Phase 3 RCT — oncbrain

PrTK03 (aglatimagene besadenovec + EBRT) NCT01436968

ForIntermediate/high-risk localized prostate cancer, ECOG 0–2, planning definitive

TL;DRDFS HR 0.70 (0.52–0.94), p=0.016 favoring aglatimagene + valacyclovir + EBRT vs placebo in intermediate/high-risk localized prostate cancer.

Combined Curative Phase 3 RCT Practice-changing

10 details

Methods

🔍 Phase 3 double-blind placebo-controlled, N=745, 2:1 allocation, 51 US/Puerto Rico centers
🔍 Intermediate or high-risk M0 localized prostate cancer; ECOG 0–2; EBRT 78 Gy/2 Gy or hypofractionated; ADT optional
💊 Intraprostatic aglatimagene (CAN-2409, replication-defective adenoviral HSV-TK vector) × 3 courses + valacyclovir prodrug; immune bystander cytotoxicity mechanism

CONSORT flow

Randomized 745

↓

Aglatimagene + valacyclovir + EBRT

allocated 496

analyzed 479

Placebo + valacyclovir + EBRT

allocated 249

analyzed 232

Results

📊 1° EP: DFS HR 0.70 (95% CI 0.52–0.94), p=0.016
📊 Median DFS not reached (aglatimagene) vs 86.1 months (IQR 29.7–143.0) in placebo
📐 Median follow-up 50.3 months (IQR 35.2–63.3)

Critique

⚠️ G3+ TEAEs similar between arms
- Aglatimagene: 8% (40/479); placebo: 7% (17/232)
- Most common G3+: AKI — 2% both arms
- SAEs: 6% aglatimagene vs 7% placebo; treatment-related SAEs 2% both arms
- No treatment-related deaths
⚠️ 1° EP is DFS (composite: recurrence or death), not OS; OS data not reported in source
⚠️ 50-month median f/u likely underpowers late events; prostate cancer recurrences extend 10+ years post-RT
⚠️ Sponsor-funded (Candel Therapeutics + NIH); 79% White cohort — generalizability to diverse populations limited

Open questions

OS benefit not yet established; long-term follow-up ongoing
Differential effect by risk category (intermediate vs high-risk)?
Sequencing with ARPI intensification for STAMPEDE-eligible pts

📚 Sources · 📄 1 paper

📄 PAPER Dykstra, Michael P.; Regan, Samuel N.; Yin, Huiying (Maggie) et al. · JCO Oncology Practice (2025-09)

Androgen Deprivation Therapy Practice Patterns in High-Risk Prostate Cancer Treated With Definitive Radiotherapy: Prospective Results From a Statewide Quality Consortium

PMID → doi

Abstract

PURPOSE The 2022 AUA/ASTRO guidelines recommend 18-36 months of androgen deprivation therapy (ADT) with definitive radiotherapy for localized, high-risk prostate cancer. The STAMPEDE M0 trial supports intensification with androgen receptor pathway inhibitors (ARPIs) for patients with ≥2 cT3/T4, Grade Group [GG] 4-5, prostate-specific antigen (PSA) ≥40 ng/mL, or cN1. Given advances in imaging, risk stratification, and treatment delivery, we characterized contemporary practice patterns using prospective data from the Michigan Radiation Oncology Quality Consortium (MROQC). METHODS Patients enrolled in MROQC with intact, high-risk M0/N0-1 prostate cancer were included. Clinical information, including intended ADT duration and ARPI use, was prospectively collected. The primary outcome was intended guideline-concordant ADT (GC-ADT, ≥18 months). Multivariable analyses (MVA) assessed associations between clinical factors and GC-ADT recommendations. We compared the adoption of ARPI with standard therapies before and after the publication of STAMPEDE M0. Facility-level variability was evaluated using a mixed-effects model, with the treatment site as a random intercept. RESULTS Between June 2020 and November 2024, 553 patients across 26 centers were included: cT3/4 (13.3%), cN1 (19.9%), GG 4-5 (75.0%), and PSA ≥20 ng/mL (40.0%). Overall, 91.3% were recommended ADT, with 67.0% being guideline-concordant. On MVA, GC-ADT was significantly associated with cN1 (odds ratio [OR], 2.94 [95% CI, 1.44 to 5.99]), GG (GG4 OR, 6.23 [95% CI, 2.85 to 13.62]; GG5 OR, 9.45 [95% CI, 4.46 to 20.06]), and PSA ≥40 (OR, 3.64 [95% CI, 1.22–10.87]). Facility-level variability persisted in the MVA ( P < .0001). Among the 27.9% who met meeting STAMPEDE criteria, ARPI recommendations increased from 0% prepublication to 23.2% afterward. CONCLUSION Within a statewide quality consortium, guideline-concordant ADT recommendations occurred in two thirds of patients, with ARPI intensification in under 25% among STAMPEDE-eligible patients. These findings highlight the need for individualized ADT strategies and collaborative efforts to standardize high-quality care.

AREST

ForpT1-2 pN0 OSCC, intermediate-risk (DOI/PNI/LVE/poor diff), post-curative surgery

TL;DR3-yr LRFS 89.2% vs 80.9%, HR 0.52 (p=0.02) favoring adj RT in pT1-2 pN0 OSCC with intermediate-risk features; DFS/OS NS.

Radiation Curative Phase 3 RCT Practice-changing

8 details

Methods

🔍 Phase III open-label RCT, N=392; 1:1 stratified by subsite, PNI/LVE, differentiation
🔍 Eligibility: pT1-2 pN0 OSCC, ≥1 intermediate-risk factor (DOI 5-10mm, PNI, LVE, poor diff); margins ≥5mm, ≥16 nodes dissected
💊 Adj RT: 60Gy/30fr to tumor-bed + at-risk neck nodes; median f/u 47.2mo (IQR 30-59)

CONSORT flow

Randomized 392

↓

Adjuvant RT

allocated 191

Observation

allocated 201

Results

📊 1° EP LRFS ITT: 3-yr 89.2% RT vs 80.9% obs, HR 0.52 (95%CI 0.30-0.91), p=0.02
📊 Competing-risk cumulative LR failure: 10.6% RT vs 18.9% obs, HR 0.52, p=0.021
📐 PP analysis: HR 0.43 (0.23-0.80), p=0.01
📊 Subgroup: oral tongue derives greater LRFS benefit than buccal mucosa

Critique

⚠️ DFS and OS not significantly different; LRC benefit does not translate to survival gain at 47mo

Open questions

Does LRC benefit translate to OS with longer follow-up?
Should adj RT selection favor oral tongue over buccal mucosa?
Does benefit differ by number of risk factors (1 vs ≥2)?

📚 Sources · 📄 1 paper

📄 PAPER Nair, Sudhir Vasudevan; Gupta, Tejpal; Rane, Swapnil Ulhas et al. · Journal of Clinical Oncology (2026-06)

Adjuvant radiotherapy versus observation following curative surgery for early-stage oral squamous cell carcinoma (AREST; CTRI/2017/07/009114).

PMID → doi

Abstract

6000 Background: The role of adjuvant radiotherapy (RT) in early-stage, node-negative oral squamous cell carcinoma (OSCC) with one or more intermediate risk factors - such as depth of invasion (DOI) ≥5 to ≤10mm, perineural invasion (PNI), lymphovascular emboli (LVE), or poor differentiation - remains debatable and is largely based on retrospective data. This multicenter, open-label, phase III randomized controlled trial was designed to assess the impact of post-operative adjuvant RT in this setting. Methods: Patients with early-stage (pT1-T2), node-negative (pN0) OSCC undergoing adequate surgery (defined as clear margins ≥5mm and at least ipsilateral level I-III neck dissection with ≥16 nodes) with presence of one or more intermediate risk factors were screened. Eligible patients underwent stratified randomization (oral cavity subsite, PNI/LVE, and differentiation) in 1:1 ratio to either observation or adjuvant RT (60Gy in 30 fractions over 6-weeks) to the resected tumor-bed and at-risk neck nodal region after written informed consent. Primary endpoint was loco-regional recurrence-free survival (LRFS) measured from randomization to first documented event of local and/or regional recurrence from index cancer. All time-to-event outcomes were computed using Kaplan-Meier (KM) method with log-rank test for comparison and expressed as 3-year point estimates with 95% confidence intervals (CI). The planned sample size (N=392) provided 80% power at an α of 0.05 to detect a Hazard Ratio (HR) of 0.6256, assuming 3-year LRFS of 70% in the observation arm. Results: Following curative surgery, a total of 392 patients were randomized (191 to adjuvant RT; 201 to observation). Baseline characteristics were balanced between the two arms. At a median follow-up of 47.2 months (inter-quartile range=30-59.4 months), 3-year KM estimate of LRFS was 89.2% in adjuvant RT arm vs 80.9% in observation arm (HR=0.52, 95%CI=0.30-0.91; p=0.02) in the intention-to-treat (ITT) population and 91.1% vs 80.9% (HR=0.43, 95%CI=0.23-0.80; p=0.01) on per-protocol (PP) analyses. Cumulative incidence of loco-regional failure with death as competing event was 10.6% (95%CI=6.1%-15.1%) with adjuvant RT and 18.9% (95%CI=13.3%-24.6%) with observation (HR=0.52, 95%CI=0.30-0.91; p=0.021) in the ITT population and 8.7% (95%CI=4.3%-13.1%) vs 18.9% (95%CI=13.3%-24.6%) (HR=0.43, 95%CI=0.23-0.79; p=0.007) on PP analyses. Disease-free and overall survival were not significantly different between the two arms. Subgroup analysis identified oral tongue deriving higher benefit of adjuvant RT compared to buccal mucosa. Conclusions: Adjuvant RT significantly reduces risk of loco-regional recurrence for early-stage, node-negative adequately resected OSCC, particularly oral tongue. However, such reduction in loco-regional failure does not translate into significant survival benefit. Clinical trial information: CTRI/2017/07/009114.

📝 https://ascopubs.org/doi/10.1200/JCO.2026.44.16_suppl.6000

mRCAT-III NCT06507371

ForpMMR/MSS LARC, cT3-4N0/+M0, tumor ≤10cm from anal verge, no positive lateral LN

TL;DRpCR 61% vs 29% (p<0.0001) with node-sparing SCRT + CAPOX + tislelizumab vs conventional SCRT + CAPOX in pMMR LARC.

Combined Curative Phase 3 RCT Early signal

mRCAT-III — Outcome Experimental (N=77) Control (N=77) p

pCR rate 61.0% (47/77) 28.6% (22/77) <0.001
MPR rate (TRG0+1) 77.9% (60/77) 50.6% (39/77) <0.001

Outcome	Experimental (N=77)	Control (N=77)	p
pCR rate	61.0% (47/77)	28.6% (22/77)	<0.001
MPR rate (TRG0+1)	77.9% (60/77)	50.6% (39/77)	<0.001

+1 more figure

9 details

Methods

🔍 Phase 3 open-label RCT, N=154 (77/arm), 17 centers China, stratified by cN stage
🔍 Node-sparing RT: 5Gy×5d targeting tumor bed only; elective tumor-draining LNs excluded from CTV
💊 Experimental: tislelizumab 200mg d1 + oxaliplatin 130mg/m² d1 + capecitabine 1000mg/m² d1-14

CONSORT flow

Randomized 154

↓

Node-sparing SCRT + CAPOX + tislelizumab

allocated 77

analyzed 77

Conventional SCRT + CAPOX

allocated 77

analyzed 77

Results

📊 1° EP (pCR, ITT): 61.0% (47/77) vs 28.6% (22/77), p<0.0001
📊 MPR (TRG0+TRG1): 77.9% (60/77) vs 50.6% (39/77), p<0.0001
📊 Severe GI AEs lower in experimental arm per investigator report; specific rates not provided in source

Critique

⚠️ pCR is surrogate; EFS/OS are secondary endpoints, not yet reported
⚠️ Small N (77/arm); single-country (China); open-label (pCR assessed by blinded central review)
⚠️ pMMR/MSS only; dMMR/MSI-H pts excluded (already IO-responsive in LARC)

Open questions

EFS and OS outcomes (secondary endpoints, not yet reported)
Organ preservation rate with node-sparing approach
Risk of elective nodal failure with lymph node omission

📚 Sources · 🐦 1 tweet

One of most interesting rectal ca studies at #ASCO26

P3 RCT in pMMR LARC: Node-sparing short-course RT + CAPOX + tislelizumab doubled pCR v conventional SCRT + CAPOX (61 v 29%)

Hypothesis = sparing elective node RT preserves antitumor immunity & improves PD1 response @OncoAlert pic.twitter.com/6xvA6ne0mg
— Dr. Nina Niu Sanford (@NiuSanford) June 2, 2026

ES-SCLC Concurrent TRT + Chemoimmunotherapy (LBA8005)

ForES-SCLC, treatment-naïve, 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) — Arm Median OS 95% CI HR (95% CI) p

ChemoIO + TRT 10.0 mo 8.3-11.7 1.14 (0.84-1.56) 0.40
ChemoIO 11.8 mo 10.0-13.6 ref n/a

Arm	Median OS	95% CI	HR (95% CI)	p
ChemoIO + TRT	10.0 mo	8.3-11.7	1.14 (0.84-1.56)	0.40
ChemoIO	11.8 mo	10.0-13.6	ref	n/a

+3 more figures

Arm	Median PFS	95% CI	HR (95% CI)	p
ChemoIO + TRT	5.1 mo	4.7-5.4	1.10 (0.84-1.45)	0.49
ChemoIO	5.0 mo	4.6-5.4	ref	n/a

Subgroup	ChemoIO+TRT median OS	ChemoIO median OS	HR (95% CI)	p
Completed all 4 cycles	11.9 mo	12.1 mo	1.02 (0.72-1.44)	0.92
No brain/liver mets	11.9 mo	13.2 mo	1.10 (0.65-1.87)	0.72

6 details

Methods

🔍 Phase III RCT, N=228 (115 vs 113); TRT 30 Gy/10 fr concurrent from day 21-28 of cycle 1
🔍 Eligibility: stage IV SCLC or stage III ineligible for curative CRT, ECOG 0-1, measurable thoracic lesion required
🔍 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

📚 Sources · 🐦 1 tweet

🚨 #ASCO26 | #️⃣LBA8005⁰☢️ Concurrent thoracic radiotherapy + chemoimmunotherapy in ES-SCLC

👥 ES-SCLC⁰Durvalumab + platinum/etoposide⁰± concurrent thoracic radiotherapy⁰TRT: 30 Gy / 10 fractions, starting day 21–28

📊 Randomized phase III⁰ChemoIO + TRT: n=115⁰ChemoIO… pic.twitter.com/TDA5amz59e
— Masahiro TORASAWA, MD. PhD. (@M_Torasawa) June 2, 2026

DeLLphi-304 (tarlatamab CNS outcomes)

For2L ES-SCLC; brain mets subgroup ≥1 BM at baseline, >70% prior CNS treatment

TL;DRCNS PFS HR 0.54 (ITT), HR 0.40 in brain mets; CNS CR 14.9% vs 5.4% with tarlatamab vs chemo 2L SCLC.

vs leading data

DeLLphi-304 primary results: tarlatamab OS + PFS benefit in 2L SCLC; CNS data extends intracranial signal

Systemic Palliative Phase 3 RCT Caveats dominate

DeLLphi-304 (tarlatamab CNS outcomes) — Arm n Median CNS PFS (mo) HR (95% CI)

Tarlatamab 67 6.5 (4.3-13.7) 0.40 (0.24-0.66)
Chemotherapy 56 4.2 (2.9-5.5) ref

Arm	n	Median CNS PFS (mo)	HR (95% CI)
Tarlatamab	67	6.5 (4.3-13.7)	0.40 (0.24-0.66)
Chemotherapy	56	4.2 (2.9-5.5)	ref

+2 more figures

Arm	n	Median CNS PFS (mo)	HR (95% CI)
Tarlatamab	254	NE (13.7, NE)	0.54 (0.39-0.75)
Chemotherapy	255	7.2 (5.6, NE)	ref

Endpoint	Tarlatamab (n=67)	Chemo (n=56)
CNS CR	10 (14.9%)	3 (5.4%)
Non-CR/Non-PD	42 (62.7%)	37 (66.1%)
CNS DCR	52 (77.6%)	40 (71.4%)
Median duration CNS CR (mo)	NE	3.6
Median duration CNS DC (mo)	8.2	5.2

5 details

Methods

🔍 Post-hoc subgroup analysis of DeLLphi-304 phase 3 RCT; ITT n=509 (254 tarlatamab / 255 chemo)
🔍 Brain mets subgroup: n=67 (tarlatamab) vs n=56 (chemo); >70% had prior CNS treatment
🔍 Data cutoff Jan 29 2025; median f/u 11.4 mo (tarlatamab), 11.5 mo (chemo)

Results

📊 Ongoing CNS complete response at cutoff: 5 (50%) tarlatamab vs 0 chemo

Critique

⚠️ CNS outcomes not prespecified; interpretability limited without a confirmatory prospective CNS endpoint

Open questions

Does tarlatamab CNS activity change the role of PCI in ES-SCLC?
Confirmatory prospective CNS endpoint needed from DeLLphi-304 or successor trial
Durability of CNS CR beyond 11mo median f/u

📚 Sources · 🐦 1 tweet

Dr. @g_mountzios #ASCO26 presents CNS outcomes with 2L tarlatamab in DeLLphi-304. Improved time to CNS progression overall (HR 0.54). In pts with brain nets, tarlatamab vs chemo CNS CR rate 15% vs 5% with DCR 78% vs 71% and time to CBS progression 6.5m vs 4.2m, HR 0.40 pic.twitter.com/5i8jL1zlKW
— Stephen V Liu, MD (@StephenVLiu) June 1, 2026

PROTEUS

ForBiochemically recurrent prostate cancer, post-radical prostatectomy

TL;DR53.0% (APA) and 60.7% (ADT) of MFS events PSMA PET-detected; APA+ADT vs ADT benefit in BCR prostate hotly contested.

Systemic Curative Phase 3 RCT Caveats dominate

6 details

Methods

🔍 Phase 3 RCT, APA + ADT vs ADT alone in BCR prostate cancer, post-RP setting

Results

📊 Full primary endpoint data pending ASCO26 presentation; no effect size reported in source tweets
📊 NEJM paper: 53.0% (APA arm) and 60.7% (ADT arm) of distant mets identified by PSMA PET, not conventional imaging

Critique

⚠️ Majority of MFS events PSMA PET-only: magnitude of conventional-imaging MFS benefit unclear
⚠️ ASCO26 preview framing: 'some may call this a homerun, others may call this the largest negative'

Notes

❓ PSMA PET-detected MFS not an established OS surrogate; does EFS benefit translate to survival?

Open questions

Does PSMA PET-detected EFS/MFS benefit translate to OS?
Magnitude of benefit by conventional imaging alone

📚 Sources · 🐦 3 tweets

#ASCO26
The PROTEUS trial results are now online...buckle up as we wait to see the full presentation. This is going to be a trial that is likely highly controversial until the full results are published.

Some may call this a homerun, others may call this the largest negative…
— Daniel E Spratt (@DrSpratticus) May 31, 2026

📝 Note until the trial is released later this is preview

Thought experiment:

Let's take a very simple hypothetical trial involving 100 patients in the APA arm and 100 patients in the ADT alone arm. Pulling from PROTEUS EFS data, assume that, by 5 years, 60 patients in the ADT arm have had a BCR compared to 50 in the ADT+APA arm.… pic.twitter.com/WJaiDlJnQs
— Sean McBride (@seanmmcbride) May 31, 2026

📝 note add commentary to proteus discussion

#ASCO26
Talk about real-time updates. NEJM paper now online and my predictions and inferences appear true.

Majority of MFS events were by PET not conventional imaging. "Most distant metastases were identified by PSMA PET (53.0% of those in the apalutamide group and 60.7% in the… https://t.co/Yz4myY0flq
— Daniel E Spratt (@DrSpratticus) May 31, 2026

📝 add to proteus data

ENZARAD

ForHigh-risk localized PCa (Gleason 8-10, T3-4, or N1, or PSA ≥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 — Arm Events/N MFS 8y HR (95% CI) 2p

Enzalutamide 98/401 74% 0.88 (0.67-1.15) 0.34
Control (NSAA) 109/401 72% ref ref

Arm	Events/N	MFS 8y	HR (95% CI)	2p
Enzalutamide	98/401	74%	0.88 (0.67-1.15)	0.34
Control (NSAA)	109/401	72%	ref	ref

+2 more figures

Arm	Events/N	OS 8y	HR (95% CI)	2p
Enzalutamide	69/401	83%	0.87 (0.63-1.20)	0.40
Control (NSAA)	77/401	80%	ref	ref

5 details

Methods

🔍 Phase 3 RCT (ANZUP), N=802, 1:1; high-risk localized PCa (Gleason 8-10, T3-4, N1, or PSA ≥20 ng/mL); median FU 8y
🔍 Enzalutamide 160mg/d x24mo + LHRH agonist x24mo vs NSAA x6mo + LHRH agonist x24mo; both arms: RT ± brachytherapy boost ± pelvic nodal RT

CONSORT flow

Randomized 802

↓

Enzalutamide

allocated 401

Control (NSAA)

allocated 401

Results

📊 Both 1° (MFS) and 2° (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

📚 Sources · 🐦 1 tweet

🚨ENZARAD at #ESMO25 presented by @DrPaulNguyen

No improvement in MFS or OS with the addition of enzalutamide to high dose radiotherapy + 2y ADT in high risk #prostatecancer

Possible benefit in cN1 pts or pts treated with pelvic RT. pic.twitter.com/vXLRKuIPeg
— Pierre Blanchard, MD (@PBlanchardMD) October 19, 2025

RASolute 302

ForPrev-treated metastatic PDAC, RAS G12 mutation, ≥1 prior systemic line

TL;DRDaraxonrasib vs IC chemo in 2L RAS G12 mPDAC: mOS 13.2 vs 6.6 mo, HR 0.40 (0.30-0.54), p<0.001.

vs leading data

2L PDAC historical: IC chemo (FOLFOX, nalirinotecan-based regimens) mOS ~5-7 mo; daraxonrasib more than doubles median in RAS G12-selected pts

Systemic Palliative Phase 3 RCT Practice-changing

RASolute 302 — Daraxonrasib Chemotherapy

RAS G12: N 228 231
RAS G12: mOS (95% CI) 13.2 mo (10.0-NR) 6.6 mo (5.4-8.2)
RAS G12: HR (95% CI), p 0.40 (0.30-0.54), p<0.001 ref
RAS G12: 12-mo OS 53.3% 8.7%
Overall: N 248 252
Overall: mOS (95% CI) 13.2 mo (10.0-NR) 6.7 mo (5.8-8.0)
Overall: HR (95% CI), p 0.40 (0.30-0.53), p<0.001 ref
Overall: 12-mo OS 53.2% 17.3%

	Daraxonrasib	Chemotherapy
RAS G12: N	228	231
RAS G12: mOS (95% CI)	13.2 mo (10.0-NR)	6.6 mo (5.4-8.2)
RAS G12: HR (95% CI), p	0.40 (0.30-0.54), p<0.001	ref
RAS G12: 12-mo OS	53.3%	8.7%
Overall: N	248	252
Overall: mOS (95% CI)	13.2 mo (10.0-NR)	6.7 mo (5.8-8.0)
Overall: HR (95% CI), p	0.40 (0.30-0.53), p<0.001	ref
Overall: 12-mo OS	53.2%	17.3%

6 details

Methods

🔍 Phase 3 RCT; RAS G12 primary analysis N=459 (228 vs 231); overall N=500 (248 vs 252); control: investigator's choice chemotherapy

CONSORT flow

Randomized 500

↓

Daraxonrasib

allocated 248

Chemotherapy

allocated 252

Results

📊 1° EP (RAS G12 population): mOS 13.2 mo (95% CI 10.0-NR) vs 6.6 mo (5.4-8.2); HR 0.40 (0.30-0.54), p<0.001
📐 12-mo OS (RAS G12): 53.3% daraxonrasib vs 8.7% chemo
📊 Consistent in overall population (all RAS mutations + no-mutation pts, N=500): HR 0.40 (0.30-0.53), p<0.001; mOS 13.2 vs 6.7 mo

Critique

⚠️ Event maturity asymmetric at datacut: 32% events in daraxonrasib arm vs 55% chemo; upper OS CI not reached (NR); follow-up ongoing
⚠️ G12 variant breakdown (G12D vs G12V vs G12R) not reported in source

Open questions

Activity by specific G12 variant (G12D vs G12V vs G12R)
Durability beyond current f/u; upper OS CI not yet reached
Optimal sequencing and potential 1L investigation

📚 Sources · 🐦 1 tweet

#ASCO26

This one is special.

This is the hottest paper of 2026 and potentially in the history of pancreatic cancer.

Let’s dive in.

RASolute 302: Daraxonrasib vs investigator’s choice chemotherapy in previously treated metastatic pancreatic cancer
Abstract LBA5 (soon!)… pic.twitter.com/Lq7PEjOWAo
— Nicholas Hornstein (@GIMedOnc) May 31, 2026

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 — Analysis Decipher Docetaxel HR (95% CI) p Interaction p

Unweighted ≤0.85 2.78 (1.49, 5.21) 0.001 0.02
Unweighted >0.85 1.13 (0.71, 1.79) 0.60 —
IPTW ≤0.85 1.94 (0.95, 3.96) 0.07 0.04
IPTW >0.85 0.75 (0.43, 1.33) 0.33 —

Analysis	Decipher	Docetaxel HR (95% CI)	p	Interaction p
Unweighted	≤0.85	2.78 (1.49, 5.21)	0.001	0.02
Unweighted	>0.85	1.13 (0.71, 1.79)	0.60	—
IPTW	≤0.85	1.94 (0.95, 3.96)	0.07	0.04
IPTW	>0.85	0.75 (0.43, 1.33)	0.33	—

+1 more figure

Decipher	OS HR triplet vs doublet (95% CI)	p
≤0.85	3.02 (1.50-5.76)	—
>0.85	1.08 (0.60-1.71)	0.73

4 details

Methods

🔍 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 — 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

📚 Sources · 🐦 2 tweets

#ASCO26 GU Oncology Spotlight 🚨

🔬 ENZAMET + Decipher | Part 2
Can genomics guide docetaxel intensification in mHSPC?
Outstanding presentation by @ChrisSweeney1.@OncoAlert @ASCO

After Part 1, the key question was:

➡️ Can a genomic classifier identify which patients with… pic.twitter.com/nJYMxuXelV
— Dra. María Natalia Gandur Quiroga (@nataliagandur) May 30, 2026

#ASCO26 GU Oncology Spotlight 🚨

🔬 Precision Oncology: How to Apply New Biomarkers in Clinical Practice
Excellent discussion by Joshua M. Lang, MD, MS@JoshLangMD @OncoAlert @ASCO
This session captured the real challenge of precision oncology in GU cancers:

A biomarker is only… pic.twitter.com/ubfk49XPiM
— Dra. María Natalia Gandur Quiroga (@nataliagandur) May 30, 2026

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 — Subgroup n (exp/ctrl) Median rPFS exp Median rPFS ctrl HR (95% CI)

ITT 300/299 NC (NC-NC) 45.8 (37.7-NC) mo 0.48 (0.36-0.65), p<0.001
BRCA 104/103 NC (NC-NC) 35.1 (18.6-NC) mo 0.37 (0.22-0.61)
Non-BRCA 196/196 NC (NC-NC) NC (40.5-NC) mo 0.57 (0.39-0.82)

Subgroup	n (exp/ctrl)	Median rPFS exp	Median rPFS ctrl	HR (95% CI)
ITT	300/299	NC (NC-NC)	45.8 (37.7-NC) mo	0.48 (0.36-0.65), p<0.001
BRCA	104/103	NC (NC-NC)	35.1 (18.6-NC) mo	0.37 (0.22-0.61)
Non-BRCA	196/196	NC (NC-NC)	NC (40.5-NC) mo	0.57 (0.39-0.82)

3 details

Methods

🔍 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

📚 Sources · 🐦 1 tweet

JUST In: TALAPRO-3 published in @NEJM

Adding #talazoparib to enzalutamide/ADT

=>3-year rPFS: 77% vs 56% in HRR-deficient metastatic prostate cancer !
Looking forward to full presentation by @neerajaiims who keeps changing SOC, one trial at a time. @ASCO #ASCO26 @OncoAlert pic.twitter.com/nXiPk4DIXg
— Toni Choueiri, MD (@DrChoueiri) May 30, 2026

OptiTROP-Lung05 NCT06448312

ForStage IIIB-IV NSCLC, PD-L1 TPS ≥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, TPS≥50%): ADC+IO > IO-mono signal emerging in 1L NSCLC

Systemic Palliative Phase 3 RCT Confirmatory

OptiTROP-Lung05 — Arm Events 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) ref —

Arm	Events 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)	ref	—

+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.

PD-L1 TPS	Sac-TMT+Pembro median PFS	Pembro median PFS	HR (95%CI)
≥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)

8 details

Methods

🔍 Phase 3 open-label RCT; N=413; stage IIIB/IIIC/IV NSCLC; PD-L1 TPS ≥1%; no EGFR/ALK; ECOG 0-1
💊 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

📊 1° 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
📊 ORR 70.2% vs 42.0%
📊 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
📊 PFS benefit consistent across both PD-L1 TPS subgroups (≥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 — 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?

📚 Sources · 🐦 2 tweets

Right patient. Right treatment. Right timing.

The result: curves like these👇#ASCO26 https://t.co/72KByLKz90
— Yakup Ergün (@dr_yakupergun) May 30, 2026

🔁REVIEW #ASCO26 #LCSM Oral
🔥OptiTROP-Lung05: 1L Sac-TMT + Pembro vs Pembro in PD-L1+ NSCLC
✅mPFS NR vs 5.7m (HR 0.35)
✅ORR 70.2% vs 42.0%
✅OS HR 0.55 (95%CI 0.36-0.85, immature)
🎙️Dr. Caicun Zhou
🔗 https://t.co/DcbK1dGrhO @OncoAlert @Larvol @ASCO @IASLC https://t.co/512k6dZviW pic.twitter.com/Vdo86N50h9
— Hidehito HORINOUCHI (@HHorinouchi) May 30, 2026

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 — Metric CRT CT

3-yr DFS 55.6% 42.4%
Median DFS 52.7 mo 24.4 mo
HR (95% CI) 0.750 (0.607-0.928) —
p 0.008 —

Metric	CRT	CT
3-yr DFS	55.6%	42.4%
Median DFS	52.7 mo	24.4 mo
HR (95% CI)	0.750 (0.607-0.928)	—
p	0.008	—

7 details

Methods

🔍 N=620, 13 Chinese centers, 2013-2022; cT3N2+ or T4 gastric/GEJ; 36.3% EGJ primary
🔍 CRT arm: 45 Gy/25 fractions concurrent after C1 chemo, with dose-reduced oxaliplatin (100 mg/m²) and capecitabine (825 mg/m²)

CONSORT flow

Randomized 620

↓

CRT (XELOX + RT)

allocated 310

CT (XELOX)

allocated 310

Results

📊 mOS 67.5 vs 37.6 months, HR 0.781 (0.628-0.970), p=0.025
📊 Locoregional recurrence in R0-resected pts: 9.4% CRT vs 18.3% CT
📊 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

📚 Sources · 🐦 1 tweet

Neo-CRAG: Ph3 RCT (n=620, gastric/GEJ) - adding neoadj chemoRT to peri-op XELOX improved OS (68 v 38 mo).

Limitation=non-FLOT, BUT still relevant IMO b/c:

1) DFS/OS benefit substantial.
2) Improvements in pCR, downstg, LRR supports plausible RT effect on OS. #ASCO26 @OncoAlert pic.twitter.com/eeM0Z8p20M
— Dr. Nina Niu Sanford (@NiuSanford) May 30, 2026

Wait or Treat — NCT05236946 (Upfront vs Delayed Brain RT in Oncogene-mutated NSCLC) NCT05236946

ForMetastatic NSCLC, EGFR or ALK mutant, completely asymptomatic BM, ECOG 0-2

TL;DRUpfront brain RT halves icPD (HR 0.35, p<0.001) but OS numerically favors delayed (HR 1.45, 2yr 60% vs 48%) in EGFR/ALK+ mNSCLC.

vs leading data

First RCT on this question; supports emerging TKI-first approach (osimertinib/alectinib CNS penetration)

Radiation Palliative Phase 3 RCT Challenges SOC

Wait or Treat — NCT05236946 (Upfront vs Delayed Brain RT in Oncogene-mutated NSCLC) — Upfront RT (n=105) Delayed RT (n=103)

Events 20 47
1-yr cumulative icPD 8.7% (2.9%, 14.5%) 25.7% (16.8%, 34.7%)
2-yr cumulative icPD 21.7% (12.6%, 30.8%) 50% (39.2%, 60.9%)
Sub-HR (95% CI) 0.35 (0.21, 0.59) ref
p-value <0.001 —

	Upfront RT (n=105)	Delayed RT (n=103)
Events	20	47
1-yr cumulative icPD	8.7% (2.9%, 14.5%)	25.7% (16.8%, 34.7%)
2-yr cumulative icPD	21.7% (12.6%, 30.8%)	50% (39.2%, 60.9%)
Sub-HR (95% CI)	0.35 (0.21, 0.59)	ref
p-value	<0.001	—

+1 more figure

7 details

Methods

🔍 Phase III open-label RCT, N=208; EGFR/ALK+ mNSCLC, completely asymptomatic BM, ECOG 0-2
🔍 Both arms: TKIs + chemotherapy; delayed arm: RT at intracranial PD or patient request
🔍 Stratification: GPA score (0-2 vs >2); synchronous vs metachronous BM

CONSORT flow

Randomized 208

↓

Upfront Cranial RT

allocated 105

Delayed Cranial RT

allocated 103

Results

📊 OS HR 1.45 favoring delayed; 2yr OS 48% upfront vs 60% delayed (secondary endpoint)

Critique

⚠️ Radiation necrosis: 6% upfront vs 0% delayed
⚠️ OS HR p-value not reported in source; trial takeaway: 'timing of RT does not affect survival'
⚠️ TKI + chemo backbone may not reflect current osimertinib or alectinib monotherapy practice

Open questions

Does icPD reduction with upfront RT translate to QoL or neurocognitive benefit?
SRS vs WBRT in upfront arm: impact on radiation necrosis rate?
Which pts (high GPA, many lesions) benefit most from upfront cranial RT?

📚 Sources · 🐦 3 tweets

#ASCO26 | Wait or Treat? Brain RT in EGFR/ALK+ NSCLC

Presented by Dr Anil Ramakant Tibdewal.

A landmark Phase III randomized trial from @TataMemorial addressed a long-standing question: should asymptomatic brain metastases in oncogene-driven NSCLC receive upfront cranial RT or… pic.twitter.com/lRy9CfyQ8r
— OncLive.com (@OncLive) May 29, 2026

Should asymptomatic brain mets await systemic response in front line within EGFR/ALK context? I think yes. Despite reducing icPD, delayed brain RT OS looked better and radiation necrosis didn’t occur vs 6% #ASCO26 pic.twitter.com/O6d7GrvtU4
— Dr Riyaz Shah (@DrRiyazShah) May 29, 2026

No improvement in survival with up front radiation. OS favored delayed radiation with 2y OS 48% with early radiation vs 60% in late (OS HR 1.45). Also, radiation necrosis less common and less severe in delayed arm. Each case unique but delayed approach appealing #ASCO26 pic.twitter.com/wIhjqxhSaq
— Stephen V Liu, MD (@StephenVLiu) May 29, 2026

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

🔍 Phase 3 NI RCT, N=2766 enrolled, 2540 per-protocol; median f/u 46.8mo (range 1.5-94.5)
🔍 Extends Z0011 eligibility: includes mastectomy, T3 tumors, extracapsular extension, male pts
🔍 Nodal RT administered in 89.9% SNB-only group, 88.4% ALND group

Results

📊 2° EP (RFS): 5yr 89.7% (95% CI 87.5-91.9) SNB-only vs 88.7% (95% CI 86.3-91.1) ALND
📐 Country-adjusted HR 0.89 (95% CI 0.66-1.19); noninferiority p<0.001 (upper CI 1.19 below margin 1.44)

Critique

⚠️ 1° 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

📚 Sources · 📄 1 paper

📄 PAPER de Boniface, Jana; Filtenborg Tvedskov, Tove; Rydén, Lisa et al. · New England Journal of Medicine (2024-04)

Omitting Axillary Dissection in Breast Cancer with Sentinel-Node Metastases

PMID → doi

Abstract

BACKGROUND 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. METHODS 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. RESULTS 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. CONCLUSIONS 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, ≥1 recurrence risk factor

TL;DRNo OS benefit from adding atezolizumab to SBRT (HR 1.15, p=0.63); closed for futility; G≥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

🔍 Phase III RCT; N=403 eligible (201 SBRT / 202 atezo+SBRT); accrual closed at first interim for OS + PFS futility per prespecified design
🔍 T1-3N0M0 NSCLC ≤7cm, inoperable or declined surgery, ≥1 recurrence risk factor; atezo 1200mg Q3W x8 cycles; SBRT 3-8 fx BED ≥100Gy initiated cycle 3
🔍 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

📊 Efficacy outcomes: SBRT vs SBRT + atezolizumab

Endpoint HR (95% CI) p 2yr SBRT 2yr SBRT+atezo

OS (1° EP) 1.15 (0.65-2.01) 0.63 82% 80%
PFS 1.35 (0.89-2.06) 0.16 71% 60%
📊 Failure patterns at cutoff

Pattern SBRT SBRT + atezo

Local 7% 13%
Regional 2% 3%
Distant 4% 5%

Endpoint	HR (95% CI)	p	2yr SBRT	2yr SBRT+atezo
OS (1° EP)	1.15 (0.65-2.01)	0.63	82%	80%
PFS	1.35 (0.89-2.06)	0.16	71%	60%

Pattern	SBRT	SBRT + atezo
Local	7%	13%
Regional	2%	3%
Distant	4%	5%

Critique

⚠️ G≥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

📚 Sources · 📄 1 paper

📄 PAPER Simone, Charles B.; Daly, Megan Eileen; Redman, Mary Weber et al. · 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 → 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 ≥1 risk factor for increased recurrence: tumor diameter ≥2 cm, ≥6.2, moderately/poorly/undifferentiated histology. Randomization was to SoC SBRT (S [3-8 fractions, biologically effective dose ≥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 (<4 cm vs ≥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) ≥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 ≥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 .

📝 https://ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.8003

Bladder Adjuvant Radiotherapy

ForHigh-risk urothelial MIBC post-RC (pT3-4, pN+, margin+, or ≤10 nodes), periopera

TL;DR2-yr LRFS 87.1% vs 76.0% (HR 0.43, p=0.04) favoring adj pelvic IMRT post-cystectomy in high-risk MIBC; DFS/OS NS.

vs leading data

Adj RT + IO interaction unstudied; generalizability to current practice uncertain

Radiation Curative Phase 3 RCT Early signal

6 details

Methods

🔍 Phase III RCT, N=153 (RT=77, Obs=76); stratified by nodal involvement and chemo timing
🔍 Eligibility: any of pT3-4, pN1-3, margin+, or ≤10 nodes dissected; 62% pT3-T4, 41% pN+
💊 Stoma-sparing IG-IMRT 50.4Gy/28fx to cystectomy bed and pelvic nodes

CONSORT flow

Randomized 153

↓

Adjuvant RT

allocated 77

Observation

allocated 76

Results

📊 RT vs observation outcomes, median f/u 47mo

Endpoint RT Obs HR (95% CI) p

2-yr LRFS (1°) 87.1% 76.0% 0.43 (0.20-0.96) 0.04
DFS 71.6% 58.7% 0.62 (0.36-1.05) —
BCSS 79.6% 65.0% 0.59 (0.33-1.10) —
OS 70.4% 57.4% 0.78 (0.49-1.26) —

Endpoint	RT	Obs	HR (95% CI)	p
2-yr LRFS (1°)	87.1%	76.0%	0.43 (0.20-0.96)	0.04
DFS	71.6%	58.7%	0.62 (0.36-1.05)	—
BCSS	79.6%	65.0%	0.59 (0.33-1.10)	—
OS	70.4%	57.4%	0.78 (0.49-1.26)	—

Critique

⚠️ Small N (153); underpowered for OS; CI crosses 1.0 on all secondary endpoints
⚠️ None received immunotherapy; cohort predates nivolumab post-cystectomy standard (CheckMate 274)

Open questions

OS benefit with longer follow-up?
Safety and efficacy of adj RT combined with IO (nivolumab) post-RC
Optimal selection: does pN+ subgroup derive greatest locoregional benefit?

📚 Sources · 📄 1 paper

📄 PAPER Murthy; Maitre; Pal et al. · Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2026-05)

Bladder Adjuvant Radiotherapy: Phase III Multicenter Randomized Controlled Trial of Adjuvant Radiotherapy or Observation for Postcystectomy Muscle-Invasive Bladder Cancer.

PMID 42166701 → doi

Abstract

PURPOSE: To report the primary analysis of a multicenter, phase III randomized trial of adjuvant radiotherapy (RT) after chemotherapy and radical cystectomy (RC) in patients with high-risk muscle-invasive bladder cancer (MIBC). METHODS: Patients with nonmetastatic urothelial MIBC at high risk after RC (any one of: T3-4, N1-3, margin positive, ≤10 nodes dissected) were randomly assigned 1:1 to adjuvant RT or observation (Obs), stratified by nodal involvement (yes/no) and chemotherapy (neoadjuvant/adjuvant/none). Stoma-sparing IG-IMRT 50.4Gy in 28 fractions was prescribed to the cystectomy bed and pelvic nodes. The primary end point was 2-year locoregional recurrence-free survival (LRFS), and the secondary end points were disease-free survival (DFS), bladder cancer-specific survival (BCSS), and overall survival (OS). RESULTS: From June 2016 to May 2024, 153 patients were randomly assigned (Obs = 76, RT = 77), with 62% and 41% of patients having pT3-T4 and pN+ stages, respectively. Over 90% of the patients received systemic chemotherapy (71% neoadjuvant and 20% adjuvant), and none received immunotherapy. After a median follow-up of 47 months, the 2-year LRFS was significantly higher with adjuvant RT versus observation (87.1% v 76.0%, hazard ratio [HR], 0.43 [95% CI, 0.20 to 0.96], P = .04). The DFS was 71.6% versus 58.7% (HR, 0.62 [95% CI, 0.36 to 1.05]), BCSS was 79.6% versus 65.0% (HR, 0.59 [95% CI, 0.33 to 1.10]), and OS was 70.4% versus 57.4% (HR, 0.78 [95% CI, 0.49 to 1.26]) for RT and Obs, respectively. CONCLUSION: Adjuvant pelvic IMRT after radical cystectomy and perioperative chemotherapy suggests an improvement in locoregional control in patients with high risk urothelial MIBC with no additional severe toxicity.

EORTC 22922/10925

ForStage I-III breast, node-positive or central/medial tumor, median age 54, post-s

TL;DR20yr OS HR 1.00 (null): BC mortality reduced HR 0.82 but non-BC deaths increased HR 1.26, offsetting benefit.

vs leading data

vs EORTC 22922 10yr data (NEJM 2015): DFS and BC mortality benefit seen at 10yr did not translate to OS by 20yr; competing-cause mortality dominant

Radiation Curative Phase 3 RCT Challenges SOC

6 details

Methods

🔍 Phase 3 RCT, N=4004 randomized 1996-2004, median f/u 22.2yr; prespecified 20yr final analysis
🔍 Eligible: women ≤75yr, stage I-III, node-positive OR central/medial tumor; post-mastectomy or BCS + ALND

Results

📊 Outcomes at 20 years (IM-MS-RT vs control)

Endpoint	Control	IM-MS-RT	HR	p
OS (20yr rate)	61.8%	61.0%	1.00	.967
DFS (20yr rate)	49.0%	48.2%	0.97	.515
DMFS (20yr rate)	59.8%	58.9%	0.97	.578
BC mortality (20yr rate)	22.4%	18.6%	0.82	.006
Non-BC deaths (20yr rate)	15.8%	20.4%	1.26	.002

Critique

⚠️ Non-BC death excess emerged after 15yr, driven by cardiac and pulmonary morbidity from IM-MS-RT
⚠️ Late RT morbidity (IM-MS-RT vs control)
- Lung fibrosis: 6.3% vs 3.2%
- Cardiac fibrosis: 2.7% vs 1.7%
- Cardiac diseases: 15.2% vs 11.7%
- Severe cardiac G3-4: 1.9% vs 1.7%
- Severe lung G3-4: 0.3% vs 0.0%
⚠️ 2D RT planning era (enrolled 1996-2004); modern cardiac-sparing techniques may attenuate the non-BC mortality signal

Open questions

Does modern cardiac-sparing IM-RT eliminate the non-BC death excess?
Which subgroups (high nodal burden, HER2+, TNBC) derive net OS benefit?
Impact of contemporary systemic therapy on IM-MS-RT benefit/harm ratio

📚 Sources · 📄 1 paper

📄 PAPER Kaidar‐Person, Orit; Weltens, Caroline G.; Fortpied, Catherine et al. · CA: A Cancer Journal for Clinicians (2026-05)

Twenty‐year results of the randomized European Organization for Research and Treatment of Cancer trial 22922/10925 evaluating internal mammary chain and medial supraclavicular lymph node irradiation in stage I–III breast cancer

PMID → doi

Abstract

Abstract European Organization for Research and Treatment of Cancer trial EORTC 22922/10925 evaluated internal mammary and medial supraclavicular (IM‐MS) lymph node irradiation (IM‐MS‐RT) in patients with stage I–III breast cancer. Eligible patients had involved axillary nodes and/or centrally/medially located tumors regardless of nodal involvement. The primary end point was overall survival, secondary end points were disease‐free survival, distant metastases‐free survival, breast cancer mortality, and any breast recurrence. Between 1996 and 2004, 4004 patients were randomized. The median patient age was 54 years. At a median follow‐up of 22.2 years, 1550 (38.7%) patients died, of whom 796 (51.4%) died from breast cancer. At 20 years, the overall survival rate was 61.8% in the control group versus 61.0% in the IM‐MS‐RT group (hazard ratio [HR], 1.00; p = .967); the disease‐free survival rate was 49.0% versus 48.2%, respectively (HR, 0.97; p = .515); and the distant metastases‐free survival rate was 59.8% versus 58.9%, respectively (HR, 0.97; p = .578). The breast cancer mortality rate was 22.4% in the control group and 18.6% in the IM‐MS‐RT group (HR, 0.82; p = .006), whereas the rate of deaths not from breast cancer or from unknown causes was 15.8% versus 20.4%, respectively (HR, 1.26; p = .002). Lung fibrosis, cardiac fibrosis, and cardiac diseases were more frequent after IM‐MS‐RT versus no IM‐MS‐RT (6.3% vs. 3.2%, 2.7% vs. 1.7%. and 15.2% vs. 11.7%, respectively); and the rates of severe cardiac and lung morbidities (scores of 3 or 4) were 1.9% versus 1.7% and 0.3% versus 0.0%, respectively. Breast cancer mortality at 20 years was statistically significantly lower after IM‐MS‐RT, but deaths not from breast cancer increased after 15 years, resulting in no long‐term benefit of IM‐MS‐RT on overall survival. Therefore, the authors strongly call for very long‐term follow‐up of treatments for prognostically favorable cancers such as breast cancer.

LS-SCLC 54 Gy Hyperfractionated RT NCT03214003

ForLS-SCLC, ECOG 0–1, age 18–70, chemo-naive or ≤1 prior platinum-etoposide cycle

TL;DRmOS 60.7 vs 39.5mo (HR 0.55, p=0.003) favoring 54 Gy hyperfractionated RT in LS-SCLC; no added toxicity.

vs leading data

vs CONVERT trial (Lancet Oncol 2017): CONVERT also BID 45 Gy SIB to 66 Gy failed to show OS benefit over 45 Gy — this trial's positive result contrasts CONVERT's null, likely due to SIB technique differences and PTV homogeneity approach

Radiation Curative Phase 3 RCT Challenges SOC

9 details

Methods

🔍 Phase 3 open-label RCT; N=224; 16 centers in China; 1:1 randomization; median f/u 46mo
🔍 54 Gy SIB to GTV in 30 BID fractions vs 45 Gy in 30 BID fractions; both arms VMAT; PTV 45 Gy both arms
🔍 Chemo-naive or ≤1 prior cisplatin/carboplatin+etoposide cycle; ECOG 0–1; age 18–70
💊 Concurrent chemotherapy + PCI (25 Gy/10 fx) for responders in both arms

CONSORT flow

Assessed / enrolled 224

↓

Randomized 224

↓

54 Gy SIB

allocated 108

analyzed 108

45 Gy

allocated 116

analyzed 116

Results

📊 1° EP (OS): mOS 60.7mo (95% CI 49.2–62.0) vs 39.5mo (27.5–51.4), HR 0.55 (0.37–0.72), p=0.003

Critique

⚠️ G3–4 RT toxicity by type
- Oesophagitis: 13% (54 Gy) vs 12% (45 Gy), p=0.84
- Pneumonitis: 5% (54 Gy) vs 6% (45 Gy), p=0.663
- 1 treatment-related death in 54 Gy arm (MI)
⚠️ Trial stopped early by DSMB (April 2021) on clinical benefit grounds; early termination inflates effect estimates
⚠️ Single-country (China), age-capped at 70, open-label; generalizability to Western populations uncertain
⚠️ 45 Gy BID (not OD) control — aligns with historical standard but not universally practiced globally

Open questions

Confirmatory data needed in non-Asian populations
Optimal dose escalation with modern immunotherapy combinations
Late cardiac/pulmonary toxicity beyond 46mo median f/u

📚 Sources · 📄 1 paper

📄 PAPER Jiayi Yu; Leilei Jiang; Lina Zhao et al. · Lancet Respiratory Medicine (2024-08)

High-dose hyperfractionated simultaneous integrated boost radiotherapy versus standard-dose radiotherapy for limited-stage small-cell lung cancer in China: a multicentre, open-label, randomised, phase 3 trial

PMID → doi

Abstract

Background For the past 20 years, twice-daily thoracic radiotherapy with concurrent chemotherapy has been the treatment of choice for limited-stage small-cell lung cancer (LS-SCLC), which has a poor prognosis. We aimed to assess the efficacy and safety of high-dose, accelerated, hyperfractionated, twice-daily thoracic radiotherapy (54 Gy in 30 fractions) versus standard-dose radiotherapy (45 Gy in 30 fractions) as a first-line treatment for LS-SCLC. Methods This open-label, randomised, phase 3 trial was performed at 16 public hospitals in China. The key inclusion criteria were patients aged 18–70 years, with histologically or cytologically confirmed LS-SCLC, who had an Eastern Cooperative Oncology Group (ECOG) performance status of 0–1, and who were previously untreated or had received one course of cisplatin or carboplatin and etoposide. Eligible patients were randomly assigned (1:1) to receive volumetric-modulated arc radiotherapy (VMAT) of 45 Gy in 30 fractions to the gross tumour volume or VMAT with a simultaneous integrated boost of 54 Gy in 30 fractions to the gross tumour volume starting 0–42 days after the first chemotherapy course. Both groups received 10 fractions of twice-daily thoracic radiotherapy per week. The planning target volume was 45 Gy in 30 fractions in both groups. Patients with responsive disease received prophylactic cranial radiotherapy (25 Gy in 10 fractions). Randomisation was performed using a centralised interactive web response system, stratified by ECOG performance status, disease stage, previous chemotherapy course, and chemotherapy choice. The primary outcome was overall survival in the intention-to-treat population. Safety was analysed in the as-treated population. This study was registered at ClinicalTrials.gov, NCT03214003. Findings From June 30, 2017, to April 6, 2021, 224 patients (102 [46%] females and 122 [54%] males; median age 64 years [IQR 58–68]) were enrolled and randomly assigned to the 54 Gy group (n=108) or 45 Gy (n=116) group. The median follow-up was 46 months (IQR 33–56). The median overall survival was significantly longer in the 54 Gy group (60·7 months [95% CI 49·2–62·0]) than in the 45 Gy group (39·5 months [27·5–51·4]; hazard ratio 0·55 [95% CI 0·37–0·72]; p=0·003). Treatment was tolerable, and the chemotherapy-related and radiotherapy-related toxicities were similar between the groups. The grade 3–4 radiotherapy toxicities were oesophagitis (14 [13%] of 108 patients in the 54 Gy group vs 14 [12%] of 116 patients in the 45 Gy group; p=0·84) and pneumonitis (five [5%] of 108 patients vs seven [6%] of 116 patients; p=0·663). Only one treatment-related death occurred in the 54 Gy group (myocardial infarction). The study was prematurely terminated by an independent data safety monitoring board on April 30, 2021, based on evidence of sufficient clinical benefit. Interpretation Compared with standard-dose thoracic radiotherapy (45 Gy), high-dose radiotherapy (54 Gy) improved overall survival without increasing toxicity in a cohort of patients aged 18–70 years with LS-SCLC. Our results support the use of twice-daily accelerated thoracic radiotherapy (54 Gy) with concurrent chemotherapy as an alternative first-line LS-SCLC treatment option.

PEACE 2

ForVHR localized prostate (≥2: Gleason ≥8, T3-T4, PSA ≥20), N0M0 on conventional im

TL;DRPelvic RT did not improve cPFS vs prostate-only RT in VHR localized prostate cancer (HR 0.81, p=0.088).

vs leading data

Contrasts with POP-RT, which showed bPFS and MFS benefit from pelvic RT in high-risk CaP; population definitions and staging modalities differ

Radiation Curative Phase 3 RCT Challenges SOC

PEACE 2 — Prostate-only RT Pelvic RT

7-yr cPFS 62.9% [57.4; 68.1] 67.1% [61.6; 72.2]
HR (95% CI) ref 0.81 [0.63; 1.03]
p 0.088

	Prostate-only RT	Pelvic RT
7-yr cPFS	62.9% [57.4; 68.1]	67.1% [61.6; 72.2]
HR (95% CI)	ref	0.81 [0.63; 1.03]
p		0.088

+1 more figure

8 details

Methods

🔍 Phase III, 4-arm: ADT × 3 yrs + prostate RT ± cabazitaxel × 4 cycles; pelvic vs prostate-only RT comparison
🔍 VHR eligibility: ≥2 of Gleason ≥8, T3-T4, PSA ≥20 ng/mL; N0M0 on conventional imaging or choline PET/CT
💊 Side effects minimal with modern RT techniques; no quantitative toxicity figures reported in source

CONSORT flow

Randomized 761

↓

Prostate-only RT (A+C pooled)

allocated 380

Pelvic RT (B+D pooled)

allocated 381

Results

📊 1° EP cPFS: HR 0.81 (95% CI 0.63-1.03), p=0.088 — non-significant
📊 7-yr cPFS: 67.1% pelvic RT vs 62.9% prostate-only RT
📊 No improvement on secondary endpoints: MFS, PCSS, OS (effect sizes not reported in source)

Critique

⚠️ Staged with conventional imaging/choline PET, not PSMA-PET; PSMA-era cohort may carry different nodal risk profile
⚠️ Presenter conclusion: pelvic RT cannot be considered SOC even in pts at high nodal extension risk without detectable disease on imaging

Open questions

Does PSMA-PET staging identify a nodal subgroup that benefits from pelvic RT?
How to reconcile with POP-RT (different risk definitions, staging modalities)?
Does cabazitaxel interaction modify pelvic RT benefit in the 4-arm design?

📚 Sources · 🐦 1 tweet

Yesterday, I presented the @GETUG_Unicancer PEACE 2 trial at #ESTRO26 on the role of pelvic RT in very high risk #prostatecancer pts (staged with conventional imaging).

Twittorial below

Key conclusion: pelvic RT did not improve clinical outcomes (cPFS, MFS, PCSS, OS)...

1/n pic.twitter.com/ZKRt2QZzt1
— Pierre Blanchard, MD (@PBlanchardMD) May 18, 2026

HEAT Trial NCT01794403

ForLow-intermediate risk localized PCa, IPSS <12, ADT-eligible

TL;DRSBRT 5 fx non-inferior to EHRT for BF (7% vs 7.4%, p-noninferiority=0.007 at 4.25y) in low-int risk PCa; interim data.

vs leading data

Prior AHRT RCTs (HYPO-RT-PC, PACE-B, NRG-GU005) excluded ADT or used heterogeneous controls; HEAT is first head-to-head with modern IMRT + ADT permitted in both arms

Radiation Curative Phase 3 RCT Early signal

HEAT Trial — Endpoint AHRT EHRT p-noninferiority

Biochemical failure (Phoenix) at 4.25y 7% 7.4% 0.007

Endpoint	AHRT	EHRT	p-noninferiority
Biochemical failure (Phoenix) at 4.25y	7%	7.4%	0.007

+1 more figure

Trial schema: AHRT 36.25 Gy/5 fx (GTV SIB 40 Gy) vs EHRT 70.2 Gy/26 fx IMRT. Accrual goal n=456; n=420 evaluable.

9 details

Methods

🔍 AHRT: 36.25 Gy in 5 fx (7.25 Gy/fx, GTV SIB to 40 Gy); EHRT: 70.2 Gy in 26 fx using IMRT
🔍 Low-intermediate risk PCa; IPSS <12; ADT permitted (≤6 months) in both arms; 28% received ADT
🔍 Median FU 59.7 months; 82.4% intermediate-risk; n=156 randomized, n=142 analyzed (interim)

Results

📊 1° EP (biochemical failure, Phoenix def): 7% AHRT vs 7.4% EHRT at 4.25y, p-noninferiority = 0.007
📊 Acute G2+ GI toxicity lower with AHRT; no absolute rates reported in source
📊 Late G2+ GI and acute/late G2+ GU toxicities comparable between arms

Critique

⚠️ Interim analysis only; accrual goal n=456 (420 evaluable planned); non-inferiority not yet confirmed at final analysis
⚠️ Non-inferiority margin 12% is wide relative to observed BF rates of 7-7.4%
⚠️ Clinician-reported toxicity; laxative/psyllium use scored as G2 GI event

Open questions

Non-inferiority confirmed at final analysis (n=456 accrual goal)?
Late toxicity differences beyond 5yr follow-up?
Does short-course ADT differentially affect BCF rates by fractionation arm?

📚 Sources · 🐦 2 tweets

Day FOUR of #ESTRO26 Coverage by OncoAlert 🚨
Results of a Randomized Non-Inferiority Trial of Hypofractionation via Extended versus Accelerated Therapy (HEAT) for Prostate Cancer Presented by Matthew C. Abramowitz🇺🇸 #RadOnc ☢️ #ProstateCancer

HEAT is an international phase… pic.twitter.com/IkSTgQHwXK
— OncoAlert (@OncoAlert) May 18, 2026

The HEAT trial is another randomized demonstration of the safety & efficacy of SBRT compared to hypofractionted RT in #prostatecancer at #ESTRO26 pic.twitter.com/c9sNb3KOqo
— Pierre Blanchard, MD (@PBlanchardMD) May 18, 2026

TORPEdO (CRUK/18/010)

ForOropharyngeal SCC requiring definitive concurrent CRT with bilateral neck treatm

TL;DRIMPT showed no HR-QoL benefit vs IMRT at 12 months in OPSCC; UW-QoL scores similar across arms to 24 months.

vs leading data

Lancet 2026 (McBride et al.): concurrent proton vs photon analysis in OPSCC

Radiation Curative Phase 3 RCT Challenges SOC

+1 more figure

Phase 3 RCT schema: IMPT vs IMRT 2:1; 205 pts; 70/56 Gy in 33 fractions; cisplatin 100mg/m² D1+D22

7 details

Methods

🔍 Phase 3 RCT; N=205; 2:1 IMPT vs IMRT; cisplatin 100mg/m² D1+D22; 70/56 Gy in 33 fractions over 6.5 weeks
🔍 HR-QoL declines at end of treatment then recovers; most pts stabilize by 12 months post-CRT

Results

📊 Patient-reported co-primary: UW-QoL physical composite (saliva, taste, chewing, swallowing, appearance, speech) at 12 months post-CRT
📊 No differences in UW-QoL scores between arms at 3, 12, or 24 months post-RT
📊 Clinician-reported co-primary (CTCAE G3 weight loss or gastrostomy dependence at 12 months): not reported in this presentation

Critique

⚠️ Meaningful HR-QoL deterioration persists in some pts up to 2 years in both arms
⚠️ Commentary: identical planning constraints and novice UK proton centers likely attenuated any IMPT advantage; high-experience centers may still see clinical benefit

Open questions

Does proton center experience modify HR-QoL or late-toxicity outcomes?
Will clinician-reported co-primary (G3 weight loss/gastrostomy) diverge from HR-QoL?
Late-effect differentiation at 5-year follow-up

📚 Sources · 🐦 2 tweets · 📄 1 paper

Day FOUR of #ESTRO26 Coverage by OncoAlert 🚨
Health-related quality of life in the phase III trial of Toxicity Reduction using Proton Beam Therapy for Oropharyngeal Cancer (TORPEdO;CRUK/18/010) Presented by Matthew Tyler🇬🇧 #RadOnc ☢️

TORPEdO, a multicentre phase 3… pic.twitter.com/ZP6yK7RThL
— OncoAlert (@OncoAlert) May 18, 2026

TORPEdO. Misma planificación + constraints idénticas y centros UK noveles probablemente limitaron el potencial de #IMPT.
Centros con alta experiencia se siguen viendo ventajas clínicas . La QA rigurosa del UK es una fortaleza, pero no maximiza la diferencia.#ESTRO26 #HNCSM https://t.co/rASp3QDIk1
— Amadeo Wals (@AmadeoWals) May 18, 2026

📄 PAPER McBride; Riaz; Sherman et al. · Lancet (London, England) (2026-05)

Proton versus photon therapy for oropharyngeal cancer.

PMID 42134353 → doi

📝 McBride SM, Riaz N, Sherman EJ, Tsai CJ, Mell LK. Proton versus photon therapy for oropharyngeal cancer. Lancet. 2026 May 16;407(10542):1917.

NRG/RTOG 1005 NCT01349322

ForPost-lumpectomy high-risk early breast: grade 3, ER-neg, LVI, or close margins

TL;DR7-yr IBR 2.6% vs 2.2%, HR 1.31 (90% CI 0.84-2.04); concurrent boost noninferior, reducing treatment to 15 fractions.

vs leading data

vs EORTC 22881-10882 (Bartelink): addresses delivery timing, not boost vs no boost; landmark context only

Radiation Curative Phase 3 RCT Practice-changing

9 details

Methods

🔍 Phase III unblinded RCT, N=2,255 analyzed; 278 sites, North America + 6 countries; median f/u 7.3 yr
🔍 High-risk post-lumpectomy: grade 3 (52.7%), ER-neg (29.6%), LVI (16.7%), close margins (16.7%), chemo (61.8%)
💊 Concurrent arm: WBI 40 Gy/15F + simultaneous boost 0.53 Gy/fx (15 total fractions)
💊 Sequential arm: WBI 50 Gy/25F or 42.7 Gy/16F + boost 12-14 Gy/6-7F after (22-32 total fractions)

Results

📊 1° EP (IBR noninferiority): HR 1.31 (90% CI 0.84-2.04), p=0.037; upper bound 2.04 < NI margin 2.12
📊 7-yr IBR: 2.6% concurrent vs 2.2% sequential; 5-yr: 1.9% vs 2.1%; 56 total events
📊 No significant differences in DFS, DDFS, OS, or RNR between arms; 7-yr RNR 1.2% overall
📊 Cosmesis at 3yr: NI met by both measures
- Physician-rated excellent/good: 82.4% concurrent vs 85.9% sequential, p=0.34
- Central digital photo review excellent/good: 72.0% vs 64.2%, p=0.11
- BCTOS mean change from baseline: 0.18 concurrent vs 0.16 sequential (NI met)

Critique

⚠️ G3-4 AEs similar between arms (p=0.81); radiation dermatitis, fatigue, breast pain most prevalent

Open questions

Long-term cosmesis and fibrosis beyond 3-yr QoL endpoint
Applicability to pts on hormonal therapy without chemo (lower baseline risk)
Integration with APBI or partial-breast techniques

📚 Sources · 📄 1 paper

📄 PAPER Vicini; Winter; Freedman et al. · Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2026-05)

Concurrent Versus Sequential Radiation Dose Escalation to the Surgical Cavity for Conservative Treatment of High-Risk Early Breast Cancer: NRG/RTOG 1005 Phase III Trial.

PMID 42114027 → doi full text (PMC)

Abstract

PURPOSE: For patients with breast cancer undergoing breast conservation, escalating the dose (boost) of radiation to the lumpectomy cavity after whole-breast irradiation (WBI) reduces ipsilateral breast recurrence (IBR) but extends treatment duration. This phase III trial investigated whether boost delivery during WBI versus after WBI provides noninferior IBR and preserves cosmetic appearance. METHODS: NRG/RTOG 1005 randomly assigned patients at higher risk for IBR after lumpectomy and axillary surgery to either a sequential boost of 12 Gy in six fractions(F) or 14 Gy in 7F after WBI of 50 Gy in 25F or 42.7 Gy in 16F (sequential arm) or a concurrent boost of 8 Gy in 15F of 0.53 Gy per day with WBI of 40 Gy in 15F (concurrent arm) using 3-dimensional conformal radiation therapy (RT) or intensity-modulated RT. Based on 1.59% 5-year IBR for the sequential arm, defining the noninferiority margin as a hazard ratio upper limit on the 90% CI of 2.12, 2,312 patients provide 80% power for noninferiority of IBR as first recurrence for the concurrent arm. Secondary end points included disease-free survival and overall survival, adverse events (AEs), and cosmetic outcomes. RESULTS: Between May 24, 2011, and June 20, 2014, 2,354 patients were randomly assigned, with 2,255 eligible for analysis (sequential arm, n = 1,118; concurrent arm, n = 1,137). With median follow-up of 7.3 years, there were 56 IBR events; 5- and 7-year IBR were 2.1% and 2.2% on the sequential arm and 1.9% and 2.6% on the concurrent arm, respectively. The noninferiority criterion was met: HR (90% CI): 1.31 (0.84 to 2.04), P = .037. No differences were observed in AEs, cosmetic outcomes, or survival between arms. CONCLUSION: Concurrent boost during WBI results in noninferior IBR compared with sequential boost without worsening toxicity or cosmetic outcomes and reduces overall treatment time.

📝 Vicini FA, Winter K, Freedman GM, Arthur DW, Rosenstein BS, Bentzen SM, Li XA, Halyard MY, Woodward WA, Bleicher RJ, Taghian A, Lyons J, Tomberlin JK, Seaward SA, Cheston SB, Hoover AC, Anderson BM, Perera FE, Poppe MM, Petersen IA, Jhawar S, Hijal T, Moughan J, Movsas B, White JR. Concurrent Versus Sequential Radiation Dose Escalation to the Surgical Cavity for Conservative Treatment of High-Risk Early Breast Cancer: NRG/RTOG 1005 Phase III Trial. J Clin Oncol. 2026 May 11:JCO2502465. ; PMCID: PMC13166090.

APBI-IMRT Florence NCT02104895

ForEarly BC post-BCS, pT <25mm, FSM ≥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 — Endpoint APBI (15-yr) WBI (15-yr) p

IBTR 20 (7.7%) 11 (4.2%) 0.14
IBTR HR 1.57 (0.82-3.04) — 0.17
Local relapse 5 (2.1%) 4 (1.6%) 0.75
New ipsilateral primary 15 (5.9%) 7 (2.7%) 0.09

Endpoint	APBI (15-yr)	WBI (15-yr)	p
IBTR	20 (7.7%)	11 (4.2%)	0.14
IBTR HR	1.57 (0.82-3.04)	—	0.17
Local relapse	5 (2.1%)	4 (1.6%)	0.75
New ipsilateral primary	15 (5.9%)	7 (2.7%)	0.09

+2 more figures

7 details

Methods

🔍 Phase III equivalence trial, N=520, 1:1 randomization, enrolled 2005-2013
🔍 APBI: IMRT 30Gy/5 fractions; WBI: 50Gy/25# + 10Gy tumor bed boost
🔍 Eligible: BCS, pT <25mm, FSM ≥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

📊 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 Δ5%; 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

📚 Sources · 🐦 1 tweet

📌 Fifteen-year outcomes of the randomised APBI-IMRT Florence phase Ill trial of partial versus whole-breast irradiation in early breast cancer ✨
Excellent presentation led by @CarlottaB 👏🏻#ESTRO26 @Icro_Meattini @ESTRO_RT @OncoAlert #OncoAlertAF pic.twitter.com/1j4bIA2nyC
— Elisabetta Bonzano MD, PhD (@to_be_elizabeth) May 17, 2026

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 — Endpoint 50 Gy/25fr 40 Gy/15fr HR (95% CI) p

10-yr G2-3 induration 24.7% 19.5% 0.76 (0.62-0.92) 0.005
10-yr OS 92.1% 93.0% 0.81 (0.63-1.04) 0.10

Endpoint	50 Gy/25fr	40 Gy/15fr	HR (95% CI)	p
10-yr G2-3 induration	24.7%	19.5%	0.76 (0.62-0.92)	0.005
10-yr OS	92.1%	93.0%	0.81 (0.63-1.04)	0.10

+1 more figure

4 details

Methods

🔍 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

📊 No significant differences in locoregional recurrence, distant failure, or breast cancer mortality at 10 yrs

Critique

⚠️ Original 1° EP was 3-yr grade ≥2 induration; 10-yr toxicity, recurrence, and survival analyses were prespecified
⚠️ Trial not powered for 10-yr OS as 1° 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)

📚 Sources · 🐦 1 tweet

Day TWO of #ESTRO26 Coverage by OncoAlert 🚨
10-year Follow-Up of the DBCG HYPO Trial: Breast Induration, Recurrence and Survival After Hypofractionated Whole Breast Irradiation Presented by Hanna Forsberg 🇩🇰 @BOffersen #RadOnc ☢️ #BreastCancer

The DBCG HYPO trial reports… pic.twitter.com/4qf9R3HZwT
— OncoAlert (@OncoAlert) May 17, 2026

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 — Arm 10-yr IBTR (95% CI)

40Gy/15F + 16Gy/8F 3.5% (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)

Arm	10-yr IBTR (95% CI)
40Gy/15F + 16Gy/8F	3.5% (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

Arm	5-yr IBTR (95% CI)
40Gy/15F + 16Gy/8F	1.9% (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

🔍 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
🔍 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

📊 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

📚 Sources · 🐦 1 tweet

Day THREE of #ESTRO26 Coverage by OncoAlert 🚨
Ten-year results of the IMPORT HIGH trial (ISRCTN47437448): Dose escalated simultaneous integrated boost radiotherapy in early breast cancer Presented by Charlotte Coles 🇬🇧 #RadOnc ☢️

Ten-year IMPORT HIGH trial data show that a… pic.twitter.com/7RqVy2SrQm
— OncoAlert (@OncoAlert) May 17, 2026

EORTC IM-MS (22922/10925)

ForStage I-III BC, node-positive or pN0, adjuvant IM-MS RT decision

TL;DR20-yr OS null (HR 1.00, p=0.967); BCM benefit offset by non-BCM excess; pN0: no benefit.

vs leading data

DBCG IMN2 (Lancet Reg Health Eur 2024): modern IM-MS RT (MHD 1.2 Gy right / 2.3 Gy left) showed BCM + DM + OS benefit at 15yr in node-positive pts

Radiation Curative Phase 3 RCT Challenges SOC

EORTC IM-MS (22922/10925) — Arm 20-yr OS HR (95% CI) p

+IM-MS RT 61.0% 1.00 (0.90-1.10) 0.967
-IM-MS RT 61.8% — —

Arm	20-yr OS	HR (95% CI)	p
+IM-MS RT	61.0%	1.00 (0.90-1.10)	0.967
-IM-MS RT	61.8%	—	—

+3 more figures

Endpoint (15yr)	+IM-MS	-IM-MS	HR (95% CI)	p
BCM	18.6%	22.4%	0.82 (0.72-0.95)	0.006
non-BCM	20.4%	15.8%	1.26 (1.09-1.46)	0.002

Late AE (absolute rate)	+IM-MS	-IM-MS
Lung fibrosis	6.3%	3.2%
Cardiac fibrosis	2.7%	1.7%
Cardiac diseases	15.2%	11.7%

Endpoint (20yr, pN0)	+IM-MS	-IM-MS	HR (95% CI)	p
DFS	53.9%	53.6%	0.93 (0.81-1.07)	0.318
DMFS	67.2%	67.4%	0.93 (0.78-1.10)	0.397

4 details

Methods

🔍 Phase III RCT, N=4004, stage I-III BC; IM + medial supraclavicular RT vs no IM-MS RT; 20-yr follow-up

CONSORT flow

Randomized 4004

↓

+IM-MS RT

allocated 2002

-IM-MS RT

allocated 2002

Results

📊 BCM reduction (HR 0.82, p=0.006 at 15yr) fully offset by non-BCM excess (HR 1.26, p=0.002); net OS nullified at 20yr

Critique

⚠️ pN0 subgroup: no DFS or DMFS benefit at 20yr; IM-MS benefit restricted to node-positive disease
⚠️ EORTC era heart doses 4-9x higher than DBCG IMN2; late cardiac mortality likely drives the non-BCM excess at 20yr

Open questions

Whether modern low-dose cardiac RT (DBCG IMN2) restores net OS benefit at 20yr
Which node-positive subgroup (pN1 vs pN2-3) retains net BCM benefit over late cardiotox
Should pN0 be excluded from IM-MS RT indications given consistently null data

📚 Sources · 🐦 2 tweets

📌 Internal Mammary and Medial Supraclavicular irradiation in stage I-III breast cancer: 20 years results of the randomised EORTC trial 22922/10925, including in pNo patients
Special Joint Presentation Led by Prof. Philip Poortmans and Orit Kaidar-Person ✨ at #ESTRO26 @ESTRO_RT… pic.twitter.com/KIoJtdhEzp
— Elisabetta Bonzano MD, PhD (@to_be_elizabeth) May 17, 2026

20-year outcomes of @EORTC internal mammary #radiotherapy trial.
➡️internal mammary improved control
➡️ survival counterbalanced by late adverse events #radiotherapy #bcsm
Great to see the long term data at #ESTRO26, and discussing Charlotte Cole suggests with modern RT, long… pic.twitter.com/yPtlfrLcri
— Shankar Siva (@_ShankarSiva) May 17, 2026

DBCG RT Natural

For≥60y, pT1N0, ER+ ≥10%, HER2-normal, grade 1-2, unifocal post-lumpectomy

TL;DR9.8% 4-yr LR without PBI vs 1.5% with PBI in pT1N0 low-risk elderly breast conservation; stopped early per pre-specified threshold.

vs leading data

PRIME II (Lancet Oncol 2015): ~10% 10-yr LR without RT in ≥65y low-risk ER+; RT benefit durable

Radiation Curative Phase 3 RCT Challenges SOC

DBCG RT Natural — Arm Events/Total CIF % (95% CI)

+RT 2/236 1.5 (0.3-5.1%)
-RT 19/272 9.8 (5.9-14.9%)
S-RT 18/278 8.2 (4.5-13.3%)

Arm	Events/Total	CIF % (95% CI)
+RT	2/236	1.5 (0.3-5.1%)
-RT	19/272	9.8 (5.9-14.9%)
S-RT	18/278	8.2 (4.5-13.3%)

+1 more figure

4 details

Methods

🔍 Phase III RCT; ≥60y, pT1N0, ER+ ≥10%, HER2-normal, grade 1-2, unifocal, non-lobular, margin ≥2mm, breast conservation
🔍 RT arm: PBI 40Gy/15fr; ET per DBCG guideline (recommended pT1c and/or grade 2); stratified by institution + ET yes/no

CONSORT flow

Randomized 508

↓

PBI 40Gy/15fr

allocated 236

No PBI

allocated 272

Critique

⚠️ Median FU 4 yrs; primary endpoint is 5-yr invasive LR; stopped early per pre-specified 4% max-LR threshold
⚠️ Suboptimal ET adherence per presenter; -ET groups drive high LR in the -RT arm; adherence confounds the no-treatment effect

Open questions

Whether WBRT (vs PBI) changes the RT-omission picture in this population
Which molecular low-risk subset, if any, can safely defer all adjuvant therapy
Duration of ET benefit when combined with PBI in ≥60y low-risk pts

📚 Sources · 🐦 2 tweets

Another trial showing even for lR optimal local control with RT and ET and suboptimal adherence to ET. In era of 5 fraction decision making is easier # Estro2026 pic.twitter.com/nkvYl3iuTn
— Sushil (@Sushilberiwal) May 17, 2026

Danish #breastcancer partial breast #radiotherapy “natural” trial.
➡️ No postoperative treatment had highest risk of recurrence
➡️either tamoxifen or #radonc reduced recurrence
➡️combined tamoxifen + RT had no recurrences
In context of EUROPA trial, RT has best QoL vs endocrine… pic.twitter.com/bDVmbDKRNb
— Shankar Siva (@_ShankarSiva) May 17, 2026

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 type n %

Isolated distant recurrence 61 51%
Second malignancy 37 31%
LRR (iLRR + cLRR) 20 16%

Event type	n	%
Isolated distant recurrence	61	51%
Second malignancy	37	31%
LRR (iLRR + cLRR)	20	16%

+1 more figure

6 details

Methods

🔍 Pre-planned secondary analysis of HypoG-01 phase III RCT (ITT); N=1260, median f/u 4.8 years
🔍 40 Gy/15fx vs 50 Gy/25fx + tumor-bed boost; endpoint: first oncological event (LRR, DR, or second malignancy)

Results

📊 118 first oncological events total; LRR lowest-frequency event (20/118, 16%)
📊 First events by type (N=118)
- Isolated distant recurrence: 61 (51%)
- Second malignancy: 37 (31%)
- LRR (isolated + concomitant): 20 (16%)
📊 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)

📚 Sources · 🐦 1 tweet

Day TWO of #ESTRO26 Coverage by OncoAlert 🚨
Patterns of locoregional and distant recurrence and dosimetric analysis in the HypoG-01 phase III trial Presented by Louis Munschi 🇫🇷 #RadOnc ☢️

In the HypoG-01 phase III trial (1260 patients, median follow-up 4.8 years), 118… pic.twitter.com/ogARInu0fB
— OncoAlert (@OncoAlert) May 16, 2026

PRIME NCT03561961

ForHigh-risk, very high-risk, or node-positive non-metastatic prostate cancer

TL;DRSBRT 5fx with pelvic RT: G3+ toxicity <1%, comparable early BFFS to moderate hypo (N~434); mature 4-5yr endpoint pending.

vs leading data

vs HYPO-RT-PC (10-yr mature, HR 0.84, CI 0.69-1.03): non-inferior but node-negative, no ADT, no pelvic RT

Radiation Curative Phase 3 RCT Early signal

PRIME — Toxicity SBRT 5fx Moderate Hypo 25fx

Acute GU G2+ ~5.4% ~4.0%
Acute GI G2+ ~2.2% ~3.7%
Acute G3+ GU/GI <1% <1%
Late GU G2+ (1-2yr) ~10-12% ~9-11%
Late GI G2+ (1-2yr) ~5-7% ~4-6%
Late G3+ GU/GI <1% <1%

Toxicity	SBRT 5fx	Moderate Hypo 25fx
Acute GU G2+	~5.4%	~4.0%
Acute GI G2+	~2.2%	~3.7%
Acute G3+ GU/GI	<1%	<1%
Late GU G2+ (1-2yr)	~10-12%	~9-11%
Late GI G2+ (1-2yr)	~5-7%	~4-6%
Late G3+ GU/GI	<1%	<1%

+1 more figure

HYPO-RT-PC 10-yr FFS: 72% (42.7 Gy/7fx) vs 65% (78 Gy/39fx), adjusted HR 0.84 (95% CI 0.69-1.03), non-inferiority confirmed. PRIME BFFS not yet mature.

7 details

Methods

🔍 Phase III open-label non-inferiority, N ~434; Tata Memorial + collaborating centers, India
🔍 High-risk, very high-risk, and/or node-positive non-metastatic prostate cancer; ECOG 0-2; PSMA PET/CT staging allowed
🔍 Both arms: prostate + whole-pelvis RT + long-course ADT (~2yr); SIB to positive nodes in SBRT arm
💊 Fractionation
- Arm A (SBRT): 36.25 Gy/5fx (7.25 Gy/fx), every other day
- Arm B (moderate hypo): ~68 Gy/25fx (2.7 Gy/fx), 5fx/wk

Results

📊 1° EP: BFFS (Phoenix nadir +2 ng/mL); interim only, mature 4-5yr data pending
📊 Early BFFS, MFS, OS: no significant differences; no inferiority signal for SBRT at interim

Critique

⚠️ Interim analysis (1-2yr f/u) only; 4-5yr primary endpoint not yet reached; non-inferiority pending

Open questions

Mature BFFS/MFS/OS at 4-5yr follow-up to confirm non-inferiority
Long-term late toxicity (>2yr) profile with 5-fraction pelvic SBRT
Impact of PSMA PET/CT staging on outcomes vs conventional imaging cohorts

📚 Sources · 🐦 1 tweet

PRIME trial

Can we safely deliver ultra-short SBRT including pelvic nodal irradiation in biologically aggressive disease treated with ADT?

With Pelvic RT

Moderate hypofractionation:
~68 Gy/25#/5w
Vs
Extreme hypofractionation/SBRT:
36.25 Gy / 5 # /1-2w

Compare HYPO RT PC pic.twitter.com/7NABknLsD5
— Rohit Malde (@roxboxfix) May 18, 2026

PIVOTALboost

ForHigh-risk localised prostate cancer, moderately fractionated 20-fraction RT

TL;DRLate G2+ bowel 6.5-8.7%, bladder 16.5-24.1% at 2yr, no increase with focal boost or pelvic node RT vs prostate-only (N=1465).

vs leading data

vs FLAME (JCO 2021): focal boost improved 5yr bFFS in high-risk prostate with no significant late GI/GU toxicity increase; PIVOTALboost 2yr safety consistent, but FLAME used conventional fractionation (39fr)

Radiation Curative Phase 3 RCT Early signal

PIVOTALboost — Arm Bowel G2+ Bladder G2+

Prostate (n=281) 8.2% (5.7-11.7) 19.5% (15.5-24.4)
Prostate+Boost (n=345) 8.7% (6.3-12.1) 24.1% (20.2-28.7)
Prostate+Nodes+Boost (n=347) 6.5% (4.5-9.5) 16.5% (13.1-20.6)

Arm	Bowel G2+	Bladder G2+
Prostate (n=281)	8.2% (5.7-11.7)	19.5% (15.5-24.4)
Prostate+Boost (n=345)	8.7% (6.3-12.1)	24.1% (20.2-28.7)
Prostate+Nodes+Boost (n=347)	6.5% (4.5-9.5)	16.5% (13.1-20.6)

+1 more figure

5 details

Methods

🔍 Phase 3 RCT, N=1465, 39 UK centres; 3 arms (prostate, prostate+boost, prostate+pelvic+boost); 20-fraction moderately hypofractionated RT
🔍 High-risk localised prostate cancer; 1° EP biochemical/clinical failure — efficacy data not reported here; secondary toxicity endpoints presented

Results

📊 Early bowel side effects increased with pelvic node RT; resolved by 18 weeks post-RT
📊 No significant differences in G2+ bowel or bladder toxicity at 2 years across arms (973 pts, 74% with ≥2yr f/u)

Critique

⚠️ 2-year late toxicity is preliminary for prostate RT; G3+ late effects can emerge at 5+ years

Open questions

Primary efficacy (biochemical/clinical failure) not yet reported
Late toxicity beyond 2 years needed to confirm durability

📚 Sources · 🐦 1 tweet

Day THREE of #ESTRO26 Coverage by OncoAlert 🚨
Moderately fractionated prostate radiotherapy with a focal boost: acute and preliminary late side effects from the phase 3 PIVOTALboost trial Presented by Isabel Syndikus 🇬🇧 #RadOnc ☢️

In the PIVOTALboost trial, we treated 1314… pic.twitter.com/cGuR1j2Qos
— OncoAlert (@OncoAlert) May 17, 2026

PACE-NODES

ForHigh-risk localised prostate (T3a-T4, Gleason 8-10, or PSA >20), planned ADT 12-

TL;DRPPN-SBRT increases G≥2 GI toxicity (28% vs 21%) vs prostate-only SBRT; symptoms resolved by 12wk; GU toxicity equivalent; efficacy endpoint pending.

vs leading data

POP-RT (NEJM 2021): nodal RT improved bFFS with moderate hypofractionation in high-risk pts; PEACE-2 showed no nodal RT benefit (conventional fractionation); PACE-NODES tests the same hypothesis with SBRT fractionation for nodes

Radiation Curative Phase 3 RCT Early signal

PACE-NODES — Endpoint PPN-SBRT P-SBRT

G≥2 GI toxicity (12wk) 28% 21%

Endpoint	PPN-SBRT	P-SBRT
G≥2 GI toxicity (12wk)	28%	21%

+1 more figure

8 details

Methods

🔍 Phase 3 RCT, 1:1; high-risk localised prostate (T3a-T4, Gleason 8-10, or PSA >20), planned ADT 12-36mo; target N=1128, 1166 randomised
💊 P-SBRT: 36.25Gy/5f (prostate); PPN-SBRT: 36.25Gy/5f (prostate) + 25Gy/5f (nodes), alternate days

Results

📊 G≥2 GI toxicity over 12wk: 28% PPN-SBRT vs 21% P-SBRT
📊 GI symptoms resolved; no difference between arms at 12 weeks
📊 EPIC-26 bowel domain worse at 4 weeks in PPN-SBRT arm
📊 No difference in acute GU toxicity (CTCAE or patient-reported)

Critique

⚠️ 11% PPN-SBRT vs 4% P-SBRT did not receive allocated treatment, mostly due to planning constraints not being met
⚠️ Primary endpoint (time to biochemical/clinical failure) not yet mature; this is an acute toxicity interim report only

Open questions

Does nodal SBRT improve bFFS/cFFS vs prostate-only SBRT (primary endpoint pending)?
Late GI/GU toxicity profile with extended follow-up
Whether SBRT nodal fractionation recapitulates bFFS benefit seen with POP-RT moderate hypofractionation

📚 Sources · 🐦 1 tweet

Day THREE of #ESTRO26 Coverage by OncoAlert 🚨
Acute toxicity in PACE-NODES: A randomised trial of 5 fraction (f) prostate stereotactic body radiotherapy (SBRT) vs 5f prostate and pelvic nodal SBRT
Presented by Angela Pathmanathan 🇬🇧 #RadOnc ☢️ #ProstateCancer

PACE-NODES is a… pic.twitter.com/z9bAOiKSIy
— OncoAlert (@OncoAlert) May 17, 2026

PEACE-2

ForVery high-risk localized prostate Ca (≥2 of Gleason ≥8, T3-T4, PSA ≥20), N0M0

TL;DRPelvic RT adds no significant cPFS benefit over prostate-only RT in very high-risk PCa with 3yr ADT (HR 0.81, p=0.088) at interim analysis.

vs leading data

POP-RT (2yr ADT, conventional imaging, 74-76 Gy EQD2) showed significant pelvic RT benefit across bFFS, cFFS, MFS

Radiation Curative Phase 3 RCT Early signal

Arm	7-yr cPFS	HR (95% CI)	p
Pelvic RT	67.1% [61.6; 72.2]	0.81 [0.63; 1.03]	0.088
Prostate-only RT	62.9% [57.4; 68.1]	reference	—

+1 more figure

Endpoint	POP-RT HR (95% CI)	POP-RT p	PEACE-2 HR (95% CI)	PEACE-2 p
bFFS/bPFS	0.50 (0.42-0.61)	<0.001	0.97 (0.81-1.16)	0.73
cFFS/cPFS	0.74 (0.61-0.90)	0.002	0.81 (0.63-1.03)	0.09
MFS	0.72 (0.58-0.89)	0.002	0.93 (0.74-1.17)	0.54

7 details

Methods

🔍 Trial design
- Phase III 2×2 factorial (pelvic vs prostate-only RT × ± cabazitaxel ×4)
- Very high-risk PCa: N0M0, ≥2 of Gleason ≥8, T3-T4, PSA ≥20
- ADT 3yr + 78 Gy EQD2 dose-escalated IMRT; PSMA PET/CT staging; accrual 2018-2023

CONSORT flow

Randomized 761

↓

Pelvic RT

allocated 381

Prostate-only RT

allocated 380

Results

📊 All secondary endpoints (bPFS, MFS, CSS, OS) also non-significant with pelvic RT

Critique

⚠️ Interim analysis at ESTRO 2026 (median f/u ~5.5yr); final prespecified primary analysis pending
⚠️ PSMA PET/CT may exclude occult metastatic pts who drove pelvic RT benefit in the conventional-imaging era
⚠️ Longer ADT (3yr vs 2yr) + dose escalation may reduce incremental pelvic RT gain
⚠️ No added toxicity: comparable G≥2 GU rates in both arms
⚠️ Blanchard: <1 in 10 dying from PCa at 10yr challenges the 'very high-risk' label in modern-imaged pts

Open questions

Will final analysis confirm null benefit of pelvic RT with modern staging and 3yr ADT?
Does PSMA PET/CT staging explain divergence from POP-RT by excluding occult metastatic pts?
Which pts still benefit from elective pelvic RT in the contemporary dose-escalated ADT era?

📚 Sources · 🐦 2 tweets

📣@PBlanchardMD shows #ESTRO26 that pelvic #radiotherapy in high risk #prostatecancer does not have a large improve in outcomes.
- With only 1 in 10 dying of prostate cancer in 10 years, are these patients truly “high risk”? #pcsm #radonc pic.twitter.com/D0XrGD6iNX
— Shankar Siva (@_ShankarSiva) May 17, 2026

POP RT Vs PEACE II

2 years ADT + WPRT

Vs 3 years ADT + Prostate Only RT

Tough to choose or you already have a choice ?? pic.twitter.com/42kdSKQYKW
— Rohit Malde (@roxboxfix) May 18, 2026