onc brain

About · curated by Nick Boehling, MD · @nb2276

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    PrTK03 (aglatimagene besadenovec + EBRT) NCT01436968

    ForIntermediate/high-risk localized prostate cancer, ECOG 0–2, planning definitive

    TL;DRDFS HR 0.70 (0.52–0.94), p=0.016 favoring aglatimagene + valacyclovir + EBRT vs placebo in intermediate/high-risk localized prostate cancer.

    Combined Curative Phase 3 RCT Practice-changing

    10 details
    Methods
    • 🔍 Phase 3 double-blind placebo-controlled, N=745, 2:1 allocation, 51 US/Puerto Rico centers
    • 🔍 Intermediate or high-risk M0 localized prostate cancer; ECOG 0–2; EBRT 78 Gy/2 Gy or hypofractionated; ADT optional
    • 💊 Intraprostatic aglatimagene (CAN-2409, replication-defective adenoviral HSV-TK vector) × 3 courses + valacyclovir prodrug; immune bystander cytotoxicity mechanism
    CONSORT flow
    Randomized 745
    ↓
    Aglatimagene + valacyclovir + EBRT
    allocated 496
    analyzed 479
    Placebo + valacyclovir + EBRT
    allocated 249
    analyzed 232
    Results
    • 📊 1° EP: DFS HR 0.70 (95% CI 0.52–0.94), p=0.016
    • 📊 Median DFS not reached (aglatimagene) vs 86.1 months (IQR 29.7–143.0) in placebo
    • 📐 Median follow-up 50.3 months (IQR 35.2–63.3)
    Critique
    • ⚠️ G3+ TEAEs similar between arms
      • Aglatimagene: 8% (40/479); placebo: 7% (17/232)
      • Most common G3+: AKI — 2% both arms
      • SAEs: 6% aglatimagene vs 7% placebo; treatment-related SAEs 2% both arms
      • No treatment-related deaths
    • ⚠️ 1° EP is DFS (composite: recurrence or death), not OS; OS data not reported in source
    • ⚠️ 50-month median f/u likely underpowers late events; prostate cancer recurrences extend 10+ years post-RT
    • ⚠️ Sponsor-funded (Candel Therapeutics + NIH); 79% White cohort — generalizability to diverse populations limited
    Open questions
    • OS benefit not yet established; long-term follow-up ongoing
    • Differential effect by risk category (intermediate vs high-risk)?
    • Sequencing with ARPI intensification for STAMPEDE-eligible pts
    📚 Sources · 📄 1 paper
    📄 PAPER Dykstra, Michael P.; Regan, Samuel N.; Yin, Huiying (Maggie) et al. · JCO Oncology Practice (2025-09)
    Androgen Deprivation Therapy Practice Patterns in High-Risk Prostate Cancer Treated With Definitive Radiotherapy: Prospective Results From a Statewide Quality Consortium
    PMID → doi
    Abstract
    PURPOSE The 2022 AUA/ASTRO guidelines recommend 18-36 months of androgen deprivation therapy (ADT) with definitive radiotherapy for localized, high-risk prostate cancer. The STAMPEDE M0 trial supports intensification with androgen receptor pathway inhibitors (ARPIs) for patients with ≥2 cT3/T4, Grade Group [GG] 4-5, prostate-specific antigen (PSA) ≥40 ng/mL, or cN1. Given advances in imaging, risk stratification, and treatment delivery, we characterized contemporary practice patterns using prospective data from the Michigan Radiation Oncology Quality Consortium (MROQC). METHODS Patients enrolled in MROQC with intact, high-risk M0/N0-1 prostate cancer were included. Clinical information, including intended ADT duration and ARPI use, was prospectively collected. The primary outcome was intended guideline-concordant ADT (GC-ADT, ≥18 months). Multivariable analyses (MVA) assessed associations between clinical factors and GC-ADT recommendations. We compared the adoption of ARPI with standard therapies before and after the publication of STAMPEDE M0. Facility-level variability was evaluated using a mixed-effects model, with the treatment site as a random intercept. RESULTS Between June 2020 and November 2024, 553 patients across 26 centers were included: cT3/4 (13.3%), cN1 (19.9%), GG 4-5 (75.0%), and PSA ≥20 ng/mL (40.0%). Overall, 91.3% were recommended ADT, with 67.0% being guideline-concordant. On MVA, GC-ADT was significantly associated with cN1 (odds ratio [OR], 2.94 [95% CI, 1.44 to 5.99]), GG (GG4 OR, 6.23 [95% CI, 2.85 to 13.62]; GG5 OR, 9.45 [95% CI, 4.46 to 20.06]), and PSA ≥40 (OR, 3.64 [95% CI, 1.22–10.87]). Facility-level variability persisted in the MVA ( P < .0001). Among the 27.9% who met meeting STAMPEDE criteria, ARPI recommendations increased from 0% prepublication to 23.2% afterward. CONCLUSION Within a statewide quality consortium, guideline-concordant ADT recommendations occurred in two thirds of patients, with ARPI intensification in under 25% among STAMPEDE-eligible patients. These findings highlight the need for individualized ADT strategies and collaborative efforts to standardize high-quality care.

    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

    Breast RT + Systemic Therapy Concurrency Review (Speers)

    TL;DRT-DXd ILD 9.6% vs T-DM1 1.6% (DESTINY-Breast05); ASCO26 PK-guided concurrency framework for breast RT + systemic agents.

    Combined Curative Consensus / guideline Confirmatory

    Breast RT + Systemic Therapy Concurrency Review (Speers)
    +3 more figures
    DESTINY-Breast05: ILD 9.6% T-DXd vs 1.6% T-DM1. RT timing (T-DXd arm): 10.7% sequential vs 9.6% concurrent. PI (5.4 mg/kg): ILD ~12%, fatal ~0.9%. COMBART 40 pts: acute tox 20%.
    DESTINY-Breast05: ILD 9.6% T-DXd vs 1.6% T-DM1. RT timing (T-DXd arm): 10.7% sequential vs 9.6% concurrent. PI (5.4 mg/kg): ILD ~12%, fatal ~0.9%. COMBART 40 pts: acute tox 20%.
    KEYNOTE-522 post-hoc: 1,174 pts, 715 received RT. Concurrent pembro + RT: numerically fewer G3-5 AEs vs sequential.
    KEYNOTE-522 post-hoc: 1,174 pts, 715 received RT. Concurrent pembro + RT: numerically fewer G3-5 AEs vs sequential.
    Breast RT + Systemic Therapy Concurrency Review (Speers)
    9 details
    Methods
    • 🔍 ASCO26 educational review: PK-guided concurrency framework for systemic therapy during breast/CW + RNI (adapted from ASCO Educational Book 2026)
    • 💊 Traffic-light summary: concurrent RT safety by agent class
      • CONTINUE: endocrine therapy (minimal radiosensitization), trastuzumab + pertuzumab (standard; no serious AEs concurrent)
      • CAUTION: T-DXd, CDK4/6i (large fields), T-DM1, pembro, olaparib, mTOR/PI3K agents
      • HOLD/SEQUENCE: anthracyclines/taxanes/platinum, capecitabine, veliparib, talazoparib
    • 💊 T-DXd (t½=6d): ILD dominant toxicity; reasonable concurrent with monitoring
      • PI (5.4 mg/kg): ILD ~12%, fatal ~0.9%
      • DESTINY-Breast05: ILD 9.6% T-DXd vs 1.6% T-DM1
      • RT timing in T-DXd arm: 10.7% sequential vs 9.6% concurrent - no effect on ILD
      • COMBART (40 pts concurrent RT/SRT): acute tox 20%
    • 💊 T-DM1 (t½=4d): CONTINUE during locoregional RT; CNS SRS radionecrosis is the do-not-ignore signal
    • 🔍 P-RAD (TBCRC-053): preop RT (0/9/24 Gy) + pembro in HR+/HER2-; 24 Gy arm: statistically significant T-cell infiltration increase at 2 weeks
    • 💊 PARPi sequencing
      • Olaparib: RT must complete 2-12 wks before starting; RadioPARP suggests concurrent safety in limited settings
      • Veliparib: AVOID concurrent (TBCRC 024: severe moist desquamation + fibrosis)
      • Talazoparib (t½=90hr): long PK tail favors sequential strategy
    • 💊 CDK4/6i: hold during large-field RT
      • Abemaciclib/ribociclib (t½=24-55hr): hold for large fields; concurrent feasible in trial setting only (NCT05996107)
      • Palbociclib (t½=28.8hr): practical to hold around RT; resume promptly after
    Results
    • 📊 KEYNOTE-522 post-hoc (1,174 pts, 715 received RT): concurrent pembro + RT numerically fewer G3-5 AEs vs sequential
    Critique
    • ⚠️ All concurrency guidance rests on post-hoc analyses, small prospective series, or retrospective cohorts; PK washout + sequential is safer default outside protocol
    Open questions
    • Optimal T-DXd concurrency window as ILD outcomes mature
    • Prospective CDK4/6i + RT data beyond NCT05996107
    • Whether P-RAD immune priming translates to survival benefit
    📚 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

    Neo-CRAG

    ForLocally advanced gastric/GEJ adenocarcinoma (cT3N2+, T4), peri-op XELOX eligible

    TL;DRAdding neoadj CRT to peri-op XELOX: mDFS 52.7 vs 24.4 mo, mOS 67.5 vs 37.6 mo in high-risk LAGC.

    vs leading data
    • LRR halved despite D2 resection: supports a genuine RT contribution beyond chemo-alone locoregional control

    Combined Curative Phase 3 RCT Confirmatory

    Neo-CRAG
    MetricCRTCT
    3-yr DFS55.6%42.4%
    Median DFS52.7 mo24.4 mo
    HR (95% CI)0.750 (0.607-0.928)—
    p0.008—
    7 details
    Methods
    • 🔍 N=620, 13 Chinese centers, 2013-2022; cT3N2+ or T4 gastric/GEJ; 36.3% EGJ primary
    • 🔍 CRT arm: 45 Gy/25 fractions concurrent after C1 chemo, with dose-reduced oxaliplatin (100 mg/m²) and capecitabine (825 mg/m²)
    CONSORT flow
    Randomized 620
    ↓
    CRT (XELOX + RT)
    allocated 310
    CT (XELOX)
    allocated 310
    Results
    • 📊 mOS 67.5 vs 37.6 months, HR 0.781 (0.628-0.970), p=0.025
    • 📊 Locoregional recurrence in R0-resected pts: 9.4% CRT vs 18.3% CT
    • 📊 Pathologic response (CRT vs CT)
      • pCR: 14.8% vs 6.2%
      • ypN0: 56.1% vs 36.4%
      • Tumor downstaging (ypT0-2): 42.6% vs 23.6%
    Critique
    • ⚠️ G3+ toxicity (CRT vs CT)
      • Hematologic: 14.6% vs 10.3%
      • Postop complications: 9.0% vs 7.6%
    • ⚠️ Backbone is XELOX, not FLOT; limits direct applicability to FLOT-era Western practice
    Open questions
    • Does adding RT to FLOT peri-op chemo confer similar DFS/OS benefit?
    • Optimal RT dose-fractionation in FLOT-era perioperative settings
    • Long-term LRR and OS durability beyond 5 years
    📚 Sources · 🐦 1 tweet

    SWOG/NRG S1914 NCT04214262

    ForInoperable early-stage NSCLC T1-3N0M0 ≤7cm, ≥1 recurrence risk factor

    TL;DRNo OS benefit from adding atezolizumab to SBRT (HR 1.15, p=0.63); closed for futility; G≥3 AEs 12% vs 2%.

    vs leading data
    • Contradicts prior phase II (PMID 37478883) that suggested IO benefit added to SBRT

    Combined Curative Phase 3 RCT Confirmatory

    7 details
    Methods
    • 🔍 Phase III RCT; N=403 eligible (201 SBRT / 202 atezo+SBRT); accrual closed at first interim for OS + PFS futility per prespecified design
    • 🔍 T1-3N0M0 NSCLC ≤7cm, inoperable or declined surgery, ≥1 recurrence risk factor; atezo 1200mg Q3W x8 cycles; SBRT 3-8 fx BED ≥100Gy initiated cycle 3
    • 🔍 Former/never smoker subgroup (56%): AS worse than S
      • OS: HR 2.50 (1.11-5.59), p=0.03
      • PFS: HR 2.16 (1.15-4.04), p=0.01
    CONSORT flow
    Assessed / enrolled 417
    ↓ 14 excluded
    Randomized 403
    ↓
    SBRT
    allocated 201
    SBRT + atezolizumab
    allocated 202
    Results
    • 📊 Efficacy outcomes: SBRT vs SBRT + atezolizumab
      EndpointHR (95% CI)p2yr SBRT2yr SBRT+atezo
      OS (1° EP)1.15 (0.65-2.01)0.6382%80%
      PFS1.35 (0.89-2.06)0.1671%60%
    • 📊 Failure patterns at cutoff
      PatternSBRTSBRT + atezo
      Local7%13%
      Regional2%3%
      Distant4%5%
    Critique
    • ⚠️ G≥3 AEs: 12% atezo arm (21 G3, 1 G4, 1 G5 respiratory failure) vs 2% SBRT (3 G3, 1 G4)
    • ⚠️ Median f/u 12 mo among survivors; 49 OS events at cutoff; local recurrence central review, PD-L1, and QoL analyses pending
    Open questions
    • Whether PD-L1-high or other biomarker-defined subsets benefit from IO addition
    • Mechanism behind excess local failures in the atezo arm
    • Durability of SBRT-alone outcomes beyond 2 years in high-risk pts
    📚 Sources · 📄 1 paper
    📄 PAPER Simone, Charles B.; Daly, Megan Eileen; Redman, Mary Weber et al. · Journal of Clinical Oncology (2025-06)
    SWOG/NRG S1914: Randomized phase III trial of induction/consolidation atezolizumab + SBRT versus SBRT alone in high risk, early-stage NSCLC.
    PMID → doi
    Abstract
    8003 Background: Stereotactic body radiation therapy (SBRT) is the standard of care (SoC) for early stage, medically inoperable non-small cell lung cancer (NSCLC). While rates of in-field control exceed 90%, regional and distant control after SBRT remain suboptimal. A prior phase II randomized trial suggested a benefit to adding immunotherapy (PMID 37478883). SWOG/NRG S1914 (NCT#04214262) is a randomized phase III trial evaluating neoadjuvant, concurrent and adjuvant atezolizumab plus SBRT for early-stage NSCLC vs SoC. Methods: Eligible patients (pts) had T1-3N0M0 NSCLC ≤7cm, were medically inoperable or declined surgery, and had ≥1 risk factor for increased recurrence: tumor diameter ≥2 cm, ≥6.2, moderately/poorly/undifferentiated histology. Randomization was to SoC SBRT (S [3-8 fractions, biologically effective dose ≥100 Gy]) or neoadjuvant, concurrent and adjuvant atezolizumab (AS [1200 mg IV Q3 week, 8 cycles]) with SBRT initiated with cycle 3, stratifying by tumor location (central vs peripheral), size (&lt;4 cm vs ≥4cm) and ECOG performance status (PS, 0-1 vs 2). The primary objective was to compare overall survival (OS) between the arms. Secondary objectives included comparisons of progression free survival (PFS), failure patterns, toxicity and quality of life (QoL). OS and PFS were compared using a 1-sided stratified log-rank test at the 2.5% level, confidence intervals (CI) are 95%. The accrual goal was 432 eligible pts. Results: From 8/13/20 - 9/6/24, 417 pts were randomized, 403 met eligibility [201 to S, 202 to AS]. Accrual closed at the first interim analysis for futility based on OS and PFS per design. Median follow-up for pts still alive was 12 (range: 0.03-49) months. Median age was 73 (41-91) years and 89% had PS 0-1. Median tumor diameter was 2.3 cm. No protocol treatment was received for 6 pts on S and 8 on AS. With 49 deaths, OS was not different between the arms (HR (CI): 1.15(0.65-2.01), p=0.63; 2-year OS: 82% S vs 80% AS). With 88 events, PFS was not better with AS (HR (CI): 1.35(0.89-2.06), p=0.16); 2-year PFS was 71% on S vs 60% on AS. Regional (2% vs 3%) and distant (4% vs 5%) failures were not different; there were more local failures with AS (13% vs 7%). Among former (53%)/never (3%) smokers, AS had worse OS and PFS than S (HR(CI): 2.50 (1.11-5.59), p=0.03); HR(CI): 2.16(1.15-4.04), p=0.01), respectively. Grade (G) ≥3 adverse event (AE) rates were 12% on AS (N=21 G3, 1 G4, 1 G5 respiratory failure) vs 2% on S (N=3 G3, 1 G4). Conclusions: In the first reported phase III trial to assess immunotherapy (IO) added to SBRT in early-stage NSCLC, IO failed to improve survival. More G ≥3 adverse events were reported with AS. Central review of local recurrence events is ongoing. Additional investigation into subgroups, PD-L1 status, QoL and blood/tissue are pending to determine whether there are subsets who can benefit from this combination and shed further insights into these findings. Clinical trial information: NCT04214262 .
    📝 https://ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.8003

    Bladder-preserving TMT for MIBC: prognostic factors (ESTRO 2026)

    ForcT2-T4aNOMO MIBC, median age 76, selected for organ-preserving TMT

    TL;DRCLR 63.7% in 369 MIBC pts on TMT; 5-FU-based CRT (OR 4.9) and portal imaging frequency independently predicted CLR.

    vs leading data
    • CLR 63.7% and salvage cystectomy 9.7% consistent with published international TMT series

    Combined Curative Retrospective Confirmatory

    Bladder-preserving TMT for MIBC: prognostic factors (ESTRO 2026)
    8 details
    Methods
    • 🔍 Multicenter retrospective cohort, Spain 2010-2022; N=369, median age 76, 85% male, cT2-T4aNOMO
    • 🔍 TMT = maximal TURBT + concurrent chemoradiotherapy; 1° EP: CLR; multivariable logistic regression
    Results
    • 📊 CLR: 63.7%; salvage cystectomy: 9.7%
    • 📊 Disease progression 28.8%: local 10.1%, systemic 10.7%, combined 8.7%
    • 📊 CLR associated with lower local recurrence and better survival (no OS/CSS HR in source)
    • 📐 Independent predictors of CLR (multivariable)
      • 5-FU-based CRT → higher CLR: OR 4.9 (95% CI 1.1-22.1), p=0.038
      • Weekly portal imaging → lower CLR: OR 0.35 (95% CI 0.20-0.60), p<0.001
    Critique
    • ⚠️ Retrospective, 12-yr accrual (2010-2022): era effects likely across RT technique and CRT regimen selection
    • ⚠️ Portal imaging OR 0.35 is counterintuitive; probably proxies older/less precise RT delivery, not a causal detriment
    Open questions
    • 5-FU vs gemcitabine vs other radiosensitizers: prospective CRT regimen comparison needed
    • Whether modern IGRT (VMAT, CBCT) improves CLR vs older portal imaging techniques
    📚 Sources · 🐦 1 tweet

    RADIOSA

    ForOligorecurrent prostate cancer, SBRT candidates, median f/u ~4yr

    TL;DRPost-hoc: SBRT + 6mo ADT vs SBRT alone in oligorecurrent prostate; median MFS 16.6mo vs NR, HR 0.39, p=0.0012.

    Combined Curative Phase 2 trial Caveats dominate

    RADIOSA
    EndpointArm A (SBRT)Arm B (SBRT+ADT)
    Metastatic progression32/51 (62.7%)19/51 (37.3%)
    Median MFS16.6mo (95% CI 12.83-NA)Not reached
    HR (95% CI)0.3894 (0.2201-0.6888)—
    p (Cox)0.00119—
    p (log-rank)0.00079—
    8 details
    Methods
    • 🔍 Phase II RCT, N=102, 1:1; Arm A: SBRT alone vs Arm B: SBRT + 6mo ADT; oligorecurrent prostate cancer
    • 🔍 49/51 Arm B pts achieved testosterone recovery within follow-up; benefit persisted after castration resolved
    CONSORT flow
    Randomized 102
    ↓
    Arm A (SBRT)
    allocated 51
    Arm B (SBRT + ADT)
    allocated 51
    Results
    • 📐 Median follow-up 49.23mo (95% CI 42.47-54.8) by reverse KM
    • 📊 Metastatic progression: 32/51 (62.7%) Arm A vs 19/51 (37.3%) Arm B
    • 📊 Median MFS 16.6mo (95% CI 12.83-NR) Arm A vs not reached Arm B; HR 0.3894 (0.2201-0.6888), p=0.00119
    • 📊 Eugonadal MFS (post-testosterone recovery) significantly longer in Arm B (p<0.05)
    Critique
    • ⚠️ Post-hoc analysis of MFS and eugonadal MFS; neither was a prespecified primary endpoint of the parent RADIOSA trial
    • ⚠️ Small N (51/arm); post-hoc design; MFS not powered; results hypothesis-generating only
    Open questions
    • OS benefit of adding short-term ADT to SBRT in oligorecurrent disease?
    • Which pts benefit most: PSA kinetics, lesion count, PSMA avidity?
    • Optimal ADT duration (6mo vs longer) for oligorecurrent SBRT candidates?
    📚 Sources · 🐦 1 tweet