onc brain

About Β· curated by Nick Boehling, MD Β· @nb2276

    Confirmatory

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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
    • πŸ” ASCO26 educational review: PK-guided concurrency framework for systemic therapy during breast/CW + RNI (adapted from ASCO Educational Book 2026)
    • πŸ’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
    • πŸ’Š T-DXd (tΒ½=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%
    • πŸ’Š T-DM1 (tΒ½=4d): CONTINUE during locoregional RT; CNS SRS radionecrosis is the do-not-ignore signal
    • πŸ” 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
    • πŸ’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 (tΒ½=90hr): long PK tail favors sequential strategy
    • πŸ’Š CDK4/6i: hold during large-field RT
      • Abemaciclib/ribociclib (tΒ½=24-55hr): hold for large fields; concurrent feasible in trial setting only (NCT05996107)
      • Palbociclib (tΒ½=28.8hr): practical to hold around RT; resume promptly after
    Results
    • πŸ“Š 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
    πŸ“š Sources Β· 🐦 1 tweet

    ES-SCLC Concurrent TRT + Chemoimmunotherapy (LBA8005)

    ForES-SCLC, treatment-naΓ―ve, 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
    • πŸ” Phase III RCT, N=228 (115 vs 113); TRT 30 Gy/10 fr concurrent from day 21-28 of cycle 1
    • πŸ” Eligibility: stage IV SCLC or stage III ineligible for curative CRT, ECOG 0-1, measurable thoracic lesion required
    • πŸ” 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
    πŸ“š Sources Β· 🐦 1 tweet

    ENZARAD

    ForHigh-risk localized PCa (Gleason 8-10, T3-4, or N1, or PSA β‰₯20 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
    Methods
    • πŸ” Phase 3 RCT (ANZUP), N=802, 1:1; high-risk localized PCa (Gleason 8-10, T3-4, N1, or PSA β‰₯20 ng/mL); median FU 8y
    • πŸ” Enzalutamide 160mg/d x24mo + LHRH agonist x24mo vs NSAA x6mo + LHRH agonist x24mo; both arms: RT Β± brachytherapy boost Β± pelvic nodal RT
    CONSORT flow
    Randomized 802
    ↓
    Enzalutamide
    allocated 401
    Control (NSAA)
    allocated 401
    Results
    • πŸ“Š Both 1Β° (MFS) and 2Β° (OS) endpoints not met; overall trial negative
    Critique
    • ⚠️ Pelvic RT and cN1 subgroup interactions are exploratory in a negative trial; hypothesis-generating, not sufficient for practice change
    • ⚠️ ICECAP surrogacy framework cited validating MFS as OS surrogate; both concordantly null, no hidden OS benefit suggested
    Open questions
    • Whether pelvic RT selection prospectively enriches for ARSI benefit in high-risk localized PCa
    • Optimal ADT intensification strategy for cN1 high-risk prostate cancer
    πŸ“š Sources Β· 🐦 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
    • πŸ” Randomized open-label phase 2, N=111 (mHSPC, nmCRPC, mCRPC), DAR vs ENZ; enrolled 8/2021-3/2025
    • πŸ” MCCD = maximally changed cognitive domain across 5 remote CANTAB tests: executive function, visual memory, attention, working memory
    • πŸ’Š Darolutamide provided by study; enzalutamide through standard of care
    Results
    • πŸ“Š 1Β° EP: CANTAB MCCD at 24wk median change -36.1 (ENZ, N=47) vs -15.8 (DAR, N=48), p=0.009
    Critique
    • ⚠️ Open-label; crossover allowed before 24wk, analyzed at crossover timepoint in randomized arm
    • ⚠️ 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)
    πŸ“š Sources Β· 🐦 2 tweets

    OptiTROP-Lung05 NCT06448312

    ForStage IIIB-IV NSCLC, PD-L1 TPS β‰₯1%, no EGFR/ALK, treatment-naive, ECOG 0-1

    TL;DRmPFS NR vs 5.7mo, HR 0.35 (0.26-0.47), p<0.0001 favoring sac-TMT + pembro in 1L PD-L1+ NSCLC.

    vs leading data
    • Converges with TROPION-Lung08 (Dato-DXd+durvalumab vs pembro, TPSβ‰₯50%): ADC+IO > IO-mono signal emerging in 1L NSCLC

    Systemic Palliative Phase 3 RCT Confirmatory

    OptiTROP-Lung05
    ArmEvents n (%)Median PFS (95%CI)HR (95%CI)p
    Sac-TMT+Pembro (n=208)66 (31.7%)NR (13.6, NE)0.35 (0.26, 0.47)<0.0001
    Pembro (n=205)128 (62.4%)5.7mo (4.3, 7.0)refβ€”
    +3 more figures
    Descriptive OS (immature): HR 0.55 (95%CI 0.36-0.85). Events 33 (15.9%) vs 54 (26.3%). Median f/u 10.5 months.
    Descriptive OS (immature): HR 0.55 (95%CI 0.36-0.85). Events 33 (15.9%) vs 54 (26.3%). Median f/u 10.5 months.
    OptiTROP-Lung05
    PD-L1 TPSSac-TMT+Pembro median PFSPembro median PFSHR (95%CI)
    β‰₯50%NR (NE, NE)9.5mo (6.9, 13.8)0.47 (0.29, 0.77)
    1-49%NR (11.1, NE)4.3mo (2.9, 5.5)0.28 (0.19, 0.41)
    OptiTROP-Lung05
    8 details
    Methods
    • πŸ” Phase 3 open-label RCT; N=413; stage IIIB/IIIC/IV NSCLC; PD-L1 TPS β‰₯1%; no EGFR/ALK; ECOG 0-1
    • πŸ’Š Sac-TMT 4mg/kg Q2W + pembro 400mg Q6W vs pembro 400mg Q6W; max 18 pembro cycles
    CONSORT flow
    Randomized 413
    ↓
    Sac-TMT + Pembro
    allocated 208
    Pembro
    allocated 205
    Results
    • πŸ“Š 1Β° EP PFS by BICR: median NR (13.6, NE) vs 5.7mo (4.3, 7.0), HR 0.35 (95%CI 0.26-0.47), p<0.0001
    • πŸ“Š ORR 70.2% vs 42.0%
    • πŸ“Š Descriptive OS (immature): HR 0.55 (95%CI 0.36-0.85); events 33 (15.9%) vs 54 (26.3%); median f/u 10.5mo
    • πŸ“Š PFS benefit consistent across both PD-L1 TPS subgroups (β‰₯50% and 1-49%)
    Critique
    • ⚠️ OS immature at primary PFS analysis (10.5mo median f/u); definitive OS benefit not yet established
    • ⚠️ Control is pembro mono; for TPS 1-49%, pembro+platinum chemo is also SOC β€” no head-to-head vs chemo-IO doublet
    Open questions
    • Will PFS benefit translate to OS with longer follow-up?
    • Superiority vs. pembro + platinum chemo for TPS 1-49%?
    • Predictive biomarker beyond PD-L1 TPS for TROP2 ADC benefit?
    πŸ“š Sources Β· 🐦 2 tweets

    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
    • πŸ” International RCT; nipple-sparing or skin-sparing mastectomy; therapeutic + risk-reduction setting
    • πŸ” 1Β° EP: BREAST-Q physical well-being (chest) at 24 months; LS mean from linear mixed model; longitudinal completion 83-95%
    CONSORT flow
    Randomized 380
    ↓
    Pre-pectoral IBBR
    allocated 194
    analyzed 191
    Sub-pectoral IBBR
    allocated 186
    analyzed 189
    Critique
    • ⚠️ Main secondary safety EP missed non-inferiority: pre-pectoral had higher unplanned implant loss/replacement
    • ⚠️ 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?
    πŸ“š Sources Β· 🐦 1 tweet

    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)β€”
    p0.008β€”
    7 details
    Methods
    • πŸ” N=620, 13 Chinese centers, 2013-2022; cT3N2+ or T4 gastric/GEJ; 36.3% EGJ primary
    • πŸ” CRT arm: 45 Gy/25 fractions concurrent after C1 chemo, with dose-reduced oxaliplatin (100 mg/mΒ²) and capecitabine (825 mg/mΒ²)
    CONSORT flow
    Randomized 620
    ↓
    CRT (XELOX + RT)
    allocated 310
    CT (XELOX)
    allocated 310
    Results
    • πŸ“Š mOS 67.5 vs 37.6 months, HR 0.781 (0.628-0.970), p=0.025
    • πŸ“Š Locoregional recurrence in R0-resected pts: 9.4% CRT vs 18.3% CT
    • πŸ“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%
    Critique
    • ⚠️ G3+ toxicity (CRT vs CT)
      • Hematologic: 14.6% vs 10.3%
      • Postop complications: 9.0% vs 7.6%
    • ⚠️ Backbone is XELOX, not FLOT; limits direct applicability to FLOT-era Western practice
    Open questions
    • Does adding RT to FLOT peri-op chemo confer similar DFS/OS benefit?
    • Optimal RT dose-fractionation in FLOT-era perioperative settings
    • Long-term LRR and OS durability beyond 5 years
    πŸ“š Sources Β· 🐦 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
    Methods
    • πŸ” Phase 3 NI RCT, N=2766 enrolled, 2540 per-protocol; median f/u 46.8mo (range 1.5-94.5)
    • πŸ” Extends Z0011 eligibility: includes mastectomy, T3 tumors, extracapsular extension, male pts
    • πŸ” Nodal RT administered in 89.9% SNB-only group, 88.4% ALND group
    Results
    • πŸ“Š 2Β° EP (RFS): 5yr 89.7% (95% CI 87.5-91.9) SNB-only vs 88.7% (95% CI 86.3-91.1) ALND
    • πŸ“ Country-adjusted HR 0.89 (95% CI 0.66-1.19); noninferiority p<0.001 (upper CI 1.19 below margin 1.44)
    Critique
    • ⚠️ 1Β° EP (OS) not yet reported; only prespecified secondary RFS analysis shown here
    • ⚠️ Near-universal nodal RT in both arms: noninferiority may not hold where nodal RT is routinely omitted
    Open questions
    • 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
    πŸ“š Sources Β· πŸ“„ 1 paper
    πŸ“„ PAPER de Boniface, Jana; Filtenborg Tvedskov, Tove; RydΓ©n, Lisa et al. Β· New England Journal of Medicine (2024-04)
    Omitting Axillary Dissection in Breast Cancer with Sentinel-Node Metastases
    PMID β†’ doi
    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, ≀20 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 biopsy–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 biopsy–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 ≀7cm, β‰₯1 recurrence risk factor

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

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

    Combined Curative Phase 3 RCT Confirmatory

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

    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
    • πŸ” Expert opinion + systematic literature review; no randomized dose-comparison trials completed for any cutaneous lymphoma entity
    • πŸ’Š Low-dose RT endorsed for T-cell (MF, SΓ©zary) and B-cell entities (PCMZL, PCFCL, PCDLBCL-leg type)
    • πŸ” 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
    πŸ“š Sources Β· πŸ“„ 1 paper
    πŸ“„ PAPER Khaled Elsayad; Emmanuella Guenova; Chalid Assaf et al. Β· European Journal of Cancer (2024)
    Radiotherapy in cutaneous lymphomas: Recommendations from the EORTC cutaneous lymphoma tumour group
    PMID β†’ 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.

    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
    Methods
    • πŸ” Prospective nationwide cohort, N=4541, Jan 2007-May 2014; median f/u 13.7 yr
    • πŸ” Allocation: right-sided β†’ IMNI, left-sided β†’ no IMNI; 6 RT centres, 3D-based RT
    • πŸ” Systemic: taxane-based chemo, AIs, trastuzumab
    Results
    • πŸ“Š Primary EP OS: 15-yr 65.0% (IMNI) vs 60.8% (no IMNI)
    • πŸ“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
    Critique
    • ⚠️ Cohort design, not RCT; laterality-based allocation; baseline characteristics balanced but not randomized
    • ⚠️ No subgroup identified favoring IMNI omission, including 1-3 positive axillary nodes
    Notes
    • 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
    Open questions
    • 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
    πŸ“š Sources Β· πŸ“„ 1 paper
    πŸ“„ PAPER Anders W. MΓΈlby Nielsen; Lise B. J. Thorsen; Demet Γ–zcan et al. Β· 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
    PMID β†’ doi
    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 2007–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, 0.76–0.94; p = 0.0016) for OS. Corresponding HRs were 0.84 (95% CI, 0.74–0.95; p = 0.0077) for breast cancer mortality and HR 0.87 (95% CI, 0.78–0.98; 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, 0.0–0.5) in right-sided and 0.7% (95% CI, 0.4–1.2) 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-preserving TMT for MIBC: prognostic factors (ESTRO 2026)

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

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

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

    Combined Curative Retrospective Confirmatory

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

    HCC EBRT Multinational IPD Cohort

    ForHCC BCLC-0 or BCLC-A, treatment-naΓ―ve 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
    Methods
    • πŸ” Systematic review + IPD meta-analysis; 4,913 HCC pts treated with EBRT; median f/u 5.0yr; multinational institutions
    Results
    • πŸ“Š OS by BCLC stage (all pts)
      StageMedian OS95% CI
      BCLC-06.8yr5.7-8.7
      BCLC-A4.6yr4.1-5.1
    • πŸ“Š OS in treatment-naΓ―ve pts
      StageMedian OS95% CI
      BCLC-0NR8.6yr-NR
      BCLC-A5.4yr4.5-6.7
    • πŸ“ Multivariable: ablative RT dose and more recent treatment year both associated with reduced mortality risk
    • πŸ“ Higher BCLC stage, greater tumor burden, worse PS, Child-Pugh B/C associated with higher mortality risk
    Critique
    • ⚠️ No randomized comparator vs resection or ablation; historical cross-study comparison subject to selection bias
    • ⚠️ Dose heterogeneity across contributing institutions; ablative and non-ablative RT pooled together
    Open questions
    • 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
    πŸ“š Sources Β· πŸ“„ 1 paper
    πŸ“„ PAPER Moon; Yanagihara; Dawson et al. Β· 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.
    PMID 42139645 β†’ doi
    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.
    πŸ“ 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, MΓ©ndΓ¨z 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
    Methods
    • πŸ” 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)
    • πŸ’Š MDT was RT in 98% of treated mets (370/379)
    • πŸ” Exploratory ctDNA findings
      • Detectable ctDNA at enrollment correlated with shorter PFS + survival
      • ctDNA clearance at 3mo post-enrollment correlated with improved survival
    Results
    • πŸ“Š 1Β° EP PFS: HR 0.54 (95% CI 0.41-0.72), p<0.001, MDT+SOC vs SOC; median f/u 53 mo
    • πŸ“Š Excluding prostate baskets: PFS HR 0.60 (95% CI 0.40-0.89)
    • πŸ“Š Basket-level PFS superiority
      • Superiority demonstrated: pancreas, prostate, Other baskets
      • Inconclusive: breast, kidney baskets
    Critique
    • ⚠️ 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?
    πŸ“š Sources Β· πŸ“„ 1 paper
    πŸ“„ PAPER Sherry; Haymaker; Wang et al. Β· 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 β†’ 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.
    πŸ“ 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.

    APBI-IMRT Florence NCT02104895

    ForEarly BC post-BCS, pT <25mm, FSM β‰₯5mm, 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)β€”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
    Methods
    • πŸ” Phase III equivalence trial, N=520, 1:1 randomization, enrolled 2005-2013
    • πŸ” APBI: IMRT 30Gy/5 fractions; WBI: 50Gy/25# + 10Gy tumor bed boost
    • πŸ” Eligible: BCS, pT <25mm, FSM β‰₯5mm, age >40; ITT for survival, per-protocol for toxicity/cosmesis
    CONSORT flow
    Randomized 520
    ↓
    PBI IMRT (30Gy/5#)
    allocated 260
    WBI (50Gy/25# + 10Gy TBB)
    allocated 260
    Results
    • πŸ“Š Secondary oncological outcomes at 15 years
    Critique
    • ⚠️ IBTR excess in APBI driven by new ipsilateral primaries, not true local recurrence
    • ⚠️ Equivalence powered for 5-yr IBTR Ξ”5%; underpowered to exclude small absolute OS differences at 15 years
    • ⚠️ 2005-2013 enrollment; applicability with contemporary genomic risk stratification uncertain
    Open questions
    • 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
    πŸ“š Sources Β· 🐦 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
    Methods
    • πŸ” Phase III non-inferiority RCT (1:1), N=1,882, node-negative BC or DCIS, Denmark/Norway/Germany, 2009-2014
    CONSORT flow
    Randomized 1882
    ↓
    50 Gy/25fr
    allocated 949
    analyzed 936
    40 Gy/15fr
    allocated 933
    analyzed 917
    Results
    • πŸ“Š No significant differences in locoregional recurrence, distant failure, or breast cancer mortality at 10 yrs
    Critique
    • ⚠️ Original 1Β° EP was 3-yr grade β‰₯2 induration; 10-yr toxicity, recurrence, and survival analyses were prespecified
    • ⚠️ Trial not powered for 10-yr OS as 1Β° endpoint; HR 0.81 (p=0.10) non-significant and should not be over-interpreted
    Open questions
    • Whether 10-yr induration benefit extends to pts receiving regional nodal RT
    • Long-term comparison with ultra-hypofractionation (FAST-FORWARD 26Gy/5fr)
    πŸ“š Sources Β· 🐦 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
    Methods
    • πŸ” 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
    • πŸ” SIB delivers boost in 15 fractions (3 weeks) vs 23 total for sequential 40+16Gy; reduced pt visits
    CONSORT flow
    Randomized 2617
    ↓
    40Gy/15F + 16Gy/8F (sequential)
    allocated 871
    48Gy/15F SIB (3.2Gy/F)
    allocated 874
    53Gy/15F SIB (3.5Gy/F)
    allocated 872
    Results
    • πŸ“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)
    Critique
    • ⚠️ 53Gy/15F: numerically higher 10-yr IBTR than control; dose escalation beyond 48Gy adds no benefit
    • ⚠️ Moderate/marked late AEs at 10yr (all arms)
      • Breast distortion/shrinkage: <18%
      • Induration: <10%
      • Telangiectasia: <2%
      • Breast oedema: <2%
    • ⚠️ 10-yr IBTR in both boost groups remains below the 5% control estimate used in original sample size calculations
    Open questions
    • Any subgroup that benefits from 53Gy escalation
    • Very long-term (>10yr) toxicity trajectory
    • Applicability to post-mastectomy or regional nodal RT settings
    πŸ“š Sources Β· 🐦 1 tweet

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