onc brain

About · curated by Nick Boehling, MD · @nb2276

    2026-11-02

    digest generated 2026-11-03

    AGITG MASTERPLAN: adding SBRT 40 Gy/5fx to chemo cut 12-mo LRR 20.2% vs 52.0% (P=0.022), mOS 22.0 vs 14.0 mo in high-risk operable/borderline/LA pancreas.
    TL;DR
    Local control led the day. MASTERPLAN isolates the SBRT benefit on LRR in pancreas. UNION's 3-yr EFS 91.3% vs 77.4% (HR 0.33) in LARC bundles SCRT with camrelizumab, so the RT share can't be separated. TOP-1 points the other way: omitting RT and ET at age ≥70 gave 5-yr LR 14.8%, with the lower CI bound above the 10% threshold.

    Prostate

    Unclear

    Decipher and PAM50 in NRG/RTOG 9601 and 0534

    ForPost-prostatectomy prostate cancer, salvage RT candidates

    TL;DRNo effect size reported in source tweets: Decipher and PAM50 biomarker analyses for guiding hormone therapy with salvage RT, presented by MD Anderson investigators.

    6 details
    Design

    Biomarker analyses (Decipher, PAM50) drawn from the postoperative trials NRG/RTOG 9601 and 0534. Analysis design, N and endpoints not stated in source.

    Applies to
    post-prostatectomy pts being considered for salvage RT with or without hormone therapy
    Does not represent the definitive (intact prostate) RT setting.
    Rationale

    Source gives no effect sizes, cohort sizes or endpoints for the biomarker analyses; the image content was not accessible.

    Open questions
    • Which Decipher or PAM50 strata benefit from hormone therapy with salvage RT?
    • Can low-risk genomic pts safely omit hormone therapy with salvage RT?

    Sourced from @urotoday

    📚 Sources · 🐦 1 tweet

    Curative Unclear

    GI Lower

    SCRT-based TNT plus PD-1 blockade beats LCCRT on EFS, but the pCR primary endpoint is not reported in source.

    Caveats dominate

    UNION NCT04928807

    ForcT3-4 or N+ rectal adenocarcinoma ≤10 cm from anal verge

    TL;DR3-yr EFS 91.3% vs 77.4%, HR 0.33 (0.15-0.71), P=0.0029: SCRT → camrelizumab + CAPOX vs long-course CRT → CAPOX in LARC.

    Why it mattersRadiation oncology

    The control is long-course CRT, so the EFS gain (HR 0.33) comes with a switch to 25 Gy/5f. That makes SCRT the RT backbone for an IO-containing TNT, not a compromise. Because RT schedule and camrelizumab were changed together, the trial cannot say whether SCRT itself is what lets IO work in largely pMMR disease.

    Monday clinic

    In cT3-4 or node-positive low/mid rectal adenocarcinoma, this supports SCRT followed by PD-1 inhibitor plus CAPOX as an evidence-backed TNT option. It does not settle IO use when no PD-1 agent equivalent to camrelizumab is available, or questions of organ preservation. The longer read

    8 details 2 trials watching
    Design

    Phase 3, randomized 1:1, N=231 (113 vs 118), accrued July 2021 to March 2023. Median follow-up 36.8 vs 35.6 mo at the October 1, 2025 cutoff.

    Population & inclusion

    cT3-4 or N+ rectal adenocarcinoma, tumor ≤10 cm from the anal verge. MMR/MSI composition of the enrolled cohort is not reported in source.

    Radiotherapy

    Experimental: SCRT 25 Gy/5f. Control: 50.4 Gy/28f with concurrent capecitabine 825 mg/m2 BID. Target volumes are not reported in source.

    Regimen

    Both arms: 2 neoadjuvant + 6 adjuvant cycles of CAPOX. Experimental adds camrelizumab 200 mg d1 given alongside CAPOX for up to 17 cycles.

    Endpoints

    Primary: BIRC-assessed pCR rate (result not in source). Key secondary endpoints with prespecified α: investigator-assessed EFS and OS.

    Safety

    G≥3 TRAE over the whole treatment period 51.3% (59/115) vs 48.2% (54/112). The RT-attributable split is not reported.

    vs leading data

    RAPIDO set SCRT followed by consolidation chemo as a TNT option, and PRODIGE 23 did the same for an LCCRT-based approach. UNION is the first phase 3 to layer a PD-1 inhibitor onto SCRT in LARC, building on earlier SCRT + IO phase 2 signals such as TORCH.

    Applies to
    cT3-4 or N+ rectal adenocarcinoma ≤10 cm from the anal verge treated with curative-intent TNT
    Does not represent upper rectal tumors beyond 10 cm, watch-and-wait candidates, or settings without camrelizumab.
    Limitations

    The safety population (115 vs 112) does not match randomization (113 vs 118), so some pts received the other arm's treatment. Neoadjuvant CAPOX was only 2 cycles in the control arm, lighter than full TNT backbones. OS and surgical or organ-preservation outcomes are absent.

    Discussion

    The EFS effect is large and was tested under alpha control, but it comes from a two-variable comparison. It supports the whole package and does not establish what SCRT or camrelizumab contributes individually.

    Results
    EndpointSCRT + camrelizumab + CAPOXLCCRT + CAPOXEffect
    3-yr EFS (investigator)91.3% (83.9-95.4)77.4% (67.9-84.4)HR 0.33 (0.15-0.71), P=0.0029
    G≥3 TRAE51.3% (59/115)48.2% (54/112)n/a
    Median f/u36.8 mo (34.8-37.8)35.6 mo (34.3-36.9)n/a
    Enrolment
    CONSORT flow
    Randomized231
    ↓
    SCRT + camrelizumab + CAPOX
    allocated 113
    LCCRT + CAPOX (SOC)
    allocated 118
    Rationale

    Randomized phase 3, but the primary pCR result is not in source and EFS is secondary. SCRT and camrelizumab change together, so the benefit cannot be attributed to either.

    Open questions

    Sourced from Zhen Yu Lin

    📚 Sources · 📄 1 paper
    📄 PAPER Zhen Yu Lin · ESMO Congress 2026 (2026-10)
    Neoadjuvant short-course radiotherapy followed by camrelizumab and chemotherapy in locally advanced rectal cancer (LARC): The phase 3 UNION trial
    article →
    Abstract
    ESMO Congress 2026 abstract 3530O · Proffered paper: Gastrointestinal tumours, lower digestive · 2026-10-25 · presented by Zhen Yu Lin (Wuhan, China) · NCT04928807<br/><br/>Background: Despite the use of neoadjuvant chemoradiotherapy, recurrence and distant metastasis remain common in LARC. Effective immunotherapy-based strategies for the predominantly proficient mismatch repair/microsatellite-stable population remain limited. UNION is the first phase 3 trial to evaluate a neoadjuvant strategy incorporating radiotherapy, immunotherapy, and chemotherapy in LARC. Here we present the prespecified event-free survival (EFS) analysis.<br/>Methods: Patients with cT3-4 or N+ rectal adenocarcinoma (tumor located ≤10 cm from the anal verge) were randomly assigned (1:1) to receive short-course radiotherapy (SCRT; 25 Gy/5f; experimental group) or long-course chemoradiotherapy (50.4 Gy/28f with concurrent capecitabine 825 mg/m2 twice daily; standard of care group) followed by 2 neoadjuvant cycles and 6 adjuvant cycles of capecitabine and oxaliplatin (CAPOX). The experimental group additionally received neoadjuvant and adjuvant camrelizumab (200 mg, day 1) since CAPOX treatment for up to 17 cycles. The primary endpoint was blinded independent review committee (BIRC)-assessed pathological complete response rate. Key secondary endpoints with prespecified α allocation were investigator-assessed EFS and overall survival.<br/>Results: Between July 2021 and March 2023, 231 patients were randomized to the experimental group (n=113) and standard of care group (n=118). As of October 1, 2025, the median follow-up duration was 36.8 months (95% CI, 34.8-37.8) and 35.6 months (95% CI, 34.3-36.9), respectively. The 3-year EFS rate was significantly higher in the experimental group compared with standard of care (91.3% [95% CI, 83.9-95.4] vs 77.4% [95% CI, 67.9-84.4], hazard ratio=0.33 [95% CI, 0.15-0.71], P=0.0029). BIRC-assessed EFS consistently favored the experimental group. During the whole treatment period, the incidence of grade ≥3 treatment-related adverse events was 51.3% (59/115) and 48.2% (54/112), respectively.<br/>Conclusions: UNION is the first phase 3 trial to demonstrate a significant improvement in EFS with an immunotherapy-based regimen in LARC. This neoadjuvant strategy represents a new standard of care.<br/>Clinical trial identification: NCT04928807.

    Combined Curative Phase 3 RCT Caveats dominate ESMO Congress 2026

    Breast

    TOP-1 tests omitting both RT and ET in low-risk elderly ER+ BC; 5-yr LR exceeds the bound the design was meant to exclude.

    Early signal

    TOP-1 (BOOG 2016-01)

    ForWomen ≥70, low-risk ER+ HER2- T1 BC after BCS, no endocrine therapy

    TL;DR5-yr local recurrence 14.8% (95% CI 12.3-17.5) after BCS alone without RT or ET in women ≥70 with low-risk ER+ HER2- BC.

    Why it mattersRadiation oncology

    The trial removed endocrine therapy as well as RT, which earlier omission trials never did, and LR reached 14.8%, above the 10% ceiling it was powered to exclude. Salvage was mostly feasible (86 repeat BCS), but 70 pts received RT at recurrence anyway. So in ET-untreated older women, omitting RT often postpones it rather than avoiding it.

    Monday clinic

    In a woman ≥70 with ≤2cm low-grade ER+ HER2- BC after BCS who will not take ET, this questions RT omission as low-risk; it does not test RT omission in women who do take ET. The longer read

    10 details 2 trials watching
    Design

    Prospective, multicenter, observational, single-arm cohort; N=792 of 800 planned (80% power to exclude a 10% 5-yr LR). Median f/u 5.1y; cumulative incidence with death as competing event.

    Population & inclusion

    Women ≥70y, ER ≥50%, HER2-negative, ≤1cm grade 1/2 or ≤2cm grade 1, free margins, after BCS with no RT and no ET. Median age 73.6y.

    Endpoints

    Primary: 5-yr LR, a histologically confirmed invasive ipsilateral event. Secondary: contralateral BC, OS, BC-specific survival.

    Results

    5-yr LR 14.8% (95% CI 12.3-17.5), exceeding the prespecified 10% threshold. 2 of 81 deaths BC-related.

    EndpointResult
    Local recurrence (invasive ipsilateral)123 pts · 5-yr 14.8% (95% CI 12.3-17.5)
    Contralateral BC32 (4.0%)
    Deaths, any cause81 (10.2%)
    Deaths, BC-related2 (2.5% of deaths)
    vs leading data

    PRIME II and CALGB 9343 supported RT omission in older women who received ET; TOP-1 tests the population that skips both. The trial's own benchmark is a national registry LR of 1.3% with RT, not a randomized arm.

    Applies to
    women ≥70 with low-risk ER+ HER2- T1 BC after BCS who receive neither RT nor ET
    Does not represent older women who take adjuvant ET after RT omission.
    Limitations

    Only invasive ipsilateral events counted, so DCIS recurrence is excluded from the primary. Registry comparator differs in era and selection, and ER+ low-grade recurrences accrue well beyond 5y.

    Discussion

    Dropping both adjuvant therapies failed the study's own safety bar, while salvage remained mostly breast-conserving. The authors keep RT omission as a shared-decision option, but the result does not show which omitted therapy drove the excess.

    Rationale

    Single-arm observational cohort against a historical registry benchmark; no concurrent RT or ET arm, and 5.1y f/u is short for low-grade ER+ recurrence kinetics.

    Open questions

    Sourced from Lotte Bouwman

    📚 Sources · 📄 2 papers
    📄 PAPER Lotte Bouwman · ESMO Congress 2026 (2026-10)
    Omission of adjuvant radiotherapy after breast-conserving surgery in systemically untreated older patients with early-stage estrogen receptor positive breast cancer: 5-year results of the TOP-1 study (BOOG 2016-01)
    article →
    Abstract
    ESMO Congress 2026 abstract 545RO · Rapid oral: Breast cancer, early stage · 2026-10-23 · presented by Lotte Bouwman (Leiden, Netherlands)<br/><br/>Background: Adjuvant radiotherapy (RT) following breast-conserving surgery (BCS) is standard of care in women with early-stage estrogen-receptor positive (ER+) breast cancer (BC). Previous studies on RT omission involved older patients treated with BCS and endocrine therapy (ET), showing low local recurrence (LR) risks. According to Dutch guidelines, ET is not advised in T1, low-grade early-stage BC. This study assessed 5-year LR risk after BCS without RT, in older patients with ER+ BC without ET.<br/>Methods: The prospective, multicenter, observational, single-arm TOP-1 study included women aged ≥70 years with low-risk BC (ER+ ≥50%, HER2-negative, ≤1cm and grade 1/2, or ≤2cm grade 1 with free surgical margins). Primary endpoint was 5-year LR risk, defined as a histologically confirmed invasive ipsilateral event. Secondary endpoints included contralateral BC, overall and BC specific survival. Cumulative incidence analysis was performed with death as competing event. With a 1.3% (99%CI 0.6-2.5%; national registry) 5-year LR risk with RT, and the upper CI limit tripled without RT (7.5%), 800 patients (power 80%) were needed to exclude a 10% 5-year LR risk, acceptable to patient advocates.<br/>Results: Between January 2017 and September 2021, 792 patients were included. Median age was 73.6 years (IQI 71.9-75.5). Median follow-up was 5.1 years (IQR 4.9-5.2). In total, 123 patients developed a LR, resulting in a 5-year LR risk of 14.8% (95%CI 12.3-17.5). Treatment of LR was surgical in 114 (92.7%) patients, of whom 86 (75.4%) BCS, 70 (56.7%) patients received RT and 43 (35.0%) ET. Contralateral BC was diagnosed in 32 (4.0%) patients. Death occurred in 81 (10.2%) patients, of whom 2 (2.5%) BC related.<br/>Conclusions: Omission of adjuvant RT resulted in a 5-year LR risk of 14.8% after BCS without ET, in women aged ≥70 with low-grade T1, ER+ BC. Although the LR risk exceeded prior estimates, BCS was possible in most patients and BC specific survival was excellent. Therefore, in a shared decision setting, RT omission is an option for a subgroup of older patients. Follow-up is needed to assess longer-term survival and other secondary endpoints.<br/>Clinical trial identification: National Trial Register: 6147 (however, nowadays outdated). Also registered in the CCMO Research Portal as NL-008797.
    📄 PAPER · Oncodaily - Oncology News, Insights, Stories (2026-10)
    TOP-1 Study Reports 14.8% Five-Year Local Recurrence After Radiotherapy Omission in Older Women With Breast Cancer - OncoDaily
    article →
    Abstract
    TOP-1 Study Reports 14.8% Five-Year Local Recurrence After Radiotherapy Omission in Older Women With Breast Cancer / Breast Cancer, ESMO, esmo 2026, ESMO 26,

    Radiation Curative Early signal ESMO Congress 2026

    GI Upper

    Randomized evidence that SBRT adds locoregional control to modern chemo in high-risk pancreas, with OS and PFS gains as secondary endpoints.

    Early signal

    AGITG MASTERPLAN

    ForHigh-risk operable, borderline resectable, or locally advanced pancreatic cancer

    Locoregional recurrence at 12 months local control

    20.2% vs 52.0%

    P=0.022

    TL;DR12-mo locoregional recurrence 20.2% vs 52.0% (P=0.022) adding SBRT 40 Gy/5fx to chemo in high-risk operable, borderline, or locally advanced pancreatic cancer.

    Reported via OncoDaily →

    Why it mattersRadiation oncology

    The LRR benefit held in the potentially operable stratum (19.7% vs 52.9%, P=0.031) but not the inoperable one (P=0.16, n=26), so the strongest RT read is neoadjuvant SBRT 40 Gy/5fx after 3 mo of modern chemo in borderline or high-risk operable disease. That benefit came despite only 80% of the SBRT arm starting RT.

    Monday clinic

    In borderline resectable or high-risk operable pancreatic cancer after 3 mo of mFOLFIRINOX or gem/nab-paclitaxel, this supports considering SBRT 40 Gy/5fx before surgical reassessment; the inoperable-stratum signal is too small to settle locally advanced disease. The longer read

    11 details 4 trials watching
    Design

    Randomized 2:1, chemo + SBRT vs chemo alone, 75 enrolled and 74 eligible across 14 centers. Phase not stated in source.

    Population & inclusion

    Potentially operable (n=48): borderline resectable, or operable with tumor >4 cm, extrapancreatic extension, or nodal involvement. Inoperable (n=26): locally advanced or medically inoperable.

    Regimen

    Three months of mFOLFIRINOX or gemcitabine + nab-paclitaxel by clinician choice, then reassessment for surgery. Resected pts received 3 more months adjuvant; unresected pts 3 more months systemic chemo.

    Radiotherapy

    SBRT 40 Gy in 5 fractions with fiducial marker guidance and real-time RT quality assurance. 39 of 49 (80%) assigned to SBRT initiated it.

    Endpoints

    Primary: locoregional recurrence at 12 months. Secondary: PFS, OS, surgical outcomes, toxicity.

    Results

    Primary endpoint met; benefit significant in the potentially operable stratum, not significant in inoperable disease (P=0.16). Resection and R0 rates numerically higher with SBRT, both non-significant.

    EndpointChemo + SBRTChemo aloneP
    12-mo LRR, all20.2%52.0%0.022
    12-mo LRR, POPC19.7%52.9%0.031
    12-mo LRR, IPC21.4%50.0%0.16
    mPFS11.9 mo6.3 mo0.002
    mOS22.0 mo14.0 mo0.006
    Resection (POPC)21/31 (68%)10/17 (59%)0.54
    R0 (>1 mm), resected62%40%0.44
    G3+ toxicity70.2%64.0%0.27
    Safety

    G3+ toxicity 70.2% vs 64.0% (P=0.27), no significant increase with SBRT. RT-specific and late toxicity not broken out in source.

    vs leading data

    Randomized evidence for adding RT to chemo in pancreatic cancer has been inconsistent: LAP07 tested conventional chemoRT in locally advanced disease, and PREOPANC tested preoperative chemoRT in resectable and borderline disease. MASTERPLAN differs by pairing short-course SBRT with modern multiagent chemo and by powering on local control rather than OS.

    Applies to
    borderline resectable or high-risk operable pancreatic cancer receiving 3 mo of mFOLFIRINOX or gem/nab-paclitaxel before SBRT 40 Gy/5fx
    Does not represent standard-risk resectable disease, and the locally advanced/inoperable stratum is too small to support a conclusion.
    Limitations

    Incomplete SBRT uptake (80%) and clinician-chosen chemo add noise to a small trial. The OS gain sits on a secondary endpoint with no HR reported in the source, and late GI toxicity is not described.

    Discussion

    A local control benefit of this size, carried into PFS and OS, makes a larger confirmatory trial a priority. It does not yet settle which stratum benefits, whether the OS signal is real, or how SBRT should be sequenced with surgery.

    Rationale

    Randomized with primary endpoint met, but N=74 across heterogeneous strata, 80% SBRT uptake, and OS/PFS secondary; phase not stated, conference trade-press source only.

    Open questions
    📚 Sources · 📄 1 paper
    📄 PAPER · Oncodaily - Oncology News, Insights, Stories (2026-10)
    AGITG MASTERPLAN Trial Shows Improved Local Control and Survival With SBRT Plus Chemotherapy in Pancreatic Cancer - OncoDaily
    article →
    Abstract
    AGITG MASTERPLAN Trial Shows Improved Local Control and Survival With SBRT Plus Chemotherapy in Pancreatic Cancer / AGITG MASTERPLAN Trial, esmo 2026, ESMO

    Radiation Early signal

    Build disclosures

    4 of 5 study clusters analyzed successfully.

    1 cluster dropped
    • CLERAD-PROBE (clerad-probe)
      suppressed via override