onc brain

About · curated by Nick Boehling, MD · @nb2276

    2026-06-02

    digest generated 2026-06-03

    mRCAT-III: pCR 61% vs 29% (p<0.0001); tislelizumab + node-sparing SCRT doubles pCR in pMMR LARC.
    TL;DR
    Lower-GI led the day: mRCAT-III delivers a striking IO-augmented pCR signal in pMMR LARC, a population previously IO-refractory. Thoracic closed a chapter (concurrent TRT, HR 1.14, null in ES-SCLC chemoIO). Breast offered a practical PK-guided concurrency map for modern systemic agents.

    GI Lower

    IO breaks into pMMR LARC: node-sparing SCRT + tislelizumab triples pCR rate over conventional chemoradiation.

    mRCAT-III NCT06507371

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

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

    Combined Curative Phase 3 RCT Early signal

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

    Sourced from @NiuSanford

    📚 Sources · 🐦 1 tweet

    Breast

    ASCO26 PK framework operationalizes which agents to continue, hold, or sequence around breast and RNI fields.

    Breast RT + Systemic Therapy Concurrency Review (Speers)

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

    Combined Curative Consensus / guideline Confirmatory

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

    Sourced from @dr_yakupergun

    📚 Sources · 🐦 1 tweet

    Thoracic / Lung

    CREST-era TRT rationale doesn't survive the IO era; concurrent thoracic RT adds no OS in ES-SCLC chemoIO.

    ES-SCLC Concurrent TRT + Chemoimmunotherapy (LBA8005)

    ForES-SCLC, treatment-naïve, ECOG 0-1, measurable thoracic lesion

    TL;DRmOS 10.0 vs 11.8mo, HR 1.14, p=0.40: concurrent TRT adds no OS benefit to chemoIO in ES-SCLC.

    vs leading data
    • vs CREST (Lancet 2015): TRT 30 Gy/10 fr post-induction improved 1yr OS in pre-IO ES-SCLC; not replicated here in IO era

    Radiation Palliative Phase 3 RCT Confirmatory

    ES-SCLC Concurrent TRT + Chemoimmunotherapy (LBA8005)
    ArmMedian OS95% CIHR (95% CI)p
    ChemoIO + TRT10.0 mo8.3-11.71.14 (0.84-1.56)0.40
    ChemoIO11.8 mo10.0-13.6refn/a
    +3 more figures
    ES-SCLC Concurrent TRT + Chemoimmunotherapy (LBA8005)
    ArmMedian PFS95% CIHR (95% CI)p
    ChemoIO + TRT5.1 mo4.7-5.41.10 (0.84-1.45)0.49
    ChemoIO5.0 mo4.6-5.4refn/a
    ES-SCLC Concurrent TRT + Chemoimmunotherapy (LBA8005)
    ES-SCLC Concurrent TRT + Chemoimmunotherapy (LBA8005)
    SubgroupChemoIO+TRT median OSChemoIO median OSHR (95% CI)p
    Completed all 4 cycles11.9 mo12.1 mo1.02 (0.72-1.44)0.92
    No brain/liver mets11.9 mo13.2 mo1.10 (0.65-1.87)0.72
    6 details
    Methods
    • 🔍 Phase III RCT, N=228 (115 vs 113); TRT 30 Gy/10 fr concurrent from day 21-28 of cycle 1
    • 🔍 Eligibility: stage IV SCLC or stage III ineligible for curative CRT, ECOG 0-1, measurable thoracic lesion required
    • 🔍 PCI 25-30 Gy optional for responders per local routine; durvalumab 1500 mg Q4W maintenance until PD
    CONSORT flow
    Randomized 228
    ↓
    ChemoIO + TRT
    allocated 115
    ChemoIO
    allocated 113
    Critique
    • ⚠️ Control arm mOS (11.8mo) consistent with CASPIAN durvalumab arm (~12.9mo); TRT arm numerically inferior at 10.0mo
    • ⚠️ Pre-specified OS subgroups (completed all 4 cycles, no brain/liver mets) both null, consistent with ITT
    • ⚠️ PCI optional per local routine; differential PCI use between arms unreported, potential survival confound
    Open questions
    • Whether consolidative rather than concurrent TRT sequencing improves outcomes
    • Role of PCI in IO-era ES-SCLC given uncontrolled differential use in this trial
    • Optimal ES-SCLC subpopulation (if any) for TRT in the IO era

    Sourced from @M_Torasawa

    📚 Sources · 🐦 1 tweet