Phase 3 RCT
NRG Oncology/RTOG 0848
ForResected pancreatic head adenocarcinoma, progression-free after adjuvant chemo
HR 0.96
90% CI 0.79-1.18, 1-sided P=.38; primary EP not met
TL;DROS primary EP not met (HR 0.96, 90% CI 0.79-1.18) adding adjuvant CXRT to gemcitabine; node-negative subgroup OS benefit on interaction (P=.0063).
The RT read is the node-negative interaction: CXRT improved OS (P=.0063) and DFS (P=.014) in node-negative pts, though the subgroup HR/median isn't in the source text. Unlike ESPAC-1's older 5-FU CXRT, modern CXRT showed no OS harm. Moves selective adjuvant CXRT for node-negative resected head tumors, pending FOLFIRINOX-era confirmation.
This reopens selective adjuvant CXRT in node-negative resected head tumors (OS interaction P=.0063), where modern technique avoided the OS harm ESPAC-1 saw. Cost is doubled grade 3 toxicity (38% vs 19%); dose and target volume aren't in the source, and node-positive pts got no benefit.
Adjuvant gemcitabine-based chemo alone stays the reference: adding CXRT didn't improve OS (HR 0.96) or DFS (HR 0.82, P=.089) overall and raised grade 3 toxicity to 38% vs 19%. The node-negative interaction (P=.0063) would need retesting against FOLFIRINOX before altering adjuvant sequencing.
8 details 3 trials watching
Multicenter phase IIR/III, two-step RCT. Step 1: gemcitabine vs gemcitabine + erlotinib. Step 2 (reported here): random assignment to a sixth chemo cycle ± CXRT after 5 progression-free cycles. N=354 (180 CXRT, 174 chemo).
Curative-intent resected pancreatic head adenocarcinoma, progression-free on adjuvant chemo. Median age 63, 55% male, 56% PS 1.
Fluoropyrimidine-sensitized CXRT added to the sixth cycle. Dose, fractionation, and target volume not stated in the source excerpt.
Primary: overall survival. Secondary: DFS. Powered for HR 0.76 (316 events, 80% power, 1-sided α=.05).
Primary OS not met (HR 0.96). The one positive signal was the treatment-by-nodal-status interaction (OS P=.0063, DFS P=.014) favoring CXRT in node-negative pts; subgroup effect size not in source.
| Endpoint | Chemo + CXRT | Chemo alone |
|---|---|---|
| Median OS | 2.3 yr (2.0-2.6) | 2.6 yr (2.1-3.1) |
| 5-yr OS | 27.9% (22.2-33.6) | 23.1% (17.7-28.6) |
| OS HR (90% CI) | 0.96 (0.79-1.18), P=.38 | ref |
No increase in grade 4/5 toxicity. Grade 3 toxicity higher with CXRT: 38% vs 19% (P<.001).
ESPAC-1's older 5-FU-based CXRT suggested inferior outcomes; here modern CXRT shows no OS harm but no all-comer benefit. Backbone predates FOLFIRINOX-type adjuvant chemo, named in the source as current SOC.
Node-negative benefit rests on a subgroup interaction, not the prespecified primary. Trial underwent multiple mid-course modifications (LAP07, accrual, slow event rate), and no local-control or pattern-of-failure endpoint is reported despite RT's locoregional rationale.
Clean negative primary OS (HR 0.96) reinforces no routine adjuvant CXRT; node-negative benefit is a subgroup interaction needing confirmation; gemcitabine backbone predates FOLFIRINOX.
In resected node-negative pancreatic head adenocarcinoma completing adjuvant gemcitabine, this offers a subgroup signal favoring fluoropyrimidine-sensitized CXRT (OS interaction P=.0063); it does not extend to node-positive pts, where CXRT showed no OS or DFS benefit.
- Does node-negative CXRT benefit hold with mFOLFIRINOX backbone? n=770 · primary completion 2028-06 · phase 3 adjuvant CXRT vs chemo, resected high-risk
- Neoadjuvant vs adjuvant CXRT sequencing in node-negative resected pancreas recruiting Preoperative Stereotactic Body Radiation Therapy in Patients With Resectable Pancreatic Cancer Phase 2n=25 · primary completion 2026-09 · preop SBRT then resection in resectable pancreas
- Local-regional control and pattern of failure with modern CXRT n=30 · primary completion 2028-10 · freedom from local failure at 12mo, SBRT
📚 Sources · 📄 1 paper
Abstract
TROG 08.03 RAVES QOL Substudy
ForPost-RP prostate cancer with adverse pathology or PSA >0.2 ng/ml
TL;DRAt 5yr, 16% vs 2% severe urinary leakage aRT vs no RT (p=0.01); sRT timing had no QOL effect.
The mechanism of sRT's benefit is sparing, not delay: time from RP to RT showed no association with any QOL domain at 3-5 yr (all coefficients ns), and irradiated sRT pts looked like aRT pts. The gain sits entirely with the men who never need RT, so late salvage confers no functional dividend over early salvage.
9 details 4 trials watching
Planned secondary analysis of the TROG 08.03 RAVES randomised trial comparing adjuvant RT with salvage RT delivered at PSA >0.2 ng/ml after radical prostatectomy. Patient-reported QOL collected prospectively across multiple Australian and New Zealand sites.
EORTC QLQ-C30 and QLQ-PR25. The unit of analysis is a minimal clinically important change (MCIC), a decline of >0.5 SD from baseline, in bowel symptoms, urinary symptoms, sexual activity, and sexual functioning.
The aRT arm (n=166) reported more bowel-symptom MCIC at 1-5 yr than sRT pts who never required RT. Against pts in the sRT group who did receive RT, no consistent differences in urinary, bowel, or sexual domains emerged.
| Timepoint | Adjuvant RT | No RT | p |
|---|---|---|---|
| 4 yr | 15/124 (12%) | 1/59 (1.7%) | 0.02 |
| 5 yr | 18/111 (16%) | 1/50 (2%) | 0.01 |
| Domain / timepoint | aRT | sRT | p |
|---|---|---|---|
| Sexual activity MCIC, 3 yr | 32% | 58% | 0.004 |
| Sexual activity MCIC, 4 yr | 43% | 65% | 0.038 |
| Urinary symptom MCIC, 2 yr | 23% | 38% | 0.036 |
| Severe urinary leakage, 5 yr | 16% | 13% | 0.7 |
Dose, fractionation, and target volume are not reported in the source text. Median follow-up from RT was 2.6 yr in the salvage group who received RT (IQR 1.2-5.2), and aRT pts started RT younger (63.9 vs 66.8 yr, p=0.01).
Self-reported QOL in an unblinded trial, so expectancy cuts toward the arm that knows it was irradiated. Denominators thin sharply by 5 yr (23 sRT pts post-RT; 8 in the no-RT sexual-functioning group), and the scattered significant timepoints in the aRT-vs-sRT comparison are fragile at that N.
Reframes the early-salvage rationale: the QOL dividend is sparing roughly the share of men who never trigger RT, not delaying exposure. That matters because delay was the intuitive mechanism, and the regression data do not support it.
Prespecified secondary QOL analysis of a randomised trial; supports the already-guideline-endorsed early-salvage strategy. Small late-timepoint denominators and unblinded self-report temper it.
In post-RP men with adverse pathology deciding adjuvant versus PSA-triggered salvage, this supports counselling that the QOL advantage comes from avoiding RT altogether rather than from postponing it; it does not inform men who already have a rising PSA and will be irradiated either way.
- Does hypofractionated post-prostatectomy RT alter the late incontinence signal? recruiting Hypofractionated Post-prostatectomy Radiotherapy (HYPORT)for Localized Prostate Cancer Phase NAn=428 · primary completion 2026-02 · hypofx vs conventional post-RP RT, safety endpointn=538 · primary completion 2029-09 · phase 3 hypofx vs conventional salvage bed RT
- Does PSMA-guided salvage timing change functional outcomes? recruiting PSMA-PET Guided De-escalation of Salvage Radiation Treatment in Recurrent Prostate Cancer Phase 2n=54 · primary completion 2029-09 · PSMA-guided de-escalated SRT; 1° EP acute G≥2 toxn=380 · primary completion 2032-12 · eSRT at PSA 0.2 vs dSRT 0.4-0.5; safety endpoint
📚 Sources · 📄 1 paper
NRG-GU005
ForLocalized intermediate-risk prostate cancer, definitive RT candidates
HR 1.38
95% CI 0.91-2.09, p=0.13; DFS superiority not met (futility crossed)
TL;DRDFS superiority not met (HR 1.38, futility crossed); SBRT improved 2y bowel QoL (35% vs 44% MCID decline, p=0.034) vs MH-IMRT.
Reported via UroToday →
The urinary-irritation co-primary SBRT was powered for came back flat (35% vs 34%, p=0.68); the QoL edge is bowel and incontinence, not irritation. DFS superiority failed and 3y biochemical failure ran numerically higher on SBRT (8% vs 4%), so the case for 5-fx SBRT is convenience and lower GU/bowel toxicity, not better control.
8 details 3 trials watching
Phase 3, randomized, non-blinded, international; N=698 (SBRT 353 / MH-IMRT 345). Co-primary: disease-free survival (superiority) and EPIC-26 bowel + urinary-irritation QoL at 24 mo. Interim futility analyses prespecified.
Localized intermediate-risk prostate cancer, median age 68. Stratified by Gleason score, PSA, and rectal manipulation (SpaceOAR in ~55%).
SBRT 36.25 Gy/5 fx (7.25 Gy/fx, 2-3×/wk) vs MH-IMRT 70 Gy/28 fx or 60 Gy/20 fx. CTV = prostate ±1 cm proximal SV; SBRT PTV margin 5 mm radial / 3 mm AP. Fiducials, MRI fusion, daily IGRT mandated.
Co-primary DFS powered for a 38% relative improvement (target HR 0.62). Co-primary QoL: absolute reduction in MCID for EPIC bowel (≥4) and urinary irritation/obstruction (≥5) at 24 mo.
DFS superiority not met (futility bound crossed); QoL split, bowel favored SBRT while urinary irritation did not. Effect sizes in the tables above.
| Endpoint | SBRT | MH-IMRT | Effect / p |
|---|---|---|---|
| 5y DFS | 89% (85-92%) | 92% (89-95%) | HR 1.38 (0.91-2.09), p=0.13 |
| 3y cum. biochemical failure | 8% (5.2-11.0) | 4% (2.3-7.0) | p=0.037 |
| 5y OS | 91% (85-95%) | 94% (90-97%) | p=0.66 |
| Domain · MCID decline | SBRT | MH-IMRT | p |
|---|---|---|---|
| Bowel, 2y | 35% | 44% | 0.034 |
| Urinary irritation/obstruction, 2y | 35% | 34% | 0.68 |
| Bowel, 1y | 33% | 46% | 0.002 |
| Sexual, 1y | 34% | 44% | 0.026 |
| Urinary incontinence, 2y | 26% | 35% | 0.023 |
| AE (any grade unless noted) | SBRT | MH-IMRT | p |
|---|---|---|---|
| G≥3 GU | 0.6% | 2.5% | 0.04 |
| Rectal hemorrhage | 10.5% | 17.3% | 0.01 |
| Fatigue | 39.2% | 50.8% | 0.0025 |
Investigator-reported toxicity favored SBRT: fewer G≥3 GU events, less rectal hemorrhage, less fatigue (all p<0.05). Table above.
Consistent with PACE-B: both show lower urinary-incontinence decline with SBRT vs MH-IMRT. MH-IMRT SOC anchored by RTOG 0415.
Non-blinded, so patient-reported QoL endpoints are unblinded. SBRT was designed to prove superiority and failed it; 3y biochemical failure ran numerically higher with SBRT.
Prespecified phase III; SBRT failed DFS superiority (futility crossed) and did not beat MH-IMRT on the urinary-irritation co-primary. Confirms SBRT as a safe equivalent option, not an upgrade.
In localized intermediate-risk prostate cancer weighing definitive RT fractionation, this supports 5-fraction SBRT as a shorter option with comparable disease control and a bowel and GU-toxicity edge over moderate hypofractionation; it does not establish SBRT as more effective.
- Durability of SBRT biochemical control beyond 3 years n=310 · primary completion 2025-12 · phase 3 prostate SBRT, bDFS primary endpoint
- Whether rectal spacer drives the bowel QoL benefit n=150 · primary completion 2027-09 · perirectal spacer efficacy in localized prostate RTn=500 · primary completion 2027-12 · SpaceOAR Vue for late GI toxicity in prostate SBRT
📚 Sources · 📄 2 papers
Abstract
Abstract
SUPREMO
ForpT1-2N1, pT3N0, or pT2N0 grade 3/LVI breast; post-mastectomy + systemic Rx
81.4% vs 81.9% (10-yr OS)
HR 1.04, 95% CI 0.82-1.30, P=0.80; did not meet OS
TL;DR10-yr OS 81.4% vs 81.9% (HR 1.04, P=0.80): chest-wall RT gives no OS benefit in intermediate-risk post-mastectomy breast cancer.
The RT read is local control without survival: CWI halved chest-wall recurrence (9 vs 20, HR 0.45) but the absolute gap stayed under 2 points and never reached OS or DFS. Fields were chest-wall-only (SCF 12%, IMC 1.5%), so this supports omitting CWI in intermediate-risk pN1 on modern systemic therapy, not nodal-RT calls.
Also covered Jul 9
8 details 5 trials watching
Phase 3 open-label RCT, 1:1, N=1607 ITT (808 CWI vs 799 no CWI) across 173 UK, European, and international sites. Median follow-up 9.6y, with 295 OS events (150 vs 145).
Intermediate-risk early breast: pT1N1, pT2N1, pT3N0, or pT2N0 with grade 3 and/or LVI. All had mastectomy, an axillary procedure, and adjuvant systemic therapy.
CWI 40-50 Gy to the chest wall. Supraclavicular fossa irradiated in only 97/808 CWI pts and IMC in 12/808 — this was chest-wall-only treatment, not comprehensive regional nodal RT.
Contemporary systemic backbone: 85% chemotherapy, 79% endocrine therapy, 19% trastuzumab.
OS, DFS, and DMFS were all null; the only endpoint favoring CWI was chest-wall recurrence (see table).
| Endpoint | CWI | No CWI | Effect |
|---|---|---|---|
| Overall survival | 81.4% | 81.9% | HR 1.04 (0.82-1.30), P=0.80 |
| Disease-free survival | 76.2% | 75.5% | HR 0.97 (0.79-1.18) |
| Distant MFS | 78.2% | 79.2% | HR 1.06 (0.86-1.31) |
| Chest-wall recurrence | 9 (1.1%) | 20 (2.5%) | HR 0.45 (0.20-0.99) |
EBCTCG PMRT meta-analysis (Lancet 2014) showed reduced recurrence and breast-cancer mortality in node-positive disease; SUPREMO finds no OS benefit in the intermediate-risk 1-3 node group treated in a modern systemic era.
Open-label; SCF/IMC coverage was sparse and non-standardized, so it does not test comprehensive regional nodal RT. Enrolment 2006-2013 predates some contemporary systemic regimens.
Adequately powered phase 3, prespecified OS endpoint, 10-yr f/u; null result diverges from EBCTCG-based routine PMRT for intermediate-risk 1-3 node disease.
In intermediate-risk post-mastectomy breast (pT1-2N1, pT3N0, or pT2N0 grade 3/LVI) on contemporary systemic therapy, this supports omitting chest-wall RT for survival; it does not extend to ≥4 positive nodes or to the comprehensive regional-nodal RT question.
- Does CWI omission hold in HER2+ and triple-negative intermediate-risk subgroups n=1106 · primary completion 2026-12 · phase 3 PMRT omission in pN1, 7y DFS non-inferiority
- Role of comprehensive regional nodal RT vs chest-wall-only in this population recruiting Evaluating Omitting of Internal Mammary Irradiation Among Early Stage Intermediate Risk (N1) Breast Cancer Phase NAn=214 · primary completion 2025-10 · omits IMN RT in N1 intermediate-riskactive Postmastecomy Internal Mammary Nodal Irradiation for High-risk Breast Cancer Patients Phase 3n=2400 · primary completion 2025-11 · phase 3 postmastectomy IMN RT vs none, DFSrecruiting The T-REX Trial: Tailored Regional External Beam Radiotherapy in Clinically Node-negative Breast Cancer Patients With 1-2 Sentinel Node Macrometastases. Phase NAn=1350 · primary completion 2028-12 · omits regional RT in 1-2 node macrometsrecruiting RecurIndex Guided Avoidance of Regional Nodal Irradiation for Node Positive Breast Cancer Phase NAn=540 · primary completion 2029-08 · RecurIndex-guided RNI vs none in N1
- Local control durability beyond 10 years
📚 Sources · 📄 1 paper
Abstract
EORTC 22033-26033
ForHigh-risk WHO grade 2 low-grade glioma, first-line
No PFS or OS difference between arms
ns regardless of molecular subtype
TL;DRNo PFS/OS difference between first-line RT and TMZ in high-risk WHO grade 2 LGG; only IDH-wildtype favored TMZ (HR 0.47).
Upfront RT (28 × 1.8 Gy) and TMZ were survival-equivalent in every IDH-mutant subtype, including radiosensitive codeleted oligodendroglioma (OS 12.9 vs 14.9 yr, HR 0.88). The lone modality signal favored TMZ in IDH-wildtype (OS 4.7 vs 2.5 yr, HR 0.47), so molecular status, not modality, gates the first-line choice; combined-modality is now standard for IDH-mutant astrocytoma.
6 details 2 trials watching
Phase 3 RCT (EORTC 22033-26033 with NCIC-CTG/TROG/MRC-CTU), N=478 clinical high-risk WHO grade 2 LGG, randomized to RT vs dose-dense TMZ. Mature results, with post-hoc 2021 WHO molecular reclassification in 73% (351/478).
RT 28 × 1.8 Gy, standard fractionation, as the single-modality comparator arm.
Dose-dense TMZ 75 mg/m² once daily, 21 of 28 days, up to 12 cycles.
Primary: progression-free survival; overall survival co-reported. No significant difference in PFS or OS between arms.
Neither PFS nor OS differed by arm overall; molecular-subgroup OS is in the detail table, with only IDH-wildtype favoring TMZ.
| Subgroup (2021 WHO), n | RT OS | TMZ OS | HR (95% CI), p |
|---|---|---|---|
| Astrocytoma IDHmt non-codel, n=178 | 6.6-6.7 yr | 6.6-6.7 yr | HR CI 0.67-1.44, P=.93 |
| Oligo IDHmt codel, n=109 | 12.9 yr (9.4-NR) | 14.9 yr (10.1-NR) | 0.88 (0.52-1.49), P=.63 |
| IDH-wildtype, n=64 | 2.5 yr (1.8-3.3) | 4.7 yr (2.2-7.2) | 0.47 (0.27-0.82), P=.0068 |
Combined-modality (RT + chemo) was not tested here but has since become standard for IDH-mutant astrocytoma (e.g. RTOG 9802, RT+PCV).
Molecular subtypes are post-hoc reclassification (tissue in 73%); the IDH-wildtype subgroup is small (n=64). Combined-modality untested.
Mature phase 3; the null modality comparison confirms combined-modality's rise as SOC. Molecular subgroups reclassified post-hoc, so no single-modality practice change lands.
In high-risk WHO grade 2 IDH-mutant glioma, this supports that first-line RT versus TMZ monotherapy does not change PFS or OS; it does not extend to IDH-wildtype tumors, where a small post-hoc subgroup favored TMZ.
- Combined-modality vs single-modality first-line in IDH-mutant low-grade glioma active Radiation Therapy With or Without Temozolomide in Treating Patients With Low-Grade Glioma Phase 3n=540 · primary completion 2026-12 · phase 3 RT vs RT+TMZ, grade 2 glioma
- Does temozolomide outperform RT in IDH-wildtype grade 2 glioma? recruiting Chemotherapy and Radiation Therapy for the Treatment of IDH Wildtype Gliomas or Non-histological (Molecular) Glioblastomas Phase 2n=40 · primary completion 2026-12 · TMZ+RT in IDH-wildtype lower-grade glioma
📚 Sources · 📄 1 paper
Abstract
NRG/RTOG 1112 NCT01730937
ForLocally advanced HCC, macrovascular invasion (74%), 1L systemic candidates
15.8 vs 12.3 mo
HR 0.77 (90% CI 0.59-1.01), 1-sided P=.06, ns; adjusted HR 0.72, P=.04
TL;DRAdding SBRT to sorafenib: mOS 15.8 vs 12.3mo (HR 0.77, 1-sided P=.06, ns primary); mPFS 9.2 vs 5.5mo, HR 0.55, P<.001.
The RT read is PFS, not the ns OS primary: mPFS 9.2 vs 5.5mo (HR 0.55, P<.001), a locoregional-control signal in a cohort 74% macrovascular-invasion, where liver-directed RT is hardest. Personalized 27.5-50Gy/5fx, no excess G3+ toxicity. Open decision: does SBRT still add over a modern IO backbone (sorafenib obsolete)?
8 details 3 trials watching
Phase 3 open-label RCT, 1:1, 193 randomized (177 eligible), stratified by performance status, liver function, degree of metastases, and macrovascular invasion. Accrual stopped early after first-line systemic SOC shifted.
Locally advanced HCC unsuitable for or refractory to standard locoregional therapy, fit for first-line systemic. 84.7% male, median age 66; macrovascular invasion in 74%.
Personalized SBRT, 27.5 to 50 Gy in 5 fractions, dose adapted to liver function, delivered before sorafenib.
Primary: overall survival. Secondary: progression-free survival, adverse events, quality of life.
Primary OS trend favored SBRT but missed the prespecified 1-sided threshold (P=.06); stratification-adjusted OS and the secondary PFS were both significant. See the endpoint table.
| Endpoint | SBRT+sorafenib | Sorafenib | Effect (HR/P) |
|---|---|---|---|
| mOS | 15.8 mo | 12.3 mo | HR 0.77 (90% CI 0.59-1.01), 1-sided P=.06 |
| mPFS | 9.2 mo | 5.5 mo | HR 0.55 (0.40-0.75), P<.001 |
| G3+ TRAE | 47% (39/83) | 42% (37/88) | P=.52 |
G3+ treatment-related AEs similar (47% vs 42%, P=.52). Treatment-related deaths: 2 with sorafenib (liver failure, death NOS), 1 with SBRT+sorafenib (lung infection). No excess RT-attributable toxicity.
Predates modern first-line combinations (atezolizumab-bevacizumab, durvalumab-tremelimumab); the sorafenib-alone comparator is now obsolete, leaving open whether SBRT adds over an IO backbone.
Open-label; accrual stopped early (underpowered); primary OS not significant unadjusted; comparator superseded; QoL assessed in small subsets (n=17-20).
Randomised phase 3 argues for adding SBRT to systemic in MVI-heavy HCC, but primary OS not significant (1-sided P=.06), stopped early, sorafenib comparator obsolete.
In locally advanced HCC with macrovascular invasion refractory to or unsuitable for standard locoregional therapy, this supports adding SBRT to first-line systemic as contested evidence; it does not establish benefit over a modern IO-based first-line backbone.
- Does SBRT add over modern IO-based first-line systemic therapy? recruiting Testing Immunotherapy With or Without Stereotactic Body Radiation Therapy in Patients With Advanced Liver Cancer, HELIO-RT Trial Phase 3n=226 · primary completion 2029-03 · phase 3 IO+SBRT vs IO alone
- Optimal SBRT dose and fractionation with impaired liver function recruiting A Pilot Study of Liver Protection Using Prednisone for Patients Receiving Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma Phase 2n=20 · primary completion 2026-08 · prednisone liver-protection during SBRTn=18 · primary completion 2026-12 · phase 1 repeated-dose SBRT dose escalation
📚 Sources · 📄 1 paper
Abstract
BART
ForHigh-risk (T3-4/N+/R+) MIBC, post-cystectomy + chemo, no immunotherapy
HR 0.43
95% CI 0.20-0.96, p=0.04; 2y LRFFS 87.1% vs 76.0% (ITT)
TL;DR2y locoregional FFS 87.1% vs 76.0% (HR 0.43, p=0.04) with adjuvant pelvic RT post-cystectomy; OS not significant (HR 0.78, p=0.31).
Reported via UroToday →
The LRFFS benefit concentrates in the pN+ and T3+ subgroups (2y HR 0.22 and 0.25), and per-protocol it widens to HR 0.27 (93.2% vs 75.0%) once the 14 who never received RT are analysed as observation. Standard 50.4Gy/28fx to bed plus pelvic nodes transfers directly, so this moves the adjuvant-pelvic-RT decision for node-positive or margin-positive disease.
9 details 2 trials watching
Phase 3 multicentre RCT, 1:1, N=153 (RT 77 / obs 76), enrolled 2016-2024, stratified by nodal stage (N0/N+) and chemotherapy. Median follow-up 47 mo. Underpowered: accrual fell short of the sample-size goal.
High-risk (T3-4, N1-3, or R+) non-metastatic urothelial MIBC after radical cystectomy. 62% pT3-4, 41% pN+, 28% variant-histology component; median age 57, median 20 nodes dissected, 4.6% positive margins, 2.6% neobladder.
50.4 Gy / 28 fx to cystectomy bed plus pelvic nodes (common / internal / external iliac, presacral, obturator). Stoma- and bowel-sparing IMRT with daily onboard image guidance.
Primary: 2-year locoregional failure-free survival. Secondary: bladder-cancer-specific survival, DFS, overall survival. Fine-Gray competing-risk analysis (distant mets, non-cancer death).
Primary met; the time-to-event secondaries (DFS, BCSS, OS) all favoured RT numerically but none reached significance.
| Endpoint (2y) | Adjuvant RT | Observation | HR (95% CI), p |
|---|---|---|---|
| LRFFS (ITT) | 87.1% | 76.0% | 0.43 (0.20-0.96), p=0.04 |
| LRFFS (per-protocol) | 93.2% | 75.0% | 0.27 (0.10-0.71), p=0.008 |
| DFS | 71.6% | 58.7% | 0.62 (0.36-1.05), p=0.07 |
| BCSS | 79.6% | 65.0% | 0.59 (0.33-1.10), p=0.09 |
| OS | 70.4% | 57.4% | 0.78 (0.49-1.26), p=0.31 |
| Subgroup | HR (95% CI) |
|---|---|
| T3+ and N+ | 0.25 (0.07-0.84) |
| N+ disease | 0.22 (0.06-0.75) |
| Adverse event | Adjuvant RT | Observation |
|---|---|---|
| Late G3+ | 8.4% | 10.5% (p=0.60) |
| Acute G3 GI | 1.6% | 4.1% |
| Acute G2 GI | 17.5% | 1.4% |
Late grade 3+ toxicity comparable between arms; acute grade 2 GI higher with RT while grade 3 GI was lower, with no toxicity-related discontinuation.
Adjuvant RT after cystectomy is not routine (historic locoregional recurrence ~30% in high-risk pts); BART is the largest RCT in this space. A planned MERCY individual-patient-data meta-analysis will test the OS question.
Underpowered, OS not significant (HR 0.78, p=0.31) on a locoregional surrogate primary. 14/77 RT-arm pts never received RT, so the ITT HR (0.43) understates the per-protocol effect (HR 0.27). No immunotherapy used.
Randomised phase III, prespecified 2y LRFFS primary hit, diverging from the current no-adjuvant-RT norm. Underpowered and OS not significant, so short of practice-changing.
In pN+ or margin-positive high-risk MIBC after cystectomy and cisplatin chemo, this supports weighing adjuvant pelvic RT for locoregional control; it does not establish an OS benefit and does not extend to low-risk node-negative, margin-negative disease.
- OS benefit of adjuvant RT (planned MERCY IPD meta-analysis) n=76 · primary completion 2018-10 · adjuvant EBRT post-cystectomy, ≥pT3 high-riskactive 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-cystectomy, survival
- Adjuvant RT plus immunotherapy after cystectomy
📚 Sources · 📄 1 paper
Abstract
ENZARAD (ANZUP 1303)
ForHigh-risk clinically-localized/locally-advanced prostate, EBRT + 2yr ADT
8yr 74% vs 72%, HR 0.88
95% CI 0.67-1.15, p=0.34; 1° endpoint not met
TL;DRMFS 8yr 74% vs 72%, HR 0.88 (0.67-1.15) p=0.34; enza on an RT+ADT backbone missed 1° endpoint, benefit isolated to cN1/pelvic-RT.
Reported via UroToday →
The intensification benefit tracks the pelvic-RT-planned subgroup (MFS HR 0.47, OS HR 0.53), but that arm was enriched for cN1 (28% vs 0%), so nodal burden, not the RT field itself, likely drives it. Planning whole-pelvis RT for cN1 disease is where adding enzalutamide over 6mo NSAA earns its place; cN0 pts gained nothing.
8 details
Phase 3 open-label RCT, N=802 across 8 countries (2014-2018), median follow-up 8 years. Primary: metastasis-free survival (switched from OS mid-trial for fewer-than-expected deaths). Enzalutamide 160mg × 24mo vs conventional NSAA × 6mo, both on 24mo LHRH agonist + EBRT.
High-risk clinically-localized or locally-advanced prostate, EBRT-suitable. 90% Gleason 8-10, 36% PSA >20, 12% cN1 by conventional imaging. 40% planned pelvic RT, 8% brachytherapy boost.
Prostate to 78Gy, or 46Gy + brachy boost. Pelvic nodal RT 46Gy elective + boost to gross nodes, required for cN1, optional (pre-declared) for cN0. Intensive QA: credentialing, real-time review of first 5 plans per site, 20% sampling thereafter.
Primary MFS not met; PFS positive, OS neutral; benefit isolated to the cN1 and pelvic-RT-planned subgroups (see tables).
| Endpoint | Enza | Control | HR (95% CI), p |
|---|---|---|---|
| MFS (1°) | 74% | 72% | 0.88 (0.67-1.15), p=0.34 |
| PFS | 67% | 62% | 0.78 (0.61-0.99), p=0.044 |
| OS | 83% | 80% | 0.87 (0.63-1.20), p=0.40 |
| Subgroup | MFS HR (95% CI) | OS HR (95% CI) |
|---|---|---|
| cN1 nodal | 0.43 (0.20-0.92) | 0.46 (0.17-1.26) |
| Pelvic RT planned | 0.47 (0.29-0.76) | 0.53 (0.30-0.95) |
| Very high-risk | 0.85 (0.64-1.13) | 0.81 (0.57-1.13) |
| STAMPEDE | ENZARAD | |
|---|---|---|
| cN1 | 39% | 11% |
| Median PSA | 35 ng/ml | 14 ng/ml |
| cT3-4 | 92% | 47% |
| Overall MFS HR | 0.53 | 0.88 |
The cN1 MFS benefit mirrors STAMPEDE abiraterone; the weaker overall effect reflects ENZARAD's more favorable baseline risk (lower cN1 fraction, lower PSA, less cT3-4).
Active NSAA control (not placebo) narrows the measured enzalutamide effect. Subgroup benefits are prespecified but hypothesis-generating, and the pelvic-RT arm is confounded by nodal enrichment. Primary endpoint switched from OS to MFS mid-trial.
Phase 3, prespecified MFS primary, 8yr f/u, active-NSAA control; negative overall reinforces restrained intensification, cN1/pelvic-RT benefit mirrors STAMPEDE. Subgroups prespecified, not practice-defining alone.
In high-risk localized prostate with cN1 disease or planned pelvic-nodal RT, the data support enzalutamide intensification over 6mo NSAA; it does not extend to cN0 pts, who showed no MFS benefit.
- Which pelvic-RT subgroups drive the enzalutamide benefit
- Biomarkers to identify who needs treatment intensification
- Does nodal RT sterilization enable enzalutamide's distant-metastasis benefit
📚 Sources · 📄 1 paper
Abstract
PRIMARY2 NCT05154162
ForBiopsy-naive men, high clinical risk, PI-RADS 2-3 MRI, PSA ≤20, ≤cT2
TL;DRNon-inferior csPCa detection (12% vs 16%, diff -3.7%) with PSMA-PET biopsy triage, avoiding biopsy in 49% of equivocal/negative-MRI men.
10 details 2 trials watching
Multicentre non-inferiority phase 3 RCT, 7 Australian hospitals, N=660 biopsy-naive men, randomised 1:1, unmasked, stratified by site. Recruited Mar 2022 to Aug 2025; follow-up ongoing.
Clinical suspicion of significant prostate cancer with non-suspicious or equivocal MRI (PI-RADS 2 in 51%, PI-RADS 3 in 49%) plus high clinical risk (PSA density >0.1, abnormal DRE, family history, BRCA, PSA >10). PSA ≤20 ng/mL, ≤cT2; median age 61, median PSA 5.2.
Co-primary: proportion with clinically significant cancer (Gleason ≥3+4, ≥10% pattern 4; non-inferiority margin 10%) and proportion of the PET arm avoiding biopsy by 6 months (20% threshold), by intention-to-treat.
Both co-primary endpoints met: csPCa detection non-inferior with PET triage, and biopsy avoided in nearly half the PET arm. Post-biopsy AE rates similar between arms.
| AE | PSMA-PET | Systematic biopsy |
|---|---|---|
| Pain | 33 (21%) | 62 (21%) |
| Haematuria | 60 (38%) | 126 (43%) |
| Haematospermia | 77 (48%) | 133 (45%) |
Open-label with no masking; follow-up ongoing, so long-term safety of avoided biopsies is unconfirmed. Single-country, single tracer ([68Ga]PSMA-11); health-economic and cross-radiopharmaceutical generalisability untested.
Phase 3 non-inferiority RCT met both co-primary endpoints; PSMA-PET biopsy triage diverges from biopsy-all standard. Open-label, single-country, follow-up ongoing.
- Safety of avoiding biopsy in PET-negative men over longer follow-up recruiting Image-guided Focal Dose Escalation- Primary pc Treated With Primary External Beam Hypofract.Stereotactic rt Phase NAn=374 · primary completion 2025-08 · candidate match
- Generalisability beyond Australia and to other PSMA radiopharmaceuticals n=18 · primary completion 2023-07 · candidate match
- Health-economic impact of PSMA-PET-first diagnostic pathway
📚 Sources · 📄 1 paper
NRG Oncology/RTOG 0848 NCT01013649
ForResected pancreatic head adenocarcinoma, post adjuvant gemcitabine-based chemo
HR 0.96
90% CI 0.79-1.18, p=0.38 (1-sided log-rank); primary OS endpoint not met
TL;DROS HR 0.96 (90% CI 0.79-1.18), p=0.38: adjuvant chemoRT adds no OS benefit over chemo alone after pancreatic head resection.
The RT read is the node-negative subgroup: 5-yr OS 28.6→48.1% and median OS 3.0→3.9 yr with added CXRT (interaction p=0.022), while node-positive pts gained nothing (21.2 vs 20.9%). Subgroup-only (n=91), but it isolates who might still warrant adjuvant CXRT once modern systemic therapy is optimized.
7 details 3 trials watching
RT randomization of NRG/RTOG 0848 phase 3. After curative-intent resection and adjuvant gemcitabine-based chemo without progression, N=354 randomized to no further therapy (n=174) vs fluoropyrimidine-sensitized CXRT (n=180). Primary: overall survival.
Resected pancreatic head adenocarcinoma; mix of N0 (n=91) and N1 (n=263), predominantly T3 (n=288 vs T1/T2 n=66), mostly negative margins (n=295). Only pts completing adjuvant chemo without progression.
Adjuvant systemic backbone gemcitabine-based: gemcitabine alone (n=236), non-oxaliplatin gemcitabine combinations (n=18), gemcitabine+erlotinib (n=100). Added arm was fluoropyrimidine-sensitized CXRT.
CXRT was fluoropyrimidine-sensitized chemoradiotherapy delivered after completion of adjuvant chemo. RT dose, fractionation, and target volume not reported in source text.
Primary: overall survival. Prespecified 5-yr OS subgroup estimates with interaction tests by nodal status, T stage, margins, CA19-9, sex, age, and systemic regimen.
Primary OS negative: HR 0.96 (90% CI 0.79-1.18), p=0.38; median OS 2.6 vs 2.3 yr. Nodal-status interaction p=0.022 with a node-negative gain (see table).
| Nodal status | Chemo 5-yr OS | Chemo+CXRT 5-yr OS |
|---|---|---|
| N0 (n=91) | 28.6% (14.9-42.2) | 48.1% (33.3-62.9) |
| N1 (n=263) | 21.2% (13.8-28.5) | 20.9% (13.8-28.0) |
| Endpoint | Chemo | Chemo+CXRT |
|---|---|---|
| Median OS | 3.0 yr (2.2-4.0) | 3.9 yr (2.5-NR) |
| Median DFS | 1.5 yr (0.8-2.7) | 2.3 yr (1.4-NR) |
Gemcitabine backbone predates FOLFIRINOX-era adjuvant standard; authors note the node-negative signal needs confirmation in trials using FOLFIRINOX/FOLFOXIRI.
Node-negative OS benefit is a subgroup finding (n=91, interaction p=0.022), hypothesis-generating. Dated gemcitabine backbone; RT technique not reported in source.
Prospective phase III, primary OS endpoint not met (HR 0.96); reinforces omitting adjuvant CXRT. Node-negative benefit is subgroup-only (interaction p=0.022), needs independent confirmation.
In resected pancreatic head adenocarcinoma who completed adjuvant gemcitabine-based chemo, this supports omitting fluoropyrimidine-sensitized CXRT overall and in node-positive pts; the node-negative subgroup gain is hypothesis-generating, not yet grounds to add RT.
- Does adjuvant CXRT benefit node-negative resected pancreatic cancer? n=770 · primary completion 2028-06 · phase 3 adjuvant chemoRT vs chemo, resected PDACrecruiting Radiotherapy With GX Regimen as Adjuvant Therapy for High-risk Patients Following Pancreatic Cancer Surgery Phase 3n=288 · primary completion 2029-05 · phase 3 adjuvant RT+chemo vs chemo alone
- Confirmation with modern FOLFIRINOX adjuvant backbone active Testing the Use of the Usual Chemotherapy Before and After Surgery for Removable Pancreatic Cancer Phase 3n=358 · primary completion 2028-12 · peri-op vs adjuvant FOLFIRINOX, resectable PDAC
📚 Sources · 📄 1 paper
AREST
ForAdequately resected pT1-2N0 oral SCC with ≥1 intermediate-risk feature
HR 0.52
3-yr LRFS 89.2% vs 80.9%, 95% CI 0.30-0.91, p=0.02 (ITT)
TL;DR3-yr LRFS 89.2% vs 80.9%, HR 0.52 (0.30-0.91) p=0.02 favoring adjuvant RT in resected intermediate-risk pT1-2N0 oral SCC; no OS/DFS gain.
The move is observe-vs-treat in adequately resected pT1-2N0 OSCC with one adverse feature: 60Gy/30fx to tumor bed plus at-risk neck cut 3-yr loco-regional failure (HR 0.52), strongest in oral tongue over buccal mucosa (exploratory). The gain is loco-regional only, so weigh it against RT morbidity when baseline LRR risk is low.
| Arm | 3-yr LRFS | 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) | ref | — |
8 details 2 trials watching
Phase 3, open-label, multicenter RCT (India); 1:1 to adjuvant RT vs observation, N=392 (191 RT, 201 observation), stratified by subsite, PNI/LVE, differentiation. Median follow-up 47.2 months.
pT1-2 pN0 OSCC with ≥1 intermediate-risk feature (DOI 5-10mm, PNI, LVE, or poor differentiation), after adequate surgery: margins ≥5mm and ipsilateral level I-III neck dissection with ≥16 nodes.
60Gy in 30 fractions over 6 weeks to the resected tumor bed and at-risk neck nodal region.
Primary: 3-yr loco-regional recurrence-free survival (LRFS), KM with log-rank. Secondary: DFS, OS, and cumulative incidence of loco-regional failure (competing-risk).
Per-protocol LRFS 91.1% vs 80.9%, HR 0.43 (0.23-0.80), p=0.01. DFS and OS not significantly different between arms.
| Analysis | Adjuvant RT | Observation | HR (95% CI), p |
|---|---|---|---|
| ITT | 10.6% (6.1-15.1) | 18.9% (13.3-24.6) | 0.52 (0.30-0.91), p=0.021 |
| Per-protocol | 8.7% (4.3-13.1) | 18.9% (13.3-24.6) | 0.43 (0.23-0.79), p=0.007 |
Prior evidence for adjuvant RT in this pN0 intermediate-risk setting was retrospective (per the abstract); AREST is the first randomized confirmation.
Open-label, abstract-only; benefit is loco-regional control only, no OS/DFS at 47.2-mo median. Observation LRFS (80.9%) exceeded the 70% powering assumption, so the absolute LRFS gain is modest.
First randomized backing for the guideline-listed retrospective signal that RT cuts LRR in adverse-feature pN0 OSCC; loco-regional benefit only, no OS/DFS, open-label abstract.
In an adequately resected pT1-2N0 oral tongue SCC with a single intermediate-risk feature, this supports adjuvant RT for loco-regional control but not survival, and it does not extend to buccal mucosa (weaker signal) or node-positive disease.
- Does loco-regional control benefit translate to survival with longer follow-up? n=85 · primary completion 2026-08 · postop RT vs PD-1 maintenance, survival endpoint
- Optimal adjuvant approach for buccal mucosa vs oral tongue subsites? recruiting A Study of Radiation Therapy After Surgery in People With Oral Tongue Squamous Cell Carcinoma Phase 2n=24 · primary completion 2027-06 · postop IMRT tailored to oral tongue subsite
- Which single intermediate-risk feature drives the RT benefit?
📚 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
mRCAT-III NCT06507371
ForpMMR/MSS LARC, cT3-4N0/+, tumor ≤10cm from verge, no lateral node
61.0% vs 28.6%
P<0.0001, ITT, blinded central review
TL;DRpCR 61.0% vs 28.6% (P<0.0001) with node-sparing SCRT + tislelizumab + CAPOX vs conventional SCRT + CAPOX in pMMR LARC.
The RT read is a confound, not a green light for nodal omission: the experimental arm changed two things at once, tumor-bed-only targeting AND added tislelizumab, so node-sparing's own contribution to the pCR doubling (61.0% vs 28.6%) can't be isolated. Node-sparing plausibly drove the lower severe-GI toxicity, but this doesn't yet license dropping elective nodal RT.
| Endpoint | Experimental | Control | P |
|---|---|---|---|
| pCR (ITT) | 61.0% (47/77) | 28.6% (22/77) | <0.0001 |
| MPR (TRG0+1) | 77.9% (60/77) | 50.6% (39/77) | <0.0001 |
+1 more figure
6 details 5 trials watching
Open-label, multicenter phase 3 RCT across 17 China hospitals; randomized 1:1, 77 pts per arm, stratified by clinical N stage (cN0 vs cN+). Primary pCR read by blinded independent central review.
pMMR/MSS rectal adenocarcinoma, cT3-4N0/+M0, tumor lower edge ≤10cm from the anal verge, ECOG 0-1, age 18-75, no positive lateral pelvic node.
Both arms CAPOX (oxaliplatin 130mg/m² d1, capecitabine 1000mg/m² d1-14). Experimental adds tislelizumab 200mg d1; control is chemo + RT only.
Both arms short-course 5Gy×5. Experimental is node-sparing (tumor bed only, spares tumor-draining nodes); control is conventional elective-nodal coverage. This target-volume contrast is the RT question.
Primary: pCR (ITT). Secondary: MPR, TRG, organ-preservation rate, EFS, OS, AEs.
Primary pCR and secondary MPR both favored the experimental arm (see figure); EFS, OS, organ-preservation not reported in source.
Experimental arm reported fewer severe GI AEs (author takeaway), plausibly from the smaller node-sparing volume; numeric AE rates not in source.
Control pCR 28.6% matches short-course RT + consolidation chemo benchmarks (RAPIDO ~28%). The novelty is a PD-1 benefit in an MSS population usually IO-refractory, with nodal-RT omission as the immunologic rationale.
Open-label; pCR is a surrogate with EFS/OS immature; the experimental arm confounds node-sparing target volume with added tislelizumab, so the RT-attributable effect can't be isolated; N=154, single country.
Divergent MSS-rectal result from a randomized P3 with blinded-review primary; kept off practice-changing because pCR is a surrogate (EFS/OS immature) and node-sparing is confounded with added tislelizumab.
In pMMR/MSS LARC (cT3-4, tumor ≤10cm from verge), this is a trial-stage signal that neoadjuvant PD-1 may help an IO-resistant group; it does not extend to dMMR disease and does not yet displace conventional elective-nodal short-course RT off-protocol.
- Node-sparing RT's independent contribution vs added tislelizumab
- Whether pCR gain translates to EFS, OS, organ preservation n=30 · primary completion 2025-01 · 1° endpoint organ-retention, MSS/pMMR SCRT+IOrecruiting Node-sparing Radiotherapy Combined With Total Neoadjuvant CAPOX and Sintilimab for MSS Middle and Low Rectal Cancer Phase 2n=37 · primary completion 2027-09 · node-sparing SCRT+PD-1, W&W organ preservation
- PD-1 benefit reproducibility in MSS/pMMR rectal cancer recruiting A Series of Neoadjuvant Chemoradiotherapy Combined With Immunotherapy for Locally Advanced Rectal Cancer Phase 2/3n=375 · primary completion 2026-12 · RCT chemoRT ± tislelizumab, pMMR/MSS LARCrecruiting Neoadjuvant Chemoradiotherapy Plus Tislelizumab With or Without Probio-M9 in pMMR/MSS Locally Advanced Rectal Cancer Phase 2n=50 · primary completion 2027-05 · pMMR/MSS chemoRT+tislelizumab vs CRT-only armnot yet Neoadjuvant Chemoradiotherapy Followed by Chemotherapy With or Without Tislelizumab for Resectable Ultra-low Rectal Cancer: The RELIEVE-02 Study Phase 3n=154 · primary completion 2027-12 · phase 3 chemoRT ± tislelizumab, pMMR/MSS
📚 Sources · 🐦 1 tweet
One of most interesting rectal ca studies at #ASCO26
— Dr. Nina Niu Sanford (@NiuSanford) June 2, 2026
P3 RCT in pMMR LARC: Node-sparing short-course RT + CAPOX + tislelizumab doubled pCR v conventional SCRT + CAPOX (61 v 29%)
Hypothesis = sparing elective node RT preserves antitumor immunity & improves PD1 response @OncoAlert pic.twitter.com/6xvA6ne0mg
LBA8005: Concurrent Thoracic RT + Chemoimmunotherapy in ES-SCLC
ForTreatment-naïve ES-SCLC, stage IV or III ineligible for curative chemoRT
HR 1.14
10.0 vs 11.8 mo, 95% CI 0.84-1.56, p=0.40; OS not met
TL;DROS 10.0 vs 11.8 mo, HR 1.14 (0.84-1.56), p=0.40: concurrent thoracic RT added no benefit to durvalumab-based chemoIO in ES-SCLC.
The tested RT is concurrent (30 Gy/10 fx, day 21-28 with chemoIO), not CREST's consolidative post-chemo RT in responders, so the consolidative question stays open. Even the low-burden subgroup without brain or liver metastases was null (HR 1.10). Adding concurrent thoracic RT to chemoIO carries no OS benefit.
| Arm | Median OS | HR (95% CI) | p |
|---|---|---|---|
| ChemoIO + TRT | 10.0 mo | 1.14 (0.84-1.56) | 0.40 |
| ChemoIO | 11.8 mo | n/a | n/a |
+2 more figures
| Subgroup | ChemoIO+TRT | ChemoIO | HR (95% CI) | p |
|---|---|---|---|---|
| Completed 4 chemoIO courses | 11.9 mo | 12.1 mo | 1.02 (0.72-1.44) | 0.92 |
| No brain/liver mets | 11.9 mo | 13.2 mo | 1.10 (0.65-1.87) | 0.72 |
| Arm | Median PFS | HR (95% CI) | p |
|---|---|---|---|
| ChemoIO + TRT | 5.1 mo | 1.10 (0.84-1.45) | 0.49 |
| ChemoIO | 5.0 mo | n/a | n/a |
7 details 5 trials watching
Randomized phase III, 1:1 (chemoIO+TRT n=115, chemoIO n=113). Stratified by liver and brain metastases. Primary: overall survival; secondary ORR, PFS, toxicity.
Treatment-naïve ES-SCLC, stage IV or stage III ineligible for curative chemoRT, ECOG 0-1, ≥1 measurable thoracic lesion. Asymptomatic or stable brain metastases allowed.
Four cycles durvalumab 1500 mg + carboplatin AUC 5 + etoposide (100 mg/m² IV days 1-3, or 200 mg/m² PO days 2-4) Q3W, then durvalumab 1500 mg Q4W maintenance.
Concurrent thoracic RT 30 Gy in 10 fractions, starting day 21-28. PCI 25-30 Gy offered to responders in both arms; WBRT 20-30 Gy for brain metastases per routine.
Primary OS not met and numerically favored chemoIO alone; PFS and both prespecified subgroups (course completers, no brain/liver metastases) were also null. Effect sizes in figures.
CREST (Slotman, Lancet 2015) used the same 30 Gy/10 fx but as consolidative RT after chemotherapy in responders, before immunotherapy, and suggested a survival benefit. Adding RT concurrently to chemoIO shows none.
Open-label (RT cannot be blinded). Tests only the concurrent schedule, not the consolidative timing prior data supported. No toxicity or RT-delivery data in source to explain the numerically inferior OS.
Randomised phase III, prespecified OS primary, null; contests the CREST-era expectation that thoracic RT benefits ES-SCLC, now tested concurrently with chemoIO.
In treatment-naïve ES-SCLC beginning durvalumab plus platinum/etoposide, this questions adding concurrent thoracic RT (no OS benefit); it does not extend to consolidative thoracic RT given after chemotherapy in responders.
- Does consolidative thoracic RT after chemoimmunotherapy still benefit ES-SCLC? n=150 · primary completion 2025-03 · RT to all residual lesions after chemoIO in ES-SCLCrecruiting Phase II Trial of Consolidative Thoracic Radiotherapy for ES-SCLC After Standard Care of Chemo-immunotherapy Phase NAn=104 · primary completion 2025-09 · single-arm consolidative TRT after PD-1/L1 chemoIOrecruiting Association of Thoraco-mediastinal Radiotherapy With Maintenance Immunotherapy Treatment With Atezolizumab Phase 2n=37 · primary completion 2026-12 · thoraco-mediastinal RT + maintenance atezolizumab
- Optimal timing and sequencing of thoracic RT with chemoimmunotherapy active Low-dose Radiotherapy Combined With Durvalumab, Chemotherapy(EP) in the Treatment of ES-SCLC Phase 2n=30 · primary completion 2023-02 · low-dose RT concurrent with 1L durvalumab chemon=46 · primary completion 2027-12 · sequential TRT after 1L durvalumab chemoIO
📚 Sources · 🐦 1 tweet
🚨 #ASCO26 | #️⃣LBA8005⁰☢️ Concurrent thoracic radiotherapy + chemoimmunotherapy in ES-SCLC
— Masahiro TORASAWA, MD. PhD. (@M_Torasawa) June 2, 2026
👥 ES-SCLC⁰Durvalumab + platinum/etoposide⁰± concurrent thoracic radiotherapy⁰TRT: 30 Gy / 10 fractions, starting day 21–28
📊 Randomized phase III⁰ChemoIO + TRT: n=115⁰ChemoIO… pic.twitter.com/TDA5amz59e
DeLLphi-304
ForRelapsed SCLC with brain mets, >70% prior CNS-directed therapy
TL;DRIntracranial: time-to-CNS-progression HR 0.54 ITT; in brain-mets pts CNS PFS 6.5 vs 4.2mo (HR 0.40), CNS CR 15% vs 5% for tarlatamab.
The RT read is intracranial control without new radiation: brain-mets CNS PFS 6.5 vs 4.2mo (HR 0.40) and CNS CR 15% vs 5%. But >70% had prior CNS-directed therapy, so this is salvage intracranial activity, not a defer-brain-RT signal in RT-naive disease. Informs sequencing systemic ahead of repeat cranial RT.
| Arm | Median CNS PFS | HR (95% CI) |
|---|---|---|
| Tarlatamab (n=254) | NE (13.7-NE) | 0.54 (0.39-0.75) |
| Chemotherapy (n=255) | 7.2 mo (5.6-NE) | n/a |
+2 more figures
| Arm | Median CNS PFS | HR (95% CI) |
|---|---|---|
| Tarlatamab (n=67) | 6.5 mo (4.3-13.7) | 0.40 (0.24-0.66) |
| Chemotherapy (n=56) | 4.2 mo (2.9-5.5) | n/a |
| CNS endpoint | Tarlatamab (n=67) | Chemotherapy (n=56) |
|---|---|---|
| Complete response | 10 (14.9%) | 3 (5.4%) |
| Disease control rate | 52 (77.6%) | 40 (71.4%) |
| Median duration CNS disease control | 8.2 mo | 5.2 mo |
5 details 2 trials watching
Post hoc intracranial analysis of DeLLphi-304, a phase 3 RCT of tarlatamab vs chemotherapy in relapsed SCLC. CNS endpoints were not prespecified primary. Data cutoff Jan 29 2025; median follow-up 11.4 mo (tarlatamab), 11.5 mo (chemo).
Relapsed SCLC. ITT CNS cohort n=254 tarlatamab vs 255 chemo; brain-mets subgroup n=67 vs 56. >70% of brain-mets pts had prior CNS-directed therapy.
Time to CNS progression or death (ITT, RECIST per investigator); brain-mets CNS PFS by mRANO-BM (BICR); best CNS response, CNS disease control rate, and response durations.
ITT time to CNS progression HR 0.54 (0.39-0.75), median NE vs 7.2 mo. Brain-mets CNS PFS and response detail in figures.
First DLL3xCD3 bispecific intracranial signal in SCLC; CNS control historically relied on WBRT/SRS and prophylactic cranial irradiation, not a systemic agent.
Post hoc, unstratified brain-mets HRs, small subgroup N. >70% prior CNS therapy confounds de novo intracranial activity. No new safety data in source.
Post hoc CNS analysis; brain-mets HRs unstratified with small N (67 vs 56), and >70% had prior CNS-directed therapy, confounding de novo intracranial activity.
For relapsed SCLC with previously-treated brain mets, this supports systemic intracranial control as an option before committing to repeat cranial RT; it does not inform RT-naive or symptomatic brain mets, where upfront local therapy still applies.
- Durability of intracranial response beyond current follow-up
- Activity in RT-naive or untreated brain metastases n=35 · primary completion 2029-02 · candidate match
- Sequencing tarlatamab vs cranial radiotherapy in SCLC brain mets n=39 · primary completion 2027-12 · candidate match
📚 Sources · 🐦 1 tweet
Dr. @g_mountzios #ASCO26 presents CNS outcomes with 2L tarlatamab in DeLLphi-304. Improved time to CNS progression overall (HR 0.54). In pts with brain nets, tarlatamab vs chemo CNS CR rate 15% vs 5% with DCR 78% vs 71% and time to CBS progression 6.5m vs 4.2m, HR 0.40 pic.twitter.com/5i8jL1zlKW
— Stephen V Liu, MD (@StephenVLiu) June 1, 2026
PROTEUS
TL;DRMost distant mets PSMA PET-detected (53.0% APA vs 60.7% control); preview NEJM data, MFS benefit's clinical meaning contested.
6 details 1 trial watching
Randomized, apalutamide + ADT vs ADT alone. Results just posted (NEJM online); full ASCO26 presentation pending, so this is a preview read.
Most distant metastases were PSMA PET-detected: 53.0% in the apalutamide group vs 60.7% in the control group. Primary MFS effect size not reported in source.
MFS events were predominantly PET-detected, raising lead-time / detection-bias concerns about the endpoint. The 50-vs-60 BCR/100 figures circulating are an illustrative hypothetical, not PROTEUS primary data.
Curator frames it as 'homerun vs largest negative' pending full data. A companion thought experiment argues PSMA PET vs conventional detection differences could account for much of the apparent metastasis delta.
Preview NEJM data; primary effect size not in source. Most MFS events PSMA PET-detected (53.0% vs 60.7%), raising lead-time/detection bias that undermines the MFS read.
- Does the MFS benefit hold on OS or conventional-imaging endpoints? n=1503 · primary completion 2026-06 · apalutamide MFS by conventional imaging (BICR)
- How much of the MFS delta reflects PSMA PET lead-time bias?
📚 Sources · 🐦 3 tweets
#ASCO26
— Daniel E Spratt (@DrSpratticus) May 31, 2026
The PROTEUS trial results are now online...buckle up as we wait to see the full presentation. This is going to be a trial that is likely highly controversial until the full results are published.
Some may call this a homerun, others may call this the largest negative…
Thought experiment:
— Sean McBride (@seanmmcbride) May 31, 2026
Let's take a very simple hypothetical trial involving 100 patients in the APA arm and 100 patients in the ADT alone arm. Pulling from PROTEUS EFS data, assume that, by 5 years, 60 patients in the ADT arm have had a BCR compared to 50 in the ADT+APA arm.… pic.twitter.com/WJaiDlJnQs
#ASCO26
— Daniel E Spratt (@DrSpratticus) May 31, 2026
Talk about real-time updates. NEJM paper now online and my predictions and inferences appear true.
Majority of MFS events were by PET not conventional imaging. "Most distant metastases were identified by PSMA PET (53.0% of those in the apalutamide group and 60.7% in the… https://t.co/Yz4myY0flq
CAN-2409 NCT01436968
ForIntermediate or high-risk localised prostate cancer, EBRT candidates
TL;DRDFS HR 0.70 (0.52-0.94, p=0.016) adding intraprostatic CAN-2409 to EBRT in intermediate/high-risk localised prostate; OS and PCSM immature.
The RT read is local control: 2yr biopsy positivity fell 36.4% to 19.6% (p=0.0015), comparable to adding ADT (RTOG 9408) but on standard 78Gy without a brachy or SIB boost. Whether it adds over modern dose-intensification plus ADT is the open integration question, since ADT was optional and no boost was used.
| Endpoint | CAN-2409 | Placebo | HR / p |
|---|---|---|---|
| DFS median | NR | 86.1 mo | HR 0.7 (0.52-0.94), p=0.0155 |
| 2yr biopsy pCR | 80.4% | 63.6% | n/a |
| 2yr local recurrence | 19.6% | 36.4% | p=0.0015 |
+1 more figure
| Trial | Intensifier | Local endpoint: control → intensified |
|---|---|---|
| RTOG 9408 | +4mo ADT | 2yr biopsy+ 40% → 20% |
| ASCENDE-RT | LDR brachy boost | 10y local failure 7.1% → 1.5% |
| FLAME | SIB 95Gy | Crude local failure 7.7% → 2.7% |
| CAN-2409 | +CAN-2409 | 2yr biopsy+ 36.4% → 19.6% |
8 details
Phase 3, double-blind, placebo-controlled RCT, 2:1 randomisation, N=745 across 51 US and Puerto Rico centres. Median follow-up 50.3 mo.
Intermediate or high-risk localised prostate cancer, ECOG 0-2, planned for EBRT. Stratified by risk category and ADT use. 79% White, 16% Black.
EBRT 78 Gy/2 Gy, or hypofractionated 60 Gy/3 Gy or 70 Gy/2.5 Gy. ADT optional. No dose-escalation or brachytherapy boost mandated.
Three intraprostatic aglatimagene injections (5×10^11 viral particles) plus valacyclovir prodrug, versus placebo plus valacyclovir.
Primary: disease-free survival (recurrence or death, ITT). Secondary/exploratory: OS, PCSM, 2-year post-RT biopsy pathologic response.
Primary met: DFS favoured aglatimagene; OS and PCSM immature, not significantly different. Arm-by-endpoint values in the results figure.
| Event (G3+) | Aglatimagene | Placebo |
|---|---|---|
| Any TEAE | 8% (40/479) | 7% (17/232) |
| Acute kidney injury | 2% (9/479) | 2% (4/232) |
| Serious AEs | 6% (28/479) | 7% (17/232) |
Grade 3+ TEAEs 8% vs 7%; most common acute kidney injury (2% both arms). Serious AEs 6% vs 7%. No treatment-related deaths.
Discussant benchmarked the biopsy-positivity gain against ADT (RTOG 9408), brachytherapy boost (ASCENDE-RT), and SIB (FLAME) as established local-control intensifiers.
DFS is a composite surrogate; OS and PCSM immature. ADT optional, no boost mandated, confounding added value over modern intensification. Accrual (2012-2021) predates PSMA staging.
Positive phase 3 primary (DFS) but on a surrogate/composite; OS and PCSM immature (1 event/arm). Additive benefit over modern dose-intensification plus ADT unproven.
In intermediate or high-risk localised prostate cancer planned for definitive EBRT, this informs whether an added intraprostatic biologic could improve local control; it does not extend to post-prostatectomy, salvage, or metastatic settings.
- Does the local-control gain add over modern dose-escalation and ADT?
- Do DFS and pCR gains translate to overall or cancer-specific survival?
- Optimal ADT and RT-intensification pairing with intraprostatic CAN-2409
📚 Sources · 🐦 1 tweet · 📄 1 paper
🗣️Prostate Oral Abstract #ASCO25
— Michael Serzan, MD (@MikeSerzanMD) June 3, 2025
👉Dr @angela_jia_ discusses "Better Treatments, Better Selection: Improving Patient Outcomes in Localized Prostate Cancer"
🔑 KEY TAKE AWAYS
- #CAN2409 improves DFS and 2yr PathCR however PCSM and OS remain immature.
❓How to integrate with… pic.twitter.com/WamsneYBI1
Abstract
RASolute 302
ForPreviously treated metastatic pancreatic cancer (RAS-mut or WT)
HR 0.40
95% CI 0.30-0.53, P<0.001; mOS 13.2 vs 6.7 mo (overall pop)
TL;DRmOS 13.2 vs 6.7mo, HR 0.40 (0.30-0.53), P<0.001 for daraxonrasib vs investigator's-choice chemo in previously treated metastatic pancreatic cancer.
In previously treated metastatic pancreatic cancer with a RAS mutation, daraxonrasib's OS benefit supports it as a systemic option over chemotherapy; the signal does not extend to treatment-naive or localized disease.
| Population · Arm | Median OS | HR (death) | 12-mo OS |
|---|---|---|---|
| G12 · Daraxonrasib | 13.2 mo (10.0-NR) | 0.40 (0.30-0.54) | 53.3% |
| G12 · Chemo | 6.6 mo (5.4-8.2) | — | 8.7% |
| Overall · Daraxonrasib | 13.2 mo (10.0-NR) | 0.40 (0.30-0.53) | 53.2% |
| Overall · Chemo | 6.7 mo (5.8-8.0) | — | 17.3% |
7 details 1 trial watching
Phase 3 RCT, daraxonrasib vs investigator's-choice chemotherapy in previously treated metastatic pancreatic cancer. Two prespecified populations: RAS G12-mutant and overall (G12/G13/Q61 or no RAS mutation identified).
Previously treated metastatic pancreatic cancer. RAS G12 arm n=228 vs 231; overall n=248 vs 252. Overall population also includes tumors with no identified RAS mutation.
Daraxonrasib, an oral RAS(ON) multi-selective inhibitor targeting active GTP-bound RAS, vs investigator's choice cytotoxic chemotherapy.
Primary OS met: median 13.2 vs 6.7 mo, HR 0.40 (0.30-0.53), P<0.001 (overall); HR 0.40 (0.30-0.54) in RAS G12. 12-mo OS 53% vs 17% (overall). Deaths 32% vs 55-56%.
Chemo control (6.6-6.7 mo) matches the historic 2L metastatic PDAC benchmark; no prior targeted agent has shown an OS signal of this magnitude in this setting.
Data limited to a single ASCO LBA OS figure; full safety and PFS not yet reported. Open-label; daraxonrasib median OS upper CI not reached (10.0-NR), so tail durability is immature.
Randomized phase 3, OS primary hit HR 0.40 in 2L metastatic PDAC where no targeted SOC exists; hard endpoint, unprecedented magnitude. Full LBA data pending.
- Sequencing and combination with 1L chemotherapy recruiting Study of Daraxonrasib and Daraxonrasib + GnP as First-line Treatment in Patients With Metastatic Pancreatic Adenocarcinoma Phase 3n=900 · primary completion 2028-06 · 1L daraxonrasib + gem/nab-paclitaxel combination
- Efficacy across RAS-WT vs RAS-mutant subsets
- Full safety and toxicity profile
📚 Sources · 🐦 1 tweet
#ASCO26
— Nicholas Hornstein (@GIMedOnc) May 31, 2026
This one is special.
This is the hottest paper of 2026 and potentially in the history of pancreatic cancer.
Let’s dive in.
RASolute 302: Daraxonrasib vs investigator’s choice chemotherapy in previously treated metastatic pancreatic cancer
Abstract LBA5 (soon!)… pic.twitter.com/Lq7PEjOWAo
ENZAMET + Decipher (Part 2)
FormHSPC on ADT + enzalutamide, Decipher genomic classifier available
TL;DRDecipher >0.85 predicts docetaxel OS benefit on an ADT+enza backbone (HR 0.75 vs 1.94, interaction p=0.04); ≤0.85 can skip docetaxel.
In mHSPC starting ADT + enzalutamide, a Decipher score >0.85 is where the docetaxel OS benefit concentrates while ≤0.85 sees little added benefit; the read informs docetaxel selection, not any radiotherapy decision.
| Treatment arm | Decipher >0.85 vs ≤0.85 OS HR | p |
|---|---|---|
| ADT + ENZA | 3.02 (1.50-5.76) | — |
| ADT + ENZA + Doce | 1.08 (0.60-1.71) | 0.73 |
+1 more figure
| Decipher stratum | Unweighted HR (doce vs none) | IPTW-weighted HR |
|---|---|---|
| ≤0.85 | 2.78 (1.49-5.21) | 1.94 (0.95-3.96) |
| >0.85 | 1.13 (0.71-1.79) | 0.75 (0.43-1.33) |
7 details
Preplanned biomarker analysis of the phase 3 ENZAMET RCT. Decipher genomic classifier (DPMC, cutpoint >0.85) applied to the ADT + enzalutamide backbone cohort, N=320.
Metastatic hormone-sensitive prostate cancer on an ADT + enzalutamide backbone with an available Decipher score. A low-volume subset was analysed separately.
ADT + enzalutamide ± early docetaxel. Docetaxel was given at investigator discretion (a stratification factor), so the docetaxel comparison is not randomised.
Two-part signal: Decipher >0.85 is prognostic for worse OS on ADT+enza, and by IPTW interaction (p=0.04) predicts OS benefit from added docetaxel; ≤0.85 derives little benefit. Effect sizes in the figures.
Consistent with docetaxel OS benefit in CHARTED and STAMPEDE for high-volume/high-risk mHSPC; positions Decipher as a molecular refinement of that selection. Presented as Level 1B evidence.
Docetaxel not randomised (IPTW-weighted, residual imbalance after scoring); the high-Decipher benefit's CI crosses 1 and rests on a subgroup interaction. Hypothesis-generating, not yet practice-defining.
Post-hoc biomarker-by-docetaxel interaction; docetaxel not randomised (IPTW-weighted, residual imbalance acknowledged). High-Decipher benefit CI crosses 1, rests on interaction p=0.04, strengthened only after weighting.
- Prospective validation of Decipher-guided docetaxel selection in mHSPC
- Whether DPMC ≤0.85 pts can safely omit docetaxel
- Decipher predictive value across other intensification agents (ARSI, PARP)
📚 Sources · 🐦 1 tweet
#ASCO26 GU Oncology Spotlight 🚨
— Dra. María Natalia Gandur Quiroga (@nataliagandur) May 30, 2026
🔬 ENZAMET + Decipher | Part 2
Can genomics guide docetaxel intensification in mHSPC?
Outstanding presentation by @ChrisSweeney1.@OncoAlert@ASCO
After Part 1, the key question was:
➡️ Can a genomic classifier identify which patients with… pic.twitter.com/nJYMxuXelV
TALAPRO-3
ForHRR-deficient metastatic prostate cancer
HR 0.48
95% CI 0.36-0.65, P<0.001; 3yr rPFS 77% vs 56% (ITT)
TL;DR3yr rPFS 77% vs 56%, HR 0.48 (0.36-0.65), adding talazoparib to enzalutamide/ADT in HRR-deficient metastatic prostate cancer.
In HRR-deficient metastatic prostate cancer, this supports intensifying enzalutamide/ADT with talazoparib, benefit steepest in the BRCA subgroup; it does not extend to HRR-intact disease.
| Population | HR (95% CI) | Median rPFS, mo |
|---|---|---|
| ITT | 0.48 (0.36-0.65) | NC vs 45.8 |
| BRCA | 0.37 (0.22-0.61) | NC vs 35.1 |
| Non-BRCA | 0.57 (0.39-0.82) | NC vs NC |
6 details 2 trials watching
Randomized, placebo-controlled trial: talazoparib+enzalutamide vs placebo+enzalutamide, 300 vs 299 pts. Published NEJM May 30, 2026.
HRR-deficient metastatic prostate cancer, enzalutamide/ADT backbone both arms. Prespecified BRCA (104/103) and non-BRCA HRR (196/196) strata.
Talazoparib (PARP inhibitor) added to enzalutamide plus ADT; control substituted placebo for talazoparib on the same ARSI backbone.
Primary: imaging-based (radiographic) PFS. OS and other secondaries not reported in source.
ITT 3yr rPFS 77% vs 56%, P<0.001; per-population HRs and medians in the figure. Benefit concentrated in the BRCA subgroup.
Extends PARP+ARSI combinations (TALAPRO-2, PROpel, MAGNITUDE) that established the class in HRR-altered mCRPC toward the enzalutamide/ADT-backbone metastatic setting.
Primary endpoint is rPFS, a surrogate; OS not reported in source. Non-BRCA benefit is modest, so the HRR-wide result leans on BRCA. Talazoparib medians not reached, so follow-up is immature.
Randomized phase 3, rPFS primary hit (HR 0.48); but rPFS is a surrogate and OS not reported. Aligns with PARP+ARSI direction (TALAPRO-2, PROpel, MAGNITUDE).
- Overall survival benefit, given rPFS is the surrogate primary endpoint n=1054 · primary completion 2022-10 · mature phase 3, same combo vs enza, mCRPC
- Whether non-BRCA HRR alterations derive benefit comparable to BRCA recruiting A Study of Talazoparib With or Without Enzalutamide in People With Prostate Cancer Who Have Previously Received Abiraterone Acetate Phase 2n=126 · primary completion 2029-03 · talazoparib in broad HRR-mutant mCRPC
📚 Sources · 🐦 1 tweet
JUST In: TALAPRO-3 published in @NEJM
— Toni Choueiri, MD (@DrChoueiri) May 30, 2026
Adding #talazoparib to enzalutamide/ADT
=>3-year rPFS: 77% vs 56% in HRR-deficient metastatic prostate cancer !
Looking forward to full presentation by @neerajaiims who keeps changing SOC, one trial at a time. @ASCO #ASCO26 @OncoAlert pic.twitter.com/nXiPk4DIXg
PREPEC
ForSkin/nipple-sparing mastectomy, implant reconstruction, prevention/therapeutic
Δ4.8 pts (79.2 vs 74.3)
95% CI 1.0-8.7, p=0.01; 24mo, pre- vs sub-pectoral
TL;DRPre-pectoral implant improved 2yr chest well-being +4.8 pts (BREAST-Q, p=0.01) vs sub-pectoral, but more unplanned implant loss (21% vs 15%).
In pts undergoing skin- or nipple-sparing mastectomy (therapeutic or risk-reducing) who choose implant reconstruction, this supports pre-pectoral placement for better 2yr patient-reported chest well-being, weighed against numerically higher unplanned implant loss (21% vs 15%).
| Endpoint (24mo) | Pre-pectoral (N=191) | Sub-pectoral (N=189) | Difference |
|---|---|---|---|
| Physical well-being, chest (BREAST-Q) | 79.2 (75.5-82.8) | 74.3 (70.7-78.0) | 4.8 (1.0-8.7), p=0.01 |
+1 more figure
| Unplanned implant loss/replacement (24mo) | Pre-pectoral | Sub-pectoral | Adj. difference (95% CI) |
|---|---|---|---|
| Crude % (n/N) | 21.1% (41/194) | 14.5% (27/186) | 5.7% (-2.4 to 13.8) |
8 details 3 trials watching
International randomized phase 3 trial (OPBC-02): pre- vs sub-pectoral implant reconstruction after skin- or nipple-sparing mastectomy. Open-label; patient-reported primary endpoint analyzed by multiple imputation and linear mixed models.
Women undergoing skin- or nipple-sparing mastectomy for cancer treatment or risk reduction, opting for implant reconstruction. Primary QoL analysis N=191 pre- vs 189 sub-pectoral.
Primary: long-term patient-reported physical well-being (chest), BREAST-Q, at 24 months. Main secondary safety: unplanned loss or replacement of expander/implant.
BREAST-Q chest well-being 79.2 vs 74.3 at 24mo, difference 4.8 (95% CI 1.0-8.7, p=0.01), favoring pre-pectoral. Longitudinal completion 83-95%.
Point estimate showed more implant loss with pre-pectoral (21.1% vs 14.5%), failing the trial's non-inferiority safety hypothesis; the adjusted-difference 95% CI (-2.4 to 13.8) crosses zero.
Open-label with a patient-reported primary endpoint, so awareness of implant type could bias PROs. The 4.8-point gain is significant but modest, and the safety signal trended against pre-pectoral.
A major RCT in an area of genuine equipoise. It supports pre-pectoral for patient-reported chest well-being while flagging a higher implant-loss signal, so the choice reads as a real trade-off, not a clean win.
Randomized phase 3, primary endpoint met, but a modest patient-reported surrogate and an unmet non-inferiority safety endpoint keep it short of practice-changing.
- Durability of the QoL benefit and implant-loss gap beyond 24 months n=300 · primary completion 2024-12 · prepectoral vs subpectoral head-to-head, n=300n=88 · primary completion 2025-03 · prepectoral vs subpectoral breast satisfaction
- Do outcomes differ in patients receiving post-mastectomy radiation? n=104 · primary completion 2027-03 · prepectoral recon in adjuvant RT patients
- Which patients accept higher implant-loss risk for better chest well-being?
📚 Sources · 🐦 1 tweet
📌 Surgical de-escalation of implant-based breast reconstruction after mastectomy for breast cancer treatment or prevention: The international randomized phase I|I
— Elisabetta Bonzano MD, PhD (@to_be_elizabeth) May 30, 2026
PREPEC trial (ОРBC-02).
Presented by Walter Weber ✨#ASCO26 @OncoAlert #OncoAlertAF #BreastCancer pic.twitter.com/WE20JcBQG0
ROADS
ForResected brain metastasis > 2 cm, post-op cavity RT candidates
NR vs 17 mo
Surg bed recurrence 1% GammaTile vs 12% SRS
TL;DRSurgical bed recurrence 1% vs 12% and 2yr OS 62% vs 36% favoring intraoperative GammaTile brachytherapy over post-op SRS for resected brain mets >2cm.
The safety tradeoff the headline buries: leptomeningeal disease ran 10% with GammaTile vs 3% with SRS, even as surgical-bed recurrence fell to 1% vs 12%. Radiation necrosis was comparable (8% vs 7%). This moves the intraoperative-brachytherapy-vs-staged-cavity-SRS decision for resected mets >2 cm, where SRS local control is weakest.
| Endpoint | GammaTile | SRS |
|---|---|---|
| Time to surg bed recurrence | NR | 17 mo |
| Surg bed recurrence-free survival | NR | 11 mo |
| 2-yr OS | 62% | 36% |
8 details 2 trials watching
Randomized trial, N=230, resected brain metastasis > 2 cm. GammaTile (Cs-131 collagen-tile brachytherapy) placed in the cavity at resection vs post-op stereotactic radiosurgery. ASCO 2026 final results. Primary: time to surgical bed recurrence and surgical-bed recurrence-free survival.
Resected brain metastasis > 2 cm, the larger-cavity setting where single-fraction post-op SRS local control is weakest. Histology / primary tumor not specified in source.
Experimental: intraoperative permanent Cs-131 seed brachytherapy (GammaTile) at resection. Control: post-op cavity SRS. Dose, fractionation, and cavity margin not reported in source.
Both primary endpoints and 2yr OS favored GammaTile. Safety: radiation necrosis comparable (8% vs 7%), leptomeningeal disease higher with brachytherapy (10% vs 3%).
Post-op cavity SRS is the current standard for resected brain mets (N107C, Mahajan). ROADS challenges it, favoring intraoperative brachytherapy on local control.
Abstract-only, not yet peer-reviewed; open-label. The 2yr OS advantage is large for a local therapy and OS was not a stated primary endpoint, raising the question of baseline arm imbalance.
Randomized, primary endpoint (surg bed control) hit favoring intraop brachy over the post-op SRS standard; but abstract-only, open-label, and the large OS gain warrants scrutiny.
In pts with a resected brain metastasis >2 cm needing cavity radiotherapy, this supports intraoperative brachytherapy as an alternative to post-op SRS for local control; it does not extend to intact (unresected) mets or cavities ≤2 cm.
- Whether the large OS gain reflects arm imbalance vs true benefit active Post-Surgical Stereotactic Radiotherapy (SRT) Versus GammaTile-ROADS (Radiation One and Done Study) Phase 3n=230 · primary completion 2029-08 · randomized phase 3 GammaTile vs SRT
- Leptomeningeal failure risk with intraoperative brachytherapy active Intracavitary Carrier-embedded Cs131 Brachytherapy for Recurrent Brain Metastases: a Randomized Phase II Study Phase 2n=103 · primary completion 2026-12 · randomized brachytherapy vs surgery-alone safety
- Applicability to resection cavities ≤ 2 cm
📚 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
OptiTROP-Lung05 NCT06448312
For1L IIIB/IIIC-IV PD-L1≥1% NSCLC, EGFR/ALK wild-type
HR 0.35
95% CI 0.26-0.47, p<0.0001; median NR vs 5.7 mo
TL;DRmPFS NR vs 5.7 mo, HR 0.35, adding Sac-TMT (TROP2 ADC) to pembrolizumab in 1L PD-L1+ NSCLC.
| Arm | PFS events n (%) | Median PFS | HR (95% CI) |
|---|---|---|---|
| Sac-TMT+Pembro | 66 (31.7%) | NR (13.6-NE) | 0.35 (0.26-0.47) |
| Pembro | 128 (62.4%) | 5.7 mo (4.3-7.0) | — |
+2 more figures
| PD-L1 TPS | mPFS combo | mPFS pembro | HR (95% CI) |
|---|---|---|---|
| ≥50% | NR | 9.5 mo | 0.47 (0.29-0.77) |
| 1-49% | NR | 4.3 mo | 0.28 (0.19-0.41) |
| Arm | OS events n (%) | Median OS | HR (95% CI) |
|---|---|---|---|
| Sac-TMT+Pembro | 33 (15.9%) | NR | 0.55 (0.36-0.85) |
| Pembro | 54 (26.3%) | NR | — |
8 details 2 trials watching
Phase 3, open-label, multicenter RCT (NCT06448312); 1:1, N=413. Primary PFS by BICR crossed its interim efficacy boundary at 194 events; median follow-up 10.5 mo.
1L stage IIIB/IIIC or IV NSCLC, PD-L1 TPS ≥1% (22C3), EGFR/ALK wild-type, ECOG 0-1. Stratified by histology, PD-L1 (1-49 vs ≥50), ECOG.
Sac-TMT (TROP2 ADC) 4 mg/kg Q2W + pembrolizumab 400 mg Q6W vs pembrolizumab alone; pembro capped at 18 cycles.
ORR 70.2% vs 42.0%. PFS gain held across PD-L1 strata, strongest in TPS 1-49% where pembro monotherapy is weakest. OS immature, formal testing pending.
Current 1L PD-L1+ NSCLC standard is pembrolizumab ± chemotherapy. This tests a chemo-free ADC+IO doublet; no head-to-head vs chemo-IO.
Open-label; OS immature at 10.5-mo follow-up and formally untested; PFS reported at an interim efficacy boundary. No safety data in source.
PFS crossed an interim efficacy boundary; key-secondary OS descriptive/immature at 10.5-mo f/u; open-label. Strong but not yet mature enough to move 1L SOC.
- Will the OS benefit mature and hold? n=30 · primary completion 2026-06 · candidate match
- How does the chemo-free ADC+IO doublet compare to chemo+IO? n=30 · primary completion 2026-06 · candidate match
- Safety of adding a TROP2 ADC to pembrolizumab
📚 Sources · 🐦 2 tweets
🔁REVIEW #ASCO26 #LCSM Oral
— Hidehito HORINOUCHI (@HHorinouchi) May 30, 2026
🔥OptiTROP-Lung05: 1L Sac-TMT + Pembro vs Pembro in PD-L1+ NSCLC
✅mPFS NR vs 5.7m (HR 0.35)
✅ORR 70.2% vs 42.0%
✅OS HR 0.55 (95%CI 0.36-0.85, immature)
🎙️Dr. Caicun Zhou
🔗 https://t.co/DcbK1dGrhO@OncoAlert @Larvol @ASCO @IASLC https://t.co/512k6dZviW pic.twitter.com/Vdo86N50h9
Right patient. Right treatment. Right timing.
— Yakup Ergün (@dr_yakupergun) May 30, 2026
The result: curves like these👇#ASCO26 https://t.co/72KByLKz90
Neo-CRAG
ForHigh-risk locally advanced gastric/EGJ (cT3N2-3 to cT4), fit for D2 resection
mDFS 52.7 vs 24.4 mo
HR 0.750 (95% CI 0.607-0.928), P=0.008
TL;DRAdding neoadjuvant chemoRT (45Gy/25fx) to periop XELOX improved mDFS 52.7 vs 24.4mo (HR 0.75) and mOS 67.5 vs 37.6mo in high-risk LAGC.
The RT read is clean attribution: both arms share the XELOX backbone and the CRT arm got dose-reduced chemo during RT, yet locoregional recurrence halved (9.4% vs 18.3%) with more ypN0 and downstaging. On 45Gy/25fx, this revives neoadjuvant chemoRT for high-risk D2-resected gastric/EGJ, on a non-FLOT backbone.
| Endpoint | CRT | CT | HR (95% CI), P |
|---|---|---|---|
| Median DFS | 52.7 mo | 24.4 mo | 0.750 (0.607-0.928), P=0.008 |
| 3-yr DFS | 55.6% | 42.4% | — |
| Median OS | 67.5 mo | 37.6 mo | 0.781 (0.628-0.970), P=0.025 |
| 5-yr OS | 50.1% | 44.2% | — |
7 details 2 trials watching
Phase 3 open-label RCT, 1:1, N=620 (310/arm), 13 Chinese referral centers, enrolled 2013-2022. Primary: disease-free survival; secondary OS, pCR, R0, safety.
High-risk locally advanced gastric/EGJ adenocarcinoma: cT3N2-3M0, cT4aN+M0, or cT4bNanyM0; 36.3% EGJ (Siewert II/III). All planned standardized D2 gastrectomy.
Both arms: 3 cycles preoperative + 3 cycles adjuvant XELOX (oxaliplatin 130, capecitabine 1000 BID D1-14, Q3W) around D2 gastrectomy.
CRT arm only: concurrent 45 Gy/25 fx begun after chemo cycle 1, with dose-reduced XELOX (oxaliplatin 100, capecitabine 825) during RT. RT is the sole added variable between arms.
Primary DFS met and secondary OS positive, both favoring CRT; pathologic downstaging, ypN0, and locoregional control also improved (see figure and table).
Contrasts with CRITICS and TOPGEAR, where adding radiotherapy to a chemo backbone did not improve survival. A positive DFS/OS here reopens neoadjuvant chemoRT in high-risk, D2-resected LAGC.
Open-label; non-FLOT XELOX backbone limits transfer to current perioperative standard. Single-country (China) with high D2-resection quality; DFS (not OS) was the primary endpoint.
Randomised phase 3, primary DFS and OS both hit, but positive chemoRT diverges from negative CRITICS/TOPGEAR; non-FLOT XELOX backbone limits transfer to current SOC.
In high-risk cT3N2-3/cT4 gastric or EGJ adenocarcinoma planned for D2 gastrectomy on a XELOX backbone, these data support a DFS/OS and locoregional-control benefit from adding neoadjuvant chemoRT; the signal does not extend to FLOT-backbone or metastatic patients.
- Incremental benefit of RT on a FLOT chemo backbone n=776 · primary completion 2023-06 · candidate match
- Generalizability beyond high-quality-D2 Asian centers
- Whether EGJ and distal gastric benefit equally n=4 · primary completion 2024-03 · candidate match
📚 Sources · 🐦 1 tweet
Neo-CRAG: Ph3 RCT (n=620, gastric/GEJ) - adding neoadj chemoRT to peri-op XELOX improved OS (68 v 38 mo).
— Dr. Nina Niu Sanford (@NiuSanford) May 30, 2026
Limitation=non-FLOT, BUT still relevant IMO b/c:
1) DFS/OS benefit substantial.
2) Improvements in pCR, downstg, LRR supports plausible RT effect on OS. #ASCO26 @OncoAlert pic.twitter.com/eeM0Z8p20M
Wait or Treat? NCT05236946
ForAsymptomatic brain mets, EGFR/ALK-mutant metastatic NSCLC, on TKI + chemo
Sub-HR 0.35
95% CI 0.21-0.59, p<0.001; favors upfront RT
TL;DRUpfront cranial RT cut 2y intracranial progression (21.7% vs 50%, sub-HR 0.35) but no OS gain; survival numerically favored delayed (HR 1.45).
The primary endpoint actually favored upfront RT (2y intracranial progression 21.7% vs 50%, sub-HR 0.35), yet OS trended toward delayed (2y 48% vs 60%) with 6% radiation necrosis vs none. Better CNS control bought no survival and added toxicity, so upfront cranial RT can be safely deferred to intracranial progression.
| Endpoint | Upfront RT | Delayed RT |
|---|---|---|
| Events | 20 | 47 |
| 1-yr intracranial PD | 8.7% (2.9-14.5) | 25.7% (16.8-34.7) |
| 2-yr intracranial PD | 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 |
8 details 4 trials watching
Phase 3 open-label RCT, 1:1, N=208 (105 upfront cranial RT vs 103 delayed) at a single center (Tata Memorial). Median follow-up 30.6 mo; stratified by GPA and synchronous vs metachronous BM.
Metastatic EGFR- or ALK-mutant NSCLC with radiologically measurable, completely asymptomatic brain metastases, ECOG 0-2. Both arms received TKI + chemotherapy.
Delayed arm held cranial RT until intracranial progression or patient request, with MRI brain q3mo for year 1 then q6mo. RT dose, fractionation, and technique (SRS vs WBRT) not reported in source.
Primary: intracranial PFS. Secondary: OS, PFS, toxicity, ORR, neurocognition, PROM.
Primary endpoint met for intracranial control but did not translate to survival; the OS trend and radiation-necrosis signal both favored deferral. See the intracranial-progression figure and survival table for effect sizes.
First randomized evidence on RT timing in this population. Consistent with the CNS-active TKI era (osimertinib, alectinib, lorlatinib), where strong systemic intracranial control supports deferring RT.
Open-label and single-institution. Powered for intracranial PFS, not OS, so the survival and necrosis signals favoring deferral are secondary. RT technique not reported.
Randomized phase 3, primary intracranial-PFS endpoint met, but no OS benefit and less necrosis with deferral; backs the emerging TKI-first, defer-RT approach in oncogene-driven NSCLC.
In asymptomatic brain metastases from EGFR/ALK-mutant metastatic NSCLC on TKI plus chemo, this supports deferring cranial RT until intracranial progression; it does not extend to symptomatic brain mets or oncogene-negative NSCLC.
- Neurocognition and PRO outcomes by RT timing (not reported in source)
- Does RT technique (SRS vs WBRT) change the deferral tradeoff? n=115 · primary completion 2026-07 · randomizes SRT vs hippocampal-sparing WBRT
- Durability of TKI-first intracranial control beyond 2 years n=162 · primary completion 2024-12 · osi alone vs early SRS, asymptomatic BMactive Study of Osimertinib + SRS vs Osimertinib Alone for Brain Metastases in EGFR Positive Patients With NSCLC Phase 2n=40 · primary completion 2025-04 · osimertinib-alone arm tests TKI-first controlrecruiting Early or Delayed Intervention of Brain Radiotherapy Combined With Almonertinib in EGFR Mutated NSCLC With Brain Metastases Phase 3n=232 · primary completion 2028-12 · randomizes early vs delayed RT on EGFR-TKI
📚 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
SENOMAC NCT02240472
ForcN0 T1-T3 breast cancer, 1-2 sentinel-node macrometastases
HR 0.89
95% CI 0.66-1.19, NI met (margin 1.44); primary OS not yet reported
TL;DR5-yr RFS 89.7% vs 88.7%, HR 0.89 (0.66-1.19): omitting completion ALND noninferior, with nodal RT given in ~90% of both arms.
Nodal RT with nodal target volumes reached ~90% in both arms (89.9% vs 88.4%), so SENOMAC validates dropping completion ALND within regional nodal irradiation, not omitting axillary treatment. For the RT reader it positions nodal RT as the axillary treatment when SNB shows 1-2 macromets; it does not test omitting both surgery and RT.
8 details 4 trials watching
Phase 3 noninferiority RCT, 1:1, N=2766 enrolled (2540 per-protocol), 67 sites across 5 countries; median follow-up 46.8 mo. Reports the prespecified secondary RFS; primary OS not yet reported.
cN0 T1-T3 breast cancer with 1-2 sentinel-node macrometastases (>2mm). Extends eligibility beyond Z0011 to mastectomy, T3, extracapsular extension, and men.
Nodal RT including nodal target volumes reached 89.9% (SNB-only) and 88.4% (cALND). ALND omission was therefore tested within regional nodal irradiation, not as omission of axillary treatment.
Primary: overall survival (not reported in source). This analysis: prespecified secondary recurrence-free survival, per-protocol and modified ITT.
Noninferiority met: the upper confidence bound stayed below the prespecified 1.44 margin (P<0.001) across 191 recurrence-or-death events.
| Endpoint | SNB only | cALND |
|---|---|---|
| 5-yr RFS | 89.7% (87.5-91.9) | 88.7% (86.3-91.1) |
| HR recurrence/death | 0.89 (0.66-1.19) | ref |
Consistent with Z0011 (breast-conserving + whole-breast RT) and AMAROS (axillary RT replacing ALND), both null for ALND benefit at 10 yr. SENOMAC adds the macromet-only, mastectomy/T3/ECE/male groups in a larger cohort.
This is the secondary RFS endpoint, not the OS primary, at a 46.8-mo median follow-up short for ER+ biology. The HR 1.44 noninferiority margin is generous, and ~90% nodal RT confounds attribution to surgical omission alone.
Randomised phase 3 noninferiority; prespecified secondary RFS met, extends Z0011/AMAROS de-escalation to mastectomy/T3/ECE/men. Primary OS not yet reported.
In cN0 breast cancer with 1-2 sentinel-node macrometastases who receive regional nodal RT, this supports omitting completion ALND, including mastectomy, T3, extracapsular extension, and men; it does not extend to patients treated without nodal radiotherapy.
- Overall survival (primary endpoint) result still pending
- Can nodal RT be omitted alongside ALND in this population? recruiting Evaluating Omitting of Internal Mammary Irradiation Among Early Stage Intermediate Risk (N1) Breast Cancer Phase NAn=214 · primary completion 2025-10 · randomized omit internal mammary RT in N1active Postmastecomy Internal Mammary Nodal Irradiation for High-risk Breast Cancer Patients Phase 3n=2400 · primary completion 2025-11 · phase 3 IMN RT vs no IMN RT, DFS endpointrecruiting The T-REX Trial: Tailored Regional External Beam Radiotherapy in Clinically Node-negative Breast Cancer Patients With 1-2 Sentinel Node Macrometastases. Phase NAn=1350 · primary completion 2028-12 · omit regional RT, 1-2 SN macromets, ER+/HER2-recruiting RecurIndex Guided Avoidance of Regional Nodal Irradiation for Node Positive Breast Cancer Phase NAn=540 · primary completion 2029-08 · RecurIndex-guided RNI avoidance in N1
- Durability beyond 5 years in ER+ disease
📚 Sources · 📄 1 paper
SWOG/NRG S1914 NCT04214262
ForEarly-stage inoperable/surgery-declined NSCLC (T1-3N0M0 ≤7cm), ≥1 risk factor
HR 1.15
95% CI 0.65-2.01, p=0.63; did not meet primary
TL;DROS HR 1.15 (0.65-2.01), p=0.63: adding atezolizumab to SBRT did not improve survival in early-stage inoperable NSCLC; futility-stopped, excess toxicity.
Local control got worse with IO, not better: local failures 13% vs 7% adding atezolizumab, alongside null OS/PFS and a former/never-smoker harm signal (OS HR 2.50). SBRT alone stays standard for inoperable early-stage NSCLC, closing the add-IO-to-SBRT question negatively.
6 details
Phase 3 open-label RCT, 1:1, SWOG/NRG; N=403 eligible (201 S / 202 AS). Stopped at first interim for futility on OS and PFS. Median follow-up 12 mo (0.03-49).
T1-3N0M0 NSCLC ≤7cm, medically inoperable or declined surgery, ≥1 recurrence risk factor (diameter ≥2cm, SUV ≥6.2, moderate/poor/undifferentiated). Median age 73, median tumor 2.3cm, 89% ECOG 0-1.
SBRT both arms (SoC backbone): 3-8 fractions, BED ≥100 Gy. Stratified by central vs peripheral, <4 vs ≥4cm, PS 0-1 vs 2.
Atezolizumab 1200mg IV Q3wk ×8 (neoadjuvant, concurrent, adjuvant); SBRT initiated at cycle 3.
Primary: overall survival. Secondary: PFS, failure patterns, toxicity, QoL. 1-sided stratified log-rank at 2.5%.
G≥3 AEs 12% AS (21 G3, 1 G4, 1 G5 respiratory-failure death) vs 2% S. Excess toxicity with no efficacy gain.
Prior randomized phase 2 (**PMID 37478883, I-SABR, nivolumab+SBRT) suggested benefit adding IO; S1914 with atezolizumab does not confirm** and shows harm signals.
Open-label; stopped early at interim (median f/u 12mo, only 49 deaths). Former/never-smoker harm is an exploratory subgroup; central review of local recurrence ongoing.
| Endpoint | S | AS | HR (95% CI), p |
|---|---|---|---|
| 2yr OS | 82% | 80% | 1.15 (0.65-2.01), p=0.63 |
| 2yr PFS | 71% | 60% | 1.35 (0.89-2.06), p=0.16 |
| Failure | S | AS |
|---|---|---|
| Local | 7% | 13% |
| Regional | 2% | 3% |
| Distant | 4% | 5% |
| Endpoint (never/former smokers) | HR (95% CI), p |
|---|---|
| OS | 2.50 (1.11-5.59), p=0.03 |
| PFS | 2.16 (1.15-4.04), p=0.01 |
Phase 3 stopped for futility; adding IO to SBRT gave no OS/PFS benefit and excess toxicity, reaffirming SBRT-alone SOC and not confirming the prior phase 2 signal.
In medically inoperable or surgery-declined early-stage (T1-3N0) NSCLC treated with definitive SBRT, this argues against adding atezolizumab, and does not extend to node-positive or locally advanced disease.
- Biomarker/PD-L1 subset that benefits from adding IO to SBRT
- Whether excess local failures with IO hold on central review
- Reconciling harm signal with prior phase 2 IO+SBRT benefit
📚 Sources · 📄 1 paper
Abstract
EORTC 22922/10925
ForStage I-III breast, medial/central primary or axillary node-positive
HR 1.00
95% CI 0.90-1.10, p=.967; 20yr OS 61.0% vs 61.8% (ns)
TL;DR20yr OS 61.0% vs 61.8%, HR 1.00 (p=.967): IM-MS-RT cut breast cancer mortality (HR 0.82) but raised non-BC deaths (HR 1.26).
The RT read is competing mortality: IM-MS-RT's breast cancer mortality benefit (HR 0.82) is fully offset by excess cardiac and lung deaths (HR 1.26) at 20yr. With 1996-2004 planning the survival case nets to zero, so contemporary heart-sparing (DIBH/IMRT) is the variable that decides whether IM-MS nodal coverage still pays off.
7 details 5 trials watching
Phase 3 multicenter RCT with central RT quality assurance; 4004 women randomized 1996-2004 to added IM-MS nodal RT vs none. Prespecified for final analysis at 20yr on a delayed-benefit hypothesis; median follow-up 22.2yr.
Stage I-III breast adenocarcinoma, age ≤75. Eligible if central/medial primary (any nodal status) OR any-quadrant primary with axillary node involvement. Surgery was mastectomy or BCS plus ALND; median age 54.
Intervention added internal-mammary + medial-supraclavicular (levels 3-4) nodal irradiation on top of standard breast/chest-wall RT. 1996-2004 planning era (2D/3D, pre-DIBH/IMRT); dose and fractionation not specified in source text.
Primary: overall survival. Secondary: disease-free survival, distant metastasis-free survival, breast cancer mortality, any breast recurrence.
Primary OS was flatly null; the significant efficacy signals (lower breast cancer mortality, fewer breast recurrences) were offset in OS terms by excess non-breast-cancer deaths. Per-endpoint numbers in the table.
| Endpoint (20yr) | IM-MS-RT | Control | HR (95% CI), p |
|---|---|---|---|
| Overall survival | 61.0% | 61.8% | 1.00 (0.90-1.10), p=.967 |
| Disease-free survival | 48.2% | 49.0% | 0.97 (0.89-1.06), p=.515 |
| Distant metastasis-free | 58.9% | 59.8% | 0.97 (0.88-1.08), p=.578 |
| Breast cancer mortality | 18.6% | 22.4% | 0.82 (0.72-0.95), p=.006 |
| Non-BC/unknown deaths | 20.4% | 15.8% | 1.26, p=.002 |
| Late morbidity | IM-MS-RT | No IM-MS-RT |
|---|---|---|
| Lung fibrosis | 6.3% | 3.2% |
| Cardiac fibrosis | 2.7% | 1.7% |
| Cardiac disease | 15.2% | 11.7% |
| Severe cardiac (G3-4) | 1.9% | 1.7% |
| Severe lung (G3-4) | 0.3% | 0.0% |
Excess late lung fibrosis, cardiac fibrosis, and cardiac disease with IM-MS-RT is the mechanism behind the competing non-breast-cancer mortality; severe grade 3-4 cardiac and lung events stayed rare in both arms (table).
Aligns with the 10-yr EORTC 22922 report (Poortmans, NEJM 2015) and MA.20 in showing regional nodal RT improves disease control more than OS. The new 20yr signal: late cardiopulmonary deaths neutralize the breast cancer mortality gain.
1996-2004 planning predates modern cardiac-sparing, so the non-breast-cancer-death penalty likely overstates contemporary risk. Systemic therapy followed era standards (tamoxifen era), not current regimens. OS as primary is a high bar a single nodal-RT field rarely clears.
Large randomized phase 3, OS-primary, 22yr f/u: internally valid to contest the IM-MS-RT survival rationale, which the mortality-toxicity tradeoff nullifies. Divergence is the headline.
In a woman with a medial/central or node-positive stage I-III breast tumor, this tempers the survival rationale for adding the internal-mammary + medial-supraclavicular field specifically; it does not change breast/chest-wall or axillary RT indications.
- Does modern heart-sparing RT (DIBH/IMRT) preserve the mortality benefit without the cardiac penalty? recruiting Robustness Evaluation of Deep Inspiration Breath-Hold (DIBH) Plans in Internal Mammary Irradiationn=25 · primary completion 2026-12 · DIBH heart sparing while covering IMNn=500 · primary completion 2029-11 · IMPT vs IMRT toxicity for nodal breast RT
- Which subgroups still net an OS gain from IM-MS-RT coverage? active Postmastecomy Internal Mammary Nodal Irradiation for High-risk Breast Cancer Patients Phase 3n=2400 · primary completion 2025-11 · IMN vs no-IMN on DFS in high-risk pts
- Optimal patient selection for internal-mammary chain coverage in the contemporary era recruiting Evaluating Omitting of Internal Mammary Irradiation Among Early Stage Intermediate Risk (N1) Breast Cancer Phase NAn=214 · primary completion 2025-10 · clinical-genomic model to omit IMI in N1recruiting Radiotherapy Dose Adaptation Based on Tumor Biology in Patients With cN2b-N3 Breast Cancer Phase NAn=120 · primary completion 2028-03 · dose adaptation for IM/SCV nodal mets
📚 Sources · 📄 1 paper
Abstract
Bladder Adjuvant Radiotherapy Trial
ForHigh-risk MIBC post-cystectomy (pT3-4, N+, or margin+), chemo-treated
HR 0.43
2y LRFS 87.1% vs 76.0%; 95% CI 0.20-0.96, P=.04
TL;DR2y LRFS 87.1% vs 76.0%, HR 0.43 (0.20-0.96) P=.04 favoring adjuvant pelvic IMRT after cystectomy; DFS/BCSS/OS all NS.
Locoregional control is the RT read: 2y LRFS 87.1% vs 76.0% (HR 0.43) with stoma-sparing IG-IMRT 50.4Gy/28fx to the cystectomy bed plus pelvic nodes, no added severe toxicity. DFS, BCSS, and OS all trended toward RT but none significant at N=153, reopening adjuvant pelvic RT for high-risk MIBC without settling survival benefit.
8 details 3 trials watching
Phase 3 multicenter RCT, 1:1, N=153 (RT=77 vs Obs=76); stratified by nodal involvement and chemotherapy timing (neoadjuvant/adjuvant/none). Median follow-up 47 mo.
High-risk nonmetastatic urothelial MIBC after radical cystectomy: any of pT3-4, N1-3, margin-positive, or ≤10 nodes dissected. Enrolled 62% pT3-4, 41% pN+.
Stoma-sparing IG-IMRT, 50.4Gy in 28 fractions to the cystectomy bed and pelvic nodes.
Over 90% received perioperative chemotherapy (71% neoadjuvant, 20% adjuvant). None received immunotherapy.
Primary: 2-year locoregional recurrence-free survival. Secondary: disease-free survival, bladder-cancer-specific survival, overall survival.
Primary LRFS met (HR 0.43, P=.04); DFS, BCSS, and OS all favored RT but none reached significance (see table).
| Endpoint | RT | Obs | HR (95% CI) |
|---|---|---|---|
| 2y 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) |
No additional severe toxicity reported with adjuvant pelvic IMRT versus observation.
Reopens the adjuvant-RT-after-cystectomy question that prior Egyptian NCI trials raised for local control; first randomized test in the modern IG-IMRT era.
Small (N=153); primary endpoint is a locoregional-control surrogate, and survival endpoints were underpowered and nonsignificant. No immunotherapy-era comparator.
Randomised phase III hit prespecified primary LRFS endpoint favoring adjuvant RT (non-standard); but N=153 and DFS/BCSS/OS all NS. Field reopened, not settled.
In high-risk post-cystectomy MIBC (pT3-4, N+, or margin+) after perioperative chemo, this supports adjuvant pelvic IMRT as a locoregional-control option but not a proven survival gain; it does not extend to organ-confined, node-negative low-risk disease.
- Does the locoregional control benefit translate to overall survival in a larger trial? active Adjuvant Radiotherapy in Patients With Pathological High-risk Bladder Cancer (GETUG-AFU 30) Phase NAn=81 · primary completion 2027-12 · randomized adjuvant post-cystectomy RT, survival EP
- How does adjuvant RT integrate with adjuvant immunotherapy (nivolumab)? active Adjuvant Nivolumab Following Chemo-Radiation in Localized Muscle-Invasive Bladder Cancer Phase 2n=200 · primary completion 2025-02 · adjuvant nivolumab after chemoRT, 2y FFS EPrecruiting Adjuvant Concurrent Immunotherapy and Radiotherapy for the Treatment of Bladder Cancer Phase 1n=10 · primary completion 2027-04 · adjuvant concurrent IO + RT for bladder cancer
- Which high-risk subgroup (pN+ vs margin+) benefits most from adjuvant RT?
📚 Sources · 📄 1 paper
Abstract
High-Dose Hyperfractionated SIB RT vs Standard RT for LS-SCLC NCT03214003
ForLS-SCLC, age 18-70, ECOG 0-1, ≤1 prior chemo course
TL;DRmOS 60.7 vs 39.5mo, HR 0.55 (0.37-0.72), p=0.003 favoring dose-escalated 54Gy BID SIB over standard 45Gy BID in LS-SCLC.
The escalation route is the RT read: 54Gy/30fx twice-daily via SIB beat the 45Gy BID standard (HR 0.55) where prior once-daily escalation (CONVERT, CALGB 30610) didn't, with grade 3-4 oesophagitis (13% vs 12%) and pneumonitis (5% vs 6%) flat. Moves the dose-escalation decision toward hyperfractionation, not once-daily.
7 details 3 trials watching
Open-label phase 3 RCT at 16 Chinese public hospitals, randomised 1:1 (54Gy n=108, 45Gy n=116), N=224. Median follow-up 46 mo. DSMB stopped the trial early for benefit (Apr 2021).
LS-SCLC, age 18-70, ECOG 0-1, previously untreated or ≤1 course of platinum-etoposide. Median age 64 (IQR 58-68), 54% male. Stratified by ECOG, stage, prior chemo course and choice.
Both arms VMAT twice-daily, 10 fx/week, PTV 45Gy/30fx. Experimental arm adds a simultaneous integrated boost to 54Gy/30fx to the gross tumour volume. PCI 25Gy/10fx for responders.
Primary: overall survival in the ITT population. Safety analysed as-treated.
mOS 60.7 mo (95% CI 49.2-62.0) with 54Gy vs 39.5 mo (27.5-51.4) with 45Gy, HR 0.55 (0.37-0.72), p=0.003.
Grade 3-4 oesophagitis 13% vs 12% (p=0.84) and pneumonitis 5% vs 6% (p=0.663), no excess with dose escalation. One treatment-related death (MI) in the 54Gy arm.
Prior escalation via once-daily RT (CONVERT, CALGB 30610) did not beat 45Gy BID; this instead escalates the twice-daily schedule with a SIB and shows an OS gain.
Open-label; early DSMB termination for benefit can overestimate the effect. Single-country, modest N=224, and predates adjuvant durvalumab consolidation (ADRIATIC).
Randomised phase 3, primary OS hit (HR 0.55), diverges from the 20-yr 45Gy BID standard. Open-label and DSMB-stopped-early temper it, but design is valid for the divergence.
In fit LS-SCLC pts aged 18-70 with ECOG 0-1 on concurrent chemoradiation, this supports 54Gy/30fx twice-daily thoracic RT over the 45Gy standard; it does not extend to pts over 70, ECOG 2+, or the durvalumab-consolidation era.
- Generalizability beyond age ≤70, ECOG 0-1, Asian cohort
- Optimal RT dose alongside durvalumab consolidation n=65 · primary completion 2027-01 · SIB high-dose RT then PD-L1 maintenance, LS-SCLC
- Confirmation in a multinational trial given early stopping active Two Schedules of Hyperfractionated Thoracic Radiotherapy in Limited Disease Small Cell Lung Cancer Phase NAn=177 · primary completion 2020-07 · randomised 45 vs 60Gy BID hyperfractionated TRTrecruiting Dose-Escalation Radiotherapy in Limited-Stage Small Cell Lung Cancer: A Phase III Randomized Trial Phase 3n=300 · primary completion 2028-09 · phase 3 RCT: 45 vs 60 vs SIB 45-54Gy BID
📚 Sources · 📄 1 paper
OPERA Trial (5-year)
ForRectal cancer, post-neoadjuvant therapy
TL;DR76% achieved a good clinical response at W14 (DRE+rectoscopy); nCR matched cCR for 5yr organ preservation (77% vs 81%), enabling early W&W selection.
nCR carries the same 5yr organ-preservation prognosis as cCR (77% vs 81%) and reflects RT-related mucosal change, not residual tumor, so an nCR at reassessment shouldn't route a patient to salvage TME. Early W14 clinical exam (DRE+rectoscopy) matched MRI TRG1-2 in 98%, letting W&W selection move up from W24.
8 details 3 trials watching
Post-hoc analysis of the randomised OPERA trial, N=141 evaluable. Tests an earlier response timepoint (W14, ~1 mo after NAT end) against the protocol W24 triad, scoring clinical tumor response (CTRE) by DRE + rectoscopy as cCR / nCR / PR.
OPERA randomised the boost after neoadjuvant chemoradiotherapy (EBRT boost vs contact X-ray brachytherapy boost); these slides don't label which arm is which. The higher early good-response rate in one arm did not translate to a 5yr organ-preservation difference (see table).
Post-hoc, non-randomised comparison of response groups; W14 selection not prospectively validated against the protocol W24 assessment. Single-trial, modest N; 5yr OP differences underpowered (p=0.24).
Authors' RT-relevant read: nCR reflects radiation change, not residual tumor, and matches cCR for organ preservation (77% vs 81%), so an nCR should not trigger salvage TME. Early DRE + rectoscopy can move W&W selection up to W14 with MRI confirmation.
| Endpoint | Arm A | Arm B | p |
|---|---|---|---|
| W14 good response (cCR+nCR) | 65% | 88% | 0.004 |
| 5yr organ preservation | 75% | 83% | 0.24 |
Post-hoc analysis of an alternate (W14 vs protocol W24) timepoint; response-group comparison non-randomised and not prospectively validated for W&W selection.
In a rectal-cancer pt with a near-complete clinical response after chemoradiotherapy, this supports continued watch-and-wait over radical TME; the 24% with only a partial response stay surgical candidates and aren't covered.
- Prospective validation of W14 vs W24 response assessment for W&W selection active Short RT Versus RCT,Followed by Chemo.and Organ Preservation for Interm and High-risk Rectal Cancer Patients Phase 3n=702 · primary completion 2023-09 · candidate match
- Optimal RT boost technique to maximise early complete clinical response active Short RT Versus RCT,Followed by Chemo.and Organ Preservation for Interm and High-risk Rectal Cancer Patients Phase 3n=702 · primary completion 2023-09 · candidate match
- Long-term regrowth risk in nCR pts managed by watch-and-wait recruiting Organ Preservation First Strategy and Intentional Watch and Wait for MRI Defined Low-risk Rectal Cancer Phase NAn=96 · primary completion 2025-09 · candidate match
📚 Sources · 🐦 1 tweet
Day FOUR of #ESTRO26 Coverage by OncoAlert 🚨
— OncoAlert (@OncoAlert) May 18, 2026
Five-year Results of the OPERA Trial: When and How to Assess Tumor Response to Guide Rectal Preservation Presented by Syrine Ben Dhia 🇫🇷 #RadOnc ☢️
This post-hoc analysis of the OPERA trial evaluated early tumor response… pic.twitter.com/KUanFTxeFh
HEAT Trial NCT01794403
ForLocalized low- to intermediate-risk prostate cancer, IPSS <12
7% vs 7.4% (AHRT vs EHRT)
Non-inferior, P=0.007 at 4.25y; NI margin 12%
TL;DRAHRT 5fx non-inferior to EHRT 26fx for biochemical failure, 7% vs 7.4% (P_NI=0.007) at 4.25y; less acute GI toxicity.
The head-to-head prior SBRT trials skipped: 5fx AHRT (36.25 Gy, SIB 40 Gy) vs 26fx EHRT, both IMRT with ADT allowed, isolating fractionation from technique and hormones. Acute G2+ GI toxicity favored the 5fx arm at equal biochemical control, moving the ultrahypofractionation choice for low- to intermediate-risk pts.
| Arm | Biochemical failure (4.25y) | P (NI) |
|---|---|---|
| AHRT | 7% | 0.007 |
| EHRT | 7.4% | ref |
+1 more figure
8 details 4 trials watching
Phase 3 international non-inferiority RCT, 1:1, biochemical failure (Phoenix) primary, NI margin 12%. Interim analysis at 142 analyzed of 456 planned; median follow-up 59.7 mo.
Localized low- to intermediate-risk prostate cancer, IPSS <12. 82.4% intermediate-risk; stratified by risk, gland volume (<60 vs 60-80cc), and ADT. 28% received ADT (≤6 mo, both arms).
AHRT 36.25 Gy/5 fx (7.25 Gy/fx) + GTV SIB to 40 Gy vs EHRT 70.2 Gy/26 fx (2.7 Gy/fx), IMRT in all patients.
AHRT non-inferior to EHRT for biochemical failure: 7% vs 7.4%, P non-inferiority=0.007 at 4.25y.
| Arm | Dose / fractionation | Boost / technique |
|---|---|---|
| AHRT | 36.25 Gy / 5 fx (7.25 Gy/fx) | GTV SIB to 40 Gy |
| EHRT | 70.2 Gy / 26 fx (2.7 Gy/fx) | IMRT all pts |
Acute G2+ GI toxicity lower with AHRT. No significant difference in late G2+ GI or acute/late G2+ GU toxicity. Supportive-med use (laxatives, psyllium) counted as G2.
First RCT comparing AHRT vs EHRT 1:1 with modern IMRT and ADT. Prior ultrahypofractionation trials (HYPO-RT-PC, PACE-B, NRG-GU005) used heterogeneous or no-ADT controls.
Interim analysis at roughly one-third of planned accrual; full pre-specified primary pending. Small analyzed N (142); biochemical, not clinical, endpoint.
Interim analysis at 142 of 456 planned pts; non-inferiority met but full pre-specified primary analysis pending. Underpowered vs accrual goal.
In localized low- to intermediate-risk prostate with IPSS <12, this supports 5fx AHRT as non-inferior to 26fx EHRT with less acute GI toxicity; it does not extend to high-risk disease or glands >80cc, which the trial excluded.
- Durability of biochemical control at full accrual and longer follow-up recruiting Androgen Suppression Combined With Nodal Irradiation and Dose Escalated Prostate Treatment Phase 3n=710 · primary completion 2032-10 · phase 3 SBRT vs EBRT + brachytherapy boostrecruiting PRO-BOOST-LC: Whole-Gland Boost Strategies Versus SBRT Monotherapy in PSMA-Staged Localized and Locally Advanced Prostate Cancer Phase 2/3n=1200 · primary completion 2033-12 · SBRT monotherapy vs whole-gland boost
- Does 5fx AHRT benefit extend to high-risk or larger-gland prostate? recruiting Testing Shorter Duration Radiation Therapy Versus the Usual Radiation Therapy in Patients With High Risk Prostate Cancer Phase 3n=1209 · primary completion 2036-03 · phase 3 5fx SBRT vs usual RT, high-risk
- Long-term late GU/GI toxicity with 5fx AHRT n=42 · primary completion 2028-01 · 5fx SABR, urethra/rectum-sparing, GU/GI AE
📚 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
PEACE 2
ForcN0 very-high-risk localized prostate (Gleason≥8, T3-4, or PSA≥20)
HR 0.81, ns
95% CI 0.63-1.03, p=0.088; primary endpoint not met
TL;DRPelvic nodal RT missed 1° endpoint: 7yr cPFS 67.1% vs 62.9% prostate-only, HR 0.81 (0.63-1.03) p=0.088; no MFS/PCSS/OS gain.
The RT decision is elective nodal coverage: a randomized head-to-head (n=380 vs 381) shows whole-pelvic RT adds no cPFS, MFS, PCSS or OS benefit over prostate-only in cN0 very-high-risk disease, with modern-technique toxicity minimal. Staging was conventional imaging/choline PET, not PSMA, so PSMA-defined N0 pts remain untested.
Also covered May 17
| Arm | 7yr cPFS (95% CI) | HR (95% CI) | p |
|---|---|---|---|
| Prostate-only RT | 62.9% [57.4-68.1] | ref | |
| Pelvic RT | 67.1% [61.6-72.2] | 0.81 [0.63-1.03] | 0.088 |
+1 more figure
8 details 2 trials watching
Phase 3 randomized 2×2 factorial (pelvic vs prostate-only RT × cabazitaxel ×4 vs none), ADT ×3 yr in all arms. Pelvic-RT comparison n=380 vs 381, 7-year outcomes reported. Multicenter GETUG/Unicancer.
Very high-risk localized prostate: ≥2 of Gleason ≥8, T3-T4, PSA ≥20 ng/mL. N0M0 by conventional imaging or choline PET/CT, not PSMA.
High-dose RT to prostate vs whole pelvis. Dose, fractionation and nodal target volume not reported in source.
Primary: clinical PFS. Secondary: PSA response at 3 mo, bPFS, MFS, PCSS, OS, tolerance, QoL, biopsy biomarkers.
cPFS 7yr 67.1% pelvic vs 62.9% prostate-only, HR 0.81 (0.63-1.03), p=0.088, primary endpoint not met. No benefit on MFS, PCSS or OS per authors.
Authors report side effects minimal with modern RT technique; per-arm toxicity rates not reported in source.
POP-RT (2021) found whole-pelvic RT improved biochemical control in PSMA-staged high-risk N0. PEACE 2's conventionally-staged cohort shows no benefit.
Conference presentation, not peer-reviewed. Non-PSMA staging risks occult nodal misclassification. cPFS is a surrogate; RT dose/technique unspecified in source.
Randomized phase 3, prespecified cPFS not met (p=0.088); null across all clinical endpoints diverges from POP-RT's whole-pelvic benefit, so the WPRT question is contested.
In cN0 very-high-risk localized prostate staged by conventional imaging or choline PET, this questions routine elective whole-pelvic RT; it does not address PSMA-staged N0 or radiologic node-positive disease.
- Whether PSMA-staged N0 pts benefit from elective pelvic RT
- Cabazitaxel's effect and interaction with pelvic RT active A Phase III of Cabazitaxel and Pelvic Radiotherapy in Localized Prostate Cancer and High-risk Features of Relapse Phase 3n=761 · primary completion 2025-12 · phase 3 cabazitaxel + pelvic RT, high-risk localized
- A nodal-risk subgroup that still benefits from pelvic RT recruiting Abi/Pred + ADT vs ADT in PSMA-Positive, Conventionally Node-Negative Prostate Cancer Phase 2n=140 · primary completion 2033-04 · PSMA-avid occult nodes; RT + abiraterone ADT
📚 Sources · 🐦 1 tweet
Yesterday, I presented the @GETUG_Unicancer PEACE 2 trial at #ESTRO26 on the role of pelvic RT in very high risk #prostatecancer pts (staged with conventional imaging).
— Pierre Blanchard, MD (@PBlanchardMD) May 18, 2026
Twittorial below
Key conclusion: pelvic RT did not improve clinical outcomes (cPFS, MFS, PCSS, OS)...
1/n pic.twitter.com/ZKRt2QZzt1
TORPEdO
ForOropharyngeal SCC requiring bilateral-neck concurrent chemoradiotherapy
No between-arm difference
No effect size reported in source; assessed at 3/12/24mo post-RT
TL;DRUW-QoL physical composite similar IMPT vs IMRT at 3/12/24mo in OPSCC; no proton QoL-toxicity benefit (no effect size reported in source).
The proton premise, less QoL toxicity, didn't show: UW-QoL physical composite tracked identically IMPT vs IMRT from 6 weeks through 24 months, both arms at 70/56 Gy in 33fx. That undercuts routing OPSCC pts to protons for QoL benefit, though identical planning constraints and novel UK proton centres may have capped IMPT's achievable dosimetric edge.
+1 more figure
9 details 2 trials watching
Phase 3 multicentre RCT (CRUK/18/010), N=205 oropharyngeal SCC, 2:1 IMPT:IMRT, stratified by T-stage, N-stage, p16 status, and smoking history.
Oropharyngeal SCC requiring concurrent chemoradiotherapy with bilateral neck treatment. p16 status was a stratification factor, so both HPV-associated and HPV-independent disease are included.
70 Gy / 56 Gy in 33 fractions over 6.5 weeks, identical for both arms; IMPT vs IMRT is the only difference. Identical planning constraints applied across modalities.
Concurrent cisplatin 100 mg/m² on D1 and D22.
Co-primary PRO: UW-QoL physical composite at 12mo (saliva, taste, chewing, swallowing, appearance, speech). Co-primary clinician: CTCAE grade 3 weight loss (≥20% from baseline) or gastrostomy dependence at 12mo.
No between-arm difference in UW-QoL physical composite at 3/12/24mo, similar from 6 weeks post-CRT, with similar trajectories across multiple PRO questionnaires. No effect size reported in source.
Support for protons in OPSCC has rested on dosimetric and single-institution toxicity data; this randomised HR-QoL readout does not confirm a patient-reported advantage for IMPT.
Only the HR-QoL co-primary is presented; the clinician co-primary (weight loss/gastrostomy) and 5yr late-effects follow-up are unreported. No effect sizes or CIs given. Novel UK proton centres and identical constraints may cap IMPT's achievable edge.
Randomised co-primary QoL null (IMPT≈IMRT), consistent with IMRT-based CRT remaining standard. Only HR-QoL co-primary shown; clinician co-primary and 5yr late effects still maturing.
In oropharyngeal SCC planned for definitive cisplatin chemoradiotherapy, these HR-QoL data give no patient-reported reason to prefer IMPT over IMRT; they don't address the clinician co-primary (weight loss/gastrostomy) or unilateral-neck cases that could still differ.
- Does IMPT reduce 5-year late effects vs IMRT? recruiting Comparing an Investigational Scan (F-18 NaF PET/CT) to Standard of Care Imaging (F-18 FDG PET/CT) for Evaluating Vascular Complications in Patients Receiving Radiation Therapy for Head and Neck Cancer Phase Early 1n=20 · primary completion 2026-08 · candidate match
- Clinician co-primary (weight loss/gastrostomy at 12mo) result?
- Does IMPT advantage emerge only at high-experience proton centres? n=7 · primary completion 2024-11 · candidate match
📚 Sources · 🐦 2 tweets
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
NRG/RTOG 1005 NCT01349322
ForHigh-risk early breast cancer post-lumpectomy, receiving WBI plus cavity boost
HR 1.31
90% CI 0.84-2.04, P=.037; NI margin 2.12
TL;DR7-yr IBR 2.6% vs 2.2%, HR 1.31 (90% CI 0.84-2.04): concurrent boost noninferior to sequential, cutting WBI+boost to 15 fractions.
The transferable parameter is the boost itself: 8 Gy in 15F at 0.53 Gy per day, a lower cavity total than 12 Gy/6F sequential, with 7-yr IBR 2.6% vs 2.2%. Blinded photo cosmesis at 3y numerically favored concurrent (72.0% vs 64.2%, p=0.11). This moves boost technique, not whether to boost.
9 details 4 trials watching
Randomized, unblinded, phase 3 noninferiority trial across 278 sites in North America and 6 other countries. 2,354 randomized May 2011 to June 2014, 2,255 eligible for analysis. Median follow-up 7.3 years.
Higher risk of IBR after lumpectomy and axillary surgery. Median age 55 (IQR 47-64), 35.6% under 50; 96.8% invasive, 52.7% grade 3, 29.6% ER-negative, 16.3% node-positive, 16.7% LVI, 16.7% close (<2 mm) or focally positive margins. 61.8% received chemotherapy.
Concurrent arm: WBI 40 Gy/15F with concurrent boost 8 Gy/15F at 0.53 Gy per day. Sequential arm: WBI 50 Gy/25F (52.4%) or 42.7 Gy/16F (47.6%), then 12 Gy/6F (84.9%) or 14 Gy/7F. 3DCRT in 59%, photons in 73.8%; QART scored 92.8% of contours and 91.9% of dose plans per protocol or acceptable variation.
Primary: IBR as first recurrence, noninferiority defined as an HR upper 90% CI limit below 2.12. Secondary: DFS, OS, adverse events, and cosmesis (BCTOS, physician Global Cosmesis Score, blinded central digital photo review).
56 IBR events, 24 sequential and 32 concurrent. Noninferiority held on cause-specific hazards, Fine-Gray (HR 1.31, 90% CI 0.84-2.03), and against each sequential WBI fractionation separately; the triggered superiority test was not significant. 7-yr regional nodal recurrence 1.2% (95% CI 0.8-1.7) with no difference by arm, and no differences in DFS, DDFS, or OS.
| Endpoint | Sequential (n=1,118) | Concurrent (n=1,137) |
|---|---|---|
| 5-yr IBR | 2.1% | 1.9% |
| 7-yr IBR | 2.2% (90% CI 1.5-3.0) | 2.6% (90% CI 1.9-3.5) |
| IBR HR (90% CI) | reference | 1.31 (0.84-2.04), P=.037 |
Toxicity above grade 2 was uncommon, with no significant difference in grade 3-4 events (p=0.81); radiation dermatitis, fatigue, and breast pain were most prevalent. 3-yr excellent/good cosmesis by physician rating 85.9% vs 82.4% (p=0.34) and by central photo review 64.2% vs 72.0% (p=0.11).
IMPORT HIGH tested a simultaneous integrated boost in 15 fractions against a sequential boost in the same setting; its effect sizes are not in this source. This is the larger North American test of the same question, enriched for grade 3 and node-positive disease.
Unblinded. The noninferiority margin (HR 2.12) was set under a protocol redesign against an assumed 1.59% 5-yr IBR, and the point estimate favored sequential (HR 1.31) on 56 total events. Cosmesis response rates fell to 50.5% (physician) and 47.1% (central photo) by 3 years.
Randomized phase 3, prespecified noninferiority met at 7.3-yr median follow-up; wide NI margin (HR 2.12) and a point estimate favoring sequential keep it below practice-changing.
In high-risk early breast cancer after lumpectomy (grade 3, ER-negative, node-positive, or close margins) this supports a 15-fraction concurrent boost in place of a sequential boost; it does not address boost omission, partial breast irradiation, or post-mastectomy RT.
- Durability of the concurrent boost beyond 7 years recruiting 5 fr Ultrahypofractionated WBI and SIB for Breast Cancer With Unfavorable Characteristics Phase NAn=458 · primary completion 2029-06 · randomised 5fr WBI+SIB vs 15fr WBI+SIB noninferiority
- Whether a concurrent boost transfers to regional nodal irradiation active Hypofractionated Loco-regional Adjuvant Radiation Therapy of Breast Cancer Combined With a Simultaneous Integrated Boost Phase NAn=2963 · primary completion 2021-07 · loco-regional hypofx with SIB, late morbidity 1° EPrecruiting Ultra-Hypofractionated vs Moderate Hypofractionated Radiotherapy for Regional Lymph Nodes in High Risk Breast Cancer Phase NAn=1950 · primary completion 2034-03 · randomised ultrahypofx vs moderate hypofx RNI, n=1950
- Boost omission versus concurrent boost in high-risk pts n=400 · primary completion 2025-11 · WBI +/- tumor bed boost in HER2+, 7y IBTR endpoint
📚 Sources · 📄 1 paper
Abstract
PRIME NCT03561961
ForHigh-risk, very high-risk and/or node-positive non-metastatic prostate, 2y ADT
Not yet mature
Interim: no signal of inferiority for SBRT arm; 4-5y data awaited
TL;DRInterim data: 36.25 Gy/5 fx SBRT with whole-pelvis RT and 2y ADT shows no inferiority signal vs 68 Gy/25 fx; BFFS immature.
The transferable point is the pelvic dose: 25 Gy / 5 fx elective nodal with SIB permitted to involved nodes, grade 3+ under 1%, which is the constraint question that has kept 5-fraction prescribing confined to node-negative prostate-only. HYPO-RT-PC never tested nodes or ADT, so this extends the ultrahypofractionation toxicity envelope, not its efficacy.
| Toxicity (Grade ≥2) | SBRT (5 fx) | Moderate Hypo (25 fx) | p |
|---|---|---|---|
| Acute GU | ~5.4% | ~4.0% | 0.59 |
| Acute GI | ~2.2% | ~3.7% | 0.20 |
| Late GU | ~10-12% | ~9-11% | NS |
| Late GI | ~5-7% | ~4-6% | NS |
| Grade 3+ GU/GI | <1% | <1% | n/a |
+1 more figure
| HYPO-RT-PC | PRIME | |
|---|---|---|
| Experimental arm | 42.7 Gy / 7 fx | 36.25 Gy / 5 fx |
| Control arm | 78 Gy / 39 fx | ~68 Gy / 25 fx |
| Accrual | 2010 - 2015 | 2018 - 2023 |
| Primary endpoint result | 10y FFS 72% vs 65%, HR 0.84 (0.69-1.03) | Not yet mature |
10 details 5 trials watching
Phase III, open-label, randomized non-inferiority trial, Tata Memorial Centre and collaborating Indian centers. Accrual 2018-2023, completed at N~434, randomized 1:1 stratified by risk group and nodal status. Median follow-up is interim, 1-2 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 permitted, which matters for how the node-positive stratum was defined relative to older conventionally-staged trials.
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 prostate plus whole-pelvis elective nodal RT at 25 Gy / 5 fx (or equivalent), with SIB to positive nodes allowed in the SBRT arm. Delivered in the modern IMRT/VMAT with daily IGRT era.
Long-course ADT, ~2 years, in both arms. ADT is not a randomized variable here, so the trial isolates fractionation, not the systemic question.
Primary: biochemical failure-free survival (Phoenix, nadir + 2 ng/mL). Secondary: acute and late toxicity (RTOG/CTCAE v4.0/5.0), OS, MFS, clinical failure-free survival, QoL (QLQ-C30, QLQ-PR25, IPSS), cost-effectiveness.
Interim only. Source reports no signal of inferiority for the SBRT arm on BFFS and no difference in MFS or OS in early follow-up; no HR, CI, or non-inferiority margin is reported in source. OS data explicitly immature.
No significant difference in grade ≥2 toxicity between arms: acute GU ~5.4% vs ~4.0% (p=0.59), acute GI ~2.2% vs ~3.7% (p=0.20); late grade ≥2 GU ~10-12% vs ~9-11% and GI ~5-7% vs ~4-6%, both NS. Grade 3+ under 1% in both arms, acute and late. Urinary and bowel QoL domains stable and comparable.
HYPO-RT-PC established ultrahypofractionation non-inferiority (10y FFS 72% vs 65%, adjusted HR 0.84, 95% CI 0.69-1.03) but in node-negative disease, prostate plus proximal seminal vesicles only, no pelvic RT, no ADT, mostly 3D-CRT. PRIME is testing a different question: 5 fractions with elective nodal coverage on top of 2y ADT.
Interim analysis at 1-2 years against a BFFS primary read under 2 years of ADT, where testosterone suppression flattens both curves and early concordance is close to uninformative. Toxicity is reported as approximate ranges rather than point estimates with CIs. Open-label, though toxicity grading and PSA endpoints are only modestly susceptible to that.
Interim analysis at 1-2y of a BFFS primary that needs 4-5y maturity; safety-only read. Interim data cannot promote past early-signal regardless of clean design.
In high-risk or node-positive non-metastatic prostate going to whole-pelvis RT with long-course ADT, this supports 5-fraction SBRT as tolerable but not yet as an efficacy-equivalent substitute; it says nothing about omitting ADT or treating without pelvic coverage.
- Mature 4-5y BFFS and non-inferiority margin recruiting Androgen Suppression Combined With Nodal Irradiation and Dose Escalated Prostate Treatment Phase 3n=710 · primary completion 2032-10 · ph3 nodal RT + prostate SBRT vs EBRT/brachy boost
- Late GU toxicity beyond 2y with nodal SIB active Hypofractionated Whole-Pelvis Radiotherapy (WPRT) vs Conventionally-Fractionated WPRT in Prostate Cancer Phase 2n=58 · primary completion 2024-03 · 5fx vs 25fx whole-pelvis RT, QoL primaryrecruiting Phase III Adaptive Adaptive Stereostactic Body Radiotherapy (SBRT) With Dose Escalation for High-Risk Prostate Cancer Phase NAn=390 · primary completion 2033-04 · adaptive SBRT with WPRT plus DIL boost, 5y outcomes
- Whether pelvic nodal RT itself adds benefit in this population n=224 · primary completion 2017-08 · whole-pelvis vs prostate-only RT, high risk, 5y EPrecruiting A Trial of 5 Fraction Prostate SBRT Versus 5 Fraction Prostate and Pelvic Nodal SBRT Phase 3n=1128 · primary completion 2028-06 · randomises 5fx prostate vs prostate+pelvic nodal SBRT
📚 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;DRLate 2yr G2+ bowel 8.2% / 8.7% / 6.5% and bladder 19.5% / 24.1% / 16.5% across prostate, +boost, +pelvic nodes arms.
The late bladder G2+ signal sits with the boost, not the nodes: 24.1% in P+B vs 19.5% prostate-only and 16.5% in PPN+B, so adding elective nodal volume did not track with worse 2yr bladder or bowel toxicity. That makes the 20-fraction focal boost plus pelvic node volume a tolerable technique choice while the biochemical/clinical failure endpoint matures.
| Arm (n) | 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) |
+2 more figures
| Arm | Received |
|---|---|
| Prostate IMRT | 388 |
| Prostate IMRT + Boost (P+B) | 464 |
| Prostate + Pelvic IMRT + Boost (PPN+B) | 462 |
8 details 5 trials watching
Phase 3 RCT, N=1465 randomised across 39 UK centres. Primary endpoint: biochemical/clinical failure; the side-effect endpoints presented here are secondary.
Localised prostate cancer; the trial rationale states high-risk localised pts are most likely to benefit from pelvic node RT. Full eligibility criteria not reported in source.
20-fraction moderately hypofractionated IMRT. Arms as received: prostate alone (388), prostate + focal prostate boost (464), prostate + pelvic nodes + boost (462). Boost dose and nodal dose not reported in source.
Reported here: early bowel and bladder side effects (<18 weeks) and late (2-year, 6-24 month) G2+ events. Cancer-outcome follow-up is ongoing.
Nodal RT increased early bowel side effects, which resolved by 18 weeks post-RT. At 2 years G2+ bowel and bladder rates were similar across arms, with the numerically highest late bladder rate in the boost-without-nodes arm.
Late analysis covers only the 973 (74%) with ≥2yr follow-up, and no between-arm p-values are reported in source. The efficacy primary endpoint is unreported, so the toxicity read cannot yet be set against a benefit.
Randomised phase 3, prespecified secondary toxicity endpoint, 2yr follow-up. Efficacy 1° EP not yet reported, so it supports safety only, not a practice change.
In high-risk localised prostate pts being planned for 20-fraction IMRT, this supports the safety of adding a focal intraprostatic boost and elective pelvic nodal coverage; it does not yet speak to whether either improves biochemical or clinical control.
- Does focal boost or pelvic nodal RT improve biochemical/clinical failure 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 prostate-only vs prostate + pelvic nodal SBRTn=250 · primary completion 2031-05 · PSMA-N0M0 high risk, PORT vs whole pelvis RTrecruiting Addition of Focal Boost to Primary Radiotherapy for Prostate Cancer in 12 or 20 Fractions Phase NAn=1016 · primary completion 2040-10 · tests if intraprostatic boost improves cure rates
- Do late toxicity differences emerge beyond 2 years n=700 · primary completion 2021-12 · longitudinal GI/GU toxicity after whole-pelvis IMRTn=68 · primary completion 2025-10 · 5y accumulated GI/GU toxicity, integrated index boost
- Boost and nodal dose/fractionation details for reproducibility
📚 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), planned 12-36mo…
28% vs 21%
PPN-SBRT vs P-SBRT; no difference at 12wk, symptoms resolved quickly
TL;DRGrade ≥2 GI toxicity 28% vs 21% with added pelvic nodal SBRT over 12wk; GU unchanged, symptoms resolved by 12wk.
The deliverability number is the buried read: 11% of PPN-SBRT pts never received the allocated treatment vs 4% prostate-only, mostly unmet constraints. Nodal dose was 25Gy/5f alongside 36.25Gy/5f prostate on alternate days. That gates whether 5f elective nodal coverage is exportable outside high-volume centres, before any efficacy signal arrives.
| Endpoint | PPN-SBRT | P-SBRT |
|---|---|---|
| CTCAE grade ≥2 GI to 12wk | 28% | 21% |
| Did not receive allocation | 11% | 4% |
+2 more figures
7 details 5 trials watching
Phase 3 randomised, 1:1, multicentre. 1166 pts randomised against a target of 1128. This report is the prespecified acute toxicity analysis; the trial's primary endpoint, time to biochemical or clinical failure, is not yet mature.
High-risk localised prostate cancer: T3a-T4 and/or Gleason 8-10 and/or PSA >20 ng/ml. All planned for 12-36 months ADT.
Both arms 36.25Gy in 5f to prostate on alternate days. PPN-SBRT adds 25Gy in 5f to pelvic nodes. 11% of PPN-SBRT vs 4% of P-SBRT did not receive allocation, mostly because dose constraints were not met.
Co-primary for this analysis: CTCAE grade ≥2 GI and GU toxicity to 12 weeks. Patient-reported EPIC-26 domain scores collected at 4 weeks.
Grade ≥2 GI symptoms were more frequent with PPN-SBRT (28% vs 21%) across the 12-week window, with no difference at 12 weeks. No difference in acute GU toxicity by clinician or patient report. EPIC-26 bowel domain at 4 weeks mirrored the clinician-scored GI gap.
Acute window only, capped at 12 weeks; late GI/GU effects and cancer control are still accruing. Toxicity scoring is unblinded, which matters most for clinician-graded GI events. Effect sizes for the GI difference (CI, p) were not reported in source.
Randomised, but this is an acute-toxicity readout only; the primary biochemical/clinical failure endpoint is explicitly immature. Safety supports feasibility, not adoption.
In high-risk localised prostate on long-course ADT, this supports 5f nodal SBRT as tolerable in the acute window; it does not yet inform whether to cover nodes, since the biochemical/clinical failure endpoint is immature.
- Late GI/GU toxicity beyond 12 weeks n=68 · primary completion 2025-10 · 5y cumulative GI/GU toxicity after prostate SBRTn=500 · primary completion 2027-12 · 1° EP is late GI toxicity after prostate SBRT
- Biochemical and clinical failure benefit from nodal coverage 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 prostate vs prostate+pelvic nodal SBRT, n=1128recruiting 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 · PSA-adapted sequential pelvic nodal RT in salvage fossarecruiting PRO-BOOST-N: Prostate-First Versus Combined Prostate and Nodal Dose Escalation in PSMA PET-Staged Node-Positive Prostate Cancer Phase 2/3n=1600 · primary completion 2033-12 · randomises nodal dose escalation in cN1M0 PSMA-staged
- Whether unmet nodal dose constraints limit delivery outside trial centres
📚 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 N0M0 prostate ca (≥2 of GS≥8, T3-T4, PSA≥20)
67.1% vs 62.9% at 7yr
HR 0.81, 95% CI 0.63-1.03, p=0.088; primary endpoint not met
TL;DR7yr cPFS 67.1% pelvic vs 62.9% prostate-only RT, HR 0.81 (0.63-1.03), p=0.088: primary endpoint not met.
The elective pelvic nodal decision in very high-risk N0 disease loses its randomized support: 4.2 absolute points of 7yr cPFS, HR 0.81, CI crossing 1. Staging was conventional or choline PET, so pts PSMA PET would now upstage sat in both arms, diluting any true nodal benefit. Toxicity by arm not reported in source.
Also covered May 18
| 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
7 details 5 trials watching
International multicenter randomized trial with four arms crossing RT volume (prostate vs pelvis) with cabazitaxel ×4 cycles, all on ADT ×3 years. Readout presented at ESTRO 2026 with 7-year outcomes and follow-up extending to 120 months.
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.
The randomized comparison is target volume: prostate-only versus pelvic irradiation. Dose, fractionation, and nodal CTV definition are not reported in the source.
Primary: cPFS. Secondary: PSA response at 3 months, bPFS, metastasis-free survival, CaP-specific survival, OS, acute and long-term tolerance, QoL, and biopsy biomarkers.
Pelvic RT did not significantly improve cPFS on multivariable analysis. Secondary endpoints including MFS, CaP-specific survival, and OS are not reported in the source.
Effect estimate is from multivariable analysis; the 2×2 cabazitaxel randomization complicates attribution of the RT-volume effect. RT-attributable GU/GI toxicity by arm is not reported in source, which is the other half of the elective-nodal decision.
The investigators' own conclusion pivots from the RT question to the definition of "very high-risk": with <1 in 10 men dying of prostate cancer in the first decade, the population may be over-labeled. They call for biomarkers to guide intensification or de-intensification rather than uniform volume escalation.
Randomised, prespecified primary cPFS, mature 7yr readout, null result against a widely adopted practice. Design internally valid; the divergence is the headline.
In very high-risk localized N0M0 prostate cancer staged without PSMA PET, this questions routine whole-pelvis coverage over prostate-only RT with 3yr ADT; it does not speak to pts with PSMA-detected nodal disease, who were not enrolled.
- Does pelvic RT help when PSMA PET stages N0 more accurately? recruiting Extended vs. No Pelvic Lymph Node Dissection During Radical Prostatectomy. DISSECTION 2.0. Phase NAn=400 · primary completion 2027-02 · ePLND vs none in PSMA-PET node-negative high-riskn=250 · primary completion 2031-05 · randomises PORT vs whole-pelvis RT in PSMA-N0M0 pts
- RT-attributable late GU/GI toxicity by target volume n=700 · primary completion 2021-12 · longitudinal GU/GI/heme toxicity after WPRT, n=700n=400 · primary completion 2027-03 · late GI toxicity endpoint, whole-pelvis protons vs photons
- Biomarkers to select pts for treatment intensification vs de-intensification recruiting Treatment of High-Risk Prostate Cancer Guided by Novel Diagnostic Radio- and Molecular Tracers Phase 2/3n=493 · primary completion 2030-07 · tracer-guided darolutamide intensification + de-intens arm
📚 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
APBI-IMRT Florence NCT02104895
ForPost-BCS early breast cancer, pT <25mm, margins ≥5mm, age >40
7.7% vs 4.2% at 15yr
HR 1.57 (95% CI 0.82-3.04), p=0.17
TL;DR15yr IBTR 7.7% APBI vs 4.2% WBI, HR 1.57 (0.82-3.04) p=0.17; excess is new primaries, not true local relapse.
The 15yr excess sits in new ipsilateral primaries (5.9% vs 2.7%, p=0.09), not true local relapse (2.1% vs 1.6%). That splits the decision: 30Gy in 5# to the tumour bed holds the bed, but leaves untreated breast tissue at risk, which is a surveillance and endocrine-adherence question rather than an argument for whole-breast coverage.
| Endpoint (15-year) | APBI N (%) | WBI N (%) | P-value |
|---|---|---|---|
| Ipsilateral breast tumour recurrence | 20 (7.7) | 11 (4.2) | 0.14 |
| Local relapse | 5 (2.1) | 4 (1.6) | 0.75 |
| New ipsilateral breast cancer | 15 (5.9) | 7 (2.7) | 0.09 |
| Locoregional tumour recurrence | 20 (7.2) | 13 (5.0) | 0.28 |
| Contralateral breast tumour | 10 (3.8) | 13 (5.0) | 0.67 |
| Distant metastasis | 7 (2.7) | 12 (4.6) | 0.35 |
| Deaths | 56 (21.5) | 51 (19.6) | 0.66 |
+2 more figures
10 details 1 trial watching
Phase III equivalence trial, n=520, 1:1 randomisation, accrued 2005-2013, single institution. Powered on a 5-year estimated IBTR of 3% with a 5% equivalence margin and 80% power. Survival outcomes analysed ITT; toxicity and cosmesis per protocol after 14 withdrawals.
Post breast-conserving surgery, pT <25 mm, final surgical margins ≥5 mm, age >40 years. Nodal status and receptor subtype not specified in the source slides.
APBI arm: 30 Gy in 5 fractions IMRT to the partial breast. WBI arm: 50 Gy in 25 fractions plus a 10 Gy in 5 fraction tumour-bed boost. The comparator is a conventionally fractionated whole-breast course, not a modern hypofractionated 26 Gy/5 or 40 Gy/15 schedule.
IBTR HR 1.57 (95% CI 0.82-3.04), p=0.17 at 15 years. The gap widens across timepoints (5yr 2.3% vs 1.2%, 10yr 4.2% vs 2.7%, 15yr 7.7% vs 4.2%) but never reaches significance.
The only 5-fraction PBI dataset reporting to 15 years. IMPORT LOW and NSABP B-39 support PBI at shorter follow-up with different fractionation, so this trial carries the durability question for the ultrahypofractionated schedule specifically.
Powered for 5-year equivalence, so the 15-year read is descriptive rather than a met endpoint. Single institution. The local relapse vs new primary split that carries the interpretation is investigator-adjudicated, not molecularly confirmed.
Randomised phase III, prespecified 5yr equivalence endpoint, 15yr mature f/u, no significant divergence on any oncologic endpoint. Reinforces PBI as a listed option.
In the post-BCS pt over 40 with a pT <25mm tumour and ≥5mm margins, this supports 5-fraction PBI as a durable option out to 15 years; it does not extend to node-positive disease, close margins, or younger pts, and the untreated-breast new-primary rate is the tradeoff to counsel.
- Does the new-primary excess keep widening past 15 years
- Do modern hypofractionated WBI schedules change the comparison recruiting Ultra-hypofractionated for Whole Breast Irradiation (WBI) Compared to Partial Breast Irradiation (PBI) Phase 2n=100 · primary completion 2026-05 · randomised 26 Gy/5 fx WBI vs same-dose PBI
📚 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
DBCG RT Natural
For≥60yr, pT1N0 unifocal non-lobular ER≥10% HER2-normal grade 1-2, margin ≥2mm
1.5% vs 9.8%
+RT 2/236 (0.3-5.1%) vs -RT 19/272 (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; RT+ET arm had zero events.
The RT read is the 2x2: +RT+ET was 0/105 events while -RT-ET hit 12.2%, and +RT-ET (3.0%) tracked -RT+ET (3.7%). PBI at 40Gy/15fr can therefore substitute for endocrine therapy in a woman who will not take or tolerate ET, rather than only supplement it.
| 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%) |
+2 more figures
10 details 4 trials watching
Phase III randomised Danish (DBCG) trial of PBI vs no PBI after breast conservation, stratified by institution and ET yes/no, with a third self-selecting no-PBI cohort. Planned 926 randomised, interim at 200 pts with 2yr f/u; median follow-up 4 years at this first report.
≥60 years, unilateral unifocal pT1N0 breast cancer, non-lobular, ER≥10%, HER2 normal, grade 1-2, limited DCIS, margin ≥2mm, treated with breast conservation. ET given per DBCG guideline (recommended for pT1c and/or grade 2).
Partial breast irradiation, 40Gy in 15 fractions. No whole-breast or nodal arm, so the result speaks to PBI specifically, not to omission of comprehensive breast RT.
Primary: 5-year invasive local recurrence, assumed 2% with an accepted maximum of 4%. Secondary: loco-regional side effects and QoL, neither reported in source.
All 41 recurrences were invasive, 36 isolated, and 39 of 41 occurred in pts without PBI. Distant failure was rare (4 events, 2 per group). The no-RT arms crossed the prespecified 4% threshold.
PRIME II and CALGB 9343 licensed RT omission in older low-risk pts on the strength of low absolute LR with ET, but both assumed ET adherence. Here the -RT -ET group reached 12.2%, which is the population omission actually creates when ET is declined or stopped.
Median f/u 4 years for a 5-year endpoint, and the trial was stopped early by the DMC, both of which favour an inflated effect estimate. The self-selecting no-PBI cohort is not randomised, and the 2x2 treatment-received analysis is not the randomised comparison. Toxicity and QoL, the secondary endpoints that would price the cost of PBI, are not in source.
The discussant framed it as RT or ET giving similar local control in low-risk pts, with surgery alone carrying high LR even here. That reframes the omission question from "can we drop RT" to "which single adjuvant modality, and what happens when the pt takes neither".
Randomised, prespecified LR endpoint, stopped early for excess recurrence without PBI. Directly contests RT omission in the ≥60yr low-risk group PRIME II / CALGB 9343 licensed.
In a woman ≥60 with pT1N0 grade 1-2 ER+ HER2-normal disease after breast conservation, this questions omitting PBI on PRIME II grounds, particularly where ET adherence is doubtful; it does not speak to lobular histology, ER<10%, or node-positive disease.
- Does the 1.5% LR hold at the full 5-year endpoint
- PBI toxicity and QoL vs endocrine therapy in this group n=168 · primary completion 2030-07 · 30 vs 26 Gy/5 fx APBI, 1° breast-related QoL
- Whether 5-fraction PBI reproduces this local control recruiting Accelerated Partial Breast Irradiation (APBI) Using Stereotactic Body Radiation Therapy (SBRT)n=200 · primary completion 2024-08 · 30 Gy/5 fx APBI registry, 5y f/u, n=200n=134 · primary completion 2029-08 · single-fx vs 5-fx APBI, 1° local controln=910 · primary completion 2029-11 · phase 3 5-fx PBI vs WBI, 1° LR non-inferiority
📚 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
EORTC IM-MS (22922/10925)
ForStage I-III breast cancer, incl. pN0, considering IM + medial supraclavicular RT
61.0% vs 61.8%
HR=1.00; 95% CI 0.90-1.10, P=0.967 (ns)
TL;DR20yr OS 61.0% vs 61.8%, HR 1.00 (0.90-1.10), P=0.967: early 15yr survival signal gone, BCM benefit offset by non-BCM deaths.
The mortality split is the RT read: BCM 18.6% vs 22.4% (HR 0.82) bought at a non-BCM cost of 20.4% vs 15.8% (HR 1.26), with cardiac disease 15.2% vs 11.7%. Since DBCG IMN2 heart doses ran 4-9× lower, the target-volume decision hinges on achievable MHD, not on abandoning IM coverage.
| Endpoint | IM-MS RT | No IM-MS RT | HR (95% CI) | P |
|---|---|---|---|---|
| BCM | 18.6% | 22.4% | 0.82; 0.72-0.95 | 0.006 |
| non-BCM | 20.4% | 15.8% | 1.26; 1.09-1.46 | 0.002 |
+3 more figures
| 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 (95% CI) | P |
|---|---|---|---|---|
| DFS | 53.9% | 53.6% | 0.93; 0.81-1.07 | 0.318 |
| DMFS | 67.2% | 67.4% | 0.93; 0.78-1.10 | 0.397 |
8 details 5 trials watching
Randomised EORTC phase 3 (22922/10925), stage I-III breast cancer, ± internal mammary and medial supraclavicular irradiation. This is the 20-year ITT readout, presented as an ESTRO 2026 plenary, with a prespecified pN0 analysis.
The randomised question is target volume, not dose: adding IM-MS fields to standard breast/chest-wall treatment. Dose and fractionation are not reported in source. Mean heart dose is the operative technical variable, and the discussant contrasts it with DBCG IMN2 (MHD 1.2 Gy right-sided, 2.3 Gy left-sided, 4-9× lower than in this trial).
Primary: overall survival (ITT). Secondary reported here: DFS and DMFS (DATECAN definitions, so DFS includes all deaths and all breast events including DCIS and contralateral), breast-cancer mortality, non-breast-cancer mortality, second cancers, and late RT toxicity.
OS was flat at 20 years (HR=1.00, P=0.967), as were DFS 48.2% vs 49.0% (HR=0.97, P=0.515) and DMFS 58.9% vs 59.8% (HR=0.97, P=0.578). The signal sits in the competing-mortality split shown in the table above, not in any composite endpoint.
Cardiac disease 15.2% vs 11.7%, lung fibrosis 6.3% vs 3.2%, cardiac fibrosis 2.7% vs 1.7%. No statistical difference in second cancers or second breast cancers between arms, so the excess non-breast-cancer mortality tracks with cardiopulmonary late effects rather than second malignancy.
DBCG IMN2 (irradiation 2007-2014) reported reduced distant metastasis, reduced BCM and improved OS in node-positive pts at 15 years, with mean heart doses 4-9× lower than here. The two trials disagree on OS, and heart dose is the most plausible discriminator.
Toxicity and the competing-mortality penalty are technique-era dependent; RT dose, fractionation and delivery details are not reported in source. The pN0 analysis is a subgroup, though the null OS is the trial-level primary result.
The 15-year positive read did not hold to 20 years because non-breast-cancer deaths kept accruing. The clinical question shifts from whether IM-MS coverage works (it lowered BCM) to whether the heart dose it costs can be made small enough to let that benefit surface in OS.
Randomised, prespecified OS primary, 20y follow-up, now null after a positive 15y read. Divergence is internally valid; era-dependent heart dose is the caveat, not a design flaw.
In pN0 stage I-III breast cancer this does not support adding internal mammary and medial supraclavicular coverage (DFS HR 0.93, P=0.318); it does not settle the node-positive question, where modern low heart-dose technique still carries a 15-year benefit signal.
- Does IM-MS benefit survive at modern mean heart doses?
- Which node-positive subsets justify IM coverage? active Standard or Comprehensive Radiation Therapy in Treating Patients With Early-Stage Breast Cancer Previously Treated With Chemotherapy and Surgery Phase NAn=1636 · primary completion 2023-09 · randomised comprehensive nodal vs standard RT fieldsrecruiting RecurIndex Guided Avoidance of Regional Nodal Irradiation for Node Positive Breast Cancer Phase NAn=540 · primary completion 2029-08 · RecurIndex-gated RNI in clinically low-risk N1
- Do proton or DIBH techniques eliminate the non-BCM excess? recruiting Robustness Evaluation of Deep Inspiration Breath-Hold (DIBH) Plans in Internal Mammary Irradiationn=25 · primary completion 2026-12 · DIBH dose coverage + OAR params in IM irradiationn=220 · primary completion 2027-01 · proton locoregional RT, 10-15y cardiac mortality + SMNn=750 · primary completion 2027-12 · IMPT vs IMRT/VMAT, cardiac + lung toxicity endpoints
📚 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
IMPORT HIGH
ForInvasive early breast pT1-3 pN0-pN3a M0 post-BCS requiring tumour bed boost
3.5% vs 3.7% vs 5.5% at 10yr
95% CI 2.4-5.0 / 2.6-5.3 / 4.1-7.3
TL;DR10yr IBTR 3.5% vs 3.7% vs 5.5% across 40+16Gy, 48Gy SIB, 53Gy SIB; further escalation adds nothing.
The transferable parameter is 48Gy/15F in 3 weeks with the boost built in, no separate 8-fraction phase, holding IBTR at 3.7% at 10yr with moderate/marked distortion under 18%. The 53Gy arm settles the escalation question: 5.5% IBTR, worse not better, so the decision this moves is boost delivery (SIB vs sequential), not boost dose.
| Arm | 10-yr IBTR (95% CI) | Absolute OS 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) |
+2 more figures
| Arm | N | 5-yr IBTR (95% CI) |
|---|---|---|
| 40Gy/15F + 16Gy/8F | 871 | 1.9% (1.2, 3.1) |
| 48Gy/15F (3.2Gy/F) | 874 | 2.0% (1.2, 3.2) |
| 53Gy/15F (3.5Gy/F) | 872 | 3.2% (2.2, 4.7) |
9 details 4 trials watching
Phase 3 randomised 1:1:1, N=2617 across 76 UK hospitals, accrued 2009-2015. Annual clinical follow-up to 10 years; PROs and photographs collected only to 5 years.
Women ≥18 years after breast conserving surgery for invasive early breast cancer, pT1-3, pN0-pN3a, M0, all requiring tumour bed boost RT. Described by the investigators as a higher-than-average risk group.
Control was 40Gy/15F whole breast plus sequential 16Gy/8F boost. Both experimental arms used a simultaneous integrated boost in 15 fractions over 3 weeks, 48Gy (3.2Gy/F) or 53Gy (3.5Gy/F) to the tumour bed, with a modest dose reduction to whole breast distant from the tumour.
Primary: ipsilateral breast tumour relapse (IBTR), reported here at 10 years. Secondary reporting covers overall survival and clinician-assessed late normal tissue effects.
Moderate/marked AEs at 10 years were low across all randomised groups: breast distortion/shrinkage <18%, induration <10%, telangiectasia <2%, breast oedema <2%. No arm-specific late toxicity split is given in the source.
At 5 years (Coles, Lancet 2023) IBTR was 1.9% / 2.0% / 3.2%, and 48Gy was declared non-inferior in absolute terms. The 10-year data preserve that ordering, and both 40+16Gy and 48Gy stay below the 5% control estimate assumed in the original sample size calculation.
Source reports absolute rates only, no between-arm HRs or non-inferiority p-values at 10 years. PRO and photographic cosmesis stopped at 5 years, so 10-year toxicity is clinician-scored. Conference presentation, not yet a full peer-reviewed 10-year report.
The practical yield is logistic as much as oncologic: SIB collapses boost into the same 15 fractions, cutting visits without paying an IBTR or late-toxicity penalty. Further escalation to 53Gy does not help, which closes the dose-escalation arm of this question in a boost-indicated population.
Randomised 3-arm phase 3, prespecified 10-yr follow-up of a published primary; reaffirms 48Gy/15F SIB rather than changing it. No new comparator.
In pT1-3 pN0-pN3a post-BCS pts you would otherwise book for 40Gy/15F plus a sequential 16Gy boost, this supports a 15-fraction 48Gy SIB as an equivalent-control option; it does not speak to boost omission in low-risk pts, who were not the population studied.
- Does SIB benefit extend to post-mastectomy or nodal RT settings?
- Which boost-indicated subgroups could safely omit boost entirely? n=295 · primary completion 2029-11 · RT omission in low-risk DCIS, age >=50
- Five-fraction SIB as the next de-escalation step? recruiting Ultra-hypofractioNated Adjuvant Radiotherapy ± sImultaneous Integrated Boost for Low-risk Breast Cancer Patients Phase 2n=65 · primary completion 2025-10 · phase 2 ultrahypofx WBI +/- SIB, feasibilityn=50 · primary completion 2029-02 · ultra-short WBI with SIB, cosmesis + PROM endpointsrecruiting 5 fr Ultrahypofractionated WBI and SIB for Breast Cancer With Unfavorable Characteristics Phase NAn=458 · primary completion 2029-06 · randomised 26/30Gy 5fr SIB vs 40.05/48Gy 15fr 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
HypoG-01
ForBreast cancer receiving adjuvant RT + tumour-bed boost per HypoG-01 eligibility
TL;DR118 first events at 4.8y median f/u; LRR infrequent and mostly in-volume, patterns comparable between 40Gy/15fx and 50Gy/25fx.
The contouring read matters more than the fractionation read here: 20/30 recurrence sites fell in-volume and 19/30 nodal recurrences sat in L1-L2, so ESTRO CTV definitions covered where disease actually came back. That supports keeping current axillary level coverage rather than expanding target volumes when moving to 40 Gy/15 fx.
| Event type | n |
|---|---|
| Isolated LRR | 19 |
| Concomitant LRR | 1 |
| Isolated distant recurrence | 61 |
| Second malignancy | 37 |
| Total first events | 118 |
+1 more figure
9 details
Pre-planned secondary analysis (ITT) of the HypoG-01 phase III randomised trial. N=1,260, median follow-up 4.8 years.
Randomisation was 40 Gy/15 fractions over 3 weeks vs 50 Gy/25 fractions over 5 weeks, each with a tumour-bed boost. Target volumes followed ESTRO contouring guidelines.
First oncological event: locoregional recurrence (LRR), distant recurrence (DR), or second malignancy. LRR classified against the CTV as in-volume, marginal (outside CTV, ≥50% prescribed dose), or out-of-volume (<50%), with planned dose at the recurrence site re-estimated on the initial RT-plan CT.
118 first events. LRR was the lowest-frequency event type; distant recurrence (n=61) and second malignancy (n=37) dominated. 20/30 recurrence sites were in-volume (67%) and 19/30 nodal sites were mainly levels I and II.
Arm-level event counts are not reported in the source, so the "no obvious difference" claim between arms cannot be checked. With roughly 20 LRR events total, the analysis is descriptive and underpowered to exclude a modest fractionation effect on failure pattern.
The actionable signal is target-volume adequacy rather than fractionation: recurrences clustered inside the treated volume and in axillary levels I-II, which argues the ESTRO CTV is catching the right anatomy rather than that coverage needs widening. Out-of-volume failures would have been the argument for larger fields; they were the minority.
Pre-planned secondary analysis of a randomised phase III; supports moderate hypofractionation and ESTRO contouring. Event count (19 iLRR) too small for a powered arm comparison.
In breast pts eligible for adjuvant RT with a tumour-bed boost, this supports 40 Gy/15 fx with standard ESTRO-guided CTVs without widening nodal volumes; it does not address ultra-hypofractionation or pts whose recurrence risk sits outside the trial's eligibility.
- Do failure patterns hold with ultra-hypofractionation (5-fraction) schedules?
- Does boost technique alter in-volume vs marginal recurrence distribution?
📚 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
DBCG HYPO
ForNode-negative early breast cancer or DCIS after breast-conserving surgery
24.7% vs 19.5% at 10 yr
HR 0.76 (95% CI 0.62-0.92), p=0.005 favouring 40 Gy/15 fx
TL;DR10-yr grade 2-3 breast induration 19.5% with 40Gy/15fx vs 24.7% with 50Gy/25fx, HR 0.76, p=0.005; no recurrence or survival cost.
The induration difference is not just non-inferiority, it favours 40 Gy/15 fx (24.7% vs 19.5%, HR 0.76, p=0.005), so the shorter course is the lower-fibrosis option, not merely the more convenient one. Applies to node-negative and DCIS whole-breast fields; boost and nodal coverage are not addressed in source.
| Endpoint | 50 Gy/25 fx | 40 Gy/15 fx | Effect size |
|---|---|---|---|
| 10-yr grade 2-3 induration | 24.7% | 19.5% | HR 0.76 (95% CI 0.62-0.92), p=0.005 |
| 10-yr overall survival | 92.1% | 93.0% | HR 0.81 (95% CI 0.63-1.04), p=0.10 |
+1 more figure
9 details 5 trials watching
Phase III randomised non-inferiority trial, 1:1, run across Denmark, Norway and Germany with accrual 2009-2014. Median follow-up 12.8 years; these are the prespecified 10-year analyses.
1,882 women with node-negative breast cancer or DCIS. Allocation was 949 to 50 Gy and 933 to 40 Gy after exclusions; 936 and 917 women respectively carried forward in the flow diagram.
Whole-breast RT only: 50 Gy in 25 fractions vs 40 Gy in 15 fractions. No boost, nodal target volume, or technique detail (IMRT vs 3D, prone vs supine) is reported in the source.
Primary: grade ≥2 breast induration at 3 years, scored at two consecutive visits or at final follow-up. Morbidity assessed at years 0, 1, 2, 3, 4, 5 and 10; recurrence and survival were prespecified 10-year secondary analyses.
Induration is the toxicity endpoint here and it favours the hypofractionated arm. No other late-effect domain (cardiac, pneumonitis, cosmesis scoring, second malignancy) is reported in the source.
Consistent with START-B and the UK long-term hypofractionation experience, but adds prospectively scored induration out to 10 years in a trial that also enrolled DCIS.
Locoregional recurrence, distant failure and breast cancer mortality are reported only as not significantly different, with no event counts, HRs, or non-inferiority margin in the source. Induration scoring is clinician-assessed and not blinded to fractionation.
Prespecified 10-yr analysis of a randomised phase III with 12.8-yr median f/u; reinforces moderate hypofractionation already standard worldwide.
In node-negative invasive breast cancer or DCIS after lumpectomy, this supports 40 Gy/15 fx over 50 Gy/25 fx on long-term induration as well as convenience; it does not speak to node-positive pts needing regional nodal irradiation.
- Does the induration advantage hold with a tumour bed boost? active Hypofractionation With Simultaneous Integrated Boost vs. Standard Fractionation in Early Breast Cancer Phase NAn=2324 · primary completion 2019-01 · hypofx + SIB vs standard fractionation, n=2324n=132 · primary completion 2026-03 · 40 Gy/15 fx + SIB boost, 4y fibrosis 1° endpoint
- How does 40 Gy/15 fx compare with 26 Gy/5 fx at 10 years? n=2100 · primary completion 2029-03 · 1 wk vs 3 wk adjuvant RT, non-inferiority, n=2100recruiting 5 fr Ultrahypofractionated WBI and SIB for Breast Cancer With Unfavorable Characteristics Phase NAn=458 · primary completion 2029-06 · randomised 26 Gy/5 fx vs 40.05 Gy/15 fx, both SIBrecruiting 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 fx vs 40 Gy/15 fx nodal RT, f/u to 2034
📚 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