ASTRO Annual Meeting 2026
TRIDENT NCT04471844
ForndGBM (WHO 2016), post maximal safe resection or biopsy, pre-RT/TMZ
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.
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.
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
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 nothing here argues for building arrays into the chemoRT course.
Sequencing stays as is: TTFields with adjuvant TMZ gave mOS 17.5 m vs 17.7 m with early start (HR 0.953, p=0.52). The MGMT-methylated signal (HR 0.683, p=0.03) comes from a post hoc per-protocol-usage subset with no n reported, so MGMT status is not yet a selector for earlier start.
7 details
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.
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.
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.
RT with TMZ in both arms. Dose, fractionation, target volume and array management during RT are not reported in source.
Primary: overall survival. Secondary: PFS, 1-, 2- and 3-year survival rate, ORR, safety. Kaplan-Meier with stratified log-rank test.
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 |
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.
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.
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.
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.
CONSORT flow
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.
- Does early TTFields improve OS in MGMT-methylated ndGBM when tested prospectively?
- Scalp dose and RT interruption with arrays worn during RT/TMZ
📚 Sources · 📄 1 paper
Abstract
NRG-CC009
ForSCLC brain mets, no cap on BM number (median 2, IQR 1-5)
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.
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).
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
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 seen in other histologies did not appear (adjusted HR 0.83, 95% CI 0.53-1.28).
10 details 2 trials watching
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.
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.
SRS vs HA-WBRT + memantine. Dose, fractionation, and SRS platform are not reported in source.
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.
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 |
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.
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.
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.
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.
- 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 NAn=100 · primary completion 2024-04 · SRS instead of WBRT in SCLC with 1-10 BMactive Hippocampal Sparing Whole Brain Radiation Versus Stereotactic Radiation in Patients With 5-20 Brain Metastases: A Phase III, Randomized Trial Phase NAn=196 · primary completion 2024-11 · randomised HA-WBRT vs SRS, 5-20 BM, any solid tumor
- SRS dose, fractionation, and surveillance schedule used
📚 Sources · 📄 1 paper
Abstract
Alliance A071801 NCT04114981
For1-4 brain metastases, one lesion >2cm resected, postop cavity RT
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.
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.
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
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.
10 details 3 trials watching
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.
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).
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.
Primary: time to surgical bed failure. Secondary: local control of intact brain metastases, overall survival, radiation necrosis.
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 |
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.
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.
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.
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.
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.
- 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 NAn=90 · primary completion 2027-05 · preop vs intraop vs postop RT for resected brain metsrecruiting Trial of Preoperative Radiosurgery Versus Postoperative Stereotactic Radiotherapy for Resectable Brain Metastases Phase NAn=200 · primary completion 2028-12 · 1-fx preop SRS vs 5-fx postop SRT; 12 mo LMD incidencenot yet Study Comparing Neoadjuvant Versus Adjuvant Stereotactic Radiotherapy of Brain Metastases Phase NAn=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?
📚 Sources · 📄 1 paper
Abstract
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).
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.
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
No ADT was permitted, so the SBRT trajectory (median EPIC-26 79 to 58) is attributable to 36.25Gy/5 fractions alone. 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.
Median EPIC-26 sexual score fell from 62 to 17 after prostatectomy, with 18/22 (82%) crossing the MCID. Approach was mixed (open, laparoscopic, robot assisted) and nerve-sparing use is not reported, so the figure may not reflect a contemporary nerve-sparing robotic series. Analysis was by treatment received.
Also covered Sep 28
12 details
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.
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.
36.25Gy/5 fractions delivered in 1-2 weeks. ADT not permitted. Platform, margins and target volume not stated in source.
Comparator was prostatectomy by open, laparoscopic or robot-assisted approach. Nerve-sparing status not stated in source.
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.
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 |
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.
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.
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.
CONSORT flow
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.
- 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
📚 Sources · 📄 1 paper
Abstract
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.
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.
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
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 ranks risk more reliably than it selects for hormones. RT dose and volume not reported.
11 details
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.
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.
sRT with or without high-dose bicalutamide (AAT). Bicalutamide dose and duration not reported in source.
Salvage RT in both arms. Dose, fractionation and target volume not reported in source.
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).
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% |
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.
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.
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.
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.
- 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?
📚 Sources · 📄 1 paper
Abstract
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.
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.
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
62.5 Gy/25 fx to the prostate bed carries more physician-graded grade 3 cystitis (7% vs 0%) and hematuria (6% vs 0.7%) than 66.6 Gy/37 fx, while 5-yr EPIC urinary change (-8.0 vs -5.7, p=0.4) and 5-yr BF (21% vs 18%, p=0.3) do not separate. This informs the prostate-bed fractionation choice, with bleeding risk part of consent.
12 details 3 trials watching
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.
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.
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.
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 "=").
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 |
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).
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.
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.
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.
CONSORT flow
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.
- 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 2n=136 · primary completion 2026-11 · randomized ph2 SBRT vs mod hypofx post-RP, 2-yr QOLrecruiting Salvage Stereotactic Body Radiotherapy of the Prostate Bed for Biochemical Recurrence After Radical Prostatectomy. Phase NAn=284 · primary completion 2029-02 · randomized ph2/3 salvage bed SBRT vs SOC RTn=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?
📚 Sources · 📄 1 paper
Abstract
SOFT Preop
ForResectable, borderline or LA type A PDAC, ECOG 0-2, post >1 mo neoadj chemo
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.
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.
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
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 fractionation choice moves toward SBRT on QOL only where that nodal volume and platform are reproduced.
83/98 (84.7%) reached resection, 41 SBRT and 42 chemo-RT, with no difference in surgical complications, so the 5-fraction course did not cost operability. Node positivity was 41% vs 38%; margin negativity and pathologic response are called equal but no figures appear in the abstract.
11 details 1 trial watching
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.
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.
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.
Primary: pathologic node positivity, hypothesizing lower rates with chemo-RT. Secondary: PFS, OS, patient-reported QOL (PROMIS), physician-reported toxicity, surgical complications, translational endpoints.
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 |
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).
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.
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.
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.
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.
- 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 2n=256 · primary completion 2027-12 · preop mFOLFIRINOX +/- isotoxic high-dose SBRT in BRPC
📚 Sources · 📄 1 paper
Abstract
NRG-HN009 (p16-negative phase II toxicity)
Forp16-negative locoregionally advanced SCCHN, 70 Gy RT + concurrent cisplatin
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.
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.
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
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, the concurrent schedule is the variable to weigh for locoregional control.
Weekly 40 mg/m2 traded toxicities instead of lowering them: G3-4 AKI 11% vs 3% and nausea 12% vs 4% on Q3, WBC decrease 28% vs 14% and hypomagnesemia 8% vs 2% on weekly. Chemotherapy delivery was per protocol or acceptable in 80% on Q3 vs 98% on weekly; cumulative dose not reported.
12 details 1 trial watching
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.
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.
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.
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.
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).
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 |
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.
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.
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.
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.
CONSORT flow
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.
- 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 n=100 · primary completion 2028-09 · randomized weekly LD vs HD cisplatin CRT, p16-stratified
📚 Sources · 📄 1 paper
Abstract
30 Gy vs 40 Gy consolidative RT, limited-stage DLBCL
ForStage I-II DLBCL, CR/CRu after anthracycline-based chemo ± rituximab
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.
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.
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
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.
12 details 1 trial watching
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.
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.
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.
Primary: 5-year PFS, tested for non-inferiority of 30 Gy. Also reported: OS, locoregional recurrence, acute and late toxicity including second malignancies.
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 |
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.
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.
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.
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.
CONSORT flow
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.
- 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 NAn=243 · primary completion 2025-07 · 30 Gy to 20 Gy consolidation RT after PET-neg R-chemo
📚 Sources · 📄 1 paper
Abstract
TORCH-iTNT NCT06281405
ForpMMR LARC, T3-4/N+ M0, 96.6% with at least one high-risk feature
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.
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.
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
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 an unreported rate.
CAPOX plus toripalimab without RT gave a 37.1% (26/70) CR rate in pMMR LARC, but with no chemotherapy-alone arm the PD-1 inhibitor's contribution is unmeasured. G3-4 thrombocytopenia was similar across arms (12.9% vs 14.1%), so adding SCRT did not visibly cost hematologic tolerance of six cycles.
Omitting RT sent more pts to resection: 58 of 70 in the no-RT arm had surgery vs 52 of 78 after SCRT, with 7 vs 25 entering W&W. pCR among resected was 32.8% vs 44.2%. Margin status, sphincter preservation and anorectal function are not yet reported.
11 details 1 trial watching
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.
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+.
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.
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.
Primary: complete response rate, defined as pCR plus cCR. Secondary: organ preservation rate, anorectal function, adverse events and survival outcomes.
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.
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.
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.
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.
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.
- 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 NAn=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?
📚 Sources · 📄 1 paper
Abstract
STELLAR II NCT05484024
ForMid-to-low pMMR LARC; T3-4 94.9%, node-positive 92.9%
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.
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.
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
The RT backbone is 5 Gy x5 with 100% completion, so the CR gain comes on a schedule any department can deliver. Fewer iTNT pts reached surgery (211 vs 247 operated), though the per-arm W&W split is not reported. This informs SCRT-based TNT plus PD-1 blockade as an organ-preservation route; technique and target volumes are not in source.
Sintilimab was the only randomized variable on a fixed SCRT + CAPOX backbone, and 86.1% received at least 4 cycles without loss of chemo completion (92.9% vs 94.1%). The price is grade 3-4 toxicity of 27.7% vs 19.9%. This is a checkpoint-inhibitor signal in pMMR disease, with DFS still unreported.
pCR was 41.7% (88/211) vs 19.4% (48/247) among operated pts, and 92 pts (15.6%) entered W&W after cCR. In a cohort with 71.3% lower tumors, that bears on sphincter preservation. Regrowth rates, salvage outcomes and surgical morbidity are not reported in source.
9 details 4 trials watching
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.
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%.
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.
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.
Primary: CR rate for phase 2 and 3-year DFS for phase 3. This report covers short-term efficacy and safety only.
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 |
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.
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.
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.
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.
CONSORT flow
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.
- 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 2n=192 · primary completion 2026-06 · W&W for cCR after SCRT + toripalimab-CAPOX iTNTrecruiting Personalized Long-course Radiotherapy Plus Chemotherapy With or Without Immunotherapy for LARC: PALACE Study Phase 3n=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 3n=184 · primary completion 2027-07 · phase 3 long-course RT + chemo ± serplulimab, CR endpointrecruiting Neoadjuvant Chemoradiotherapy Followed by Chemotherapy With or Without Tislelizumab for Resectable Ultra-low Rectal Cancer: The RELIEVE-02 Study Phase 3n=196 · primary completion 2027-12 · phase 3 long-course CRT then CAPOX ± tislelizumab, pMMR
📚 Sources · 📄 1 paper
Abstract
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.
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.
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
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.
12 details
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.
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.
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.
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.
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%) |
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.
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.
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.
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.
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.
- 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?
📚 Sources · 📄 1 paper
Abstract
NRG-GI003 NCT03186898
ForUnresectable or locally recurrent HCC, CP A or B7, 1-3 lesions, PS 0-1
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.
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.
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
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.
11 details
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.
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.
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.
Primary: overall survival (Kaplan-Meier, log-rank). Secondary: PFS, local progression, adverse events (CTCAEv4).
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 |
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.
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.
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.
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.
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.
- 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)?
📚 Sources · 📄 1 paper
Abstract
CHN HYPOPMRT (10-year) NCT00793962
ForHigh-risk breast cancer, post-mastectomy and axillary dissection
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%.
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.
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
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.
11 details 3 trials watching
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).
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.
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.
Primary: 5-year cumulative incidence of locoregional recurrence. Secondary: DFS, OS, late radiation-related toxicity. Outcomes through 10 years were analyzed descriptively.
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 |
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.
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.
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.
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.
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.
- 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 3n=276 · primary completion 2038-02 · phase 3 hypo vs conv proton RNI, IMN in target volume
- Safety of hypofractionated PMRT with breast reconstruction n=506 · primary completion 2029-03 · phase 3 43.5 Gy/15fx vs 50 Gy/25fx after implant reconrecruiting Hypofractionated vs. Conventionally Fractionated Postmastectomy Radiotherapy After Implant-Based Reconstruction Phase NAn=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?
📚 Sources · 📄 1 paper
Abstract
NRG/RTOG 0815 Decipher GC
ForIntermediate-risk prostate cancer, dose-escalated RT, biopsy Decipher GC available
p-interaction <0.001
10-yr DM absolute benefit 11% high GC vs 1% low GC
TL;DR10-yr DM absolute benefit from adding STAD to dose-escalated RT: 11% in high GC vs 1% in low GC, p-interaction <0.001.
The omission read is the low-GC group: 44% of the cohort had GC <0.45 and a 10-yr DM absolute difference of 1% with STAD. The slide pools int/high GC at 8% while the abstract gives 11% for high GC alone, so where GC 0.45-0.6 falls is not resolved in source. RT dose and fractionation are not stated.
In intermediate-risk prostate cancer planned for dose-escalated RT, a low Decipher GC (<0.45) supports discussing STAD omission and a GC >0.6 argues against it; it does not settle the GC 0.45-0.6 group or pts outside intermediate-risk disease. The longer read
The omission read is the low-GC group: 44% of the cohort had GC <0.45 and a 10-yr DM absolute difference of 1% with STAD added to dose-escalated RT. Slide pools int/high GC at 8% vs 11% for high GC alone in the abstract, so GC 0.45-0.6 stays unresolved. RT dose and fractionation not stated in source.
| GC group | Absolute 10-yr DM benefit from adding STAD |
|---|---|
| Int/High GC | 8% |
| Low GC | 1% |
+1 more figure
12 details 2 trials watching
Ancillary study of NRG/RTOG 0815, a phase 3 randomized trial of dose-escalated RT with or without 6 months of STAD. Prespecified analysis plan with NCI approval, GC data linked to updated outcomes at 10.2 years median follow-up (IQR 8.4-11.4).
Intermediate-risk prostate cancer. GC scores were obtained for 395 pts of 856 with available tissue, with baseline characteristics balanced between arms. GC distribution: low (<0.45) 44%, intermediate (0.45-0.6) 24%, high (>0.6) 32%.
6 months of STAD added to dose-escalated RT vs RT alone. Agents not stated in source.
Dose-escalated RT in both arms. Dose, fractionation, modality mix and target volume are not stated in source, though RT modality was a covariate in the multivariable models.
Primary: distant metastasis. Secondary: biochemical failure, MFS, PCSM, OS. Cox and Fine-Gray competing risk MVA adjusted for age, race, clinical risk factors, comorbidity score and RT modality.
GC-STAD interaction for DM p<0.001 and for PCSM p-interaction <0.001. 10-yr DM absolute difference 1% in low GC vs absolute benefit 11% in high GC. Slide 2 shows predicted 10-yr DM rising with GC score after RT alone and staying low with RT + STAD.
| Endpoint | sHR (95% CI) | p |
|---|---|---|
| Biochemical failure | 2.19 (1.36-3.53) | <0.001 |
| Distant metastasis | 4.89 (0.98-24.3) | 0.05 |
The parent NRG/RTOG 0815 trial set the question of STAD with dose-escalated RT for intermediate-risk disease as a whole. Decipher has prior ancillary validation in NRG/RTOG 0126 and 9601. This analysis adds a treatment interaction inside a trial that randomized the therapy in question.
The slide and the abstract cut the cohort differently (int/high GC pooled at 8% vs high GC at 11%), leaving the GC 0.45-0.6 group unresolved. The prognostic DM estimate has a CI of 0.98-24.3. No favorable vs unfavorable intermediate-risk breakdown in source.
The predictive claim is for DM and PCSM, not OS or MFS, for which no interaction is reported in source. The low-GC finding is the clinically usable half, since it identifies a large group with no clear benefit from intensification. The authors themselves defer to NRG GU010 for prospective validation.
Ancillary biomarker analysis in the 395 pts with GC scores; interaction rests on 16 DM and 7 PCSM events. Prespecified plan, but prospective validation (NRG GU010) pending.
- Does GC-guided STAD omission hold prospectively in NRG GU010? n=2050 · primary completion 2026-11 · phase 3 Decipher-guided de-intensification in UIRn=222 · primary completion 2027-12 · phase 2 SBRT without ADT in UIR, Decipher-guided
- STAD benefit in intermediate GC (0.45-0.6) reported on its own?
- Does the interaction hold within favorable vs unfavorable intermediate-risk disease?
📚 Sources · 🐦 1 tweet · 📄 1 paper
🚨Decipher score predictive of ADT benefit for preventing metastasis in patients with intermediate-risk #ProstateCancer in secondary analysis of @NRGonc RTOG 0815 RCT@angela_jia_ @ASTRO_org #ASTRO26 pic.twitter.com/YokjDQVxKa
— Tyler Seibert MD PhD (@TylerSbrt) September 29, 2026
Abstract
NRG/RTOG 0534 PAM50
ForPost-RP salvage RT, PSA 0.1-2.0 ng/mL, pT2 or pT3 N0M0, Gleason ≤9
TL;DR5-y FFP benefit from adding ADT to post-RP salvage RT was 31% vs 10% by PAM50 Luminal B status (p-int=.01), secondary biomarker analysis.
The decision in play is ADT with salvage RT, not target volume. The FFP interaction (P=0.01) rests on pooled STADT arms vs PBRT alone, HR 0.34 (0.23-0.52) in one subtype panel. In the three-arm slide, Arm 3 vs 2 reads HR 0.64 (0.34-1.20), p=0.16, so what PLNRT adds within subtype is unresolved.
In men post-RP with PSA 0.1-2.0 ng/mL and pT2 or pT3 N0M0 disease heading to salvage RT, PAM50 Luminal B status supports the case for adding STADT; it does not establish that non-Luminal B men can omit ADT. The longer read
The decision in play is ADT with salvage RT, not target volume. The FFP interaction (P=0.01) rests on pooled STADT arms vs PBRT alone, HR 0.34 (0.23-0.52) in one subtype panel. In the three-arm slide, Arm 3 vs 2 reads HR 0.64 (0.34-1.20), p=0.16, so what PLNRT adds within subtype is unresolved.
For the ADT decision, PAM50 Luminal B is offered as a selection marker: 5-y FFP benefit 31% vs 10% (p-int=.01), with a weaker 10-y MFS interaction (p-int=.05). STADT duration and agent are not reported in source, and the non-Luminal B estimate is too imprecise to support omission.
+2 more figures
10 details
PAM50 molecular subtyping on biorepository tissue from NRG/RTOG 0534, a three-arm randomised trial of post-prostatectomy salvage RT. Analytic cohort n=709 from 1792 enrolled and evaluable. Phase, prespecification of this analysis and median follow-up are not stated in source.
Parent trial eligibility per slide: post-RP, PSA 0.1-2.0 ng/mL, pT2 or pT3 N0M0, Gleason ≤9. Of 1039 consented pts with samples, 3 had insufficient RNA, 120 failed cDNA QC and 207 failed microarray QC.
Arm 1 PBRT alone (n=215), Arm 2 PBRT + STADT (n=247), Arm 3 PBRT + STADT + PLNRT (n=247). Dose, fractionation, pelvic nodal volume and STADT duration are not reported in source tweets.
Reported: FFP at 5 y and MFS at 10 y, each tested for subtype-by-treatment interaction. The primary endpoint of this biomarker analysis is not stated in source.
Tweet: 5-y FFP benefit from postop ADT 31% vs 10% (p-int=.01) and 10-y MFS 20% vs -3% (p-int=.05). FFP slide: pooled STADT arms vs PBRT alone HR 0.34 (0.23-0.52), p<0.001 in one subtype panel; the other panel's HR is garbled in OCR with CI 0.43-1.00.
The parent trial (Pollack et al, Lancet Onc 2022) is the slide's stated reference for the unselected result. GETUG-AFU 16 and RADICALS-HD tested ADT with post-RP RT without molecular selection, and NRG GU006 used PAM50 subtype prospectively with salvage RT; none of their figures appear in source.
Subtype panel labels and one HR are not legible in OCR, so effect sizes by subtype rest partly on the tweet's framing. The MFS interaction sits at p-int=.05. No multiplicity handling, event counts or Luminal B prevalence in source.
A treatment-by-subtype interaction on FFP is the claim that would let PAM50 select for ADT; a prognostic signal alone would not. The MFS interaction is weaker and the three-arm comparisons are underpowered within subtype, so this reads as support for biomarker-directed ADT rather than a rule for omission.
Biomarker subset analysis of a completed randomised trial, prespecification not stated; analytic cohort is a tissue- and QC-selected fraction. Interaction on MFS is borderline.
- Does PAM50 Luminal B predict ADT benefit independent of entry PSA and grade?
- Can non-Luminal B men omit ADT with salvage RT?
- Does pelvic nodal RT benefit differ by PAM50 subtype?
📚 Sources · 🐦 1 tweet
New #ASTRO2026 data from @NRGOnc /RTOG 0534 SPPORT 🔬🧬 presented by Shuang (George) Zhao @UTMDAnderson. PAM50 Luminal B = both prognostic & predictive of benefit from postop ADT.
— Lauren Henke, MD, MSCI (@lauren_henke) September 27, 2026
📈 5-y FFP benefit: 31% vs 10% (p-int=.01)
🎯 10-y MFS: 20% vs -3% (p-int=.05)#Pcsm @Astro_org pic.twitter.com/BRJsYDWiQS
GETUG P05 NCT02271659
ForIntermediate-risk prostate cancer, no ADT, IPSS ≤15, no T3a or nodal disease
87.8% vs 88.8%
brachy boost vs EBRT 80 Gy, p=0.86; primary not met
TL;DR5-yr PSA-PFS 87.8% vs 88.8% (p=0.86): brachy boost no better than 80 Gy EBRT in intermediate-risk prostate cancer without ADT, with more late GU toxicity.
Late GU toxicity is the cost side: any-grade 82.2% vs 63.6% (p=0.0006) and grade 2 34.1% vs 17.9% with brachy boost, for near-identical 5-yr PSA-PFS. The control was 80 Gy at 2 Gy/fraction to prostate only without ADT, so the read applies to conventionally fractionated dose-escalated EBRT; hypofractionated and SBRT comparators were not tested.
In intermediate-risk prostate cancer treated without ADT, this questions adding an LDR or HDR brachytherapy boost to 46 Gy EBRT over dose-escalated 80 Gy EBRT for 5-yr biochemical control; it does not extend to T3a, node-positive, or ADT-treated pts. The longer read
The boost decision is the read: an LDR 110 Gy or HDR 14 Gy boost after 46 Gy gave the same 5-yr PSA-PFS as EBRT to 80 Gy at 2 Gy/fraction, with late GU toxicity 82.2% vs 63.6% (p=0.0006). Applies to intermediate-risk disease without ADT; hypofractionated and SBRT comparators were not tested.
+3 more figures
| Toxicity | Brachytherapy boost | Exclusive EBRT | p |
|---|---|---|---|
| Acute GU, all grades | 79.3% | 79.7% | 0.92 |
| Acute GI, all grades | 29.9% | 41.2% | 0.03 |
| Late global, all grades | 96.3% | 91.4% | 0.02 |
| Late global, grade 3 | 10.4% | 6.6% | n/a |
| Late GU, all grades | 82.2% | 63.6% | 0.0006 |
| Late GU, grade 2 | 34.1% | 17.9% | n/a |
| Late GU, grade 3 | 3.0% | 1.3% | n/a |
| Late GI, all grades | 50.4% | 43.7% | 0.48 |
12 details 2 trials watching
Open-label randomized phase III, 1:1, 298 randomized at 27 centers (16/12/2013 to 20/03/2017), 296 evaluable: 141 brachytherapy boost, 155 EBRT. Median PFS follow-up 61.7 months (55.5-62.8).
Intermediate-risk prostate cancer: PSA 10 to 20 ng/ml and/or Gleason 7 and/or T2b; age 18-80, ECOG PS ≤ 2, expected survival ≥ 10y. Excluded: ADT, T3a, nodal or distant disease, IPSS >15, active inflammatory bowel disease. Median age 69; 60.5% Gleason 3+4, 27% 4+3, 12.5% Gleason 6; mean PSA 8.90.
Both arms: EBRT 46 Gy at 2 Gy/fraction to prostate + first cm of seminal vesicles. Arm A: brachytherapy boost to prostate, I-125 permanent implant 110 Gy or Ir-192 HDR 14 Gy, technique chosen by center (79 LDR, 55 HDR, 7 unknown). Arm B: EBRT boost 34 Gy at 2 Gy/fraction to prostate only, total 80 Gy.
Primary: PSA-PFS at 5 years by Phoenix criteria. Secondary: OS, PCSS, MFS, adverse events, QoL (IPSS, IIEF-5, QLQ-C30). PCSS and MFS results not reported in source.
5-yr PSA-PFS 87.8% vs 88.8% (brachy vs EBRT, p=0.86) on 35 events; 5-yr OS 96.0% vs 92.7% (p=0.30). No benefit in either the 3+4 or 4+3 subgroup, and LDR vs HDR did not influence PSA-PFS.
Abstract: more acute and late urinary toxicity with brachy boost (55% vs 26%, p<0.0001; 82% vs 64%, p=0.0007), mostly grade 1-2 (pollakiuria, dysuria), no difference in grade 3, no grade 4. The slide's acute GU all-grade rates (79.3% vs 79.7%, p=0.92) and its acute GI difference (29.9% vs 41.2%, p=0.03) do not match the abstract text.
ASCENDE-RT is the randomized trial that established a biochemical control advantage for an LDR boost over dose-escalated EBRT, in a higher-risk cohort that all received ADT. GETUG P05 asks the same question in intermediate-risk disease without ADT and finds no PSA-PFS difference.
35 events leaves room for a modest difference either way, and the source states neither the hypothesized effect nor power. Two boost techniques at center discretion make the experimental arm heterogeneous. Toxicity figures differ between the abstract and the presented slide.
For intermediate-risk disease without ADT, 80 Gy EBRT matched a brachytherapy boost on 5-yr biochemical control with less late GU toxicity. It does not settle whether curves separate later, or whether a boost adds value in unfavorable intermediate-risk disease managed with ADT.
Completed randomized phase III with a prespecified primary endpoint, null for brachy boost where prior randomized data favored it. Low event count and internally inconsistent toxicity reporting are secondary caveats.
- Does PSA-PFS diverge with follow-up beyond 5 years?
- Brachy boost value in unfavorable intermediate-risk disease treated with ADT
- Brachy boost vs moderately hypofractionated or SBRT dose escalation recruiting Androgen Suppression Combined With Nodal Irradiation and Dose Escalated Prostate Treatment Phase 3n=710 · primary completion 2032-10 · phase 3 SBRT vs EBRT + brachy boost, unfavourable risk + ADTrecruiting PRO-BOOST-LC: Whole-Gland Boost Strategies Versus SBRT Monotherapy in PSMA-Staged Localized and Locally Advanced Prostate Cancer Phase 2/3n=1000 · primary completion 2033-12 · phase 2/3 HDR/LDR/SBRT boost vs SBRT monotherapy
📚 Sources · 🐦 1 tweet · 📄 1 paper
GETUG P05: Ph 3 RCT of 46 Gy EBRT + LDR/HDR brachy boost vs dose-escalated 80 Gy EBRT in IR PCa, no ADT (n=288)
— Rashid K. Sayyid (@RKSayyid) September 28, 2026
🔹5-yr bPFS: 88% vs 88.2% (p=0.90)
🔹No bPFS benefit in iether GG2 or 3 pts
🔹5-yr OS: 96% vs 92.7% (p=0.30)
🔹Acute GI toxicity lower w/ brachy: 30% vs 41% (p=0.03)… pic.twitter.com/qoxDCnJV4b
Abstract
PROSTOX Ultra (SCIMITAR, EXCALIBUR)
ForPost-prostatectomy prostate cancer, 5-fx SBRT to prostate fossa ± pelvic nodes
TL;DRContinuous AUC 0.814 (SCIMITAR) and 0.824 (EXCALIBUR) for late G2+ GU AEs after post-prostatectomy SBRT; intact-prostate 0.50 cutoff failed, 0.25 recalibrated.
Reported via UroToday →
The cutoff, not the signature, is what breaks post-op: in EXCALIBUR every pt with toxicity scored below 0.50, and the median score with toxicity was 0.338. A result reported against the intact-prostate 0.50 threshold can therefore read low-risk in a man who goes on to late G2+ GU toxicity after 5-fx fossa SBRT.
In men post-prostatectomy weighing 5-fraction SBRT to the prostate bed ± nodes, this questions reading a PROSTOX Ultra score against the intact-prostate 0.50 cutoff; it does not extend to conventionally fractionated post-op RT, which neither cohort tested. The longer read
The cutoff, not the signature, is what breaks post-op: in EXCALIBUR every pt with toxicity scored below 0.50, and the median score with toxicity was 0.338. Read against the intact-prostate threshold, a score can look low-risk before late G2+ GU toxicity after 5-fx fossa SBRT (30-34 Gy in SCIMITAR).
12 details
Biomarker evaluation in two prospective post-op SBRT cohorts (SCIMITAR, EXCALIBUR). Risk scores came from the original intact-prostate model without refitting. Discrimination assessed as continuous AUC and as dichotomized performance at the prespecified 0.50 threshold, then exploratory threshold recalibration; AUCs bootstrapped (1,000 iterations) and pooled by fixed-effects meta-analysis.
Post-prostatectomy pts receiving SBRT to the prostate fossa. SCIMITAR: 100 enrolled, 89 evaluable. EXCALIBUR: 74 evaluable. Adjuvant vs salvage mix, PSA at RT and ADT use not reported in source.
SCIMITAR: 30-34 Gy in 5 fractions to the prostate fossa ± pelvic nodes. EXCALIBUR: 5-fraction SBRT to the prostate bed ± nodes, dose not reported in source. Toxicity by nodal coverage not reported in source.
Outcome: late grade 2+ GU adverse events. Predictor: PROSTOX Ultra score, continuous and dichotomized. Toxicity scale and follow-up duration not reported in source.
Per-cohort discrimination is in the table. Pooled AUC at 0.25 was 0.748. Clinical covariates (age, baseline pad use, IPSS, time from RP to SBRT) were not associated with toxicity (all p>0.2).
| Metric | SCIMITAR | EXCALIBUR |
|---|---|---|
| Continuous AUC | 0.814 | 0.824 |
| Binary AUC at 0.50 (intact cutoff) | 0.755 | <0.50 |
| Specificity at 0.50 | 0.985 | 0.926 |
| Sensitivity at 0.50 | 0.546 | not reported in source |
| Binary AUC at 0.25 (post-op cutoff) | 0.750 | 0.727 |
| Median score, toxicity vs none | 0.547 vs 0.049, p<0.0001 | 0.338 vs 0.043, p=0.009 |
The signature was built and thresholded for late GU AEs after intact-prostate SBRT, where 0.50 was prespecified. Post-op, risk ordering held (continuous AUC 0.814 and 0.824) but the 0.50 cutoff did not transfer: EXCALIBUR binary AUC was <0.50.
Sensitivity and specificity at 0.25 are not reported in the source text, only AUC. EXCALIBUR's event count and both cohorts' follow-up duration are missing, so the stability of the EXCALIBUR estimates cannot be judged. Source is a trade-press account of a talk, not a full report.
The read is a stable germline signal with a downward-shifted trigger after prostatectomy. That supports the biology and leaves the clinical tool unfinished: a cutoff tuned on these cohorts needs an independent post-op set before it gates fractionation or counseling.
Prespecified 0.50 threshold failed in EXCALIBUR; the 0.25 cutoff is exploratory, chosen and scored on the same two cohorts with no external validation.
- Independent prospective validation of the 0.25 post-op threshold
- Does a high score warrant conventional fractionation, lower dose, or smaller volume?
- Does the signature predict late GU toxicity after conventionally fractionated post-op RT?
📚 Sources · 📄 1 paper
Abstract
GUAM International Consensus Guideline
ForProstate cancer RT, intact or post-prostatectomy, acute or late GU AEs
TL;DR48-expert modified Delphi (15 countries) sets first RT-specific GU adverse event management consensus; 76% favor moderate hypofractionation over SBRT at baseline IPSS 15–19.
Reported via UroToday →
The RT-technique domain is the read: 76% favored moderate hypofractionation over SBRT at baseline IPSS 15–19 and 85% a full bladder at simulation and treatment, yet no dose-volume constraint reached consensus. The presenter pointed to margin reduction instead, citing MIRAGE (2-mm MRI-guided vs 4-mm CT-guided, late G≥2 GU 51% → 27%).
In a man with severe LUTS headed for prostate cancer RT, this panel position supports considering a prophylactic bladder outlet procedure (85%) with ≥8 weeks recovery before RT (94%); it does not extend to irritative-predominant symptoms (95% against). The longer read
Fractionation choice now has an IPSS anchor: 76% favored moderate hypofractionation over SBRT at baseline IPSS 15–19, and 85% a full bladder at simulation and treatment. No dose-volume constraint reached consensus, and only 52% considered SBRT safe after a bladder outlet procedure, with 94% waiting ≥8 weeks before RT.
12 details
Systematic review (183 articles) plus 3-round modified Delphi, May 2025 to February 2026. 48 experts from 15 countries: 34 radiation oncologists, 7 medical oncologists, 7 urologic oncologists. Consensus = ≥75% agreement; independently peer reviewed, endorsed by ASTRO and ESTRO.
Men with GU adverse events associated with prostate cancer RT, split by intact prostate vs postoperative and, when intact, obstructive vs irritative predominance. Five domains: acute medical management, RT technique, bladder outlet obstruction, urology referral indications, hyperbaric oxygen. Recommendations assume UTI has been excluded.
76% favored moderate hypofractionation over SBRT at baseline IPSS 15–19; 85% recommended a full bladder at simulation and treatment. After a bladder outlet procedure, 94% would wait ≥8 weeks and 66% ≥12 weeks before RT; only 52% considered SBRT safe afterward. No dose-volume constraint reached consensus.
Agreement figures and IPSS threshold distributions are tabulated in the bullets. The manuscript reports consensus on 31 key questions; the source covers a subset.
| Setting | Preferred first-line | Subsequent options, in order |
|---|---|---|
| Intact prostate, obstructive | Alpha blockers | PDE5-Is, NSAIDs, steroids, anti-spasmodics |
| Intact prostate, irritative | Anti-spasmodics | Alpha blockers, NSAIDs, phenazopyridine, cranberry products |
| Post-prostatectomy | Anti-spasmodics | Not reported in source |
| Statement | Panel agreement |
|---|---|
| Against prophylactic medication before symptom onset | 80% |
| Add a second agent rather than switch when first-line inadequate | 80% |
| Alpha blockers do not or probably do not help postoperatively | 74% |
| Moderate hypofractionation over SBRT at baseline IPSS 15–19 | 76% |
| Full bladder at simulation and treatment | 85% |
| Refer IPSS ≥20 for bladder outlet procedure consideration | 74% |
| Wait ≥8 weeks after outlet procedure before RT | 94% |
| Wait ≥12 weeks after outlet procedure before RT | 66% |
| SBRT safe after outlet procedure once obstruction resolved | 52% |
| Consider prophylactic outlet procedure pre-RT for severe LUTS | 85% |
| No outlet procedure when irritative symptoms predominate | 95% |
| IPSS threshold | Panelists selecting |
|---|---|
| 10–14 | 16% |
| 15–19 | 61% |
| 20–24 | 21% |
| ≥25 | 2% |
| IPSS threshold | Panelists selecting |
|---|---|
| 15–19 | 34% |
| 20–24 | 47% |
| 25–29 | 15% |
| ≥30 | 4% |
The presenter cited MIRAGE for margin reduction (2-mm MRI-guided vs 4-mm CT-guided, late G≥2 GU 51% → 27%) and CHHiP, PROFIT, RTOG 0415 and the HYDRA meta-analysis as showing no consistent late GU increase with moderate hypofractionation. RICH-ART was cited as randomized support for hyperbaric oxygen in late radiation cystitis; no effect size reported in source.
Several quoted positions fall below the group's own ≥75% bar (74%, 74%, 66%, 52%). The source gives 60% for IPSS ≥15 and 61% for the 15–19 band without reconciling them. Outlet-procedure questions were voted by a panel with 34 radiation oncologists and 7 urologic oncologists.
A default sequence for symptom management and an IPSS-anchored fractionation preference now exist where practice was improvised. Still unsettled, per the working group: dose-volume constraints, reliability of urethral contouring, and RT-specific evidence for commonly used medications. Four ongoing trials are named (BEFORE, RadTARGET, RELIEF, DESTINATION-2) and the document is intended to be living.
Modified Delphi guideline; every percentage is panel opinion, not an outcome. Changes practice by standardizing GU symptom management and IPSS-based fractionation choice where no RT-specific guideline existed.
- Optimal dose-volume constraints for GU adverse events
- Reliability of urethral contouring
- RT-specific evidence for commonly used GU symptom medications
📚 Sources · 📄 1 paper
Abstract
NRG/RTOG 0815
ForNon-metastatic intermediate-risk prostate cancer, GS 7 in 92%, median age 68
HR 0.87
95% CI 0.72-1.04, p=0.13 (ns); 14-y OS 53% vs 58%
TL;DR14-y OS 53% vs 58% (HR 0.87, p=0.13) adding 6 mo STAD to dose-escalated RT in intermediate-risk prostate cancer; PSA failure HR 0.60.
Dose escalation did not make STAD redundant: local failure still fell (HR 0.44) and the PSA-failure benefit held in single-risk-factor pts (HR 0.66). With 88% treated by EBRT alone to 79.2 Gy, the trial cannot say whether a brachytherapy boost substitutes for ADT. 422 of 446 deaths were non-prostate, which is why OS stayed flat.
In non-metastatic intermediate-risk prostate cancer planned for dose-escalated EBRT, this supports discussing 6 months of STAD as a disease-control gain (PSA failure, distant metastasis, salvage ADT) without a proven OS gain; it does not extend to pts with all 3 risk factors and ≥50% positive cores, who were ineligible. The longer read
Dose escalation did not make STAD redundant: local failure still fell (HR 0.44) and the PSA-failure benefit held in single-risk-factor pts (HR 0.66). With 88% treated by EBRT alone to 79.2 Gy, the trial cannot say whether a brachytherapy boost substitutes for ADT.
Six months of LHRH agonist/antagonist plus antiandrogen roughly halved later salvage ADT (15% vs 7% at 14 y) and cut distant metastasis (40 vs 14 events) without an OS gain. The cost is more grade ≥3 cardiac (26 vs 10) and metabolic (20 vs 4) events, though non-prostate mortality was not higher (HR 0.93).
| Arm | 10-yr OS | 14-yr OS | HR (95% CI) | p |
|---|---|---|---|---|
| RT Alone | 70% | 53% | Referent | n/a |
| RT + STAD | 74% | 58% | 0.87 (0.72, 1.04) | 0.13 |
+3 more figures
| Arm | 10-yr PSA failure | 14-yr PSA failure | HR (95% CI) | p |
|---|---|---|---|---|
| RT Alone | 25% | 34% | Referent | n/a |
| RT + STAD | 16% | 19% | 0.60 (0.48, 0.76) | < 0.001 |
10 details
Phase III prospective randomized trial, accrued 1538 pts 2009-2016, 1493 eligible for analysis (751 RT alone, 742 RT + STAD). Stratified by number of risk factors (1 vs 2-3), ACE-27 (≥2 vs <2), and RT modality. Median follow-up 9.4 years (10.3 years in survivors).
Non-metastatic intermediate-risk prostate cancer with ≥1 of: clinical stage T2b-T2c, Gleason score 7, PSA >10 but ≤20 ng/mL. Ineligible: all 3 risk factors with ≥50% positive cores. Median age 68, 67% single risk factor, 92% Gleason 7, median PSA 8.1 ng/mL, 67% ACE-27 <2.
STAD: LHRH agonist/antagonist plus oral antiandrogen for 6 months, added to dose-escalated RT. Protocol-compliant or acceptable variation in 91% for the LHRH component and 87% for the antiandrogen.
Physician's choice of EBRT alone to 79.2 Gy or EBRT 45 Gy plus LDR or HDR brachytherapy boost. EBRT alone in 88% (abstract) to 89% (slide). Over 90% of RT plans scored per protocol or variation acceptable for contours and dose.
Primary: overall survival, powered to detect 5-year OS 90% to 93% (HR 0.66) with 85% power. Secondary: biochemical failure, local failure, distant metastasis, prostate cancer death, initiation of salvage therapy, non-prostate cancer death.
Primary OS not met (HR 0.87, p=0.13). Every disease-control secondary favored STAD, including local failure HR 0.44 (per-arm local failure rates not reported in source).
| Endpoint | RT + STAD | RT alone | Effect size |
|---|---|---|---|
| MFS, 10-y | 72% | 67% | n/a |
| MFS, 14-y | 57% | 50% | HR 0.83 (0.69-0.99), p=0.042 |
| Distant metastasis, events | 14 | 40 | HR 0.35 (0.19-0.64), p<0.001 |
| Prostate cancer deaths | 5 | 19 | HR 0.26 (0.10-0.70), p=0.004 |
| PCSM, 10-y | 0.4% | 2.7% | n/a |
| PCSM, 14-y | 2.1% | 3.3% | n/a |
| Salvage ADT, 10-y | 7% | 13% | n/a |
| Salvage ADT, 14-y | 7% | 15% | HR 0.53 (0.38-0.75), p<0.001 |
| Non-prostate cancer deaths | 202 | 220 | HR 0.93 (0.77-1.13) |
Overall late grade ≥3 AEs did not differ (HR 1.08, 95% CI 0.84-1.40). With STAD: grade ≥3 metabolic/lab 20 vs 4, grade 3 sexual function 71 vs 38, grade ≥3 cardiac 26 vs 10 (each p<0.01). EPIC hormone and sexual domains dropped early with STAD and largely converged by 60 months; urinary and bowel domains were similar.
The case for short-term ADT in intermediate-risk disease was built by RTOG 9408 and the D'Amico Dana-Farber trial with conventional-dose RT, leaving open whether dose escalation would erase the benefit. This trial tests that directly and finds the disease-control benefit persists with dose-escalated RT, in line with EORTC 22991.
Disease-control gains are secondary endpoints, and the source states no multiplicity adjustment. MFS (p=0.042) is driven mostly by deaths, with only 40 vs 14 distant metastasis events. Brachytherapy-boost strata are small, and subgroup HRs for OS and MFS are not reported in source.
STAD buys fewer PSA failures, fewer metastases, less salvage ADT and fewer prostate cancer deaths, not a demonstrated survival gain, in a cohort where 422 of 446 deaths were non-prostate. The investigators could not identify a subgroup without benefit for PSA failure and distant metastasis, so omission still rests on competing risk and toxicity tolerance rather than trial-defined selection.
CONSORT flow
Completed phase III with mature f/u; primary OS not met, but durable secondary disease-control gains align with existing STAD use. Powered for HR 0.66, so a smaller OS effect is unresolved.
- Does a brachytherapy boost remove the need for STAD in intermediate-risk disease?
- Can genomic classifiers or MMAI select intermediate-risk pts who can omit STAD?
📚 Sources · 🐦 1 tweet · 📄 2 papers
NRG/RTOG 0815: Ph 3 RCT of dose-escalated RT ± 6 mo STAD in IR PCa (n=1493; median f/u 10.3 y)
— Rashid K. Sayyid (@RKSayyid) September 28, 2026
🚨OS: 10-y 70% (RT alone) vs 74% (RT+STAD); 14-y 53% vs 58% (HR 0.87; p=0.13)
🔹PSA failure: 25% vs 16% at 10 y; 34% vs 19% at 14 y (HR 0.60; p<0.001)
🔹MFS: 67% vs 72% at 10 y; 50%… pic.twitter.com/G5qfgfc9CI
Abstract
Abstract
Biomarkers in Post-operative Prostate Cancer (Spratt)
TL;DR5y MFS 95% vs 82% (HR 0.27) with apalutamide + salvage RT in PAM50 luminal B, flat in non-luminal B (NRG GU006).
Reported via UroToday →
MARCAPPOSEIDONRTOG 9601RTOG 0534NRG GU002NRG GU006BALANCESYMPHONY
Pre-RT PSA, not pathology, sorted hormone therapy benefit in POSEIDON: OS HR 1.14 at PSA ≤0.20 ng/mL vs 0.72 at 0.51-1.0 and 0.69 above 1.0, while adverse feature count showed no interaction (p = 0.40). That weakens GG4-5 or SVI alone as the reason to add ADT to early salvage RT.
In post-RP men with PSA 0.1-1.0 ng/mL and N0M0 disease, a PAM50 luminal B result supports considering systemic intensification with salvage RT; non-luminal B showed no bPFS or MFS separation, and none of this extends to N+/M+ recurrence. The longer read
Pre-RT PSA, not pathology, sorted hormone therapy benefit in POSEIDON: OS HR 1.14 at PSA ≤0.20 ng/mL vs 0.72 at 0.51-1.0 and 0.69 above 1.0, while adverse feature count showed no interaction (p = 0.40). That weakens GG4-5 or SVI alone as the reason to add ADT to early salvage RT.
The systemic read is agent and duration: 24 months of ADT did not beat 4-6 months for OS (HR 0.96), and NRG GU006 tested 6 months of apalutamide, not ADT. Luminal B selected for benefit (5-year MFS 95% vs 82%); non-luminal B did not (90% vs 89%).
14 details 3 trials watching
Trade-press write-up of a single ASTRO 2026 talk (Spratt) covering the POSEIDON IPD meta-analysis (6 randomized trials, 6,057 pts, median f/u 9.0 years), an adverse-feature IPD meta-analysis, NRG GU006 (BALANCE), retrospective PAM50 work in RTOG 0534, and an MMAI digital pathology biomarker in NRG/RTOG 9601 and 0534.
NRG GU006: post-radical prostatectomy, PSA 0.1-1.0 ng/mL, N0M0, PAM50 subtyped before randomization. RTOG 0534: post-radical prostatectomy, PSA 0.1-2.0 ng/mL, N0M0.
GU006: blinded 1:1 randomization to salvage RT + 6 months of apalutamide vs RT + 6 months of placebo. RTOG 0534 arms included RT alone and RT with 6 months of ADT. POSEIDON compared short-term ADT of 4-6 months with long-term ADT of 24 months.
RT dose, fractionation and target volume for the reported trials are not stated in source. The planned SYMPHONY program tests the RT questions directly: 5-fraction vs conventional 20-33 fraction prostate bed SBRT, reduced vs normal dose, and added elective nodal RT.
Effect sizes are in the tables above. The pattern across datasets: hormone therapy benefit tracks pre-RT PSA above 0.50 ng/mL and PAM50 luminal B, and does not track adverse pathologic feature count.
| Pre-RT PSA (ng/mL) | OS HR (95% CI) | p |
|---|---|---|
| ≤0.20 | 1.14 (0.83-1.57) | 0.42 |
| 0.21-0.50 | 0.94 (0.74-1.19) | 0.70 |
| 0.51-1.0 | 0.72 (0.54-0.96) | 0.02 |
| >1.0 | 0.69 (0.48-0.98) | 0.03 |
| Endpoint | Luminal B: apalutamide vs placebo | Luminal B HR | Non-luminal B: apalutamide vs placebo | Non-luminal B HR |
|---|---|---|---|---|
| 5-year bPFS | 72% vs 54% | 0.45 (95% CI 0.24-0.86; p = 0.0062) | 70% vs 71% | 0.95 (80% CI 0.65-1.41; p = 0.44) |
| 5-year MFS | 95% vs 82% | 0.27 (95% CI 0.07-0.95; p = 0.029) | 90% vs 89% | 1.06 (95% CI 0.41-2.78; p = 0.90) |
| Sub-study | Question | Planned per arm | Planned overall |
|---|---|---|---|
| SYMPHONY-PRESTO | Prostate bed SBRT: conventional 20-33 fraction vs 5-fraction | 474 | 948 |
| SYMPHONY-ADAGIO | Normal-dose vs reduced dose RT | 474 | 948 |
| SYMPHONY-CRESCENDO | Prostate bed RT alone vs added elective nodal RT | 435 | 870 |
| SYMPHONY-FULL-SCORE | MDT vs added prostate-bed/nodal treatment in N+/M+ | 240 | 480 |
The talk frames PAM50 against Decipher, which the speaker's figure places at Simon level 1B via prospective-retrospective validation in randomized cohorts including RTOG 9601 and RTOG 0534. PAM50 is presented as a step past that, a level 1A predictive biomarker, because NRG GU006 stratified on it prospectively.
The RTOG 0534 PAM50 analysis is post-hoc and only one of three luminal B comparisons reached p = 0.004; the other two were p=0.10 and p = 0.16. MMAI figures are approximate curve reads. The write-up does not say how N0M0 was staged.
The case for intensification in luminal B is better supported than the case for omission in non-luminal B: the non-luminal B MFS estimate (HR 1.06, 95% CI 0.41-2.78) cannot exclude either benefit or harm. GU006 tested apalutamide, so it does not by itself answer whether PAM50 selects for ADT.
- Does PAM50 luminal B predict benefit from ADT, not only apalutamide, with salvage RT?
- Can non-luminal B pts safely omit systemic therapy with salvage RT?
- Does 5-fraction prostate bed SBRT match conventional fractionation after prostatectomy? recruiting Post-prostatectomy Radiation Therapy--Moderate Versus Ultra-hypofractionated (Also Known as Stereotactic Body Radiation Therapy [SBRT]) Phase 2n=136 · primary completion 2026-11 · randomized ultra- vs moderate hypofx post-RP, 2y QoLrecruiting Salvage Stereotactic Body Radiotherapy of the Prostate Bed for Biochemical Recurrence After Radical Prostatectomy. Phase NAn=284 · primary completion 2029-02 · randomized phase II/III salvage SBRT vs SOC RTn=206 · primary completion 2031-09 · phase 3: 5-fx bed SBRT vs mild hypofx, QoL non-inferiority
📚 Sources · 📄 1 paper
Abstract
REVELUTION (relugolix vs leuprolide + RT, PROs)
ForLocalized intermediate/high-risk prostate cancer, RT + ADT, ADT-naive
TL;DRAt 12 mo, relugolix vs leuprolide with RT: IPSS 5.66 vs 9.22 (p=0.039), EPIC-CP total 12.25 vs 17.25 (p=0.02); post hoc.
The PRO gap tracks with faster testosterone recovery on relugolix (mean 199.7 vs 142.0 ng/dL at 12 mo, P=.010), which plausibly explains better urinary and EPIC-CP total scores. For RT + short-course ADT, that recovery kinetic is the relevant variable when choosing GnRH agent; whether it costs anything in biochemical control is untested here.
In an ADT-naive man with localized intermediate- or high-risk prostate cancer starting RT + ADT, this offers hypothesis-level support for relugolix on 12-mo urinary and overall PRO burden; it says nothing about biochemical or oncologic control.
In RT + ADT for localized intermediate/high-risk disease, relugolix was linked to lower IPSS (5.66 vs 9.22) and EPIC-CP total (12.25 vs 17.25) at 12 mo, with higher mean testosterone. That informs agent choice when RT-related urinary and bowel symptoms are the concern, pending oncologic data.
Mean testosterone at 12 mo was higher on relugolix (199.7 vs 142.0 ng/dL), consistent with faster recovery after an oral antagonist. The PRO benefit may reflect that recovery; disease control with relugolix in this curative RT setting is not addressed by this analysis.
Also covered Jun 16
+2 more figures
| Arm | Mean testosterone at 12 MONTHS (ng/dL) | P |
|---|---|---|
| Relugolix | 199.7 | .010 |
| Leuprolide | 142.0 | .010 |
9 details 1 trial watching
Post hoc QoL analysis of a 1:1 randomized trial, N=65. Parent trial primary: 12-month change in total coronary plaque volume by coronary CT angiography.
Localized intermediate- or high-risk prostate cancer, receiving RT + ADT, no prior ADT.
Relugolix oral daily vs leuprolide injection every 3 months, each with RT.
Relugolix favored on IPSS and EPIC-CP total at 12 mo; incontinence, irritation, sexual and SHIM did not differ (all P≥.15). Mean testosterone at 12 mo 199.7 vs 142.0 ng/dL (P=.010), higher on relugolix.
| Endpoint | Relugolix + RT | Leuprolide + RT | p |
|---|---|---|---|
| IPSS | 5.66 | 9.22 | 0.039 |
| EPIC-CP total | 12.25 | 17.25 | 0.02 |
HERO compared relugolix with leuprolide in advanced prostate cancer; this analysis extends the comparison to the curative RT setting, but only on PROs and testosterone, not disease control.
Open route difference (oral vs injection) could bias self-reported outcomes. Whether pts were still on ADT at 12 mo is not stated, so the testosterone and PRO gaps may reflect recovery timing rather than on-treatment tolerability.
The urinary and global PRO advantage aligns with faster testosterone recovery on relugolix. Whether that recovery trades against biochemical control after RT is the unanswered question.
Post hoc QoL analysis of a trial powered for coronary plaque, N=65; PRO differences not a prespecified endpoint and route of administration unblinded.
- Does faster testosterone recovery on relugolix affect biochemical control after RT?
- Do PRO differences hold in a prespecified, larger trial? n=110 · primary completion 2027-07 · relugolix vs leuprolide, 6 mo ADT, QoL as stated aim
📚 Sources · 🐦 1 tweet
Relugolix vs Leuprolide + RT for Localized PCa: PROs in the REVELUTION RCT @urotoday #ASTRO26
— Zach Klaassen (@zklaassen_md) September 30, 2026
Relugolix vs Leuprolide:
📌T @ 12 mos: 199.7 vs 142.0 ng/dL; p=0.01
📌@ 12 mos:
- ⬇️ IPSS (5.66 vs 9.22; p=0.039)
- ⬇️ EPIC-CP total (12.25 vs 17.25; p=0.02)
- ⬇️ EPIC-CP bowel… pic.twitter.com/Ek2xLZsl3u
RTOG 3506 (STEEL)
ForPost-RP BCR with ≥1 high-risk feature, receiving SRT + 24mo ADT
HR 0.62
80% CI 0.42-0.91, one-sided p=0.052
TL;DRPFS HR 0.62 (80% CI 0.42-0.91, one-sided p=0.052) adding enzalutamide to SRT + 24mo ADT in high-risk post-RP BCR; BF at 2y 11% vs 19%.
Both arms received SRT + 24 months GnRHa, so the trial isolates ARSI intensification, not the RT contribution; SRT dose and field are not reported in source. BF at 2y dropped 19% to 11%, but Gr 3-4 lymphopenia rose 15% vs 5%, worth weighing if pelvic nodal fields are in the plan.
In post-RP BCR with Gleason 8-10, SVI, pN1, persistent PSA or PSA ≥0.7 already planned for SRT + 24 months ADT, this supports discussing enzalutamide as investigational intensification; it does not extend to lower-risk BCR or shorter ADT courses.
RT was fixed across arms, so this informs what to pair with SRT, not dose or field; technique is not reported in source. BF at 2y 11% vs 19% suggests the SRT + 24mo ADT backbone still leaves room for intensification in high-risk BCR.
Enzalutamide 160 mg on top of 24 months GnRHa cut PFS hazard (HR 0.62, 80% CI 0.42-0.91) in a screening design. Gr 3-4 lymphopenia 15% vs 5% and hypertension 8% vs 5% are the toxicity trade to weigh pending phase III.
| Arm | PFS HR (80% CI) | p |
|---|---|---|
| SRT+ENH ADT | 0.62 (0.42, 0.91) | one-sided p=0.052 |
| SRT+STD ADT | Referent | n/a |
+2 more figures
| AE (all grades) | SRT + enhanced AR suppression (N=89) | SRT + standard ADT (N=98) |
|---|---|---|
| Lymphocyte count decreased | 19 (21%) | 11 (11%) |
| Hot flashes | 72 (81%) | 69 (70%) |
| WBC decreased | 15 (17%) | 8 (8%) |
| Anemia | 23 (26%) | 11 (11%) |
| Diarrhea | 44 (49%) | 57 (58%) |
| Urinary incontinence | 15 (17%) | 24 (24%) |
| Hyperglycemia | 11 (12%) | 3 (3%) |
8 details
Randomized phase II, 1:1, n=188, final results. Median follow-up 33.1 mos. Designed with a one-sided type I error of 0.10.
BCR after RP with PSA ≥0.2 ng/mL (or ≥0.1 ng/mL ultrasensitive) plus ≥1 aggressive feature: Gleason 8-10, SVI, pN1, persistently elevated post-RP PSA >0.1 ng/mL, or PSA ≥0.7 ng/mL.
Control: 24 months GnRHa. Experimental: 24 months GnRHa + enzalutamide 160 mg.
Salvage RT in both arms. Dose, fractionation and target volume (prostate bed vs pelvic nodes) are not reported in source.
Primary: PFS. Secondary: biochemical failure, hormone-refractory disease, distant metastasis, cause-specific and overall mortality, physician- and patient-reported toxicity, fatigue (PROMIS-F SF 7a), global QoL (EQ-5D-5L).
PFS HR 0.62 (80% CI 0.42-0.91), one-sided p=0.052. BF at 2 yrs 11% vs 19%.
More Gr 3-4 lymphopenia with enza, 13 (15%) vs 5 (5%), and Gr 3-4 hypertension 7 (8%) vs 5 (5%). All-grade hot flashes 81% vs 70%.
RTOG 9601, GETUG-AFU 16 and SPPORT established adding ADT to SRT; STEEL asks the next question, whether an ARSI on top of long-course ADT adds further. EMBARK tested enzalutamide in high-risk BCR without RT, a different setting.
SRT technique not reported, so RT transferability can't be judged. PFS definition and blinding not stated in source. The 24-month ADT control is itself intensified relative to many current practices.
The signal clears the trial's own screening threshold, but no OS or metastasis data in source, so the cost in lymphopenia and hypertension is set against a surrogate benefit only. The question is now phase III-ready, not practice-ready.
Randomized phase II screening design: one-sided α 0.10, 80% CI, surrogate PFS endpoint, 33mo median f/u. Needs phase III confirmation before ARSI intensification with SRT.
- Does PFS gain translate to MFS or OS?
- Phase III confirmation of ARSI intensification with salvage RT
- Role of pelvic nodal RT alongside enhanced AR suppression
📚 Sources · 🐦 1 tweet
Final Results from RTOG 3506 (STEEL): Randomized Ph II -- 24 mos of Enza + ADT vs ADT in HR Pts with BCR Undergoing Salvage RT @EdwinPosadasMD @urotoday #ASTRO26
— Zach Klaassen (@zklaassen_md) September 29, 2026
📌n=188, mFU 33.1 mos
📌Enza + ADT vs ADT, PFS: HR 0.62, 80%CI 0.41-0.91; p = 0.052
📌BF @ 2 yrs: 11% vs 19% pic.twitter.com/fkHw8hzOri
PACE-A NCT01584258
ForLocalised low/intermediate-risk PCa, Gleason ≤3+4, PSA ≤20, RP candidate
TL;DRSBRT 36.25 Gy/5fx vs prostatectomy: 13 BCF events, HR 0.48 (95% CI 0.16-1.46), p=0.18; 5-yr BCF-free 94.8% vs 94.1% in localised low/intermediate-risk PCa.
Failure was scored at nadir+2 ng/ml after SBRT but >0.2 ng/ml after prostatectomy, so the BCF comparison is not symmetric; salvage is the cleaner read (RT in 5 prostatectomy pts, surgery in 1 SBRT pt). At 36.25 Gy in 5 fractions without ADT, this informs counselling surgical candidates on definitive SBRT.
In a man with low or intermediate-risk localised prostate cancer (cT1-T2, Gleason ≤3+4, PSA ≤20) who is a prostatectomy candidate, this supports presenting SBRT without ADT as a definitive alternative; it does not extend to disease above Gleason 3+4 or PSA 20. The longer read
Failure was scored at nadir+2 ng/ml after SBRT but >0.2 ng/ml after prostatectomy, so the BCF comparison is not symmetric; salvage is the cleaner read (RT in 5 prostatectomy pts, surgery in 1 SBRT pt). At 36.25 Gy in 5 fractions without ADT, this informs counselling surgical candidates on definitive SBRT.
For the operating surgeon the functional contrast is the read: ≥1 urinary pad at 5 years in 14/29 (48%) after prostatectomy vs 3/36 (8.3%) after SBRT, with 5 prostatectomy pts going on to salvage RT. Approach (open, laparoscopic, robot assisted) was mixed and its split is not reported in source.
Also covered Oct 4
| Arm | N | Events | 5-Year event-free (95% CI) | 8-Year event-free (95% CI) |
|---|---|---|---|---|
| Prostatectomy | 60 | 8 | 94% (83, 98) | 84% (68, 92) |
| SBRT | 63 | 5 | 95% (84, 98) | 91% (80, 96) |
+2 more figures
14 details
Phase III, open-label, multicohort RCT (PACE); PACE-A randomised 1:1 to SBRT or prostatectomy. N=123 (63 SBRT, 60 prostatectomy) from 8 centres per the abstract, August 2012 to February 2022. Median follow-up 8 years (IQR 6.1-8.0); analysis by intention to treat.
Men with localised prostate cancer, cT1-T2, Gleason ≤3+4, PSA ≤20 ng/mL, MRI staged, who were suitable candidates for prostatectomy. Median age 65.5 years (IQR 60.5-68.6), median PSA 7.9 ng/mL (IQR 5.9-11.0); 5.7% low-risk and 94.3% intermediate-risk.
SBRT 36.25 Gy in 5 fractions over 1-2 weeks, with no ADT permitted. Target volume, margins, platform and any intraprostatic boost are not reported in source.
Comparator was radical prostatectomy by open, laparoscopic or robot-assisted approach. The split between approaches and nodal dissection practice is not reported in source.
Freedom from biochemical/clinical failure: PSA rise (nadir+2 ng/ml post-RT or >0.2 ng/ml post-prostatectomy), ADT start, recurrence, metastases or prostate cancer death. The source does not state whether this was the prespecified primary endpoint or give a non-inferiority margin. Function by EPIC-26 and clinician-reported CTCAE.
13 BCF events (5 SBRT, 8 prostatectomy), unadjusted HR 0.48 (95% CI 0.16-1.46; p=0.18). BCF-free at 5 years 94.8% (84.6, 98.3) SBRT vs 94.1% (82.6, 98.1) prostatectomy; at 8 years 91.2% (80.1, 96.2) vs 83.7% (68.4, 92.0). Seven deaths, none from prostate cancer.
| Endpoint | SBRT | Prostatectomy |
|---|---|---|
| ≥1 urinary pad at 5 yrs (EPIC-26) | 3/36 (8.3%) | 14/29 (48%) |
| Moderate/big bowel problem (EPIC-26) | 0 | 1/28 (3.6%) |
| CTCAE G≥2 GI | 1/54 (2%) | 0 |
| CTCAE G≥2 GU | 2/53 (3.8%) | 1/40 (2.5%) |
At 5 years, ≥1 urinary pad in 3/36 (8.3%) SBRT vs 14/29 (48%) prostatectomy. Moderate/big bowel problem in 0 SBRT vs 1/28 (3.6%) prostatectomy. Clinician-reported G≥2 GI 1/54 (2%) vs 0 and G≥2 GU 2/53 (3.8%) vs 1/40 (2.5%), SBRT vs prostatectomy. Sexual function is not reported in source.
ProtecT is the randomised reference for surgery against radiotherapy in localised disease, using conventionally fractionated RT rather than SBRT. PACE-B, a sibling cohort of the same trial, compared SBRT with longer-course RT in men not headed for surgery. This is the direct randomised SBRT against prostatectomy efficacy comparison that the abstract describes as lacking.
Failure thresholds differ by arm, so PSA failure is detectable earlier after surgery than after SBRT. The 5-year pad figures rest on 36 and 29 respondents of 63 and 60 randomised. The tweet reports 10 centres against the abstract's 8, and the slide labels the absolute-difference interval 90% CI where the abstract says 95%.
The 5-year rates are near identical and the 8-year gap rests on few men at risk, so the defensible read is no detectable difference, not SBRT superiority. The continence contrast is the largest effect in the dataset and the bowel penalty usually set against RT is not visible here. It does not settle metastasis or mortality outcomes.
CONSORT flow
Randomised phase III supporting an already-listed SBRT option, but only 13 events, a CI spanning both directions, no non-inferiority margin, and arm-specific failure definitions. Supports, does not prove, equivalence.
- Metastasis and prostate cancer mortality by arm with more events
- SBRT vs prostatectomy above Gleason 3+4 or with ADT
- Sexual function by arm, not reported in source
📚 Sources · 🐦 1 tweet · 📄 1 paper
#ASTRO26 Plenary -- PACE-A: 5-yr Outcomes of RP vs SBRT for GG1-2 PCa @nickva1 @urotoday
— Zach Klaassen (@zklaassen_md) September 28, 2026
📍n=123 (60 RP, 63 SBRT), mFU 8 yrs, 10 🇬🇧 centers
📍13 BCF events: HR 0.48, 95% CI 0:16-1.46
📍7 deaths (no PCa): HR 0.55, 95% CI 0.12, 2.46
📍EPIC-26 >=1 urinary pad: 14/29 (48%) RP vs… pic.twitter.com/tSYdMxDayT
Abstract
SWOG S1827/MAVERICK
ForLS or ES-SCLC, no brain mets on MRI after first-line therapy, PS 0-2
HR 0.60
90% CI 0.46-0.78, 1-sided p=0.001 (abstract), p=0.0005 (slide)
TL;DRCFFS HR 0.60 (90% CI 0.46-0.78) favoring MRI surveillance alone over PCI 25 Gy/10 fx in LS/ES-SCLC; interim OS HR 0.90.
The HA-PCI escape route is closed: 77% of PCI was hippocampal-avoidant, and MRI-arm pts pre-declared for HA-PCI still did better than HA-PCI (HR 0.63, 90% CI 0.47-0.83). The omission decision now rests on OS, where the interim upper bound of 1.20 sits inside the 1.25 margin with 190 deaths still pending.
In LS or ES-SCLC with a clean brain MRI after first-line therapy and access to q3-month MRI in year 1, this supports surveillance alone over PCI, including HA-PCI; it does not extend to pts who cannot complete MRI surveillance. The longer read
The HA-PCI escape route is closed: 77% of PCI was hippocampal-avoidant, and MRI-arm pts pre-declared for HA-PCI still did better (HR 0.63, 90% CI 0.47-0.83). Omission of PCI at 25 Gy/10 fx now hinges on OS, where the interim upper bound of 1.20 sits inside the 1.25 margin.
The CFFS benefit of skipping PCI did not differ by receipt of upfront IO (interaction p=0.25), but only 41% received it and ADRIATIC landed mid-accrual. For referral decisions after first-line therapy, the commitment shifts to scheduled brain MRI q3 months in year 1, q6 months in year 2.
Also covered Sep 14
| Timepoint | MRI alone | MRI + PCI |
|---|---|---|
| 6 month CFFS | 37.8% (90% CI 30.0-45.5) | 16.5% (90% CI 10.7-23.4) |
| 12 month CFFS | 17.3% | 5.9% |
+2 more figures
| Characteristic | PCI + MRI (n=152) | MRI alone (n=151) |
|---|---|---|
| Limited stage | 69% | 68% |
| Performance status 0-1 | 91% | 90% |
| Immunotherapy with upfront therapy | 39% | 42% |
| HA-PCI among PCI given | 77% | NA |
11 details 3 trials watching
International randomized phase III, 304 pts randomly assigned 01/2020 to 12/2025. Stratified by stage (LS/ES), receipt of IO, and PS (0-1 vs 2). Median follow-up for living pts 22 months.
LS or ES-SCLC after completing initial therapy, with no BM on MRI before enrollment. 68% LS-SCLC, 41% received immunotherapy with upfront treatment.
PCI 25 Gy in 10 fx, hippocampal avoidance at physician discretion (77% HA-PCI). At brain metastases, RT was recommended in both arms, WBRT or SRS allowed.
Primary: CFFS, time to first cognitive failure on any of HVLT-R, COWA, or Trail Making, or death, by 1-sided 0.05 log-rank. Key secondary: OS non-inferiority with MRI alone, margin 1.25 on the upper 90% CI. MRI and cognitive testing q3 months in year 1, q6 months in year 2.
CFFS favored MRI alone across stage and HA-PCI analyses (table above). Interim OS HR 0.90 (90% CI 0.67-1.20) at 128 deaths, and cognitive failure by Fine-Gray gave a subdistribution HR of 0.62. BM were decreased with PCI with no PFS difference, magnitudes not reported in source.
| Analysis | HR | 90% CI | p |
|---|---|---|---|
| Overall (1° EP) | 0.60 | 0.46-0.78 | 0.001 abstract, 0.0005 slide |
| LS-SCLC | 0.59 | not reported in source | interaction 0.79 slide, 0.92 abstract |
| ES-SCLC | 0.65 | not reported in source | same interaction test |
| HA-PCI intended (declared pre-randomization) | 0.63 | 0.47-0.83 | 0.006 |
The toxicity signal is neurocognitive: objective failure was more frequent with PCI. Day 180 patient-reported cognitive concerns were not different (PROMIS p=0.07, MDASI p=0.69), while longitudinal modeling favored MRI alone. Other toxicities not reported in source.
The source frames the PCI benefit (fewer BM, better OS) as coming from pre-MRI era studies. Takahashi's Japanese randomized trial had already questioned PCI under MRI surveillance in ES-SCLC, and NRG CC003 tested hippocampal avoidance within PCI. This is the first randomized readout covering LS-SCLC under MRI surveillance.
The CFFS table lists 115 and 107 pts against 151 and 152 randomized, with no explanation in source. Slide and abstract p-values differ. The prespecified Day 180 PRO endpoints were negative, so the patient-reported benefit rests on longitudinal modeling.
Hippocampal avoidance did not rescue PCI on this endpoint, which leaves OS as the only argument for prophylaxis. The interim OS estimate is compatible with non-inferiority but is not the final analysis, and 22 months is short for LS pts with curative intent.
CONSORT flow
Randomized phase III, prespecified primary met against PCI. Not labelled practice-changing because the OS non-inferiority analysis is preliminary (128 of 190 deaths) and follow-up is short for LS.
- Does final OS at 190 deaths confirm non-inferiority of MRI surveillance alone? n=668 · primary completion 2026-03 · S1827 itself: MRI alone vs MRI+PCI, lifespan endpointrecruiting PRophylactic Cerebral Irradiation or Active MAgnetic Resonance Imaging Surveillance in Small-cell Lung Cancer Patients (PRIMALung Study) Phase NAn=600 · primary completion 2028-04 · phase 3 OS non-inferiority, MRI alone vs PCI+MRI
- Does omitting PCI hold in LS-SCLC treated with consolidation durvalumab?
- Optimal salvage for MRI-detected brain metastases in SCLC: SRS or WBRT? active Stereotactic Radiation in Patients With Small Cell Lung Cancer and 1-10 Brain Metastases Phase NAn=100 · primary completion 2024-04 · SRS in place of WBRT for SCLC with 1-10 brain mets
📚 Sources · 🐦 1 tweet · 📄 1 paper
In Collaboration with our partners at ASTRO we continue our coverage of #ASTRO26 🚨
— OncoAlert (@OncoAlert) September 28, 2026
LBA 03 - SWOG S1827/MAVERICK: A RANDOMIZED PHASE III TRIAL OF BRAIN MRI SURVEILLANCE WITH AND WITHOUT PROPHYLACTIC CRANIAL IRRADIATION (PCI) FOR SMALL-CELL LUNG CANCER (SCLC)
Presented by Dr.… pic.twitter.com/XwdqCUV9fN