onc brain

About · curated by Nick Boehling, MD · @nb2276

    2026-05-18 ESTRO Congress 2026

    digest generated 2026-08-11

    HEAT interim: 5-fx SBRT non-inferior to 26-fx IMRT for biochemical failure (7% vs 7.4%, p-NI 0.007) at 4.25y, ADT allowed.
    TL;DR
    Prostate carried ESTRO on both fraction count and target volume: HEAT backs 36.25 Gy/5 fx against a modern 70.2 Gy/26 fx control, while PEACE 2 misses cPFS for elective pelvic RT (HR 0.81, p=0.088) and fails to reproduce POP-RT. Breast (RTOG 1005) and oligomets (EXTEND, PFS HR 0.54) extend the shortening-and-adding theme.

    GI Lower

    OPERA post-hoc moves the organ-preservation response assessment earlier to W14 without a randomised timepoint comparison.

    Early signal

    OPERA

    ForRectal cancer on watch-and-wait pathway after neoadjuvant therapy

    TL;DRW14 clinical response (DRE+rectoscopy) identified 76% good responders; 5yr organ preservation 75% A vs 83% B, p=0.24.

    Why it mattersRadiation oncology

    The transferable read is timing: response can be called at W14, one month after NAT ends, on DRE plus rectoscopy, with MRI TRG1-2 concordance of 98% (80/82). nCR at W14 preserved organs as well as cCR (77% vs 81%), so a near-complete response reflecting radiation effect does not by itself send a patient to TME.

    Monday clinic

    In rectal pts on a watch-and-wait pathway, this supports assessing response at W14 rather than deferring to W24 and reassessing nCR rather than treating it as failure; it does not address pts never eligible for organ preservation.

    The longer read
    OPERA
    EndpointArm AArm BOverall
    W14 good response (cCR+nCR)65%88%76%
    W14 partial responsen/an/a24%
    5yr organ preservation75%83%p=0.24
    CTRE performed at W14n/an/a122/141 (87%)
    +2 more figures
    OPERA
    OPERA
    10 details
    Design

    Post-hoc analysis of the randomised OPERA trial (two arms, A and B), reporting 5-year organ-preservation outcomes. The parent trial assessed response at week 24 with a three-modality triad (DRE, rectoscopy, MRI); this analysis asks whether the week 14 read is good enough.

    Endpoints

    Week-14 clinical tumor response evaluation (CTRE) by DRE and rectoscopy, categorised CR / nCR / PR, with cCR + nCR counted as a "good" clinical response. MRI graded by TRG. CTRE was correlated with relapse and 5-year organ-preservation rates.

    Radiotherapy

    Both arms received neoadjuvant therapy with organ preservation as the goal, and good responders at W14 either proceeded to organ preservation or were reassessed at W24. Dose, fractionation, and the content distinguishing Arm A from Arm B are not reported in source, which limits how far the arm difference transfers.

    Results

    CTRE was obtainable in 122/141 (87%) at W14. MRI confirmed TRG1-2 in 98% (80/82) of clinical CR pts, and 5-year organ preservation did not differ by arm (p=0.24) or by response depth (cCR 81% vs nCR 77%).

    Applies to
    rectal cancer pts treated with neoadjuvant therapy under an organ-preservation intent and assessed clinically after NAT
    Does not represent pts with obstructing or clinically progressive disease for whom watch-and-wait was never on the table.
    vs leading data

    Watch-and-wait practice has largely settled on later response assessment, with the OPRA framing of consolidation timing and the registry experience both anchoring the decision point well beyond three months. This analysis argues the clinical exam carries most of that information a month after NAT ends, which is earlier than the field currently commits.

    Limitations

    The 19 pts without CTRE at W14 (141 minus 122) are unaccounted for in source, and selective assessability would bias the 76% good-response figure upward. The arm difference (88% vs 65%, p=0.004) is uninterpretable here because the randomised contrast is not described.

    Discussion

    The clinically useful claim is that nCR is a radiation effect, not residual tumor, and the 5-year organ-preservation parity between cCR and nCR (81% vs 77%) is the evidence for it. What the source does not settle is regrowth: organ preservation at 5 years is a net figure that can absorb salvage, so equal preservation does not establish equal local control.

    Rationale

    Post-hoc timepoint analysis of 141 pts; W14 vs W24 assessment was never randomised, and no relapse or regrowth data reported in source.

    Open questions
    • Regrowth and salvage rates behind the 5yr organ preservation figures
    • What distinguished Arm A from Arm B
    • Outcomes of the 19 pts without W14 CTRE

    Sourced from @OncoAlert

    📚 Sources · 🐦 1 tweet

    Combined Curative Phase 3 RCT Early signal ESTRO Congress 2026

    Prostate

    Two randomised reads on RT geometry: fewer fractions holds, wider fields does not.

    Early signal

    HEAT NCT01794403

    ForLocalized low- to intermediate-risk prostate, IPSS <12, gland <80 cc

    Biochemical failure (Phoenix) surrogate

    7% vs 7.4%

    p-non-inferiority = 0.007 at 4.25y, margin 12%

    TL;DRInterim: BF 7% vs 7.4% at 4.25y, p-non-inferiority 0.007, 5-fx SBRT non-inferior to 26-fx IMRT with ADT allowed.

    Why it mattersRadiation oncology

    The design detail that transfers is the SIB: 36.25 Gy/5 fx with GTV boost to 40 Gy, against a 70.2 Gy/26 fx IMRT comparator rather than conventional fractionation, with ≤6 months ADT permitted in both arms. That combination is closer to what most departments now offer than HYPO-RT-PC or PACE-B, so it addresses whether 5 fractions holds up when the control arm is already moderately hypofractionated.

    Monday clinic

    In localized low- to intermediate-risk disease with IPSS <12 and gland under 80 cc, including men receiving short-course ADT, this supports 5-fraction SBRT as an option against moderate hypofractionation; it does not speak to high-risk disease or nodal coverage.

    The longer read
    Biochemical failure (Phoenix): 7% vs 7.4%, p-non-inferiority = 0.007 at 4.25y. n = 156 randomized, n = 142 analyzed. Median FU 59.7 months.
    Biochemical failure (Phoenix): 7% vs 7.4%, p-non-inferiority = 0.007 at 4.25y. n = 156 randomized, n = 142 analyzed. Median FU 59.7 months.
    +2 more figures
    HEAT
    ArmDoseFractionsDose per fraction
    AHRT36.25 Gy (+ GTV SIB to 40 Gy)57.25 Gy
    EHRT70.2 Gy262.7 Gy
    Non-inferiority margin = 12%. Primary endpoint biochemical failure (Phoenix definition).
    Non-inferiority margin = 12%. Primary endpoint biochemical failure (Phoenix definition).
    9 details 5 trials watching
    Design

    International phase III randomized non-inferiority trial, 1:1, comparing accelerated (AHRT) vs extended (EHRT) hypofractionation. Interim analysis presented; accrual goal n = 456 with 420 evaluable, and 142 analyzed so far. Median follow-up 59.7 months.

    Population & inclusion

    Localized low- to intermediate-risk prostate cancer with IPSS <12. Stratified by risk group, prostate volume (<60 cc vs 60-80 cc) and ADT administration. 82.4% intermediate-risk; 28% received ADT.

    Radiotherapy

    AHRT: 36.25 Gy in 5 fractions (7.25 Gy per fraction) with GTV SIB to 40 Gy. EHRT: 70.2 Gy in 26 fractions (2.7 Gy per fraction), IMRT in all patients. ADT permitted in both arms, ≤6 months.

    Endpoints

    Primary: biochemical failure, Phoenix definition, with a non-inferiority margin of 12%. Clinician-reported acute and late GI and GU toxicity reported alongside.

    Results

    BF 7% vs 7.4%, p-non-inferiority = 0.007 at 4.25y, meeting the non-inferiority criterion.

    Safety

    Acute G2+ GI toxicity lower with AHRT. No significant difference in late G2+ GI or in acute or late G2+ GU. Note that use of supportive medication (laxatives, psyllium) was scored as G2.

    vs leading data

    The presenters position HEAT against HYPO-RT-PC (limited IMRT use), PACE-B and NRG-GU005 (heterogeneous control arms), all of which allowed no ADT. HEAT is framed as the first trial comparing AHRT and EHRT 1:1 with modern technique plus ADT.

    Applies to
    localized low- to intermediate-risk prostate cancer with IPSS <12 and gland up to 80 cc, with or without ≤6 months ADT
    Does not represent high-risk disease, glands above 80 cc, obstructive baseline urinary symptoms, or any indication for nodal irradiation.
    Limitations

    Event counts are low (7% vs 7.4%) against a 12% margin, so the interval around the difference is wide relative to the difference being excluded. The comparator is itself hypofractionated, so this does not test 5 fractions against conventional fractionation.

    Discussion

    The question HEAT answers is narrower than 'does SBRT work': it asks whether 5 fractions holds when the control arm is already 26 fractions of IMRT and short ADT is on the table. A positive interim read supports 5 fractions as a default offer in this risk band, but the final prespecified analysis is what settles it.

    Rationale

    Interim analysis at 142 of a planned 420 evaluable; prespecified final primary analysis is the gate. Wide 12% margin relative to observed event rates.

    Open questions

    Sourced from @OncoAlert, @PBlanchardMD

    📚 Sources · 🐦 2 tweets

    Radiation Curative Phase 3 RCT Early signal ESTRO Congress 2026

    Head & Neck

    Two de-escalation questions: proton QoL gain (TORPEdO, null) and elective nodal omission (INRT-AIR/DARTBOARD, no solitary elective nodal failures but no randomised comparator).

    Confirmatory

    TORPEdO

    ForOropharyngeal SCC requiring concurrent chemo-RT with bilateral neck treatment

    UW-QoL physical composite at 12 mo (patient-reported co-primary) safety

    No difference vs IMRT

    Mean scores similar at 3/12/24 mo post RT; no effect size reported in source

    TL;DRNo mean UW-QoL physical composite difference IMPT vs IMRT at 3/12/24 mo post RT, 205 pts.

    Why it mattersRadiation oncology

    Both arms were prescribed the same 70 Gy / 56 Gy in 33 fractions under identical constraints, so this tests IMPT under photon-derived objectives, not its dosimetric ceiling. The physical composite (saliva, taste, chewing, swallowing) separates at no timepoint from week 6, weakening the QoL case for referring unselected bilateral-neck OPSCC pts to protons.

    Monday clinic

    In oropharyngeal SCC needing bilateral-neck chemoradiotherapy, patient-reported QoL alone does not support a proton referral; it does not speak to unilateral-neck, RT-alone, or reirradiation pts, where the sparing case differs.

    The longer read
    Change in UW-QoL physical composite from baseline. IMPT vs IMRT mean (90% CI).
    Change in UW-QoL physical composite from baseline. IMPT vs IMRT mean (90% CI).
    +1 more figure
    Phase 3, 2:1 randomisation, 205 patients recruited. 70 Gy / 56 Gy in 33 fractions over 6.5 weeks. Cisplatin 100mg/m2 D1 + D22.
    Phase 3, 2:1 randomisation, 205 patients recruited. 70 Gy / 56 Gy in 33 fractions over 6.5 weeks. Cisplatin 100mg/m2 D1 + D22.
    9 details
    Design

    Multicentre phase 3 RCT, 2:1 randomisation to IMPT vs IMRT, 205 pts recruited. Stratified by T-stage, N-stage, p16 status and smoking history. This ESTRO 2026 presentation reports the longitudinal HR-QoL analysis only.

    Population & inclusion

    Oropharyngeal SCC requiring concurrent chemo-radiotherapy including bilateral neck treatment. p16 status was a stratification factor, not an exclusion, so both HPV-driven and HPV-negative disease are represented.

    Radiotherapy

    70 Gy / 56 Gy in 33 fractions over 6.5 weeks in both arms, IMPT vs IMRT. Same dose, same schedule, same constraints, so delivery technique is the only variable.

    Regimen

    Concurrent cisplatin 100mg/m2 on D1 and D22, identical in both arms. The systemic backbone is fixed, so nothing here reads on regimen choice.

    Endpoints

    Co-primary (clinician): CTCAE grade 3 weight loss (≥20% decrease from baseline) or gastrostomy dependence at 12 months post RT. Co-primary (patient): UW-QoL physical composite of saliva, taste, chewing, swallowing, appearance and speech at 12 months post CRT.

    Results

    No difference in mean UW-QoL physical composite between arms at 3, 12 and 24 months post RT, with similar trajectories from week 6 post CRT and similar results across multiple PRO instruments. Scores fell at end of treatment then recovered, most stabilising from 12 months. No effect sizes given in source.

    vs leading data

    Non-randomised proton series in oropharynx have reported lower gastrostomy dependence and xerostomia than photon comparators, and that expectation is what this trial was built to test. The randomised patient-reported comparison does not reproduce a separation. No cross-trial numbers are in the source.

    Applies to
    oropharyngeal SCC needing concurrent chemoradiotherapy with bilateral neck coverage, treated in UK centres
    Does not represent unilateral-neck, RT-alone, postoperative or reirradiation patients, where the sparing argument for protons differs.
    Limitations

    A composite of six domains dilutes a benefit confined to one, xerostomia being the obvious candidate. 90% CIs and no stated non-inferiority margin mean this is an absence of difference, not demonstrated equivalence. The commentary point that UK proton centres are early on the learning curve is untestable from the source.

    Discussion

    The clean part of this design, matched dose and matched constraints, is also what bounds the answer: IMPT was planned to objectives written for photons, so the trial measures what protons deliver under photon rules rather than what they can achieve when pushed. It supports selecting patients by individual sparing benefit rather than referring bilateral-neck OPSCC to protons as a class.

    Rationale

    Randomised phase 3 PRO co-primary shows no arm difference, supporting IMRT as standard. Clinician-reported co-primary and effect sizes absent from source.

    Open questions
    • Clinician co-primary (weight loss / gastrostomy) result not yet reported
    • Whether proton-experienced centres would show a QoL difference
    • HR-QoL beyond 2 years; follow-up ongoing to 5 years

    Sourced from @OncoAlert, @AmadeoWals, McBride et al.

    📚 Sources · 🐦 2 tweets · 📄 1 paper
    📄 PAPER McBride; Riaz; Sherman et al. · Lancet (London, England) (2026-05)
    Proton versus photon therapy for oropharyngeal cancer.
    PMID 42134353 → doi
    📝 McBride SM, Riaz N, Sherman EJ, Tsai CJ, Mell LK. Proton versus photon therapy for oropharyngeal cancer. Lancet. 2026 May 16;407(10542):1917.

    Radiation Curative Phase 3 RCT Confirmatory ESTRO Congress 2026

    Early signal

    INRT-AIR & DARTBOARD pooled analysis

    ForHNSCC oropharynx/larynx/hypopharynx, stage I-IVB, excluding T1-2N0 larynx

    TL;DR5yr solitary elective nodal recurrence 0% with ENI omission in HNSCC; 5yr OS 87%, PFS 74%, n=117.

    Why it mattersRadiation oncology

    The number that matters is 0% solitary elective nodal recurrence at 5 yrs: elective volumes are where the parotid, constrictor and pharyngeal dose lives, and this is the first pooled long-term read that omitting them does not trade nodal control. MDADI 84.9 at 12 mo with no significant decline is the swallowing correlate. No dose or CTV detail in source, so the contouring approach cannot be replicated from this abstract.

    Monday clinic

    In stage I-IVB oropharynx, larynx or hypopharynx SCC being planned for definitive chemoRT, this supports enrolling on an INRT protocol rather than adopting nodal omission off-trial; it does not extend to T1-2N0 larynx, which was excluded.

    The longer read
    117 patients, median follow-up 3.4 years. 5-yr solitary elective nodal recurrence 0%. 3-yr local recurrence 9.5%, regional recurrence 4.3%, distant metastasis 11%. 5-yr OS 87%, PFS 74%. Mean composite MDADI 84.9 at 12 months.
    117 patients, median follow-up 3.4 years. 5-yr solitary elective nodal recurrence 0%. 3-yr local recurrence 9.5%, regional recurrence 4.3%, distant metastasis 11%. 5-yr OS 87%, PFS 74%. Mean composite MDADI 84.9 at 12 months.
    +1 more figure
    INRT-AIR & DARTBOARD pooled analysis
    11 details 2 trials watching
    Design

    Patient-level pooled analysis of 2 prospective trials, INRT-AIR and DARTBOARD, both testing involved nodal radiotherapy. N=117, median follow-up 3.4 years. No randomised comparator arm receiving standard elective nodal irradiation.

    Population & inclusion

    HNSCC of oropharynx, larynx, and hypopharynx, stage I-IVB, explicitly excluding T1-2N0 larynx. Completed PET/CT and neck CT were required for eligibility, which is also the imaging substrate the nodal-selection step depends on.

    Radiotherapy

    Definitive chemoradiotherapy with omission of elective nodal irradiation (ENI), treating involved nodes only (INRT). Suspicious node identification was assisted by an artificial-intelligence model reading the staging PET/CT and neck CT. Dose, fractionation and margin expansions are not reported in the source.

    Results

    5-yr solitary elective nodal recurrence 0%. 3-yr cumulative incidence: local 9.5%, regional 4.3%, distant 11%. 5-yr OS 87%, PFS 74%. Mean composite MDADI 84.9 at 12 months with no significant decline after treatment.

    Applies to
    stage I-IVB oropharynx, larynx and hypopharynx SCC staged with PET/CT and neck CT and treated with definitive chemoradiotherapy on a prospective INRT protocol
    Does not represent T1-2N0 larynx, oral cavity or nasopharynx primaries, the postoperative setting, or any patient contoured without the trials' AI-assisted nodal selection.
    Limitations

    Pooling two protocols with different designs into one patient-level cohort assumes their INRT definitions were interchangeable, which the source does not establish. Median follow-up of 3.4 years supports a 5-year estimate on a shrinking risk set, and HPV status, which drives OS in an oropharynx-weighted cohort, is not reported.

    Discussion

    The zero solitary elective nodal failures make the mechanistic case that undissected, PET-negative elective levels rarely harbour disease that only ENI would sterilise. What the pooled cohort cannot settle is whether the result survives outside two experienced centres using an AI-assisted nodal-selection step, which is precisely the component a general department would have to reproduce.

    Rationale

    Pooled single-arm prospective cohorts, n=117, no randomised comparator against standard elective nodal RT. Presenters state randomised evidence needed before non-trial use.

    Open questions

    Sourced from @OncoAlert

    📚 Sources · 🐦 1 tweet

    Radiation Curative Phase 2 trial Early signal ESTRO Congress 2026

    Breast

    Concurrent boost at 40 Gy/15F + 8 Gy SIB clears noninferiority for in-breast recurrence in a higher-risk cohort, shortening the course by weeks.

    Practice-changing

    NRG/RTOG 1005 NCT01349322

    ForHigh-risk early breast cancer post-lumpectomy + axillary surgery, boost indicated

    Ipsilateral breast recurrence as first recurrence local control

    HR 1.31

    90% CI 0.84-2.04, P=.037 (noninferiority met)

    TL;DR7yr IBR 2.6% concurrent vs 2.2% sequential, HR 1.31 (90% CI 0.84-2.04), noninferior, one shorter course.

    Why it mattersRadiation oncology

    The concurrent arm is 15 fractions total, 40 Gy/15F whole breast with an 8 Gy SIB at 0.53 Gy/day, versus 21-32 fractions sequentially. Cosmesis was noninferior on patient BCTOS, physician rating, and blinded photo review, so the usual objection to a simultaneous integrated boost in a high-risk, 16.7% close-margin population does not hold at 3 years.

    Monday clinic

    In a post-lumpectomy patient with grade 3, ER-negative, close-margin, or node-positive disease where you would add a boost, this supports a 15-fraction SIB course instead of sequential; it does not address partial-breast, regional nodal irradiation, or ultrahypofractionated 5-fraction boost.

    The longer read
    10 details 5 trials watching
    Design

    Randomized, unblinded phase 3 noninferiority trial run by NRG Oncology, 278 sites across North America and 6 other countries, accrual May 2011 to June 2014. 2,354 randomly assigned, 2,255 eligible (sequential 1,118, concurrent 1,137). Median follow-up 7.3 years.

    Population & inclusion

    Post-lumpectomy and axillary surgery, selected for higher risk of ipsilateral breast recurrence. Median age 55 (IQR 47-64), 35.6% under 50; 96.8% invasive, 52.7% grade 3, 29.6% ER-negative, 16.7% LVI, 16.7% close (<2 mm) or focally positive margins, 16.3% node-positive, 61.8% received chemotherapy.

    Radiotherapy

    Sequential arm: WBI 50 Gy/25F or 42.7 Gy/16F, then boost 12 Gy/6F (84.9%) or 14 Gy/7F. Concurrent arm: WBI 40 Gy/15F with an 8 Gy/15F integrated boost at 0.53 Gy per day. 3DCRT in 1,290 (59%), photons in 1,614 (73.8%). QART scored contours and plans per protocol or acceptable variation in 92.8% and 91.9%.

    Endpoints

    Primary: IBR as first recurrence, noninferiority margin an HR upper 90% CI limit of 2.12, powered at 80% off an assumed 1.59% 5-year sequential-arm IBR. Secondary: DFS, OS, adverse events, and cosmesis (patient BCTOS, physician global cosmetic score, blinded central digital photo review).

    Results

    56 IBR events, 24 sequential and 32 concurrent. Cause-specific hazards and Fine-Gray gave the same HR 1.31, and noninferiority held against each sequential WBI fractionation separately. The protocol-specified superiority test was not significant, and post-hoc analyses by stratification variable showed no treatment interactions.

    ArmWBIBoost
    Sequential50 Gy/25F (575, 52.4%) or 42.7 Gy/16F (523, 47.6%)12 Gy/6F (932, 84.9%) or 14 Gy/7F, after WBI
    Concurrent40 Gy/15F8 Gy/15F at 0.53 Gy/day, during WBI
    Safety

    Grade >2 treatment-related toxicity was uncommon with no difference in grade 3-4 events (p=0.81); radiation dermatitis, fatigue, and breast pain were the most prevalent events. Physician-rated excellent/good cosmesis at 3 years was 85.9% sequential vs 82.4% concurrent (p=0.34), photo review 64.2% vs 72.0% (p=0.11).

    Applies to
    high-risk early breast cancer after lumpectomy and axillary surgery in whom a cavity boost is indicated
    Does not represent patients treated with partial-breast irradiation, regional nodal irradiation as the question, or ultrahypofractionated whole-breast schedules.
    vs leading data

    The boost itself was established by EORTC 22881-10882, where 16 Gy sequential cut IBR but added treatment time and worsened fibrosis. IMPORT HIGH tested integrated boosts on a 40 Gy/15F backbone and found 48 Gy acceptable while its 53 Gy arm carried more induration. NRG 1005 answers the delivery question at scale rather than the dose question.

    Limitations

    Cosmetic assessment thinned badly over time: blinded photo review response fell from 79.7% at baseline to 47.1% at 3 years, and physician rating from 90.3% to 50.5%, so the cosmesis conclusions rest on roughly half the cohort with unblinded delivery. The QoL substudy also had imbalances, more stage II sequentially (39.7% vs 32.5%) and more IMRT concurrently (27.1% vs 18.5%).

    Discussion

    The point estimate favors sequential (HR 1.31) even as the confidence bound clears the margin, so this is a noninferiority conclusion in the honest sense, not equivalence. With 7-year IBR at 2.2% and 2.6%, the absolute difference is under a percentage point in a deliberately high-risk cohort, which is the frame in which trading 6 to 7 fractions is reasonable.

    Enrolment
    CONSORT flow
    Assessed / enrolled 2354
    ↓ 99 excluded
    Randomized 2354
    ↓
    Sequential boost
    allocated 1118
    7yr IBR 2.2%
    Concurrent boost
    allocated 1137
    7yr IBR 2.6%
    Rationale

    Adequately powered phase III, prespecified noninferiority margin met at 7.3yr median f/u, with cosmesis and toxicity co-endpoints also noninferior. Removes 6-7 fractions.

    Open questions

    Sourced from Vicini et al.

    📚 Sources · 📄 1 paper
    📄 PAPER Vicini; Winter; Freedman et al. · Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2026-05)
    Concurrent Versus Sequential Radiation Dose Escalation to the Surgical Cavity for Conservative Treatment of High-Risk Early Breast Cancer: NRG/RTOG 1005 Phase III Trial.
    PMID 42114027 → doi full text (PMC)
    Abstract
    PURPOSE: For patients with breast cancer undergoing breast conservation, escalating the dose (boost) of radiation to the lumpectomy cavity after whole-breast irradiation (WBI) reduces ipsilateral breast recurrence (IBR) but extends treatment duration. This phase III trial investigated whether boost delivery during WBI versus after WBI provides noninferior IBR and preserves cosmetic appearance.<br/><br/>METHODS: NRG/RTOG 1005 randomly assigned patients at higher risk for IBR after lumpectomy and axillary surgery to either a sequential boost of 12 Gy in six fractions(F) or 14 Gy in 7F after WBI of 50 Gy in 25F or 42.7 Gy in 16F (sequential arm) or a concurrent boost of 8 Gy in 15F of 0.53 Gy per day with WBI of 40 Gy in 15F (concurrent arm) using 3-dimensional conformal radiation therapy (RT) or intensity-modulated RT. Based on 1.59% 5-year IBR for the sequential arm, defining the noninferiority margin as a hazard ratio upper limit on the 90% CI of 2.12, 2,312 patients provide 80% power for noninferiority of IBR as first recurrence for the concurrent arm. Secondary end points included disease-free survival and overall survival, adverse events (AEs), and cosmetic outcomes.<br/><br/>RESULTS: Between May 24, 2011, and June 20, 2014, 2,354 patients were randomly assigned, with 2,255 eligible for analysis (sequential arm, n = 1,118; concurrent arm, n = 1,137). With median follow-up of 7.3 years, there were 56 IBR events; 5- and 7-year IBR were 2.1% and 2.2% on the sequential arm and 1.9% and 2.6% on the concurrent arm, respectively. The noninferiority criterion was met: HR (90% CI): 1.31 (0.84 to 2.04), P = .037. No differences were observed in AEs, cosmetic outcomes, or survival between arms.<br/><br/>CONCLUSION: Concurrent boost during WBI results in noninferior IBR compared with sequential boost without worsening toxicity or cosmetic outcomes and reduces overall treatment time.
    📝 Vicini FA, Winter K, Freedman GM, Arthur DW, Rosenstein BS, Bentzen SM, Li XA, Halyard MY, Woodward WA, Bleicher RJ, Taghian A, Lyons J, Tomberlin JK, Seaward SA, Cheston SB, Hoover AC, Anderson BM, Perera FE, Poppe MM, Petersen IA, Jhawar S, Hijal T, Moughan J, Movsas B, White JR. Concurrent Versus Sequential Radiation Dose Escalation to the Surgical Cavity for Conservative Treatment of High-Risk Early Breast Cancer: NRG/RTOG 1005 Phase III Trial. J Clin Oncol. 2026 May 11:JCO2502465. ; PMCID: PMC13166090.

    Radiation Curative Phase 3 RCT Practice-changing ESTRO Congress 2026

    Hepatobiliary

    A 4,913-patient IPD cohort assembled to contest EBRT's absence from BCLC-0/A.

    Challenges SOC

    Multinational HCC EBRT IPD Cohort

    ForVery early / early-stage HCC (BCLC-0 or A), incl. treatment-naive

    TL;DRMedian OS 6.8y BCLC-0 and 4.6y BCLC-A across 4,913 EBRT-treated HCC pts, comparable to resection and ablation.

    Why it mattersRadiation oncology

    The modifiable RT variable in the Cox model is ablative dose, which was associated with reduced mortality, so the transferable read is that dose, not simply delivering EBRT, tracks with the outcome. Fractionation and dose thresholds are not given in the abstract. This is the citation for putting EBRT on the BCLC-0/A allocation discussion.

    Monday clinic

    In BCLC-0 or A HCC where resection, transplant, or ablation is not feasible or is declined, this supports discussing ablative-dose EBRT as a locoregional option; it does not establish EBRT over resection or ablation in a pt eligible for either.

    The longer read
    9 details 2 trials watching
    Design

    Systematic review of EBRT publications meeting prespecified HCC technical standards (search date December 15, 2022), with corresponding authors invited to contribute individual patient data. Kaplan-Meier OS and RMST stratified by BCLC stage and treatment status; random-effects Cox for covariates. No comparator arm.

    Population & inclusion

    4,913 pts treated with EBRT, median follow-up 5.0 years, multinational. Analyses split by BCLC stage and by treatment-naive vs treatment-experienced; the headline read sits in BCLC-0 and BCLC-A.

    Radiotherapy

    EBRT delivered per each contributing series, gated by the prespecified technical standards rather than one protocol. Ablative dose was associated with a reduced risk of death; specific dose levels, fractionation, and modality mix are not given in the source abstract.

    Endpoints

    Overall survival by Kaplan-Meier and restricted mean survival time, stratified by BCLC stage and treatment status. Covariate associations from multivariable random-effects Cox modeling.

    Results

    Median OS 6.8 y (95% CI 5.7-8.7) for BCLC-0 and 4.6 y (95% CI 4.1-5.1) for BCLC-A. Treatment-naive: not reached (95% CI 8.6-NR) for BCLC-0, 5.4 y (95% CI 4.5-6.7) for BCLC-A.

    CohortBCLC-0BCLC-A
    All pts6.8 y (95% CI 5.7-8.7)4.6 y (95% CI 4.1-5.1)
    Treatment-naiveNR (95% CI 8.6-NR)5.4 y (95% CI 4.5-6.7)
    vs leading data

    The authors frame these medians as comparable with resection, thermal ablation, and other ablative locoregional therapies, a cross-study benchmark rather than a randomised comparison. EBRT's exclusion from BCLC has rested on the absence of OS evidence, which is the gap this cohort is built to fill.

    Applies to
    BCLC-0 and BCLC-A HCC treated with EBRT at centers publishing outcomes, including treatment-naive pts
    Does not represent pts randomised against resection or ablation, nor advanced-stage disease where the cohort's own model shows worse survival.
    Limitations

    IPD came only from authors who published and agreed to share, so contributing centers are self-selected and unmeasured selection at the patient level (who was routed to EBRT rather than resection) is unrecoverable. More recent year of treatment predicting survival mixes technique gains with stage migration and modern systemic salvage over a multi-decade accrual window.

    Discussion

    The claim is an allocation claim, not an efficacy claim: EBRT belongs in the BCLC decision tree as an option to be weighed. It does not settle sequencing against ablation in a pt eligible for both, and the ablative-dose signal makes the quality of the RT, not its mere availability, the operative variable.

    Rationale

    Largest EBRT IPD cohort argues for a BCLC allocation change, but it is pooled non-randomised data with no head-to-head comparator against resection or ablation.

    Open questions

    Sourced from Moon et al.

    📚 Sources · 📄 1 paper
    📄 PAPER Moon; Yanagihara; Dawson et al. · Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2026-05)
    Overall Survival Among Patients With Hepatocellular Carcinoma Treated With External Beam Radiation Therapy: Individual Patient Data Outcomes From a Multinational Cohort.
    PMID 42139645 → doi
    Abstract
    PURPOSE: External beam radiation therapy (EBRT) has gained delayed acceptance as a recommended first-line treatment modality for patients with hepatocellular carcinoma (HCC), given limited evidence that it improves overall survival (OS). We analyzed individual patient data (IPD) from an international cohort to assess OS among patients with HCC treated with EBRT.<br/><br/>METHODS: We performed a systematic review of publications that assessed EBRT, met prespecified technical standards for HCC, and reported OS (search date December 15, 2022). Corresponding authors were invited to submit IPD for the study. We performed Kaplan-Meier survival analyses to determine OS and restricted mean survival time (RMST) stratified by Barcelona Clinic Liver Cancer (BCLC) stage and treatment status (ie, treatment-na&#xef;ve and experienced). We performed random effects Cox proportional hazards modeling to assess clinical characteristics associated with OS.<br/><br/>RESULTS: Data were provided on 4,913 patients treated with EBRT with a median follow-up time of 5.0 years. The median OS was 6.8 years (95% CI, 5.7 to 8.7) for BCLC-0 and 4.6 years (95% CI, 4.1 to 5.1) for BCLC-A. Among treatment-na&#xef;ve patients, the median OS was not reached (95% CI, 8.6 to not reached) for BCLC-0 and was 5.4 years (95% CI, 4.5 to 6.7) for BCLC-A. In multivariable models, more advanced BCLC stage, higher tumor burden, worse performance status, and Child-Pugh class B or C were associated with a higher risk of mortality. Ablative radiation dose and more recent year of treatment were associated with a reduced risk of death.<br/><br/>CONCLUSION: To our knowledge, this study represents the largest multinational cohort of patients with HCC treated with EBRT. OS outcomes with EBRT for very early- and early-stage HCC appear to be comparable with resection, thermal ablation, and other ablative locoregional therapies. These data support the inclusion of EBRT in the BCLC HCC clinical decision-making process.
    📝 Moon AM, Yanagihara TK, Dawson LA, Yu JI, Lawrence TS, Kim TH, Yan M, Iwata H, Nabavizadeh N, Apisarnthanarax S, Dunne EM, Lock MI, Chuong MD, Chiang CL, Scorsetti M, Katoh N, Sioshansi S, Numata K, Liu HY, Iwamoto H, Wakatsuki M, Chen Y, Pollom EL, Gkika E, Jabbour SK, Munoz-Schuffenegger P, Dutta D, Hajj C, Ueno M, Hallemeier CL, Feldman AM, Méndèz Romero A, Tan X, Molla M, Tepper JE, Torres F, Reig M; EBRT Collaboration Group. Overall Survival Among Patients With Hepatocellular Carcinoma Treated With External Beam Radiation Therapy: Individual Patient Data Outcomes From a Multinational Cohort. J Clin Oncol. 2026 May 15:JCO2502399.

    Radiation Curative Meta-analysis Challenges SOC ESTRO Congress 2026

    Oligometastatic / Mets

    EXTEND is the largest randomised MDT dataset to date, with RT delivering 98% of the local therapy.

    Confirmatory

    EXTEND

    ForOligometastatic solid tumors, 1-5 metastases, on standard systemic therapy

    Progression-free survival surrogate

    HR 0.54

    95% CI 0.41-0.72, p<0.001

    TL;DRPFS HR 0.54 (0.41-0.72), p<0.001 for MDT added to SOC across 6 oligometastatic baskets; RT delivered 98% of MDT.

    Why it mattersRadiation oncology

    The prostate-excluded HR 0.60 (0.40-0.89) is the number that matters for an RT reader: the benefit survives removal of the two prostate baskets, where MDT is already routine. RT delivered 98% of MDT (370/379), so this is a radiotherapy result, though dose and fractionation are not reported in source.

    Monday clinic

    In a patient with 1-5 metastases from pancreas or a non-breast, non-kidney histology already on standard systemic therapy, this supports discussing MDT as an addition rather than a deferral; it does not resolve the breast or kidney question, where the baskets were inconclusive.

    The longer read
    13 details 5 trials watching
    Design

    Multicenter randomized phase II basket trial, 6 histology baskets with basket-specific stratification and powering. Accrual 2018 to 2023, median follow-up 53 months.

    Population & inclusion

    Patients with 1-5 metastases on standard-of-care systemic therapy, allocated to breast, pancreas, kidney, two prostate baskets, or an "Other" basket. 521 screened, 350 randomized, 334 analyzed per protocol (MDT+SOC n=166; SOC n=168).

    Radiotherapy

    Radiotherapy delivered 98% of MDT (370/379 metastases), so this is effectively a radiotherapy trial. Dose, fractionation, technique and target-volume definition are not reported in source.

    Endpoints

    Primary: PFS, pre-specified in the per-protocol set at three levels (within each basket, across all baskets, and across all baskets excluding the prostate baskets). Exploratory: ctDNA and immune profiling.

    Results

    All-basket PFS HR 0.54 (95% CI 0.41-0.72), p<0.001; excluding prostate, HR 0.60 (95% CI 0.40-0.89). Superiority in pancreas, prostate and "Other"; breast and kidney inconclusive. No per-basket effect sizes reported in source.

    vs leading data

    SABR-COMET randomized 99 patients across mixed histologies; STOMP and ORIOLE were prostate-only and smaller. EXTEND's contribution is scale plus histology resolution: it keeps a benefit when the prostate baskets are removed, which the prostate-only trials could not address.

    Applies to
    patients with 1-5 metastases from pancreas, prostate, or the heterogeneous "Other" histologies on standard systemic therapy
    Does not represent breast or kidney oligometastatic disease, where the baskets were inconclusive.
    Limitations

    The primary analysis is per-protocol rather than ITT, and an unblinded PFS endpoint in a trial that ablates the very lesions being measured favors the intervention arm. The "Other" basket is a mixed-histology pool, so its superiority signal is the hardest of the three to carry into a single phase III.

    Discussion

    The prostate-excluded HR 0.60 is the trial's most load-bearing number, since it shows the pooled result is not simply the prostate literature reasserting itself. The ctDNA correlations (detectable at enrollment with worse PFS and survival; clearance at 3 months with better survival) point at a biological rather than anatomic definition of oligometastasis, which is the more interesting question EXTEND raises without settling.

    Enrolment
    CONSORT flow
    Randomized 350
    ↓
    MDT+SOC
    allocated 166
    SOC
    allocated 168
    Rationale

    Randomized phase II, per-protocol primary, histology-specific signals explicitly framed as hypothesis-generating for phase III. Consistent with SABR-COMET / STOMP / ORIOLE direction.

    Open questions

    Sourced from Sherry et al.

    📚 Sources · 📄 1 paper
    📄 PAPER Sherry; Haymaker; Wang et al. · Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2026-05)
    Addition of Metastasis-Directed Therapy to Standard of Care for Oligometastatic Solid Tumors: Primary Analysis of All Tumor-Histology Baskets of the Phase II Randomized EXTEND Trial.
    PMID 42142259 → doi
    Abstract
    PURPOSE: We tested the hypothesis that adding metastasis-directed therapy (MDT) to standard of care (SOC) systemic therapy improves progression-free survival (PFS) among patients with oligometastatic disease.<br/><br/>METHODS: EXTEND was a multicenter randomized phase II trial. Patients with 1-5 metastases were randomized to MDT+SOC vs SOC in 1 of 6 baskets (breast, pancreas, kidney, two prostate baskets, and an "Other" basket) with basket-specific stratification and powering. PFS, the primary endpoint, was pre-specified in the per-protocol set within each basket, across all baskets, and across all baskets excluding the prostate baskets. Exploratory endpoints included circulating tumor DNA (ctDNA) and immune profiling.<br/><br/>RESULTS: From 2018 through 2023, 521 patients were screened, 350 were randomized, and 334 were analyzed per protocol (MDT+SOC, n=166; SOC, n=168). Radiotherapy was used as MDT for 98% of metastases (370/379). Overall, after median follow-up of 53 months, PFS was improved with MDT+SOC (HR 0.54, 95% CI 0.41 to 0.72, p < 0.001). Similarly, PFS was improved when excluding the prostate baskets (HR, 0.60; 95% CI: 0.40 to 0.89). Within each basket, PFS superiority was identified for the pancreas, prostate, and "Other" baskets, whereas the breast and kidney baskets were inconclusive. At enrollment, detectable ctDNA correlated with shorter PFS and survival; by contrast, ctDNA clearance 3-months post-enrollment correlated with improved survival. MDT+SOC-induced systemic immune activation was most pronounced among baskets demonstrating PFS superiority.<br/><br/>CONCLUSION: The phase II EXTEND trial supports the addition of MDT to SOC for oligometastatic disease. Histology-specific efficacy signals were identified for phase III testing. Translational insights suggest the potential for optimizing the definition of oligometastasis using ctDNA, and point to systemic immune responses as a possible mechanism of benefit from MDT.
    📝 Sherry AD, Haymaker C, Wang S, Liu S, Bathala TK, Medina-Rosales MN, Seo A, Hara K, Reddy J, Chun SG, Mayo LL, Walker G, Pant S, Zhao D, Kovitz CA, Ramirez D, Ha CS, Smith BD, Gomez D, Cohen L, Koong AC, Reuben A, Tannir N, Corn PG, Tran PT, Siddiqui BA, Subudhi SK, Msaouel P, Ludmir EB, Tang C. Addition of Metastasis-Directed Therapy to Standard of Care for Oligometastatic Solid Tumors: Primary Analysis of All Tumor-Histology Baskets of the Phase II Randomized EXTEND Trial. J Clin Oncol. 2026 May 16:101200JCO2502856.

    Radiation Palliative Phase 2 trial Confirmatory ESTRO Congress 2026

    Kidney

    FASTRACK II now has 84-month local control, the longest prospective SABR follow-up in primary RCC, still single-arm.

    Early signal

    FASTRACK II NCT02613819

    ForPrimary RCC ≤10cm, T1b-dominant, medically inoperable or declined surgery

    Freedom from local progression local control

    100% at 36, 60, 84 mo

    ITT population, RECIST-assessed, median f/u 62 mo

    TL;DR100% freedom from local progression at 36, 60, and 84mo after single-fraction 26Gy or 42Gy/3fx SABR in inoperable primary RCC.

    Why it mattersRadiation oncology

    The transferable detail is the size-adapted prescription: 26Gy in one fraction under 4cm, 42Gy/3fx above it, with median tumour 46mm and 65% T1b or higher. That is a larger-tumour cohort than most ablation series, and zero local failures out to 84mo supports offering SABR when a 77-year-old is turned down for nephrectomy.

    Monday clinic

    In a medically inoperable or surgery-declining patient with a primary RCC up to 10cm, including T1b and larger where thermal ablation is a poor fit, this supports SABR as a durable local option; it does not speak to the operable patient, where nephrectomy remains untested against it.

    The longer read
    10 details
    Design

    Non-randomised phase 2, eight hospitals in Australia and the Netherlands, run by TROG and ANZUP. Enrolment July 28 2016 to Feb 27 2020; 71 enrolled, one withdrew consent before treatment. This report is the pre-planned final follow-up at a median of 62 months (IQR 60-72).

    Population & inclusion

    Histologically confirmed primary RCC, medically inoperable, high risk, or declined surgery, ECOG ≤2, tumours ≤10 cm, N0-N1. Median age 77 years (70-82), 49 (70%) male. Median tumour size 46 mm (37-55), with 39 (56%) T1b, six (9%) T2a and one (1%) T3a.

    Radiotherapy

    Size-adapted prescription: 26 Gy in a single fraction for tumours ≤4 cm, 42 Gy in three fractions 48 h apart for tumours >4 cm. Histological confirmation was required before treatment, so this is a biopsy-proven cohort rather than a radiographic-diagnosis one.

    Endpoints

    Primary: freedom from local progression by RECIST, assessed in the intention-to-treat population, as was safety.

    Results

    100% local control at 36, 60 and 84 months, with no local recurrences and no cancer-related deaths reported in the cohort.

    Safety

    Seven (10%) patients had at least one treatment-related grade 3 event within 9 months: pain in four (6%), nausea and vomiting in three (4%), colonic obstruction in two (3%), diarrhoea in one (1%). No grade 4 events and no treatment-related deaths; no new long-term safety signals emerged with extended follow-up.

    Applies to
    biopsy-proven primary RCC up to 10 cm in pts who are inoperable, high surgical risk, or decline surgery, median age 77 and predominantly T1b or higher
    Does not represent the operable patient choosing between SABR and partial nephrectomy, nor the small renal mass under 4 cm where thermal ablation is already established.
    Limitations

    A 100% point estimate in 70 pts carries a wide confidence bound that the headline hides, and RECIST is an imperfect local-control instrument after ablative RT, where a treated mass commonly persists without viable tumour. Renal function trajectory, the endpoint that actually competes with nephrectomy, is not reported in this source.

    vs leading data

    Prior SABR evidence in primary RCC was retrospective and pooled, so a prospective multicentre dataset at 84 months is the new contribution rather than the effect size itself. Comparison to partial nephrectomy and thermal ablation remains indirect: no randomised trial has run, and this cohort was selected against surgery by definition.

    Discussion

    The finding that transfers is durability at a tumour size where thermal ablation performs worst, with a median of 46 mm and 65% at least T1b. What it does not settle is whether SABR is a choice rather than a fallback, which needs a randomised or matched comparison in operable pts, with renal function as a co-primary.

    Rationale

    Single-arm phase 2, N=70, inoperable or surgery-declining pts only. No randomised comparator vs partial nephrectomy or thermal ablation. Maturity gate holds despite 62mo f/u.

    Open questions
    • SABR vs partial nephrectomy in operable pts
    • Renal function trajectory after SABR vs nephrectomy
    • SABR vs thermal ablation in T1b tumours

    Sourced from Siva et al.

    📚 Sources · 📄 1 paper
    📄 PAPER Siva; Pryor; Martin et al. · The Lancet. Oncology (2026-05)
    Long-term outcomes of stereotactic ablative body radiotherapy for primary kidney cancer (TROG 15.03 FASTRACK II): a multicentre, non-randomised, phase 2 study.
    PMID 42144018 → doi
    Abstract
    BACKGROUND: Stereotactic ablative body radiotherapy (SABR) is an emerging, non-invasive alternative for primary renal cell carcinoma. We aimed to provide the final long-term trial outcomes of TransTasman Radiation Oncology Group (TROG) 15.03 FASTRACK II, the first phase 2 trial investigating SABR for primary renal cell carcinoma to our knowledge.<br/><br/>METHODS: FASTRACK II was a non-randomised, phase 2 study conducted in eight hospitals in Australia and the Netherlands by TROG and the Australian and New Zealand Urogenital and Prostate (ANZUP) Cancer Trials Group. Here, we report the final pre-planned follow-up results. Adult patients (aged &#x2265;18 years) with histologically confirmed primary renal cell carcinoma, who were medically inoperable, high risk, or declined surgery, had an Eastern Cooperative Oncology Group performance status of 2 or less, had tumours 10 cm or less in size, and had N0-N1 disease were included. Patients underwent either a single fraction SABR of 26 Gy for tumours 4 cm or less in maximum diameter, or 42 Gy in three fractions delivered 48 h apart for tumours more than 4 cm in maximum diameter. The primary outcome was freedom from local progression to assess local control after SABR evaluated with the Response Evaluation Criteria in Solid Tumours. The primary endpoint and safety were evaluated in the intention-to-treat population. A patient representative was involved in the study design and conduct. The trial was registered with ClinicalTrials.gov (NCT02613819) and is closed to enrolment.<br/><br/>FINDINGS: Between July 28, 2016, and Feb 27, 2020, 71 patients were enrolled and one withdrew consent before treatment. Median follow-up was 62 months (IQR 60-72), median age was 77 years (70-82). 49 (70%) of 70 patients were male and 21 (30%) were female. Race and ethnicity data were not collected. The median tumour size was 46 mm (37-55), with 24 (34%) patients with T1a disease, 39 (56%) with T1b disease, six (9%) with T2a disease, and one (1%) with T3a disease. One patient (1%) had nodal involvement (N1). SABR resulted in 100% local control at 36 months, 60 months, and 84 months. Seven (10%) patients had at least one grade 3 adverse event within 9 months of SABR that was designated possibly, probably, or definitely related to treatment: nausea and vomiting (three [4%] events); abdominal, flank, or tumour pain (four [6%]); colonic obstruction (two [3%]); and diarrhoea (one [1%]). No new long-term safety signals, grade 4 events, or treatment-related deaths were noted.<br/><br/>INTERPRETATION: Long-term follow-up supports the safety and local control of SABR for non-surgical patients with renal cell carcinoma, with no observed local recurrences or cancer-related deaths in this cohort, which had predominantly T1b disease or higher.<br/><br/>FUNDING: The Cancer Australia Priority-driven Collaborative Cancer Research Scheme and Varian.
    📝 Siva S, Pryor D, Martin J, Hardcastle N, Moon D, Kron T, Higgs B, Foroudi F, Ruben J, Sridharan S, Montgomery R, Davey R, Lin C, Shaw M, Lawrentschuk N, Appu S, Vanneste BGL, Hofman MS, Murphy DG, De Abreu Lourenco R, Mancuso P, Brook NR, Raman A, Wong LM, Sidhom M, Wood S, Ali M, Bressel M. Long-term outcomes of stereotactic ablative body radiotherapy for primary kidney cancer (TROG 15.03 FASTRACK II): a multicentre, non-randomised, phase 2 study. Lancet Oncol. 2026 May 17:S1470-2045(26)00091-4.

    Radiation Curative Phase 2 trial Early signal ESTRO Congress 2026

    Build disclosures

    8 of 9 study clusters analyzed successfully.

    1 cluster dropped
    • PEACE 2 (peace-2)
      suppressed via override