onc brain

About · curated by Nick Boehling, MD · @nb2276

    Early signal

    27 studies Subscribe via RSS →

    NRG Oncology RTOG 0539 NCT00895622

    ForWHO grade 1-3 meningioma, post-resection (GTR or STR), newly-diagnosed or recurr

    TL;DR10-yr PFS 85.2%, 72.2%, 42.5% for low/intermediate/high-risk meningioma with risk-adapted observation or RT (median f/u ~12yr).

    vs leading data
    • Long-term benchmarks for future trials; ROAM/EORTC-1308 is ongoing randomised RT vs obs for grade 2

    Radiation Curative Phase 2 trial Early signal

    7 details 3 trials watching
    Methods
    • 🔍 Prospective phase 2, N=165 eligible (244 consented); risk-stratified by WHO grade, resection extent, recurrence status
    • 🔍 Low: grade 1 GTR/STR → obs; intermediate: recurrent grade 1 or new grade 2 post-GTR → 54 Gy; high: new grade 2 post-STR, grade 3, or recurrent grade 2/3 → 60 Gy
    • 🔍 Median PFS not reached in low- and intermediate-risk cohorts
    Results
    • 📊 10-yr outcomes by risk group
      Risk GroupRxn10-yr PFS10-yr OS10-yr prog. incidence
      LowObservation6085.2%94.1%8.9% (3.2–18.2%)
      Intermediate54 Gy/30fx5272.2%84.7%21.2% (10.8–33.9%)
      High60 Gy/30fx5342.5%51.1%39.3% (25.8–52.5%)
    Critique
    • ⚠️ G3+ RT-attributed toxicity
      • Intermediate-risk: 9.6% (5/52 pts)
      • High-risk: 15.1% (8/53 pts)
    • ⚠️ Non-randomized: risk allocation deterministic, not randomised; no RT vs obs head-to-head for intermediate group
    • ⚠️ WHO 2021 molecular criteria not applied; risk stratification reflects histologic grading (WHO 2007/2016)
    Open questions
    📚 Sources · 📄 1 paper
    📄 PAPER Kotecha, Rupesh; Polley, Mei-Yin; Vogelbaum, Michael A. et al. · Journal of Clinical Oncology (2026-05)
    Long-Term Analysis of NRG Oncology RTOG 0539: A Phase II Trial of Observation for Low-Risk Meningioma and Radiotherapy for Intermediate- and High-Risk Meningioma
    PMID → doi
    Abstract
    NRG Oncology RTOG 0539 was a prospective phase II trial of risk-adapted radiotherapy for patients with WHO grade 1-3 meningioma. Low-risk (group 1, n = 60) was defined as a grade 1 tumor after gross total resection or subtotal resection (GTR/STR) and prospectively monitored. Intermediate-risk (group 2, n = 52) was defined as recurrent grade 1 or newly diagnosed grade 2 tumor after GTR and treated with radiotherapy (54 Gy). High-risk (group 3, n = 53) included a newly diagnosed grade 2 tumor after STR, newly diagnosed grade 3 tumor, or recurrent grade 2 or 3 tumor and treated with radiotherapy (60 Gy). Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. The median follow-up times for the low-, intermediate-, and high-risk cohorts were 12.1, 12.0, and 11.1 years, respectively. The 10-year PFS and OS rates for the low-, intermediate-, and high-risk cohorts were 85.2% and 94.1%, 72.2% and 84.7%, and 42.5% and 51.1%, respectively. Five patients (9.6%) and eight patients (15.1%) had a grade 3+ toxicity attributed to radiotherapy in the intermediate- and high-risk cohorts, respectively. The long-term outcomes using this risk-adapted approach support observation for low-risk patients, inform radiotherapy patient selection and practice standards for intermediate- and high-risk patients, and provide comparative benchmarks for future trials.

    RAPCHEM (BOOG 2010-03)

    ForBreast cancer cT<5cm cN1-3, receiving NAC prior to BCS or mastectomy

    TL;DR10-yr locoregional recurrence 2.9% overall with risk-stratified RT de-escalation after NAC + surgery in cN1 breast cancer.

    vs leading data
    • NSABP RCT (NCT01872975) directly tests RT omission post-NAC in ypN0; results expected ~3 years from EBCC15 presentation

    Radiation Curative Phase 2 trial Early signal

    7 details 3 trials watching
    Methods
    • 🔍 Prospective single-arm, N=848, 17 centers (Netherlands), enrolled 2011-2015
    • 🔍 Eligibility: cT<5cm, cN1-3 at diagnosis; risk tier assigned by ypN status post-NAC + surgery
    • 🔍 RT allocation by risk tier
      • ypN0 (low): BCS → breast RT; mastectomy → RT omitted
      • ypN1-3 (intermediate): breast/chest wall RT; regional nodal RT withheld
      • ypN4+ (high): breast/chest wall + regional nodal RT
    Results
    • 📊 10-yr locoregional recurrence by risk tier
      • Low (ypN0): 7/291 (2.4%)
      • Intermediate (ypN1-3): 12/370 (3.2%)
      • High (ypN4+): 5/177 (2.8%)
    • 📊 Overall: 24/838 (2.9%) locoregional events at 10 yr
    Critique
    • ⚠️ No randomized comparator arm; low LRR rates may reflect patient selection or favorable NAC biology, not de-escalation effect per se
    • ⚠️ Most pts had ALND — less common in current practice; generalizability to sentinel node biopsy era uncertain
    Open questions
    📚 Sources · 📄 1 paper
    📄 PAPER · The ASCO Post
    Breast Cancer Recurrence Remains Low—Even After 10 Years—With Radiotherapy Tailored to Patient’s Individual Risk
    PMID →
    Abstract
    “The results of our study show that tailoring the extent of radiotherapy according to how well the chemotherapy has worked to treat cancer in the lymph nodes leads to very low and reassuring recurrenc...
    📝 Breast Cancer Recurrence Remains Low Even After 10 Years With Radiotherapy Tailored to Patient’s Individual Risk - The ASCO Post

    mRCAT-III NCT06507371

    ForpMMR/MSS LARC, cT3-4N0/+M0, tumor ≤10cm from anal verge, no positive lateral LN

    TL;DRpCR 61% vs 29% (p<0.0001) with node-sparing SCRT + CAPOX + tislelizumab vs conventional SCRT + CAPOX in pMMR LARC.

    Combined Curative Phase 3 RCT Early signal

    mRCAT-III
    OutcomeExperimental (N=77)Control (N=77)p
    pCR rate61.0% (47/77)28.6% (22/77)<0.001
    MPR rate (TRG0+1)77.9% (60/77)50.6% (39/77)<0.001
    +1 more figure
    mRCAT-III
    9 details
    Methods
    • 🔍 Phase 3 open-label RCT, N=154 (77/arm), 17 centers China, stratified by cN stage
    • 🔍 Node-sparing RT: 5Gy×5d targeting tumor bed only; elective tumor-draining LNs excluded from CTV
    • 💊 Experimental: tislelizumab 200mg d1 + oxaliplatin 130mg/m² d1 + capecitabine 1000mg/m² d1-14
    CONSORT flow
    Randomized 154
    ↓
    Node-sparing SCRT + CAPOX + tislelizumab
    allocated 77
    analyzed 77
    Conventional SCRT + CAPOX
    allocated 77
    analyzed 77
    Results
    • 📊 1° EP (pCR, ITT): 61.0% (47/77) vs 28.6% (22/77), p<0.0001
    • 📊 MPR (TRG0+TRG1): 77.9% (60/77) vs 50.6% (39/77), p<0.0001
    • 📊 Severe GI AEs lower in experimental arm per investigator report; specific rates not provided in source
    Critique
    • ⚠️ pCR is surrogate; EFS/OS are secondary endpoints, not yet reported
    • ⚠️ Small N (77/arm); single-country (China); open-label (pCR assessed by blinded central review)
    • ⚠️ pMMR/MSS only; dMMR/MSI-H pts excluded (already IO-responsive in LARC)
    Open questions
    • EFS and OS outcomes (secondary endpoints, not yet reported)
    • Organ preservation rate with node-sparing approach
    • Risk of elective nodal failure with lymph node omission
    📚 Sources · 🐦 1 tweet

    ctDNA surveillance in non-operative rectal cancer management

    ForStage I-III MSS rectal, cCR/nCR after NAT, undergoing NOM

    TL;DRctDNA sensitivity only 41% for local regrowth vs 74% for distant mets in 110 NOM rectal pts; risk stratifies but cannot replace imaging.

    Curative Real-world evidence Early signal

    ctDNA surveillance in non-operative rectal cancer management
    OutcomeSensitivitySpecificityAccuracy
    Local regrowth12/29 (41%)480/509 (94%)492/538 (91%)
    Distant metastasis31/42 (74%)611/627 (97%)642/669 (96%)
    7 details
    Methods
    • 🔍 N=110, INTERCEPT program, MD Anderson 2020-2024; stage I-III MSS rectal adenocarcinoma, cCR/nCR after NAT → NOM; Signatera™ tumor-informed ctDNA
    • 🔍 22/23 pts with local regrowth underwent salvage surgery; ctDNA-positive at regrowth: ypT3-4 75% vs 21% (ctDNA-negative), p=0.01
    Results
    • 📊 Ever-positive longitudinal ctDNA: worse 2-yr local regrowth-free survival (log-rank p=0.0002) and metastasis-free survival (p<0.0001)
    • 📊 First post-NAT ctDNA positive (within 180 days): worse regrowth-free (p=0.0006) and metastasis-free survival (p<0.0001)
    • 📊 Positive ctDNA associated with regrowth (~60%) and distant mets (~60%) in ctDNA-positive pts
    Critique
    • ⚠️ Sensitivity only 41% for local regrowth — negative ctDNA does not exclude local recurrence; endoscopy and MRI remain essential
    • ⚠️ Single-institution non-randomised cohort, N=110, median f/u 25 months; no ctDNA-guided vs standard surveillance arm
    Open questions
    • Does ctDNA-guided intensified surveillance improve salvage surgery success rates?
    • Optimal ctDNA testing frequency and timing within NOM protocols
    • Performance in dMMR/MSI-H pts (all MSS here)
    📚 Sources · 🐦 1 tweet

    CAN-2409

    ForHigh/intermediate-risk localized prostate cancer, RT 78Gy

    TL;DRDFS HR 0.70 vs placebo (p=0.0155), driven by 2yr biopsy pCR 80.4% vs 63.6%; OS/PCSM immature at 50.3mo.

    Combined Curative Early signal

    CAN-2409
    +1 more figure
    Intra-prostatic CAN-2409 reduces relative recurrence/death by 30%.
    Intra-prostatic CAN-2409 reduces relative recurrence/death by 30%.
    7 details
    Methods
    • 🔍 Intra-prostatic oncolytic viral injection (CAN-2409) + RT 78Gy vs RT + placebo; randomized
    Results
    • 📊 1° EP DFS: median NR vs 86.1mo, HR 0.70 (95% CI 0.52-0.94), p=0.0155
    • 📊 2yr post-Rx biopsy pCR: 80.4% vs 63.6%
    • 📊 2yr local persistence/recurrence: 19.6% vs 36.4%, p=0.0015
    Critique
    • ⚠️ DFS driven mainly by biopsy pCR (surrogate); MFS and BCR not reported in source
    • ⚠️ OS and PCSM not significantly different; 1 PCSM event per arm at 50.3mo median f/u
    • ⚠️ G3 tox <1% in both arms
    Open questions
    • OS/PCSM benefit with longer follow-up?
    • Role vs modern RT dose intensification (FLAME SIB 95Gy, ASCENDE-RT LDR-BT)?
    • AI biomarker utility for guiding abiraterone in very high-risk non-metastatic PCa?
    📚 Sources · 🐦 1 tweet

    MIRACLE-2

    ForMSS unresectable metastatic rectal cancer, synchronous mets, first-line

    TL;DR68% ORR, median OS 23.2mo, 18% NED in MSS unresectable metastatic rectal ca (N=50).

    vs leading data
    • MSS mCRC historically IO-refractory; RT + chemo used here as immune sensitizers to overcome PD-1 resistance

    Combined Curative Phase 1 Early signal

    MIRACLE-2
    EndpointResult (N=50)95% CI
    ETS rate (1° EP)76.0%62.4-86.8%
    ORR68.0%53.6-80.0%
    DCR88.0%76.0-95.2%
    Median OS23.2 mo15.1-31.3
    Median PFS9.3 mo7.1-11.5
    8 details
    Methods
    • 🔍 Phase I prospective single-arm; N=50; MSS RC primary ≤10cm from anal verge, synchronous unresectable mets; RAS/BRAF-mut 56%
    • 🔍 HFRT to primary + HFRT/SBRT to mets → systemic; resectable disease → primary resection + metastasectomy/ablation; primary cCR → watch-and-wait eligible
    • 💊 Systemic regimen by RAS/BRAF status
      • Mutant: FOLFOX + bevacizumab + tislelizumab
      • Wild-type: FOLFIRI + cetuximab + tislelizumab
      • Reassessment q8wk; tislelizumab 200mg Q2W
    Results
    • 📊 18% (9/50) reached NED
    • 📊 1-yr OS 93.3%; 1-yr PFS 33.4%
    • 📊 Median DOR 8.0mo (95% CI 5.2-10.8) among 34 responders; 1-yr DOR rate 20%
    Critique
    • ⚠️ Grade 3/4 TRAEs: substantial hematologic burden
      • lymphopenia 36.7%
      • neutropenia 26.5%
      • leukopenia 20.4%
      • no grade 5 events
    • ⚠️ Phase I single-arm, N=50, med f/u 19.9mo; no randomised comparator; NED durability and generalizability unproven
    Open questions
    • Predictive biomarkers for RT + IO response in MSS mCRC
    • Durability of NED beyond 2 years
    • Whether benefit extends to MSS colon (non-rectal) primaries
    📚 Sources · 🐦 1 tweet

    RAD-IO

    ForMIBC cT2-T3, 13% node-positive, 75% prior neoadjuvant chemo, median age 69

    TL;DR12-month DFS 80% (40/50; 95% CI 0.67-0.89) with durvalumab + chemoRT in MIBC, clearing GO threshold ≥75%; single-arm.

    vs leading data
    • GO/NO-GO threshold derived from BC2001 historical CRT data; BC2001 CT vs RT DFS HR 0.78 (0.60-1.02), p=0.07 used as benchmark context

    Combined Curative Phase 2 trial Early signal

    RAD-IO
    +1 more figure
    Durvalumab completion: N=54; 33 (61%) completed planned treatment; 21 (39%) discontinued early.
    Durvalumab completion: N=54; 33 (61%) completed planned treatment; 21 (39%) discontinued early.
    6 details
    Methods
    • 🔍 Multi-stage single-arm trial; durvalumab neoadjuvant, synchronous, and 12mo adjuvant with chemoRT (5FU+MMC, 55Gy/20Fr)
    • 🔍 N=55 enrolled; N=54 received ≥1 treatment dose (1 withdrew pre-treatment); 33/54 (61%) completed planned treatment, 21/54 (39%) discontinued early
    • 🔍 Node-positive subset: 55Gy/20Fr to bladder + 46Gy/20Fr to pelvic nodes
    Results
    • 📊 1° EP: 12-month DFS 80% (40/50; 95% CI 0.67-0.89); cleared pre-set GO threshold ≥75%
    Critique
    • ⚠️ Single-arm; no concurrent randomised comparator vs CRT alone; efficacy benchmarked against historical control only
    • ⚠️ 39% early durvalumab discontinuation; adjuvant IO tolerability across 12mo is a key remaining question
    Open questions
    • Randomised confirmation vs CRT alone required
    • Durability of bladder preservation beyond 12 months
    📚 Sources · 🐦 3 tweets

    MIBC Management Post-pCR / Bladder-Sparing Session

    ForMIBC (cT2-4a N0), curative-intent bladder-sparing candidates

    TL;DRDurvalumab + CRT (55 Gy/20 fr) feasible in 54 MIBC (87% full RT); pCR after NAC carries 85% 5-yr OS per SWOG 8710.

    vs leading data
    • Perioperative standard shifting: NIAGARA 24-mo OS 82.2% vs 75.2% (Gem/Cis + perioperative durvalumab vs Gem/Cis alone)
    • VESPER: ddMVAC 5-yr OS 66% vs 57% over Gem/Cis; KEYNOTE-B15 EVP improved OS vs Gem/Cis (under FDA review)
    • Bladder-sparing EVP trials underway: EV209 (cystectomy-eligible, N=240, endpoints cCR + 2-yr BIEFS) and EV309 (ineligible/refusing, N=390, endpoints BIEFS + OS)

    Combined Curative Phase 2 trial Early signal

    MIBC Management Post-pCR / Bladder-Sparing Session
    ComponentN (%)
    RT: full 55 Gy/20fr47 (87%)
    Chemo: MMC dose reduced4 (7%)
    Chemo: 5-FU Wk1 reduced9 (17%)
    Chemo: 5-FU Wk4 administered42 (78%)
    Chemo: discontinued early12 (22%)
    Durvalumab: completed33 (61%)
    Durvalumab: discontinued early21 (39%)
    +2 more figures
    MIBC Management Post-pCR / Bladder-Sparing Session
    MIBC Management Post-pCR / Bladder-Sparing Session
    5 details
    Methods
    • 🔍 Durvalumab + CRT trial: N=54 MIBC, 55 Gy/20 fr + MMC/5-FU + durvalumab, single-arm phase 2
    Results
    • 📊 RT delivery: 47/54 (87%) received full 55 Gy/20fr without extension or delay
    • 📊 Treatment delivery breakdown (N=54)
      • MMC reduced: 4 (7%); 5-FU Wk1 reduced: 9 (17%); 5-FU Wk4 administered: 42 (78%)
      • Chemo discontinued early: 12 (22%)
      • Durvalumab completed: 33 (61%), discontinued early: 21 (39%)
    • 📊 pCR (pT0N0) as prognostic marker: SWOG 8710 85% 5-yr OS if pT0; meta-analysis pooled RR 0.19 for RFS
    Critique
    • ⚠️ No efficacy endpoints reported; long-term bladder preservation, function, QOL, and safety require further follow-up
    Open questions
    • Long-term bladder preservation and QOL rates with durvalumab + CRT
    • Optimal post-pCR strategy: surveillance vs adjuvant IO
    • Will EVP bladder-sparing (EV209/EV309) improve on CRT outcomes?
    📚 Sources · 🐦 2 tweets

    NRG Clinico-Transcriptomic Risk Stratification (Abstract 5000)

    ForNCCN ≥ high-risk localized prostate cancer, RT+ADT candidates

    TL;DR22-gene GC independently predicts MFS, DM, and OS; combined NRG score reclassifies ~25% discordant NCCN high-risk pts for AAP intensification.

    vs leading data
    • STAMPEDE MO calibration anchor (Attard, Lancet 2022): HRMFS 0.53 (95% CI 0.44-0.64), HROS 0.60 (0.48-0.73), both p < 0.0001 for AAP intensification

    Radiation Curative Retrospective Early signal

    NRG Clinico-Transcriptomic Risk Stratification (Abstract 5000)
    +1 more figure
    NRG Clinico-Transcriptomic Risk Stratification (Abstract 5000)
    GC HighGC Low
    Clinical High49%15%
    Clinical Low9%27%
    5 details
    Methods
    • 🔍 Combined clinico-transcriptomic (CT) score: NCCN points + GC points
      • NCCN HR = 1 pt; NCCN VHR = 2 pts
      • GC <HR = 0 pt; GC HR = 1 pt; GC VHR = 2 pts
      • CT HR (≤2 pts) → RT+ADT; CT VHR (≥3 pts) → RT+ADT+AAP
    Results
    • 📊 22-gene GC independently predicts MFS, DM, and OS beyond clinical variables alone (p < 0.001 for each endpoint)
    • 📊 ~25% of NCCN ≥HR pts have discordant clinical vs. GC risk, warranting the combined approach
    Critique
    • ⚠️ Framework developed on existing NRG trial data; no prospective RCT validating CT-score-guided treatment allocation reported
    • ⚠️ Design not fully specified in source; likely secondary correlative analysis; GC cutoffs extend Spratt et al. (JCO 2018) prior work
    Open questions
    • Prospective RCT: does CT-score-guided allocation improve outcomes vs. clinical risk alone?
    • Generalizability to modern ARSI-backbone ADT regimens
    • GC threshold stability across contemporary cohorts
    📚 Sources · 🐦 2 tweets

    A-DREAM (ALLIANCE mAPMS)

    FormHSPC achieving PSA<0.2 after ≥18-24mo ADT+ARPI, low-volume predominant

    TL;DRADT+ARPI interruption in mHSPC: 41% treatment-free with eugonadal T at 18mo (1° EP); 38.5% still off-tx at 26.9mo FU.

    vs leading data
    • Intermittent ADT established in earlier hormone-sensitive trials; A-DREAM is first prospective signal for ADT+ARPI interruption in mHSPC

    Systemic Palliative Phase 2 trial Early signal

    A-DREAM (ALLIANCE mAPMS)
    +2 more figures
    A-DREAM (ALLIANCE mAPMS)
    A-DREAM (ALLIANCE mAPMS)
    9 details
    Methods
    • 🔍 Single-arm phase II, N=78 enrolled 07/2022-03/2024; PSA<0.2 after ≥18-24mo ADT + ≥12mo ARPI
    • 🔍 Re-initiation triggers: PSA ≥5 ng/mL, radiographic change (PCWG3), or PrCa-related sx
    Results
    • 📐 Primary EP: 80% CI 33.1-48.9%, one-sided p=0.0249; pre-specified 80% CI threshold (not 95%)
    • 📊 Median time to eugonadal T recovery: 9.0mo (95% CI 8.4-12.4)
    • 📊 Disposition at 26.9mo: 38.5% still off-tx; 37.2% resumed ADT+ARPI per protocol; 9.0% started non-protocol tx
    • 📊 rPFS from interruption: 15/78 events, median NE (32.5-NE); 12-mo est 94.6% (89.6-99.9%)
    • 📊 OS: 4/78 events, median NE; causes: prostate cancer, MDS, influenza, MI
    Critique
    • ⚠️ Single-arm; no randomized comparator vs continuous ADT+ARPI
    • ⚠️ 64.9% low-volume CHAARTED, 84.6% White; high-volume and diverse pts underrepresented
    Open questions
    • Impact on long-term OS vs continuous ADT+ARPI: randomized trial needed
    • Optimal re-initiation criteria in high-volume vs low-volume disease
    • Biomarker predictors of durable treatment-free interval
    📚 Sources · 🐦 1 tweet

    CHRYSALIS-2 (1L Ami+Laz, Atypical EGFR+)

    ForAdvanced NSCLC, atypical EGFR mutation, treatment-naive

    TL;DRMedian OS 41.0 mo (95% CI 27.7-NE) with ami+laz in 1L atypical EGFR+ advanced NSCLC; single-arm, n=49.

    vs leading data
    • Yang JCH NEJM 2025 (ami+laz 1L common EGFR): durable OS now reported in both common and atypical EGFR-mutated NSCLC populations

    Systemic Palliative Phase 2 trial Early signal

    OS: median 41.0 mo (95% CI 27.7-NE); landmark rates 85%, 72%, 55%; median f/u 31.3 mo; n at risk 49 → 10 → 0.
    OS: median 41.0 mo (95% CI 27.7-NE); landmark rates 85%, 72%, 55%; median f/u 31.3 mo; n at risk 49 → 10 → 0.
    +1 more figure
    Median treatment duration 13.3 mo (range <0.1-53.2); 39% on treatment >2 years.
    Median treatment duration 13.3 mo (range <0.1-53.2); 39% on treatment >2 years.
    7 details
    Methods
    • 🔍 Single-arm, n=49; 1L atypical EGFR-mutated advanced NSCLC
    • 💊 Median treatment duration 13.3 mo (range <0.1-53.2)
    • 💊 39% remained on treatment >2 years
    Results
    • 📊 Median OS 41.0 mo (95% CI 27.7-NE); median follow-up 31.3 mo
    Critique
    • ⚠️ Single-arm; no randomized comparator vs osimertinib or chemotherapy
    • ⚠️ Small N (49) limits any subgroup analysis by EGFR variant subtype
    • ⚠️ No clear EGFR variant subtype-outcome association found; underpowered to confirm or exclude
    Open questions
    • Randomized trial vs osimertinib in atypical EGFR needed to confirm benefit
    • CNS penetration and activity across atypical EGFR variant subtypes
    • SC amivantamab formulation (COPERNICUS) applicability in this population
    📚 Sources · 🐦 1 tweet

    PEACE V–STORM NCT03569241

    ForPelvic nodal oligorecurrence (≤5 PET+ nodes), prostate, post-radical tx, PS 0-1

    TL;DR4-yr MFS 76% (ENRT) vs 63% (MDT), HR 0.62 favoring elective nodal RT for PET+ pelvic nodal prostate oligorecurrence.

    vs leading data
    • First RCT comparing MDT vs ENRT for PET-detected pelvic nodal prostate recurrence

    Radiation Curative Phase 2 trial Early signal

    9 details
    Methods
    • 🔍 Phase 2 open-label RCT, N=196 randomized 1:1, 21 hospitals across 6 countries
    • 🔍 MDT arm: SLND or SBRT 30 Gy/3 fx every other day + 6 mo ADT
    • 🔍 ENRT arm: 45 Gy/25 fx to pelvis + SIB 65 Gy to PET+ nodes (or SLND) + 6 mo ADT
    • 🔍 Eligibility: PET+ pelvic nodal oligorecurrence ≤5 nodes post-radical local treatment, PS 0-1
    CONSORT flow
    Assessed / enrolled 198
    ↓ 2 excluded
    Randomized 196
    ↓
    MDT
    allocated 99
    analyzed 97
    ENRT
    allocated 97
    analyzed 93
    Results
    • 📊 1° EP: 4-yr metastasis-free survival
      Arm4-yr MFS80% CI
      ENRT76%69-81%
      MDT63%56-69%
    • 📐 HR 0.62 (80% CI 0.44-0.86), p=0.063; median f/u 50 mo (IQR 42-58)
    • 📊 G3 AEs
      • Urinary incontinence: 6% MDT vs 10% ENRT
      • Diarrhea: 1% MDT vs 2% ENRT
      • No treatment-related deaths
    Critique
    • ⚠️ 80% CI threshold (not 95%); p=0.063 at conventional alpha; prespecified phase 2 go/no-go design
    • ⚠️ Open-label; heterogeneous MDT arm (SLND vs SBRT); PSMA + choline PET tracers mixed
    Open questions
    • Phase 3 confirmation needed before ENRT replaces MDT as SOC
    • ENRT benefit differential by PET tracer type (PSMA vs choline)
    • Optimal ADT duration in combination with ENRT
    📚 Sources · 📄 1 paper
    📄 PAPER Piet Ost; Shankar Siva; Sigmund Brabrand et al. · The Lancet Oncology (2025-05)
    Salvage metastasis-directed therapy versus elective nodal radiotherapy for oligorecurrent nodal prostate cancer metastases (PEACE V–STORM): a phase 2, open-label, randomised controlled trial
    PMID → doi
    Abstract
    Background Various locoregional treatments exist for PET–CT-detected pelvic nodal oligorecurrences in patients with prostate cancer. We aimed to assess whether elective nodal radiotherapy (ENRT) to the pelvis would be superior to metastasis-directed therapy (MDT).<br/>Methods PEACE V–STORM is a phase 2, open-label, randomised, controlled trial conducted in 21 hospitals in Australia, Belgium, Italy, Norway, Spain, and Switzerland. Eligible participants were aged 18 years or older, with WHO performance status 0–1 and a histologically confirmed initial diagnosis of adenocarcinoma of the prostate, with a PET-detected pelvic nodal oligorecurrence (up to five nodes) following radical local treatment. Patients were randomly assigned (1:1) to MDT or ENRT. Randomisation was done online by minimisation with randomisation factor 0·80 and was stratified by type of PET tracer (choline vs prostate-specific membrane antigen) and type of MDT used (salvage lymph node dissection vs stereotactic body radiotherapy or simultaneous integrated boost). Participants and researchers were not masked to treatment assignment. Patients in the MDT group had salvage lymph node dissection or stereotactic body radiotherapy (30 Gy in three fractions every other day), with 6 months of androgen deprivation therapy. Patients in the ENRT group received a 45 Gy dose in 25 fractions to the pelvis with a simultaneous integrated boost of 65 Gy to the PET-positive nodes or salvage lymph node dissection, with 6 months of androgen deprivation therapy. The primary endpoint was metastasis-free survival, defined as the time between randomisation and the appearance of a metastatic recurrence (any M1) on PET imaging or death due to any cause, and was analysed per modified intention to treat. This study is registered with ClinicalTrials.gov, NCT03569241, and the Swiss National Clinical Trials Portal, SNCTP000002947, and is active, not recruiting.<br/>Findings Between June 11, 2018, and April 30, 2021, 198 patients were screened for eligibility, 196 of whom were randomly assigned to MDT (n=99) or ENRT (n=97), with 190 evaluable patients (MDT n=97 and ENRT n=93). All patients were male. Data on race and ethnicity were not collected. Median follow-up was 50 months (IQR 42–58). 4-year metastasis-free survival was 63% (80% CI 56–69) in the MDT group and 76% (69–81) in the ENRT group (HR 0·62 [80% CI 0·44–0·86]; p=0·063). The most common grade 3 adverse events were urinary incontinence (six [6%] of 97 in the MDT group vs nine [10%] in the ENRT group) and diarrhoea (one [1%] in the MDT group vs two [2%] in the ENRT group). No treatment-related deaths occurred.<br/>Interpretation To our knowledge, this is the first randomised trial for metachronous PET-detected nodal recurrences comparing two local treatment approaches (MDT and ENRT) in combination with 6 months of androgen deprivation therapy. By showing an improved metastasis-free survival with ENRT, this trial establishes ENRT as a potential standard treatment approach, awaiting a phase 3 trial confirming these results.<br/>Funding Movember Foundation, Kom Op Tegen Kanker, Stichting tegen Kanker.

    Bladder Adjuvant Radiotherapy

    ForHigh-risk urothelial MIBC post-RC (pT3-4, pN+, margin+, or ≤10 nodes), periopera

    TL;DR2-yr LRFS 87.1% vs 76.0% (HR 0.43, p=0.04) favoring adj pelvic IMRT post-cystectomy in high-risk MIBC; DFS/OS NS.

    vs leading data
    • Adj RT + IO interaction unstudied; generalizability to current practice uncertain

    Radiation Curative Phase 3 RCT Early signal

    6 details
    Methods
    • 🔍 Phase III RCT, N=153 (RT=77, Obs=76); stratified by nodal involvement and chemo timing
    • 🔍 Eligibility: any of pT3-4, pN1-3, margin+, or ≤10 nodes dissected; 62% pT3-T4, 41% pN+
    • 💊 Stoma-sparing IG-IMRT 50.4Gy/28fx to cystectomy bed and pelvic nodes
    CONSORT flow
    Randomized 153
    ↓
    Adjuvant RT
    allocated 77
    Observation
    allocated 76
    Results
    • 📊 RT vs observation outcomes, median f/u 47mo
      EndpointRTObsHR (95% CI)p
      2-yr LRFS (1°)87.1%76.0%0.43 (0.20-0.96)0.04
      DFS71.6%58.7%0.62 (0.36-1.05)—
      BCSS79.6%65.0%0.59 (0.33-1.10)—
      OS70.4%57.4%0.78 (0.49-1.26)—
    Critique
    • ⚠️ Small N (153); underpowered for OS; CI crosses 1.0 on all secondary endpoints
    • ⚠️ None received immunotherapy; cohort predates nivolumab post-cystectomy standard (CheckMate 274)
    Open questions
    • OS benefit with longer follow-up?
    • Safety and efficacy of adj RT combined with IO (nivolumab) post-RC
    • Optimal selection: does pN+ subgroup derive greatest locoregional benefit?
    📚 Sources · 📄 1 paper
    📄 PAPER Murthy; Maitre; Pal et al. · Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2026-05)
    Bladder Adjuvant Radiotherapy: Phase III Multicenter Randomized Controlled Trial of Adjuvant Radiotherapy or Observation for Postcystectomy Muscle-Invasive Bladder Cancer.
    PMID 42166701 → doi
    Abstract
    PURPOSE: To report the primary analysis of a multicenter, phase III randomized trial of adjuvant radiotherapy (RT) after chemotherapy and radical cystectomy (RC) in patients with high-risk muscle-invasive bladder cancer (MIBC).<br/><br/>METHODS: Patients with nonmetastatic urothelial MIBC at high risk after RC (any one of: T3-4, N1-3, margin positive, &#x2264;10 nodes dissected) were randomly assigned 1:1 to adjuvant RT or observation (Obs), stratified by nodal involvement (yes/no) and chemotherapy (neoadjuvant/adjuvant/none). Stoma-sparing IG-IMRT 50.4Gy in 28 fractions was prescribed to the cystectomy bed and pelvic nodes. The primary end point was 2-year locoregional recurrence-free survival (LRFS), and the secondary end points were disease-free survival (DFS), bladder cancer-specific survival (BCSS), and overall survival (OS).<br/><br/>RESULTS: From June 2016 to May 2024, 153 patients were randomly assigned (Obs = 76, RT = 77), with 62% and 41% of patients having pT3-T4 and pN+ stages, respectively. Over 90% of the patients received systemic chemotherapy (71% neoadjuvant and 20% adjuvant), and none received immunotherapy. After a median follow-up of 47 months, the 2-year LRFS was significantly higher with adjuvant RT versus observation (87.1% v 76.0%, hazard ratio [HR], 0.43 [95% CI, 0.20 to 0.96], P = .04). The DFS was 71.6% versus 58.7% (HR, 0.62 [95% CI, 0.36 to 1.05]), BCSS was 79.6% versus 65.0% (HR, 0.59 [95% CI, 0.33 to 1.10]), and OS was 70.4% versus 57.4% (HR, 0.78 [95% CI, 0.49 to 1.26]) for RT and Obs, respectively.<br/><br/>CONCLUSION: Adjuvant pelvic IMRT after radical cystectomy and perioperative chemotherapy suggests an improvement in locoregional control in patients with high risk urothelial MIBC with no additional severe toxicity.

    Single-fraction SABR for primary NSCLC and pulmonary oligometastases (pooled analysis, n=1687)

    ForInoperable primary NSCLC or pulmonary oligomets, multi-institution pooled cohort

    TL;DR2yr LC 90-93%, G3+ AEs 2.9% across 1687 pts treated with SF-SABR at 3 institutions.

    vs leading data
    • SAFRON-II (phase 2 RCT, Peter Mac) showed SF-SABR non-inferior vs multi-fraction for peripheral NSCLC; this series extends to central tumors and oligomets across 3 institutions

    Radiation Curative Meta-analysis Early signal

    Single-fraction SABR for primary NSCLC and pulmonary oligometastases (pooled analysis, n=1687)
    EndpointPrimary NSCLC (n=1200)Oligomets (n=487)
    1-yr OS84% (95% CI 82, 86)90% (95% CI 86, 92)
    2-yr OS67% (95% CI 64, 69)75% (95% CI 71, 79)
    Median OS (mo)40 (95% CI 36, 43)51 (95% CI 42, 58)
    +2 more figures
    LC 90-93% at 2yr; NSCLC: PFS 30mo, OS 3.5yr; oligomets: PFS 11mo, OS >4yr; G3+ 2-3%
    LC 90-93% at 2yr; NSCLC: PFS 30mo, OS 3.5yr; oligomets: PFS 11mo, OS >4yr; G3+ 2-3%
    AE (primary NSCLC, n=789): G3+ 23/789 (2.9%), G2+ 124/789 (15.7%), any AE 215/789 (27%)
    AE (primary NSCLC, n=789): G3+ 23/789 (2.9%), G2+ 124/789 (15.7%), any AE 215/789 (27%)
    7 details
    Methods
    • 🔍 Three-institution pooled retrospective: Peter Mac, Cleveland Clinic, Roswell Park
    • 🔍 N=1687: 1200 primary NSCLC + 487 pulmonary oligomets
    Results
    • 📊 LC 90-93% at 2yr across both cohorts; isolated local/locoregional failure very uncommon
    • 📊 Median PFS
      • Primary NSCLC: 30mo
      • Pulmonary oligomets: 11mo
    • 📊 AEs (primary NSCLC, n=789)
      • G3+: 23/789 (2.9%)
      • G2+: 124/789 (15.7%)
      • Any AE: 215/789 (27%)
    Critique
    • ⚠️ AE data excludes Roswell Park — toxicity rates incomplete for the full 1687-pt cohort
    • ⚠️ Single-arm pooled retrospective; no randomised comparator vs conventional multi-fraction SBRT
    Open questions
    • Non-inferiority vs multi-fraction SBRT in a phase 3 RCT?
    • Optimal pt selection for SF-SABR (tumor size, location, histology)?
    • Long-term LC durability beyond 5 years?
    📚 Sources · 🐦 1 tweet

    HEAT Trial NCT01794403

    ForLow-intermediate risk localized PCa, IPSS <12, ADT-eligible

    TL;DRSBRT 5 fx non-inferior to EHRT for BF (7% vs 7.4%, p-noninferiority=0.007 at 4.25y) in low-int risk PCa; interim data.

    vs leading data
    • Prior AHRT RCTs (HYPO-RT-PC, PACE-B, NRG-GU005) excluded ADT or used heterogeneous controls; HEAT is first head-to-head with modern IMRT + ADT permitted in both arms

    Radiation Curative Phase 3 RCT Early signal

    HEAT Trial
    EndpointAHRTEHRTp-noninferiority
    Biochemical failure (Phoenix) at 4.25y7%7.4%0.007
    +1 more figure
    Trial schema: AHRT 36.25 Gy/5 fx (GTV SIB 40 Gy) vs EHRT 70.2 Gy/26 fx IMRT. Accrual goal n=456; n=420 evaluable.
    Trial schema: AHRT 36.25 Gy/5 fx (GTV SIB 40 Gy) vs EHRT 70.2 Gy/26 fx IMRT. Accrual goal n=456; n=420 evaluable.
    9 details
    Methods
    • 🔍 AHRT: 36.25 Gy in 5 fx (7.25 Gy/fx, GTV SIB to 40 Gy); EHRT: 70.2 Gy in 26 fx using IMRT
    • 🔍 Low-intermediate risk PCa; IPSS <12; ADT permitted (≤6 months) in both arms; 28% received ADT
    • 🔍 Median FU 59.7 months; 82.4% intermediate-risk; n=156 randomized, n=142 analyzed (interim)
    Results
    • 📊 1° EP (biochemical failure, Phoenix def): 7% AHRT vs 7.4% EHRT at 4.25y, p-noninferiority = 0.007
    • 📊 Acute G2+ GI toxicity lower with AHRT; no absolute rates reported in source
    • 📊 Late G2+ GI and acute/late G2+ GU toxicities comparable between arms
    Critique
    • ⚠️ Interim analysis only; accrual goal n=456 (420 evaluable planned); non-inferiority not yet confirmed at final analysis
    • ⚠️ Non-inferiority margin 12% is wide relative to observed BF rates of 7-7.4%
    • ⚠️ Clinician-reported toxicity; laxative/psyllium use scored as G2 GI event
    Open questions
    • Non-inferiority confirmed at final analysis (n=456 accrual goal)?
    • Late toxicity differences beyond 5yr follow-up?
    • Does short-course ADT differentially affect BCF rates by fractionation arm?
    📚 Sources · 🐦 2 tweets

    INRT-AIR & DARTBOARD (ENI omission, HNSCC)

    ForHNSCC oropharynx/larynx/hypopharynx, stage I-IVB, definitive CRT candidates

    TL;DR5-yr solitary ENI recurrence 0% in 117 HNSCC pts on AI-assisted INRT omitting elective nodal fields.

    Radiation Curative Phase 2 trial Early signal

    5-yr solitary ENI recurrence 0%; 3-yr LR 9.5%, regional recurrence 4.3%, DM 11%; 5-yr OS 87%, PFS 74%; MDADI composite 84.9 at 12mo
    5-yr solitary ENI recurrence 0%; 3-yr LR 9.5%, regional recurrence 4.3%, DM 11%; 5-yr OS 87%, PFS 74%; MDADI composite 84.9 at 12mo
    8 details
    Methods
    • 🔍 INRT: AI-assisted identification of suspicious lymph nodes, ENI fields entirely omitted
    • 🔍 Eligibility
      • Sites: oropharynx, larynx, hypopharynx
      • Stage I-IVB (excl T1-2N0 larynx)
      • PET/CT + neck CT required for staging
    Results
    • 📊 5-yr risk of solitary elective nodal recurrence: 0% (N=117, median f/u 3.4yr)
    • 📊 5-yr OS 87%, 5-yr PFS 74%
    • 📊 3-yr LR 9.5%, regional recurrence 4.3%, DM 11%
    • 📊 MDADI composite 84.9 at 12mo (no significant post-treatment decline)
    Critique
    • ⚠️ No randomized comparator; toxicity reduction vs standard ENI-CRT unconfirmed
    • ⚠️ N=117 pooled from 2 trials; cross-trial heterogeneity in eligibility and AI model not reported
    Open questions
    • RCT comparing INRT vs standard ENI-CRT needed before non-trial adoption
    • Late toxicity reduction and QoL benefit beyond 12 months
    • Generalizability of AI-assisted nodal staging to community practice
    📚 Sources · 🐦 1 tweet

    FASTRACK II (TROG 15.03) NCT02613819

    ForInoperable/surgery-declining primary RCC, T1b-dominant, median age 77

    TL;DR100% LC at 84 months in primary RCC (N=70) treated with SABR; G3 AE 10%, no grade 4 events or cancer deaths.

    vs leading data
    • Thermal ablation (cryo/RFA) LC decreases for T1b+ tumours; SABR's 100% LC in this T1b-dominant cohort addresses where ablation underperforms

    Radiation Curative Phase 2 trial Early signal

    9 details
    Methods
    • 🔍 Non-randomised phase 2, N=70 (71 enrolled, 1 withdrew consent), 8 sites (AU/NL); median f/u 62 months (IQR 60-72)
    • 🔍 Eligibility: medically inoperable, high-risk, or surgery-declining; ECOG ≤2; tumour ≤10cm; N0-N1
    • 🔍 SABR dose: 26 Gy × 1 for tumour ≤4cm; 42 Gy/3fx at 48h intervals for >4cm
    • 🔍 Median age 77 (IQR 70-82); 70% male; T1b dominant (56%); median tumour 46mm (IQR 37-55)
    Results
    • 📊 1° EP: 100% freedom from local progression at 36, 60, and 84 months
    • 📊 No G4 events, no treatment-related deaths, no new long-term safety signals at 62-month median f/u
    Critique
    • ⚠️ G3 AEs within 9 months: 7 pts (10%)
      • Abdominal/flank/tumour pain: 4 (6%)
      • Nausea/vomiting: 3 (4%)
      • Colonic obstruction: 2 (3%)
      • Diarrhoea: 1 (1%)
    • ⚠️ Single-arm, all inoperable/surgery-declining; no randomised comparator vs partial nephrectomy or ablation — LC durability not generalisable to operable candidates
    • ⚠️ Varian-funded (RT equipment manufacturer); sponsor interest aligned with positive SABR outcome
    Open questions
    • Randomised comparison vs thermal ablation or partial nephrectomy in operable candidates
    • OS benefit vs active surveillance in truly inoperable primary RCC
    • Durability beyond 84 months for T2a/T3a subset (small N)
    📚 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.

    OLIGOMA NCT04495309

    ForMetastatic breast, ≤5 mets, any systemic therapy line

    TL;DRmPFS 35.8 vs 20.4 mo, HR 0.48; first RCT positive for MDT in oligometastatic breast cancer.

    vs leading data
    • Claimed first RCT positive for MDT PFS specifically in oligomet breast; confirmatory trials ongoing (TAORMINA, STEREO-SEIN, LARA, CLEAR)

    Radiation Palliative Phase 2 trial Early signal

    OLIGOMA
    +2 more figures
    QoL 12 wk: QLQ-C30 mean 72.2 vs 74.3; diff -2.1 (95% CI -9.2 to 5.1); NI margin -10 pts, met
    QoL 12 wk: QLQ-C30 mean 72.2 vs 74.3; diff -2.1 (95% CI -9.2 to 5.1); NI margin -10 pts, met
    OLIGOMA
    5 details
    Methods
    • 🔍 Randomised; metastatic breast any line, ≤5 lesions; systemic ± ablative RT to all mets
    • 🔍 >80% had 1-3 mets; 2/3 of lesions bone mets; majority ER/PR+, HER2- in 1st-line
    CONSORT flow
    Randomized 87
    ↓
    Systemic + ablative RT
    allocated 43
    Systemic alone
    allocated 44
    Results
    • 📊 QoL 12-wk co-primary met: QLQ-C30 diff -2.1 (-9.2 to 5.1), NI margin -10 pts (n=64)
    Critique
    • ⚠️ Stopped early: enrolled <20% of initial, <40% of amended target; N=87 total
    • ⚠️ HR CI very wide (0.25-0.91); no OS data reported
    Open questions
    • Which subgroups benefit most (therapy line, met burden, histology subtype)?
    • OS benefit not yet demonstrated; durability of PFS gain uncertain
    • Will confirmatory data from ongoing breast-specific MDT RCTs align?
    📚 Sources · 🐦 3 tweets

    Dutch BCRG Breast Boost (Modern Systemic Era)

    ForEarly-stage breast cancer, BCT + WBRT, modern systemic therapy era, stratified b

    TL;DR10-yr IBTR 1.2% with or without boost in 0-2 risk-factor BCT pts; boost omission appears safe in modern systemic era.

    vs leading data
    • vs EORTC 22881/10882 (Bartelink, Lancet Oncol 2015): boost reduced IBTR ~50% in pre-modern-systemic era; absolute benefit appears negligible for 0-2 rf pts now

    Radiation Curative Real-world evidence Early signal

    Dutch BCRG Breast Boost (Modern Systemic Era)
    Risk factors5yr IBTR (no boost)5yr IBTR (boost)10yr IBTR (no boost)10yr IBTR (boost)
    0-2 (N=15,085/13,845)0.6%0.7%1.2%1.2%
    ≥3 (N=149/733)1.3%2.9%2.7%3.3%
    Uncertain (N=592/944)0.8%3.3%1.4%3.6%
    +1 more figure
    Dutch BCRG Breast Boost (Modern Systemic Era)
    5 details
    Methods
    • 🔍 Dutch registry retrospective cohort, BCT pts 2012-2016; boost vs no-boost allocation was clinical, non-randomized
    • 🔍 Five risk factors scored: age ≤40, grade 3, TNBC, inadequate guideline-directed systemic therapy, no pCR post-NACT in TNBC/HER2+
      • 0-2 rf: large majority (n=15,085 no boost, n=13,845 boost)
      • ≥3 rf: small high-risk minority (n=149 no boost, n=733 boost)
    Results
    • 📊 Assisi decision thresholds: boost omissible if 10yr IBTR <3% (boosted cohort) or <6% (no-boost); only boosted ≥3-rf pts exceeded threshold at 10yr (3.3%)
    Critique
    • ⚠️ Non-randomized; no-boost selection reflects clinician risk stratification, not random allocation; confounding by indication expected
    • ⚠️ No-boost arm for ≥3 rf pts very small (n=149); insufficient to characterize boost omission in high-risk subgroup
    Open questions
    • RCT needed to confirm boost omission equivalence in 0-2 risk-factor pts
    • Optimal RT boost strategy for ≥3 risk-factor pts where boosted 10yr IBTR still exceeds Assisi threshold
    📚 Sources · 🐦 1 tweet

    RAPCHEM

    ForNode-positive breast cancer achieving pathological nodal response after neoadjuv

    TL;DR10yr locoregional recurrence <3% with nodal-response-guided RT de-escalation after neoadjuvant in breast cancer.

    vs leading data
    • Complete RT omission remains separately under validation via B-51 and other prospective studies

    Radiation Curative Phase 2 trial Early signal

    3 details
    Methods
    • 🔍 De-escalation strategy: locoregional RT field/dose reduced based on nodal pathological response after neoadjuvant chemotherapy
    Results
    • 📊 Locoregional recurrence <3% at 10yr with pathological nodal response-guided RT de-escalation post-neoadjuvant
    Critique
    • ⚠️ No CI, HR, or comparator arm outcome reported in source; design not confirmed as randomized
    Open questions
    • Can RT be safely omitted (not just de-escalated) after pathological nodal response?
    • Will B-51 confirm safety of complete locoregional RT omission post-neoadjuvant?
    📚 Sources · 🐦 1 tweet

    OligoCare

    ForOligometastatic solid tumors, multiple histologies, 1-5 mets, SABR-eligible

    TL;DR88.6% local control at 3yrs across 2447 pts; CRC shows worst local control despite highest delivered dose.

    vs leading data
    • Adds real-world multi-institutional scale to phase II RCT signals (SABR-COMET, STOMP, ORIOLE); direction consistent

    Radiation Real-world evidence Early signal

    OligoCare
    Tumor type1-yr local failure3-yr local failure
    CRC9.3%19.6%
    Breast4.1%11.3%
    NSCLC6.0%9.8%
    Prostate2.7%8.1%
    +2 more figures
    Overall local in-field progression: 5.0% at 1yr, 11.4% at 3yrs. N=2447, median f/u 31 months.
    Overall local in-field progression: 5.0% at 1yr, 11.4% at 3yrs. N=2447, median f/u 31 months.
    OligoCare
    7 details
    Methods
    • 🔍 Prospective multi-institutional EORTC registry (OligoCare), 57 sites; interim analysis
    • 🔍 2447 pts, 3533 lesions; median age 69 (range 28-94), 69% male; median f/u 31 months
    Results
    • 📊 88.6% local control at 3yrs
    • 📊 Minimum PTV dose: most critical technical factor for local control
    Critique
    • ⚠️ De novo OMD better LC than repeat OMD (attributed to higher delivered dose in de novo setting)
    • ⚠️ CRC worst LC despite highest median dose per fraction; relative radioresistance; combination treatment or dose escalation strategies may be needed
    • ⚠️ Single-arm interim registry; no comparator; histology mix and 6-yr enrollment window limit subgroup inference
    Open questions
    • Optimal approach for CRC oligomets (combination treatment, dose escalation?)
    • Minimum PTV dose thresholds for adequate LC across histologies
    • Whether LC advantage for de novo vs repeat OMD reflects dose, biology, or selection
    📚 Sources · 🐦 1 tweet

    EXTEND

    ForOligometastatic solid tumors, multiple histologies, all disease sites, systemic

    TL;DRPhase II RCT of MDT added to SOC for oligometastatic solid tumors, all histology baskets; no effect size in source tweet.

    vs leading data
    • Broadens prior oligometastatic MDT RCT signal (STOMP, ORIOLE, SINDAS) to multi-histology population with prospective design

    Radiation Curative Phase 2 trial Early signal

    5 details
    Methods
    • 🔍 Phase II randomized, multi-histology basket design; all solid tumor histologies eligible
    • 💊 MDT + SOC vs SOC alone; metastasis-directed therapy (radiation-based ablation) added to ongoing systemic SOC
    • 🔍 ctDNA correlatives presented at ESTRO26 synchronously with primary JCO publication
    Results
    • 📊 Primary aggregated analysis across all tumor histology baskets; no effect size reported in source tweet
    Critique
    • ⚠️ Basket aggregation across histologies: pooled primary estimate may obscure site-specific heterogeneity in MDT benefit
    Open questions
    • Which histology baskets drove the primary endpoint signal?
    • Do ctDNA dynamics at baseline or on-treatment predict MDT benefit?
    • Does Phase III confirmation across histologies follow?
    📚 Sources · 🐦 1 tweet

    PRIME NCT03561961

    ForHigh-risk, very high-risk, or node-positive non-metastatic prostate cancer

    TL;DRSBRT 5fx with pelvic RT: G3+ toxicity <1%, comparable early BFFS to moderate hypo (N~434); mature 4-5yr endpoint pending.

    vs leading data
    • vs HYPO-RT-PC (10-yr mature, HR 0.84, CI 0.69-1.03): non-inferior but node-negative, no ADT, no pelvic RT

    Radiation Curative Phase 3 RCT Early signal

    PRIME
    ToxicitySBRT 5fxModerate Hypo 25fx
    Acute GU G2+~5.4%~4.0%
    Acute GI G2+~2.2%~3.7%
    Acute G3+ GU/GI<1%<1%
    Late GU G2+ (1-2yr)~10-12%~9-11%
    Late GI G2+ (1-2yr)~5-7%~4-6%
    Late G3+ GU/GI<1%<1%
    +1 more figure
    HYPO-RT-PC 10-yr FFS: 72% (42.7 Gy/7fx) vs 65% (78 Gy/39fx), adjusted HR 0.84 (95% CI 0.69-1.03), non-inferiority confirmed. PRIME BFFS not yet mature.
    HYPO-RT-PC 10-yr FFS: 72% (42.7 Gy/7fx) vs 65% (78 Gy/39fx), adjusted HR 0.84 (95% CI 0.69-1.03), non-inferiority confirmed. PRIME BFFS not yet mature.
    7 details
    Methods
    • 🔍 Phase III open-label non-inferiority, N ~434; Tata Memorial + collaborating centers, India
    • 🔍 High-risk, very high-risk, and/or node-positive non-metastatic prostate cancer; ECOG 0-2; PSMA PET/CT staging allowed
    • 🔍 Both arms: prostate + whole-pelvis RT + long-course ADT (~2yr); SIB to positive nodes in SBRT arm
    • 💊 Fractionation
      • Arm A (SBRT): 36.25 Gy/5fx (7.25 Gy/fx), every other day
      • Arm B (moderate hypo): ~68 Gy/25fx (2.7 Gy/fx), 5fx/wk
    Results
    • 📊 1° EP: BFFS (Phoenix nadir +2 ng/mL); interim only, mature 4-5yr data pending
    • 📊 Early BFFS, MFS, OS: no significant differences; no inferiority signal for SBRT at interim
    Critique
    • ⚠️ Interim analysis (1-2yr f/u) only; 4-5yr primary endpoint not yet reached; non-inferiority pending
    Open questions
    • Mature BFFS/MFS/OS at 4-5yr follow-up to confirm non-inferiority
    • Long-term late toxicity (>2yr) profile with 5-fraction pelvic SBRT
    • Impact of PSMA PET/CT staging on outcomes vs conventional imaging cohorts
    📚 Sources · 🐦 1 tweet

    PIVOTALboost

    ForHigh-risk localised prostate cancer, moderately fractionated 20-fraction RT

    TL;DRLate G2+ bowel 6.5-8.7%, bladder 16.5-24.1% at 2yr, no increase with focal boost or pelvic node RT vs prostate-only (N=1465).

    vs leading data
    • vs FLAME (JCO 2021): focal boost improved 5yr bFFS in high-risk prostate with no significant late GI/GU toxicity increase; PIVOTALboost 2yr safety consistent, but FLAME used conventional fractionation (39fr)

    Radiation Curative Phase 3 RCT Early signal

    PIVOTALboost
    ArmBowel G2+Bladder G2+
    Prostate (n=281)8.2% (5.7-11.7)19.5% (15.5-24.4)
    Prostate+Boost (n=345)8.7% (6.3-12.1)24.1% (20.2-28.7)
    Prostate+Nodes+Boost (n=347)6.5% (4.5-9.5)16.5% (13.1-20.6)
    +1 more figure
    PIVOTALboost
    5 details
    Methods
    • 🔍 Phase 3 RCT, N=1465, 39 UK centres; 3 arms (prostate, prostate+boost, prostate+pelvic+boost); 20-fraction moderately hypofractionated RT
    • 🔍 High-risk localised prostate cancer; 1° EP biochemical/clinical failure — efficacy data not reported here; secondary toxicity endpoints presented
    Results
    • 📊 Early bowel side effects increased with pelvic node RT; resolved by 18 weeks post-RT
    • 📊 No significant differences in G2+ bowel or bladder toxicity at 2 years across arms (973 pts, 74% with ≥2yr f/u)
    Critique
    • ⚠️ 2-year late toxicity is preliminary for prostate RT; G3+ late effects can emerge at 5+ years
    Open questions
    • Primary efficacy (biochemical/clinical failure) not yet reported
    • Late toxicity beyond 2 years needed to confirm durability
    📚 Sources · 🐦 1 tweet

    PACE-NODES

    ForHigh-risk localised prostate (T3a-T4, Gleason 8-10, or PSA >20), planned ADT 12-

    TL;DRPPN-SBRT increases G≥2 GI toxicity (28% vs 21%) vs prostate-only SBRT; symptoms resolved by 12wk; GU toxicity equivalent; efficacy endpoint pending.

    vs leading data
    • POP-RT (NEJM 2021): nodal RT improved bFFS with moderate hypofractionation in high-risk pts; PEACE-2 showed no nodal RT benefit (conventional fractionation); PACE-NODES tests the same hypothesis with SBRT fractionation for nodes

    Radiation Curative Phase 3 RCT Early signal

    PACE-NODES
    EndpointPPN-SBRTP-SBRT
    G≥2 GI toxicity (12wk)28%21%
    +1 more figure
    PACE-NODES
    8 details
    Methods
    • 🔍 Phase 3 RCT, 1:1; high-risk localised prostate (T3a-T4, Gleason 8-10, or PSA >20), planned ADT 12-36mo; target N=1128, 1166 randomised
    • 💊 P-SBRT: 36.25Gy/5f (prostate); PPN-SBRT: 36.25Gy/5f (prostate) + 25Gy/5f (nodes), alternate days
    Results
    • 📊 G≥2 GI toxicity over 12wk: 28% PPN-SBRT vs 21% P-SBRT
    • 📊 GI symptoms resolved; no difference between arms at 12 weeks
    • 📊 EPIC-26 bowel domain worse at 4 weeks in PPN-SBRT arm
    • 📊 No difference in acute GU toxicity (CTCAE or patient-reported)
    Critique
    • ⚠️ 11% PPN-SBRT vs 4% P-SBRT did not receive allocated treatment, mostly due to planning constraints not being met
    • ⚠️ Primary endpoint (time to biochemical/clinical failure) not yet mature; this is an acute toxicity interim report only
    Open questions
    • Does nodal SBRT improve bFFS/cFFS vs prostate-only SBRT (primary endpoint pending)?
    • Late GI/GU toxicity profile with extended follow-up
    • Whether SBRT nodal fractionation recapitulates bFFS benefit seen with POP-RT moderate hypofractionation
    📚 Sources · 🐦 1 tweet

    PEACE-2

    ForVery high-risk localized prostate Ca (≥2 of Gleason ≥8, T3-T4, PSA ≥20), N0M0

    TL;DRPelvic RT adds no significant cPFS benefit over prostate-only RT in very high-risk PCa with 3yr ADT (HR 0.81, p=0.088) at interim analysis.

    vs leading data
    • POP-RT (2yr ADT, conventional imaging, 74-76 Gy EQD2) showed significant pelvic RT benefit across bFFS, cFFS, MFS

    Radiation Curative Phase 3 RCT Early signal

    PEACE-2
    Arm7-yr cPFSHR (95% CI)p
    Pelvic RT67.1% [61.6; 72.2]0.81 [0.63; 1.03]0.088
    Prostate-only RT62.9% [57.4; 68.1]reference—
    +1 more figure
    PEACE-2
    EndpointPOP-RT HR (95% CI)POP-RT pPEACE-2 HR (95% CI)PEACE-2 p
    bFFS/bPFS0.50 (0.42-0.61)<0.0010.97 (0.81-1.16)0.73
    cFFS/cPFS0.74 (0.61-0.90)0.0020.81 (0.63-1.03)0.09
    MFS0.72 (0.58-0.89)0.0020.93 (0.74-1.17)0.54
    7 details
    Methods
    • 🔍 Trial design
      • Phase III 2×2 factorial (pelvic vs prostate-only RT × ± cabazitaxel ×4)
      • Very high-risk PCa: N0M0, ≥2 of Gleason ≥8, T3-T4, PSA ≥20
      • ADT 3yr + 78 Gy EQD2 dose-escalated IMRT; PSMA PET/CT staging; accrual 2018-2023
    CONSORT flow
    Randomized 761
    ↓
    Pelvic RT
    allocated 381
    Prostate-only RT
    allocated 380
    Results
    • 📊 All secondary endpoints (bPFS, MFS, CSS, OS) also non-significant with pelvic RT
    Critique
    • ⚠️ Interim analysis at ESTRO 2026 (median f/u ~5.5yr); final prespecified primary analysis pending
    • ⚠️ PSMA PET/CT may exclude occult metastatic pts who drove pelvic RT benefit in the conventional-imaging era
    • ⚠️ Longer ADT (3yr vs 2yr) + dose escalation may reduce incremental pelvic RT gain
    • ⚠️ No added toxicity: comparable G≥2 GU rates in both arms
    • ⚠️ Blanchard: <1 in 10 dying from PCa at 10yr challenges the 'very high-risk' label in modern-imaged pts
    Open questions
    • Will final analysis confirm null benefit of pelvic RT with modern staging and 3yr ADT?
    • Does PSMA PET/CT staging explain divergence from POP-RT by excluding occult metastatic pts?
    • Which pts still benefit from elective pelvic RT in the contemporary dose-escalated ADT era?
    📚 Sources · 🐦 2 tweets

    RCC SBRT 5-year LC

    TL;DR100% 5-yr local control for RCC treated with SBRT; no additional endpoints in source.

    vs leading data
    • consistent with FASTRACK II (single-arm phase 2, primary inoperable RCC, high LC at 62-mo median f/u)

    Radiation Curative Early signal

    3 details
    Results
    • 📊 5-yr LC: 100% (per 💯 emoji in source tweet; no numeric table provided)
    Critique
    • ⚠️ N, fractionation, eligibility, and survival endpoints absent from source
    • ⚠️ design not specified; likely single-arm phase 2 — no comparator arm
    Open questions
    • OS/RFS benefit vs partial nephrectomy or thermal ablation
    • Optimal fractionation by tumor size and collecting system proximity
    📚 Sources · 🐦 1 tweet