Daniel Portik

Congrats to Reck, Spicer, Filippi and team on the full MDT-BRIDGE paper in Nature Medicine! Really appreciate seeing the RT protocol and full denominators alongside the ASTRO results. 👏 This single-arm ph2 enrolled 142 pts with resectable or borderline-resectable stage IIB-selected IIIB, EGFR/ALK-wt NSCLC. Durvalumab + platinum chemo x2c→ MDT reassessment→ additional chemoimmunotherapy and surgery, or CRT, followed by durvalumab. Resection was 74.6% (95CI 66.7-81.6), with R0 in 96.2% of those who started surgery. pCR was 27.3% in the resectable analysis cohort. The 12-mo EFS estimates are 88.5% overall and 90.1% in that resectable cohort. Different denominators, same readout. The RT protocol details are useful: nominal 60/30 (60 Gy ±10% in 2 Gy fx), 5 fx/wk for ~6 wk, concurrent or sequential platinum chemo. SBRT was not allowed. IMRT with daily CBCT was preferred, then consolidation durvalumab q4w up to 12c. All 25 pts who started CRT completed it: 21 concurrent, 4 sequential. 23 received consolidation durvalumab. The post hoc CRT-treated analysis estimated 12-mo PFS at 85% (95CI 59.8-95.0), measured from the FIRST study-treatment dose, including induction. CRT-period G3/4 AEs were 28%; pneumonitis 8% (2 pts, both G2). During consolidation, G3/4 AEs were 17.4%, AE discontinuation 13%, and pneumonitis 8.7% (G1/2). One cardiac-failure AE death occurred during consolidation; the paper reports no treatment-related AE deaths in that period. The safety windows extend beyond treatment delivery and can overlap. The ESMO ctDNA analysis adds an interesting association. Pre-Sx/CRT clearance occurred in 33/90 evaluable pts (36.7%). C2D1 clearance had an 83.3% PPV for pCR (95CI 43.6-99.1). Among resected pts, no EFS events occurred with pre-Sx clearance (n=28); 12-mo EFS without clearance was 88.9% (n=40). In CRT-treated pts, 12-mo PFS was 100% with pre-CRT clearance vs 77.5% without. The paper now supplies those subgroup sizes: just 4 vs 16 pts, with 2 vs 6 at risk at 12 mo. One later event occurred in the clearance group, so 100% is a timepoint estimate, not no events throughout follow-up. Useful prospective evidence that patients can reach definitive CRT after starting on a surgical pathway. The unanswered question remains who benefits from that sequence versus going directly to CRT or selecting for NAC-ICO with intent for organ preservation. Selected cohorts, immature EFS/PFS and no reported OS cannot settle that, and ctDNA does not yet tell us which local therapy to choose or omit. doi.org/10.1038/s41591-026-0… cslide.ctimeetingtech.com/es… #radonc #ESMO26 #LCSM

T-REX has quite a generous NI margin: Non-inferiority is declared if the de-escalation arm is not more than 4.5 percentage points worse than standard regional RT. This corresponds to an HR of about 1.41, assuming 88% 5-year RFS with standard treatment. #OncTwitter #BCSM #ASCO26

Needle biopsies are standard because knowing exactly what you’re treating overwhelmingly outweighs the exceedingly small risks. Major reviews do not show increased metastasis from routine biopsy. Fear-based misinformation harms real patients.