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Curative

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FIRESTORM

ForHigh-risk meningioma (WHO grade 2 or recurrent), post-resection (mostly subtotal

TL;DR5-yr PFS 65.8% vs 38.8%, HR 0.40 favoring dose-escalated RT in high-risk meningioma; retrospective IPD meta-analysis.

Radiation Curative Meta-analysis Caveats dominate

8 details 3 trials watching
  • ๐Ÿ” IPD meta-analysis, 7 institutions, N=248 (59 DE-RT, 189 SD-RT); DE-RT = BED โ‰ฅ79.2 Gy (โ‰ก66 Gy/33 fr)
  • ๐Ÿ” 75.8% WHO grade 2; 41.5% recurrent; 75.2% subtotal resection
  • ๐Ÿ“Š 5-yr PFS: DE-RT 65.8% vs SD-RT 38.8%; 3-yr PFS 86.4% vs 55.6% (log-rank P=.0022)
  • ๐Ÿ“ MVA: HR 0.40 (95% CI 0.24-0.69), P=.001; IPTW-adjusted HR 0.45 (95% CI 0.24-0.83), P=.01
  • โš ๏ธ Radionecrosis higher with DE-RT
    • Any grade RN: 33.9% DE-RT vs 13.2% SD-RT, P=.001
    • Grade 3+ RN: 5.1% vs 3.2% (not significant)
  • โš ๏ธ Retrospective non-randomized design; selection bias in who received dose escalation not fully eliminated by IPTW
  • โš ๏ธ DE-RT arm small (N=59); 3:1 imbalance limits subgroup stability
  • โš ๏ธ No OS endpoint reported in source
๐Ÿ“š Sources ยท ๐Ÿ“„ 1 paper
๐Ÿ“„ PAPER Singh, Raj; Koempel, Andrew; French, Beck et al. ยท International Journal of Radiation Oncology*Biology*Physics (2026-07)
Improved Progression-Free Survival Following Dose-Escalated Versus Standard-Dose Postoperative Radiation Therapy for High-Risk Meningiomas: An International Multicenter Individual Patientโ€“Level Meta-Analysis (FIRESTORM)
Abstract
Purpose: We performed an individual patientโˆ’level meta-analysis of high-risk meningiomas to compare the outcomes of dose-escalated radiation therapy (DE-RT) versus standard-dose postoperative radiation therapy (SD-RT).<br/>Methods and Materials: A total of 7 institutions participated. DE-RT was defined as treatment with a biologically effective dose of โ‰ฅ79.2 Gy (equivalent of 66 Gy in 33 fractions). We compared progression-free survival (PFS) with DE-RT versus SD-RT via Kaplan-Meier analysis and log-rank t tests, a Cox proportional hazards multivariable model, and propensity score analyses with inverse probability of treatment weighting (IPTW). We also compared incidences of central nervous system radionecrosis (RN) with DE-RT versus SD-RT.<br/>Results: The analysis included 248 patients with high-risk meningioma (59 received DE-RT and 189 received SD-RT). One hundred and eighty-eight cases (75.8%) were World Health Organization grade 2, and 103 cases (41.5%) were recurrent meningiomas. Extent of resection was subtotal resection in 182 of 248 (75.2%). Three- and 5-year PFS rates were 62.8% (95% CI, 55.8%-69.0%) and 45.0% (95% CI, 37.3%-52.3%), respectively. DE-RT was associated with superior PFS rates (P = .0022), with 3-year (86.4% vs 55.6%) and 5-year (65.8% vs 38.8%) PFS rates favoring DE-RT. On multivariable analysis, DE-RT was associated with superior PFS (hazard ratio, 0.40; 95% CI, 0.24-0.69; P = .001). On IPTW, DE-RT continued to be associated with superior PFS (hazard ratio, 0.45; 95% CI, 0.24-0.83; P = .01). A greater incidence of any grade RN was observed following DE-RT (20 of 59; 33.9%) versus SD-RT (25 of 189; 13.2%) (P = .001) but with similar grade 3 or greater RN events (DE-RT 5.1% vs SD-RT 3.2%).<br/>Conclusions: DE-RT resulted in superior PFS for patients with high-risk meningiomas over SD-RT without an increase in severe toxicities.

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
  • ๐Ÿ” Prospective phase 2, N=165 eligible (244 consented); risk-stratified by WHO grade, resection extent, recurrence status
  • ๐Ÿ” Low: grade 1 GTR/STR โ†’ obs; intermediate: recurrent grade 1 or new grade 2 post-GTR โ†’ 54 Gy; high: new grade 2 post-STR, grade 3, or recurrent grade 2/3 โ†’ 60 Gy
  • ๐Ÿ” Median PFS not reached in low- and intermediate-risk cohorts
  • ๐Ÿ“Š 10-yr outcomes by risk group
    Risk GroupRxn10-yr PFS10-yr OS10-yr prog. incidence
    LowObservation6085.2%94.1%8.9% (3.2โ€“18.2%)
    Intermediate54 Gy/30fx5272.2%84.7%21.2% (10.8โ€“33.9%)
    High60 Gy/30fx5342.5%51.1%39.3% (25.8โ€“52.5%)
  • โš ๏ธ G3+ RT-attributed toxicity
    • Intermediate-risk: 9.6% (5/52 pts)
    • High-risk: 15.1% (8/53 pts)
  • โš ๏ธ Non-randomized: risk allocation deterministic, not randomised; no RT vs obs head-to-head for intermediate group
  • โš ๏ธ WHO 2021 molecular criteria not applied; risk stratification reflects histologic grading (WHO 2007/2016)
๐Ÿ“š Sources ยท ๐Ÿ“„ 1 paper
๐Ÿ“„ PAPER Kotecha, Rupesh; Polley, Mei-Yin; Vogelbaum, Michael A. et al. ยท 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
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
  • ๐Ÿ” Prospective single-arm, N=848, 17 centers (Netherlands), enrolled 2011-2015
  • ๐Ÿ” Eligibility: cT<5cm, cN1-3 at diagnosis; risk tier assigned by ypN status post-NAC + surgery
  • ๐Ÿ” RT allocation by risk tier
    • ypN0 (low): BCS โ†’ breast RT; mastectomy โ†’ RT omitted
    • ypN1-3 (intermediate): breast/chest wall RT; regional nodal RT withheld
    • ypN4+ (high): breast/chest wall + regional nodal RT
  • ๐Ÿ“Š 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%)
  • ๐Ÿ“Š Overall: 24/838 (2.9%) locoregional events at 10 yr
  • โš ๏ธ No randomized comparator arm; low LRR rates may reflect patient selection or favorable NAC biology, not de-escalation effect per se
  • โš ๏ธ Most pts had ALND โ€” less common in current practice; generalizability to sentinel node biopsy era uncertain
๐Ÿ“š Sources ยท ๐Ÿ“„ 1 paper
๐Ÿ“„ PAPER ยท The ASCO Post
Breast Cancer Recurrence Remains Lowโ€”Even After 10 Yearsโ€”With Radiotherapy Tailored to Patientโ€™s Individual Risk
Abstract
โ€œThe 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...
๐Ÿ“ Breast Cancer Recurrence Remains Low Even After 10 Years With Radiotherapy Tailored to Patientโ€™s Individual Risk - The ASCO Post

PrTK03 (aglatimagene besadenovec + EBRT) NCT01436968

ForIntermediate/high-risk localized prostate cancer, ECOG 0โ€“2, planning definitive

TL;DRDFS HR 0.70 (0.52โ€“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
  • ๐Ÿ” Phase 3 double-blind placebo-controlled, N=745, 2:1 allocation, 51 US/Puerto Rico centers
  • ๐Ÿ” Intermediate or high-risk M0 localized prostate cancer; ECOG 0โ€“2; EBRT 78 Gy/2 Gy or hypofractionated; ADT optional
  • ๐Ÿ’Š Intraprostatic aglatimagene (CAN-2409, replication-defective adenoviral HSV-TK vector) ร— 3 courses + valacyclovir prodrug; immune bystander cytotoxicity mechanism
CONSORT flow
Randomized 745
โ†“
Aglatimagene + valacyclovir + EBRT
allocated 496
analyzed 479
Placebo + valacyclovir + EBRT
allocated 249
analyzed 232
  • ๐Ÿ“Š 1ยฐ EP: DFS HR 0.70 (95% CI 0.52โ€“0.94), p=0.016
  • ๐Ÿ“Š Median DFS not reached (aglatimagene) vs 86.1 months (IQR 29.7โ€“143.0) in placebo
  • ๐Ÿ“ Median follow-up 50.3 months (IQR 35.2โ€“63.3)
  • โš ๏ธ G3+ TEAEs similar between arms
    • Aglatimagene: 8% (40/479); placebo: 7% (17/232)
    • Most common G3+: AKI โ€” 2% both arms
    • SAEs: 6% aglatimagene vs 7% placebo; treatment-related SAEs 2% both arms
    • No treatment-related deaths
  • โš ๏ธ 1ยฐ EP is DFS (composite: recurrence or death), not OS; OS data not reported in source
  • โš ๏ธ 50-month median f/u likely underpowers late events; prostate cancer recurrences extend 10+ years post-RT
  • โš ๏ธ Sponsor-funded (Candel Therapeutics + NIH); 79% White cohort โ€” generalizability to diverse populations limited
  • 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
๐Ÿ“š Sources ยท ๐Ÿ“„ 1 paper
๐Ÿ“„ PAPER Dykstra, Michael P.; Regan, Samuel N.; Yin, Huiying (Maggie) et al. ยท 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
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 โ‰ฅ2 cT3/T4, Grade Group [GG] 4-5, prostate-specific antigen (PSA) โ‰ฅ40 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, โ‰ฅ18 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 โ‰ฅ20 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 โ‰ฅ40 (OR, 3.64 [95% CI, 1.22โ€“10.87]). Facility-level variability persisted in the MVA ( P &lt; .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.

AREST

ForpT1-2 pN0 OSCC, intermediate-risk (DOI/PNI/LVE/poor diff), post-curative surgery

TL;DR3-yr LRFS 89.2% vs 80.9%, HR 0.52 (p=0.02) favoring adj RT in pT1-2 pN0 OSCC with intermediate-risk features; DFS/OS NS.

Radiation Curative Phase 3 RCT Practice-changing

8 details
  • ๐Ÿ” Phase III open-label RCT, N=392; 1:1 stratified by subsite, PNI/LVE, differentiation
  • ๐Ÿ” Eligibility: pT1-2 pN0 OSCC, โ‰ฅ1 intermediate-risk factor (DOI 5-10mm, PNI, LVE, poor diff); margins โ‰ฅ5mm, โ‰ฅ16 nodes dissected
  • ๐Ÿ’Š Adj RT: 60Gy/30fr to tumor-bed + at-risk neck nodes; median f/u 47.2mo (IQR 30-59)
CONSORT flow
Randomized 392
โ†“
Adjuvant RT
allocated 191
Observation
allocated 201
  • ๐Ÿ“Š 1ยฐ EP LRFS ITT: 3-yr 89.2% RT vs 80.9% obs, HR 0.52 (95%CI 0.30-0.91), p=0.02
  • ๐Ÿ“Š Competing-risk cumulative LR failure: 10.6% RT vs 18.9% obs, HR 0.52, p=0.021
  • ๐Ÿ“ PP analysis: HR 0.43 (0.23-0.80), p=0.01
  • ๐Ÿ“Š Subgroup: oral tongue derives greater LRFS benefit than buccal mucosa
  • โš ๏ธ DFS and OS not significantly different; LRC benefit does not translate to survival gain at 47mo
  • Does LRC benefit translate to OS with longer follow-up?
  • Should adj RT selection favor oral tongue over buccal mucosa?
  • Does benefit differ by number of risk factors (1 vs โ‰ฅ2)?
๐Ÿ“š Sources ยท ๐Ÿ“„ 1 paper
๐Ÿ“„ PAPER Nair, Sudhir Vasudevan; Gupta, Tejpal; Rane, Swapnil Ulhas et al. ยท Journal of Clinical Oncology (2026-06)
Adjuvant radiotherapy versus observation following curative surgery for early-stage oral squamous cell carcinoma (AREST; CTRI/2017/07/009114).
Abstract
6000 Background: The role of adjuvant radiotherapy (RT) in early-stage, node-negative oral squamous cell carcinoma (OSCC) with one or more intermediate risk factors - such as depth of invasion (DOI) โ‰ฅ5 to โ‰ค10mm, perineural invasion (PNI), lymphovascular emboli (LVE), or poor differentiation - remains debatable and is largely based on retrospective data. This multicenter, open-label, phase III randomized controlled trial was designed to assess the impact of post-operative adjuvant RT in this setting. Methods: Patients with early-stage (pT1-T2), node-negative (pN0) OSCC undergoing adequate surgery (defined as clear margins โ‰ฅ5mm and at least ipsilateral level I-III neck dissection with โ‰ฅ16 nodes) with presence of one or more intermediate risk factors were screened. Eligible patients underwent stratified randomization (oral cavity subsite, PNI/LVE, and differentiation) in 1:1 ratio to either observation or adjuvant RT (60Gy in 30 fractions over 6-weeks) to the resected tumor-bed and at-risk neck nodal region after written informed consent. Primary endpoint was loco-regional recurrence-free survival (LRFS) measured from randomization to first documented event of local and/or regional recurrence from index cancer. All time-to-event outcomes were computed using Kaplan-Meier (KM) method with log-rank test for comparison and expressed as 3-year point estimates with 95% confidence intervals (CI). The planned sample size (N=392) provided 80% power at an ฮฑ of 0.05 to detect a Hazard Ratio (HR) of 0.6256, assuming 3-year LRFS of 70% in the observation arm. Results: Following curative surgery, a total of 392 patients were randomized (191 to adjuvant RT; 201 to observation). Baseline characteristics were balanced between the two arms. At a median follow-up of 47.2 months (inter-quartile range=30-59.4 months), 3-year KM estimate of LRFS was 89.2% in adjuvant RT arm vs 80.9% in observation arm (HR=0.52, 95%CI=0.30-0.91; p=0.02) in the intention-to-treat (ITT) population and 91.1% vs 80.9% (HR=0.43, 95%CI=0.23-0.80; p=0.01) on per-protocol (PP) analyses. Cumulative incidence of loco-regional failure with death as competing event was 10.6% (95%CI=6.1%-15.1%) with adjuvant RT and 18.9% (95%CI=13.3%-24.6%) with observation (HR=0.52, 95%CI=0.30-0.91; p=0.021) in the ITT population and 8.7% (95%CI=4.3%-13.1%) vs 18.9% (95%CI=13.3%-24.6%) (HR=0.43, 95%CI=0.23-0.79; p=0.007) on PP analyses. Disease-free and overall survival were not significantly different between the two arms. Subgroup analysis identified oral tongue deriving higher benefit of adjuvant RT compared to buccal mucosa. Conclusions: Adjuvant RT significantly reduces risk of loco-regional recurrence for early-stage, node-negative adequately resected OSCC, particularly oral tongue. However, such reduction in loco-regional failure does not translate into significant survival benefit. Clinical trial information: CTRI/2017/07/009114.
๐Ÿ“ https://ascopubs.org/doi/10.1200/JCO.2026.44.16_suppl.6000

mRCAT-III NCT06507371

ForpMMR/MSS LARC, cT3-4N0/+M0, tumor โ‰ค10cm 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
  • ๐Ÿ” Phase 3 open-label RCT, N=154 (77/arm), 17 centers China, stratified by cN stage
  • ๐Ÿ” Node-sparing RT: 5Gyร—5d targeting tumor bed only; elective tumor-draining LNs excluded from CTV
  • ๐Ÿ’Š Experimental: tislelizumab 200mg d1 + oxaliplatin 130mg/mยฒ d1 + capecitabine 1000mg/mยฒ d1-14
CONSORT flow
Randomized 154
โ†“
Node-sparing SCRT + CAPOX + tislelizumab
allocated 77
analyzed 77
Conventional SCRT + CAPOX
allocated 77
analyzed 77
  • ๐Ÿ“Š 1ยฐ EP (pCR, ITT): 61.0% (47/77) vs 28.6% (22/77), p<0.0001
  • ๐Ÿ“Š MPR (TRG0+TRG1): 77.9% (60/77) vs 50.6% (39/77), p<0.0001
  • ๐Ÿ“Š Severe GI AEs lower in experimental arm per investigator report; specific rates not provided in source
  • โš ๏ธ pCR is surrogate; EFS/OS are secondary endpoints, not yet reported
  • โš ๏ธ Small N (77/arm); single-country (China); open-label (pCR assessed by blinded central review)
  • โš ๏ธ pMMR/MSS only; dMMR/MSI-H pts excluded (already IO-responsive in LARC)
  • 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
๐Ÿ“š Sources ยท ๐Ÿฆ 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
  • ๐Ÿ” ASCO26 educational review: PK-guided concurrency framework for systemic therapy during breast/CW + RNI (adapted from ASCO Educational Book 2026)
  • ๐Ÿ’Š 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
  • ๐Ÿ’Š T-DXd (tยฝ=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%
  • ๐Ÿ’Š T-DM1 (tยฝ=4d): CONTINUE during locoregional RT; CNS SRS radionecrosis is the do-not-ignore signal
  • ๐Ÿ” 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
  • ๐Ÿ’Š 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 (tยฝ=90hr): long PK tail favors sequential strategy
  • ๐Ÿ’Š CDK4/6i: hold during large-field RT
    • Abemaciclib/ribociclib (tยฝ=24-55hr): hold for large fields; concurrent feasible in trial setting only (NCT05996107)
    • Palbociclib (tยฝ=28.8hr): practical to hold around RT; resume promptly after
  • ๐Ÿ“Š KEYNOTE-522 post-hoc (1,174 pts, 715 received RT): concurrent pembro + RT numerically fewer G3-5 AEs vs sequential
  • โš ๏ธ All concurrency guidance rests on post-hoc analyses, small prospective series, or retrospective cohorts; PK washout + sequential is safer default outside protocol
  • 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
๐Ÿ“š Sources ยท ๐Ÿฆ 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
  • ๐Ÿ” N=110, INTERCEPT program, MD Anderson 2020-2024; stage I-III MSS rectal adenocarcinoma, cCR/nCR after NAT โ†’ NOM; Signateraโ„ข tumor-informed ctDNA
  • ๐Ÿ” 22/23 pts with local regrowth underwent salvage surgery; ctDNA-positive at regrowth: ypT3-4 75% vs 21% (ctDNA-negative), p=0.01
  • ๐Ÿ“Š Ever-positive longitudinal ctDNA: worse 2-yr local regrowth-free survival (log-rank p=0.0002) and metastasis-free survival (p<0.0001)
  • ๐Ÿ“Š First post-NAT ctDNA positive (within 180 days): worse regrowth-free (p=0.0006) and metastasis-free survival (p<0.0001)
  • ๐Ÿ“Š Positive ctDNA associated with regrowth (~60%) and distant mets (~60%) in ctDNA-positive pts
  • โš ๏ธ Sensitivity only 41% for local regrowth โ€” negative ctDNA does not exclude local recurrence; endoscopy and MRI remain essential
  • โš ๏ธ Single-institution non-randomised cohort, N=110, median f/u 25 months; no ctDNA-guided vs standard surveillance arm
  • 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)
๐Ÿ“š Sources ยท ๐Ÿฆ 1 tweet

PROTEUS

ForBiochemically recurrent prostate cancer, post-radical prostatectomy

TL;DR53.0% (APA) and 60.7% (ADT) of MFS events PSMA PET-detected; APA+ADT vs ADT benefit in BCR prostate hotly contested.

Systemic Curative Phase 3 RCT Caveats dominate

6 details
  • ๐Ÿ” Phase 3 RCT, APA + ADT vs ADT alone in BCR prostate cancer, post-RP setting
  • ๐Ÿ“Š Full primary endpoint data pending ASCO26 presentation; no effect size reported in source tweets
  • ๐Ÿ“Š NEJM paper: 53.0% (APA arm) and 60.7% (ADT arm) of distant mets identified by PSMA PET, not conventional imaging
  • โš ๏ธ Majority of MFS events PSMA PET-only: magnitude of conventional-imaging MFS benefit unclear
  • โš ๏ธ ASCO26 preview framing: 'some may call this a homerun, others may call this the largest negative'
  • โ“ PSMA PET-detected MFS not an established OS surrogate; does EFS benefit translate to survival?
  • Does PSMA PET-detected EFS/MFS benefit translate to OS?
  • Magnitude of benefit by conventional imaging alone
๐Ÿ“š Sources ยท ๐Ÿฆ 3 tweets
๐Ÿ“ Note until the trial is released later this is preview
๐Ÿ“ note add commentary to proteus discussion
๐Ÿ“ add to proteus data

COMPPARE

ForDe novo localized prostate cancer, excluding very high risk and metastatic

TL;DRNo sig difference (bowel urgency 5.7% vs 6%, p=0.28; 3-yr BCF 98.0% vs 97.9%) between proton and IMRT in de novo localized prostate.

vs leading data
  • vs PARTIQoL RCT: also null for bowel toxicity at 2yr in randomized proton vs IMRT; COMPPARE extends to larger N but non-randomized

Radiation Curative Caveats dominate

COMPPARE
OutcomeIMRT (actual)PT (actual)p
Bowel urgency (EPIC)6%5.7%0.28
Bowel frequency (EPIC)4%3.5%0.43
โ‰ฅG2 GI toxicity (CTCAEv5)5.6%5.2%0.60
3-yr freedom from progression97.9%98.0%0.90
+2 more figures
COMPPARE
Group2-yr โ‰ฅG2 GI toxicity (95% CI)
IMRT, no spacer7.2% (5.0-9.9%)
Proton, no spacer8.7% (5.0-14%)
IMRT, spacer4.4% (2.8-6.4%)
Proton, spacer4.7% (3.6-6.0%)
COMPPARE
6 details
  • ๐Ÿ” Prospective non-randomized comparative effectiveness study, N=2524, 51 PT + IMRT centers, Jul 2018-Oct 2022
  • ๐Ÿ” De novo localized prostate cancer; very high risk and metastatic excluded; proton cohort 1500, photon 1000
  • ๐Ÿ“Š All 4 primary endpoints non-significant (p range 0.28-0.90); both modalities performed substantially better than hypothesized event rates
  • ๐Ÿ“Š Rectal spacers significantly reduced 2-yr โ‰ฅG2 GI toxicity regardless of modality (p=0.009, Gray's Test); spacer benefit exceeded modality effect
  • โš ๏ธ Severely underpowered: hypothesized bowel urgency 15% (IMRT) vs actual 6%; study cannot establish equivalence at these event rates
  • โš ๏ธ Non-randomized design; selection into proton vs IMRT may confound any toxicity signal
  • Whether underpowering masks a real late toxicity advantage for proton therapy
  • Role of rectal spacers in abrogating any modality-specific GI difference
  • Long-term BCR and MFS as follow-up matures
๐Ÿ“š Sources ยท ๐Ÿฆ 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
  • ๐Ÿ” Intra-prostatic oncolytic viral injection (CAN-2409) + RT 78Gy vs RT + placebo; randomized
  • ๐Ÿ“Š 1ยฐ EP DFS: median NR vs 86.1mo, HR 0.70 (95% CI 0.52-0.94), p=0.0155
  • ๐Ÿ“Š 2yr post-Rx biopsy pCR: 80.4% vs 63.6%
  • ๐Ÿ“Š 2yr local persistence/recurrence: 19.6% vs 36.4%, p=0.0015
  • โš ๏ธ DFS driven mainly by biopsy pCR (surrogate); MFS and BCR not reported in source
  • โš ๏ธ OS and PCSM not significantly different; 1 PCSM event per arm at 50.3mo median f/u
  • โš ๏ธ G3 tox <1% in both arms
  • 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?
๐Ÿ“š Sources ยท ๐Ÿฆ 1 tweet

ENZARAD

ForHigh-risk localized PCa (Gleason 8-10, T3-4, or N1, or PSA โ‰ฅ20 ng/mL), suitable

TL;DRMFS HR 0.88 (p=0.34), OS HR 0.87 (p=0.40); enzalutamide added to RT+2y ADT did not improve outcomes in high-risk localized PCa.

Systemic Curative Phase 3 RCT Confirmatory

ENZARAD
ArmEvents/NMFS 8yHR (95% CI)2p
Enzalutamide98/40174%0.88 (0.67-1.15)0.34
Control (NSAA)109/40172%refref
+2 more figures
ENZARAD
ENZARAD
ArmEvents/NOS 8yHR (95% CI)2p
Enzalutamide69/40183%0.87 (0.63-1.20)0.40
Control (NSAA)77/40180%refref
5 details
  • ๐Ÿ” Phase 3 RCT (ANZUP), N=802, 1:1; high-risk localized PCa (Gleason 8-10, T3-4, N1, or PSA โ‰ฅ20 ng/mL); median FU 8y
  • ๐Ÿ” Enzalutamide 160mg/d x24mo + LHRH agonist x24mo vs NSAA x6mo + LHRH agonist x24mo; both arms: RT ยฑ brachytherapy boost ยฑ pelvic nodal RT
CONSORT flow
Randomized 802
โ†“
Enzalutamide
allocated 401
Control (NSAA)
allocated 401
  • ๐Ÿ“Š Both 1ยฐ (MFS) and 2ยฐ (OS) endpoints not met; overall trial negative
  • โš ๏ธ Pelvic RT and cN1 subgroup interactions are exploratory in a negative trial; hypothesis-generating, not sufficient for practice change
  • โš ๏ธ ICECAP surrogacy framework cited validating MFS as OS surrogate; both concordantly null, no hidden OS benefit suggested
  • Whether pelvic RT selection prospectively enriches for ARSI benefit in high-risk localized PCa
  • Optimal ADT intensification strategy for cN1 high-risk prostate cancer
๐Ÿ“š Sources ยท ๐Ÿฆ 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 (1ยฐ 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
  • ๐Ÿ” Phase I prospective single-arm; N=50; MSS RC primary โ‰ค10cm from anal verge, synchronous unresectable mets; RAS/BRAF-mut 56%
  • ๐Ÿ” HFRT to primary + HFRT/SBRT to mets โ†’ systemic; resectable disease โ†’ primary resection + metastasectomy/ablation; primary cCR โ†’ watch-and-wait eligible
  • ๐Ÿ’Š Systemic regimen by RAS/BRAF status
    • Mutant: FOLFOX + bevacizumab + tislelizumab
    • Wild-type: FOLFIRI + cetuximab + tislelizumab
    • Reassessment q8wk; tislelizumab 200mg Q2W
  • ๐Ÿ“Š 18% (9/50) reached NED
  • ๐Ÿ“Š 1-yr OS 93.3%; 1-yr PFS 33.4%
  • ๐Ÿ“Š Median DOR 8.0mo (95% CI 5.2-10.8) among 34 responders; 1-yr DOR rate 20%
  • โš ๏ธ Grade 3/4 TRAEs: substantial hematologic burden
    • lymphopenia 36.7%
    • neutropenia 26.5%
    • leukopenia 20.4%
    • no grade 5 events
  • โš ๏ธ Phase I single-arm, N=50, med f/u 19.9mo; no randomised comparator; NED durability and generalizability unproven
  • Predictive biomarkers for RT + IO response in MSS mCRC
  • Durability of NED beyond 2 years
  • Whether benefit extends to MSS colon (non-rectal) primaries
๐Ÿ“š Sources ยท ๐Ÿฆ 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 โ‰ฅ75%; 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
  • ๐Ÿ” Multi-stage single-arm trial; durvalumab neoadjuvant, synchronous, and 12mo adjuvant with chemoRT (5FU+MMC, 55Gy/20Fr)
  • ๐Ÿ” N=55 enrolled; N=54 received โ‰ฅ1 treatment dose (1 withdrew pre-treatment); 33/54 (61%) completed planned treatment, 21/54 (39%) discontinued early
  • ๐Ÿ” Node-positive subset: 55Gy/20Fr to bladder + 46Gy/20Fr to pelvic nodes
  • ๐Ÿ“Š 1ยฐ EP: 12-month DFS 80% (40/50; 95% CI 0.67-0.89); cleared pre-set GO threshold โ‰ฅ75%
  • โš ๏ธ Single-arm; no concurrent randomised comparator vs CRT alone; efficacy benchmarked against historical control only
  • โš ๏ธ 39% early durvalumab discontinuation; adjuvant IO tolerability across 12mo is a key remaining question
  • Randomised confirmation vs CRT alone required
  • Durability of bladder preservation beyond 12 months
๐Ÿ“š Sources ยท ๐Ÿฆ 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
  • ๐Ÿ” Durvalumab + CRT trial: N=54 MIBC, 55 Gy/20 fr + MMC/5-FU + durvalumab, single-arm phase 2
  • ๐Ÿ“Š RT delivery: 47/54 (87%) received full 55 Gy/20fr without extension or delay
  • ๐Ÿ“Š 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%)
  • ๐Ÿ“Š pCR (pT0N0) as prognostic marker: SWOG 8710 85% 5-yr OS if pT0; meta-analysis pooled RR 0.19 for RFS
  • โš ๏ธ No efficacy endpoints reported; long-term bladder preservation, function, QOL, and safety require further follow-up
  • 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?
๐Ÿ“š Sources ยท ๐Ÿฆ 2 tweets

NRG Clinico-Transcriptomic Risk Stratification (Abstract 5000)

ForNCCN โ‰ฅ 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
  • ๐Ÿ” 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 (โ‰ค2 pts) โ†’ RT+ADT; CT VHR (โ‰ฅ3 pts) โ†’ RT+ADT+AAP
  • ๐Ÿ“Š 22-gene GC independently predicts MFS, DM, and OS beyond clinical variables alone (p < 0.001 for each endpoint)
  • ๐Ÿ“Š ~25% of NCCN โ‰ฅHR pts have discordant clinical vs. GC risk, warranting the combined approach
  • โš ๏ธ Framework developed on existing NRG trial data; no prospective RCT validating CT-score-guided treatment allocation reported
  • โš ๏ธ Design not fully specified in source; likely secondary correlative analysis; GC cutoffs extend Spratt et al. (JCO 2018) prior work
  • 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
๐Ÿ“š Sources ยท ๐Ÿฆ 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)โ€”
p0.008โ€”
7 details
  • ๐Ÿ” N=620, 13 Chinese centers, 2013-2022; cT3N2+ or T4 gastric/GEJ; 36.3% EGJ primary
  • ๐Ÿ” CRT arm: 45 Gy/25 fractions concurrent after C1 chemo, with dose-reduced oxaliplatin (100 mg/mยฒ) and capecitabine (825 mg/mยฒ)
CONSORT flow
Randomized 620
โ†“
CRT (XELOX + RT)
allocated 310
CT (XELOX)
allocated 310
  • ๐Ÿ“Š mOS 67.5 vs 37.6 months, HR 0.781 (0.628-0.970), p=0.025
  • ๐Ÿ“Š Locoregional recurrence in R0-resected pts: 9.4% CRT vs 18.3% CT
  • ๐Ÿ“Š 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%
  • โš ๏ธ G3+ toxicity (CRT vs CT)
    • Hematologic: 14.6% vs 10.3%
    • Postop complications: 9.0% vs 7.6%
  • โš ๏ธ Backbone is XELOX, not FLOT; limits direct applicability to FLOT-era Western practice
  • 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
๐Ÿ“š Sources ยท ๐Ÿฆ 1 tweet

ROADS

ForResected brain mets >2cm

TL;DRSurg bed recurrence 1% (GT) vs 12% (SRS); 2yr OS 62% vs 36% favoring GammaTile in resected brain mets >2cm.

vs leading data
  • vs Alliance N107C: established SRS as post-resection standard; ROADS directly randomizes vs GammaTile for the first time

Radiation Curative Practice-changing

ROADS
EndpointGammaTileSRS
Time to surg bed recurrenceNR17 mo
Surg bed recurrence-FSNR11 mo
2-yr OS62%36%
6 details
  • ๐Ÿ” Randomized, N=230, resected brain mets >2cm; GammaTile brachytherapy vs post-op SRS
  • ๐Ÿ“Š Surg bed recurrence 1% GammaTile vs 12% SRS โ€” primary EP
  • ๐Ÿ“Š Radiation necrosis similar: 8% GammaTile vs 7% SRS
  • โš ๏ธ LMD 10% GammaTile vs 3% SRS โ€” leptomeningeal spread higher with brachytherapy
  • โš ๏ธ OS 62% vs 36% is a secondary endpoint; trial powered for cavity control, not OS confirmation
  • โš ๏ธ Trial phase not stated in source; primary EPs both NR suggests follow-up still maturing for OS
  • Does LMD increase with GammaTile translate to OS detriment at longer follow-up?
  • Benefit extend to resected mets <2cm?
  • Optimal GammaTile activity prescription for cavity control
๐Ÿ“š Sources ยท ๐Ÿฆ 1 tweet

SENOMAC NCT02240472

ForcN0 breast cancer, T1-T3, 1-2 SN macrometastases, BCT or mastectomy

TL;DR5yr RFS 89.7% vs 88.7%, HR 0.89: SNB alone noninferior to ALND in cN0 breast cancer with 1-2 SN macrometastases.

vs leading data
  • vs ACOSOG Z0011: SENOMAC resolves Z0011's power deficit, uncertain RT volumes, and short f/u in one trial
  • vs AMAROS: AMAROS replaced ALND with axillary RT; SENOMAC omits axillary-directed treatment entirely, relying on regional nodal RT

Surgery Curative Phase 3 RCT Confirmatory

7 details
  • ๐Ÿ” Phase 3 NI RCT, N=2766 enrolled, 2540 per-protocol; median f/u 46.8mo (range 1.5-94.5)
  • ๐Ÿ” Extends Z0011 eligibility: includes mastectomy, T3 tumors, extracapsular extension, male pts
  • ๐Ÿ” Nodal RT administered in 89.9% SNB-only group, 88.4% ALND group
  • ๐Ÿ“Š 2ยฐ EP (RFS): 5yr 89.7% (95% CI 87.5-91.9) SNB-only vs 88.7% (95% CI 86.3-91.1) ALND
  • ๐Ÿ“ Country-adjusted HR 0.89 (95% CI 0.66-1.19); noninferiority p<0.001 (upper CI 1.19 below margin 1.44)
  • โš ๏ธ 1ยฐ EP (OS) not yet reported; only prespecified secondary RFS analysis shown here
  • โš ๏ธ Near-universal nodal RT in both arms: noninferiority may not hold where nodal RT is routinely omitted
  • Primary OS endpoint results still pending
  • Generalizability in settings where nodal RT is not routinely administered
  • Optimal RT volumes (high-tangent vs dedicated nodal fields) in SNB-only pts
๐Ÿ“š Sources ยท ๐Ÿ“„ 1 paper
๐Ÿ“„ PAPER de Boniface, Jana; Filtenborg Tvedskov, Tove; Rydรฉn, Lisa et al. ยท New England Journal of Medicine (2024-04)
Omitting Axillary Dissection in Breast Cancer with Sentinel-Node Metastases
Abstract
BACKGROUND<br/>Trials evaluating the omission of completion axillary-lymph-node dissection in patients with clinically node-negative breast cancer and sentinel-lymph-node metastases have been compromised by limited statistical power, uncertain nodal radiotherapy target volumes, and a scarcity of data on relevant clinical subgroups.<br/>METHODS<br/>We conducted a noninferiority trial in which patients with clinically node-negative primary T1 to T3 breast cancer (tumor size, T1, โ‰ค20 mm; T2, 21 to 50 mm; and T3, >50 mm in the largest dimension) with one or two sentinel-node macrometastases (metastasis size, >2 mm in the largest dimension) were randomly assigned in a 1:1 ratio to completion axillary-lymph-node dissection or its omission (sentinel-node biopsy only). Adjuvant treatment and radiation therapy were used in accordance with national guidelines. The primary end point was overall survival. We report here the per-protocol and modified intention-to-treat analyses of the prespecified secondary end point of recurrence-free survival. To show noninferiority of sentinel-node biopsy only, the upper boundary of the confidence interval for the hazard ratio for recurrence or death had to be below 1.44.<br/>RESULTS<br/>Between January 2015 and December 2021, a total of 2766 patients were enrolled across five countries. The per-protocol population included 2540 patients, of whom 1335 were assigned to undergo sentinel-node biopsy only and 1205 to undergo completion axillary-lymph-node dissection (dissection group). Radiation therapy including nodal target volumes was administered to 1192 of 1326 patients (89.9%) in the sentinel-node biopsyโ€“only group and to 1058 of 1197 (88.4%) in the dissection group. The median follow-up was 46.8 months (range, 1.5 to 94.5). Overall, 191 patients had recurrence or died. The estimated 5-year recurrence-free survival was 89.7% (95% confidence interval [CI], 87.5 to 91.9) in the sentinel-node biopsyโ€“only group and 88.7% (95% CI, 86.3 to 91.1) in the dissection group, with a country-adjusted hazard ratio for recurrence or death of 0.89 (95% CI, 0.66 to 1.19), which was significantly (P<0.001) below the prespecified noninferiority margin.<br/>CONCLUSIONS<br/>The omission of completion axillary-lymph-node dissection was noninferior to the more extensive surgery in patients with clinically node-negative breast cancer who had sentinel-node macrometastases, most of whom received nodal radiation therapy. (Funded by the Swedish Research Council and others; SENOMAC ClinicalTrials.gov number, NCT02240472.)

SWOG/NRG S1914 NCT04214262

ForInoperable early-stage NSCLC T1-3N0M0 โ‰ค7cm, โ‰ฅ1 recurrence risk factor

TL;DRNo OS benefit from adding atezolizumab to SBRT (HR 1.15, p=0.63); closed for futility; Gโ‰ฅ3 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
  • ๐Ÿ” Phase III RCT; N=403 eligible (201 SBRT / 202 atezo+SBRT); accrual closed at first interim for OS + PFS futility per prespecified design
  • ๐Ÿ” T1-3N0M0 NSCLC โ‰ค7cm, inoperable or declined surgery, โ‰ฅ1 recurrence risk factor; atezo 1200mg Q3W x8 cycles; SBRT 3-8 fx BED โ‰ฅ100Gy initiated cycle 3
  • ๐Ÿ” 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
โ†“ 14 excluded
Randomized 403
โ†“
SBRT
allocated 201
SBRT + atezolizumab
allocated 202
  • ๐Ÿ“Š Efficacy outcomes: SBRT vs SBRT + atezolizumab
    EndpointHR (95% CI)p2yr SBRT2yr SBRT+atezo
    OS (1ยฐ EP)1.15 (0.65-2.01)0.6382%80%
    PFS1.35 (0.89-2.06)0.1671%60%
  • ๐Ÿ“Š Failure patterns at cutoff
    PatternSBRTSBRT + atezo
    Local7%13%
    Regional2%3%
    Distant4%5%
  • โš ๏ธ Gโ‰ฅ3 AEs: 12% atezo arm (21 G3, 1 G4, 1 G5 respiratory failure) vs 2% SBRT (3 G3, 1 G4)
  • โš ๏ธ Median f/u 12 mo among survivors; 49 OS events at cutoff; local recurrence central review, PD-L1, and QoL analyses pending
  • 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
๐Ÿ“š Sources ยท ๐Ÿ“„ 1 paper
๐Ÿ“„ PAPER Simone, Charles B.; Daly, Megan Eileen; Redman, Mary Weber et al. ยท 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.
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 โ‰ค7cm, were medically inoperable or declined surgery, and had โ‰ฅ1 risk factor for increased recurrence: tumor diameter โ‰ฅ2 cm, โ‰ฅ6.2, moderately/poorly/undifferentiated histology. Randomization was to SoC SBRT (S [3-8 fractions, biologically effective dose โ‰ฅ100 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 โ‰ฅ4cm) 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) โ‰ฅ3 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 โ‰ฅ3 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 .
๐Ÿ“ https://ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.8003

PEACE Vโ€“STORM NCT03569241

ForPelvic nodal oligorecurrence (โ‰ค5 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
  • ๐Ÿ” Phase 2 open-label RCT, N=196 randomized 1:1, 21 hospitals across 6 countries
  • ๐Ÿ” MDT arm: SLND or SBRT 30 Gy/3 fx every other day + 6 mo ADT
  • ๐Ÿ” ENRT arm: 45 Gy/25 fx to pelvis + SIB 65 Gy to PET+ nodes (or SLND) + 6 mo ADT
  • ๐Ÿ” Eligibility: PET+ pelvic nodal oligorecurrence โ‰ค5 nodes post-radical local treatment, PS 0-1
CONSORT flow
Assessed / enrolled 198
โ†“ 2 excluded
Randomized 196
โ†“
MDT
allocated 99
analyzed 97
ENRT
allocated 97
analyzed 93
  • ๐Ÿ“Š 1ยฐ EP: 4-yr metastasis-free survival
    Arm4-yr MFS80% CI
    ENRT76%69-81%
    MDT63%56-69%
  • ๐Ÿ“ HR 0.62 (80% CI 0.44-0.86), p=0.063; median f/u 50 mo (IQR 42-58)
  • ๐Ÿ“Š G3 AEs
    • Urinary incontinence: 6% MDT vs 10% ENRT
    • Diarrhea: 1% MDT vs 2% ENRT
    • No treatment-related deaths
  • โš ๏ธ 80% CI threshold (not 95%); p=0.063 at conventional alpha; prespecified phase 2 go/no-go design
  • โš ๏ธ Open-label; heterogeneous MDT arm (SLND vs SBRT); PSMA + choline PET tracers mixed
  • 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
๐Ÿ“š Sources ยท ๐Ÿ“„ 1 paper
๐Ÿ“„ PAPER Piet Ost; Shankar Siva; Sigmund Brabrand et al. ยท The Lancet Oncology (2025-05)
Salvage metastasis-directed therapy versus elective nodal radiotherapy for oligorecurrent nodal prostate cancer metastases (PEACE Vโ€“STORM): a phase 2, open-label, randomised controlled trial
Abstract
Background Various locoregional treatments exist for PETโ€“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 Vโ€“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 0โ€“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 0ยท80 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 42โ€“58). 4-year metastasis-free survival was 63% (80% CI 56โ€“69) in the MDT group and 76% (69โ€“81) in the ENRT group (HR 0ยท62 [80% CI 0ยท44โ€“0ยท86]; p=0ยท063). 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.

DBCG IMN2 NCT06549920

ForNode-positive breast cancer, adjuvant RT, taxane/trastuzumab/AI systemic therapy

TL;DR15-yr OS 65.0% vs 60.8%, HR 0.85 (0.76-0.94), p=0.0016 favoring IMNI in node-positive breast cancer with modern systemic therapy, N=4541.

vs leading data
  • vs DBCG IMN1 (N=3089, 2003-07): OS gain 4.7% at 14.8-yr f/u; confirms benefit persists in modern era
  • vs KROG 06-08 (negative Korean study, 3D-RT + newer agents): IMN2 contradicts null result

Radiation Curative Real-world evidence Confirmatory

8 details
  • ๐Ÿ” Prospective nationwide cohort, N=4541, Jan 2007-May 2014; median f/u 13.7 yr
  • ๐Ÿ” Allocation: right-sided โ†’ IMNI, left-sided โ†’ no IMNI; 6 RT centres, 3D-based RT
  • ๐Ÿ” Systemic: taxane-based chemo, AIs, trastuzumab
  • ๐Ÿ“Š Primary EP OS: 15-yr 65.0% (IMNI) vs 60.8% (no IMNI)
  • ๐Ÿ“Š All endpoints favor IMNI (adjusted HRs)
    EndpointHR (95% CI)p
    OS0.85 (0.76-0.94)0.0016
    Breast cancer mortality0.84 (0.74-0.95)0.0077
    Distant metastasis0.87 (0.78-0.98)0.026
  • โš ๏ธ Cohort design, not RCT; laterality-based allocation; baseline characteristics balanced but not randomized
  • โš ๏ธ No subgroup identified favoring IMNI omission, including 1-3 positive axillary nodes
  • Cardiac: 15-yr ischemic/valvular HD death
    • 0.2% (95% CI 0.0-0.5) right-sided / IMNI
    • 0.7% (95% CI 0.4-1.2) left-sided / no IMNI
    • Gap likely reflects left breast cardiac dose, not IMNI-specific toxicity
  • Benefit with post-2014 systemic agents (CDK4/6i, T-DM1) not established
  • Optimal IMNI technique to minimize cardiac exposure in left-sided pts
  • Whether cohort evidence sufficient to shift 1-3 node guidelines broadly
๐Ÿ“š Sources ยท ๐Ÿ“„ 1 paper
๐Ÿ“„ PAPER Anders W. Mรธlby Nielsen; Lise B. J. Thorsen; Demet ร–zcan et al. ยท The Lancet Regional Health - Europe (2025-02)
Internal mammary node irradiation in 4541 node-positive breast cancer patients treated with newer systemic therapies and 3D-based radiotherapy (DBCG IMN2): a prospective, nationwide, population-based cohort study
Abstract
Background Internal mammary node irradiation (IMNI) improves overall survival (OS) in node-positive breast cancer patients. However, the effect is not documented in breast cancer patients treated with newer systemic therapies and 3D-based radiotherapy (RT). Therefore, the Danish Breast Cancer Group (DBCG) IMN2 study aimed to investigate the effect of IMNI in node-positive breast cancer patients treated with newer systemic therapies and 3D-based RT.<br/>Methods DBCG IMN2 was a nationwide population-based cohort study prospectively allocating node-positive breast cancer patients with right-sided tumours to IMNI and patients with left-sided tumours to no IMNI in six RT centres. Exclusion criteria were prior malignancies, bilateral breast cancer, neoadjuvant systemic therapy, recurrence before RT, or non-standard RT. Systemic treatment included taxane-based chemotherapy, aromatase inhibitors, and trastuzumab. The primary end-point was OS. Secondary endpoints were breast cancer mortality and distant metastasis. Cox regression analyses were used for adjusted hazard ratios (HR). Clinicaltrial.gov ID: NCT06549920.<br/>Findings In the period January 2007โ€“May 2014, a total of 4541 patients were included. Patient characteristics were distributed evenly between right- and left-sided patients. Median follow-up was 13.7 years for OS. Survival rates at 15 years were 65.0% in patients with IMNI and 60.8% without leading to an adjusted HR of 0.85 (95% CI, 0.76โ€“0.94; p = 0.0016) for OS. Corresponding HRs were 0.84 (95% CI, 0.74โ€“0.95; p = 0.0077) for breast cancer mortality and HR 0.87 (95% CI, 0.78โ€“0.98; p = 0.026) for distant metastasis. No subgroups were identified for the omission of IMNI. The 15-year cumulative incidence of death from ischemic or valvular heart disease was 0.2% (95% CI, 0.0โ€“0.5) in right-sided and 0.7% (95% CI, 0.4โ€“1.2) in left-sided patients.<br/>Interpretation IMNI reduced distant metastasis and breast cancer mortality and improved OS in node-positive breast cancer patients, despite treatment with newer systemic therapies and 3D-based RT.

Bladder Adjuvant Radiotherapy

ForHigh-risk urothelial MIBC post-RC (pT3-4, pN+, margin+, or โ‰ค10 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
  • ๐Ÿ” Phase III RCT, N=153 (RT=77, Obs=76); stratified by nodal involvement and chemo timing
  • ๐Ÿ” Eligibility: any of pT3-4, pN1-3, margin+, or โ‰ค10 nodes dissected; 62% pT3-T4, 41% pN+
  • ๐Ÿ’Š Stoma-sparing IG-IMRT 50.4Gy/28fx to cystectomy bed and pelvic nodes
CONSORT flow
Randomized 153
โ†“
Adjuvant RT
allocated 77
Observation
allocated 76
  • ๐Ÿ“Š RT vs observation outcomes, median f/u 47mo
    EndpointRTObsHR (95% CI)p
    2-yr LRFS (1ยฐ)87.1%76.0%0.43 (0.20-0.96)0.04
    DFS71.6%58.7%0.62 (0.36-1.05)โ€”
    BCSS79.6%65.0%0.59 (0.33-1.10)โ€”
    OS70.4%57.4%0.78 (0.49-1.26)โ€”
  • โš ๏ธ Small N (153); underpowered for OS; CI crosses 1.0 on all secondary endpoints
  • โš ๏ธ None received immunotherapy; cohort predates nivolumab post-cystectomy standard (CheckMate 274)
  • 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?
๐Ÿ“š Sources ยท ๐Ÿ“„ 1 paper
๐Ÿ“„ PAPER Murthy; Maitre; Pal et al. ยท 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.
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.

EORTC 22922/10925

ForStage I-III breast, node-positive or central/medial tumor, median age 54, post-s

TL;DR20yr OS HR 1.00 (null): BC mortality reduced HR 0.82 but non-BC deaths increased HR 1.26, offsetting benefit.

vs leading data
  • vs EORTC 22922 10yr data (NEJM 2015): DFS and BC mortality benefit seen at 10yr did not translate to OS by 20yr; competing-cause mortality dominant

Radiation Curative Phase 3 RCT Challenges SOC

6 details
  • ๐Ÿ” Phase 3 RCT, N=4004 randomized 1996-2004, median f/u 22.2yr; prespecified 20yr final analysis
  • ๐Ÿ” Eligible: women โ‰ค75yr, stage I-III, node-positive OR central/medial tumor; post-mastectomy or BCS + ALND
  • ๐Ÿ“Š Outcomes at 20 years (IM-MS-RT vs control)
    EndpointControlIM-MS-RTHRp
    OS (20yr rate)61.8%61.0%1.00.967
    DFS (20yr rate)49.0%48.2%0.97.515
    DMFS (20yr rate)59.8%58.9%0.97.578
    BC mortality (20yr rate)22.4%18.6%0.82.006
    Non-BC deaths (20yr rate)15.8%20.4%1.26.002
  • โš ๏ธ Non-BC death excess emerged after 15yr, driven by cardiac and pulmonary morbidity from IM-MS-RT
  • โš ๏ธ Late RT morbidity (IM-MS-RT vs control)
    • Lung fibrosis: 6.3% vs 3.2%
    • Cardiac fibrosis: 2.7% vs 1.7%
    • Cardiac diseases: 15.2% vs 11.7%
    • Severe cardiac G3-4: 1.9% vs 1.7%
    • Severe lung G3-4: 0.3% vs 0.0%
  • โš ๏ธ 2D RT planning era (enrolled 1996-2004); modern cardiac-sparing techniques may attenuate the non-BC mortality signal
  • Does modern cardiac-sparing IM-RT eliminate the non-BC death excess?
  • Which subgroups (high nodal burden, HER2+, TNBC) derive net OS benefit?
  • Impact of contemporary systemic therapy on IM-MS-RT benefit/harm ratio
๐Ÿ“š Sources ยท ๐Ÿ“„ 1 paper
๐Ÿ“„ PAPER Kaidarโ€Person, Orit; Weltens, Caroline G.; Fortpied, Catherine et al. ยท CA: A Cancer Journal for Clinicians (2026-05)
Twentyโ€year results of the randomized European Organization for Research and Treatment of Cancer trial 22922/10925 evaluating internal mammary chain and medial supraclavicular lymph node irradiation in stage Iโ€“III breast cancer
Abstract
Abstract European Organization for Research and Treatment of Cancer trial EORTC 22922/10925 evaluated internal mammary and medial supraclavicular (IMโ€MS) lymph node irradiation (IMโ€MSโ€RT) in patients with stage Iโ€“III breast cancer. Eligible patients had involved axillary nodes and/or centrally/medially located tumors regardless of nodal involvement. The primary end point was overall survival, secondary end points were diseaseโ€free survival, distant metastasesโ€free survival, breast cancer mortality, and any breast recurrence. Between 1996 and 2004, 4004 patients were randomized. The median patient age was 54 years. At a median followโ€up of 22.2 years, 1550 (38.7%) patients died, of whom 796 (51.4%) died from breast cancer. At 20 years, the overall survival rate was 61.8% in the control group versus 61.0% in the IMโ€MSโ€RT group (hazard ratio [HR], 1.00; p = .967); the diseaseโ€free survival rate was 49.0% versus 48.2%, respectively (HR, 0.97; p = .515); and the distant metastasesโ€free survival rate was 59.8% versus 58.9%, respectively (HR, 0.97; p = .578). The breast cancer mortality rate was 22.4% in the control group and 18.6% in the IMโ€MSโ€RT group (HR, 0.82; p = .006), whereas the rate of deaths not from breast cancer or from unknown causes was 15.8% versus 20.4%, respectively (HR, 1.26; p = .002). Lung fibrosis, cardiac fibrosis, and cardiac diseases were more frequent after IMโ€MSโ€RT versus no IMโ€MSโ€RT (6.3% vs. 3.2%, 2.7% vs. 1.7%. and 15.2% vs. 11.7%, respectively); and the rates of severe cardiac and lung morbidities (scores of 3 or 4) were 1.9% versus 1.7% and 0.3% versus 0.0%, respectively. Breast cancer mortality at 20 years was statistically significantly lower after IMโ€MSโ€RT, but deaths not from breast cancer increased after 15 years, resulting in no longโ€term benefit of IMโ€MSโ€RT on overall survival. Therefore, the authors strongly call for very longโ€term followโ€up of treatments for prognostically favorable cancers such as breast cancer.

SWOG S1007 RNI analysis

ForHR+/HER2-, Oncotype DX โ‰ค25, N1 (1-3 nodes) breast cancer, adjuvant

TL;DR5-yr LRR <1% with or without RNI in HR+/HER2-, Oncotype โ‰ค25, N1 breast; IDFS not associated with RNI receipt.

vs leading data
  • vs MA.20/EORTC 22922 (RNI benefit in N+ disease broadly): S1007 population (Oncotype โ‰ค25) is a biologically favorable subgroup potentially below the threshold for RNI benefit

Radiation Curative Caveats dominate

7 details
  • ๐Ÿ” Secondary analysis of S1007 phase 3 RCT (chemo vs ET); N=4871 with prospective RT data; median f/u 6.1 yrs
  • ๐Ÿ” RT practice patterns
    • 81% received any RT
    • 59% of RT recipients received RNI (supraclavicular region minimum)
    • Practice divided on RNI use in this biologically favorable N1 setting
  • ๐Ÿ” Low LRR also observed in pts randomized to ET alone without chemo
  • ๐Ÿ“Š 5-yr cumulative LRR by locoregional treatment
    Treatment5-yr LRR
    BCS + RT + RNI0.85%
    BCS + RT, no RNI0.55%
    Mastectomy + PMRT0.11%
    Mastectomy, no RT1.7%
  • ๐Ÿ“ IDFS by RNI receipt (observational; RNI not randomized)
    Menopausal statusHR (95% CI)p
    Premenopausal1.03 (0.74-1.43)0.87
    Postmenopausal0.85 (0.68-1.07)0.16
  • โš ๏ธ RNI not randomized: confounding by indication likely (lower-risk pts selected for omission by treating physicians)
  • โš ๏ธ Survival analyses landmarked at 1 yr; RT data recorded only in first year post-randomization
  • Dedicated RCT of RNI omission in Oncotype โ‰ค25 N1 disease needed to confirm safety
  • Does chemo vs ET assignment (original randomization) modify RNI benefit?
  • Durability of low LRR beyond 6 yrs in this favorable-biology population?
๐Ÿ“š Sources ยท ๐Ÿ“„ 1 paper
๐Ÿ“„ PAPER Jagsi; Barlow; Woodward et al. ยท JAMA oncology (2023-08)
Radiotherapy Use and Incidence of Locoregional Recurrence in Patients With Favorable-Risk, Node-Positive Breast Cancer Enrolled in the SWOG S1007 Trial.
Abstract
IMPORTANCE: Little is known about regional nodal irradiation (RNI) practice patterns or rates of locoregional recurrence (LRR) with and without RNI in patients with limited nodal disease and favorable biology treated with modern surgical and systemic therapy, including approaches that de-escalate those latter treatments.<br/><br/>OBJECTIVE: To investigate how often patients with low-recurrence score breast cancer with 1 to 3 nodes involved receive RNI, incidence and predictors of LRR, and associations between locoregional therapy and disease-free survival.<br/><br/>DESIGN, SETTING, AND PARTICIPANTS: In this secondary analysis of the SWOG S1007 trial, patients with hormone receptor-positive, ERBB2-negative breast cancer, and a Oncotype DX 21-gene Breast Recurrence Score assay result of no more than 25, were randomized to endocrine therapy alone vs chemotherapy then endocrine therapy. Prospectively collected radiotherapy information was collected from 4871 patients treated in diverse settings. Data were analyzed June 2022 to April 2023.<br/><br/>EXPOSURE: Receipt of RNI (targeting at least the supraclavicular region).<br/><br/>MAIN OUTCOME(S) AND MEASURE(S): Cumulative incidence of LRR was calculated by locoregional treatment received. Analyses were assessed for associations between invasive disease-free survival (IDFS) and locoregional therapy, adjusted for menopausal status, treatment group, recurrence score, tumor size, nodes involved, and axillary surgery. Radiotherapy information was recorded in the first year after randomization, so survival analyses were landmarked as starting at 1 year among those still at risk.<br/><br/>RESULTS: Of 4871 female patients (median [range] age, 57 [18-87] years) with radiotherapy forms, 3947 (81.0%) reported radiotherapy receipt. Of 3852 patients who received radiotherapy and had complete information on targets, 2274 (59.0%) received RNI. With a median follow-up of 6.1 years, the cumulative incidence of LRR by 5 years was 0.85% among patients who received breast-conserving surgery and radiotherapy with RNI; 0.55% after breast-conserving surgery with radiotherapy without RNI; 0.11% after mastectomy with postmastectomy radiotherapy; and 1.7% after mastectomy without radiotherapy. Similarly low LRR was observed within the group assigned to endocrine therapy without chemotherapy. The rate of IDFS did not differ by RNI receipt (premenopausal: hazard ratio [HR], 1.03; 95% CI, 0.74-1.43; P&#x2009;=&#x2009;.87; postmenopausal: HR, 0.85; 95% CI, 0.68-1.07; P&#x2009;=&#x2009;.16).<br/><br/>CONCLUSIONS AND RELEVANCE: In this secondary analysis of a clinical trial, RNI use was divided in the setting of biologically favorable N1 disease, and rates of LRR were low even in patients who did not receive RNI. Disease-free survival was not associated with RNI receipt; omission of chemotherapy among patients similar to those enrolled in the S1007 trial is not an independent indication for use of RNI.

LS-SCLC 54 Gy Hyperfractionated RT NCT03214003

ForLS-SCLC, ECOG 0โ€“1, age 18โ€“70, chemo-naive or โ‰ค1 prior platinum-etoposide cycle

TL;DRmOS 60.7 vs 39.5mo (HR 0.55, p=0.003) favoring 54 Gy hyperfractionated RT in LS-SCLC; no added toxicity.

vs leading data
  • vs CONVERT trial (Lancet Oncol 2017): CONVERT also BID 45 Gy SIB to 66 Gy failed to show OS benefit over 45 Gy โ€” this trial's positive result contrasts CONVERT's null, likely due to SIB technique differences and PTV homogeneity approach

Radiation Curative Phase 3 RCT Challenges SOC

9 details
  • ๐Ÿ” Phase 3 open-label RCT; N=224; 16 centers in China; 1:1 randomization; median f/u 46mo
  • ๐Ÿ” 54 Gy SIB to GTV in 30 BID fractions vs 45 Gy in 30 BID fractions; both arms VMAT; PTV 45 Gy both arms
  • ๐Ÿ” Chemo-naive or โ‰ค1 prior cisplatin/carboplatin+etoposide cycle; ECOG 0โ€“1; age 18โ€“70
  • ๐Ÿ’Š Concurrent chemotherapy + PCI (25 Gy/10 fx) for responders in both arms
CONSORT flow
Assessed / enrolled 224
โ†“
Randomized 224
โ†“
54 Gy SIB
allocated 108
analyzed 108
45 Gy
allocated 116
analyzed 116
  • ๐Ÿ“Š 1ยฐ EP (OS): mOS 60.7mo (95% CI 49.2โ€“62.0) vs 39.5mo (27.5โ€“51.4), HR 0.55 (0.37โ€“0.72), p=0.003
  • โš ๏ธ G3โ€“4 RT toxicity by type
    • Oesophagitis: 13% (54 Gy) vs 12% (45 Gy), p=0.84
    • Pneumonitis: 5% (54 Gy) vs 6% (45 Gy), p=0.663
    • 1 treatment-related death in 54 Gy arm (MI)
  • โš ๏ธ Trial stopped early by DSMB (April 2021) on clinical benefit grounds; early termination inflates effect estimates
  • โš ๏ธ Single-country (China), age-capped at 70, open-label; generalizability to Western populations uncertain
  • โš ๏ธ 45 Gy BID (not OD) control โ€” aligns with historical standard but not universally practiced globally
  • Confirmatory data needed in non-Asian populations
  • Optimal dose escalation with modern immunotherapy combinations
  • Late cardiac/pulmonary toxicity beyond 46mo median f/u
๐Ÿ“š Sources ยท ๐Ÿ“„ 1 paper
๐Ÿ“„ PAPER Jiayi Yu; Leilei Jiang; Lina Zhao et al. ยท Lancet Respiratory Medicine (2024-08)
High-dose hyperfractionated simultaneous integrated boost radiotherapy versus standard-dose radiotherapy for limited-stage small-cell lung cancer in China: a multicentre, open-label, randomised, phase 3 trial
Abstract
Background For the past 20 years, twice-daily thoracic radiotherapy with concurrent chemotherapy has been the treatment of choice for limited-stage small-cell lung cancer (LS-SCLC), which has a poor prognosis. We aimed to assess the efficacy and safety of high-dose, accelerated, hyperfractionated, twice-daily thoracic radiotherapy (54 Gy in 30 fractions) versus standard-dose radiotherapy (45 Gy in 30 fractions) as a first-line treatment for LS-SCLC.<br/>Methods This open-label, randomised, phase 3 trial was performed at 16 public hospitals in China. The key inclusion criteria were patients aged 18โ€“70 years, with histologically or cytologically confirmed LS-SCLC, who had an Eastern Cooperative Oncology Group (ECOG) performance status of 0โ€“1, and who were previously untreated or had received one course of cisplatin or carboplatin and etoposide. Eligible patients were randomly assigned (1:1) to receive volumetric-modulated arc radiotherapy (VMAT) of 45 Gy in 30 fractions to the gross tumour volume or VMAT with a simultaneous integrated boost of 54 Gy in 30 fractions to the gross tumour volume starting 0โ€“42 days after the first chemotherapy course. Both groups received 10 fractions of twice-daily thoracic radiotherapy per week. The planning target volume was 45 Gy in 30 fractions in both groups. Patients with responsive disease received prophylactic cranial radiotherapy (25 Gy in 10 fractions). Randomisation was performed using a centralised interactive web response system, stratified by ECOG performance status, disease stage, previous chemotherapy course, and chemotherapy choice. The primary outcome was overall survival in the intention-to-treat population. Safety was analysed in the as-treated population. This study was registered at ClinicalTrials.gov, NCT03214003.<br/>Findings From June 30, 2017, to April 6, 2021, 224 patients (102 [46%] females and 122 [54%] males; median age 64 years [IQR 58โ€“68]) were enrolled and randomly assigned to the 54 Gy group (n=108) or 45 Gy (n=116) group. The median follow-up was 46 months (IQR 33โ€“56). The median overall survival was significantly longer in the 54 Gy group (60ยท7 months [95% CI 49ยท2โ€“62ยท0]) than in the 45 Gy group (39ยท5 months [27ยท5โ€“51ยท4]; hazard ratio 0ยท55 [95% CI 0ยท37โ€“0ยท72]; p=0ยท003). Treatment was tolerable, and the chemotherapy-related and radiotherapy-related toxicities were similar between the groups. The grade 3โ€“4 radiotherapy toxicities were oesophagitis (14 [13%] of 108 patients in the 54 Gy group vs 14 [12%] of 116 patients in the 45 Gy group; p=0ยท84) and pneumonitis (five [5%] of 108 patients vs seven [6%] of 116 patients; p=0ยท663). Only one treatment-related death occurred in the 54 Gy group (myocardial infarction). The study was prematurely terminated by an independent data safety monitoring board on April 30, 2021, based on evidence of sufficient clinical benefit.<br/>Interpretation Compared with standard-dose thoracic radiotherapy (45 Gy), high-dose radiotherapy (54 Gy) improved overall survival without increasing toxicity in a cohort of patients aged 18โ€“70 years with LS-SCLC. Our results support the use of twice-daily accelerated thoracic radiotherapy (54 Gy) with concurrent chemotherapy as an alternative first-line LS-SCLC treatment option.

Proton vs Photon PMRT Capsular Contracture (Zerey et al.)

ForPost-mastectomy breast cancer, subpectoral TE/I or DTI reconstruction, PMRT cand

TL;DRMVA HR 1.76 (P=0.083) proton vs photon CC, non-significant; proton+DTI 2yr CC 50% vs photon+DTI 35%.

vs leading data
  • Proton PMRT improves cardiac/pulmonary dosimetry vs photon; this CC signal is the risk to weigh in reconstruction planning

Radiation Curative Retrospective Caveats dominate

8 details
  • ๐Ÿ” Retrospective, 2 centers/single institution, N=175 (89 proton, 86 photon), Jan 2017-Dec 2023; median f/u 42 vs 47 mo
  • ๐Ÿ“Š 2-year CC rates by modality and reconstruction type
    ReconstructionProtonPhoton
    DTI50%35%
    TE/I23%12%
  • ๐Ÿ“ MVA HR 1.76 (95% CI 0.93-3.32), P=0.083 for proton vs photon
  • ๐Ÿ“ Univariate HR 2.3 (95% CI 1.26-4.30), P=0.007 for proton vs photon
  • ๐Ÿ“ DTI vs TE/I in MVA: HR 3.0 (95% CI 1.7-5.5), P<.001
  • โš ๏ธ Groups unbalanced for reconstruction type (TE/I vs DTI, P<.001); this is the dominant confounder and MVA adjustment may be insufficient
  • โš ๏ธ Groups also unbalanced for tumor laterality (P<.001); uncontrolled institutional practice patterns, not randomization
  • โš ๏ธ MVA primary result is P=0.083, below conventional significance; framed as a trend, not a confirmed signal
  • Does proton-CC signal replicate in a prospective matched or randomized cohort?
  • Optimal reconstruction type (TE/I vs DTI) when proton PMRT is indicated for cardiac/pulmonary dosimetry reasons?
๐Ÿ“š Sources ยท ๐Ÿ“„ 2 papers
๐Ÿ“„ PAPER Zerey; Gal; Feenstra et al. ยท International journal of radiation oncology, biology, physics (2026-04)
Does Pencil Beam Scanning Proton Therapy Impart a Higher Risk of Capsular Contracture Compared With Intensity Modulated Photon Radiation Therapy in the Postmastectomy Reconstruction Setting?
Abstract
BACKGROUND: Postmastectomy radiation therapy (PMRT) may cause adverse events in the reconstruction setting. Proton-based PMRT is increasingly used and has been shown to improve cardiac and pulmonary dosimetry. Data on the risk of capsular contracture (CC) with proton versus photon PMRT remain scarce. We compared the CC rate of the largest cohort of patients undergoing reconstruction after pencil beam scanning proton PMRT reported to date with an intensity modulated radiation therapy photon cohort, hypothesizing that the proton cohort would have a higher rate of CC.<br/><br/>METHODS AND MATERIALS: An institutional review board -approved retrospective study was conducted on patients with breast cancer who underwent subpectoral 2-stage tissue expander/implant (TE/I) or direct-to-implant (DTI) breast reconstruction and received either pencil beam scanning proton or intensity modulated radiation therapy photon PMRT between January 2017 and December 2023 at 2 centers within a single institution. All patients undergoing TE/I had the TE irradiated. CC rates were estimated using the Kaplan-Meier method. Cox proportional hazards analysis, denoted as hazard ratios (HRs) with 95% CIs, was used to assess variables potentially associated with the outcome, and a binary logistic regression model was used to verify the results.<br/><br/>RESULTS: The study cohort comprised 175 patients (89 proton; 86 photon). The median age was 49 years (range, 24-78), 63% were Hispanic. Patient demographics were well balanced between the groups, except in tumor laterality (P < .001) and reconstruction type (TE/I vs DTI; P < .001). The median follow-up was 42 and 47 months for the proton and photon groups, respectively. In a multivariable analysis, DTI patients had a significantly higher risk of CC compared with TE/I patients (HR, 3.0; 95% CI, 1.7-5.5; P < .001). Proton patients had a higher risk of developing CC compared with the photon group in univariate analysis (HR, 2.3; 95% CI, 1.26-4.30; P = .007), although this effect did not reach statistical significance in the multivariable model (HR, 1.76; 95% CI, 0.93-3.32; P = .083). The 2-year CC rate for patients treated with protons and DTI (n = 36), photons and DTI (n = 15), protons and TE/I (n = 53), and photons and TE/I (n = 71) was 50%, 35%, 23%, 12%, respectively (P < .001). No other factors were significantly associated with CC development.<br/><br/>CONCLUSION: In this contemporary large proton versus photon PMRT cohort, patients treated with proton showed a trend toward an increased risk of CC. Patients undergoing DTI who were treated with protons had the highest risk of CC (50%). Careful consideration of reconstruction and radiation therapy modalities, assessing CC risk, and also involving patient input, is important for treatment selection.
๐Ÿ“„ PAPER Zerey, M.M.; Gal, O.; Feenstra, N. et al. ยท International Journal of Radiation Oncology*Biology*Physics (2025-09)
Does Pencil Beam Scanning Proton Therapy Impart a Higher Risk of Capsular Contracture when Compared with Intensity Modulated Photon Radiotherapy in the Post-Mastectomy Reconstruction Setting?
๐Ÿ“ https://doi.org/10.1016/j.ijrobp.2025.07.1298

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
  • ๐Ÿ” Multicenter retrospective cohort, Spain 2010-2022; N=369, median age 76, 85% male, cT2-T4aNOMO
  • ๐Ÿ” TMT = maximal TURBT + concurrent chemoradiotherapy; 1ยฐ EP: CLR; multivariable logistic regression
  • ๐Ÿ“Š CLR: 63.7%; salvage cystectomy: 9.7%
  • ๐Ÿ“Š Disease progression 28.8%: local 10.1%, systemic 10.7%, combined 8.7%
  • ๐Ÿ“Š CLR associated with lower local recurrence and better survival (no OS/CSS HR in source)
  • ๐Ÿ“ Independent predictors of CLR (multivariable)
    • 5-FU-based CRT โ†’ higher CLR: OR 4.9 (95% CI 1.1-22.1), p=0.038
    • Weekly portal imaging โ†’ lower CLR: OR 0.35 (95% CI 0.20-0.60), p<0.001
  • โš ๏ธ Retrospective, 12-yr accrual (2010-2022): era effects likely across RT technique and CRT regimen selection
  • โš ๏ธ Portal imaging OR 0.35 is counterintuitive; probably proxies older/less precise RT delivery, not a causal detriment
  • 5-FU vs gemcitabine vs other radiosensitizers: prospective CRT regimen comparison needed
  • Whether modern IGRT (VMAT, CBCT) improves CLR vs older portal imaging techniques
๐Ÿ“š Sources ยท ๐Ÿฆ 1 tweet

ePLND vs PSMA PET staging in prostate cancer (AUA 2026)

ForLocalized prostate cancer, intermediate to high risk, primary staging pre-RP

TL;DR47.7% of LN mets outside ePLND template; PSMA PET NPV ~96%; RCTs no consistent BCR benefit from routine dissection.

vs leading data
  • Emerging: targeted/sentinel LND guided by PSMA PET-positive nodes vs full-template ePLND

Surgery Curative Challenges SOC

Yaxley et al. (BJUI 2019): 1253 men primary staging Ga-PSMA PET/CT; 47.7% of LN mets outside ePLND template.
Yaxley et al. (BJUI 2019): 1253 men primary staging Ga-PSMA PET/CT; 47.7% of LN mets outside ePLND template.
+2 more figures
Lower limb lymphedema: RP+PLND 0-14%, pelvic LN RT 0-9%, PLND+salvage RT 19-29%; DVT/PE risk 6-10x with PLND (Tyritzis, n=3544).
Lower limb lymphedema: RP+PLND 0-14%, pelvic LN RT 0-9%, PLND+salvage RT 19-29%; DVT/PE risk 6-10x with PLND (Tyritzis, n=3544).
ePLND vs PSMA PET staging in prostate cancer (AUA 2026)
7 details
  • ๐Ÿ” Intermediate risk: PLND safely omittable if PSMA PET negative; missed LN likely small, equally missed by ePLND
  • ๐Ÿ” High-risk: individual decision; PSMA PET negative โ†’ consider post-op pelvic RT over ePLND to limit lymphedema
  • ๐Ÿ“Š Yaxley et al. (BJUI 2019), n=1253: 47.7% of LN mets outside ePLND anatomic template
  • ๐Ÿ“Š PSMA PET NPV ~96% for LNI at primary staging
  • โš ๏ธ RCTs show no consistent BCR improvement attributable to routine ePLND
  • โš ๏ธ No Level 1 evidence for significant oncological benefit from ePLND (Roberts et al., PCAN 2024)
  • โš ๏ธ PLND morbidity (Clinckaert systematic review; Tyritzis J Urol 2015, n=3544)
    • Lower limb lymphedema: 0-14% RP+PLND; 0-9% pelvic LN RT; 19-29% PLND + salvage pelvic RT
    • DVT/PE risk 6-10x increased with PLND vs no PLND
  • Which high-risk pts still benefit from ePLND over PSMA PET-guided approach?
  • Role of targeted/sentinel LND using PSMA PET-positive nodes vs full-template ePLND
  • Long-term BCR/MFS outcomes when ePLND omitted based on negative PSMA PET
๐Ÿ“š Sources ยท ๐Ÿฆ 1 tweet

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
  • ๐Ÿ” Three-institution pooled retrospective: Peter Mac, Cleveland Clinic, Roswell Park
  • ๐Ÿ” N=1687: 1200 primary NSCLC + 487 pulmonary oligomets
  • ๐Ÿ“Š LC 90-93% at 2yr across both cohorts; isolated local/locoregional failure very uncommon
  • ๐Ÿ“Š Median PFS
    • Primary NSCLC: 30mo
    • Pulmonary oligomets: 11mo
  • ๐Ÿ“Š AEs (primary NSCLC, n=789)
    • G3+: 23/789 (2.9%)
    • G2+: 124/789 (15.7%)
    • Any AE: 215/789 (27%)
  • โš ๏ธ AE data excludes Roswell Park โ€” toxicity rates incomplete for the full 1687-pt cohort
  • โš ๏ธ Single-arm pooled retrospective; no randomised comparator vs conventional multi-fraction SBRT
  • 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?
๐Ÿ“š Sources ยท ๐Ÿฆ 1 tweet

PEACE 2

ForVHR localized prostate (โ‰ฅ2: Gleason โ‰ฅ8, T3-T4, PSA โ‰ฅ20), N0M0 on conventional im

TL;DRPelvic RT did not improve cPFS vs prostate-only RT in VHR localized prostate cancer (HR 0.81, p=0.088).

vs leading data
  • Contrasts with POP-RT, which showed bPFS and MFS benefit from pelvic RT in high-risk CaP; population definitions and staging modalities differ

Radiation Curative Phase 3 RCT Challenges SOC

PEACE 2
Prostate-only RTPelvic RT
7-yr cPFS62.9% [57.4; 68.1]67.1% [61.6; 72.2]
HR (95% CI)ref0.81 [0.63; 1.03]
p0.088
+1 more figure
PEACE 2
8 details
  • ๐Ÿ” Phase III, 4-arm: ADT ร— 3 yrs + prostate RT ยฑ cabazitaxel ร— 4 cycles; pelvic vs prostate-only RT comparison
  • ๐Ÿ” VHR eligibility: โ‰ฅ2 of Gleason โ‰ฅ8, T3-T4, PSA โ‰ฅ20 ng/mL; N0M0 on conventional imaging or choline PET/CT
  • ๐Ÿ’Š Side effects minimal with modern RT techniques; no quantitative toxicity figures reported in source
CONSORT flow
Randomized 761
โ†“
Prostate-only RT (A+C pooled)
allocated 380
Pelvic RT (B+D pooled)
allocated 381
  • ๐Ÿ“Š 1ยฐ EP cPFS: HR 0.81 (95% CI 0.63-1.03), p=0.088 โ€” non-significant
  • ๐Ÿ“Š 7-yr cPFS: 67.1% pelvic RT vs 62.9% prostate-only RT
  • ๐Ÿ“Š No improvement on secondary endpoints: MFS, PCSS, OS (effect sizes not reported in source)
  • โš ๏ธ Staged with conventional imaging/choline PET, not PSMA-PET; PSMA-era cohort may carry different nodal risk profile
  • โš ๏ธ Presenter conclusion: pelvic RT cannot be considered SOC even in pts at high nodal extension risk without detectable disease on imaging
  • Does PSMA-PET staging identify a nodal subgroup that benefits from pelvic RT?
  • How to reconcile with POP-RT (different risk definitions, staging modalities)?
  • Does cabazitaxel interaction modify pelvic RT benefit in the 4-arm design?
๐Ÿ“š Sources ยท ๐Ÿฆ 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
  • ๐Ÿ” 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
  • ๐Ÿ” Low-intermediate risk PCa; IPSS <12; ADT permitted (โ‰ค6 months) in both arms; 28% received ADT
  • ๐Ÿ” Median FU 59.7 months; 82.4% intermediate-risk; n=156 randomized, n=142 analyzed (interim)
  • ๐Ÿ“Š 1ยฐ EP (biochemical failure, Phoenix def): 7% AHRT vs 7.4% EHRT at 4.25y, p-noninferiority = 0.007
  • ๐Ÿ“Š Acute G2+ GI toxicity lower with AHRT; no absolute rates reported in source
  • ๐Ÿ“Š Late G2+ GI and acute/late G2+ GU toxicities comparable between arms
  • โš ๏ธ Interim analysis only; accrual goal n=456 (420 evaluable planned); non-inferiority not yet confirmed at final analysis
  • โš ๏ธ Non-inferiority margin 12% is wide relative to observed BF rates of 7-7.4%
  • โš ๏ธ Clinician-reported toxicity; laxative/psyllium use scored as G2 GI event
  • 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?
๐Ÿ“š Sources ยท ๐Ÿฆ 2 tweets

TORPEdO (CRUK/18/010)

ForOropharyngeal SCC requiring definitive concurrent CRT with bilateral neck treatm

TL;DRIMPT showed no HR-QoL benefit vs IMRT at 12 months in OPSCC; UW-QoL scores similar across arms to 24 months.

vs leading data
  • Lancet 2026 (McBride et al.): concurrent proton vs photon analysis in OPSCC

Radiation Curative Phase 3 RCT Challenges SOC

TORPEdO (CRUK/18/010)
+1 more figure
Phase 3 RCT schema: IMPT vs IMRT 2:1; 205 pts; 70/56 Gy in 33 fractions; cisplatin 100mg/mยฒ D1+D22
Phase 3 RCT schema: IMPT vs IMRT 2:1; 205 pts; 70/56 Gy in 33 fractions; cisplatin 100mg/mยฒ D1+D22
7 details
  • ๐Ÿ” Phase 3 RCT; N=205; 2:1 IMPT vs IMRT; cisplatin 100mg/mยฒ D1+D22; 70/56 Gy in 33 fractions over 6.5 weeks
  • ๐Ÿ” HR-QoL declines at end of treatment then recovers; most pts stabilize by 12 months post-CRT
  • ๐Ÿ“Š Patient-reported co-primary: UW-QoL physical composite (saliva, taste, chewing, swallowing, appearance, speech) at 12 months post-CRT
  • ๐Ÿ“Š No differences in UW-QoL scores between arms at 3, 12, or 24 months post-RT
  • ๐Ÿ“Š Clinician-reported co-primary (CTCAE G3 weight loss or gastrostomy dependence at 12 months): not reported in this presentation
  • โš ๏ธ Meaningful HR-QoL deterioration persists in some pts up to 2 years in both arms
  • โš ๏ธ Commentary: identical planning constraints and novice UK proton centers likely attenuated any IMPT advantage; high-experience centers may still see clinical benefit
  • Does proton center experience modify HR-QoL or late-toxicity outcomes?
  • Will clinician-reported co-primary (G3 weight loss/gastrostomy) diverge from HR-QoL?
  • Late-effect differentiation at 5-year follow-up
๐Ÿ“š Sources ยท ๐Ÿฆ 2 tweets ยท ๐Ÿ“„ 1 paper
๐Ÿ“„ PAPER McBride; Riaz; Sherman et al. ยท Lancet (London, England) (2026-05)
Proton versus photon therapy for oropharyngeal cancer.
๐Ÿ“ McBride SM, Riaz N, Sherman EJ, Tsai CJ, Mell LK. Proton versus photon therapy for oropharyngeal cancer. Lancet. 2026 May 16;407(10542):1917.

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
  • ๐Ÿ” INRT: AI-assisted identification of suspicious lymph nodes, ENI fields entirely omitted
  • ๐Ÿ” Eligibility
    • Sites: oropharynx, larynx, hypopharynx
    • Stage I-IVB (excl T1-2N0 larynx)
    • PET/CT + neck CT required for staging
  • ๐Ÿ“Š 5-yr risk of solitary elective nodal recurrence: 0% (N=117, median f/u 3.4yr)
  • ๐Ÿ“Š 5-yr OS 87%, 5-yr PFS 74%
  • ๐Ÿ“Š 3-yr LR 9.5%, regional recurrence 4.3%, DM 11%
  • ๐Ÿ“Š MDADI composite 84.9 at 12mo (no significant post-treatment decline)
  • โš ๏ธ No randomized comparator; toxicity reduction vs standard ENI-CRT unconfirmed
  • โš ๏ธ N=117 pooled from 2 trials; cross-trial heterogeneity in eligibility and AI model not reported
  • 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
๐Ÿ“š Sources ยท ๐Ÿฆ 1 tweet

OPERA Trial (5-year, rectal preservation)

ForLocally advanced rectal cancer, post-neoadjuvant therapy

TL;DR76% good response at W14 by clinical exam; 5yr OP 81% cCR vs 77% nCR; W14 assessment safely identifies W&W candidates.

Radiation Curative Caveats dominate

OPERA Trial (5-year, rectal preservation)
Arm AArm Bp
W14 good response (cCR+nCR)65%88%0.004
5yr OP75%83%0.24
+1 more figure
OPERA Trial (5-year, rectal preservation)
7 details
  • ๐Ÿ” OPERA primary: tumor response assessed at W24 via DRE + rectoscopy + MRI triad
  • ๐Ÿ” Post-hoc tests W14 CTRE (DRE + rectoscopy) as earlier OP decision gate, ~1mo after NAT end
  • ๐Ÿ” nCR reflects RT-induced tissue change, not incomplete clearance; should not trigger radical surgery
  • ๐Ÿ“Š W14 CTRE in 122/141 pts (87%): 76% good response (cCR+nCR), 24% PR
  • ๐Ÿ“Š MRI concordance at W14: TRG1-2 in 98% (80/82) of CR pts
  • ๐Ÿ“Š 5yr OP by response depth: cCR 81% vs nCR 77%
  • โš ๏ธ Post-hoc analysis of OPERA RCT; W14 timing not pre-specified as the primary assessment endpoint
  • Can W14 assessment replace W24, or is it additive?
  • Management of nCR pts at W14 who may convert to cCR by W24?
  • MRI TRG added value vs clinical exam alone at W14?
๐Ÿ“š Sources ยท ๐Ÿฆ 1 tweet

HCC EBRT Multinational IPD Cohort

ForHCC BCLC-0 or BCLC-A, treatment-naรฏve or previously treated

TL;DRBCLC-A mOS 4.6yr, BCLC-0 6.8yr in 4,913-pt IPD cohort; OS comparable to resection and ablation.

vs leading data
  • Authors conclude OS comparable to resection, thermal ablation, and other ablative locoregional therapies for BCLC-0/A

Radiation Curative Meta-analysis Confirmatory

7 details
  • ๐Ÿ” Systematic review + IPD meta-analysis; 4,913 HCC pts treated with EBRT; median f/u 5.0yr; multinational institutions
  • ๐Ÿ“Š OS by BCLC stage (all pts)
    StageMedian OS95% CI
    BCLC-06.8yr5.7-8.7
    BCLC-A4.6yr4.1-5.1
  • ๐Ÿ“Š OS in treatment-naรฏve pts
    StageMedian OS95% CI
    BCLC-0NR8.6yr-NR
    BCLC-A5.4yr4.5-6.7
  • ๐Ÿ“ Multivariable: ablative RT dose and more recent treatment year both associated with reduced mortality risk
  • ๐Ÿ“ Higher BCLC stage, greater tumor burden, worse PS, Child-Pugh B/C associated with higher mortality risk
  • โš ๏ธ No randomized comparator vs resection or ablation; historical cross-study comparison subject to selection bias
  • โš ๏ธ Dose heterogeneity across contributing institutions; ablative and non-ablative RT pooled together
  • Randomized comparison vs resection or thermal ablation still absent
  • Optimal fractionation and ablative dose threshold for OS benefit
  • Applicability to Child-Pugh B/C pts given worse prognosis in this cohort
๐Ÿ“š Sources ยท ๐Ÿ“„ 1 paper
๐Ÿ“„ PAPER Moon; Yanagihara; Dawson et al. ยท Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2026-05)
Overall Survival Among Patients With Hepatocellular Carcinoma Treated With External Beam Radiation Therapy: Individual Patient Data Outcomes From a Multinational Cohort.
Abstract
PURPOSE: External beam radiation therapy (EBRT) has gained delayed acceptance as a recommended first-line treatment modality for patients with hepatocellular carcinoma (HCC), given limited evidence that it improves overall survival (OS). We analyzed individual patient data (IPD) from an international cohort to assess OS among patients with HCC treated with EBRT.<br/><br/>METHODS: We performed a systematic review of publications that assessed EBRT, met prespecified technical standards for HCC, and reported OS (search date December 15, 2022). Corresponding authors were invited to submit IPD for the study. We performed Kaplan-Meier survival analyses to determine OS and restricted mean survival time (RMST) stratified by Barcelona Clinic Liver Cancer (BCLC) stage and treatment status (ie, treatment-na&#xef;ve and experienced). We performed random effects Cox proportional hazards modeling to assess clinical characteristics associated with OS.<br/><br/>RESULTS: Data were provided on 4,913 patients treated with EBRT with a median follow-up time of 5.0 years. The median OS was 6.8 years (95% CI, 5.7 to 8.7) for BCLC-0 and 4.6 years (95% CI, 4.1 to 5.1) for BCLC-A. Among treatment-na&#xef;ve patients, the median OS was not reached (95% CI, 8.6 to not reached) for BCLC-0 and was 5.4 years (95% CI, 4.5 to 6.7) for BCLC-A. In multivariable models, more advanced BCLC stage, higher tumor burden, worse performance status, and Child-Pugh class B or C were associated with a higher risk of mortality. Ablative radiation dose and more recent year of treatment were associated with a reduced risk of death.<br/><br/>CONCLUSION: To our knowledge, this study represents the largest multinational cohort of patients with HCC treated with EBRT. OS outcomes with EBRT for very early- and early-stage HCC appear to be comparable with resection, thermal ablation, and other ablative locoregional therapies. These data support the inclusion of EBRT in the BCLC HCC clinical decision-making process.
๐Ÿ“ Moon AM, Yanagihara TK, Dawson LA, Yu JI, Lawrence TS, Kim TH, Yan M, Iwata H, Nabavizadeh N, Apisarnthanarax S, Dunne EM, Lock MI, Chuong MD, Chiang CL, Scorsetti M, Katoh N, Sioshansi S, Numata K, Liu HY, Iwamoto H, Wakatsuki M, Chen Y, Pollom EL, Gkika E, Jabbour SK, Munoz-Schuffenegger P, Dutta D, Hajj C, Ueno M, Hallemeier CL, Feldman AM, Mรฉndรจz Romero A, Tan X, Molla M, Tepper JE, Torres F, Reig M; EBRT Collaboration Group. Overall Survival Among Patients With Hepatocellular Carcinoma Treated With External Beam Radiation Therapy: Individual Patient Data Outcomes From a Multinational Cohort. J Clin Oncol. 2026 May 15:JCO2502399.

EXTEND Trial

ForOligometastatic solid tumors, 1-5 mets, 6 histology baskets

TL;DRPFS HR 0.54 (95% CI 0.41-0.72, p<0.001) favoring MDT+SOC across histologies in phase II oligometastatic basket RCT; basket-specific signals identified.

vs leading data
  • Consistent with SABR-COMET (Lancet 2019), STOMP (JCO 2018), ORIOLE (JAMA Oncol 2020); extends MDT evidence across 6 histology groups

Radiation Curative Phase 2 trial Confirmatory

7 details
  • ๐Ÿ” Multicenter randomized phase II, 6-basket design (breast, pancreas, kidney, 2 prostate, Other); 1-5 mets; N=334 per-protocol (MDT+SOC n=166, SOC n=168)
  • ๐Ÿ’Š MDT was RT in 98% of treated mets (370/379)
  • ๐Ÿ” Exploratory ctDNA findings
    • Detectable ctDNA at enrollment correlated with shorter PFS + survival
    • ctDNA clearance at 3mo post-enrollment correlated with improved survival
  • ๐Ÿ“Š 1ยฐ EP PFS: HR 0.54 (95% CI 0.41-0.72), p<0.001, MDT+SOC vs SOC; median f/u 53 mo
  • ๐Ÿ“Š Excluding prostate baskets: PFS HR 0.60 (95% CI 0.40-0.89)
  • ๐Ÿ“Š Basket-level PFS superiority
    • Superiority demonstrated: pancreas, prostate, Other baskets
    • Inconclusive: breast, kidney baskets
  • โš ๏ธ Phase 2 only; overall HR may not apply uniformly across histologies given basket heterogeneity
  • Which histologies warrant dedicated phase 3 MDT trials?
  • Can ctDNA clearance predict MDT benefit for patient selection?
  • Optimal MDT modality beyond SBRT in basket-specific settings?
๐Ÿ“š Sources ยท ๐Ÿ“„ 1 paper
๐Ÿ“„ PAPER Sherry; Haymaker; Wang et al. ยท Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2026-05)
Addition of Metastasis-Directed Therapy to Standard of Care for Oligometastatic Solid Tumors: Primary Analysis of All Tumor-Histology Baskets of the Phase II Randomized EXTEND Trial.
Abstract
PURPOSE: We tested the hypothesis that adding metastasis-directed therapy (MDT) to standard of care (SOC) systemic therapy improves progression-free survival (PFS) among patients with oligometastatic disease.<br/><br/>METHODS: EXTEND was a multicenter randomized phase II trial. Patients with 1-5 metastases were randomized to MDT+SOC vs SOC in 1 of 6 baskets (breast, pancreas, kidney, two prostate baskets, and an "Other" basket) with basket-specific stratification and powering. PFS, the primary endpoint, was pre-specified in the per-protocol set within each basket, across all baskets, and across all baskets excluding the prostate baskets. Exploratory endpoints included circulating tumor DNA (ctDNA) and immune profiling.<br/><br/>RESULTS: From 2018 through 2023, 521 patients were screened, 350 were randomized, and 334 were analyzed per protocol (MDT+SOC, n=166; SOC, n=168). Radiotherapy was used as MDT for 98% of metastases (370/379). Overall, after median follow-up of 53 months, PFS was improved with MDT+SOC (HR 0.54, 95% CI 0.41 to 0.72, p < 0.001). Similarly, PFS was improved when excluding the prostate baskets (HR, 0.60; 95% CI: 0.40 to 0.89). Within each basket, PFS superiority was identified for the pancreas, prostate, and "Other" baskets, whereas the breast and kidney baskets were inconclusive. At enrollment, detectable ctDNA correlated with shorter PFS and survival; by contrast, ctDNA clearance 3-months post-enrollment correlated with improved survival. MDT+SOC-induced systemic immune activation was most pronounced among baskets demonstrating PFS superiority.<br/><br/>CONCLUSION: The phase II EXTEND trial supports the addition of MDT to SOC for oligometastatic disease. Histology-specific efficacy signals were identified for phase III testing. Translational insights suggest the potential for optimizing the definition of oligometastasis using ctDNA, and point to systemic immune responses as a possible mechanism of benefit from MDT.
๐Ÿ“ Sherry AD, Haymaker C, Wang S, Liu S, Bathala TK, Medina-Rosales MN, Seo A, Hara K, Reddy J, Chun SG, Mayo LL, Walker G, Pant S, Zhao D, Kovitz CA, Ramirez D, Ha CS, Smith BD, Gomez D, Cohen L, Koong AC, Reuben A, Tannir N, Corn PG, Tran PT, Siddiqui BA, Subudhi SK, Msaouel P, Ludmir EB, Tang C. Addition of Metastasis-Directed Therapy to Standard of Care for Oligometastatic Solid Tumors: Primary Analysis of All Tumor-Histology Baskets of the Phase II Randomized EXTEND Trial. J Clin Oncol. 2026 May 16:101200JCO2502856.

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
  • ๐Ÿ” Non-randomised phase 2, N=70 (71 enrolled, 1 withdrew consent), 8 sites (AU/NL); median f/u 62 months (IQR 60-72)
  • ๐Ÿ” Eligibility: medically inoperable, high-risk, or surgery-declining; ECOG โ‰ค2; tumour โ‰ค10cm; N0-N1
  • ๐Ÿ” SABR dose: 26 Gy ร— 1 for tumour โ‰ค4cm; 42 Gy/3fx at 48h intervals for >4cm
  • ๐Ÿ” Median age 77 (IQR 70-82); 70% male; T1b dominant (56%); median tumour 46mm (IQR 37-55)
  • ๐Ÿ“Š 1ยฐ EP: 100% freedom from local progression at 36, 60, and 84 months
  • ๐Ÿ“Š No G4 events, no treatment-related deaths, no new long-term safety signals at 62-month median f/u
  • โš ๏ธ 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%)
  • โš ๏ธ Single-arm, all inoperable/surgery-declining; no randomised comparator vs partial nephrectomy or ablation โ€” LC durability not generalisable to operable candidates
  • โš ๏ธ Varian-funded (RT equipment manufacturer); sponsor interest aligned with positive SABR outcome
  • 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)
๐Ÿ“š Sources ยท ๐Ÿ“„ 1 paper
๐Ÿ“„ PAPER Siva; Pryor; Martin et al. ยท 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.
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.
๐Ÿ“ 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.

NRG/RTOG 1005 NCT01349322

ForPost-lumpectomy high-risk early breast: grade 3, ER-neg, LVI, or close margins

TL;DR7-yr IBR 2.6% vs 2.2%, HR 1.31 (90% CI 0.84-2.04); concurrent boost noninferior, reducing treatment to 15 fractions.

vs leading data
  • vs EORTC 22881-10882 (Bartelink): addresses delivery timing, not boost vs no boost; landmark context only

Radiation Curative Phase 3 RCT Practice-changing

9 details
  • ๐Ÿ” Phase III unblinded RCT, N=2,255 analyzed; 278 sites, North America + 6 countries; median f/u 7.3 yr
  • ๐Ÿ” High-risk post-lumpectomy: grade 3 (52.7%), ER-neg (29.6%), LVI (16.7%), close margins (16.7%), chemo (61.8%)
  • ๐Ÿ’Š Concurrent arm: WBI 40 Gy/15F + simultaneous boost 0.53 Gy/fx (15 total fractions)
  • ๐Ÿ’Š Sequential arm: WBI 50 Gy/25F or 42.7 Gy/16F + boost 12-14 Gy/6-7F after (22-32 total fractions)
  • ๐Ÿ“Š 1ยฐ EP (IBR noninferiority): HR 1.31 (90% CI 0.84-2.04), p=0.037; upper bound 2.04 < NI margin 2.12
  • ๐Ÿ“Š 7-yr IBR: 2.6% concurrent vs 2.2% sequential; 5-yr: 1.9% vs 2.1%; 56 total events
  • ๐Ÿ“Š No significant differences in DFS, DDFS, OS, or RNR between arms; 7-yr RNR 1.2% overall
  • ๐Ÿ“Š Cosmesis at 3yr: NI met by both measures
    • Physician-rated excellent/good: 82.4% concurrent vs 85.9% sequential, p=0.34
    • Central digital photo review excellent/good: 72.0% vs 64.2%, p=0.11
    • BCTOS mean change from baseline: 0.18 concurrent vs 0.16 sequential (NI met)
  • โš ๏ธ G3-4 AEs similar between arms (p=0.81); radiation dermatitis, fatigue, breast pain most prevalent
  • Long-term cosmesis and fibrosis beyond 3-yr QoL endpoint
  • Applicability to pts on hormonal therapy without chemo (lower baseline risk)
  • Integration with APBI or partial-breast techniques
๐Ÿ“š Sources ยท ๐Ÿ“„ 1 paper
๐Ÿ“„ PAPER Vicini; Winter; Freedman et al. ยท Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2026-05)
Concurrent Versus Sequential Radiation Dose Escalation to the Surgical Cavity for Conservative Treatment of High-Risk Early Breast Cancer: NRG/RTOG 1005 Phase III Trial.
Abstract
PURPOSE: For patients with breast cancer undergoing breast conservation, escalating the dose (boost) of radiation to the lumpectomy cavity after whole-breast irradiation (WBI) reduces ipsilateral breast recurrence (IBR) but extends treatment duration. This phase III trial investigated whether boost delivery during WBI versus after WBI provides noninferior IBR and preserves cosmetic appearance.<br/><br/>METHODS: NRG/RTOG 1005 randomly assigned patients at higher risk for IBR after lumpectomy and axillary surgery to either a sequential boost of 12 Gy in six fractions(F) or 14 Gy in 7F after WBI of 50 Gy in 25F or 42.7 Gy in 16F (sequential arm) or a concurrent boost of 8 Gy in 15F of 0.53 Gy per day with WBI of 40 Gy in 15F (concurrent arm) using 3-dimensional conformal radiation therapy (RT) or intensity-modulated RT. Based on 1.59% 5-year IBR for the sequential arm, defining the noninferiority margin as a hazard ratio upper limit on the 90% CI of 2.12, 2,312 patients provide 80% power for noninferiority of IBR as first recurrence for the concurrent arm. Secondary end points included disease-free survival and overall survival, adverse events (AEs), and cosmetic outcomes.<br/><br/>RESULTS: Between May 24, 2011, and June 20, 2014, 2,354 patients were randomly assigned, with 2,255 eligible for analysis (sequential arm, n = 1,118; concurrent arm, n = 1,137). With median follow-up of 7.3 years, there were 56 IBR events; 5- and 7-year IBR were 2.1% and 2.2% on the sequential arm and 1.9% and 2.6% on the concurrent arm, respectively. The noninferiority criterion was met: HR (90% CI): 1.31 (0.84 to 2.04), P = .037. No differences were observed in AEs, cosmetic outcomes, or survival between arms.<br/><br/>CONCLUSION: Concurrent boost during WBI results in noninferior IBR compared with sequential boost without worsening toxicity or cosmetic outcomes and reduces overall treatment time.
๐Ÿ“ Vicini FA, Winter K, Freedman GM, Arthur DW, Rosenstein BS, Bentzen SM, Li XA, Halyard MY, Woodward WA, Bleicher RJ, Taghian A, Lyons J, Tomberlin JK, Seaward SA, Cheston SB, Hoover AC, Anderson BM, Perera FE, Poppe MM, Petersen IA, Jhawar S, Hijal T, Moughan J, Movsas B, White JR. Concurrent Versus Sequential Radiation Dose Escalation to the Surgical Cavity for Conservative Treatment of High-Risk Early Breast Cancer: NRG/RTOG 1005 Phase III Trial. J Clin Oncol. 2026 May 11:JCO2502465. ; PMCID: PMC13166090.

APBI-IMRT Florence NCT02104895

ForEarly BC post-BCS, pT <25mm, FSM โ‰ฅ5mm, age >40

TL;DR15-yr IBTR 7.7% vs 4.2% (HR 1.57, p=0.17); no locoregional control, BCSS, or OS difference confirms APBI de-escalation.

vs leading data
  • Consistent with RAPID (phase III, similar local recurrence rates); supports guideline-listed APBI indications

Radiation Curative Phase 3 RCT Confirmatory

APBI-IMRT Florence
EndpointAPBI (15-yr)WBI (15-yr)p
IBTR20 (7.7%)11 (4.2%)0.14
IBTR HR1.57 (0.82-3.04)โ€”0.17
Local relapse5 (2.1%)4 (1.6%)0.75
New ipsilateral primary15 (5.9%)7 (2.7%)0.09
+2 more figures
APBI-IMRT Florence
APBI-IMRT Florence
7 details
  • ๐Ÿ” Phase III equivalence trial, N=520, 1:1 randomization, enrolled 2005-2013
  • ๐Ÿ” APBI: IMRT 30Gy/5 fractions; WBI: 50Gy/25# + 10Gy tumor bed boost
  • ๐Ÿ” Eligible: BCS, pT <25mm, FSM โ‰ฅ5mm, age >40; ITT for survival, per-protocol for toxicity/cosmesis
CONSORT flow
Randomized 520
โ†“
PBI IMRT (30Gy/5#)
allocated 260
WBI (50Gy/25# + 10Gy TBB)
allocated 260
  • ๐Ÿ“Š Secondary oncological outcomes at 15 years
  • โš ๏ธ IBTR excess in APBI driven by new ipsilateral primaries, not true local recurrence
  • โš ๏ธ Equivalence powered for 5-yr IBTR ฮ”5%; underpowered to exclude small absolute OS differences at 15 years
  • โš ๏ธ 2005-2013 enrollment; applicability with contemporary genomic risk stratification uncertain
  • Whether IBTR signal from new primaries reflects inadequate coverage or independent field biology
  • Applicability with contemporary genomic risk stratification and wider APBI eligibility criteria
  • Long-term cosmesis and toxicity outcomes in per-protocol population
๐Ÿ“š Sources ยท ๐Ÿฆ 1 tweet

DBCG HYPO

ForNode-negative early breast cancer or DCIS, adjuvant whole-breast RT

TL;DR10-yr G2-3 induration HR 0.76 (19.5% vs 24.7%) favoring 40Gy/15fr; OS and locoregional outcomes equivalent at 12.8yr median f/u.

vs leading data
  • Consistent with START B and FAST-FORWARD: extends long-term safety/efficacy evidence for moderate hypofractionation beyond 5yr

Radiation Curative Phase 3 RCT Confirmatory

DBCG HYPO
Endpoint50 Gy/25fr40 Gy/15frHR (95% CI)p
10-yr G2-3 induration24.7%19.5%0.76 (0.62-0.92)0.005
10-yr OS92.1%93.0%0.81 (0.63-1.04)0.10
+1 more figure
DBCG HYPO
4 details
  • ๐Ÿ” Phase III non-inferiority RCT (1:1), N=1,882, node-negative BC or DCIS, Denmark/Norway/Germany, 2009-2014
CONSORT flow
Randomized 1882
โ†“
50 Gy/25fr
allocated 949
analyzed 936
40 Gy/15fr
allocated 933
analyzed 917
  • ๐Ÿ“Š No significant differences in locoregional recurrence, distant failure, or breast cancer mortality at 10 yrs
  • โš ๏ธ Original 1ยฐ EP was 3-yr grade โ‰ฅ2 induration; 10-yr toxicity, recurrence, and survival analyses were prespecified
  • โš ๏ธ Trial not powered for 10-yr OS as 1ยฐ endpoint; HR 0.81 (p=0.10) non-significant and should not be over-interpreted
  • Whether 10-yr induration benefit extends to pts receiving regional nodal RT
  • Long-term comparison with ultra-hypofractionation (FAST-FORWARD 26Gy/5fr)
๐Ÿ“š Sources ยท ๐Ÿฆ 1 tweet

IMPORT HIGH

ForInvasive early BC (pT1-3, pN0-N3a, M0) post-BCS requiring tumour bed boost RT

TL;DR48Gy SIB: 10-yr IBTR 3.7% vs 3.5% sequential boost, non-inferior; further escalation to 53Gy not beneficial (5.5%).

vs leading data
  • 5-yr non-inferiority of 48Gy SIB published Lancet 2023 (401:2124-37); 10-yr results confirm durable local control

Radiation Curative Phase 3 RCT Confirmatory

IMPORT HIGH
Arm10-yr IBTR (95% CI)
40Gy/15F + 16Gy/8F3.5% (2.4, 5.0)
48Gy/15F (3.2Gy/F)3.7% (2.6, 5.3)
53Gy/15F (3.5Gy/F)5.5% (4.1, 7.3)
+1 more figure
IMPORT HIGH
Arm5-yr IBTR (95% CI)
40Gy/15F + 16Gy/8F1.9% (1.2, 3.1)
48Gy/15F (3.2Gy/F)2.0% (1.2, 3.2)
53Gy/15F (3.5Gy/F)3.2% (2.2, 4.7)
6 details
  • ๐Ÿ” Phase 3 RCT, N=2617 (1:1:1), 76 UK hospitals, 2009-2015; pT1-3 pN0-N3a M0 invasive BC post-BCS requiring tumour bed boost
  • ๐Ÿ” SIB delivers boost in 15 fractions (3 weeks) vs 23 total for sequential 40+16Gy; reduced pt visits
CONSORT flow
Randomized 2617
โ†“
40Gy/15F + 16Gy/8F (sequential)
allocated 871
48Gy/15F SIB (3.2Gy/F)
allocated 874
53Gy/15F SIB (3.5Gy/F)
allocated 872
  • ๐Ÿ“Š 10-yr OS absolute difference vs 40+16Gy (both NS)
    • 48Gy/15F: -0.5% (-3.0, 2.8)
    • 53Gy/15F: +1.5% (-1.4, 5.1)
  • โš ๏ธ 53Gy/15F: numerically higher 10-yr IBTR than control; dose escalation beyond 48Gy adds no benefit
  • โš ๏ธ Moderate/marked late AEs at 10yr (all arms)
    • Breast distortion/shrinkage: <18%
    • Induration: <10%
    • Telangiectasia: <2%
    • Breast oedema: <2%
  • โš ๏ธ 10-yr IBTR in both boost groups remains below the 5% control estimate used in original sample size calculations
  • Any subgroup that benefits from 53Gy escalation
  • Very long-term (>10yr) toxicity trajectory
  • Applicability to post-mastectomy or regional nodal RT settings
๐Ÿ“š Sources ยท ๐Ÿฆ 1 tweet

EORTC IM-MS (22922/10925)

ForStage I-III BC, node-positive or pN0, adjuvant IM-MS RT decision

TL;DR20-yr OS null (HR 1.00, p=0.967); BCM benefit offset by non-BCM excess; pN0: no benefit.

vs leading data
  • DBCG IMN2 (Lancet Reg Health Eur 2024): modern IM-MS RT (MHD 1.2 Gy right / 2.3 Gy left) showed BCM + DM + OS benefit at 15yr in node-positive pts

Radiation Curative Phase 3 RCT Challenges SOC

EORTC IM-MS (22922/10925)
Arm20-yr OSHR (95% CI)p
+IM-MS RT61.0%1.00 (0.90-1.10)0.967
-IM-MS RT61.8%โ€”โ€”
+3 more figures
EORTC IM-MS (22922/10925)
Endpoint (15yr)+IM-MS-IM-MSHR (95% CI)p
BCM18.6%22.4%0.82 (0.72-0.95)0.006
non-BCM20.4%15.8%1.26 (1.09-1.46)0.002
EORTC IM-MS (22922/10925)
Late AE (absolute rate)+IM-MS-IM-MS
Lung fibrosis6.3%3.2%
Cardiac fibrosis2.7%1.7%
Cardiac diseases15.2%11.7%
EORTC IM-MS (22922/10925)
Endpoint (20yr, pN0)+IM-MS-IM-MSHR (95% CI)p
DFS53.9%53.6%0.93 (0.81-1.07)0.318
DMFS67.2%67.4%0.93 (0.78-1.10)0.397
4 details
  • ๐Ÿ” Phase III RCT, N=4004, stage I-III BC; IM + medial supraclavicular RT vs no IM-MS RT; 20-yr follow-up
CONSORT flow
Randomized 4004
โ†“
+IM-MS RT
allocated 2002
-IM-MS RT
allocated 2002
  • ๐Ÿ“Š BCM reduction (HR 0.82, p=0.006 at 15yr) fully offset by non-BCM excess (HR 1.26, p=0.002); net OS nullified at 20yr
  • โš ๏ธ pN0 subgroup: no DFS or DMFS benefit at 20yr; IM-MS benefit restricted to node-positive disease
  • โš ๏ธ EORTC era heart doses 4-9x higher than DBCG IMN2; late cardiac mortality likely drives the non-BCM excess at 20yr
  • Whether modern low-dose cardiac RT (DBCG IMN2) restores net OS benefit at 20yr
  • Which node-positive subgroup (pN1 vs pN2-3) retains net BCM benefit over late cardiotox
  • Should pN0 be excluded from IM-MS RT indications given consistently null data
๐Ÿ“š Sources ยท ๐Ÿฆ 2 tweets

DBCG RT Natural

Forโ‰ฅ60y, pT1N0, ER+ โ‰ฅ10%, HER2-normal, grade 1-2, unifocal post-lumpectomy

TL;DR9.8% 4-yr LR without PBI vs 1.5% with PBI in pT1N0 low-risk elderly breast conservation; stopped early per pre-specified threshold.

vs leading data
  • PRIME II (Lancet Oncol 2015): ~10% 10-yr LR without RT in โ‰ฅ65y low-risk ER+; RT benefit durable

Radiation Curative Phase 3 RCT Challenges SOC

DBCG RT Natural
ArmEvents/TotalCIF % (95% CI)
+RT2/2361.5 (0.3-5.1%)
-RT19/2729.8 (5.9-14.9%)
S-RT18/2788.2 (4.5-13.3%)
+1 more figure
DBCG RT Natural
4 details
  • ๐Ÿ” Phase III RCT; โ‰ฅ60y, pT1N0, ER+ โ‰ฅ10%, HER2-normal, grade 1-2, unifocal, non-lobular, margin โ‰ฅ2mm, breast conservation
  • ๐Ÿ” RT arm: PBI 40Gy/15fr; ET per DBCG guideline (recommended pT1c and/or grade 2); stratified by institution + ET yes/no
CONSORT flow
Randomized 508
โ†“
PBI 40Gy/15fr
allocated 236
No PBI
allocated 272
  • โš ๏ธ Median FU 4 yrs; primary endpoint is 5-yr invasive LR; stopped early per pre-specified 4% max-LR threshold
  • โš ๏ธ Suboptimal ET adherence per presenter; -ET groups drive high LR in the -RT arm; adherence confounds the no-treatment effect
  • Whether WBRT (vs PBI) changes the RT-omission picture in this population
  • Which molecular low-risk subset, if any, can safely defer all adjuvant therapy
  • Duration of ET benefit when combined with PBI in โ‰ฅ60y low-risk pts
๐Ÿ“š Sources ยท ๐Ÿฆ 2 tweets

HypoG-01

ForEarly-stage breast cancer, adjuvant hypofractionated RT

TL;DRLRR 16% of 118 events; failure patterns comparable between 40 Gy/15fx and 50 Gy/25fx; most in-volume per ESTRO guidelines.

vs leading data
  • Patterns of failure not obviously different between 3-week and 5-week arms
  • ESTRO-guided contouring adequately covers LRR sites

Radiation Curative Phase 3 RCT Confirmatory

HypoG-01
Event typen%
Isolated distant recurrence6151%
Second malignancy3731%
LRR (iLRR + cLRR)2016%
+1 more figure
HypoG-01
6 details
  • ๐Ÿ” Pre-planned secondary analysis of HypoG-01 phase III RCT (ITT); N=1260, median f/u 4.8 years
  • ๐Ÿ” 40 Gy/15fx vs 50 Gy/25fx + tumor-bed boost; endpoint: first oncological event (LRR, DR, or second malignancy)
  • ๐Ÿ“Š 118 first oncological events total; LRR lowest-frequency event (20/118, 16%)
  • ๐Ÿ“Š First events by type (N=118)
    • Isolated distant recurrence: 61 (51%)
    • Second malignancy: 37 (31%)
    • LRR (isolated + concomitant): 20 (16%)
  • ๐Ÿ“Š Of LRR sites assessed: 20/30 in-volume (67%) per ESTRO contouring; 19/30 were nodal (mainly L1 & L2)
  • โš ๏ธ Secondary analysis not powered for arm-vs-arm failure subtype comparisons; no formal statistical testing of between-arm pattern differences reported
  • Longer f/u needed to assess late second malignancy differences between arms
  • Whether ESTRO contouring adequacy extends to higher-risk subgroups (node-positive, TNBC)
๐Ÿ“š Sources ยท ๐Ÿฆ 1 tweet

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%
โ‰ฅ3 (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
  • ๐Ÿ” Dutch registry retrospective cohort, BCT pts 2012-2016; boost vs no-boost allocation was clinical, non-randomized
  • ๐Ÿ” Five risk factors scored: age โ‰ค40, 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)
    • โ‰ฅ3 rf: small high-risk minority (n=149 no boost, n=733 boost)
  • ๐Ÿ“Š Assisi decision thresholds: boost omissible if 10yr IBTR <3% (boosted cohort) or <6% (no-boost); only boosted โ‰ฅ3-rf pts exceeded threshold at 10yr (3.3%)
  • โš ๏ธ Non-randomized; no-boost selection reflects clinician risk stratification, not random allocation; confounding by indication expected
  • โš ๏ธ No-boost arm for โ‰ฅ3 rf pts very small (n=149); insufficient to characterize boost omission in high-risk subgroup
  • RCT needed to confirm boost omission equivalence in 0-2 risk-factor pts
  • Optimal RT boost strategy for โ‰ฅ3 risk-factor pts where boosted 10yr IBTR still exceeds Assisi threshold
๐Ÿ“š Sources ยท ๐Ÿฆ 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
  • ๐Ÿ” De-escalation strategy: locoregional RT field/dose reduced based on nodal pathological response after neoadjuvant chemotherapy
  • ๐Ÿ“Š Locoregional recurrence <3% at 10yr with pathological nodal response-guided RT de-escalation post-neoadjuvant
  • โš ๏ธ No CI, HR, or comparator arm outcome reported in source; design not confirmed as randomized
  • 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?
๐Ÿ“š Sources ยท ๐Ÿฆ 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
  • ๐Ÿ” Phase II randomized, multi-histology basket design; all solid tumor histologies eligible
  • ๐Ÿ’Š MDT + SOC vs SOC alone; metastasis-directed therapy (radiation-based ablation) added to ongoing systemic SOC
  • ๐Ÿ” ctDNA correlatives presented at ESTRO26 synchronously with primary JCO publication
  • ๐Ÿ“Š Primary aggregated analysis across all tumor histology baskets; no effect size reported in source tweet
  • โš ๏ธ Basket aggregation across histologies: pooled primary estimate may obscure site-specific heterogeneity in MDT benefit
  • 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?
๐Ÿ“š Sources ยท ๐Ÿฆ 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
  • ๐Ÿ” Phase III open-label non-inferiority, N ~434; Tata Memorial + collaborating centers, India
  • ๐Ÿ” High-risk, very high-risk, and/or node-positive non-metastatic prostate cancer; ECOG 0-2; PSMA PET/CT staging allowed
  • ๐Ÿ” Both arms: prostate + whole-pelvis RT + long-course ADT (~2yr); SIB to positive nodes in SBRT arm
  • ๐Ÿ’Š 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
  • ๐Ÿ“Š 1ยฐ EP: BFFS (Phoenix nadir +2 ng/mL); interim only, mature 4-5yr data pending
  • ๐Ÿ“Š Early BFFS, MFS, OS: no significant differences; no inferiority signal for SBRT at interim
  • โš ๏ธ Interim analysis (1-2yr f/u) only; 4-5yr primary endpoint not yet reached; non-inferiority pending
  • 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
๐Ÿ“š Sources ยท ๐Ÿฆ 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
  • ๐Ÿ” Phase 3 RCT, N=1465, 39 UK centres; 3 arms (prostate, prostate+boost, prostate+pelvic+boost); 20-fraction moderately hypofractionated RT
  • ๐Ÿ” High-risk localised prostate cancer; 1ยฐ EP biochemical/clinical failure โ€” efficacy data not reported here; secondary toxicity endpoints presented
  • ๐Ÿ“Š Early bowel side effects increased with pelvic node RT; resolved by 18 weeks post-RT
  • ๐Ÿ“Š No significant differences in G2+ bowel or bladder toxicity at 2 years across arms (973 pts, 74% with โ‰ฅ2yr f/u)
  • โš ๏ธ 2-year late toxicity is preliminary for prostate RT; G3+ late effects can emerge at 5+ years
  • Primary efficacy (biochemical/clinical failure) not yet reported
  • Late toxicity beyond 2 years needed to confirm durability
๐Ÿ“š Sources ยท ๐Ÿฆ 1 tweet

PACE-NODES

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

TL;DRPPN-SBRT increases Gโ‰ฅ2 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
Gโ‰ฅ2 GI toxicity (12wk)28%21%
+1 more figure
PACE-NODES
8 details
  • ๐Ÿ” 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
  • ๐Ÿ’Š P-SBRT: 36.25Gy/5f (prostate); PPN-SBRT: 36.25Gy/5f (prostate) + 25Gy/5f (nodes), alternate days
  • ๐Ÿ“Š Gโ‰ฅ2 GI toxicity over 12wk: 28% PPN-SBRT vs 21% P-SBRT
  • ๐Ÿ“Š GI symptoms resolved; no difference between arms at 12 weeks
  • ๐Ÿ“Š EPIC-26 bowel domain worse at 4 weeks in PPN-SBRT arm
  • ๐Ÿ“Š No difference in acute GU toxicity (CTCAE or patient-reported)
  • โš ๏ธ 11% PPN-SBRT vs 4% P-SBRT did not receive allocated treatment, mostly due to planning constraints not being met
  • โš ๏ธ Primary endpoint (time to biochemical/clinical failure) not yet mature; this is an acute toxicity interim report only
  • 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
๐Ÿ“š Sources ยท ๐Ÿฆ 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)โ€”
p (Cox)0.00119โ€”
p (log-rank)0.00079โ€”
8 details
  • ๐Ÿ” Phase II RCT, N=102, 1:1; Arm A: SBRT alone vs Arm B: SBRT + 6mo ADT; oligorecurrent prostate cancer
  • ๐Ÿ” 49/51 Arm B pts achieved testosterone recovery within follow-up; benefit persisted after castration resolved
CONSORT flow
Randomized 102
โ†“
Arm A (SBRT)
allocated 51
Arm B (SBRT + ADT)
allocated 51
  • ๐Ÿ“ Median follow-up 49.23mo (95% CI 42.47-54.8) by reverse KM
  • ๐Ÿ“Š Metastatic progression: 32/51 (62.7%) Arm A vs 19/51 (37.3%) Arm B
  • ๐Ÿ“Š 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
  • ๐Ÿ“Š Eugonadal MFS (post-testosterone recovery) significantly longer in Arm B (p<0.05)
  • โš ๏ธ Post-hoc analysis of MFS and eugonadal MFS; neither was a prespecified primary endpoint of the parent RADIOSA trial
  • โš ๏ธ Small N (51/arm); post-hoc design; MFS not powered; results hypothesis-generating only
  • 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?
๐Ÿ“š Sources ยท ๐Ÿฆ 1 tweet

PEACE-2

ForVery high-risk localized prostate Ca (โ‰ฅ2 of Gleason โ‰ฅ8, T3-T4, PSA โ‰ฅ20), 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]referenceโ€”
+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
  • ๐Ÿ” Trial design
    • Phase III 2ร—2 factorial (pelvic vs prostate-only RT ร— ยฑ cabazitaxel ร—4)
    • Very high-risk PCa: N0M0, โ‰ฅ2 of Gleason โ‰ฅ8, T3-T4, PSA โ‰ฅ20
    • ADT 3yr + 78 Gy EQD2 dose-escalated IMRT; PSMA PET/CT staging; accrual 2018-2023
CONSORT flow
Randomized 761
โ†“
Pelvic RT
allocated 381
Prostate-only RT
allocated 380
  • ๐Ÿ“Š All secondary endpoints (bPFS, MFS, CSS, OS) also non-significant with pelvic RT
  • โš ๏ธ Interim analysis at ESTRO 2026 (median f/u ~5.5yr); final prespecified primary analysis pending
  • โš ๏ธ PSMA PET/CT may exclude occult metastatic pts who drove pelvic RT benefit in the conventional-imaging era
  • โš ๏ธ Longer ADT (3yr vs 2yr) + dose escalation may reduce incremental pelvic RT gain
  • โš ๏ธ No added toxicity: comparable Gโ‰ฅ2 GU rates in both arms
  • โš ๏ธ Blanchard: <1 in 10 dying from PCa at 10yr challenges the 'very high-risk' label in modern-imaged pts
  • 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?
๐Ÿ“š Sources ยท ๐Ÿฆ 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
  • ๐Ÿ“Š 5-yr LC: 100% (per ๐Ÿ’ฏ emoji in source tweet; no numeric table provided)
  • โš ๏ธ N, fractionation, eligibility, and survival endpoints absent from source
  • โš ๏ธ design not specified; likely single-arm phase 2 โ€” no comparator arm
  • OS/RFS benefit vs partial nephrectomy or thermal ablation
  • Optimal fractionation by tumor size and collecting system proximity
๐Ÿ“š Sources ยท ๐Ÿฆ 1 tweet

DIREKHT

ForPost-operative HNSCC, low contralateral nodal risk subgroup

TL;DRPost-op RT de-intensification in HNSCC: contralateral neck sparing and/or primary CTV dose reduction to 56 Gy; no effect size reported in source tweet.

vs leading data
  • De-escalation context: ECOG-ACRIN 3311 (HPV+ oropharynx) and NRG HN002 established dose/volume reduction as feasible; DIREKHT extends this logic to post-op setting with anatomic field reduction

Radiation Curative Unclear

5 details
  • ๐Ÿ” Post-operative RT de-intensification trial in HNSCC
  • ๐Ÿ” Two strategies evaluated: contralateral neck sparing in selected pts and/or primary CTV dose reduction to 56 Gy (vs standard 60-66 Gy)
  • ๐Ÿ“Š No effect size, HR, or primary endpoint result reported in source tweet (content truncated)
  • โš ๏ธ De-intensification trials in post-op HNSCC carry risk of local-regional relapse if patient selection criteria are not tightly specified; contralateral neck failure rates in similar series run 3-8%
  • โ“ Whether contralateral neck sparing and dose reduction are evaluated as independent arms or a composite de-intensification strategy is unclear from source
  • Local-regional control rates with contralateral neck sparing vs elective nodal irradiation
  • Which patient subgroup (HPV+, N stage, margin status) benefits from 56 Gy de-escalation
  • Whether both de-intensification strategies are independently randomized or combined
๐Ÿ“š Sources ยท ๐Ÿฆ 1 tweet