onc brain

Multicentre randomised (1:1) phase II, N=140 across 22 UK centres, Oct 2016 to Jul 2023. Stratified by SACT, histology, N-stage, number of metastases, brain mets and site. Median follow-up 37.4 mo.

Synchronous oligometastatic AGA-negative NSCLC, 1-5 metastases in ≤3 organs, all sites amenable to SABR/SRS, randomised after initial SACT with CR, PR or SD. Median age 68, 58.6% adenocarcinoma, 52.9% N2/3, 62.9% a single OM site.

SACT was 40.0% chemo, 15.0% IO and 45.0% chemo-IO; the control arm changed to include IO in January 2020. Median SACT cycles was 4 in both arms, with maintenance permitted.

Radical RT to the lung primary ± locoregional nodes plus SABR to all OM sites. 62/70 (88.6%) received RT: 51 conventional and 11 SABR to the primary, 54 SABR to ≥1 OM site. Dose and fractionation not reported in source.

OS. Major secondary: PFS. Also reported: cumulative incidence of local failure and new distant metastasis, AEs, EORTC QLQ-C30/LC13.

G≥3 AE rate 28.6% in both arms; 6 pts had a G3 event possibly RT-related. QoL similar between arms.

The Gomez LCT phase II reported OS 41.2 vs 17.0 mo, but in 49 pts before routine IO. SABR-COMET supported the oligometastatic paradigm with few lung primaries. SARON is the larger NSCLC-specific randomised test and does not reproduce the OS benefit.

Systemic backbone shifted mid-accrual, so the RT effect on a uniform chemo-IO backbone is not isolated. Post-progression therapy, including salvage RT in the control arm, is not reported in source and could compress OS.

RT did what it was aimed at: local failure fell and PFS improved, while new distant metastasis was unchanged. The OS null points to systemic relapse as the limiting event, so lesion count alone selects poorly for the pts in whom ablation alters natural history.

Randomised, completed analysis with OS as stated primary and null result, diverging from prior small LCT trial OS signal. Phase II size leaves OS CI wide.

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.

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.

Randomized, open-label, non-inferiority phase 3 across 32 US centers; 240 consented, 230 randomized 1:1 pre-operatively (115 per arm). Efficacy in the pre-specified mITT population (103 R+TBRT, 101 R+SRT). Median follow-up 12.9 mo (IQR 5.9-22.8); data cut-off October 2025.

Newly diagnosed brain metastases indicated for resection, with one surgical index metastasis 2.0-7.0 cm. mITT required surgery, pathologically confirmed metastasis, and any follow-up information; 14 did not have surgery, 11 had ineligible pathology, 1 had no follow-up.

R+TBRT: collagen tiles each carrying four Cs-131 seeds implanted in the cavity at resection, with post-op CT for dosimetry; prescription dose not reported in source text. R+SRT: volume-dependent cavity SRT, 17-20 Gy/1, 27 Gy/3 or 30 Gy/5, planned 21±7 days from surgery, multi-fraction in 92.2%, median start 27.0 days (range 6-47). Non-index metastases received SRT in both arms.

Co-primary: time-to-SBR (death censored) and SB-RFS (SBR or death), with site-reported SBR centrally reviewed by two neuroradiologists. Secondary: OS, FACT-Br QoL, KPS, Barthel ADL, neurocognition, LMD, RN (site-reported). NI margin HR 1.26; fixed hierarchy from non-inferiority to superiority to OS.

Non-inferiority and then superiority were met for both co-primaries. Local control findings held across mITT, ITT and per-protocol populations; the OS difference did not hold in per-protocol.

Any AE in 83 pts (79.0%) with R+TBRT vs 67 (80.7%) with R+SRT, risk difference -1.7% (95% CI -13.2 to 9.8). ≥G3 TRAEs 20.0% vs 21.7%. 12-mo RN 5.3% vs 5.7% (HR 0.85, p=0.76). No differences in FACT-Br, KPS, Barthel ADL or neurocognition.

Post-op cavity SRT became standard on trials showing better surgical bed control than observation; Mahajan et al. reported 12-month freedom-from-SBR of 72% with single-fraction SRT vs 43% with observation. Multi-institutional fractionated series report 84-87%, and the ROADS control arm (12-mo SBR 15.4%) sits in that range, so tiles beat a contemporary comparator.

Central reviewers were not told the assignment, but seed susceptibility artifact on MRI may have revealed it, and RN was site-reported. The SB-RFS definition was corrected in May 2025 (death had been specified as a censoring event), creating two co-primaries. No granular systemic therapy data, so the OS mechanism cannot be examined.

The surgical bed control result is consistent across analysis populations and rests on few events (1 vs 12). The OS difference is unexplained by distant brain failure or LMD, did not persist in per-protocol, and the authors state it requires validation. How tiles compare with pre-operative SRT (NCT03741673, NCT05438212) is untested.

Randomized phase 3 beat contemporary fractionated SRT on both co-primaries, but 12.9-mo follow-up, 1 vs 12 SBR events, open-label, and 17.8% SRT non-completion hold it short of practice-changing.

Phase 3, international, open-label, 1:1 randomized superiority trial across 136 centers, accruing November 2017 to June 2022 with last follow-up October 2024. N=698 randomized (353 SBRT, 345 MH-IMRT), median follow-up 3.2 years. Two coprimary end points, patient-reported QoL and DFS, each tested at 2-sided alpha .05 with no study-wise correction, so both had to be positive for a positive trial.

Localized cT1-T2b, either Gleason 3+4 (GG2) with PSA <20 ng/mL or Gleason 3+3 (GG1) with PSA 10-20 ng/mL. Median age 68 (range 42-84); 80% White, 13% Black, 3% Asian; 81.7% T1c and 88.1% Zubrod 0. Stratified by risk group and by rectal manipulation, of whom 55.6% used spacer alone and 40.3% no device.

SBRT 36.25 Gy in 5 fractions (7.25 Gy per fraction), delivered as prescribed in 96.6%; MH-IMRT 70 Gy/28 fx in 70.6% or 60 Gy/20 fx in 26.6%. Rectal constraints were max 38 Gy to 0.03 mL and 18 Gy to 50%; bladder 39 Gy and 15 Gy. Where PTV max exceeded 38.78 Gy the urethra had to be contoured and capped at 38.78 Gy, a deliberately uniform, non-escalated prescription. Protocol-compliant or acceptable variation in 97.7% and 97.2% of arms.

Coprimary: MCID frequency in EPIC-26 urinary irritative/obstructive and bowel domains at 24 months, and DFS at 3 years (powered for HR 0.62). Secondary: the other EPIC-26 domains at 12 and 24 months, overall survival, biochemical DFS, regional and distant failure. EPIC-26 adherence was 82% at 1yr and 84% at 2yr.

Urinary irritative/obstructive MCID was flat (35.4% vs 33.7%, P=.68); bowel MCID favored SBRT (34.9% vs 43.8%, P=.03). DFS superiority was rejected at a 91-event interim (HR 1.38, 0.91-2.09), with 3yr rates 88.6% vs 92.1% and no adjusted difference (HR 1.40, P=.12).

Grade 3+4 GU adverse events were lower with SBRT (0.6% vs 2.5%, P=.04), as were any-grade rectal hemorrhage (10.5% vs 17.3%, P=.01) and fatigue (39.2% vs 50.8%, P=.002). Longitudinal bowel scores favored SBRT (LS mean 2.68 [1.02-4.34], P=.002) and urinary incontinence scores likewise (LS mean 2.91 [0.85-4.97], P=.006).

PACE-B and HYPO-RT-PC established that 5-fraction prostate SBRT is tolerable and non-inferior on biochemical control; this trial asked the harder superiority question and lost it, and adds a rectal-manipulation stratification neither predecessor used, which balanced spacer use across arms rather than leaving it a center-level confounder.

The biochemical failure signal, the one result that argues against SBRT, sits on 3-year rates with a CI whose lower bound touches unity (adj HR 1.82, 1.01-3.27) and cannot be separated from the higher benign PSA bounce rate after SBRT, which the trial was not designed to distinguish from true failure. Local, regional and distant failure events were too few to analyze (8 vs 7, 4 vs 2, 4 vs 4), so the mechanism behind the PSA gap is unobserved.

The authors attribute the PSA-control gap to a possible lower biologically effective dose and smaller SBRT margins, the same two choices that plausibly produced the bowel benefit. If that trade is real, it is tunable: focal boost to the dominant intraprostatic lesion was explicitly excluded here and is where the next version of this question belongs.

Randomised phase 3, prespecified coprimary endpoints, ITT: the DFS superiority hypothesis was rejected and biochemical failure ran higher with SBRT, contesting the assumption 5 fractions cost nothing.

Secondary margin-width analysis of NRG Oncology/NSABP B-35, a double-blind randomised trial of tamoxifen vs anastrozole that enrolled 3,104 postmenopausal women 2003-2006. Because local recurrence did not differ between the two endocrine arms, the arms were pooled and margin width analysed across the whole population. Margin data were collected prospectively by participating pathologists.

Postmenopausal women with hormone receptor-positive DCIS treated with lumpectomy. Two overlapping analysis cohorts: n=2,707 with margins classifiable as <1mm (close/indefinite) vs ≥1mm, and n=2,546 with the closest margin measured, permitting a <2mm vs ≥2mm cutoff.

All patients received whole-breast irradiation with an optional boost. Dose, fractionation and boost uptake are not reported in the source, so the RT exposure behind these recurrence rates cannot be characterised beyond "whole breast, boost optional".

Primary endpoint of interest: cumulative incidence of ipsilateral breast tumor recurrence at 10 years, analysed at both the 1mm and 2mm cutoffs. A secondary analysis of all breast cancer events, including contralateral disease, was also performed.

The prevailing 2mm threshold rests largely on the SSO/ASTRO/ASCO DCIS consensus, whose meta-analytic base drew heavily on series with variable and often absent adjuvant therapy. This analysis puts the same question to a uniformly irradiated, uniformly endocrine-treated randomised trial population, which is why the residual margin effect looks so much smaller.

Margin width was not randomised, and patients re-excised on trial carry their final margin, so the narrow-margin group is enriched for disease that could not be cleared. Source reports no hazard ratios, confidence intervals or event counts, and no multivariable adjustment for grade, size, age or boost use.

The claim is that a 1.5% to 1.6% absolute 10-year difference does not justify routine reoperation, which is a value judgment about the trade against anxiety, cosmesis and cost rather than a statistical one. The difference was statistically significant at the 1mm cutoff, so the argument turns on clinical meaningfulness, and a patient who weighs local recurrence heavily could reasonably read the same number differently.

Prospectively collected margin data from a large RCT population directly contests the 2mm re-excision threshold, but the margin comparison itself is non-randomised and abstract-only.

IPD meta-analysis of six randomised phase 3 trials via the MARCAP consortium (PROSPERO CRD42019134376), one-stage Cox stratified by trial. 6057 pts, median follow-up 9.0y (IQR 7.2–10.7).

Men receiving PORT after radical prostatectomy for recurrent prostate cancer. Median pre-PORT PSA 0.3 ng/mL in the any-HT and short-term sets, 0.5 ng/mL in the long-term set. Race and ethnicity data not available.

Short-term HT 4–6 mo (GETUG-AFU 16, NRG/RTOG 0534, RADICALS-HD two-way and three-way), predominantly GnRH agonist. Long-term HT 24 mo (RADICALS three-way, RTOG 9601); RTOG 9601 used high-dose bicalutamide monotherapy.

Primary: overall survival. Secondary: MFS, event-free survival, biochemical recurrence; prespecified interaction tests for pre-PORT PSA and HT duration.

No OS benefit overall (HR 0.87, p=0.06) despite MFS gain (HR 0.79, p<0.001). OS benefit limited to pre-PORT PSA >0.5 ng/mL (interaction p=0.02), with NNT 22 at 0.51–1.00 and 12 at >1.00 ng/mL.

GETUG-AFU 16 and RTOG 0534 established HT with salvage RT on biochemical endpoints; per the ASCO Post write-up only RTOG 9601, a late-salvage trial, had shown an OS benefit. POSEIDON pools these trials and finds the OS signal tracks pre-PORT PSA rather than HT duration.

Duration comparison is confounded: long-term HT trials enrolled higher-PSA, higher-risk pathology. The PSA interaction is model-dependent (continuous PSA: one-stage p=0.19, two-stage p=0.04) and no multiplicity correction was applied. RT dose and field detail not reported in source excerpt.

The trial-level MFS gains held but did not clear the ICECaP surrogate threshold, so the historical case for routine HT with low-PSA salvage rests on endpoints that do not predict OS here. Short-term HT may suffice where HT is used; NRG GU006 (PAM50, apalutamide) tests biomarker selection.

Pooled randomised IPD with prespecified OS primary not met, undercutting routine HT with low-PSA PORT. The PSA >0.5 benefit rests on subgroup interaction, not a primary comparison.

Multicenter open-label phase 2 randomized trial (TREASURE, AIO-TRK-0320) at 20 sites in Germany and Austria, accrual September 2020 to August 2022, follow-up to September 2024, database lock April 2025, post hoc OS update April 2026. Planned 104 randomized for 80% power on a 20% absolute 12-month OS improvement; halted at 68 on SMC recommendation.

ES-SCLC with at least stable disease after induction carboplatin-etoposide-atezolizumab. 34 per arm, mean age 63.3 vs 65.6 y, 63.2% male, ECOG 0-1, thoracic PR in 82.4% overall. Randomization stratified by brain metastases, induction response, and prophylactic cranial irradiation.

30 Gy in 10 fractions to the postinduction thoracic primary and involved lymph node volume. Doses and volumes sat within or below typical clinical ranges and below established organ-at-risk thresholds, and concurrent versus sequential delivery relative to atezolizumab made no difference to AE occurrence.

Primary: overall survival from randomization, by stratified log-rank and multivariable Cox in the ITT population. Secondary: PFS and frequency plus severity of AEs and SAEs. Sensitivity analyses in per-protocol and an adjusted ITT excluding fatal AEs.

SAEs 61.3% vs 18.2% (P < .001) and fatal AEs 19.4% vs 3.0% (P = .04), dominated by infection and respiratory events. Grade 3 or greater trAE rate in arm A (26%) exceeded published benchmarks for atezolizumab monotherapy and for consolidative TRT without immunotherapy, which is the argument for an interaction between the two modalities rather than either alone.

Arm B tracked or beat the IMpower133 atezolizumab benchmark (13.4 mo and 56.6% 1-yr vs 12.3 mo and 51.7%), so the control arm was not underperforming; arm A fell well below it. Prior prospective single-arm series of TRT added to chemoimmunotherapy reported no toxicity increase, while randomized PACIFIC-2 and CheckMate-73L in NSCLC both showed more fatal infections in the concurrent thoracic RT plus IO arms.

Early termination at 68 of 104 makes every efficacy estimate exploratory, and the OS confidence interval (0.90-2.69) crosses 1. Causal attribution of the deaths was contested: investigators called 4 of the arm A fatalities unrelated, the SMC reclassified 3 of those as possibly or probably related. Risk-factor analyses (DLCO SB, GTV, dosimetry) are small-N and post hoc.

The PFS/OS dissociation is the load-bearing observation. Identical PFS argues the RT did nothing systemically, so the OS gap most plausibly reflects treatment-related deaths rather than faster progression, a reading the adjusted-ITT sensitivity analysis complicates by remaining consistent after excluding fatal AEs.

Randomized, prespecified OS primary, halted early for fatal SAEs; result contests the single-arm safety data that encouraged consolidative TRT in the IO era.

ASO Perspectives editorial in Annals of Surgical Oncology, not new trial data. Two radiation oncologists re-read SUPREMO against the PMRT and RNI evidence base. PMRT after neoadjuvant therapy is explicitly out of scope.

The central claim is that SUPREMO tested chest wall alone, not PMRT: RNI was prohibited, supraclavicular nodes were covered in 12% of PMRT-arm pts (n=97), and internal mammary irradiation occurred in fewer than 2% across both arms. Non-UK centres could give RNI in the observation arm, and 12 control pts received supraclavicular RNI.

Only 25% were truly node-negative and would not be offered PMRT under current guidelines; the majority had N1 disease (1-3 nodes). 65% were hormone-receptor positive, TNBC was 10%, and only 14% had SLNB alone with the majority undergoing ALND.

SUPREMO's 10-year chest-wall recurrence fell from 2.5% to 1.1% (HR 0.45) with no gain in overall LRR, DFS or OS. The supplement carries the signal the headline drops: LRR 4.8% to 3.3%, HR 0.51 (95% CI 0.27-0.96) in node-positive pts, not in node-negative.

EBCTCG 2014 found PMRT cut 10-year LRR by 17.9% and 20-year breast cancer mortality by 8% in 1-3 node-positive women, persisting with a single positive node, with no node-negative benefit. MA-20 and EORTC 22922 both showed RNI benefit in 1-3 node-positive disease despite near-universal ALND, and a later EBCTCG RNI meta-analysis showed gains at 15 years including in contemporary systemic-therapy trials.

This is a single-perspective editorial from two radiation oncologists, so the framing selects evidence favouring comprehensive RNI, and the reader gets no independent re-analysis of SUPREMO's data. Its strongest number, the node-positive LRR HR 0.51, comes from a supplementary subgroup the trial did not power for.

The authors leave the genuinely open questions to trials in progress: MA.39 (Tailor-RT) for RNI omission at low recurrence score, T-Rex for RNI omission in hormone-sensitive disease with one to two macrometastatic SLNs. They also note the surgical corollary, that ALND should not be chosen to earn a PMRT omission, since ALND is the dominant lymphedema driver.

Editorial, no new data; contests the omission reading of SUPREMO on field design and population grounds, aligning with ASTRO 2025 and NCCN rather than the trial's public messaging.

Phase III multicenter RCT, 1:1 adjuvant radiotherapy versus observation, N=153 accrued 2016-2024 (RT 77, observation 76). Stratified by nodal stage (N0 vs N+) and chemotherapy timing. Median follow-up 47 months; per-protocol comparison by log rank, with Fine-Gray competing-risk subdistribution HRs for LRFFS (competing risks distant metastases, non-cancer death) and DFS.

High-risk non-metastatic urothelial MIBC post radical cystectomy: T3-4, N1-3, or R+. 62% pT3-T4, 41% pN+, variant histology component in 28%. Median age 57, median nodes dissected 20, positive margin rate 4.6%, neobladder in 2.6%.

Chemotherapy was neoadjuvant in 71% and adjuvant in 20%; 9.2% received none. No patient received immunotherapy in either arm.

50.4Gy in 28 fractions to the cystectomy bed and pelvic nodes. CTV covered common iliac, internal and external iliac, presacral and obturator nodes plus the cystectomy bed. Stoma and bowel sparing IMRT with daily onboard image guidance. 63 of 77 allocated received planned RT.

Primary: 2-year locoregional failure-free survival. Secondary: bladder cancer-specific survival, disease-free survival, overall survival.

Primary endpoint met. Overall 37% recurred, 18% locoregionally (8% RT vs 26% observation, p=0.006), and there were no isolated locoregional recurrences in the RT arm. Survival endpoints all favored RT numerically without reaching significance.

Grade 3 GI events were low and no higher with RT (1.6% vs 4.1%); the cost was grade 2 GI (17.5% vs 1.4%) with no toxicity-related discontinuation. Late grade 3+ toxicity was similar (8.4% vs 10.5%, p=0.60).

The comparator that defines current adjuvant practice is CheckMate 274 (adjuvant nivolumab), which no BART patient received, so this addresses a locoregional failure mode nivolumab was never shown to control. Prior adjuvant RT evidence in this space is the smaller Egyptian NCI randomised experience; BART is described as the largest RCT here.

Accrual over eight years fell short of target, so the survival endpoints are underpowered rather than negative: the OS CI (0.49-1.26) is compatible with both a substantial benefit and modest harm. 14 of 77 allocated to RT never received it and were analyzed with observation (n=90), which is the per-protocol comparison the headline HR 0.27 comes from.

This establishes that pelvic RT after cystectomy does what RT does elsewhere: it controls the field it treats, at an acceptable late-toxicity cost. What it does not establish is whether preventing a locoregional recurrence in a disease this systemically aggressive translates into survival, which the planned MERCY IPD meta-analysis is meant to answer.

Randomised, primary endpoint met, prespecified stratification. Adjuvant RT is not standard post-cystectomy; this is the first positive phase III. Underpowered for OS, no IO backbone.

Prospective randomized phase IIR/III, two-step, multicenter (RTOG then NRG). Step 2 opened November 2009, closed October 2018, analyzed December 2023. Randomization 1:1, unmasked, stratified by nodal status, CA19-9, margins and adjuvant systemic treatment.

Curative-intent gross total resection of pancreatic head adenocarcinoma with documented microscopic margin status; body/tail excluded. Only pts without recurrence after five cycles of chemotherapy entered step 2: 546 entered step 1, 354 randomized (174 chemo, 180 chemo+CXRT). 74% node-positive, 17% margin-positive, 81% T3.

Step 1 was gemcitabine (67%), gemcitabine plus erlotinib (28%) or non-oxaliplatin gemcitabine combinations (5%); no pt received FOLFIRINOX. Both arms then took a sixth cycle; the experimental arm followed with CXRT within 21 days, sensitized by capecitabine (83%) or infusional 5-FU (15%).

50.4 Gy in 28 fractions to the postoperative tumor bed, pancreatojejunostomy and regional nodes; median delivered dose 50.4 Gy over 28 fractions and 38 days. 81% IMRT, 19% 3D conformal, 79% with no interruptions, 88% received ≥50 Gy. Centers were IROC-credentialed and every plan underwent real-time central review before start.

Primary: overall survival from second-step randomization. Secondary: DFS and adverse events (CTCAE v4.0). Final analysis triggered at the earlier of 316 OS events or 5 years of potential follow-up for all pts; it fired on the latter with 270 events, cutting power to 72%.

Grade 4 or 5 AEs were not increased (6% v 5%, P=.68), with one grade 5 in each arm (hepatic failure, sepsis). Grade 3 rose to 38% v 19% (P<.001), driven by GI events and decreased lymphocyte count; grade 3 nonhematologic 22% v 11% (P=.004).

ESPAC-1 reported adjuvant CXRT as detrimental, but accrued 1994-2000 with split-course lower-dose 2D planning, no postoperative imaging to exclude incomplete resection or early metastases, and no QA. RTOG 9704's post hoc analysis linked RT protocol deviations to worse survival, the specific failure mode 0848 designed its real-time review to prevent.

Accrual took almost 9 years and the OS event rate ran below projection, so the trial read out on a follow-up trigger at 270 of 316 planned events (power 72% for the hypothesized HR 0.76). The node-negative arms hold 42 and 49 pts, and the subgroup rests on an interaction P=.022 across nine tested subgroups.

The negative primary settles that unselected adjuvant CXRT adds nothing after gemcitabine-based chemotherapy, while the safety profile removes the ESPAC-1-era objection that RT here is harmful. What stays open is whether the node-negative signal reflects a real locoregional benefit in pts with lower competing distant risk, and whether it survives a modern FOLFIRINOX backbone.

Prespecified stratified phase III, primary OS endpoint negative overall. Node-negative benefit rests on a subgroup interaction (P=.022) in 91 pts, hypothesis-generating not definitive.

Individual patient-level meta-analysis pooling 248 patients from 7 international institutions, all retrospective except one prospective trial. Median follow-up 67.1 months (range 2.13-178). PFS was the primary outcome, analyzed by Kaplan-Meier, Cox MVA, and IPTW propensity weighting.

High-risk meningioma per RTOG 0539: newly diagnosed WHO grade 2 after STR/biopsy, any recurrent grade 2, or any grade 3. 188 (75.8%) were grade 2, 103 (41.5%) recurrent, and 182 (75.2%) had Simpson grade 4/STR. Median age 60; 55 (22.2%) had prior RT.

DE-RT was defined by biologically effective dose ≥79.2 Gy (equivalent to 66 Gy in 33 fractions) or receipt of a carbon-ion boost; anything below that threshold counted as SD-RT. Photon DE-RT used a sequential or simultaneous integrated boost with a 0.5 to 2 mm PTV margin, versus 1-2 cm CTV margins in the SD-RT arm. Carbon DE-RT boosted 16 Gy/8 fx after 50 Gy/25 fx photons with a 6 mm CTV margin.

Whole-cohort 3- and 5-yr PFS were 62.8% and 45.0%. DE-RT improved 3-yr (86.4% vs 55.6%) and 5-yr PFS (65.8% vs 38.8%), P = .0022, holding on stratified Cox by grade (HR 0.40, 0.22-0.73) and after IPTW (3-yr 84.7% vs 55.8%). OS was not improved on MVA or IPTW.

Any-grade radionecrosis was 33.9% with DE-RT vs 13.2% with SD-RT (P = .001), but grade ≥3 RN did not differ (5.1% vs 3.2%, P = .47). All 3 grade ≥3 events in the DE-RT arm occurred in the mixed carbon-photon cohort; the photon-alone DE-RT cohort had none, and its any-grade RN rate was not significantly higher than SD-RT (P = .41). One grade 5 event occurred in each arm.

Published series anchored on RTOG 0539 report 5-yr PFS of roughly 40% to 60% with 60 Gy/30 fx, which is what the SD-RT arm reproduces (45.0% overall). The escalation signal draws on MARCIE (carbon boost) and the Zeng et al. photon series, both contributors to this pool, so the comparison is partly internal rather than independent.

DE-RT was delivered at only 2 of 7 institutions, one carbon-only and one photon-only, so treatment arm is nearly collinear with center, and unmeasured practice differences (DOTATATE PET planning, response assessment, supportive care) travel with it. Molecular classification was unavailable, and P values were not adjusted for multiple testing across the subgroup analyses.

The Simpson 1-3 subgroup showed absolute separation as large as Simpson 4-5 (5-yr PFS 70.0% vs 40.0%) without reaching significance (P = .08 on MVA), which the authors attribute to a smaller GTR subset and fewer events rather than an absent effect. Whether escalation belongs in fully resected disease is the open question, and the PFS-only benefit means the case rests on avoiding local progression and its neurologic morbidity, not on survival.

Retrospective IPD pooling, DE-RT confined to 2 centers, no randomization; IPTW cannot remove selection. Direction consistent across every sensitivity analysis, but prospective randomization still needed.

Secondary analysis of the randomized SWOG S1007 trial (endocrine therapy alone vs chemotherapy then endocrine therapy). Radiotherapy data were prospectively collected across diverse practice settings, but RNI receipt itself was not randomized. Data analyzed June 2022 to April 2023.

Hormone receptor-positive, ERBB2-negative breast cancer with 1 to 3 involved nodes and Oncotype DX 21-gene Recurrence Score ≤25. 4871 female patients had radiotherapy forms; median age 57 (range 18-87).

RNI defined as targeting at least the supraclavicular region. 3947 (81.0%) reported radiotherapy receipt; of 3852 with complete target information, 2274 (59.0%) received RNI. Dose, fractionation, and internal mammary coverage are not reported in source.

Cumulative incidence of locoregional recurrence by locoregional treatment received, plus association between invasive disease-free survival and locoregional therapy, adjusted for menopausal status, treatment group, recurrence score, tumor size, nodes involved, and axillary surgery.

Median follow-up 6.1 years. See the LRR and IDFS tables above; IDFS did not differ by RNI receipt in either menopausal stratum.

MA.20 and EORTC 22922 established the regional irradiation question in node-positive disease, both without an overall survival gain, in cohorts assembled before genomic risk stratification. This analysis reads that question in the population those trials could not define, biologically favorable N1, and finds an LRR floor low enough that a relative benefit has little absolute room to operate.

Radiotherapy information was recorded only in the first year after randomization, forcing a 1-year landmark that excludes the earliest events. Target detail stops at supraclavicular coverage, so internal mammary treatment cannot be separated, and the low absolute event count leaves the IDFS confidence intervals wide enough to accommodate a small effect in either direction.

The finding that matters is the floor, not the comparison: with 5yr LRR at or below 1.7% in every locoregional strategy examined, the population has too few events for regional irradiation to demonstrate meaningful absolute benefit. The explicit conclusion is that omission of chemotherapy is not an independent indication for RNI, which addresses a specific compensatory reflex rather than the general RNI question.

Prospectively collected RT data in a large trial cohort, but RNI receipt was not randomized; observational comparison, so an unmeasured-confounding read is unavoidable.

Prospective multicenter randomized phase 3 trial, accrual 1996-2004, 4004 pts, with an RT quality-assurance program built in. The last analysis was planned at 20 years on the assumption that any survival effect of IM-MS-RT would be delayed. Median follow-up 22.2 years.

Women ≤75 yrs, unilateral histologically confirmed breast adenocarcinoma, stage I-III. Gate was tumor location or nodal status: centrally or medially located primary irrespective of axillary involvement, or any quadrant with axillary involvement. Median age 54.

Randomization was to internal mammary and medial supraclavicular (levels 3-4) nodal irradiation or not, layered on standard breast or chest wall treatment. Dose and fractionation are not given in the source excerpt. Planning ran in the two-dimensional and early-conformal era, when IM coverage at least doubled heart dose.

Primary: overall survival. Secondary: disease-free survival, distant metastases-free survival, breast cancer mortality, any breast recurrence.

Lung fibrosis 6.3% vs 3.2%, cardiac fibrosis 2.7% vs 1.7%, cardiac disease 15.2% vs 11.7% with IM-MS-RT. Severe (grade 3-4) events were uncommon and near-equal: cardiac 1.9% vs 1.7%, lung 0.3% vs 0.0%, so the excess sits in lower-grade, chronic morbidity rather than catastrophic events.

MA.20 and DBCG-IMN both read regional nodal RT positively at roughly ten-year horizons, and DBCG-IMN reported an OS gain. This trial covers the same anatomic question at twice that follow-up and shows the disease-specific gain surviving while the survival gain does not, which is the read those trials were too short to produce.

Systemic therapy was left to physician and institutional preference across an eight-year accrual, so the systemic backbone is heterogeneous and predates current regimens. The competing-mortality signal is a cause-of-death attribution over two decades in a population whose baseline cardiovascular risk rises independently, and the source does not report a cardiac-specific mortality breakdown separating RT-attributable from age-attributable death.

The two effects are both real and point opposite ways: HR 0.82 on breast cancer mortality, HR 1.26 on other deaths, netting HR 1.00 on OS. That arithmetic is the finding, and it argues the relevant question is not whether IM-MS coverage works but whether its cost can be engineered down.

Randomised, prespecified 20yr primary analysis, adequate power, endpoint reported honestly. Divergence from the 10yr-era read of nodal RT is internally valid, not a design artifact.

Multicenter phase III RCT, 1:1 adjuvant RT versus observation after radical cystectomy. 153 patients randomly assigned June 2016 to May 2024 (Obs 76, RT 77), stratified by nodal involvement and chemotherapy timing. Median follow-up 47 months.

Nonmetastatic urothelial MIBC, high risk after RC by any one of T3-4, N1-3, positive margin, or ≤10 nodes dissected. Baseline load was heavy: 62% pT3-T4 and 41% pN+.

Over 90% received systemic chemotherapy (71% neoadjuvant, 20% adjuvant). None received immunotherapy in either arm.

Stoma-sparing IG-IMRT, 50.4Gy in 28 fractions, prescribed to the cystectomy bed and pelvic nodes. Elective nodal coverage was part of the treated volume, not an optional add-on.

Primary: 2-year locoregional recurrence-free survival. Secondary: disease-free survival, bladder cancer-specific survival, overall survival.

The primary endpoint was met; secondary endpoints all favored RT numerically without reaching significance. See the endpoint table for arm-level rates and hazard ratios.

The authors report no additional severe toxicity with adjuvant pelvic IMRT. Grade-level AE breakdown is not reported in the source abstract.

The primary endpoint is a 2-year locoregional readout under a 47-month median follow-up, so the headline reports early control rather than durability. Accrual spanned eight years, during which adjuvant immunotherapy entered practice in this exact population, and the control arm reflects none of it.

Adjuvant pelvic RT after cystectomy has been an open question since the older Egyptian NCI randomized experience, which used larger fields and conventional technique. This is the modern IMRT-era answer, and it lands positive on local control only, not survival.

A HR of 0.43 on locoregional control with an upper CI bound of 0.96 is a real but fragile signal in 153 patients. The consistent numeric direction across DFS (HR 0.62), BCSS (HR 0.59), and OS (HR 0.78) is reassuring but underpowered, and none of it settles whether locoregional control converts to survival.

Randomised, prespecified 2yr LRFS primary endpoint met in a setting where adjuvant RT is not standard. Small N and borderline CI limit confidence, not internal validity.

Systematic review of EBRT publications meeting prespecified HCC technical standards (search date December 15, 2022), with corresponding authors invited to contribute individual patient data. Kaplan-Meier OS and RMST stratified by BCLC stage and treatment status; random-effects Cox for covariates. No comparator arm.

4,913 pts treated with EBRT, median follow-up 5.0 years, multinational. Analyses split by BCLC stage and by treatment-naive vs treatment-experienced; the headline read sits in BCLC-0 and BCLC-A.

EBRT delivered per each contributing series, gated by the prespecified technical standards rather than one protocol. Ablative dose was associated with a reduced risk of death; specific dose levels, fractionation, and modality mix are not given in the source abstract.

Overall survival by Kaplan-Meier and restricted mean survival time, stratified by BCLC stage and treatment status. Covariate associations from multivariable random-effects Cox modeling.

Median OS 6.8 y (95% CI 5.7-8.7) for BCLC-0 and 4.6 y (95% CI 4.1-5.1) for BCLC-A. Treatment-naive: not reached (95% CI 8.6-NR) for BCLC-0, 5.4 y (95% CI 4.5-6.7) for BCLC-A.

The authors frame these medians as comparable with resection, thermal ablation, and other ablative locoregional therapies, a cross-study benchmark rather than a randomised comparison. EBRT's exclusion from BCLC has rested on the absence of OS evidence, which is the gap this cohort is built to fill.

IPD came only from authors who published and agreed to share, so contributing centers are self-selected and unmeasured selection at the patient level (who was routed to EBRT rather than resection) is unrecoverable. More recent year of treatment predicting survival mixes technique gains with stage migration and modern systemic salvage over a multi-decade accrual window.

The claim is an allocation claim, not an efficacy claim: EBRT belongs in the BCLC decision tree as an option to be weighed. It does not settle sequencing against ablation in a pt eligible for both, and the ablative-dose signal makes the quality of the RT, not its mere availability, the operative variable.

Largest EBRT IPD cohort argues for a BCLC allocation change, but it is pooled non-randomised data with no head-to-head comparator against resection or ablation.