ASTRO Annual Meeting 2026

CNS

Three phase III readouts: fSRS over single-fraction SRS for resection cavities, SRS vs HA-WBRT + memantine in SCLC brain mets (neurocognitive 1° EP not met), and a null TTFields timing trial in ndGBM.

Confirmatory

TRIDENT NCT04471844

ForndGBM (WHO 2016), post maximal safe resection or biopsy, pre-RT/TMZ

Overall survival

HR 0.953

95% CI 0.82-1.10, p=0.52; mOS 17.7 vs 17.5 m, not met

TL;DRNo OS gain starting TTFields with RT/TMZ vs at maintenance TMZ in ndGBM: mOS 17.7 vs 17.5 m, HR 0.953, p=0.52.

Why it mattersRadiation oncology

The RT read is toxicity without payoff: wearing TTFields through RT/TMZ raised device-related AEs to 76.2% vs 59.2% (mostly grade 1-2 skin) with no OS, PFS or ORR difference. RT dose, fractionation and array handling during RT are not reported in source, so the trial gives no reason to build arrays into the chemoRT course.

Monday clinic

In ndGBM pts about to begin RT/TMZ after maximal safe resection or biopsy, this does not support moving TTFields start forward from maintenance TMZ; it does not extend to selecting MGMT-methylated pts for early start, which rests on a post hoc subset. The longer read

7 details

Design

Randomized, open-label, global phase 3, 1:1, randomized before RT/TMZ. N=981, accrued Dec 2020 to Jan 2024. Stratified by MGMT promoter methylation status and extent of resection.

Population & inclusion

Adults with ndGBM (WHO 2016 classification), recovered from maximal safe resection (biopsy allowed), KPS threshold 70 (inequality sign not rendered in source), RT/TMZ planned <8 weeks after surgery. Median age 60 (22-86), 65.1% male, 38.9% MGMT methylated, 5.4% IDH mutant.

Regimen

TTFields (200 kHz) started concurrently with RT/TMZ (Early Start, n=492) or with adjuvant TMZ (Maintenance Start, n=489). TTFields recommended until second disease progression in both arms. Median device use 7.7 m vs 6.1 m.

Radiotherapy

RT with TMZ in both arms. Dose, fractionation, target volume and array management during RT are not reported in source.

Endpoints

Primary: overall survival. Secondary: PFS, 1-, 2- and 3-year survival rate, ORR, safety. Kaplan-Meier with stratified log-rank test.

Results

Primary not met in ITT (see table). PFS and ORR not different between arms, values not reported in source.

Endpoint	Early Start (with RT/TMZ)	Maintenance Start (with adjuvant TMZ)	Effect
mOS (95% CI)	17.7 m (16.0-18.8)	17.5 m (15.9-19.0)	HR 0.953 (95% CI 0.82-1.10), p=0.52
1-year survival	70.9%	72.0%	NS
2-year survival	33.9%	31.6%	NS
3-year survival	22.5%	18.4%	NS
Device-related AEs	76.2%	59.2%	mostly grade 1-2 skin
Median TTFields duration (range)	7.7 m (0-49)	6.1 m (0-43)	not reported

Safety

Device-related AEs 76.2% Early Start vs 59.2% Maintenance Start, mostly grade 1-2 skin-related. Grade 3+ rates and RT interruption not reported in source.

vs leading data

EF-14 established TTFields added to maintenance TMZ after chemoRT, which the source names as current standard and which is the control arm here. TRIDENT asks only whether starting earlier adds to that, and in ITT it does not.

Applies to

adults with ndGBM (WHO 2016) after maximal safe resection or biopsy who are planned for RT/TMZ and TTFields

Does not represent pts not receiving TTFields at all, since both arms used the device.

Limitations

The between-arm exposure contrast is small (median use 7.7 m vs 6.1 m) and ~25% never started maintenance, which dilutes a timing effect. The MGMT signal conditions on device usage after randomization, with no subgroup n, interaction test or ITT MGMT-methylated result in source.

Discussion

A timing-null result, not a device-null one. The post hoc MGMT-methylated finding (HR 0.683, p=0.03) is a hypothesis for a prospective trial, and the abstract's "clinically meaningful" framing outruns a per-protocol-usage subset.

Enrolment

CONSORT flow

Randomized981

↓

Early Start (TTFields with RT/TMZ)

allocated 492

mOS 17.7 m

Maintenance Start (TTFields with adjuvant TMZ)

allocated 489

mOS 17.5 m

Rationale

Randomized phase 3 with prespecified OS primary not met, so maintenance-start TTFields stands. MGMT-methylated benefit is post hoc in a per-protocol-usage subset, not grounds for change.

Open questions

Does early TTFields improve OS in MGMT-methylated ndGBM when tested prospectively?
Scalp dose and RT interruption with arrays worn during RT/TMZ

Sourced from W. Shi et al.

📚 Sources · 📄 1 paper

📄 PAPER W. Shi; M. Glas; S. Lapointe et al. · ASTRO 2026 Annual Meeting (2026-09)

TRIDENT: Phase 3 Trial of Tumor Treating Fields (TTFields) Therapy Concurrent with Temozolomide (TMZ) Radiochemotherapy Followed by Maintenance TMZ and TTFields for Newly Diagnosed Glioblastoma (ndGBM)

doi article →

Abstract

ASTRO 2026 abstract LBA 04 · LBA 01 - Late-breaking Abstract Session · 2026-09-29 · presented by Wenyin Shi, MD, PhD Purpose/Objective(s): Standard treatment for newly diagnosed glioblastoma (ndGBM) is maximal safe resection followed by radiotherapy (RT) with temozolomide (TMZ) then maintenance TMZ and TTFields therapy. TRIDENT evaluated whether earlier initiation of TTFields therapy concurrently with RT/TMZ improves survival compared with current utilization. Materials/Methods: TRIDENT (NCT04471844) was a randomized, open-label, global phase 3 clinical trial. Adults with ndGBM (WHO 2016 classification) were randomized 1:1 prior to RT/TMZ to receive TTFields (200 kHz) initiated concurrently with RT/TMZ (Early Start arm) or with adjuvant TMZ (Maintenance Start arm). Patients (pts) were stratified by MGMT promoter methylation status and extent of resection. TTFields were recommended until second disease progression in both arms. Key inclusion criteria: recovered from maximal safe resection (biopsy allowed); KPS =70; and planned initiation of RT/TMZ <8 weeks after surgery. Primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), 1-, 2-, and 3-year survival rate, overall response rate (ORR), and safety. Survival data were compared using the Kaplan-Meier method and a stratified log-rank test. Results: A total of 981 pts were randomized Dec 2020–Jan 2024 globally to the Early Start (n=492) or Maintenance Start (n=489) arms. Baseline characteristics were balanced (overall: median age 60 [22–86] years, 65.1% male, 38.4% KPS =80, 38.9% MGMT methylated, 5.4% IDH mutant). ~25% of pts did not initiate the maintenance phase across both arms. Median duration of TTFields use was 7.7 months (m) (0-49) and 6.1 m (0-43) with Early and Maintenance Start, respectively. In the intention to treat (ITT) population, there was no significant difference in median OS (mOS). mOS (95% CI) was 17.7 m (16.0–18.8 ) with Early Start vs 17.5 m (15.9–19.0 ) with Maintenance Start, (HR 0.953 [95% CI 0.82–1.10]; p=0.52). 1, 2, and 3-year survival rates were 70.9% vs 72.0%, 33.9% vs 31.6%, and 22.5% vs 18.4%, respectively (all NS). PFS and ORR were not significantly different between arms. Device-related adverse events (AEs) occurred in 76.2% of Early Start pts vs. 59.2% of Maintenance Start pts but remained mostly grade 1-2 skin-related. In post hoc analysis of pts with per protocol device usage during RT/TMZ, pts with MGMT-methylated tumors showed a significant survival benefit with Early Start (mOS of 33.8 m vs 23.8 m; HR 0.683 [95% CI 0.484–0.963]; p=0.03). Conclusion: TTFields concurrent with RT/TMZ was feasible and safe. Although earlier TTFields initiation did not improve survival in the ITT population, durable long-term survival was observed regardless of TTFields start time. Post hoc analyses identified a clinically meaningful survival benefit from early TTFields initiation in pts with MGMT-methylated tumors.

📝 https://amportal.astro.org/sessions/lba-01-22916/trident-phase-3-trial-of-tumor-treating-fields-ttfields-therapy-concurrent-with-temozolomide-113296 10.1016/j.ijrobp.2026.06.2464

Combined Phase 3 RCT Confirmatory ASTRO Annual Meeting 2026

Challenges SOC

NRG-CC009

ForSCLC brain mets, no cap on BM number (median 2, IQR 1-5)

Time to neurocognitive failure safety

HR 0.83

95% CI 0.53-1.28, p=0.39; Gray's test p=0.66, not met

TL;DRNeurocognitive failure no different for SRS vs HA-WBRT + memantine in SCLC brain mets (adjusted HR 0.83, p=0.39); OS 17.4 vs 8.6 mo favoring SRS.

Why it mattersRadiation oncology

The RT read is what SRS did not cost: adjusted intracranial failure, neurological death, and salvage therapy were no different from HA-WBRT + memantine, so omitting whole-brain coverage carried no measured CNS penalty. The neurocognitive advantage that justifies SRS in other histologies did not appear here (adjusted HR 0.83, 95% CI 0.53-1.28).

Monday clinic

In SCLC with a limited number of brain mets (trial median 2, IQR 1-5), this supports SRS as an alternative to HA-WBRT + memantine; pts with many BM were eligible (range up to 26) but sparsely represented, so the read is thinner there. The longer read

10 details 2 trials watching

Design

Phase III, randomized 1:1, 151 pts assigned February 2021 to June 2026. Stratified by DS-GPA and number of BM. Median follow-up for surviving pts 9.5 months.

Population & inclusion

SCLC brain metastases, no upper limit on BM number (initially 10, later amended). Median BM 2 (range 1-26, IQR 1-5). Size and volume thresholds (5 mm from the hippocampi, 4 cm largest diameter, 30 cm total volume) print without inequality symbols in the portal text.

Radiotherapy

SRS vs HA-WBRT + memantine. Dose, fractionation, and SRS platform are not reported in source.

Endpoints

Primary: time to neurocognitive failure (HVLT-R, COWA, Trail Making), cumulative incidence with death without failure as a competing risk. Secondary: OS, intracranial progression, neurological death, salvage therapies, AEs. Powered at 85% for a 17% absolute reduction with 91 events.

Results

Primary not met; OS favored SRS. Arm-level figures are in the table. CNS control endpoints and G3-5 treatment-related AEs showed no difference in adjusted analyses, with no effect sizes given.

Endpoint	SRS	HA-WBRT + memantine	Effect (SRS arm)
Neurocognitive failure (1°)	per-arm rate not reported	per-arm rate not reported	adjusted HR 0.83 (95% CI 0.53-1.28), p=0.39
Median OS	17.4 mo	8.6 mo	adjusted HR 0.60 (95% CI 0.39-0.91), p=0.016

vs leading data

Historical SRS vs WBRT trials excluded SCLC, which left WBRT as the default here. NRG CC001 set HA-WBRT + memantine as the neurocognitive-sparing WBRT standard, so this comparator is the strongest WBRT arm available. FIRE-SCLC supplied the retrospective case for first-line SRS that this trial tests prospectively.

Applies to

SCLC brain metastases with a limited number of lesions (median 2, IQR 1-5)

Does not represent pts with extensive BM burden, who were eligible but few.

Limitations

The observed event count is not reported against the 91 events the design required. No per-arm neurocognitive failure rates, no data on systemic therapy or extracranial disease by arm, and no account of what drove the OS gap.

Discussion

The trial failed its own hypothesis and still weakens the case for WBRT: without a neurocognitive or CNS-control advantage for whole-brain treatment, the argument for it rests on habit. The OS difference is hypothesis-generating, not a tested claim.

Rationale

Randomised phase III against the WBRT standard: neurocognitive primary not met, but OS and CNS control did not favor WBRT. OS is secondary, f/u 9.5 mo.

Open questions

What drives the OS gap when intracranial failure and neurological death were no different?
Does SRS hold up in SCLC with high BM number?

active Stereotactic Radiation in Patients With Small Cell Lung Cancer and 1-10 Brain Metastases Phase NA

n=100 · primary completion 2024-04 · SRS instead of WBRT in SCLC with 1-10 BM

active Hippocampal Sparing Whole Brain Radiation Versus Stereotactic Radiation in Patients With 5-20 Brain Metastases: A Phase III, Randomized Trial Phase NA

n=196 · primary completion 2024-11 · randomised HA-WBRT vs SRS, 5-20 BM, any solid tumor
SRS dose, fractionation, and surveillance schedule used

Sourced from C. G. Rusthoven et al.

📚 Sources · 📄 1 paper

📄 PAPER C. G. Rusthoven; R. Paulus; V. Gondi et al. · ASTRO 2026 Annual Meeting (2026-09)

NRG-CC009: A Phase III Trial of Stereotactic Radiosurgery (SRS) vs. Hippocampal-Avoidant Whole Brain Radiotherapy (HA-WBRT) for Brain Metastases from Small Cell Lung Cancer (SCLC)

doi article →

Abstract

ASTRO 2026 abstract LBA 02 · PL 01 - Plenary Session · 2026-09-28 · presented by Chad Rusthoven, MD Purpose/Objective(s): SRS is the preferred treatment for brain metastases (BM) from most tumor histologies due to superior neurocognitive preservation and quality of life compared to WBRT. However, patients with SCLC BM were excluded from historical SRS trials, and WBRT has remained the standard of care in this population. In patients receiving WBRT, HA-WBRT and memantine offer superior neurocognitive preservation compared to conventional WBRT. NRG-CC009 compared SRS to HA-WBRT + memantine for patients with SCLC BM. Materials/Methods: This phase III trial enrolled patients with SCLC BM, with all BM =5 mm outside the hippocampi, =4 cm in largest diameter, and total BM volume =30 cm, without an upper limit on BM number (initially =10, subsequently amended). Patients were stratified by disease-specific graded prognostic assessment (DS-GPA) score and number of BM and randomized 1:1 to SRS or HA-WBRT + memantine. Cumulative incidence and Gray’s test were used to estimate and compare arms for the primary endpoint, time to neurocognitive failure. Assessment was conducted using the Hopkins Verbal Learning Test-Revised, Controlled Oral Word Association, and Trail Making Test, with a competing risk of death without failure. Cox proportional models were used to estimate hazard ratios (HR) with adjustment for DS-GPA and patient-specific factors. Secondary endpoints included overall survival (OS), intracranial disease progression, neurological death, salvage therapies, and adverse events (AEs). With 91 events, the study had 85% power to detect a 17% absolute reduction in neurocognitive failure between arms using a two-sided type I error of 0.05, assuming a rate of death without failure of 29.8% in both arms. Results: From February 2021 to June 2026, 151 patients were randomly assigned. Baseline characteristics were well balanced between the arms. The median number of BM was 2 (range, 1-26; interquartile range, 1-5). Median follow-up for surviving patients was 9.5 months. There was no significant difference in neurocognitive failure between the arms (Gray’s test, p=0.66; adjusted HR for SRS arm = 0.83; 95% CI, 0.53–1.28; p=0.39). OS was superior in the SRS arm (median 17.4 vs. 8.6 months; adjusted HR for SRS arm = 0.60; 95% CI, 0.39–0.91; p=0.016). No significant differences were observed in adjusted analyses of intracranial failure, neurological mortality, salvage therapy, or treatment-related grade 3-5 AEs. Conclusion: Although no difference in neurocognitive failure was observed, SRS was associated with superior OS and comparable CNS control outcomes to HA-WBRT plus memantine. These results support SRS as a standard of care option for SCLC BM.

📝 https://amportal.astro.org/sessions/pl-01-22946/nrg-cc009-a-phase-iii-trial-of-stereotactic-radiosurgery-srs-vs-hippocampal-avoidant-whole-br-114061 10.1016/j.ijrobp.2026.06.2462

Radiation Palliative Phase 3 RCT Challenges SOC ASTRO Annual Meeting 2026

Confirmatory

Alliance A071801 NCT04114981

For1-4 brain metastases, one lesion >2cm resected, postop cavity RT

Time to surgical bed failure local control

87% vs 81%

1 year surgical bed control, fSRS vs SRS, p=0.046

TL;DR1 year surgical bed control 87% vs 81% (p=0.046) favoring fSRS over single-fraction SRS after brain met resection; mOS 29 vs 20 mo.

Why it mattersRadiation oncology

Intact metastases were also treated per arm, so the OS signal (median 29 vs 20 months, HR=0.69, p=0.035) reflects a fractionation strategy across all treated lesions, not only the cavity. fSRS did not lower grade 1+ radiation necrosis (14% vs 10%), so the case for fractionating rests on control, not safety.

Monday clinic

In pts with 1 to 4 brain metastases after resection of a lesion >2cm, this supports fractionated over single-fraction cavity SRS; it does not address unresected-only disease, neoadjuvant SRS, or WBRT. The longer read

10 details 3 trials watching

Design

Phase III multi-institutional cooperative group randomized trial, 242 randomized between October 2019 and October 2022. Stratified by age (60 years cut), targeted therapy or immunotherapy use within 4 weeks after RT, and maximal resection cavity diameter (3cm cut). Median follow-up 48 months.

Population & inclusion

1 to 4 brain metastases with resection of one lesion >2cm. Baseline characteristics reported as well-balanced; median surgical cavity target volume 16.5 for fSRS and 14.8 for SRS (p=0.41, units printed as cm in source).

Radiotherapy

SRS: 12-20Gy by volume in 1 fraction. fSRS: 27Gy/3 for <30cc or 30Gy/5 for >30cc. Intact metastases received SRS or fSRS per assigned arm, so fractionation differed across all treated lesions, not only the cavity.

Endpoints

Primary: time to surgical bed failure. Secondary: local control of intact brain metastases, overall survival, radiation necrosis.

Results

Primary endpoint met in favor of fSRS, with OS and intact-lesion control moving the same direction (see table). No HR or CI for the primary endpoint in source.

Endpoint	fSRS	SRS	Effect
Surgical bed control, 1 year	87%	81%	p=0.046
Failure of treated intact mets	4%	11%	p=0.063
Median OS	29 months	20 months	HR=0.69, p=0.035
Grade 1+ radiation necrosis	14%	10%	no significant difference
Grade 1+ cerebral edema	8%	9%	no significant difference

Safety

No significant differences in adverse event rates between arms. Grade 1+ radiation necrosis 14% fSRS vs 10% SRS; grade 1+ cerebral edema 8% vs 9%. Symptomatic or higher-grade necrosis not broken out in source.

vs leading data

N107C set postoperative single-fraction SRS as a standard against WBRT, and the MD Anderson randomised trial of cavity SRS vs observation tied local failure to larger cavities. This trial tests fractionation as the answer to that size problem, a practice the source describes as often favored but lacking high-level comparison.

Applies to

pts with 1 to 4 brain metastases after resection of one lesion >2cm, treated with postoperative cavity radiosurgery

Does not represent unresected-only disease, neoadjuvant SRS candidates, or pts managed with WBRT.

Limitations

Abstract only: the time-to-event primary is reported as a 1 year rate with a p-value near threshold, with no HR, CI, or per-arm N. Cavity-size subgroup results, the split between 27Gy/3 and 30Gy/5, leptomeningeal failure, and cause of death are not reported.

Discussion

The local-control gain is modest and the survival difference is larger than that gain alone would predict, which points at intact-lesion control, neurologic death, or chance in a secondary endpoint. Authors conclude fSRS should be considered a standard of care after resection of larger brain metastasis; the necrosis data do not add a safety argument.

Rationale

Randomised cooperative-group phase III, primary endpoint met with 48-month median f/u. fSRS already often favored for large cavities per source; this supplies the missing high-level data.

Open questions

Does the fSRS benefit hold in cavities 3cm or smaller?
Postoperative fSRS vs neoadjuvant SRS for resectable brain metastasis

active Neoadjuvant vs. Intraoperative vs. Adjuvant Resection Cavity Radiotherapy of Brain Metastases Phase NA

n=90 · primary completion 2027-05 · preop vs intraop vs postop RT for resected brain mets

recruiting Trial of Preoperative Radiosurgery Versus Postoperative Stereotactic Radiotherapy for Resectable Brain Metastases Phase NA

n=200 · primary completion 2028-12 · 1-fx preop SRS vs 5-fx postop SRT; 12 mo LMD incidence

not yet Study Comparing Neoadjuvant Versus Adjuvant Stereotactic Radiotherapy of Brain Metastases Phase NA

n=68 · primary completion 2030-06 · neoadjuvant vs adjuvant SRT; local control at 6/12/24 mo
What drives the OS difference: neurologic death or intact-lesion control?

Sourced from P. D. Brown et al.

📚 Sources · 📄 1 paper

📄 PAPER P. D. Brown; K. V. Ballman; A. A. Aizer et al. · ASTRO 2026 Annual Meeting (2026-09)

Alliance A071801 Phase III Trial Postoperative Single Fraction Stereotactic Radiosurgery (SRS) vs. Fractionated SRS (fSRS) for Resected Brain Metastasis

doi article →

Abstract

ASTRO 2026 abstract LBA 01 · PL 01 - Plenary Session · 2026-09-28 · presented by Ayal Aizer, MD Purpose/Objective(s): In patients with brain metastases, post-operative SRS delivered in 1 fraction is a standard of care but local control decreases with increasing target size. To improve tumor control, fractionated SRS (fSRS) is often favored for large surgical cavities. However, there is a lack of high-level data comparing the efficacy of fSRS versus SRS. The primary objective of Alliance A071801 was to ascertain if time to surgical bed failure is increased with fSRS compared to SRS in patients with resected brain metastasis. Materials/Methods: This multi-institutional cooperative group trial randomized patients with 1 to 4 brain metastases to either SRS (12-20Gy by volume) or fSRS (27Gy/3 <30cc or 30Gy/5 > 30cc) after resection of one lesion > 2cm. Intact metastases were treated with either SRS or fSRS per study arm. Stratification included age (< 60 years vs. = 60 years), use or planned use of either targeted therapy or immunotherapy within 4 weeks after radiotherapy, and maximal diameter of the resection cavity (=3cm vs. >3cm). The primary endpoint was time to surgical bed failure. Major secondary endpoints included local control of intact brain metastases, overall survival, and radiation necrosis. Results: Between October 2019 and October 2022, 242 patients were randomized. Baseline characteristics were well-balanced. Median surgical cavity target volumes were 16.5 cm for fSRS and 14.8 cm for SRS (p=0.41). With a median follow-up of 48 months, surgical bed control was significantly higher in the fSRS arm as compared to the SRS arm (1 year rate 87% versus 81%, p=0.046). Failure of treated, unresected brain metastases occurred in 11% with SRS versus 4% with fSRS (p=0.063). Overall survival (OS) favored fSRS over SRS (median OS 29 versus 20 months; p=0.035; stratified Cox HR=0.69). A stratified multivariable model that included the other baseline variables found a similar association between study arm and OS (HR=0.68; p=0.032). There were no significant differences in adverse event rates between study arms; grade 1+ radiation necrosis and cerebral edema were 14% and 8% in the fSRS arm and 10% and 9% in the SRS arm, respectively. Conclusion: After resection of larger brain metastasis, fSRS offers superior surgical bed control and should be considered a standard of care. Support: U10CA180821, U10CA180882; NCT04114981; https://acknowledgments.alliancefound.org

📝 https://amportal.astro.org/sessions/pl-01-22946/alliance-a071801-phase-iii-trial-postoperative-single-fraction-stereotactic-radiosurgery-srs-114060 10.1016/j.ijrobp.2026.06.2461

Radiation Palliative Phase 3 RCT Confirmatory ASTRO Annual Meeting 2026

Prostate

Toxicity and selection rather than efficacy: late G3 GU AEs with postop hypofractionation, 5y sexual function after SBRT vs prostatectomy, and GC as a prognostic (not predictive) marker at salvage RT.

Caveats dominate

PACE-A (sexual function, 5-year) NCT01584258

ForLocalised prostate cT1-T2, Gleason ≤3+4, PSA ≤20, surgical candidates, no ADT

TL;DR5y median EPIC-26 sexual score change -42 after prostatectomy vs -17 after SBRT (p=0.02); IIEF-5 median 5 vs 19 (p<0.001).

Why it mattersRadiation oncology

No ADT was permitted, so the SBRT trajectory (median EPIC-26 79 to 58) is attributable to 36.25Gy/5 fractions alone, not a hormonal confound. By the trial's own p<0.01 rule only IIEF-5 (median 19 vs 5) is positive, and clinician-graded ED was similar (27% vs 35%). Counselling data, not a claim of preserved function.

Monday clinic

In men with cT1-T2, Gleason ≤3+4 localised prostate cancer who are prostatectomy candidates and weight erectile function heavily, this informs the SBRT vs surgery discussion with randomised 5-year PRO data; it does not extend to disease treated with ADT or address cancer control. The longer read

Also covered Sep 28

12 details

Design

PACE is a phase III open-label multiple-cohort RCT; PACE-A randomised 1:1 to SBRT or prostatectomy. 123 randomised (60 prostatectomy, 63 SBRT) between August 2012 and February 2022. Sexual outcomes analysed by treatment received.

Population & inclusion

Early localised prostate cancer, cT1-T2, Gleason ≤3+4, PSA ≤20 ng/mL, and suitable for prostatectomy. Baseline median EPIC-26 sexual domain score was 62 in the prostatectomy group and 79 in the SBRT group.

Radiotherapy

36.25Gy/5 fractions delivered in 1-2 weeks. ADT not permitted. Platform, margins and target volume not stated in source.

Regimen

Comparator was prostatectomy by open, laparoscopic or robot-assisted approach. Nerve-sparing status not stated in source.

Endpoints

Co-primary (previously reported): 2-year bowel and urinary symptoms. Secondary, reported here through 5 years: EPIC-26 sexual domain score, proportion with MCID (≥11-point reduction), IIEF-5, clinician-reported CTCAE grade ≥2 erectile dysfunction. Significance threshold p<0.01.

Results

All patient-reported measures favoured SBRT in direction; only IIEF-5 met the prespecified p<0.01 threshold. Clinician-graded erectile dysfunction was similar between groups.

Endpoint	SBRT	Prostatectomy	p
EPIC-26 sexual domain, median baseline → 5y	79 → 58	62 → 17	n/a
EPIC-26 median change from baseline	-17 (IQR -43 to 0)	-42 (IQR -58 to -24)	0.02
MCID (≥11-point reduction)	19/35 (54%)	18/22 (82%)	0.03
IIEF-5 median	19	5	<0.001
CTCAE G≥2 erectile dysfunction	13/48 (27%)	13/37 (35%)	0.48

vs leading data

ProtecT randomised prostatectomy against external beam RT given with ADT, so its sexual-function comparison carried a hormonal confound that PACE-A avoids. PACE-A is described by its authors as the first randomised comparison of SBRT and prostatectomy with long-term sexual outcomes.

Applies to

men with cT1-T2, Gleason ≤3+4, PSA ≤20 ng/mL localised prostate cancer who are fit for prostatectomy and treated without ADT

Does not represent higher-risk disease, men receiving ADT with RT, or men unfit for surgery.

Limitations

Baseline sexual scores were unbalanced (median 62 vs 79), and the MCID analysis rests on 22 and 35 men. Surgical approach was mixed and nerve-sparing use is not reported. Accrual ran from 2012 to 2022, so technique on both sides spans a decade.

Discussion

The direction is consistent across three patient-reported measures, which carries more weight than any single p-value here. SBRT still produced a decline (median change -17), so the result is a relative advantage, not preserved function. Cancer control is not reported in this abstract.

Enrolment

CONSORT flow

Randomized123

↓

SBRT

allocated 63

Prostatectomy

allocated 60

Rationale

Secondary PRO endpoint, open-label, analysed as treated; EPIC-26 and MCID p-values miss the trial's own p<0.01 threshold. PRO return 60% and 63% at 5y.

Open questions

Does the sexual-function gap hold against nerve-sparing robotic prostatectomy alone?
Does SBRT erectile function keep declining beyond 5 years?
Oncologic outcomes for SBRT vs prostatectomy in PACE-A

Sourced from B. Yasar et al.

📚 Sources · 📄 1 paper

📄 PAPER B. Yasar; J. Patel; A. Tree et al. · ASTRO 2026 Annual Meeting (2026-09)

Long term outcomes of sexual function in the PACE-A trial: A multicentre randomised study of radical prostatectomy vs stereotactic body radiotherapy (SBRT) for early localised prostate cancer

doi article →

Abstract

ASTRO 2026 abstract LBA 10 · LBA 01 - Late-breaking Abstract Session · 2026-09-29 · presented by Nicholas van As, MD, MB Purpose/Objective(s): Treatment selection for early localised prostate cancer (LPCa) is largely driven by functional outcomes. We aimed to compare long-term sexual function, a key and often distressing side effect, following prostatectomy versus stereotactic body radiotherapy (SBRT). Materials/Methods: PACE (NCT01584258) is a phase III open-label multiple-cohort randomised control trial. In PACE-A, men with LPCa (cT1-T2, Gleason score =3+4, PSA =20 ng/mL) and suitable for prostatectomy were randomised (1:1) to SBRT or prostatectomy. SBRT dose was 36.25Gy/5 fractions in 1-2 weeks. Prostatectomy could be open, laparoscopic, or robot assisted. Androgen deprivation therapy was not permitted. Previously reported co-primary endpoints were 2-year bowel and urinary symptoms. Secondary sexual function outcomes, reported here through 5 years, included the EPIC-26 sexual domain score, the proportion of patients experiencing a minimally clinically important deterioration (MCID =11-point reduction), IIEF-5 score, and clinician-reported CTCAE grade =2 erectile dysfunction. Analyses were performed according to treatment received. A p-value <0.01 was considered statistically significant. Results: Between August 2012 and February 2022, 123 participants were randomised (60 prostatectomy; 63 SBRT). Fifty patients received prostatectomy as allocated (1 SBRT, 3 chemoradiotherapy, 6 withdrew), while 60 received SBRT as allocated (2 prostatectomy, 1 withdrew). At 5 years, participant- and clinician-reported data were available for 30/50 (60%) and 43/50 (86%) of the prostatectomy group, and 38/60 (63%) and 57/60 (95%) of the SBRT group. At 5 years, sexual function was significantly worse following prostatectomy than SBRT. Over the 5-year period, median EPIC-26 sexual domain scores declined from 62 to 17 after prostatectomy and from 79 to 58 after SBRT; median change from baseline: -42 (IQR: -58 to -24) and -17 (IQR: -43 to 0) respectively (p = 0.02). A greater proportion of prostatectomy patients had reductions exceeding the MCID: (18/22 [82%] vs 19/35 [54%]; p=0.03). IIEF-5 scores were also lower following prostatectomy (median 5 vs 19; p<0.001). Rates of clinician-reported CTCAE grade =2 erectile dysfunction were similar between groups (13/37 [35%] vs 13/48 [27%]; p=0.48). Conclusion: PACE-A provides the first randomised comparison of SBRT and prostatectomy for localised prostate cancer with long-term patient- and clinician-reported sexual outcomes. Prostatectomy was associated with substantially greater deterioration in sexual function and worse overall sexual outcomes than SBRT at 5 years, providing important information for shared treatment decision-making.

📝 https://amportal.astro.org/sessions/lba-01-22916/long-term-outcomes-of-sexual-function-in-the-pace-a-trial-a-multicentre-randomised-study-of-r-114059 10.1016/j.ijrobp.2026.06.3107

Radiation Curative Phase 3 RCT Caveats dominate ASTRO Annual Meeting 2026

Caveats dominate

NRG/RTOG 9601 (transcriptomic analysis)

ForProstate cancer, salvage RT ± high-dose bicalutamide, GC score available

TL;DRSecondary analysis, n=352, 18.2y median f/u: GC per 0.1 prognostic for PCSM, sHR 1.34 (1.17-1.54); AAT benefit by GC showed no significant interaction.

Why it mattersRadiation oncology

The sRT decision in play is hormone omission at low pre-sRT PSA: at PSA <0.7, 15y PCSM benefit from AAT was -2% with GC <0.6 vs 16% with GC ≥0.6. At PSA ≥0.7 the gradient reverses (12% vs 6%), so GC here ranks risk more reliably than it selects for hormones.

Monday clinic

In sRT candidates with pre-sRT PSA <0.7 and GC <0.6, this informs the discussion of sRT without hormone therapy as hypothesis-level evidence (15y PCSM benefit with AAT -2%); it does not extend to contemporary ADT, which this trial did not test. The longer read

11 details

Design

Secondary analysis of NRG/RTOG 9601, a phase 3 trial of sRT ± high-dose bicalutamide, using GC scores (Veracyte) from a prior translational project. GC-available cohort n=352, median follow-up 18.2 years. Multivariable Cox or Fine-Gray models, adjusted (s)HR with 95% CI.

Population & inclusion

Pts treated with sRT on NRG/RTOG 9601 who had a GC score. Median GC 0.59 (Q1-Q3 0.42-0.76); 29%, 23%, 38% and 11% were low, intermediate, high and very high risk. Other baseline features not reported in source.

Regimen

sRT with or without high-dose bicalutamide (AAT). Bicalutamide dose and duration not reported in source.

Radiotherapy

Salvage RT in both arms. Dose, fractionation and target volume not reported in source.

Endpoints

Primary objective: prognostic impact of GC (per 0.1) on PCSM. Secondary: OS, MFS, DM. Additional: PCSM and OS by pre-defined GC strata, and PCSM benefit of AAT by GC (<0.6 vs ≥0.6) within pre-sRT PSA subgroup (<0.7 vs ≥0.7).

Results

GC was independently prognostic for every profiled endpoint (tables above). The AAT-by-GC estimates are absolute 15-year PCSM differences with no significant interaction in either PSA stratum.

Endpoint	Adjusted (s)HR	95% CI
PCSM (primary objective)	sHR 1.34	1.17-1.54
OS	HR 1.18	1.09-1.27
MFS	HR 1.16	1.08-1.25
DM	sHR 1.20	1.07-1.35

Endpoint at 15 years	Low GC	Very high GC	Difference
PCSM	4%	52%	48%
OS	75%	25%	50%

Pre-sRT PSA	GC <0.6	GC ≥0.6
<0.7	-2%	16%
≥0.7	12%	6%

vs leading data

Extends the earlier GC validation in this same trial with final outcomes, and layers GC onto the prior 9601 finding that pre-sRT PSA predicts AAT benefit. GETUG-AFU 16, NRG/RTOG 0534 (SPPORT) and RADICALS-HD tested ADT with post-prostatectomy RT; none is addressed in this source.

Applies to

pts given sRT ± high-dose bicalutamide on NRG/RTOG 9601 with a GC score available (n=352)

Does not represent pts receiving contemporary ADT with sRT, which this analysis did not test.

Limitations

AAT benefit by GC is given as point estimates only: no CIs, no cell sizes. PCSM was chosen as primary for this secondary analysis because of suspected other-cause mortality with bicalutamide, which sets aside the endpoint where AAT harm would show. Whether the GC-available subset matches the full trial is not reported.

Discussion

The prognostic claim is well supported at long follow-up. The predictive claim is not: the GC gradient runs in opposite directions in the two PSA strata. The authors frame GC-guided selection for modern ADT in early sRT as a hypothesis, which is the right ceiling.

Rationale

Secondary biomarker analysis of a GC-available subset; predictive claim rests on non-significant interactions, and the hormone agent was high-dose bicalutamide, not contemporary ADT.

Open questions

Does GC predict benefit from contemporary ADT with early sRT?
Do intermediate and high GC strata separate on 15-year PCSM and OS?
Does the AAT-by-GC pattern hold for OS, not just PCSM?

Sourced from K. Patel et al.

📚 Sources · 📄 1 paper

📄 PAPER K. Patel; E. Feng; E. Walker et al. · ASTRO 2026 Annual Meeting (2026-09)

Long-Term Transcriptomic Analysis of NRG/RTOG 9601: A Phase 3 Study of Salvage Radiotherapy for Prostate Cancer with or without Anti-Androgen Therapy

doi article →

Abstract

ASTRO 2026 abstract 315 · SS 36 - Predicting Benefit and Toxicity: Biomarkers in Prostate Radiotherapy · 2026-09-29 · presented by Krishnan Patel, MD Purpose/Objective(s): The prognostic utility of a genomic classifier (GC) on overall survival (OS), prostate cancer-specific mortality (PCSM), and distant metastasis (DM) after salvage radiotherapy (sRT) was previously validated in NRG/RTOG 9601, a phase 3 trial of sRT ± high-dose bicalutamide [anti-androgen therapy (AAT)]. A separate analysis of NRG/RTOG 9601 showed that AAT may increase cardiovascular mortality and that pre-sRT PSA was predictive of the benefit from AAT. Here, we update the prior work with final outcomes data from NRG/RTOG 9601 to characterize the clinical utility of modern clinico-transcriptomic risk stratification. Materials/Methods: This is a secondary analysis of NRG/RTOG 9601 with GC scores (Veracyte; San Diego, CA) from a prior National Clinical Institute-translational science project. The primary objective was to estimate the prognostic impact of GC score (per 0.1) on PCSM, and secondarily on OS, metastasis-free survival (MFS), and DM. Additional objectives were the estimation of PCSM and OS by pre-defined GC strata [low (=0.4), intermediate (0.4-0.6), high (0.6-0.85), and very high (>0.85)] and the estimation of the PCSM benefit of AAT by GC (<0.6 vs =0.6) within pre-sRT PSA subgroup (<0.7 vs =0.7). PCSM was selected as the primary endpoint in this secondary analysis to evaluate disease-specific prognosis and AAT treatment effect, given the suggestion of increased other-cause mortality with high-dose bicalutamide, which may not occur with contemporary androgen deprivation therapy (ADT). Multivariable Cox or Fine-Gray models were fit and adjusted (subdistribution) hazard ratios [(s)HR] were reported with 95% confidence intervals. Results: A total of 352 patients were included in the GC-available cohort with a median follow-up of 18.2 years. The median GC score was 0.59 (Q1-Q3: 0.42-0.76), and 29%, 23%, 38%, and 11% had low, intermediate, high, and very high GC risk scores, respectively. GC was independently prognostic for all profiled endpoints [sHR PCSM 1.34 (1.17-1.54); HR OS 1.18 (1.09-1.27); HR MFS 1.16 (1.08-1.25); sHR DM 1.20 (1.07-1.35); all p=0.002]. Furthermore, there was a clinically meaningful difference in prognosis between the low and very high GC subgroup at 15 years: ?PCSM 15-Year of 48% (4% vs. 52%) and ?OS 15-Year of 50% (75% vs. 25%). Within the high pre-sRT PSA (=0.7) subgroup, the absolute improvement in 15 year PCSM with AAT was clinically meaningful across GC risk (GC<0.6: 12%; GC=0.6: 6%), whereas in the low pre-sRT PSA (<0.7) subgroup, only the high GC risk patients derived a clinically meaningful 15-year PCSM benefit (GC<0.6: -2%; GC=0.6: 16%). However, there was no significant interaction between GC and AAT effect within either PSA strata (both p>0.05) likely due to limited power. Conclusion: With the long-term update of NRG/RTOG 9601, GC score continues to provide clinically meaningful prognostic information beyond clinical data. These analyses support the hypothesis that GC may have clinical utility in selecting early sRT candidates for modern ADT.

📝 https://amportal.astro.org/sessions/ss-36-22888/long-term-transcriptomic-analysis-of-nrg-rtog-9601-a-phase-3-study-of-salvage-radiotherapy-fo-112073 10.1016/j.ijrobp.2026.06.227

Combined Curative Caveats dominate ASTRO Annual Meeting 2026

Confirmatory

NRG-GU003

ForPostprostatectomy, pT2/3 pNX/0: detectable PSA, or undetectable with pT3/margin+

TL;DR5-yr: G3 GU AEs 13% HYPORT (62.5 Gy/25 fx) vs 3% COPORT (66.6 Gy/37 fx), p=0.003; EPIC scores and 5-yr BF (21% vs 18%) no different.

Why it mattersRadiation oncology

Physician-graded and patient-reported toxicity diverge: grade 3 cystitis (7% vs 0%) and hematuria (6% vs 0.7%) are higher with 62.5 Gy/25 fx, yet 5-yr EPIC urinary change (-8.0 vs -5.7, p=0.4) does not separate, on 56% EPIC compliance. The decision is prostate-bed hypofractionation with a disclosed bleeding-type GU risk, not a toxicity-neutral swap.

Monday clinic

In men after prostatectomy with pT2/3 pNX/0 disease and a detectable PSA, or an undetectable PSA with pT3 or margin-positive pT2, this supports prostate-bed HYPORT as an option alongside COPORT; it does not extend to pelvic nodal RT, which the source does not report. The longer read

12 details 3 trials watching

Design

Phase 3 trial, 296 men randomized (152 COPORT, 144 HYPORT). This is the 5-year report; median follow-up 7 years (range: 0 to 8). Blinding, stratification and site count are not stated in source.

Population & inclusion

Postprostatectomy men with either a detectable post-op PSA (source prints "=0.1 ng/mL") and pT2/3 pNX/0 disease, or an undetectable PSA (<0.1 ng/mL) with pT3 disease or pT2 with a positive surgical margin. The split between these two groups is not reported in source.

Radiotherapy

HYPORT: 62.5 Gy to the prostate bed in 25 fractions of 2.5 Gy. COPORT: 66.6 Gy in 37 fractions of 1.8 Gy, 48% more fractions. Pelvic nodal RT, technique and ADT use are not reported in source.

Endpoints

Primary (reported at 2 years): patient-reported GU and GI toxicity by EPIC, where HYPORT was noninferior. Secondary, reported here: EQ-5D quality of life, AEs, overall survival, prostate-cancer specific survival, and biochemical failure (PSA 0.4 ng/mL and rising; source prints the operator as "=").

Results

Arm-level figures are in the table. No difference in 5-yr EPIC bowel or urinary change scores, EQ-5D change, or 5-yr BF; 31 deaths, 4 (13%) due to prostate cancer.

Endpoint	HYPORT	COPORT	p
Grade 3 AEs	16% (23 men)	7% (11 men)	p=0.02
Grade 3 renal and urinary disorders	13% (18 men)	3% (5 men)	p=0.003
Noninfective cystitis	7%	0%	not reported
Hematuria	6%	0.7%	not reported
5-yr EPIC bowel change score	-2.0	0.6	p=0.1
5-yr EPIC urinary change score	-8.0	-5.7	p=0.4
EQ-5D change, baseline to 5 yr	0.0	-0.01	p=0.5
5-yr biochemical failure	21%	18%	p=0.3

Safety

Grade 3 AEs 16% (23 men) HYPORT vs 7% (11 men) COPORT, p=0.02, driven by grade 3 renal and urinary disorders, 13% vs 3% (p=0.003): noninfective cystitis 7% vs 0%, hematuria 6% vs 0.7%. No grade 4-5 RT-related AEs, one grade 3 stricture (COPORT), and time to grade 3 AEs did not differ (p=0.4).

vs leading data

Moderate hypofractionation for the intact prostate rests on large randomized trials such as CHHiP and PROFIT; the postoperative bed has lacked comparable randomized data. The authors state the grade 3 GU rates, including the excess with HYPORT, were consistent with contemporary series, which the source does not name.

Applies to

men after prostatectomy with pT2/3 pNX/0 disease and a detectable PSA, or an undetectable PSA with pT3 or margin-positive pT2, treated to the prostate bed

Does not represent pelvic nodal RT or any setting outside these eligibility groups, and ADT use is not reported in source.

Limitations

The patient-reported reassurance rests on 56% EPIC and 51% EQ-5D compliance at 5 years, with no account of who dropped out. BF is a secondary endpoint with no stated noninferiority margin, and p-values for the cystitis and hematuria differences are not given.

Discussion

HYPORT buys a shorter course at the cost of a physician-reported grade 3 cystitis/hematuria excess that patient-reported scores do not register. Biochemical control looks comparable (5-yr BF 21% vs 18%, p=0.3) but the trial was built around toxicity, so equivalence of disease control is suggested, not established.

Enrolment

CONSORT flow

Randomized296

↓

HYPORT

allocated 144

COPORT

allocated 152

Rationale

Phase 3 RCT with its primary PRO noninferiority endpoint met at 2 yr; 5-yr update agrees on PROs and BF but adds a physician-reported G3 GU excess. Abstract only.

Open questions

Does prostate-bed hypofractionation hold with pelvic nodal RT or concurrent ADT?
Ultrahypofractionated (SBRT) prostate-bed RT vs moderate hypofractionation

recruiting Post-prostatectomy Radiation Therapy--Moderate Versus Ultra-hypofractionated (Also Known as Stereotactic Body Radiation Therapy [SBRT]) Phase 2

n=136 · primary completion 2026-11 · randomized ph2 SBRT vs mod hypofx post-RP, 2-yr QOL

recruiting Salvage Stereotactic Body Radiotherapy of the Prostate Bed for Biochemical Recurrence After Radical Prostatectomy. Phase NA

n=284 · primary completion 2029-02 · randomized ph2/3 salvage bed SBRT vs SOC RT

not yet RIsk aDapted Stereotactic Radiotherapy vs. standarD of Care Radiotherapy in Patients With Prostate Cancer in the Adjuvant or saLvage sEtting With or Without Lymph Node Irradiation (RIDDLELN) - A Phase III Trial Phase 3

n=206 · primary completion 2031-09 · ph3 5-fx bed SBRT vs mild hypofx, PRO QOL non-inferiority
Do grade 3 cystitis/hematuria events keep accruing beyond 7-yr follow-up?

Sourced from M. K. Buyyounouski et al.

📚 Sources · 📄 1 paper

📄 PAPER M. K. Buyyounouski; M. Borges; R. C. Chen et al. · ASTRO 2026 Annual Meeting (2026-09)

Five-Year Results of a Phase 3 Trial of Hypofractionated vs. Conventional Postprostatectomy Radiotherapy: NRG Oncology GU003

doi article →

Abstract

ASTRO 2026 abstract 7 · CT 01 - Clinical Trials Session · 2026-09-27 · presented by Mark Buyyounouski, MD, MS, FASTRO Purpose/Objective(s): Biopsy Gleason 8–10 disease and MRI-suspected extracapsular extension identify men at high risk for adverse pathologic features at prostatectomy, observed in ~55–75% of cases. For a substantial subset, surgery alone is not curative, and PSA recurrence leads to radiotherapy (RT) to preserve curative intent. Conventionally fractionated postprostatectomy RT (COPORT) requires 37 fractions, 48% more than hypofractionated RT (HYPORT). In the primary 2-year analysis of this trial, HYPORT was noninferior to COPORT for patient-reported genitourinary and gastrointestinal toxicity. We now report longer-term 5-year results. Materials/Methods: A total of 296 men were randomized (152 to COPORT and 144 to HYPORT). Men with a detectable post-op PSA (=0.1 ng/mL) with pT2/3pNX/0 disease or an undetectable PSA (<0.1 ng/mL) with either pT3 or pT2 disease with a positive surgical margin were eligible. HYPORT was 62.5 Gy to the prostate bed in 25 fractions of 2.5 Gy. COPORT was 66.6 Gy in 37 fractions of 1.8 Gy. Patient-reported GU and GI toxicity was measured using the Expanded Prostate Index Composite (EPIC). Other secondary endpoints include quality of life as measured by EQ-5D, adverse events (AEs), overall survival, prostate-cancer specific survival, and biochemical failure (BF; PSA = 0.4 ng/mL and rising). Results: No grade 4–5 AEs related to RT were reported. Grade 3 AEs occurred in 7% (11 men) with COPORT and 16% (23 men) with HYPORT (p=0.02). Grade 3 renal and urinary disorders occurred in 3% (5 men) with COPORT and 13% (18 men) with HYPORT (p=0.003). This difference reflected higher rates of noninfective cystitis (0% vs 7%) and hematuria (0.7% vs 6%) with HYPORT vs COPORT. There was only one grade 3 urinary tract obstruction (stricture) on the COPORT arm. Time to grade 3 AEs did not differ between arms (p=0.4). At 5 years, EPIC compliance was 56% (58% in the COPORT arm and 55% in the HYPORT arm), while EQ-5D compliance was 51% in both arms. No significant differences were observed in 5-year EPIC bowel (0.6 vs -2.0; p=0.1) or urinary change scores (-5.7 vs -8.0; p=0.4) between COPORT and HYPORT. No significant difference was observed in EQ-5D score change from baseline to 5 years between COPORT and HYPORT (-0.01 vs 0.0; p=0.5). Median follow-up is 7 years (range: 0 to 8). A total of 31 deaths have been reported (14 on COPORT and 17 on HYPORT), 4 (13%) due to prostate cancer. There was no difference in BF (5-year rate: 18% for COPORT vs. 21% for HYPORT; p=0.3). Conclusion: The rates of grade 3 GU AEs (3% with COPORT and 13% with HYPORT), including the higher incidence with HYPORT and the predominance of cystitis and hematuria, were consistent with contemporary series. Despite a small absolute increase in physician-reported cystitis (7%) and hematuria (5%), HYPORT showed no differences in patient-reported outcomes compared with COPORT and comparable biochemical control, supporting HYPORT as an effective, patient-centered, and acceptable treatment approach.

📝 https://amportal.astro.org/sessions/ct-01-22948/five-year-results-of-a-phase-3-trial-of-hypofractionated-vs-conventional-postprostatectomy-ra-113319 10.1016/j.ijrobp.2026.06.009

Radiation Curative Phase 3 RCT Confirmatory ASTRO Annual Meeting 2026

GI Upper

Preop RT schedule in PDAC after neoadjuvant chemo: chemo-RT did not lower path node positivity vs SBRT, with survival numerically favoring chemo-RT and none significant.

Early signal

SOFT Preop

ForResectable, borderline or LA type A PDAC, ECOG 0-2, post >1 mo neoadj chemo

Pathologic node positivity surrogate

41% vs 38%

SBRT vs Chemo-RT, p = 0.754, ns; chemo-RT superiority hypothesis not met

TL;DRPath node positivity 41% SBRT vs 38% chemo-RT (p = 0.754) preop in PDAC; mOS 26.04 vs 42.96 mo (p= 0.639); QOL favored SBRT.

Why it mattersRadiation oncology

Local/regional recurrence split 6 SBRT vs 2 chemo-RT (8 events, 7.8%) at median follow-up 3.4 years, with elective nodes at 25 Gy/5 and primary at 33-40 Gy in 5, mostly on 1.5 T adaptive MR guidance. The preop fractionation choice moves toward SBRT on QOL only where that nodal volume and platform are reproduced.

Monday clinic

In resectable, borderline, or LA type A PDAC already through >1 month of neoadjuvant chemo and planned for preop RT, this informs choosing 5-fraction SBRT over 28-fraction chemo-RT on QOL grounds; it does not address whether preop RT adds to chemo alone. The longer read

11 details 1 trial watching

Design

Prospective, randomized phase II, 1:1 allocation after neoadjuvant chemo. 102 pts targeted and enrolled, anticipating a 15% drop out before surgery; 4 withdrew after enrollment. Median follow-up among all enrolled pts 3.4 [2.6, 5.1] years.

Population & inclusion

Resectable, borderline, or locally advanced (LA) type A PDAC, ECOG 0-2, > 1 month of neoadjuvant chemo. Median age 65 (34-82); 38%/42%/20% resectable, borderline, and LA type A. Prior chemo was FOLFIRINOX (79%), gemcitabine/nab-paclitaxel (12%), or other (9%), with 92% receiving more than 2 months.

Radiotherapy

Chemo-RT: 50.4 Gy/28 fractions with weekly gemcitabine or capecitabine. SBRT: 25 Gy/5 to elective nodes and 33-40 Gy in 5 to the primary, without concurrent chemo. Most SBRT pts were treated using 1.5 T adaptive MRI guidance.

Endpoints

Primary: pathologic node positivity, hypothesizing lower rates with chemo-RT. Secondary: PFS, OS, patient-reported QOL (PROMIS), physician-reported toxicity, surgical complications, translational endpoints.

Results

Arm-level figures are in the table. 83/98 (84.7%) completed all intended therapy including surgical resection, equal in both arms.

Endpoint	SBRT	Chemo-RT	p
Path node positivity	41%	38%	p = 0.754
Median OS	26.04 mo (95% CI 17.9 to 59.28)	42.96 mo (95% CI 18.72 to 54.72)	p= 0.639
Alive at 3 years	42.6%	57.5%	p = 0.198
PFS	14.28 mo (95% CI 9-29.64)	21.6 mo (95% CI 10.56-38.04)	p = 0.96
Local/regional recurrence (events)	6	2	not reported
Completed all therapy incl. resection	41	42	not reported

Safety

No difference in surgical complications; no rates given. Physician-reported toxicity was a secondary endpoint but is not reported in the abstract. PROMIS physical function, global physical health, and fatigue were better preserved with SBRT (p = < 0.05).

vs leading data

Alliance A021501 tested preop SBRT or hypofractionated RT against chemotherapy alone, and PREOPANC established gemcitabine-based preop chemo-RT against upfront surgery. Neither compared one RT schedule with another. The authors describe this as the first randomized trial comparing SBRT with chemo-RT in the neoadjuvant setting for PDAC.

Applies to

resectable, borderline, or LA type A PDAC, ECOG 0-2, after > 1 month of neoadjuvant chemo and planned for preop RT then resection

Does not represent pts with no neoadjuvant chemo or those not headed to surgical resection.

Limitations

Abstract only: no per-arm allocation counts, no QOL magnitudes or timepoints, and no figures for pathologic response or margin negativity despite the conclusion citing them. QOL is patient-reported in an unblinded comparison. Concurrent agent varied in the chemo-RT arm and primary SBRT dose ranged 33-40 Gy.

Discussion

The trial shows SBRT is deliverable preop with equal resection completion and better QOL, and it does not show nodal sterilization differs. It does not settle survival equivalence: median OS 26.04 vs 42.96 mo and LRR 6 vs 2 point the same direction in a sample too small to resolve them.

Rationale

Randomised phase II, N=102, built to show chemo-RT superiority on nodal positivity and null. Not an equivalence design; survival and LRR lean numerically toward chemo-RT.

Open questions

Is preop SBRT non-inferior to chemo-RT for OS in PDAC?
Does 25 Gy/5 elective nodal SBRT give adequate regional control?
Does any preop RT add to neoadjuvant FOLFIRINOX alone?

recruiting Preoperative mFOLFIRINOX (or Gem-Nab-P) +/- Isotoxic High-dose SBRT for Borderline Resectable Pancreatic Adenocarcinoma Phase 2

n=256 · primary completion 2027-12 · preop mFOLFIRINOX +/- isotoxic high-dose SBRT in BRPC

Sourced from W. A. Hall et al.

📚 Sources · 📄 1 paper

📄 PAPER W. A. Hall; S. Tsai; A. Banerjee et al. · ASTRO 2026 Annual Meeting (2026-09)

A Randomized, Phase II Clinical Trial of Stereotactic Body Radiation Therapy Or Conventionally Fractionated Concurrent Chemotherapy and Radiation Therapy Preoperatively for Pancreatic Adenocarcinoma, the SOFT Preop Study

doi article →

Abstract

ASTRO 2026 abstract LBA 08 · LBA 01 - Late-breaking Abstract Session · 2026-09-29 · presented by William Hall, MD Purpose/Objective(s): Neoadjuvant therapy for operable PDAC has become a standard of care, yet the optimal sequence and duration of therapies remain less well defined. We conducted a prospective, randomized, phase II trial testing two different modalities of RT preoperatively. Materials/Methods: Eligibility criteria included resectable, borderline, or locally advanced (LA) type A PDAC , ECOG 0-2, and > 1 month of neoadjuvant chemotherapy (chemo). Patients were enrolled and randomized 1:1 after neoadjuvant chemo to: RT with concurrent chemo (Chemo-RT: 50.4 Gy/28 fractions with weekly gemcitabine or capecitabine); versus, stereotactic body RT (SBRT: 25 Gy/5 to elective nodes and 33-40 Gy in 5 to the primary without concurrent chemo). Most patients in the SBRT cohort were treated using 1.5 T adaptive MRI guidance. The primary endpoint was pathologic node positivity hypothesizing that chemo-RT would have lower rates of nodal positivity. Secondary endpoints included: progression-free survival (PFS), overall survival (OS), patient-reported quality of life (QOL), physician-reported toxicity, surgical complications, and translational endpoints. 102 patients were targeted for enrollment, anticipating a 15% drop out before surgery. Patient-reported QOL was assessed using the PROMIS instrument. Results: 102 patients were enrolled; 4 withdrew after enrollment. Median age was 65 (34-82), 38%/42%/20% were resectable, borderline, and LA type A respectively. 92% of patients had more than 2 months of chemotherapy before enrollment, including FOLFIRINOX (79%), gemcitabine/nab-paclitaxel (12%), or other (9%). 83/98 (84.7%) completed all intended therapy to include surgical resection; equal in both arms (41 SBRT and 42 Chemo-RT). The rate of node positivity was 41% (SBRT) vs 38% (Chemo-RT), p = 0.754. Median OS in all patients (measured from date of enrollment) was 26.04 mo (95% CI 17.9 to 59.28) in the SBRT cohort and 42.96 mo (95% CI 18.72 to 54.72) in the Chemo-RT cohort, p= 0.639. At 3 years from date of enrollment, 42.6% of the SBRT cohort, and 57.5% of the Chemo-RT cohort were alive, p = 0.198. PFS was 14.28 mo in the SBRT cohort (95% CI of 9-29.64) and 21.6 mo in the chemo-RT (95% CI 10.56-38.04), p = 0.96. Local/regional recurrence occurred in 8 (7.8%) of patients (6 SBRT and 2 chemo-RT) with a median follow - up among all enrolled patients of 3.4 [2.6, 5.1] years. There was no difference in surgical complications. Patient reported QOL was better preserved across physical function, global physical health, and fatigue using SBRT compared to Chemo-RT (p = < 0.05). Conclusion: In the first randomized trial comparing SBRT with Chemo-RT in the neoadjuvant setting for PDAC, there was no difference in node positivity, completed surgical resection, pathologic response, margin negativity, PFS, or OS. SBRT was associated with a significant preservation in QOL compared with Chemo-RT. This is one of the first prospective randomized trials comparing two different RT types and supporting SBRT in the neoadjuvant setting for PDAC.

📝 https://amportal.astro.org/sessions/lba-01-22916/a-randomized-phase-ii-clinical-trial-of-stereotactic-body-radiation-therapy-or-conventionally-114057 10.1016/j.ijrobp.2026.06.3105

Radiation Curative Phase 2 trial Early signal ASTRO Annual Meeting 2026

Head & Neck

Weekly cisplatin was not less toxic than Q3 with 70 Gy in p16-negative SCCHN, and 6-month LRF ran 9.6% vs 4.6%.

Confirmatory

NRG-HN009 (p16-negative phase II toxicity)

Forp16-negative locoregionally advanced SCCHN, 70 Gy RT + concurrent cisplatin

Acute toxicity T-score ratio (weekly/Q3) safety

T-score ratio 1.11

90% upper confidence bound 1.33, p=0.77 · phase III criteria not met

TL;DRT-score ratio (weekly/Q3) 1.11, p=0.77: weekly cisplatin not less toxic with 70 Gy in p16-negative locoregionally advanced SCCHN, no phase III.

Why it mattersRadiation oncology

6-mo LRF was 4.6% (Q3) vs 9.6% (weekly), absolute difference 5.0% (95% CI 1.0, 8.9), despite worse RT QA on Q3 (81% vs 94% per protocol or acceptable). RT quality does not explain the gap. With 70 Gy fixed, schedule choice rests on toxicity type, not total G3-4 burden.

Monday clinic

In p16-negative locoregionally advanced SCCHN receiving 70 Gy with concurrent cisplatin, this questions choosing weekly 40 mg/m2 on tolerability grounds, since G3-4 event counts were not lower; it does not extend to the p16-positive cohort, reported separately. The longer read

12 details 1 trial watching

Design

Randomized phase II/III; this is the phase II acute toxicity report for the p16-negative cohort. 234 randomized (118 Q3, 116 Q1) between Oct 2021 and Sept 2025; 91% completed all follow-up up to 6 months. QA modality reviews were done on a random sample of cases.

Population & inclusion

p16-negative locoregionally advanced SCCHN. Median age 60; 76% male; 58% Zubrod 0; 87% former or current smokers, 70% >10 pack-years. 57% larynx, 28% oropharynx, 15% hypopharynx; 83% T1-3 and 74% node-positive.

Regimen

Cisplatin 100 mg/m2 Q3 weeks (Q3) vs cisplatin 40 mg/m2 weekly (Q1), each with RT. Chemotherapy delivery scored per protocol or acceptable variation in 80% on Q3 vs 98% on Q1. Cumulative cisplatin dose delivered is not reported in source.

Radiotherapy

70 Gy in both arms; fractionation, technique and target volumes are not reported in source. RT reviews were completed for 91% of sampled pts, scored per protocol or acceptable variation in 81% on Q3 vs 94% on Q1.

Endpoints

acute toxicity by T-score, the number of all treatment-related grade 3-4 AEs during treatment or within six months. To proceed to phase III, the mean T-score ratio (Q1/Q3) had to be below 1 at 1-sided p<0.1, together with a 6-month locoregional failure difference criterion (printed as '= 8%' absolute in the portal text).

Results

The cohort did not meet criteria for continuing to phase III; arm-level values are in the tables.

Endpoint	Q1 Cis (weekly)	Q3 Cis	Effect
Mean T-score	2.48 (95% CI 1.97, 2.99)	2.23 (95% CI 1.81, 2.65)	Ratio 1.11 (90% upper bound 1.33), p=0.77
6-month locoregional failure	9.6%	4.6%	Absolute difference 5.0% (95% CI 1.0, 8.9)

AE term	Q3 Cis	Q1 Cis
Nausea	12	4
WBC decreased	14	28
Dehydration	9	1
Hypomagnesemia	2	8
Acute kidney injury	11	3

Safety

Total G3-4 burden was similar, but the profile differed by schedule. Q3 carried more G3-4 nausea (12% vs 4%), dehydration (9% vs 1%) and acute kidney injury (11% vs 3%); weekly carried more WBC decrease (28% vs 14%) and hypomagnesemia (8% vs 2%). Late toxicity is not reported in source.

vs leading data

The Tata Memorial randomized trial (Noronha et al.) favored Q3 over a lower weekly dose for locoregional control in a mostly postoperative population, while JCOG1008 supported weekly dosing after surgery. This cohort tests the schedule question with 70 Gy RT in p16-negative disease and gives no toxicity support for weekly; the source draws no comparison to either trial.

Applies to

p16-negative locoregionally advanced SCCHN, larynx-dominant with heavy smoking history, treated with 70 Gy RT and concurrent cisplatin

Does not represent the p16-positive cohort (241 pts, reported separately) or settings other than 70 Gy RT with concurrent cisplatin.

Limitations

The T-score weighs every G3-4 event equally, so marrow and renal events are interchangeable in the primary. QA was scored on a random sample, not all cases, and per-arm cumulative cisplatin dose is missing. The portal text has lost the inequality in the LRF criterion, so the abstract alone does not show whether that half of the rule passed.

Discussion

The tolerability premise for weekly cisplatin did not hold here: toxicity was redistributed, not reduced. The LRF difference favors Q3 but rests on a 6-month read in a toxicity-driven phase II, so it is a direction, not an efficacy result. Pooled results for all 475 pts were deferred to the presentation.

Enrolment

CONSORT flow

Randomized234

↓

Q3 Cis 100 mg/m2 + 70 Gy

allocated 118

Mean T-score 2.23

Q1 weekly Cis 40 mg/m2 + 70 Gy

allocated 116

Mean T-score 2.48

Rationale

Randomized, prespecified phase II go/no-go analysis; weekly failed its toxicity criterion, leaving Q3 as the reference schedule. Abstract only; 6-month LRF is immature and not an efficacy test.

Open questions

Does the 6-month LRF gap persist in longer-term locoregional control and survival?
Do pooled p16+ and p16- results (475 pts) show the same toxicity pattern?
Late toxicity and hearing outcomes by cisplatin schedule

recruiting Low-Dose Weekly vs High-Dose Cisplatin Phase NA

n=100 · primary completion 2028-09 · randomized weekly LD vs HD cisplatin CRT, p16-stratified

Sourced from P. M. Harari et al.

📚 Sources · 📄 1 paper

📄 PAPER P. M. Harari; K. Attwood; F. Siddiqui et al. · ASTRO 2026 Annual Meeting (2026-09)

NRG-HN009 Randomized Phase II/III Trial of RT + Cisplatin Q3 Weeks vs RT + Cisplatin Weekly for Patients with Locoregionally Advanced SCCHN: p16-Negative Phase II Toxicity Results

doi article →

Abstract

ASTRO 2026 abstract LBA 06 · LBA 01 - Late-breaking Abstract Session · 2026-09-29 · presented by Paul Harari, MD, FASTRO Purpose/Objective(s): To provide first report of phase II acute toxicity results for the p16-negative cohort of 234 patients from NRG-HN009. The phase II acute toxicity results for the p16-positive cohort of 241 patients were presented at the Multidisciplinary HNC Symposium in Feb 2026. Materials/Methods: Eligible patients with p16-negative SCCHN were randomly assigned to receive 70 Gy RT + Cis at 100 mg/m2 Q3 weeks (Q3) vs 70 Gy RT + Cis weekly at 40 mg/m2 (Q1). Acute toxicity was measured by T-score, defined as the number of all treatment-related grade 3-4 adverse events during treatment or within six months. To proceed to phase III, the mean T-score ratio (Q1/Q3) from negative binomial regression must be significantly (1-sided p<0.1) < 1 ( i.e. , Q1 toxicity < Q3 toxicity) and the difference in 6-month locoregional failure estimates (Q1-Q3) must be = 8% (absolute difference). Quality assurance modality reviews for a random sample of cases were performed for radiation and chemotherapy delivery quality. Results: Between Oct 2021-Sept 2025, 234 patients were randomized, 118 patients to Q3 and 116 to Q1. 91% of patients completed all follow-up up to 6 months. Median age was 60 years; 76% male; 80% white; 58% Zubrod 0; 87% former or current smokers; 70% >10 pack-years smoking history; 57% larynx, 28% oropharynx, 15% hypopharynx; 83% T1-3 tumors and 74% node-positive disease. Mean T-score ratio was 1.11 (90% upper confidence bound 1.33; p=0.77) with mean T-scores of 2.23 (95% confidence interval 1.81, 2.65) for Q3 and 2.48 (95% CI 1.97, 2.99) for Q1. There were absolute differences in acute grade 3-4 rates between arms of = 5% in the following terms as shown in Table 1. The Q3 Cis arm showed higher acute grade 3-4 toxicity rates of nausea, dehydration and acute kidney injury, whereas the Q1 Cis arm showed higher rates of WBC and magnesium decrease. The 6-month locoregional failure rates were 4.6% for Q3 and 9.6% for Q1 [absolute difference 5.0% (95% CI 1.0, 8.9)]. RT reviews were completed for 91% of sampled patients with overall score per protocol or acceptable variation in 81% on Q3 and 94% on Q1. Chemotherapy reviews were completed for 100% of sampled patients with overall score per protocol or acceptable variation in 80% on Q3 and 98% on Q1. Conclusion: The phase II toxicity results for the p16-negative cohort of NRG-HN009 did not meet criteria for continuing to phase III. Acute grade 3-4 AE rates between arms with = 5% difference varied across the Q3 and Q1 Cis treatment arms as depicted in Table 1. The overall acute toxicity and locoregional control results at 6 months for all 475 patients enrolled on the NRG-HN009 phase II study (p16+ and p16-) will be summarized at presentation. Treatment-Related Grade 3-4 Acute AE Rate (%) Nausea WBC decreased Dehydration Hypomagnesemia Acute kidney injury Q3 Cis 12 14 9 2 11 Q1 Cis 4 28 1 8 3

📝 https://amportal.astro.org/sessions/lba-01-22916/nrg-hn009-randomized-phase-ii-iii-trial-of-rt-cisplatin-q3-weeks-vs-rt-cisplatin-weekly-for-p-113301 10.1016/j.ijrobp.2026.06.2466

Combined Curative Phase 2 trial Confirmatory ASTRO Annual Meeting 2026

Lymphoma

Consolidative RT dose de-escalation: 30 Gy non-inferior to 40 Gy for 5-yr PFS in stage I-II DLBCL in CR after chemo.

Practice-changing

30 Gy vs 40 Gy consolidative RT, limited-stage DLBCL

ForStage I-II DLBCL, CR/CRu after anthracycline-based chemo ± rituximab

5-year progression-free survival surrogate

90.5% vs 87.2%

HR 0.87, 95% CI 0.59-1.28; one-sided P = 0.0013 for non-inferiority

TL;DR5-yr PFS 90.5% (30 Gy) vs 87.2% (40 Gy), HR 0.87 (0.59-1.28), non-inferiority met in stage I-II DLBCL in CR after chemo.

Why it mattersRadiation oncology

The local-regional read backs the PFS headline: locoregional recurrence did not differ between 30 Gy and 40 Gy involved-site/field RT, though no rates are given in the source text. Toxicity, including second malignancies, was also comparable at 7.2 years median f/u, so the late-effect gain from de-escalation is inferred, not shown.

Monday clinic

In stage I-II DLBCL in CR/CRu after anthracycline-based chemo with or without rituximab, this supports 30 Gy over 40 Gy as the consolidative dose; it does not extend to pts short of CR, and it does not test omitting RT. The longer read

12 details 1 trial watching

Design

Multicenter, open-label, non-inferiority phase 3, randomized 1:1. 432 pts enrolled April 14, 2010 to July 1, 2019; median follow-up 7.2 years. Non-inferiority margin not reported in source.

Population & inclusion

Newly diagnosed stage I-II DLBCL achieving CR/CRu after anthracycline-based chemo with/without rituximab. Age criterion printed as '=15 years' in the portal text. Bulk, IPI and PET status at response not reported in source.

Radiotherapy

30 Gy vs 40 Gy consolidative involved-site/field RT. Fraction size, technique and the split between involved-site and involved-field volumes are not reported in source.

Endpoints

Primary: 5-year PFS, tested for non-inferiority of 30 Gy. Also reported: OS, locoregional recurrence, acute and late toxicity including second malignancies.

Results

Primary endpoint met (table). OS and locoregional recurrence showed no difference between arms; the source gives no rates or HRs for either.

Endpoint	30 Gy	40 Gy	Effect
Randomized	n=216	n=216	1:1
ITT analysis	212	213	n/a
5-yr PFS (95% CI)	90.5% (86.5-94.7)	87.2% (82.7-91.9)	HR 0.87 (0.59-1.28), one-sided P = 0.0013 for non-inferiority

Safety

Acute and late toxicities, including second malignancies, were comparable between arms. No rates or grades reported in source, so no measured toxicity advantage for 30 Gy.

vs leading data

The source states no prior randomized trial compared these two doses in DLBCL specifically. The UK NHL dose-reduction RCT (Lowry et al.) asked a similar de-escalation question in aggressive NHL more broadly, and ILROG guidance already favors the lower consolidative dose after CR, so this result is concordant with that direction.

Applies to

stage I-II DLBCL in CR/CRu after anthracycline-based chemo with or without rituximab, receiving consolidative involved-site/field RT

Does not represent pts with partial response or residual disease, advanced-stage DLBCL, or the question of omitting RT altogether.

Limitations

Enrollment spans 2010 to 2019 with rituximab optional and response graded as CR/CRu, so systemic therapy and response assessment may not match current PET-adapted practice. Mixed involved-site/field volumes are not broken out. Abstract only: no event counts, no margin.

Discussion

With PFS near 90% in both arms and locoregional recurrence no different, the higher dose bought no measurable disease control in pts already in CR. What the trial does not settle is whether the lower dose reduces late effects (not shown at 7.2 years) and whether any RT is needed after a PET-negative response.

Enrolment

CONSORT flow

Assessed / enrolled 432

↓

Randomized432

↓

30 Gy

allocated 216

analyzed 212

5yr PFS 90.5%

40 Gy

allocated 216

analyzed 213

5yr PFS 87.2%

Rationale

Randomised phase 3, prespecified non-inferiority primary met at 7.2-year median f/u; source calls 30 Gy the new standard. Caveats: margin and fractionation unreported, rituximab optional.

Open questions

Can consolidative RT be omitted after PET-negative CR in limited-stage DLBCL?
Does 30 Gy reduce late toxicity or second malignancies with longer follow-up?
Is a dose below 30 Gy adequate after CR to rituximab-containing chemo?

active Dose-Reduced Consolidation Radiation Therapy in Patients With Diffuse Large B-cell Lymphoma Phase NA

n=243 · primary completion 2025-07 · 30 Gy to 20 Gy consolidation RT after PET-neg R-chemo

Sourced from X. Liu et al.

📚 Sources · 📄 1 paper

📄 PAPER X. Liu; T. WU; Y. Shi et al. · ASTRO 2026 Annual Meeting (2026-09)

30Gy vs 40Gy Consolidative Radiotherapy for Limited-Stage Diffuse Large B cell Lymphoma Achieving Complete Remission after Chemotherapy: A Randomized, Open-Label, Non-Inferiority, Multicenter Phase 3 Clinical Trial

doi article →

Abstract

ASTRO 2026 abstract 205 · SS 22 - Some crHEME With Your Coffee? A Winning Blend of Radiation and Systemic Therapy in Hematologic Malignancies · 2026-09-28 · presented by Shunan Qi, MD, MB Purpose/Objective(s): Consolidative radiotherapy (RT) remains an important component in the management of limited-stage diffuse large B-cell lymphoma (DLBCL). However, the optimal consolidative RT dose remains undefined, with heterogeneous doses ranging from 30 to 55 Gy being used. To our knowledge, no randomized study has directly compared consolidative dose of 30 Gy versus 40 Gy in DLBCL patients. This study aimed to determine whether 30 Gy is non-inferior to 40 Gy in patients achieving complete remission (CR) following immunochemotherapy. Materials/Methods: In this multicenter, non-inferiority, open-label, phase 3 trial, patients aged =15 years with newly diagnosed stage I-II DLBCL who achieved complete response (CR)/CRu after anthracycline-based chemotherapy with/without rituximab were randomly assigned (1:1) to 30 Gy or 40 Gy involved-site/field RT. The primary endpoint was 5-year progression-free survival (PFS). Results: Between April 14, 2010, and July 1, 2019, 432 patients were enrolled and randomly assigned to the 40 Gy (n=216) or 30 Gy (n=216) group. A total of 213 in the 40 Gy group and 212 in the 30 Gy group were included in intention-to-treat analyses. After a median follow-up of 7.2 years, the 5-year PFS was 90.5% (95% CI 86.5–94.7) in the 30 Gy group and 87.2% (95% CI 82.7–91.9) in the 40 Gy group (hazard ratio 0.87; 95% CI 0.59–1.28; one-sided P = 0.0013 for non-inferiority). No significant differences were observed in overall survival or locoregional recurrence between groups. Subgroup analyses showed consistent treatment effects across prognostic factors. Acute and late toxicities, including second malignancies, were comparable between the two arms. Conclusion: For patients with limited-stage DLBCL who achieve CR after chemotherapy, consolidative RT at 30 Gy provides non-inferior PFS compared with 40 Gy, with similar survival outcomes and toxicity profiles. These findings establish 30 Gy as a new standard of care in this setting, enabling reduced treatment intensity and potential long-term toxicity without compromising disease control.

📝 https://amportal.astro.org/sessions/ss-22-22854/30gy-vs-40gy-consolidative-radiotherapy-for-limited-stage-diffuse-large-b-cell-lymphoma-achie-113815 10.1016/j.ijrobp.2026.06.118

Radiation Curative Phase 3 RCT Practice-changing ASTRO Annual Meeting 2026

GI Lower

Two pMMR LARC trials bracket the SCRT + PD-1 question: TORCH-iTNT tests omitting SCRT, STELLAR II tests adding sintilimab to SCRT + CAPOX. Both read out CR only, survival pending.

Early signal

TORCH-iTNT NCT06281405

ForpMMR LARC, T3-4/N+ M0, 96.6% with at least one high-risk feature

Complete response rate (pCR + cCR) surrogate

61.5% vs 37.1%

48/78 with SCRT vs 26/70 without; no p-value or CI reported

TL;DRCR (pCR + cCR) 61.5% with SCRT 25Gy/5Fx → CAPOX + toripalimab vs 37.1% without RT in pMMR LARC; no p-value reported.

Why it mattersRadiation oncology

The RT read sits in cCR, not pCR: 25 pts after SCRT 25Gy/5Fx vs 7 without RT reached cCR and went to W&W, so the short course is what opened the organ-preservation route. The no-RT arm still carried adjuvant chemoradiotherapy for positive circumferential margins, at a rate the source does not report.

Monday clinic

In pMMR LARC (T3-4/N+ M0) with high-risk features where organ preservation is the aim, this supports retaining SCRT ahead of CAPOX plus PD-1 inhibitor; it does not extend to dMMR disease, and it does not show that omitting RT preserves function. The longer read

11 details 1 trial watching

Design

Multicenter randomized phase II, 192 pMMR LARC pts enrolled. Initial results as of January 31, 2026 cover the 148 who completed treatment (70 in Group A, 78 in Group B). Allocation ratio, stratification and follow-up duration are not stated in source.

Population & inclusion

pMMR LARC, T3-4/N+ M0. Baseline characteristics described as balanced. 96.6% (143/148) had at least one high-risk feature: low tumor location, cT4, cN2, MRF+ or EMVI+.

Regimen

Group A: 6 cycles of CAPOX plus toripalimab. Group B: SCRT followed by the same 6 cycles. cCR pts were offered W&W, non-cCR pts were recommended for surgery.

Radiotherapy

SCRT 25Gy/5Fx before immunochemotherapy in Group B. Group A received no neoadjuvant RT, with adjuvant chemoradiotherapy reserved for positive circumferential margins. Target volumes, technique and the interval from SCRT to response assessment are not reported in source.

Endpoints

Primary: complete response rate, defined as pCR plus cCR. Secondary: organ preservation rate, anorectal function, adverse events and survival outcomes.

Safety

Thrombocytopenia was the most common grade 3-4 AE, 12.9% in Group A and 14.1% in Group B. No other AE data, and no RT-attributable or surgical toxicity, are reported in source.

vs leading data

TORCH, the same group's predecessor, tested induction vs consolidation sequencing of SCRT with CAPOX and toripalimab; this trial asks instead whether SCRT can be dropped. UNION set SCRT followed by immunochemotherapy against long-course chemoradiotherapy. PROSPECT asked the RT-omission question with chemotherapy alone in a lower-risk population than the one enrolled here.

Applies to

pMMR LARC (T3-4/N+ M0) carrying at least one high-risk feature such as low tumor location, cT4, cN2, MRF+ or EMVI+

Does not represent dMMR rectal cancer or pts treated with long-course chemoradiotherapy.

Limitations

cCR criteria and the assessment timepoint are not stated, and cCR calls cannot be blinded to arm. The pCR denominator in Group B excludes the 25 cCR pts who went to W&W, so resected-only pCR is not a like-for-like comparison. No chemotherapy-alone arm, so toripalimab's contribution is unmeasured.

Discussion

The gap in CR is carried mostly by clinical responses, which is the outcome that matters for W&W and also the softer of the two components. The rationale for the no-RT arm was functional sparing, yet 58 of 70 Group A pts went to surgery vs 52 of 78 in Group B, and anorectal function is not yet reported. Regrowth after W&W will decide whether the cCR advantage holds.

Rationale

Initial results in 148 completers of 192 enrolled; no p-value or CI; CR is an early response endpoint, and organ preservation, function and survival readouts are pending.

Open questions

Local regrowth rate after W&W in each arm

not yet the Efficacy of MR-guided Online Adaptive Radiotherapy for Locally Advanced Rectal Cancer Phase NA

n=49 · primary completion 2026-12 · SCRT on MR-linac; W&W local recurrence rate endpoint
Anorectal function with vs without SCRT
Does toripalimab add to CAPOX alone in pMMR LARC without RT?

Sourced from Y. Wang et al.

📚 Sources · 📄 1 paper

📄 PAPER Y. Wang; L. Shen; J. Wan et al. · ASTRO 2026 Annual Meeting (2026-09)

Immunotherapy Based Total Neoadjuvant Therapy with or without Short-Course Radiotherapy for Locally Advanced Rectal Cancer: Initial Results of TORCH-iTNT

doi article →

Abstract

ASTRO 2026 abstract 168 · SS 14 - Now Is a STELLAR Time to TORCH Colorectal Cancer · 2026-09-28 · presented by Fan Xia, MD, PhD Purpose/Objective(s): For patients with proficient mismatch repair (pMMR) locally advanced rectal cancer (LARC), combining PD-1 inhibitors with total neoadjuvant chemoradiotherapy (iTNT) has shown significant potential to improve complete response (CR) rates and facilitate organ preservation. However, the combination of radiotherapy and surgery often results in greater functional impairment compared to using either treatment alone. Meanwhile, the synergy between chemotherapy and PD-1 inhibitors has been observed to enhance tumor downstaging, facilitating sphincter-preserving surgery and reducing radiation-related damage. This trial aims to assess the efficacy and functional outcomes of two iTNT regimens: CAPOX combined with PD-1 inhibitor, either with or without short-course radiotherapy (SCRT), in the neoadjuvant treatment of pMMR LARC patients. Materials/Methods: The TORCH-iTNT trial is a multicenter phase II randomized trial which enrolled 192 pMMR LARC (T3-4/N+M0) patients. Patients were assigned to either Group A, receiving 6 cycles of CAPOX plus Toripalimab, or Group B, undergoing SCRT (25Gy/5Fx) followed by 6 cycles of CAPOX plus Toripalimab. Patients with clinical complete response (cCR) were offered an option of watch-and-wait (W&W) approach, while non-cCR patients were recommended for surgery. In Group A, adjuvant chemoradiotherapy was administered to patients with positive circumferential margins. The primary endpoint was the complete response (CR) rate, defined as the combination of pathological complete response (pCR) and cCR. Secondary endpoints encompassed organ preservation rate, anorectal function, adverse events, and survival outcomes. Results: By January 31, 2026, a total of 192 patients were enrolled, with 148 completing the treatment (70 in Group A and 78 in Group B). Baseline characteristics were well-balanced, and 96.6% (143/148) of patients presented with at least one high-risk feature, including low tumor location (=5 cm), cT4, cN2, MRF+, or EMVI+. Seven patients in Group A and 25 patients in Group B achieved cCR and adopted W&W strategy. Among the 58 and 52 patients in Group A and Group B who received surgery, pCR rates were 32.8% (19/58) and 44.2% (23/52), respectively. Four non-cCR patients in Group A either declined surgery or were still undergoing further treatment. Disease progression was recorded in one patient from each group. The overall CR rates were 37.1% (26/70) in Group A and 61.5% (48/78) in Group B. Thrombocytopenia was the most common grade 3-4 adverse event, occurring in 12.9% of Group A and 14.1% of Group B patients. Conclusion: This study is the first comparative analysis of two iTNT regimens in LARC. Unprecedentedly, the neoadjuvant combination of CAPOX and PD-1 inhibitor showed an encouraging CR rate in pMMR LARC patients, and this CR rate can be further enhanced with the addition of SCRT prior to immunochemotherapy. Extended follow-up is essential to evaluate long-term therapeutic efficacy and functional outcomes. (NCT06281405)

📝 https://amportal.astro.org/sessions/ss-14-22849/immunotherapy-based-total-neoadjuvant-therapy-with-or-without-short-course-radiotherapy-for-l-113721 10.1016/j.ijrobp.2026.06.081

Combined Curative Phase 2 trial Early signal ASTRO Annual Meeting 2026

Early signal

STELLAR II NCT05484024

ForMid-to-low pMMR LARC; T3-4 94.9%, node-positive 92.9%

Complete response rate (phase 2 primary) surrogate

51.9% vs 26.8%

150/289 vs 78/291, P<0.001; phase 3 primary 3-year DFS not yet reported

TL;DROverall CR 51.9% vs 26.8% (P<0.001) adding sintilimab to SCRT (5 Gy x5) + CAPOX TNT in pMMR LARC; 3-year DFS pending.

Why it mattersRadiation oncology

The RT backbone is 5 Gy x5 with 100% completion, so the CR gain comes on a schedule any department can deliver. The surgical denominators (211 iTNT vs 247 TNT) show fewer iTNT pts reached the OR, though the per-arm split of the 92 W&W pts is not reported. The decision in play is SCRT-based TNT plus PD-1 blockade as an organ-preservation route.

Monday clinic

In mid-to-low pMMR LARC planned for SCRT-based TNT where organ preservation is a goal, this supports sintilimab as a CR-raising addition at the cost of more grade 3-4 toxicity; it does not yet inform DFS and does not extend to long-course CRT-based TNT. The longer read

9 details 4 trials watching

Design

Multicenter, randomized, phase 2/3 trial. 658 screened and 588 randomized from August 2022 to August 2025 (296 iTNT, 292 TNT). Data as of February 6, 2026; blinding not stated in source.

Population & inclusion

Mid-to-low pMMR LARC. Median age 59, 71.1% male. T3-4 94.9%, node-positive 92.9%, lower tumors 71.3%, MRF+ 48.8%, EMVI 45.4%.

Regimen

SCRT followed by 4 cycles of CAPOX with sintilimab (iTNT) or the same regimen without sintilimab (TNT). After evaluation, resection or W&W, then 2 additional cycles of the same prior regimen.

Radiotherapy

SCRT 5 Gy x5 in both arms, delivered first. All pts completed SCRT. Technique, target volumes and the interval to surgery are not reported in source.

Endpoints

Primary: CR rate for phase 2 and 3-year DFS for phase 3. This report covers short-term efficacy and safety only.

Results

Arm-level CR, pCR, toxicity and compliance are in the table above. 92 pts (15.6%) adopted W&W after cCR, and 458 had undergone surgery with 8 awaiting.

Endpoint	iTNT (SCRT + CAPOX + sintilimab)	TNT (SCRT + CAPOX)	P
Overall CR	51.9% (150/289)	26.8% (78/291)	P<0.001
pCR (operated pts)	41.7% (88/211)	19.4% (48/247)	not reported
Grade 3-4 toxicity	27.7%	19.9%	not reported
4-cycle chemo completion	92.9%	94.1%	not reported

Safety

Grade 3-4 toxicities 27.7% (iTNT) vs 19.9% (TNT). Grade 3-5 immune-related AEs in 3.4% of pts. Chemotherapy completion was similar (92.9% vs 94.1%); surgical morbidity is not reported.

vs leading data

Per the source, several phase II studies suggested that adding immunotherapy to TNT raises CR, but phase 3 comparisons of TNT with vs without immunotherapy were lacking. RAPIDO and the original STELLAR trial established SCRT-based TNT, while UNION and TORCH tested SCRT plus checkpoint blockade without an otherwise-identical immunotherapy-free TNT control.

Applies to

mid-to-low pMMR LARC, mostly T3-4 and node-positive, treated with SCRT-based TNT

Does not represent dMMR disease, upper rectal tumors, or long-course CRT-based TNT.

Limitations

Overall CR pools pathological and clinical response, and whether cCR assessment was blinded is not stated. pCR is computed on operated pts only, with unequal denominators (211 vs 247). The per-arm W&W split is not reported.

Discussion

The randomized variable is sintilimab alone, so the trial isolates the drug and says nothing about SCRT vs long-course CRT as its partner. A higher CR opens an organ-preservation route, but whether it converts to DFS in pMMR disease is unsettled until the phase 3 primary reads out.

Enrolment

CONSORT flow

Randomized588

↓

iTNT (SCRT + CAPOX + sintilimab)

allocated 296

Overall CR 51.9%

TNT (SCRT + CAPOX)

allocated 292

Overall CR 26.8%

Rationale

Randomized and fully accrued, but this is a short-term CR readout; the phase 3 primary (3-year DFS) and W&W regrowth data are not yet reported.

Open questions

Does the higher CR rate translate into a 3-year DFS benefit?
Regrowth rate and durability of W&W after iTNT

recruiting CAPOX and PD-1 Antibody Combined With or Without Radiotherapy for MSS Locally Advanced Rectal Cancer Phase 2

n=192 · primary completion 2026-06 · W&W for cCR after SCRT + toripalimab-CAPOX iTNT

recruiting Personalized Long-course Radiotherapy Plus Chemotherapy With or Without Immunotherapy for LARC: PALACE Study Phase 3

n=184 · primary completion 2027-07 · CR endpoint requires cCR sustained over 1 year
Does the PD-1 benefit hold with long-course CRT-based TNT?

recruiting Personalized Long-course Radiotherapy Plus Chemotherapy With or Without Immunotherapy for LARC: PALACE Study Phase 3

n=184 · primary completion 2027-07 · phase 3 long-course RT + chemo ± serplulimab, CR endpoint

recruiting Neoadjuvant Chemoradiotherapy Followed by Chemotherapy With or Without Tislelizumab for Resectable Ultra-low Rectal Cancer: The RELIEVE-02 Study Phase 3

n=196 · primary completion 2027-12 · phase 3 long-course CRT then CAPOX ± tislelizumab, pMMR

Sourced from H. Li et al.

📚 Sources · 📄 1 paper

📄 PAPER H. Li; L. Wei; W. Zhang et al. · ASTRO 2026 Annual Meeting (2026-09)

Short-Course Radiotherapy-Based Total Neoadjuvant Therapy with or without a PD-1 Inhibitor in pMMR Locally Advanced Rectal Cancer: Short-Term Results from a Randomized Phase 3 Trial (STELLAR II)

doi article →

Abstract

ASTRO 2026 abstract 165 · SS 14 - Now Is a STELLAR Time to TORCH Colorectal Cancer · 2026-09-28 · presented by Yuan Tang, MD Purpose/Objective(s): Total neoadjuvant therapy (TNT) is the standard of care for proficient mismatch repair (pMMR) locally advanced rectal cancer (LARC). While several phase II studies have suggested that adding immunotherapy to TNT can increase the complete response (CR) rate, phase 3 trials directly comparing TNT with versus without immunotherapy are lacking. The STELLAR II trial (NCT05484024) was therefore designed to conduct a head-to-head comparison, evaluating whether short-course radiotherapy (SCRT)-based TNT combined with a PD-1 inhibitor (iTNT) can safely improve the CR rate and survivals. Materials/Methods: This was a multicenter, randomized, phase 2/3 trial involving patients with mid-to-low pMMR LARC. Eligible patients were randomly assigned to iTNT or TNT group . The iTNT group received SCRT (5 Gy x5) followed by 4 cycles of CAPOX and sintilimab. The TNT group received the same regimen without sintilimab. After neoadjuvant therapy, treatment strategy either resection or watch-and-wait (W&W) was determined based on evaluation, followed by 2 additional cycles of same prior regimen. Primary endpoints were the CR rate for phase 2 and 3-year DFS for phase 3. Interim phase II results were previously reported at ESTRO 2025; here, we present the short-term efficacy and safety data from the fully accrual of trial. Results: From August 2022 to August 2025, 658 patients were screened and 588 were randomized, with 296 assigned to the iTNT group and 292 to the TNT group. Median age was 59 years, and 71.1% were male. Most patients had T3–4 (94.9%), node-positive (92.9%), and lower tumors (71.3%). 48.8% of patients had MRF+ disease and 45.4% had EMVI. All patients completed SCRT. Completion rates for 4-cycle of chemotherapy were 92.9% in the iTNT group and 94.1% in the TNT group. In the iTNT group, 254 patients (86.1%) received at least 4 cycles of sintilimab. Grade 3-4 toxicities occurred in 27.7% (iTNT) and 19.9% (TNT) of patients, and grade 3-5 immune-related adverse events occurred in 3.4% of patients. As of February 6, 2026, 458 patients had undergone surgery, with 8 awaiting surgery. Pathological complete response (pCR) was achieved in 41.7% (88/211) of the iTNT group versus 19.4% (48/247) of the TNT group. Ninety-two patients (15.6%) adopted a W&W strategy after clinical complete response (cCR). The overall CR rate was 51.9% (150/289) in the iTNT group, significantly higher than the 26.8% (78/291) in the TNT group ( P <0.001). Short-term efficacy and survival outcomes continue to be followed. Conclusion: This study provides the first substantial and reliable short-term efficacy and safety data for SCRT-based TNT combined with a PD-1 inhibitor in pMMR LARC. The significantly improved CR rate with iTNT offers a promising new option for organ preservation. Further 3-year survival outcomes are eagerly awaited.

📝 https://amportal.astro.org/sessions/ss-14-22849/short-course-radiotherapy-based-total-neoadjuvant-therapy-with-or-without-a-pd-1-inhibitor-in-113668 10.1016/j.ijrobp.2026.06.078

Combined Curative Phase 3 RCT Early signal ASTRO Annual Meeting 2026

Myeloma / Plasma Cell

Single-arm phase II of 4Gy for painful MM bone lesions, with 24% needing a second RT course.

Early signal

Ultralow-dose 4 Gy RT for myeloma bone metastases

ForMultiple myeloma, uncomplicated painful bone lesion; 79% prior chemo

TL;DRPain response 59% at 4 wks (per protocol; ITT 40/70, 57%) after 4Gy to painful MM bone lesions; 24% needed a second RT course.

Why it mattersRadiation oncology

The ITT read runs opposite to the abstract's framing: CR+PR was 40/70 (57%) at 4 wks, 33/70 (47%) at 8 wks and 37/70 (53%) at 6 mo, with 25/70 (36%) not completing the 6 mo assessment. The decision in play is 4Gy first with reRT held in reserve; 24% needed a second course.

Monday clinic

In MM with an uncomplicated painful bone lesion, this supports 4Gy as a response-adapted first step with reirradiation in reserve; it does not extend to complicated lesions or to pts who need fast relief, given a median 36 days to pain relief. The longer read

12 details

Design

Prospective, multi-institutional, single-arm phase II. 63 evaluable pts with 70 lesions from 7 institutions, treated 4/2019-9/2025. Median follow-up after RT 186 days.

Population & inclusion

Multiple myeloma with an uncomplicated painful bone lesion. Median age 66, 49% female, 89% ECOG 0-1, 79% prior chemo (median 1 line), 40% prior RT to a different area. Median baseline BPI 4.8.

Radiotherapy

4Gy total, delivered as 2Gy x 2 or 4Gy x 1 (29% received 4Gy x 1). Reirradiation with a clinician-choice regimen could be considered at 4 weeks after initial treatment for inadequately controlled pain (the inequality symbol is garbled in the source). Target volume and technique not stated in source.

Endpoints

Primary: proportion with self-reported pain response at 4 weeks. Response was scored on average BPI and oral morphine equivalent dosing per the International Consensus on Palliative RT, assessed at 4 weeks, 8 weeks and 6 months.

Results

Response rates by timepoint are in the table. Median BPI and OMED decreases were 2.25 and 5mg at 4 weeks and 2.75 and 6.2mg at 8 weeks. Median time to pain relief was 36 days, median duration 148 days, with no difference by fractionation.

Timepoint	ITT CR+PR	Per protocol CR+PR	Did not complete
4 wks	40/70 (57%)	40/68 (59%)	2/70 (2%)
8 wks	33/70 (47%)	33/52 (63%)	18/70 (26%)
6 mo	37/70 (53%)	37/45 (82%)	25/70 (36%)

Safety

No grade 3+ treatment-related toxicity. Lower-grade events and hematologic toxicity are not reported in the source, although marrow sparing was the stated rationale.

vs leading data

The source states there is no consensus on the most effective palliative dose in MM. The ultralow-dose concept comes from indolent lymphoma, where FoRT tested it against a conventional dose. With no comparator arm here, the 59% at 4 weeks cannot be ranked against conventional palliative fractionation.

Applies to

MM pts with an uncomplicated painful bone lesion, mostly ECOG 0-1 (89%) with a median of 1 prior line

Does not represent complicated bone lesions or bone metastases from solid tumors.

Limitations

Missing assessments grow from 2/70 at 4 weeks to 25/70 at 6 months, and reasons are not given, so the late per-protocol rates are vulnerable to informative dropout. Handling of reirradiated lesions in the 6 month response is not stated. Pain response is self-reported in an unblinded single-arm design.

Discussion

Best read as a strategy: 4Gy first, escalate on failure. A 63% response at 4 weeks after reirradiation suggests the low first dose did not obviously compromise salvage, at the cost of time (median 95 days to relief after reRT). It does not settle whether 4Gy matches conventional dosing up front, or whether it spares marrow.

Rationale

Single-arm phase II, 63 pts, no comparator against conventional palliative fractionation; late responses rest on a per-protocol denominator with 36% non-completion at 6 mo.

Open questions

4Gy vs conventional palliative fractionation in MM bone lesions: randomised comparison needed
Does 4Gy reduce hematologic toxicity vs higher-dose palliative RT?
Which lesions fail 4Gy and need reirradiation?

Sourced from L. K. Ballas et al.

📚 Sources · 📄 1 paper

📄 PAPER L. K. Ballas; A. A. Garsa Jr; Z. He et al. · ASTRO 2026 Annual Meeting (2026-09)

Phase II Multi-Institutional Study of Ultralow-Dose (4Gy) Response-Adapted Radiotherapy for Symptomatic Bone Metastases from Multiple Myeloma

doi article →

Abstract

ASTRO 2026 abstract 10 · CT 01 - Clinical Trials Session · 2026-09-27 · presented by Leslie Ballas, MD, FASTRO Purpose/Objective(s): Palliative radiation therapy (RT) is a critical component of multiple myeloma (MM) care. Given the nature of MM, RT commonly exposes bone marrow to cytotoxic treatment. Data exists showing that a bone marrow dose of 10 Gy causes hematologic toxicity (HT). Since there is no consensus as to the most effective dose for palliation, this study hypothesized that ultralow dose RT (4Gy) could provide a pain response while minimizing HT. Materials/Methods: This prospective multi-institutional single-arm phase II trial evaluated clinical pain response, both based on the average Brief Pain Inventory (BPI) and oral morphine equivalent dosing (OMED) according to the International Consensus on Palliative RT, in patients who received 4Gy (either 2Gy x 2 or 4Gy x 1) to an uncomplicated painful bone lesion at 4, 8 weeks and 6 months. The primary endpoint was the proportion of patients with self-reported pain response at 4 weeks. Reirradiation with clinician-choice regimens could be considered at =4 weeks following initial treatment for inadequately controlled pain. Results: 63 evaluable patients with 70 lesions from 7 institutions received 4Gy from 4/2019-9/2025. 29% of patients received 4Gy x 1. 49% were female, with median age of 66 years. 89% had an ECOG performance status 0-1, 79% had prior chemo (median number of lines of therapy was 1), and 40% had prior RT to a different area. The median baseline BPI was 4.8. The median follow-up after RT was 186 days. The pain response rate in those that completed questionnaires at 4 and 8 weeks was 59% and 63% (median BPI and OMED decrease of 2.25, 5mg, and 2.75, 6.2mg, respectively), with pain response of 82% at 6 months. The median time to pain relief was 36 days with a median duration of 148 days. There was no difference in pain relief based on fractionation. 24% of patients received a second course of RT, with a median dose of 20Gy at a median of 71 days after completion of the 4Gy treatment. Following reirradiation, the pain response rate was 63% after 4 weeks with a median time to pain relief of 95 days. There was no grade 3+ treatment related toxicity. Conclusion: Ultralow dose radiation improved pain and produced durable responses in the majority of patients. The proportion of patients with improved pain increased over time. Notably, relatively few patients required a second course of RT (24%). This response-adapted approach allowed for selective augmentation of pain control with minimal toxicity. Abstract 10 - Table 1: Pain Response in patients on protocol based on intention to treat analysis and per protocol analysis (CR: complete response, PR: partial response) Assessment time point Intention to treat Per Protocol 4 wks CR+PR 40/70 (57%) 40/68 (59%) Did not complete 2/70 (2%) 8 wks CR+PR 33/70 (47%) 33/52 (63%) Did not complete 18/70 (26%) 6 mo CR+PR 37/70 (53%) 37/45 (82%) Did not complete 25/70 (36%)

📝 https://amportal.astro.org/sessions/ct-01-22948/phase-ii-multi-institutional-study-of-ultralow-dose-4gy-response-adapted-radiotherapy-for-sym-113322 10.1016/j.ijrobp.2026.06.011

Radiation Palliative Phase 2 trial Early signal ASTRO Annual Meeting 2026

Hepatobiliary

Randomized protons vs photons in unresectable HCC stopped for futility at the planned interim; LP and PFS no different.

Early signal

NRG-GI003 NCT03186898

ForUnresectable or locally recurrent HCC, CP A or B7, 1-3 lesions, PS 0-1

Overall survival

HR 1.30

90% CI 0.83-2.04, 1-sided p=0.83; not met, futility boundary crossed

TL;DRProtons did not improve OS vs photons in unresectable HCC: HR 1.30 (90% CI 0.83-2.04), futility boundary crossed at planned interim.

Why it mattersRadiation oncology

Local progression was no different (24-mo LP 19.8% vs 22.3%, HR 0.80, 95% CI 0.36-1.77) even though dose was individualized on liver-GTV mean dose, the parameter protons should improve. Delivered dose by arm is not reported, so whether protons bought escalation is unknown. The modality choice for HCC does not rest on OS or LC here.

Monday clinic

In unresectable or locally recurrent HCC with CP A or B7 liver function and 1-3 lesions planned for a 5 or 15 fx course, this does not support selecting protons over photons for survival; it does not address pts beyond CP B7 or with more than 3 lesions. The longer read

11 details

Design

Phase III randomized trial, 1:1 protons vs photons, stratified by planned fractions (5 vs 15) and tumor vascular thrombosis. 117 screened June 2017 to January 2026, 116 randomized, 115 eligible/analyzed (protons 57, photons 58). Powered for HR 0.58 with 112 eligible pts and 88 OS events (80% power, 1-sided alpha 0.05), with 1 interim at 63 OS events.

Population & inclusion

Unresectable or locally recurrent HCC, pathologically or radiographically proven, Zubrod PS 0-1, Child-Pugh A or B7, 1-3 HCCs with size limits of 15, 10 and 6 cm for 1, 2 and 3 lesions; TVT allowed with a single lesion. Median age 72, 93% CP A, 75% no prior treatment, 57% single tumor, 23% TVT.

Radiotherapy

Protons or photons in 5 fx (30-50 Gy) or 15 fx (37.5-67.5 Gy), dose individualized on liver-GTV mean dose in both arms. Delivered dose by arm, proton delivery technique and motion management are not reported in source.

Endpoints

Primary: overall survival (Kaplan-Meier, log-rank). Secondary: PFS, local progression, adverse events (CTCAEv4).

Results

Trial released at the planned interim after the futility boundary was crossed (HR>1), median follow-up 20 months. No endpoint favored protons with statistical support; arm-level figures are in the table.

Endpoint	Protons	Photons	Effect
24-mo OS	56.2% (43.9-68.4)	69.3% (57.3-81.2)	HR 1.30 (90% CI 0.83-2.04), 1-sided p=0.83
24-mo PFS	31.6% (17.8-45.4)	30.4% (15.9-44.8)	HR 1.02 (95% CI 0.65-1.62), p=0.92
24-mo LP	19.8% (9.6-32.7)	22.3% (11.3-35.5)	HR 0.80 (95% CI 0.36-1.77), p=0.54
Treatment-related G3+ AEs	11%	24%	p=0.09

Safety

Treatment-related grade 3+ AEs were 11% with protons vs 24% with photons (p=0.09), numerically lower but not statistically different. AE type, hepatic decompensation and late effects are not broken out in source.

vs leading data

Retrospective proton vs photon comparisons in HCC had suggested a survival advantage attributed to liver sparing, and that hypothesis set the effect size this trial was powered for. Under randomization the OS estimate sits on the other side of unity. The source cites no comparator trial.

Applies to

unresectable or locally recurrent HCC with Child-Pugh A or B7 function, PS 0-1 and 1-3 lesions, mostly previously untreated

Does not represent pts beyond Child-Pugh B7, more than 3 lesions, or resectable disease.

Limitations

Cause of death is not reported, so an OS gap alongside PFS HR 1.02 and similar LP cannot be attributed to liver toxicity, competing mortality at median age 72, or chance. Subsequent systemic therapy by arm is unreported across an accrual period running June 2017 to January 2026. No subgroup data by Child-Pugh class, tumor size or fraction schedule in the abstract.

Discussion

The trial rules against the large OS benefit it was designed to find; with a 90% CI of 0.83-2.04 it does not establish harm. The only signal in the hypothesized direction is the G3+ AE rate, which is underpowered. What stays open is whether protons help where liver reserve is the binding constraint, a group this cohort (93% CP A) barely samples.

Rationale

Reported at planned interim after futility boundary crossed, abstract only, 115 pts with wide CIs. Negative for proton superiority, not evidence of harm; photons remain the default.

Open questions

Cause of the numerically worse OS with protons: hepatic decompensation, competing mortality, or chance?
Does the lower G3+ AE rate with protons hold in the full report?
Any proton benefit where liver reserve is limiting (CP B7, large tumors)?

Sourced from T. S. Hong et al.

📚 Sources · 📄 1 paper

📄 PAPER T. S. Hong; K. Winter; E. J. Koay et al. · ASTRO 2026 Annual Meeting (2026-09)

Initial Results of NRG Oncology NRG-GI003: A Phase III Randomized Trial of Protons vs. Photons for Hepatocellular Carcinoma (HCC)

doi article →

Abstract

ASTRO 2026 abstract 2 · PL 01 - Plenary Session · 2026-09-28 · presented by Theodore Hong, MD Purpose/Objective(s): Protons may benefit patients with HCC due to favorable dose distributions and the ability to spare non-target liver. This study hypothesized that overall survival (OS) would improve with proton therapy vs photon therapy in patients with advanced HCC. Materials/Methods: Eligible patients had pathologically or radiographically-proven unresectable or locally recurrent HCC, Zubrod performance status (PS) 0-1, Child-Pugh (CP) A or B7, 1-3 HCCs (1 HCC =15 cm, 2 HCC largest =10 cm, 3 HCC largest =6 cm) with tumor vascular thrombus (TVT) allowed if combined with a single lesion =1 cm and =15 cm. Patients were stratified by planned fractions (5 vs 15) and tumor vascular thrombosis (Yes vs No) and then randomized 1:1 to proton therapy or photon therapy given in 5 fractions (30-50 Gy) or 15 fractions (37.5-67.5 Gy) individualized based on liver-GTV mean dose. The primary endpoint was OS and secondary endpoints were progression-free survival (PFS), local progression (LP), and adverse events (AEs – CTCAEv4). An eligible sample size of 112 patients for 88 OS events provides 80% power with a 1-sided alpha=0.05 to detect the hypothesized OS hazard ratio (HR)=0.58 favoring protons, including 1 interim analysis at 63 OS events. OS was estimated by the Kaplan-Meier method and treatment arms were compared using a log-rank test. Results: Of the 117 patients screened from June 2017 to January 2026, 116 patients were randomized and 115 eligible/analyzed: protons (n=57) and photons (n=58). Median age was 72; 93% had CP A cirrhosis; 75% had no prior treatment; 57% had single tumors, 17% 2 tumors, 3% 3 tumors, and 23% had TVT with a single lesion. At the planned interim analysis, the trial was released for reporting by the NRG Oncology Data Monitoring Committee based on the futility boundary being crossed (HR>1). Median (min-max) follow-up was 20 months (0.13-81.7). Protons did not show an improvement in OS compared to photons (1-sided p=0.83, HR=1.30, 90% CI 0.83-2.04). Univariate 24-month OS (90% CIs) was 56.2% (43.9-68.4) for protons and 69.3% (57.3-81.2) for photons. Protons did not show an improvement in PFS (2-sided p=0.92, HR=1.02, 95% CI 0.65-1.62). The 24-month PFS (95% CIs) was 31.6% (17.8-45.4) for protons and 30.4% (15.9-44.8) for photons. Protons did not show a significant improvement in LP (2-sided p=0.54, HR=0.80, 95% CI 0.36-1.77). The 24-month LP (95% CIs) was 19.8% (9.6-32.7) for protons and 22.3% (11.3-35.5) for photons. Treatment-related grade 3+ AEs were lower for the protons arm, but not significantly different (protons 11%, photons 24%; p=0.09). Conclusion: Proton therapy did not improve OS, PFS, LP, or AEs in patients with advanced HCC. Clinical Trial Number: NCT03186898

📝 https://amportal.astro.org/sessions/pl-01-22946/initial-results-of-nrg-oncology-nrg-gi003-a-phase-iii-randomized-trial-of-protons-vs-photons-113309 10.1016/j.ijrobp.2026.06.004

Radiation Phase 3 RCT Early signal ASTRO Annual Meeting 2026

Breast

10-yr PMRT hypofractionation follow-up: LRR similar, more late G1-2 pulmonary fibrosis with 43.5 Gy/15fx.

Confirmatory

CHN HYPOPMRT (10-year) NCT00793962

ForHigh-risk breast cancer, post-mastectomy and axillary dissection

5-year cumulative incidence of locoregional recurrence local control

HR 1.13

90% CI 0.77-1.66; 9.6% hypofractionated vs 8.6% conventional

TL;DR10yr LRR 12.0% (43.5 Gy/15fx) vs 10.3% (50 Gy/25fx), HR 1.19 (95% CI 0.79-1.82); G1-2 pulmonary fibrosis 19.7% vs 11.7%.

Why it mattersRadiation oncology

Late lung is the additive read: G1-2 pulmonary fibrosis 19.7% with hypofractionation vs 11.7% (p=0.008), against no G4-5 late toxicity and no brachial plexopathy at median 11.5 yr. Fields were chest wall plus supraclavicular only, so the plexus safety transfers to that volume, not to IMN-inclusive RNI.

Monday clinic

In high-risk breast cancer after mastectomy and axillary dissection, this supports 43.5 Gy in 15 fractions to chest wall and supraclavicular region as an alternative to 50 Gy in 25; it does not extend to reconstruction or IMN-inclusive fields, which the source does not describe. The longer read

11 details 3 trials watching

Design

Open-label, phase 3, randomized, non-inferiority trial at a single national cancer center in China, 1:1. 820 enrolled (June 2008 to June 2016), 810 in mITT (409 conventional, 401 hypofractionated). Median follow-up 11.5 yr (IQR 9.6 to 13.8).

Population & inclusion

Women with high-risk breast cancer after mastectomy and axillary dissection. Stage, nodal burden, receptor status, systemic therapy and reconstruction status are not given in the source.

Radiotherapy

43.5 Gy in 15 fractions over 3 weeks vs 50 Gy in 25 fractions over 5 weeks, to the chest wall and supraclavicular region. Technique, IMN or axillary coverage, bolus and boost are not described in the source.

Endpoints

Primary: 5-year cumulative incidence of locoregional recurrence. Secondary: DFS, OS, late radiation-related toxicity. Outcomes through 10 years were analyzed descriptively.

Results

LRR and fibrosis by arm are in the table. 10-yr DFS (65.2% vs 69.9%) and OS (72.9% vs 77.5%) showed no significant difference; the source does not make the arm order explicit for these two.

Endpoint	43.5 Gy/15 fx	50 Gy/25 fx	Effect
5-yr LRR (1° EP)	9.6%	8.6%	HR 1.13 (90% CI 0.77-1.66; 95% CI 0.72-1.79)
10-yr LRR	12.0%	10.3%	HR 1.19 (95% CI 0.79-1.82)
Late G1-2 pulmonary fibrosis	19.7%	11.7%	p=0.008

Safety

No G4-5 late toxicity and no brachial plexopathy in either arm. G1-2 pulmonary fibrosis was more frequent with hypofractionation: 19.7% vs 11.7%, p=0.008. Other late endpoints (lymphedema, skin, cardiac) are not reported in the source.

vs leading data

The START trials established moderate hypofractionation mainly for whole-breast RT after breast conservation, with few mastectomy pts and limited nodal irradiation. This trial fills that PMRT plus supraclavicular gap with long follow-up. DBCG Skagen and HypoG-01 address hypofractionated nodal RT, and RT CHARM and FABREC address the reconstructed chest wall.

Applies to

high-risk breast cancer after mastectomy and axillary dissection treated to chest wall and supraclavicular region

Does not represent reconstructed chest walls, IMN-inclusive fields, or sentinel-node-only axillary staging.

Limitations

The source does not restate the non-inferiority margin, and the 10-yr 95% CI reaches 1.82. Fibrosis ascertainment method is not stated, and grading was unblinded. Accrual ran 2008 to 2016 with RT technique undescribed, so transfer to modern planning is uncertain.

Discussion

The 10-yr data show no late divergence in locoregional control and no plexus injury after a hypofractionated supraclavicular field. What it leaves open is whether the low-grade fibrosis excess is specific to this schedule and era, and whether the result holds with IMN coverage or reconstruction.

Rationale

Randomized phase 3 with non-inferiority already shown at 5 yr per source; 10-yr read is descriptive, single-center, open-label. Aligns with the field's adoption of hypofractionated PMRT.

Open questions

Does hypofractionated PMRT hold with IMN-inclusive regional nodal fields?

recruiting Conventionally Fractionated vs. Hypofractionated Comprehensive Nodal Irradiation for Breast Cancer Using Pencil Beam Scanning Proton Therapy Phase 3

n=276 · primary completion 2038-02 · phase 3 hypo vs conv proton RNI, IMN in target volume
Safety of hypofractionated PMRT with breast reconstruction

recruiting Hypofractionated vs Conventional RT After Prosthetic Breast Reconstruction Phase 3

n=506 · primary completion 2029-03 · phase 3 43.5 Gy/15fx vs 50 Gy/25fx after implant recon

recruiting Hypofractionated vs. Conventionally Fractionated Postmastectomy Radiotherapy After Implant-Based Reconstruction Phase NA

n=534 · primary completion 2033-10 · randomized NI, 1° EP unplanned reoperation, implant recon
Is the G1-2 pulmonary fibrosis excess clinically relevant with modern planning?

Sourced from G. Y. Sun et al.

📚 Sources · 📄 1 paper

📄 PAPER G. Y. Sun; S. Y. Chen; T. Yu et al. · ASTRO 2026 Annual Meeting (2026-09)

Hypofractionated vs. Conventional Fractionated Postmastectomy Radiotherapy in High-Risk Breast Cancer: 10-Year Outcomes from a Phase 3 Randomized Trial

doi article →

Abstract

ASTRO 2026 abstract 1 · PL 01 - Plenary Session · 2026-09-28 · presented by Guang-Yi Sun, MD Purpose/Objective(s): Hypofractionated radiotherapy is an established alternative to conventional fractionation for breast cancer, but long-term evidence supporting its use after mastectomy with regional nodal irradiation remains limited. The CHN HYPOPMRT trial previously demonstrated non-inferiority of hypofractionated postmastectomy radiotherapy at 5 years. We report the 10-year outcomes to assess durability of tumor control and late safety. Materials/Methods: In this open-label, phase 3, randomized, non-inferiority trial conducted at a national cancer center in China, women with high-risk breast cancer who had undergone mastectomy and axillary dissection were randomly assigned (1:1) to receive conventional fractionated radiotherapy (50 Gy in 25 fractions over 5 weeks) or hypofractionated radiotherapy (43·5 Gy in 15 fractions over 3 weeks) to the chest wall and supraclavicular region. The primary endpoint was 5-year cumulative incidence of locoregional recurrence. Long-term outcomes through 10 years were analyzed descriptively. Secondary endpoints included disease-free survival, overall survival, and late radiation-related toxicities. Results: Between June 2008 and June 2016, 820 patients were enrolled; 810 were included in the modified intention-to-treat analysis (409 conventional fractionation, 401 hypofractionation). At a median follow-up of 11.5 years (interquartile range 9.6 to 13.8), the cumulative incidence of locoregional recurrence at 5 years was 8.6% in the conventional fractionation group and 9.6% in the hypofractionation group (hazard ratio 1.13, 90% confidence interval 0.77 to 1.66; 95% confidence interval 0.72 to 1.79). At 10 years, locoregional recurrence remained similar between groups (10.3% versus 12.0%; hazard ratio 1.19, 95% confidence interval 0.79 to 1.82). For secondary endpoints, no significant differences were observed at 10 years in disease-free survival (65.2% versus 69.9%) or overall survival (72.9% versus 77.5%). No grade 4–5 late toxicities or cases of brachial plexopathy were observed. Grade 1–2 pulmonary fibrosis was more frequent with hypofractionation. (19.7% versus 11.7%; p=0.008). Conclusion: Hypofractionated postmastectomy radiotherapy provides durable locoregional control, comparable survival outcomes, and acceptable long-term toxicity in high-risk breast cancer. These findings support hypofractionation as a safe and efficient alternative to conventional fractionation in this setting. This trial is registered at ClinicalTrials.gov, number NCT00793962.

📝 https://amportal.astro.org/sessions/pl-01-22946/hypofractionated-vs-conventional-fractionated-postmastectomy-radiotherapy-in-high-risk-breast-113308 10.1016/j.ijrobp.2026.06.003

Radiation Curative Phase 3 RCT Confirmatory ASTRO Annual Meeting 2026

onc brain

2026-10-04 ASTRO Annual Meeting 2026

CNS

TRIDENT NCT04471844

NRG-CC009

Alliance A071801 NCT04114981

Prostate

PACE-A (sexual function, 5-year) NCT01584258

NRG/RTOG 9601 (transcriptomic analysis)

NRG-GU003

GI Upper

SOFT Preop

Head & Neck

NRG-HN009 (p16-negative phase II toxicity)

Lymphoma

30 Gy vs 40 Gy consolidative RT, limited-stage DLBCL

GI Lower

TORCH-iTNT NCT06281405

STELLAR II NCT05484024

Myeloma / Plasma Cell

Ultralow-dose 4 Gy RT for myeloma bone metastases

Hepatobiliary

NRG-GI003 NCT03186898

Breast

CHN HYPOPMRT (10-year) NCT00793962