onc brain

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

    2026-05-30

    digest generated 2026-05-31

    OptiTROP-Lung05: mPFS NR vs 5.7mo, HR 0.35; sac-TMT+pembro challenges pembro mono as 1L standard in PD-L1+ NSCLC.
    TL;DR
    Thoracic dominated: OptiTROP-Lung05 (phase 3, HR 0.35) and ESAONA (phase 2, iORR 95.5% for asandeutertinib in 1L EGFR+/brain mets). Prostate highest volume: TALAPRO-3 extended PARP inhibition to HRR-def mHSPC, ARACOG confirmed darolutamide's cognitive edge vs enza, A-DREAM piloted ADT+ARPI interruption.

    Bladder

    Two studies share the IO+CRT theme: RAD-IO hits its GO threshold (12-mo DFS 80%) while the session overview contextualizes pCR as a prognostic gate and positions ongoing bladder-sparing trials (EV209/EV309).

    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 β‰₯75%; 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
    • πŸ” Multi-stage single-arm trial; durvalumab neoadjuvant, synchronous, and 12mo adjuvant with chemoRT (5FU+MMC, 55Gy/20Fr)
    • πŸ” N=55 enrolled; N=54 received β‰₯1 treatment dose (1 withdrew pre-treatment); 33/54 (61%) completed planned treatment, 21/54 (39%) discontinued early
    • πŸ” Node-positive subset: 55Gy/20Fr to bladder + 46Gy/20Fr to pelvic nodes
    Results
    • πŸ“Š 1Β° EP: 12-month DFS 80% (40/50; 95% CI 0.67-0.89); cleared pre-set GO threshold β‰₯75%
    Critique
    • ⚠️ Single-arm; no concurrent randomised comparator vs CRT alone; efficacy benchmarked against historical control only
    • ⚠️ 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

    Sourced from @katy_beckermann, @nataliagandur, @dralvaropinto

    πŸ“š Sources Β· 🐦 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
    • πŸ” Durvalumab + CRT trial: N=54 MIBC, 55 Gy/20 fr + MMC/5-FU + durvalumab, single-arm phase 2
    Results
    • πŸ“Š RT delivery: 47/54 (87%) received full 55 Gy/20fr without extension or delay
    • πŸ“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%)
    • πŸ“Š pCR (pT0N0) as prognostic marker: SWOG 8710 85% 5-yr OS if pT0; meta-analysis pooled RR 0.19 for RFS
    Critique
    • ⚠️ 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?

    Sourced from @nataliagandur

    πŸ“š Sources Β· 🐦 2 tweets

    Prostate

    Highest-volume site: TALAPRO-3 extends PARP inhibition to HRR-def mHSPC, A-DREAM pilots ADT+ARPI interruption, ARACOG settles the enza vs daro cognitive question, and NRG adds GC-score biomarker stratification for AAP intensification.

    NRG Clinico-Transcriptomic Risk Stratification (Abstract 5000)

    ForNCCN β‰₯ high-risk localized prostate cancer, RT+ADT candidates

    TL;DR22-gene GC independently predicts MFS, DM, and OS; combined NRG score reclassifies ~25% discordant NCCN high-risk pts for AAP intensification.

    vs leading data
    • STAMPEDE MO calibration anchor (Attard, Lancet 2022): HRMFS 0.53 (95% CI 0.44-0.64), HROS 0.60 (0.48-0.73), both p < 0.0001 for AAP intensification

    Radiation Curative Retrospective Early signal

    NRG Clinico-Transcriptomic Risk Stratification (Abstract 5000)
    +1 more figure
    NRG Clinico-Transcriptomic Risk Stratification (Abstract 5000)
    GC HighGC Low
    Clinical High49%15%
    Clinical Low9%27%
    5 details
    Methods
    • πŸ” Combined clinico-transcriptomic (CT) score: NCCN points + GC points
      • NCCN HR = 1 pt; NCCN VHR = 2 pts
      • GC <HR = 0 pt; GC HR = 1 pt; GC VHR = 2 pts
      • CT HR (≀2 pts) β†’ RT+ADT; CT VHR (β‰₯3 pts) β†’ RT+ADT+AAP
    Results
    • πŸ“Š 22-gene GC independently predicts MFS, DM, and OS beyond clinical variables alone (p < 0.001 for each endpoint)
    • πŸ“Š ~25% of NCCN β‰₯HR pts have discordant clinical vs. GC risk, warranting the combined approach
    Critique
    • ⚠️ Framework developed on existing NRG trial data; no prospective RCT validating CT-score-guided treatment allocation reported
    • ⚠️ Design not fully specified in source; likely secondary correlative analysis; GC cutoffs extend Spratt et al. (JCO 2018) prior work
    Open questions
    • Prospective RCT: does CT-score-guided allocation improve outcomes vs. clinical risk alone?
    • Generalizability to modern ARSI-backbone ADT regimens
    • GC threshold stability across contemporary cohorts

    Sourced from @nataliagandur, @chavarriagaj

    πŸ“š Sources Β· 🐦 2 tweets

    A-DREAM (ALLIANCE mAPMS)

    FormHSPC achieving PSA<0.2 after β‰₯18-24mo ADT+ARPI, low-volume predominant

    TL;DRADT+ARPI interruption in mHSPC: 41% treatment-free with eugonadal T at 18mo (1Β° 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
    • πŸ” Single-arm phase II, N=78 enrolled 07/2022-03/2024; PSA<0.2 after β‰₯18-24mo ADT + β‰₯12mo ARPI
    • πŸ” Re-initiation triggers: PSA β‰₯5 ng/mL, radiographic change (PCWG3), or PrCa-related sx
    Results
    • πŸ“ Primary EP: 80% CI 33.1-48.9%, one-sided p=0.0249; pre-specified 80% CI threshold (not 95%)
    • πŸ“Š Median time to eugonadal T recovery: 9.0mo (95% CI 8.4-12.4)
    • πŸ“Š Disposition at 26.9mo: 38.5% still off-tx; 37.2% resumed ADT+ARPI per protocol; 9.0% started non-protocol tx
    • πŸ“Š rPFS from interruption: 15/78 events, median NE (32.5-NE); 12-mo est 94.6% (89.6-99.9%)
    • πŸ“Š OS: 4/78 events, median NE; causes: prostate cancer, MDS, influenza, MI
    Critique
    • ⚠️ Single-arm; no randomized comparator vs continuous ADT+ARPI
    • ⚠️ 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

    Sourced from @mjuanfi81

    πŸ“š Sources Β· 🐦 1 tweet

    ENZAMET + Decipher Biomarker Analysis

    FormHSPC, ADT + enzalutamide backbone, tumor tissue available for Decipher testing

    TL;DRDecipher >0.85 identifies mHSPC pts with OS benefit from docetaxel intensification; IPTW interaction p=0.04, HR 0.75 (0.43-1.33).

    vs leading data
    • Framed as Level 1B evidence; consistent with CHARTED and STAMPEDE docetaxel predictive patterns

    Systemic Palliative Phase 3 RCT Caveats dominate

    ENZAMET + Decipher Biomarker Analysis
    AnalysisDecipherDocetaxel HR (95% CI)pInteraction p
    Unweighted≀0.852.78 (1.49, 5.21)0.0010.02
    Unweighted>0.851.13 (0.71, 1.79)0.60β€”
    IPTW≀0.851.94 (0.95, 3.96)0.070.04
    IPTW>0.850.75 (0.43, 1.33)0.33β€”
    +1 more figure
    ENZAMET + Decipher Biomarker Analysis
    DecipherOS HR triplet vs doublet (95% CI)p
    ≀0.853.02 (1.50-5.76)β€”
    >0.851.08 (0.60-1.71)0.73
    4 details
    Methods
    • πŸ” Biomarker analysis within ENZAMET phase 3 RCT; ADT+enza+doce cohort N=320 with evaluable Decipher; DPMC 0.85 cutoff per statistical analysis plan
    Critique
    • ⚠️ Individual arm HRs non-significant in IPTW-MVA (Decipher >0.85: HR 0.75, p=0.33; Decipher ≀0.85: HR 1.94, p=0.07); signal rests on interaction term only
    • ⚠️ Tissue available in only ~427/3816 ENZAMET pts; representativeness of the analyzed subset uncertain
    • ⚠️ ENZAMET predated current ARSI-doublet SOC; Decipher model trained pre-ARPI β€” applicability to modern ADT+ARSI backbone unvalidated
    Open questions
    • Prospective Decipher-guided triplet selection trial in ARPI-era mHSPC needed
    • Optimal DPMC cutoff in pts receiving ADT+ARSI (not ENZA) doublets

    Sourced from @nataliagandur

    πŸ“š Sources Β· 🐦 2 tweets

    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)

    Sourced from @nataliagandur, @katy_beckermann

    πŸ“š Sources Β· 🐦 2 tweets

    TALAPRO-3

    ForHRR-deficient metastatic hormone-sensitive prostate cancer

    TL;DR3yr rPFS 77% vs 56% (HR 0.48, p<0.001) favoring talazoparib+enza+ADT in HRR-deficient mHSPC.

    vs leading data
    • vs TALAPRO-2 (talazoparib+enza, mCRPC, HRR+, HR ~0.46): class effect now established in hormone-sensitive setting

    Systemic Palliative Phase 3 RCT Practice-changing

    TALAPRO-3
    Subgroupn (exp/ctrl)Median rPFS expMedian rPFS ctrlHR (95% CI)
    ITT300/299NC (NC-NC)45.8 (37.7-NC) mo0.48 (0.36-0.65), p<0.001
    BRCA104/103NC (NC-NC)35.1 (18.6-NC) mo0.37 (0.22-0.61)
    Non-BRCA196/196NC (NC-NC)NC (40.5-NC) mo0.57 (0.39-0.82)
    3 details
    Methods
    • πŸ” Phase 3 RCT; N=599; HRR-deficient mHSPC; talazoparib+enza+ADT vs placebo+enza+ADT
    CONSORT flow
    Randomized 599
    ↓
    Talazoparib+enzalutamide
    allocated 300
    analyzed 300
    Placebo+enzalutamide
    allocated 299
    analyzed 299
    Critique
    • ⚠️ Primary endpoint imaging-based rPFS, not OS; OS maturity not reported in source
    • ⚠️ Non-BRCA HRR effect attenuated (HR 0.57 vs BRCA HR 0.37); non-BRCA HRR subset heterogeneous
    Open questions
    • OS benefit magnitude and maturity
    • Which non-BRCA HRR alterations drive clinically meaningful rPFS benefit
    • Post-progression sequencing in PARP-pretreated pts transitioning to mCRPC

    Sourced from @DrChoueiri

    πŸ“š Sources Β· 🐦 1 tweet

    Thoracic / Lung

    NSCLC carried a phase 3 ADC+IO vs IO-mono readout (OptiTROP-Lung05, HR 0.35) and the first randomized EGFR TKI head-to-head in brain-met-enriched 1L disease (ESAONA), plus maturing OS data for ami+laz in atypical EGFR+ (CHRYSALIS-2).

    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 β†’ 10 β†’ 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 β†’ 10 β†’ 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
    • πŸ” Single-arm, n=49; 1L atypical EGFR-mutated advanced NSCLC
    • πŸ’Š Median treatment duration 13.3 mo (range <0.1-53.2)
    • πŸ’Š 39% remained on treatment >2 years
    Results
    • πŸ“Š Median OS 41.0 mo (95% CI 27.7-NE); median follow-up 31.3 mo
    Critique
    • ⚠️ Single-arm; no randomized comparator vs osimertinib or chemotherapy
    • ⚠️ Small N (49) limits any subgroup analysis by EGFR variant subtype
    • ⚠️ 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

    Sourced from @chulkimMD

    πŸ“š Sources Β· 🐦 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
    • πŸ” Phase II, randomized, N=224; 1L EGFR-mutated NSCLC with brain mets, asandeutertinib (n=111) vs osimertinib (n=113)
    • πŸ’Š Asandeutertinib: next-generation EGFR TKI evaluated head-to-head vs established osimertinib SOC
    CONSORT flow
    Randomized 224
    ↓
    Asandeutertinib
    allocated 111
    Osimertinib
    allocated 113
    Critique
    • ⚠️ Safety (TRAEs)
      • Any TRAEs: 99.1% (asandeutertinib) vs 95.6% (osimertinib)
      • Serious TRAEs: 10.8% vs 7.1% β€” slightly higher in experimental arm
    • ⚠️ Phase 2 only, N=224; PFS medians not reached in experimental arm (immature); OS data not reported in source
    • ⚠️ 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

    Sourced from @DrRishabhOnco

    πŸ“š Sources Β· 🐦 1 tweet

    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?

    Sourced from @dr_yakupergun, @HHorinouchi

    πŸ“š Sources Β· 🐦 2 tweets

    Breast

    PREPEC is the first RCT to quantify the PRO advantage of pre-pectoral IBBR; the BREAST-Q gain is statistically significant but modest, offset by higher implant loss.

    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?

    Sourced from @to_be_elizabeth

    πŸ“š Sources Β· 🐦 1 tweet

    GI Upper

    Neo-CRAG adds CRT to peri-op chemotherapy in high-risk LAGC, halving locoregional recurrence and extending OS; XELOX backbone limits direct FLOT-era applicability.

    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

    Sourced from @NiuSanford

    πŸ“š Sources Β· 🐦 1 tweet

    CNS

    ROADS is the first randomized comparison of GammaTile vs post-op SRS in resected brain mets >2cm; striking cavity control benefit, but higher LMD rate with brachytherapy warrants close attention.

    ROADS

    ForResected brain mets >2cm

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

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

    Radiation Curative Practice-changing

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

    Sourced from @PDBrownOnc

    πŸ“š Sources Β· 🐦 1 tweet

    Supportive / QoL

    SPIN score offers pre-treatment patient selection for celiac plexus SRS, though the SPIN-2 subgroup (N=19) is too small for confident clinical adoption without external validation.

    SPIN Score (Celiac Plexus SRS) NCT03323489

    ForPancreatic cancer, intractable retroperitoneal pain, planned celiac plexus SRS

    TL;DR89% pain response in SPIN-2 pts (baseline pain >6 + no prior neurotoxic chemo) vs 32% SPIN-0 after celiac SRS.

    Radiation Supportive Caveats dominate

    SPIN Score (Celiac Plexus SRS)
    SPIN scoreResponse raten
    032%31
    153%40
    289%19
    8 details
    Methods
    • πŸ” Post-hoc analysis of 90 evaluable pts from pivotal ph2 (NCT03323489; Lancet Oncol 2024:25:1070-79)
    Results
    • πŸ“Š Pain response by SPIN score
    • πŸ“Š Pivotal ph2 overall response: 53% (95% CI 42-64%)
    • πŸ“ Multivariate predictors: no prior neurotoxic chemo (OR 5.1, p=0.009); baseline pain >6 (OR 1.8, p=0.003)
    • πŸ“ Optimism-corrected AUC 0.714 (bootstrap 500 iterations)
    • πŸ“ Pain threshold dose-response: >6 optimal (65.8%); >7 (83.3%); >8 (85.7%)
    Critique
    • ⚠️ Post-hoc design; internal validation only; external validation required before clinical use
    • ⚠️ SPIN-2 subgroup N=19; response estimate imprecise
    Open questions
    • External validation before clinical implementation
    • Applicability to non-pancreatic retroperitoneal malignancies
    • How early before neurotoxic chemo should SRS be offered?

    Sourced from @NiuSanford

    πŸ“š Sources Β· 🐦 1 tweet