Jeff Ryckman

Thank you! This is really helpful to consider. Looking back at both protocols: Yes, 305 also allowed palliative RT for new/progressive/sx lesions in pts continuing to benefit, after discussion with the medical monitor. Study treatment was to be held during RT, with ≥7 days from RT completion to the next dose. No specific pre-RT washout was stated. Interesting difference: 304 explicitly excluded the thoracic field; that restriction isn't in 305's salvage-RT section. The 305 exclusion I mentioned was prior/planned consolidative chest RT. Neither specifies dose/fx. Would be helpful to see how many pts actually received RT while staying on treatment, the sites treated, and time to the next systemic therapy. I'm particularly interested in how RT was interdigitated with tarla, including the actual treatment holds, to help guide real-world use. #DeLLphi305 #DeLLphi304 #ESMO26 #OncTwitter

Full DeLLphi-305 paper is out! (NEJM) That answers my RT question. Pts who had received or planned consolidative chest RT for ES-SCLC were excluded. PCI was allowed before enrollment. How to interdigitate thoracic consolidation remains unanswered. https://t.co/8m5snFgLER

DeLLphi-305 (LBA3): tarlatamab + durva vs durva maintenance in ES-SCLC without progression after durva + platinum-etoposide. OS HR 0.42 (CI 0.32-0.54); 12-mo OS 79% vs 53%, median OS 21 vs 13 mo. Impressive OS signal. Was thoracic consolidation RT allowed? The abstract doesn't say. If so, would be interested to see fractionation/dosing schemes and how RT was interdigitated. #ESMO26 #radonc https://t.co/wazLJ6ejpv

Proud of @ASTRO_org for this formal statement. Among other things, Proteus did not include a standard of care control arm (!) #PROTEUS #ASCO26 #PCSM @urotoday https://t.co/D1QOqre6qE

@miszczyk_marcin @seanmmcbride @DrSpratticus Love this! By the way - What is going on with amendment 6? So much added in section 5.4 February 2026 #Proteus #ASCO26 #PCSM https://t.co/FA1mVVSaA0

#Proteus #ASCO26 #OncTwitter #PCSM https://t.co/x6AlHv14oF

Long-term OS benefit w/ abiraterone in PEACE-1 (2215O). Note this is triplet vs ADT + docetaxel, not vs ADT + ARPI. 📌 Randomized phase 3, 2x2 factorial, 1,173 men w/ de novo mCSPC. High / low volume 57 / 43%. 📌 R 1:1:1:1 to SoC (ADT ± docetaxel), SoC + prostate RT 74/37, SoC + abi/prednisone, or SoC + abi/prednisone + RT. 📌 Median follow-up 7.7y. Among control-arm pts whose disease progressed, 86% received an ARPI. 📌 Adding abi to SoC: OS HR 0.75 (95% CI 0.65-0.87; p=0.0001). Pooled mOS 4.6→ 6.1y (ESMO press release). 📌 ADT + docetaxel ± abi (n=710): mOS 4.4→ 6.2y; HR 0.68 (95% CI 0.56-0.82). 8y OS 27.1→ 40.3%. This was not triplet vs ADT + ARPI doublet. 📌 High-volume mOS 3.5→ 4.6y, HR 0.68 (95% CI 0.54-0.85); low-volume 6.2→ 7.8y, HR 0.74 (95% CI 0.52-1.05). No detected volume interaction (p=0.56); low-volume OS not independently significant. 📌 G3-4 AEs, doublet→ triplet without RT (press release): HTN 14→ 21%; hypokalemia 1→ 4%. No new long-term safety signal reported. Side note on RT: in the 2024 Lancet RT analysis, prostate RT did not improve OS, but improved CRPC-free survival regardless of burden (HR 0.79, 95% CI 0.69-0.90), low-volume rPFS w/ abi (4.4→ 7.5y; aHR 0.65, 99.9% CI 0.36-1.19; RT effect p=0.019; no rPFS gain w/o abi; RT x abi interaction p=0.026), and reduced serious GU events (22.3→ 12.2%). ESMO 2026 reports RT only through four-arm mOS: SoC / SoC + RT / SoC + abi / SoC + abi + RT 4.6 / 4.6 / 5.7 / 6.4y. No new CRPC-free or GU-event RT data. https://t.co/q9jg8xElSt #ESMO26 #PCSM #radonc

@TonyFelefly @ChapinMD @piet_ost Totally agree, also delaying or preventing development of CRPC is meaningful endpoint, especially impressive in context of triplet therapy (recall: ~50% rec’d docetaxel on PEACE-1). Although PEACE-1 was not designed in this way, it would have been nice to see the high volume

A few details beyond the headline on KEYNOTE-975 RT dose wasn't randomized. Sites chose FP + 50 Gy, FP + 60 Gy, or FOLFOX + 50 Gy, and dose was a stratification factor. The 50 vs 60 Gy and SCC vs adeno breakdowns will be worth seeing, with the caveat that dose was site-selected. Grade 5 AEs: 10% placebo vs 13% pembro. Discontinuation for any AE: 27% vs 34%. The abstract lists grade ≥3 AEs in 100% of both arms. I'd want to see the slides or paper before taking that at face value. Still missing: RTQA, pneumonitis and esophagitis data. Abstract 2875O: https://t.co/wrEj8dPXY9 #ESMO26 #radonc

KEYNOTE-975: adding pembro to definitive CRT didn't improve EFS in CPS>=10 esophageal/GEJ cancer. HR 0.97 (95% CI 0.77-1.23). Hierarchy stopped there; OS wasn't formally tested. Another reason not to assume IO helps every CRT backbone. #ESMO26 #radonc https://t.co/JCWWmcCZHS https://t.co/SCdkZqxsjS

Full SANO paper is out! (Ann Oncol, open access) What it adds: Death from esophageal cancer at 5y: 40% with active surveillance vs 30% with surgery (HR 1.67, 95% CI 1.02–2.73). Other-cause death: 10% vs 15% (HR 0.49, 0.22–1.09). These are competing-risk secondary outcomes. Of 91 metastases in the surveillance arm, 44 came after delayed oesophagectomy, a median 11.1 mo after regrowth (not after surgery). 22 were found within 6 mo of nCRT. Regrowth was associated with later metastasis (HR 2.49), but the trial can't separate seeding from biology. Regrowth risk comes early: ~21% remaining if still in cCR at 1 year, 2% at 3 years. The "43% spared esophagectomy" figure includes patients with early metastases. Durable organ preservation: 32% in cCR at last evaluation, and 21% completed 5 years of surveillance. The protocol does define volumes (§8.3.2): regional nodes within ≥3 cm craniocaudal, 3 mm radial CTV, 1 cm PTV. There's no RTQA or adherence analysis. Adjuvant systemic therapy isn't reported. The authors now call it "selectively delayed surgery rather than surgery avoidance." Fair. #ESMO26 #radonc @KrishanJethwa https://t.co/n5RpZK9zls

🚨SANO 5y: surveillance vs surgery after cCR OS 50% vs 54% (NS) Distant mets 46% vs 29% (P<.01) Reminder: only 41.4 Gy/23 fx, a pre-op, arguably non-definitive dose, especially with/ ~75% adenocarcinoma. Nonsignificant OS doesn't establish noninferiority. #ESMO26 #RadOnc #OncTwitter

PE-PE is a fantastic study, giving us randomized data on adding pembrolizumab to MDT in oligometastatic RCC! Phase II, open-label, multicenter trial: 85 pts with prior nephrectomy and ≤3 mets within 5y of nephrectomy or previous metastasectomy, all amenable to surgery or SABR. Randomized 2:1 favoring pembro: MDT alone (n=29) vs pembro + MDT (n=56). Pembro 400 mg q6w x9c (1y). First dose BEFORE MDT; registry specifies MDT on C1d21-42. At MFU 17.5 mo, median RFS was 11→ 25.4 mo (HR 0.47, 95CI 0.24-0.92, p=0.024), MDT alone→ pembro + MDT. 35 RFS events, 16→ 19. SABR 72→ 73%; surgery 28→ 23%. SABR dose/fx and per-site data weren't reported. I'd like to see those details along with local vs distant relapse. Any AE 21→ 80%; G3 AEs 3→ 7%. The 21% control rate is with no study systemic therapy. Pembro-related AEs occurred in 59%, including G3 in 2 pts; no G4/5 pembro-related events were reported. Four pts stopped pembro for AEs. Both groups received MDT, so the randomized question is what pembro adds. This doesn't establish the benefit of MDT itself or RT-ICI synergy. With 1 death/arm and no QoL results reported, an OS/QoL benefit remains unestablished. I'd also like the prior systemic therapy history and the timing/burden at first metastatic presentation. The eligibility window alone doesn't tell us whether these pts were oligometastatic from the outset. Congratulations to the investigators on this important work! https://t.co/i8P1uvW9y4 #radonc #ESMO26 #RCC

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. https://t.co/he6OT4TsJ5 https://t.co/LaiIFjAdII #radonc #ESMO26 #LCSM

Longer CNS-PFS w/ T-DXd + pertuzumab in the DESTINY-Breast09 (DB-09) brain mets subgroup (LBA49). 📌 Exploratory subgroup of randomized phase 3 DESTINY-Breast09: 61 pts w/ HER2+ advanced/metastatic breast cancer, baseline brain mets by BICR and ≥1 follow-up brain scan. T-DXd + pertuzumab (n=31) vs taxane + trastuzumab + pertuzumab (THP, n=30). 📌 Median follow-up 23.6 mo. mCNS-PFS NE vs 9.7 mo; HR 0.26 (95% CI 0.11-0.57). 📌 CNS-cORR 51.6% (95% CI 33.1-69.8) vs 26.7% (95% CI 12.3-45.9), by BICR. 📌 mPFS 36.5 vs 11.1 mo. 📌 Parent-trial drug-related ILD/pneumonitis: 12.1% (incl 2 grade 5) vs 1.0%. Brain mets subgroup AE rates aren't reported. Side note: prior CNS local therapy and the active/treated brain mets split aren't reported in the abstract. https://t.co/1kEnVk7VEw #ESMO26 #BCSM