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About · curated by Nick Boehling, MD · @nb2276

    Consensus / guideline

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    Breast RT + Systemic Therapy Concurrency Review (Speers)

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

    Combined Curative Consensus / guideline Confirmatory

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

    EORTC Cutaneous Lymphoma RT Recommendations

    TL;DREORTC expert consensus formalizes low-dose RT recommendations across all primary cutaneous lymphoma entities; no RCT dose-comparison data exist.

    vs leading data
    • Low-dose rationale: characteristic radiosensitivity of cutaneous lymphoma lesions enables high efficacy with low toxicity and repeatable treatment

    Radiation Consensus / guideline Confirmatory

    5 details
    Methods
    • 🔍 Expert opinion + systematic literature review; no randomized dose-comparison trials completed for any cutaneous lymphoma entity
    • 💊 Low-dose RT endorsed for T-cell (MF, Sézary) and B-cell entities (PCMZL, PCFCL, PCDLBCL-leg type)
    • 🔍 TSEBT for advanced-stage MF addressed; limited prospective registry data recently published
    Critique
    • ⚠️ Underlying evidence base largely retrospective case series; controlled trials defining standard dose per entity not yet completed
    • ⚠️ Recommendations aim to reduce individualized decision-making variation until prospective trial data mature
    Open questions
    • RCT defining optimal radiation dose per cutaneous lymphoma entity
    • Factors influencing pt outcomes across dose levels
    📚 Sources · 📄 1 paper
    📄 PAPER Khaled Elsayad; Emmanuella Guenova; Chalid Assaf et al. · European Journal of Cancer (2024)
    Radiotherapy in cutaneous lymphomas: Recommendations from the EORTC cutaneous lymphoma tumour group
    PMID → doi
    Abstract
    The number of primary cutaneous lymphoma patients receiving low-dose radiotherapy is increasing, though controlled clinical trials defining the standard radiation dose for each specific entity have not yet been completed. Radiation oncologists are left with making highly individualized decisions that would be better enriched by additional clinical evidence. In this expert opinion, we aim to provide a clear recommendation to improve the current practice of radiation oncology. In addition, existing literature has been reviewed to develop recommendations for all types of primary cutaneous lymphoma. A prospective trial is urgently needed to identify the factors influencing patient outcomes following different radiation doses.