2026-05-18

Prostate

Two opposing prostate RT questions answered: ultrahypofx holds (HEAT), elective pelvic nodal escalation doesn't (PEACE 2).

PEACE 2

ForVery high-risk localized N0M0 prostate, conventional/choline staging, ≥2 risk fa

TL;DRPelvic RT missed 1° EP cPFS (HR 0.81, p=0.088) in very high-risk N0M0 prostate; no MFS, OS, or PCSS benefit.

Why it mattersRadiation oncology

The decision is elective pelvic nodal coverage in conventionally-staged very-high-risk N0M0 disease: don't add it. The non-significant cPFS trend (p=0.088) rests on the softest endpoint while MFS, OS, and PCSS are flat. Staging was conventional/choline, not PSMA, so PSMA-selected pts (cf. POP-RT) stay an open question.

vs leading data

vs POP-RT (JCO 2021): whole-pelvis RT improved biochemical control in high-risk N0; PEACE 2 null. Key difference: POP-RT enriched with PSMA/choline staging and a nodal boost

Radiation Curative Phase 3 RCT Challenges SOC

PEACE 2 — Arm 7yr 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) ref n/a

Arm	7yr 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)	ref	n/a

+1 more figure

8 details 1 trial watching

Methods

🔍 Phase III 2×2 factorial (±pelvic RT × ±cabazitaxel); pelvic-RT axis analyzed here, 761 at risk (380 prostate-only vs 381 pelvic)
🔍 Pts: very high-risk localized N0M0, ≥2 of Gleason ≥8, T3-T4, PSA ≥20; staged by conventional imaging or choline PET/CT
💊 All arms: ADT ×3yr + high-dose prostate RT; the pelvic axis adds elective whole-pelvis nodal volume
🔍 Author reports minimal added toxicity from pelvic nodal RT with modern technique (no effect size reported in source)

CONSORT flow

Randomized 761

↓

Prostate-only RT

allocated 380

Pelvic RT

allocated 381

Results

📊 1° EP cPFS not met: pelvic RT gave only a non-significant trend (p=0.088)

Critique

⚠️ No pelvic-RT effect on the hard endpoints MFS, OS, or PCSS (effect sizes not reported in source)
⚠️ Even the favorable direction sits on cPFS, the softest endpoint; the clinically meaningful endpoints are flat
⚠️ Conventional/choline staging may miss occult PSMA-avid nodal disease, diluting any pelvic-RT signal

Open questions

Does whole-pelvis RT benefit PSMA-PET-staged node-negative pts?

not yet PSMA-PET Directed Radiation Therapy for High-Risk Prostate Cancer Phase 2

n=250 · primary completion 2031-05 · WPRT vs prostate-only RT in PSMA-N0M0 high-risk
Did cabazitaxel add benefit in the factorial's systemic axis?

Sourced from @PBlanchardMD

📚 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

ForLocalized low- to intermediate-risk prostate, IPSS <12

TL;DRAHRT (5 fx SBRT) non-inferior to EHRT (26 fx IMRT) for biochemical failure: 7% vs 7.4%, P=0.007 at 4.25y in localized low-int-risk PCa.

Why it mattersRadiation oncology

The RT read is toxicity, not just equivalence: acute G2+ GI was lower with 5 fx AHRT despite a GTV SIB to 40 Gy, with no late GI or GU penalty vs 26 fx EHRT. For low- to int-risk PCa weighing 5 vs 26 fractions, this backs SBRT on access without a control or toxicity cost. ADT was permitted (28%), unlike PACE-B and HYPO-RT-PC.

vs leading data

Unlike HYPO-RT-PC, PACE-B, NRG-GU005 (all barred ADT), HEAT permitted ≤6 mo ADT

Radiation Curative Phase 3 RCT Early signal

HEAT Trial — Endpoint AHRT EHRT P (NI)

Biochemical failure, 4.25y 7% 7.4% 0.007

Endpoint	AHRT	EHRT	P (NI)
Biochemical failure, 4.25y	7%	7.4%	0.007

+1 more figure

AHRT 36.25 Gy/5 fx (7.25 Gy/fx) + GTV SIB to 40 Gy vs EHRT 70.2 Gy/26 fx (2.7 Gy/fx)

8 details 5 trials watching

Methods

🔍 First randomized phase III comparing AHRT (5 fx) vs EHRT (26 fx) head-to-head 1:1, modern IMRT + ADT permitted
🔍 Eligibility: localized low- to intermediate-risk PCa, IPSS <12
🔍 Cohort characteristics
- 82.4% intermediate-risk
- Median follow-up 59.7 mo
- 28% received ADT (≤6 mo permitted both arms)

Results

📊 Acute G2+ GI toxicity lower with AHRT vs EHRT
📊 No significant difference in late G2+ GI or acute/late G2+ GU

Critique

⚠️ Interim analysis: 142 analyzed vs accrual goal 456 (420 evaluable), well short of full accrual
⚠️ Supportive meds (laxatives, psyllium) counted as G2 toxicity, inflating reported GI rates
⚠️ Wide 12% non-inferiority margin (Phoenix BF) could mask a clinically meaningful difference

Open questions

Durability of non-inferiority at full accrual (n=456) and longer follow-up

recruiting Two-fraction Versus Five-fraction Stereotactic Radiotherapy for Localized Prostate Cancer Phase NA

n=562 · primary completion 2027-12 · RCT 2-fx vs 5-fx SBRT, low/fav int-risk localized
Generalizability to high-risk or larger-volume (>80cc) prostate

recruiting Standard Moderately Hypofractionated RT vs. Ultra-hypofractionated Focal Lesion Ablative Microboost in Prostate Cancer Phase NA

n=484 · primary completion 2032-01 · RCT ultra-hypofx vs moderate, int/high-risk

recruiting PRospective Observational Study of STereotactic Body rAdiation Therapy With Androgen Deprivation Therapy for Organ-confined High-risk Prostate Cancer: the PROSTAR Trial

n=49 · primary completion 2032-05 · SBRT+ADT cohort, organ-confined high-risk PCa

recruiting Androgen Suppression Combined With Nodal Irradiation and Dose Escalated Prostate Treatment Phase 3

n=710 · primary completion 2032-10 · phase 3 SBRT vs brachy boost, unfavourable risk

recruiting Phase III Adaptive Adaptive Stereostactic Body Radiotherapy (SBRT) With Dose Escalation for High-Risk Prostate Cancer Phase NA

n=390 · primary completion 2033-04 · phase 3 SBRT dose escalation, high-risk PCa

Sourced from @OncoAlert, @PBlanchardMD

📚 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

Head & Neck

De-intensification on two fronts: protons add no QoL benefit (TORPEdO), elective nodal omission preserves nodal control (INRT).

TORPEdO (CRUK/18/010)

ForOropharyngeal SCC requiring concurrent chemoRT, bilateral neck treatment

TL;DRNo HR-QoL difference IMPT vs IMRT in OPSCC: UW-QoL physical composite similar at 3/12/24 mo, undercutting the toxicity-reduction case for protons.

Why it mattersRadiation oncology

The RT read is proton referral for OPSCC: no UW-QoL physical-composite separation IMPT vs IMRT from 6 wk to 24 mo, so protons' toxicity-reduction premise isn't supported here. But identical constraints and novel UK proton centres may cap IMPT's contrast, and the clinician co-primary (gastrostomy/grade-3 weight loss) plus 5-yr late effects aren't in source.

vs leading data

Parallel Lancet correspondence (McBride et al, May 2026) on proton vs photon for oropharyngeal cancer

Radiation Curative Phase 3 RCT Confirmatory

UW-QoL physical composite (saliva, taste, chewing, swallowing, appearance, speech) change from baseline, 90% CI; 3/12/24 mo

+1 more figure

IMPT vs IMRT 2:1; 70/56 Gy in 33 fx over 6.5 wk; cisplatin 100 mg/m² D1+D22; N=205

8 details 3 trials watching

Methods

🔍 Phase 3 RCT, N=205, 2:1 IMPT vs IMRT, OPSCC requiring concurrent chemoRT with bilateral neck treatment
🔍 70 Gy / 56 Gy in 33 fx over 6.5 wk, same prescription both arms
💊 Concurrent cisplatin 100 mg/m² D1 + D22
🔍 Two co-primary endpoints (late-effect reduction at 12 mo)
- Clinician: CTCAE grade 3 weight loss (≥20% from baseline) or gastrostomy dependence
- Patient: UW-QoL physical composite (saliva, taste, chewing, swallowing, appearance, speech)

Results

📊 PRO co-primary (UW-QoL physical composite) showed no between-arm difference IMPT vs IMRT at 3/12/24 mo post-RT

Critique

⚠️ Only the PRO co-primary appears in this readout; clinician co-primary (gastrostomy/weight loss) not in source
⚠️ Discussant: identical planning + constraints and novel UK proton centres may have limited IMPT's contrast vs experienced centres
⚠️ Some pts had meaningful HR-QoL deterioration to 2 yr post-CRT; follow-up ongoing to 5 yr

Open questions

Does IMPT reduce late toxicity at high-experience proton centres?

active Intensity Modulated Proton or X-Ray Therapy After Surgery for Treatment of Head and Neck Cancer, the HEADLIGHT Study Phase 2

n=174 · primary completion 2027-11 · IMPT vs IMRT postop H&N, toxicity + QoL

recruiting Photon Therapy Versus Proton Therapy in Early Tonsil Cancer. Phase NA

n=100 · primary completion 2028-01 · 1:1 protons vs photons, early tonsil OPSCC

active Intensity-Modulated Proton Beam Therapy or Intensity-Modulated Photon Therapy in Treating Patients With Stage III-IVB Oropharyngeal Cancer Phase 3

n=440 · primary completion 2031-12 · randomised phase 3 IMPT vs IMRT in OPSCC, QoL
IMPT effect on the clinician co-primary (gastrostomy, grade 3 weight loss)
Late HR-QoL divergence from 2 to 5 years post-CRT

Sourced from @OncoAlert, @AmadeoWals, McBride et al.

📚 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.

INRT-AIR & DARTBOARD (ENI omission in HNSCC)

ForHNSCC oropharynx/larynx/hypopharynx, stage I-IVB (excl T1-2N0 larynx)

TL;DR5y solitary elective nodal recurrence 0% with ENI omission (INRT) in HNSCC; 5y OS 87%, PFS 74%, n=117 pooled.

Why it mattersRadiation oncology

The number licensing ENI omission is the 0% 5y solitary elective nodal recurrence: out-of-field nodal failures didn't materialize. The 9.5% 3y local recurrence is in-field, a dose/target question not an omission failure. Preserved MDADI (84.9 at 12mo) is the toxicity payoff for narrowing target volumes. Moves the elective-nodal-coverage decision.

Radiation Curative Meta-analysis Early signal

8 details 1 trial watching

Methods

🔍 Patient-level pooled analysis of 2 prospective single-arm INRT trials (INRT-AIR + DARTBOARD), n=117, median f/u 3.4y
🔍 HNSCC oropharynx/larynx/hypopharynx, stage I-IVB (excl T1-2N0 larynx); AI model flagged suspicious nodes for inclusion

Results

📊 5y solitary elective nodal recurrence 0%, the key safety signal for ENI omission
📊 3y cumulative incidence
- Local recurrence 9.5%
- Regional recurrence 4.3%
- Distant metastasis 11%
📊 5y OS 87%, PFS 74%
📊 MDADI composite 84.9 at 12mo, no significant decline post-treatment (swallowing QoL preserved)

Critique

⚠️ 3y local recurrence 9.5% is in-field (dose/target question), not an out-of-field ENI-omission failure
⚠️ Single-arm pooled, no randomized comparator vs standard ENI; authors call for RCT before non-trial use

Open questions

Randomized comparison of INRT vs standard elective nodal irradiation

recruiting Invert-Prospective Phase II Randomized Trial of Involved Nodal Versus Elective Neck RadioTherapy Phase 2

n=80 · primary completion 2028-07 · phase 2 RCT of involved-nodal vs elective neck RT
Durability of nodal control beyond 5 years
Generalizability of AI-assisted nodal selection across centers

Sourced from @OncoAlert

📚 Sources · 🐦 1 tweet

Day FOUR of #ESTRO26 Coverage by OncoAlert 🚨
Omission of elective nodal irradiation in HNSCC: long-term results and patient-level pooled analysis from 2 prospective trials (INRT-AIR & DARTBOARD)
Presenter Sympascho Young 🇺🇸

A patient-level pooled analysis of 117 patients… pic.twitter.com/KaaT70nSNH
— OncoAlert (@OncoAlert) May 18, 2026

GI Lower

W14 clinical exam reliably flags responders for rectal organ preservation, moving the decision earlier than W24.

OPERA Trial (5-year rectal preservation)

ForRectal cancer s/p neoadjuvant therapy, organ-preservation candidates

TL;DRW14 clinical exam (DRE+rectoscopy±MRI) reliably flags complete response; 5-yr organ preservation similar for cCR vs nCR (81% vs 77%).

Why it mattersRadiation oncology

The RT read: near-complete response carries nearly the same 5-yr organ-preservation rate as complete response (77% vs 81%), so radiation-induced nCR shouldn't trigger salvage TME. W14 clinical exam (DRE+rectoscopy, 98% MRI-concordant) lets you commit to watch-and-wait a month after NAT rather than waiting to W24.

Radiation Curative Phase 3 RCT Caveats dominate

8 details 3 trials watching

Methods

🔍 Post-hoc analysis of OPERA (phase 3 rectal organ-preservation RCT), N=141; tests W14 decision vs the trial's prespecified W24 assessment.
🔍 Arms not labeled in source slides; per published OPERA, Arm B = contact X-ray brachytherapy boost, Arm A = EBRT boost.

Results

📊 W14 clinical tumor response eval feasible in 122/141 (87%): 76% good response (cCR+nCR), 24% PR.
📊 W14 good response and 5-yr organ preservation by arm

Endpoint Arm A Arm B p

W14 good response 65% 88% 0.004
5-yr organ preservation 75% 83% 0.24
📊 MRI concordance high: TRG1-2 in 98% (80/82) of clinical-CR pts.
📊 5-yr OP similar for cCR vs nCR (81% vs 77%): near-complete response not prognostically inferior.

Endpoint	Arm A	Arm B	p
W14 good response	65%	88%	0.004
5-yr organ preservation	75%	83%	0.24

Critique

⚠️ nCR reflects radiation side effects, not residual tumor (authors); should not justify radical surgery.
⚠️ W14-vs-W24 timing not a randomized comparison; who proceeds to OP is selected, so the timing read is confounded.

Open questions

Prospective validation of W14 versus W24 response-assessment timing

active Longitudinal Multimodal Response Assessment During Neoadjuvant Treatment of Rectal Cancer

n=40 · primary completion 2026-01 · prospective longitudinal multimodal response assessment
Durability of watch-and-wait organ preservation beyond 5 years

active Short RT Versus RCT,Followed by Chemo.and Organ Preservation for Interm and High-risk Rectal Cancer Patients Phase 3

n=702 · primary completion 2023-09 · randomized W&W arm for cCR after TNT

not yet Neoadjuvant FOLFOXIRI and Chemoradiotherapy Versus Neoadjuvant CAPOX/FOLFOX and Chemoradiotherapy Followed by Surgery or a Watch-and-Wait Approach in High Risk Locally Advanced Rectal Cancer Phase 3

n=394 · primary completion 2030-03 · phase 3 W&W arm, long-term oncologic outcomes

Sourced from @OncoAlert

📚 Sources · 🐦 1 tweet

Day FOUR of #ESTRO26 Coverage by OncoAlert 🚨
Five-year Results of the OPERA Trial: When and How to Assess Tumor Response to Guide Rectal Preservation Presented by Syrine Ben Dhia 🇫🇷 #RadOnc ☢️

This post-hoc analysis of the OPERA trial evaluated early tumor response… pic.twitter.com/KUanFTxeFh
— OncoAlert (@OncoAlert) May 18, 2026

Hepatobiliary

4,913-pt IPD cohort positions EBRT alongside resection and ablation for early-stage HCC.

HCC EBRT Multinational IPD Cohort

ForEarly-stage HCC (BCLC 0-A), treatment-naïve and experienced

TL;DRMedian OS 6.8yr (BCLC-0) and 4.6yr (BCLC-A) with EBRT in 4,913-pt multinational IPD cohort; comparable to resection/ablation for early HCC.

Why it mattersRadiation oncology

Ablative dose mattered: it was independently associated with reduced mortality, arguing for ablative-intent dosing rather than palliative fractionation in early HCC. With BCLC-0/A OS (6.8/4.6 yr) tracking resection and ablation, this moves EBRT from salvage toward a first-line ablative option in the BCLC algorithm.

vs leading data

Authors: early-stage EBRT OS comparable to resection, thermal ablation, other ablative locoregional Rx; backs EBRT in BCLC algorithm.

Radiation Curative Meta-analysis Confirmatory

6 details 3 trials watching

Methods

🔍 IPD pooled from multinational cohort via systematic review (prespecified HCC technical standards); N=4,913, median f/u 5.0 yr.

Results

📊 Median OS by BCLC stage × treatment status

BCLC stage All pts mOS (95% CI) Treatment-naïve mOS (95% CI)

BCLC-0 6.8 yr (5.7-8.7) NR (8.6-NR)
BCLC-A 4.6 yr (4.1-5.1) 5.4 yr (4.5-6.7)
📐 Multivariable Cox — covariates associated with OS
- Protective: ablative radiation dose, more recent treatment year
- Harmful: advanced BCLC stage, higher tumor burden, worse PS, Child-Pugh B/C

BCLC stage	All pts mOS (95% CI)	Treatment-naïve mOS (95% CI)
BCLC-0	6.8 yr (5.7-8.7)	NR (8.6-NR)
BCLC-A	4.6 yr (4.1-5.1)	5.4 yr (4.5-6.7)

Critique

⚠️ No internal comparator; resection/ablation 'comparability' is a cross-study benchmark, not head-to-head.
⚠️ Selection bias plausible: EBRT pts often poorer surgical/ablation candidates than the benchmark series.
⚠️ Dose-response observational; ablative dose likely confounded with smaller tumors and better liver function.

Open questions

Randomised EBRT vs resection/ablation in early-stage HCC

active Stereotactic Body Radiotherapy Versus Radiofrequency Ablation for Unresectable, Small (≤ 3 cm) HCC Phase NA

n=178 · primary completion 2026-12 · SBRT vs RFA, unresectable HCC ≤3cm

not yet SBRT Versus Surgical Resection for Small HCC Phase 3

n=312 · primary completion 2031-12 · phase 3 SBRT vs resection, solitary HCC ≤5cm

recruiting A Study of Standard Of Care Versus Radio Ablation in Early Stage HCC Phase NA

n=218 · primary completion 2032-04 · randomised SABR vs ablation, early HCC (BCLC 0/A)
Optimal ablative dose and fractionation for HCC EBRT

Sourced from Moon et al.

📚 Sources · 📄 1 paper

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

Overall Survival Among Patients With Hepatocellular Carcinoma Treated With External Beam Radiation Therapy: Individual Patient Data Outcomes From a Multinational Cohort.

PMID 42139645 → doi

Abstract

PURPOSE: External beam radiation therapy (EBRT) has gained delayed acceptance as a recommended first-line treatment modality for patients with hepatocellular carcinoma (HCC), given limited evidence that it improves overall survival (OS). We analyzed individual patient data (IPD) from an international cohort to assess OS among patients with HCC treated with EBRT. METHODS: We performed a systematic review of publications that assessed EBRT, met prespecified technical standards for HCC, and reported OS (search date December 15, 2022). Corresponding authors were invited to submit IPD for the study. We performed Kaplan-Meier survival analyses to determine OS and restricted mean survival time (RMST) stratified by Barcelona Clinic Liver Cancer (BCLC) stage and treatment status (ie, treatment-naïve and experienced). We performed random effects Cox proportional hazards modeling to assess clinical characteristics associated with OS. RESULTS: Data were provided on 4,913 patients treated with EBRT with a median follow-up time of 5.0 years. The median OS was 6.8 years (95% CI, 5.7 to 8.7) for BCLC-0 and 4.6 years (95% CI, 4.1 to 5.1) for BCLC-A. Among treatment-naïve patients, the median OS was not reached (95% CI, 8.6 to not reached) for BCLC-0 and was 5.4 years (95% CI, 4.5 to 6.7) for BCLC-A. In multivariable models, more advanced BCLC stage, higher tumor burden, worse performance status, and Child-Pugh class B or C were associated with a higher risk of mortality. Ablative radiation dose and more recent year of treatment were associated with a reduced risk of death. CONCLUSION: To our knowledge, this study represents the largest multinational cohort of patients with HCC treated with EBRT. OS outcomes with EBRT for very early- and early-stage HCC appear to be comparable with resection, thermal ablation, and other ablative locoregional therapies. These data support the inclusion of EBRT in the BCLC HCC clinical decision-making process.

📝 Moon AM, Yanagihara TK, Dawson LA, Yu JI, Lawrence TS, Kim TH, Yan M, Iwata H, Nabavizadeh N, Apisarnthanarax S, Dunne EM, Lock MI, Chuong MD, Chiang CL, Scorsetti M, Katoh N, Sioshansi S, Numata K, Liu HY, Iwamoto H, Wakatsuki M, Chen Y, Pollom EL, Gkika E, Jabbour SK, Munoz-Schuffenegger P, Dutta D, Hajj C, Ueno M, Hallemeier CL, Feldman AM, Méndèz Romero A, Tan X, Molla M, Tepper JE, Torres F, Reig M; EBRT Collaboration Group. Overall Survival Among Patients With Hepatocellular Carcinoma Treated With External Beam Radiation Therapy: Individual Patient Data Outcomes From a Multinational Cohort. J Clin Oncol. 2026 May 15:JCO2502399.

Kidney

First prospective phase 2 of SABR for primary RCC, 100% local control but single-arm and non-surgical.

FASTRACK II (TROG 15.03) NCT02613819

ForInoperable/high-risk primary RCC, T1b-dominant, median age 77

TL;DR100% local control at 36/60/84 mo with SABR for primary RCC, no local recurrences or cancer deaths at median 62-mo f/u.

Why it mattersRadiation oncology

The actionable RT read: 100% local control at 36/60/84 mo under a size-stratified scheme transferable to practice, 26Gy×1 for ≤4cm and 42Gy/3fx for >4cm. Predominantly T1b (56%) with some T2a extends SABR past the small-renal-mass niche thermal ablation owns, moving the non-surgical-candidate decision toward SABR.

vs leading data

First prospective phase 2 of SABR for primary RCC; prior evidence was retrospective (IROCK pooled cohorts)

Radiation Curative Phase 2 trial Early signal

9 details 3 trials watching

Methods

🔍 SABR dose by tumour size: 26 Gy single fraction for ≤4 cm; 42 Gy/3 fx (48h apart) for >4 cm
🔍 Non-randomised phase 2, 8 sites (Australia + Netherlands, TROG/ANZUP); 71 enrolled, 70 treated; median f/u 62 mo (IQR 60-72)
🔍 Eligible: medically inoperable, high risk, or declined surgery; ECOG ≤2; tumours ≤10 cm; N0-N1
🔍 Predominantly T1b; median tumour 46 mm (37-55), median age 77 (70-82)
- T1a: 24 (34%)
- T1b: 39 (56%)
- T2a: 6 (9%)
- T3a: 1 (1%)
- N1 nodal involvement: 1 (1%)

Results

📊 1° EP freedom from local progression (RECIST, ITT): 100% local control at 36, 60, and 84 months

Critique

⚠️ Grade 3 AEs ≤9 mo in 7 (10%) pts, treatment-related; no grade 4, no treatment-related deaths, no new long-term signals
- Nausea/vomiting: 3 (4%) events
- Abdominal/flank/tumour pain: 4 (6%)
- Colonic obstruction: 2 (3%)
- Diarrhoea: 1 (1%)
⚠️ Single-arm: no randomised comparator vs partial nephrectomy or thermal ablation; non-inferiority not established
⚠️ Selected non-surgical cohort, T1b-dominant favourable biology; competing mortality high at median age 77
⚠️ Local control by RECIST: ablated masses can persist radiographically, so RECIST freedom-from-progression ≠ pathologic control

Open questions

Randomised SABR vs surgery or thermal ablation in operable candidates
Local control and toxicity in tumours larger than 7 cm

recruiting A Phase II Study of Cyberknife Radiosurgery for Renal Cell Carcinoma Phase NA

n=46 · primary completion 2025-01 · Cyberknife radiosurgery, primary RCC up to 8 cm

recruiting Interstitial Brachytherapy for the Treatment of Unresectable/Unablatable Kidney Cancer Phase 1

n=17 · primary completion 2026-06 · interstitial brachytherapy for large kidney masses

recruiting Ablative Radioembolization of Renal Cell Carcinoma Trial Phase 2

n=16 · primary completion 2028-12 · Y-90 radioembolization for T1b/T2 RCC >4 cm
Long-term metastatic spread and cancer-specific survival

Sourced from Siva et al.

📚 Sources · 📄 1 paper

📄 PAPER Siva; Pryor; Martin et al. · The Lancet. Oncology (2026-05)

Long-term outcomes of stereotactic ablative body radiotherapy for primary kidney cancer (TROG 15.03 FASTRACK II): a multicentre, non-randomised, phase 2 study.

PMID 42144018 → doi

Abstract

BACKGROUND: Stereotactic ablative body radiotherapy (SABR) is an emerging, non-invasive alternative for primary renal cell carcinoma. We aimed to provide the final long-term trial outcomes of TransTasman Radiation Oncology Group (TROG) 15.03 FASTRACK II, the first phase 2 trial investigating SABR for primary renal cell carcinoma to our knowledge. METHODS: FASTRACK II was a non-randomised, phase 2 study conducted in eight hospitals in Australia and the Netherlands by TROG and the Australian and New Zealand Urogenital and Prostate (ANZUP) Cancer Trials Group. Here, we report the final pre-planned follow-up results. Adult patients (aged ≥18 years) with histologically confirmed primary renal cell carcinoma, who were medically inoperable, high risk, or declined surgery, had an Eastern Cooperative Oncology Group performance status of 2 or less, had tumours 10 cm or less in size, and had N0-N1 disease were included. Patients underwent either a single fraction SABR of 26 Gy for tumours 4 cm or less in maximum diameter, or 42 Gy in three fractions delivered 48 h apart for tumours more than 4 cm in maximum diameter. The primary outcome was freedom from local progression to assess local control after SABR evaluated with the Response Evaluation Criteria in Solid Tumours. The primary endpoint and safety were evaluated in the intention-to-treat population. A patient representative was involved in the study design and conduct. The trial was registered with ClinicalTrials.gov (NCT02613819) and is closed to enrolment. FINDINGS: Between July 28, 2016, and Feb 27, 2020, 71 patients were enrolled and one withdrew consent before treatment. Median follow-up was 62 months (IQR 60-72), median age was 77 years (70-82). 49 (70%) of 70 patients were male and 21 (30%) were female. Race and ethnicity data were not collected. The median tumour size was 46 mm (37-55), with 24 (34%) patients with T1a disease, 39 (56%) with T1b disease, six (9%) with T2a disease, and one (1%) with T3a disease. One patient (1%) had nodal involvement (N1). SABR resulted in 100% local control at 36 months, 60 months, and 84 months. Seven (10%) patients had at least one grade 3 adverse event within 9 months of SABR that was designated possibly, probably, or definitely related to treatment: nausea and vomiting (three [4%] events); abdominal, flank, or tumour pain (four [6%]); colonic obstruction (two [3%]); and diarrhoea (one [1%]). No new long-term safety signals, grade 4 events, or treatment-related deaths were noted. INTERPRETATION: Long-term follow-up supports the safety and local control of SABR for non-surgical patients with renal cell carcinoma, with no observed local recurrences or cancer-related deaths in this cohort, which had predominantly T1b disease or higher. FUNDING: The Cancer Australia Priority-driven Collaborative Cancer Research Scheme and Varian.

📝 Siva S, Pryor D, Martin J, Hardcastle N, Moon D, Kron T, Higgs B, Foroudi F, Ruben J, Sridharan S, Montgomery R, Davey R, Lin C, Shaw M, Lawrentschuk N, Appu S, Vanneste BGL, Hofman MS, Murphy DG, De Abreu Lourenco R, Mancuso P, Brook NR, Raman A, Wong LM, Sidhom M, Wood S, Ali M, Bressel M. Long-term outcomes of stereotactic ablative body radiotherapy for primary kidney cancer (TROG 15.03 FASTRACK II): a multicentre, non-randomised, phase 2 study. Lancet Oncol. 2026 May 17:S1470-2045(26)00091-4.

Breast

Concurrent SIB boost folded into hypofractionated WBI, non-inferior and a shorter course.

NRG/RTOG 1005 NCT01349322

ForHigh-risk early breast cancer, post-lumpectomy (G3/ER−/node+/close margin)

TL;DRConcurrent SIB boost (40Gy/15F) noninferior to sequential boost for IBR: HR 1.31 (90% CI 0.84-2.04), equal cosmesis and toxicity, shorter overall time.

Why it mattersRadiation oncology

The decision it moves: collapse the boost into the whole-breast course. Concurrent delivers everything in 15 fractions (40Gy/15F + SIB 8Gy/15F) vs a separate post-WBI boost, with non-inferior 3-yr cosmesis and matched G3-4 toxicity. For high-risk pts needing a boost, this is the shorter, equally safe option.

vs leading data

Boost-reduces-IBR established by EORTC 22881-10882; this keeps the boost but folds it into hypofractionated WBI to shorten the course

Radiation Curative Phase 3 RCT Confirmatory

10 details 4 trials watching

Methods

🔍 Phase III noninferiority RCT, N=2255 analyzed (1118 sequential / 1137 concurrent), 278 sites, median f/u 7.3yr
🔍 RT regimens by arm
- Concurrent: 40Gy/15F WBI + simultaneous integrated boost 8Gy/15F (0.53Gy/day)
- Sequential: 50Gy/25F or 42.7Gy/16F WBI, then separate boost 12Gy/6F or 14Gy/7F
- 3DCRT most common (59%), photons 73.8%; IMRT also used
🔍 Higher-risk population enriched for recurrence
- 52.7% grade 3, 29.6% ER-negative
- 16.3% node-positive, 16.7% LVI, 16.7% close (<2mm)/focally positive margins
- median age 55, 35.6% <50yo; 61.8% received chemo

CONSORT flow

Randomized 2354

↓

Sequential boost

allocated 1118

Concurrent boost

allocated 1137

Results

📊 1° EP IBR noninferiority met: HR 1.31 (90% CI 0.84-2.04), P=.037; upper 90% CI bound 2.04 < 2.12 margin
📊 IBR as first recurrence, by arm

Endpoint Sequential Concurrent

5-yr IBR 2.1% 1.9%
7-yr IBR 2.2% (90% CI 1.5-3.0) 2.6% (90% CI 1.9-3.5)
IBR events (of 56) 24 32
📊 3-yr excellent/good cosmesis (noninferior, both measures)

Measure Sequential Concurrent p

Physician-rated 85.9% 82.4% 0.34
Central photo review 64.2% 72.0% 0.11
📊 No difference in grade 3-4 toxicity (p=0.81); dermatitis, fatigue, breast pain most common
📊 7-yr regional nodal recurrence 1.2% (95% CI 0.8-1.7), 28 events; no arm difference in RNR, DFS, DDFS, or OS

Endpoint	Sequential	Concurrent
5-yr IBR	2.1%	1.9%
7-yr IBR	2.2% (90% CI 1.5-3.0)	2.6% (90% CI 1.9-3.5)
IBR events (of 56)	24	32

Measure	Sequential	Concurrent	p
Physician-rated	85.9%	82.4%	0.34
Central photo review	64.2%	72.0%	0.11

Critique

⚠️ NI margin generous (HR upper limit 2.12); point estimate 1.31 favors sequential, with numerically more IBR events concurrent (32 vs 24)
⚠️ Only 56 IBR events → wide CI; protocol superiority test (triggered by meeting NI) was not significant

Open questions

Does concurrent SIB hold atop 5-fraction (FAST-Forward) whole-breast schedules?

recruiting Ultra-hypofractioNated Adjuvant Radiotherapy ± sImultaneous Integrated Boost for Low-risk Breast Cancer Patients Phase 2

n=65 · primary completion 2025-10 · ± SIB design on ultra-hypofx WBI

recruiting Ultra Hypo-fractionated Adjuvant Whole Breast Radiation Therapy With Simultaneous Integrated Boost for Early-Stage Breast Cancer (H-ASSIST) Phase 2

n=90 · primary completion 2028-02 · 5fr WBI + SIB, built on FAST-Forward

recruiting 5 fr Ultrahypofractionated WBI and SIB for Breast Cancer With Unfavorable Characteristics Phase NA

n=458 · primary completion 2029-06 · randomized 5fr WBI+SIB vs 15fr WBI+SIB
Concurrent boost in node-positive pts also needing regional nodal RT

active Hypofractionated Loco-regional Adjuvant Radiation Therapy of Breast Cancer Combined With a Simultaneous Integrated Boost Phase NA

n=2963 · primary completion 2021-07 · SIB atop loco-regional RNI, node-positive
10-year IBR and late cosmesis durability

Sourced from Vicini et al.

📚 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.

Oligometastatic / Mets

Randomized MDT benefit across histology baskets, with RT delivering 98% of treatment.

EXTEND Trial

ForOligometastatic solid tumors, 1-5 metastases, mixed histologies

TL;DRPFS HR 0.54 (0.41-0.72), p<0.001 with added MDT across oligomet baskets; RT delivered 98% of MDT.

Why it mattersRadiation oncology

RT was the MDT for 98% of metastases (370/379), so HR 0.54 is effectively an RT-attributable effect, and it holds across non-prostate histologies (HR 0.60, 0.40-0.89). That widens the oligomet MDT offer beyond the prostate-dominated prior RCTs, though breast and kidney baskets stayed inconclusive, so gate those. RT dose/fractionation not in source, so transfer specifics are uncertain.

Radiation Phase 2 trial Confirmatory

8 details 5 trials watching

Methods

🔍 Multicenter randomized phase II, 1-5 mets, 6 histology baskets (breast/pancreas/kidney/2 prostate/Other) with basket-specific powering
🔍 521 screened → 350 randomized → 334 per-protocol (MDT+SOC n=166, SOC n=168); median f/u 53mo, 2018-2023
🔍 Translational signals (exploratory)
- Detectable ctDNA at enrollment → shorter PFS and survival
- ctDNA clearance at 3mo post-enrollment → improved survival
- MDT-induced systemic immune activation greatest in PFS-superior baskets

Results

📊 PFS by analysis set (MDT+SOC vs SOC)

Analysis set HR (95% CI) p

All baskets 0.54 (0.41-0.72) <0.001
Excluding prostate 0.60 (0.40-0.89) n/a
📐 RT delivered MDT for 98% of metastases (370/379); the measured effect is essentially RT-attributable
📊 Basket-level PFS superiority: pancreas, prostate, Other positive; breast and kidney inconclusive

Analysis set	HR (95% CI)	p
All baskets	0.54 (0.41-0.72)	<0.001
Excluding prostate	0.60 (0.40-0.89)	n/a

Critique

⚠️ Primary PFS pre-specified per-protocol, not ITT; per-protocol analysis can favor the intervention arm
⚠️ RT dose, fractionation, and SBRT vs conventional technique not reported in source abstract

Open questions

Phase III confirmation of histology-specific MDT efficacy signals

recruiting Extending Outcomes for Pancreas Cancer Patients With Nominal Oligometastatic Disease (EXPAND): A Randomized Phase III Trial Phase 3

n=80 · primary completion 2029-06 · phase 3 MDT, PFS/OS primary in oligomet pancreas
Can ctDNA dynamics refine oligometastasis definition and patient selection?

recruiting SMC Radiation Oncology SABR Cohort for Oligometastasis

n=60 · primary completion 2027-12 · ctDNA biomarker dynamics in SABR oligomet cohort

recruiting Phase II Non-Randomized Study Evaluating POSLUMA-PSMA PET Response After Oligo- Metastatic/Progressive-directed Treatment With Radiotherapy (PROMPT-R) Phase 2

n=50 · primary completion 2028-05 · ctDNA dynamics after ablative RT to mets
Why were breast and kidney baskets inconclusive (power vs biology)?

recruiting Metastasis-directed Therapy for Oligometastases of Breast Cancer Phase 3

n=340 · primary completion 2026-11 · phase 3 RCT of SBRT/RT MDT in oligomet breast

recruiting Cemiplimab or Cemiplimab and Fianlimab After Stereotactic Body Radiotherapy in Clear Cell Renal Cell Carcinoma Phase 2

n=72 · primary completion 2029-08 · kidney-specific MDT trial: SBRT in oligomet ccRCC

Sourced from Sherry et al.

📚 Sources · 📄 1 paper

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

Addition of Metastasis-Directed Therapy to Standard of Care for Oligometastatic Solid Tumors: Primary Analysis of All Tumor-Histology Baskets of the Phase II Randomized EXTEND Trial.

PMID 42142259 → doi

Abstract

PURPOSE: We tested the hypothesis that adding metastasis-directed therapy (MDT) to standard of care (SOC) systemic therapy improves progression-free survival (PFS) among patients with oligometastatic disease. METHODS: EXTEND was a multicenter randomized phase II trial. Patients with 1-5 metastases were randomized to MDT+SOC vs SOC in 1 of 6 baskets (breast, pancreas, kidney, two prostate baskets, and an "Other" basket) with basket-specific stratification and powering. PFS, the primary endpoint, was pre-specified in the per-protocol set within each basket, across all baskets, and across all baskets excluding the prostate baskets. Exploratory endpoints included circulating tumor DNA (ctDNA) and immune profiling. RESULTS: From 2018 through 2023, 521 patients were screened, 350 were randomized, and 334 were analyzed per protocol (MDT+SOC, n=166; SOC, n=168). Radiotherapy was used as MDT for 98% of metastases (370/379). Overall, after median follow-up of 53 months, PFS was improved with MDT+SOC (HR 0.54, 95% CI 0.41 to 0.72, p < 0.001). Similarly, PFS was improved when excluding the prostate baskets (HR, 0.60; 95% CI: 0.40 to 0.89). Within each basket, PFS superiority was identified for the pancreas, prostate, and "Other" baskets, whereas the breast and kidney baskets were inconclusive. At enrollment, detectable ctDNA correlated with shorter PFS and survival; by contrast, ctDNA clearance 3-months post-enrollment correlated with improved survival. MDT+SOC-induced systemic immune activation was most pronounced among baskets demonstrating PFS superiority. CONCLUSION: The phase II EXTEND trial supports the addition of MDT to SOC for oligometastatic disease. Histology-specific efficacy signals were identified for phase III testing. Translational insights suggest the potential for optimizing the definition of oligometastasis using ctDNA, and point to systemic immune responses as a possible mechanism of benefit from MDT.

📝 Sherry AD, Haymaker C, Wang S, Liu S, Bathala TK, Medina-Rosales MN, Seo A, Hara K, Reddy J, Chun SG, Mayo LL, Walker G, Pant S, Zhao D, Kovitz CA, Ramirez D, Ha CS, Smith BD, Gomez D, Cohen L, Koong AC, Reuben A, Tannir N, Corn PG, Tran PT, Siddiqui BA, Subudhi SK, Msaouel P, Ludmir EB, Tang C. Addition of Metastasis-Directed Therapy to Standard of Care for Oligometastatic Solid Tumors: Primary Analysis of All Tumor-Histology Baskets of the Phase II Randomized EXTEND Trial. J Clin Oncol. 2026 May 16:101200JCO2502856.