numbers.
Both levers are RT-side decisions: whether to cover the contralateral neck electively, and whether 56 Gy suffices for the primary CTV in selected post-op pts. The source names the approach but gives no selection rule and no control or toxicity numbers, so it flags a trial to read rather than a volume or dose change to adopt.
6 details
Two de-escalation levers reported in source: contralateral neck sparing in a specified subgroup, and reduction of the primary CTV dose to 56 Gy. Fractionation, technique, and the dose to involved or high-risk volumes are not stated in the source text.
Described as a trial, but phase, randomisation, N, sites, and follow-up are not stated in the source tweet.
No primary endpoint, effect size, or toxicity result reported in source. The tweet is commentary on the trial's approach, not its results.
Everything that would let a reader act on this is missing from the source: the selection rule for contralateral neck omission, the comparator, and any locoregional control or late-toxicity figures. A de-escalation result is only interpretable against its non-inferiority margin, which is not given.
Source is a single commentary tweet with no design, N, endpoint, or effect size. Nothing to classify beyond the de-escalation concept.
- Which pts qualify for contralateral neck sparing post-operatively
- Whether 56 Gy primary CTV holds locoregional control vs standard dose
📚 Sources · 🐦 1 tweet
There are tremendous opportunities to improve post-operative radiotherapy in HNSCC. The DIREKHT trial is an excellent example of such work, in which they spared the contralateral neck in a specified group of patients and/or reduced the primary CTV dose to 56 Gy.
— David Sher (@DavidSherMD) May 16, 2026
The details… https://t.co/7W84LYIofR