onc brain

About ยท curated by Nick Boehling, MD ยท @nb2276

    Phase 2 trial

    17 studies Subscribe via RSS โ†’

    NRG Oncology RTOG 0539 NCT00895622

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

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

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

    Radiation Curative Phase 2 trial Early signal

    7 details 3 trials watching
    Methods
    • 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
    Results
    • 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%)
    Critique
    • 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)
    Open questions
    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
    PMID โ†’ doi
    Abstract
    NRG Oncology RTOG 0539 was a prospective phase II trial of risk-adapted radiotherapy for patients with WHO grade 1-3 meningioma. Low-risk (group 1, n = 60) was defined as a grade 1 tumor after gross total resection or subtotal resection (GTR/STR) and prospectively monitored. Intermediate-risk (group 2, n = 52) was defined as recurrent grade 1 or newly diagnosed grade 2 tumor after GTR and treated with radiotherapy (54 Gy). High-risk (group 3, n = 53) included a newly diagnosed grade 2 tumor after STR, newly diagnosed grade 3 tumor, or recurrent grade 2 or 3 tumor and treated with radiotherapy (60 Gy). Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. The median follow-up times for the low-, intermediate-, and high-risk cohorts were 12.1, 12.0, and 11.1 years, respectively. The 10-year PFS and OS rates for the low-, intermediate-, and high-risk cohorts were 85.2% and 94.1%, 72.2% and 84.7%, and 42.5% and 51.1%, respectively. Five patients (9.6%) and eight patients (15.1%) had a grade 3+ toxicity attributed to radiotherapy in the intermediate- and high-risk cohorts, respectively. The long-term outcomes using this risk-adapted approach support observation for low-risk patients, inform radiotherapy patient selection and practice standards for intermediate- and high-risk patients, and provide comparative benchmarks for future trials.

    RAPCHEM (BOOG 2010-03)

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

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

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

    Radiation Curative Phase 2 trial Early signal

    7 details 3 trials watching
    Methods
    • 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
    Results
    • 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
    Critique
    • 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
    Open questions
    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
    PMID โ†’
    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

    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
    Methods
    • 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
    Results
    • ๐Ÿ“Š 1ยฐ EP: 12-month DFS 80% (40/50; 95% CI 0.67-0.89); cleared pre-set GO threshold โ‰ฅ75%
    Critique
    • 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
    Open questions
    • 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
    Methods
    • ๐Ÿ” Durvalumab + CRT trial: N=54 MIBC, 55 Gy/20 fr + MMC/5-FU + durvalumab, single-arm phase 2
    Results
    • 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
    Critique
    • โš ๏ธ No efficacy endpoints reported; long-term bladder preservation, function, QOL, and safety require further follow-up
    Open questions
    • Long-term bladder preservation and QOL rates with durvalumab + CRT
    • Optimal post-pCR strategy: surveillance vs adjuvant IO
    • Will EVP bladder-sparing (EV209/EV309) improve on CRT outcomes?
    ๐Ÿ“š Sources ยท ๐Ÿฆ 2 tweets

    A-DREAM (ALLIANCE mAPMS)

    FormHSPC achieving PSA<0.2 after โ‰ฅ18-24mo ADT+ARPI, low-volume predominant

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

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

    Systemic Palliative Phase 2 trial Early signal

    A-DREAM (ALLIANCE mAPMS)
    +2 more figures
    A-DREAM (ALLIANCE mAPMS)
    A-DREAM (ALLIANCE mAPMS)
    9 details
    Methods
    • ๐Ÿ” Single-arm phase II, N=78 enrolled 07/2022-03/2024; PSA<0.2 after โ‰ฅ18-24mo ADT + โ‰ฅ12mo ARPI
    • ๐Ÿ” Re-initiation triggers: PSA โ‰ฅ5 ng/mL, radiographic change (PCWG3), or PrCa-related sx
    Results
    • ๐Ÿ“ Primary EP: 80% CI 33.1-48.9%, one-sided p=0.0249; pre-specified 80% CI threshold (not 95%)
    • ๐Ÿ“Š Median time to eugonadal T recovery: 9.0mo (95% CI 8.4-12.4)
    • ๐Ÿ“Š Disposition at 26.9mo: 38.5% still off-tx; 37.2% resumed ADT+ARPI per protocol; 9.0% started non-protocol tx
    • ๐Ÿ“Š rPFS from interruption: 15/78 events, median NE (32.5-NE); 12-mo est 94.6% (89.6-99.9%)
    • ๐Ÿ“Š OS: 4/78 events, median NE; causes: prostate cancer, MDS, influenza, MI
    Critique
    • โš ๏ธ Single-arm; no randomized comparator vs continuous ADT+ARPI
    • โš ๏ธ 64.9% low-volume CHAARTED, 84.6% White; high-volume and diverse pts underrepresented
    Open questions
    • Impact on long-term OS vs continuous ADT+ARPI: randomized trial needed
    • Optimal re-initiation criteria in high-volume vs low-volume disease
    • Biomarker predictors of durable treatment-free interval
    ๐Ÿ“š Sources ยท ๐Ÿฆ 1 tweet

    ARACOG (AFT-47)

    FormHSPC, nmCRPC, or mCRPC on ARSI; cognitive toxicity a concern

    TL;DRMCCD median -36.1 (ENZ) vs -15.8 (DAR) at 24wk, p=0.009; enzalutamide caused significantly greater cognitive decline.

    vs leading data
    • Consistent with pharmacology: darolutamide has substantially lower CNS penetration vs enzalutamide, predicting less cognitive toxicity mechanistically

    Systemic Phase 2 trial Confirmatory

    ARACOG (AFT-47)
    Arm (N)MCCD ModuleMedian Change
    Darolutamide (48)PALFAM-15.8
    Enzalutamide (47)SWM-36.1
    P-value0.009
    +1 more figure
    ARACOG (AFT-47)
    6 details
    Methods
    • ๐Ÿ” Randomized open-label phase 2, N=111 (mHSPC, nmCRPC, mCRPC), DAR vs ENZ; enrolled 8/2021-3/2025
    • ๐Ÿ” MCCD = maximally changed cognitive domain across 5 remote CANTAB tests: executive function, visual memory, attention, working memory
    • ๐Ÿ’Š Darolutamide provided by study; enzalutamide through standard of care
    Results
    • ๐Ÿ“Š 1ยฐ EP: CANTAB MCCD at 24wk median change -36.1 (ENZ, N=47) vs -15.8 (DAR, N=48), p=0.009
    Critique
    • โš ๏ธ Open-label; crossover allowed before 24wk, analyzed at crossover timepoint in randomized arm
    • โš ๏ธ CANTAB modules are research instruments, not clinical cognitive diagnostic tools
    Open questions
    • Cognitive difference durability beyond 24 weeks
    • Whether MCCD effect size translates to clinically meaningful QoL impact
    • Disease-state subgroup breakdown (mHSPC vs nmCRPC vs mCRPC)
    ๐Ÿ“š Sources ยท ๐Ÿฆ 2 tweets

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

    ForAdvanced NSCLC, atypical EGFR mutation, treatment-naive

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

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

    Systemic Palliative Phase 2 trial Early signal

    OS: median 41.0 mo (95% CI 27.7-NE); landmark rates 85%, 72%, 55%; median f/u 31.3 mo; n at risk 49 โ†’ 10 โ†’ 0.
    OS: median 41.0 mo (95% CI 27.7-NE); landmark rates 85%, 72%, 55%; median f/u 31.3 mo; n at risk 49 โ†’ 10 โ†’ 0.
    +1 more figure
    Median treatment duration 13.3 mo (range <0.1-53.2); 39% on treatment >2 years.
    Median treatment duration 13.3 mo (range <0.1-53.2); 39% on treatment >2 years.
    7 details
    Methods
    • ๐Ÿ” Single-arm, n=49; 1L atypical EGFR-mutated advanced NSCLC
    • ๐Ÿ’Š Median treatment duration 13.3 mo (range <0.1-53.2)
    • ๐Ÿ’Š 39% remained on treatment >2 years
    Results
    • ๐Ÿ“Š Median OS 41.0 mo (95% CI 27.7-NE); median follow-up 31.3 mo
    Critique
    • โš ๏ธ Single-arm; no randomized comparator vs osimertinib or chemotherapy
    • โš ๏ธ Small N (49) limits any subgroup analysis by EGFR variant subtype
    • โš ๏ธ No clear EGFR variant subtype-outcome association found; underpowered to confirm or exclude
    Open questions
    • Randomized trial vs osimertinib in atypical EGFR needed to confirm benefit
    • CNS penetration and activity across atypical EGFR variant subtypes
    • SC amivantamab formulation (COPERNICUS) applicability in this population
    ๐Ÿ“š Sources ยท ๐Ÿฆ 1 tweet

    ESAONA

    For1L EGFR-mutated NSCLC with active brain metastases

    TL;DRIntracranial ORR 95.5% vs 79.6% (p=0.0004), iPFS HR 0.46 favoring asandeutertinib over osimertinib in 1L EGFR+ NSCLC with brain mets.

    vs leading data
    • Osimertinib established 1L SOC via FLAURA; ESAONA is first randomized head-to-head with a next-gen EGFR TKI in the brain-met-enriched setting

    Systemic Palliative Phase 2 trial Challenges SOC

    ESAONA
    EndpointAsandeutertinibOsimertinibHR / p
    iORR (BICR)95.5% (89.8-98.5%)79.6% (71.0-86.6%)p=0.0004
    Intracranial PFSNR17.5 mo (15.18-NA)HR 0.46, p=0.0020
    Overall PFSNR17.2 mo (15.18-19.55)HR 0.64, p=0.0473
    5 details
    Methods
    • ๐Ÿ” Phase II, randomized, N=224; 1L EGFR-mutated NSCLC with brain mets, asandeutertinib (n=111) vs osimertinib (n=113)
    • ๐Ÿ’Š Asandeutertinib: next-generation EGFR TKI evaluated head-to-head vs established osimertinib SOC
    CONSORT flow
    Randomized 224
    โ†“
    Asandeutertinib
    allocated 111
    Osimertinib
    allocated 113
    Critique
    • โš ๏ธ Safety (TRAEs)
      • Any TRAEs: 99.1% (asandeutertinib) vs 95.6% (osimertinib)
      • Serious TRAEs: 10.8% vs 7.1% โ€” slightly higher in experimental arm
    • โš ๏ธ Phase 2 only, N=224; PFS medians not reached in experimental arm (immature); OS data not reported in source
    • โš ๏ธ Primary EP was iORR (response endpoint), not PFS or OS; longer follow-up required for survival readout
    Open questions
    • Phase 3 OS confirmatory data needed before practice adoption
    • Activity after progression on prior osimertinib unknown
    • Optimal sequencing vs osimertinib + chemo (FLAURA2) in brain-met population
    ๐Ÿ“š Sources ยท ๐Ÿฆ 1 tweet

    PREPEC

    ForNipple-sparing or skin-sparing mastectomy for breast cancer treatment or risk re

    TL;DRBREAST-Q chest score 79.2 vs 74.3 (diff 4.8, p=0.01) favoring pre-pectoral IBBR; implant loss 21% vs 15%.

    vs leading data
    • Prior observational series suggested PRO advantage with pre-pectoral IBBR; PREPEC is first large RCT to test this directly

    Surgery Phase 2 trial Confirmatory

    PREPEC
    ArmLS mean (95% CI) at 24 mo
    Pre-pectoral IBBR (N=191)79.2 (75.5-82.8)
    Sub-pectoral IBBR (N=189)74.3 (70.7-78.0)
    Difference4.8 (1.0-8.7), p=0.01
    +2 more figures
    PREPEC
    ArmCrude % at 24 mo (n/N)Adj diff (95% CI)
    Pre-pectoral IBBR21.1% (41/194)5.7% (-2.4 to 13.8)
    Sub-pectoral IBBR14.5% (27/186)ref
    PREPEC
    4 details
    Methods
    • ๐Ÿ” International RCT; nipple-sparing or skin-sparing mastectomy; therapeutic + risk-reduction setting
    • ๐Ÿ” 1ยฐ EP: BREAST-Q physical well-being (chest) at 24 months; LS mean from linear mixed model; longitudinal completion 83-95%
    CONSORT flow
    Randomized 380
    โ†“
    Pre-pectoral IBBR
    allocated 194
    analyzed 191
    Sub-pectoral IBBR
    allocated 186
    analyzed 189
    Critique
    • โš ๏ธ Main secondary safety EP missed non-inferiority: pre-pectoral had higher unplanned implant loss/replacement
    • โš ๏ธ 4.8-point BREAST-Q difference is modest; minimum clinically important difference for this subscale is debated
    Open questions
    • Does PRO benefit persist beyond 24 months?
    • Which pts tolerate higher implant failure risk of pre-pectoral?
    • Phase III confirmation warranted before routine adoption?
    ๐Ÿ“š Sources ยท ๐Ÿฆ 1 tweet

    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
    Methods
    • 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
    Results
    • 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
    Critique
    • 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
    Open questions
    • Phase 3 confirmation needed before ENRT replaces MDT as SOC
    • ENRT benefit differential by PET tracer type (PSMA vs choline)
    • Optimal ADT duration in combination with ENRT
    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
    PMID โ†’ doi
    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.

    INRT-AIR & DARTBOARD (ENI omission, HNSCC)

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

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

    Radiation Curative Phase 2 trial Early signal

    5-yr solitary ENI recurrence 0%; 3-yr LR 9.5%, regional recurrence 4.3%, DM 11%; 5-yr OS 87%, PFS 74%; MDADI composite 84.9 at 12mo
    5-yr solitary ENI recurrence 0%; 3-yr LR 9.5%, regional recurrence 4.3%, DM 11%; 5-yr OS 87%, PFS 74%; MDADI composite 84.9 at 12mo
    8 details
    Methods
    • 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
    Results
    • 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)
    Critique
    • 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
    Open questions
    • RCT comparing INRT vs standard ENI-CRT needed before non-trial adoption
    • Late toxicity reduction and QoL benefit beyond 12 months
    • Generalizability of AI-assisted nodal staging to community practice
    ๐Ÿ“š Sources ยท ๐Ÿฆ 1 tweet

    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
    Methods
    • 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
    Results
    • 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
    Critique
    • โš ๏ธ Phase 2 only; overall HR may not apply uniformly across histologies given basket heterogeneity
    Open questions
    • 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.
    PMID 42142259 โ†’ doi
    Abstract
    PURPOSE: We tested the hypothesis that adding metastasis-directed therapy (MDT) to standard of care (SOC) systemic therapy improves progression-free survival (PFS) among patients with oligometastatic disease.<br/><br/>METHODS: EXTEND was a multicenter randomized phase II trial. Patients with 1-5 metastases were randomized to MDT+SOC vs SOC in 1 of 6 baskets (breast, pancreas, kidney, two prostate baskets, and an "Other" basket) with basket-specific stratification and powering. PFS, the primary endpoint, was pre-specified in the per-protocol set within each basket, across all baskets, and across all baskets excluding the prostate baskets. Exploratory endpoints included circulating tumor DNA (ctDNA) and immune profiling.<br/><br/>RESULTS: From 2018 through 2023, 521 patients were screened, 350 were randomized, and 334 were analyzed per protocol (MDT+SOC, n=166; SOC, n=168). Radiotherapy was used as MDT for 98% of metastases (370/379). Overall, after median follow-up of 53 months, PFS was improved with MDT+SOC (HR 0.54, 95% CI 0.41 to 0.72, p < 0.001). Similarly, PFS was improved when excluding the prostate baskets (HR, 0.60; 95% CI: 0.40 to 0.89). Within each basket, PFS superiority was identified for the pancreas, prostate, and "Other" baskets, whereas the breast and kidney baskets were inconclusive. At enrollment, detectable ctDNA correlated with shorter PFS and survival; by contrast, ctDNA clearance 3-months post-enrollment correlated with improved survival. MDT+SOC-induced systemic immune activation was most pronounced among baskets demonstrating PFS superiority.<br/><br/>CONCLUSION: The phase II EXTEND trial supports the addition of MDT to SOC for oligometastatic disease. Histology-specific efficacy signals were identified for phase III testing. Translational insights suggest the potential for optimizing the definition of oligometastasis using ctDNA, and point to systemic immune responses as a possible mechanism of benefit from MDT.
    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
    Methods
    • 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)
    Results
    • 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
    Critique
    • 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
    Open questions
    • Randomised comparison vs thermal ablation or partial nephrectomy in operable candidates
    • OS benefit vs active surveillance in truly inoperable primary RCC
    • Durability beyond 84 months for T2a/T3a subset (small N)
    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.
    PMID 42144018 โ†’ doi
    Abstract
    BACKGROUND: Stereotactic ablative body radiotherapy (SABR) is an emerging, non-invasive alternative for primary renal cell carcinoma. We aimed to provide the final long-term trial outcomes of TransTasman Radiation Oncology Group (TROG) 15.03 FASTRACK II, the first phase 2 trial investigating SABR for primary renal cell carcinoma to our knowledge.<br/><br/>METHODS: FASTRACK II was a non-randomised, phase 2 study conducted in eight hospitals in Australia and the Netherlands by TROG and the Australian and New Zealand Urogenital and Prostate (ANZUP) Cancer Trials Group. Here, we report the final pre-planned follow-up results. Adult patients (aged &#x2265;18 years) with histologically confirmed primary renal cell carcinoma, who were medically inoperable, high risk, or declined surgery, had an Eastern Cooperative Oncology Group performance status of 2 or less, had tumours 10 cm or less in size, and had N0-N1 disease were included. Patients underwent either a single fraction SABR of 26 Gy for tumours 4 cm or less in maximum diameter, or 42 Gy in three fractions delivered 48 h apart for tumours more than 4 cm in maximum diameter. The primary outcome was freedom from local progression to assess local control after SABR evaluated with the Response Evaluation Criteria in Solid Tumours. The primary endpoint and safety were evaluated in the intention-to-treat population. A patient representative was involved in the study design and conduct. The trial was registered with ClinicalTrials.gov (NCT02613819) and is closed to enrolment.<br/><br/>FINDINGS: Between July 28, 2016, and Feb 27, 2020, 71 patients were enrolled and one withdrew consent before treatment. Median follow-up was 62 months (IQR 60-72), median age was 77 years (70-82). 49 (70%) of 70 patients were male and 21 (30%) were female. Race and ethnicity data were not collected. The median tumour size was 46 mm (37-55), with 24 (34%) patients with T1a disease, 39 (56%) with T1b disease, six (9%) with T2a disease, and one (1%) with T3a disease. One patient (1%) had nodal involvement (N1). SABR resulted in 100% local control at 36 months, 60 months, and 84 months. Seven (10%) patients had at least one grade 3 adverse event within 9 months of SABR that was designated possibly, probably, or definitely related to treatment: nausea and vomiting (three [4%] events); abdominal, flank, or tumour pain (four [6%]); colonic obstruction (two [3%]); and diarrhoea (one [1%]). No new long-term safety signals, grade 4 events, or treatment-related deaths were noted.<br/><br/>INTERPRETATION: Long-term follow-up supports the safety and local control of SABR for non-surgical patients with renal cell carcinoma, with no observed local recurrences or cancer-related deaths in this cohort, which had predominantly T1b disease or higher.<br/><br/>FUNDING: The Cancer Australia Priority-driven Collaborative Cancer Research Scheme and Varian.
    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.

    OLIGOMA NCT04495309

    ForMetastatic breast, โ‰ค5 mets, any systemic therapy line

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

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

    Radiation Palliative Phase 2 trial Early signal

    OLIGOMA
    +2 more figures
    QoL 12 wk: QLQ-C30 mean 72.2 vs 74.3; diff -2.1 (95% CI -9.2 to 5.1); NI margin -10 pts, met
    QoL 12 wk: QLQ-C30 mean 72.2 vs 74.3; diff -2.1 (95% CI -9.2 to 5.1); NI margin -10 pts, met
    OLIGOMA
    5 details
    Methods
    • ๐Ÿ” Randomised; metastatic breast any line, โ‰ค5 lesions; systemic ยฑ ablative RT to all mets
    • ๐Ÿ” >80% had 1-3 mets; 2/3 of lesions bone mets; majority ER/PR+, HER2- in 1st-line
    CONSORT flow
    Randomized 87
    โ†“
    Systemic + ablative RT
    allocated 43
    Systemic alone
    allocated 44
    Results
    • ๐Ÿ“Š QoL 12-wk co-primary met: QLQ-C30 diff -2.1 (-9.2 to 5.1), NI margin -10 pts (n=64)
    Critique
    • โš ๏ธ Stopped early: enrolled <20% of initial, <40% of amended target; N=87 total
    • โš ๏ธ HR CI very wide (0.25-0.91); no OS data reported
    Open questions
    • Which subgroups benefit most (therapy line, met burden, histology subtype)?
    • OS benefit not yet demonstrated; durability of PFS gain uncertain
    • Will confirmatory data from ongoing breast-specific MDT RCTs align?
    ๐Ÿ“š Sources ยท ๐Ÿฆ 3 tweets

    RAPCHEM

    ForNode-positive breast cancer achieving pathological nodal response after neoadjuv

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

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

    Radiation Curative Phase 2 trial Early signal

    3 details
    Methods
    • ๐Ÿ” De-escalation strategy: locoregional RT field/dose reduced based on nodal pathological response after neoadjuvant chemotherapy
    Results
    • ๐Ÿ“Š Locoregional recurrence <3% at 10yr with pathological nodal response-guided RT de-escalation post-neoadjuvant
    Critique
    • โš ๏ธ No CI, HR, or comparator arm outcome reported in source; design not confirmed as randomized
    Open questions
    • Can RT be safely omitted (not just de-escalated) after pathological nodal response?
    • Will B-51 confirm safety of complete locoregional RT omission post-neoadjuvant?
    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
    Methods
    • 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
    Results
    • ๐Ÿ“Š Primary aggregated analysis across all tumor histology baskets; no effect size reported in source tweet
    Critique
    • โš ๏ธ Basket aggregation across histologies: pooled primary estimate may obscure site-specific heterogeneity in MDT benefit
    Open questions
    • Which histology baskets drove the primary endpoint signal?
    • Do ctDNA dynamics at baseline or on-treatment predict MDT benefit?
    • Does Phase III confirmation across histologies follow?
    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
    Methods
    • 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
    Results
    • 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)
    Critique
    • 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
    Open questions
    • OS benefit of adding short-term ADT to SBRT in oligorecurrent disease?
    • Which pts benefit most: PSA kinetics, lesion count, PSMA avidity?
    • Optimal ADT duration (6mo vs longer) for oligorecurrent SBRT candidates?
    ๐Ÿ“š Sources ยท ๐Ÿฆ 1 tweet