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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 randomised phase 3 trials of PORT with or without hormone therapy, MARCAP consortium, PROSPERO CRD42019134376. One-stage framework, univariable Cox stratified by trial, intention-to-treat. Six randomised comparisons, 6057 pts, median follow-up 9·0 years.

Post-radical-prostatectomy pts receiving prostate-bed radiotherapy, adjuvant or salvage. Median pre-PORT PSA 0·3 ng/mL overall (0·5 in the long-term cohort). Positive margins in 57–60%, Gleason 7 in about two-thirds, seminal vesicle invasion 16–17%. Race and ethnicity data were not available.

Short-term arm was 4–6 months, predominantly GnRH agonist. Long-term was 24 months, GnRH agonist in 425 (86%) of 492 RADICALS three-way pts, with RTOG 9601 contributing bicalutamide monotherapy rather than castration.

PORT to the prostate bed with or without pelvic nodes, per each contributing trial. Dose, fractionation and nodal-volume detail are not reported in the source text, so the RT technique is not standardised across the six randomisations.

Primary: overall survival. Secondary MFS, event-free survival, biochemical recurrence (Fine–Gray). Prespecified interaction testing on pre-PORT PSA and hormone therapy duration, plus 10-year restricted mean survival time and NNT.

The primary endpoint was not met. The signal sits entirely in the PSA interaction and in MFS, both shown in the detail tables.

RTOG 9601 remains the only contributing trial to show an OS benefit, and it enrolled late salvage at higher PSA with bicalutamide, exactly the high-PSA stratum where benefit persists here. The contrast with intact-prostate radiotherapy, where the same consortium's 2022 Lancet Oncology analysis found an OS benefit for added ADT, is the point: the postoperative setting does not inherit it.

The short-term and long-term comparisons draw on different trial populations, and the long-term cohort carried higher PSA and worse pathology, so the duration read is not a clean randomised contrast outside the 1523-pt RADICALS exploratory analysis. Spline thresholds of 1·6 and 2·0 ng/mL sit at the sparse tail of a cohort with median PSA 0·3.

MFS improved while OS did not, and the authors show the MFS effect never clears the ICECaP 0·81 threshold, so the divergence is not simply immature follow-up. What the analysis cannot settle is whether hormone therapy is inert at low PSA or whether its cancer-specific benefit is cancelled by other-cause mortality in pts with indolent disease.

IPD meta-analysis of six randomised trials, prespecified PSA interaction, 9-yr follow-up. Contradicts routine hormone therapy with PORT at low PSA. Duration contrast is exploratory.

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.

Multicenter phase 3 RCT, 1:1, stratified by performance status, liver function, degree of metastases and macrovascular invasion. 193 randomized, 177 eligible; accrual April 2013 to March 2021, stopped early once standard-of-care systemic therapy changed.

HCC unsuitable for or refractory to standard local-regional therapies and candidates for first-line systemic therapy. 150 of 177 (84.7%) male, median age 66 (IQR 60-72), macrovascular invasion in 131 (74.0%).

Personalized SBRT, 27.5 to 50 Gy in 5 fractions, delivered before sorafenib. The dose range is individualized rather than fixed, so the prescription reflects liver reserve and target geometry, not a single protocol dose.

Sorafenib in both arms; the experimental arm added SBRT first. The systemic backbone is identical, so the difference is attributable to radiation.

Primary: overall survival. Secondary: progression-free survival, adverse events, quality of life. The primary OS comparison was tested 1-sided with 90% CIs.

OS 15.8 vs 12.3 mo, HR 0.77 (90% CI 0.59-1.01), 1-sided P=.06; adjusted for stratification factors HR 0.72 (95% CI 0.52-0.99), 2-sided P=.04. PFS 9.2 vs 5.5 mo, HR 0.55 (95% CI 0.40-0.75), P<.001.

Treatment-related G3+ AEs 47% (39 of 83) with SBRT vs 42% (37 of 88) with sorafenib alone, P=.52. Treatment-related deaths: 2 sorafenib (unspecified, liver failure), 1 SBRT arm (lung infection).

The sorafenib comparator is the SHARP-era standard, and 1L HCC has since moved to IO-based combinations, which is why accrual closed. No randomised trial has yet tested SBRT against, or added to, those current regimens.

Early closure leaves the OS test underpowered, and the 2-sided P=.04 comes from the stratification-adjusted model rather than the primary unadjusted analysis. QoL was assessed in only 20 and 17 evaluable pts at 6 months, too few to weigh against the toxicity comparison.

The consistency between an OS HR of 0.77 and a PFS HR of 0.55 in a 74% macrovascular-invasion cohort argues the local effect is real and that OS dilution reflects competing liver and systemic events, not absence of benefit. What it does not settle is whether that local effect survives on top of a systemic backbone that already controls disease better than sorafenib did.

Randomised phase 3, prespecified OS primary, but 1-sided P=.06 misses and accrual closed early; comparator arm is sorafenib, now superseded.

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.

Investigator-initiated, multicentre, non-inferiority phase 3 RCT at seven Australian hospitals, randomised 1:1 (block sizes 2 or 4, stratified by site) via a central web system. No masking of participants or investigators. Enrolment March 2, 2022 to Aug 24, 2025; data cutoff Dec 5, 2025; median follow-up 6.0 months (IQR 5.1-7.0).

Biopsy-naive men with clinical suspicion of significant prostate cancer and PI-RADS 2 or 3 mpMRI plus at least one red flag (PSA density >0.1 ng/mL/mL, abnormal DRE, strong family history, BRCA mutation, PSA >10, PSA doubling time <36 months, or PSA velocity >0.75 ng/mL per year), PSA ≤20 ng/mL, clinical T2 or less. Median age 61 (IQR 56-66), median PSA 5.2 ng/mL, median PSA density 0.13; PI-RADS 2 in 335 (51%) and PI-RADS 3 in 325 (49%).

Experimental: pelvic-only [68Ga]Ga-PSMA-11 PET-CT within 28 days of randomisation, 1.8-2.2 MBq/kg, furosemide 20 mg recommended, acquisition 60-70 min post-injection, low-dose CT without contrast. PRIMARY score 3-5 → PSMA-targeted (plus MRI-targeted) transperineal biopsy; score 1-2 → no biopsy, PSA surveillance at 6, 12, 18 and 24 months. Control: systematic transperineal biopsy, minimum 12 cores.

Co-primary: proportion with clinically significant cancer (Gleason 3+4 with ≥10% pattern 4 or higher) on biopsy within 3 months, non-inferiority margin 10%; and proportion in the PET arm avoiding biopsy within 6 months, threshold 20%. Secondary: clinically insignificant cancer, alternate csPCa definitions, core number, interobserver variability, and patient-reported outcomes.

Both co-primaries met. Covariate-adjusted sensitivity analysis gave 8% vs 13%, difference -4.8% (95% CI -9.5 to -0.1); per-protocol gave 27 (11%) of 236 vs 47 (18%) of 255, difference -7.0% (-13.3 to -0.7). In the PET arm 166 (50%) of 329 scanned were PRIMARY-negative and 163 (50%) positive.

Post-biopsy symptoms were similar between arms: pain 33 (21%) experimental vs 62 (21%) control, haematuria 60 (38%) vs 126 (43%), haematospermia 77 (48%) vs 133 (45%). SHIM-assessed erectile dysfunction did not increase after biopsy (50 [31%] of 160 vs 91 [31%] of 294). The real safety argument is exposure avoided rather than toxicity reduced: 159 men had no biopsy at all.

The only prior evidence was the non-randomised PRIMARY cohort (2021), which reported improved NPV for csPCa in an MRI-triaged population going to systematic biopsy. A literature search to Dec 11, 2025 found no randomised trials of PSMA-PET in the diagnostic setting, so this is the first randomised test of the question rather than a confirmation of one.

Missing protocol biopsies were differential (35 [11%] control vs 7 [2%] experimental), and the prespecified worst-case scenario crosses the 10% margin once four of the 35 unbiopsied controls truly had csPCa, so the non-inferiority claim rests on how those men are counted. The 159 men who avoided biopsy carry no confirmatory histology at a median 6.0 months, and the trial reports 51 (8%) prostatectomies and 7 (1%) radiotherapy with definitive management deferred to the final analysis.

The trial answers a triage question, not a detection-accuracy question: it shows a PSMA-negative result can stand in for a negative biopsy over 6 months in a low-yield population, and that the biopsies still done return less indolent disease. What it does not settle is whether the avoided biopsies were truly negative, or whether the same result holds with an 18F-labelled tracer, at a non-accredited site, or in a health system where a PET costs more than the biopsy it replaces.

Randomised phase 3, prespecified co-primaries both met, so a triage step that halves biopsies is now tested evidence against a biopsy-everyone pathway. Short follow-up limits durability, not internal validity.

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.

Nationwide population-based prospective cohort across six Danish RT centres, 2007-14, allocating IMNI by tumour laterality (right yes, left no) under national guideline. N=4541 of 5206 assessed. Median follow-up 13.7 years for OS, 13.2 for distant metastasis; analysis was intention-to-treat by side.

Macrometastatic node-positive breast cancer receiving locoregional RT; median age 59; 68.3% had 1-3 positive nodes. Excluded: prior malignancy, bilateral disease, neoadjuvant systemic therapy, recurrence before RT, non-standard RT. Axillary surgery was always axillary dissection.

Chemotherapy was three cycles EC (epirubicin 900 mg/m2, cyclophosphamide 600 mg/m2) then three cycles docetaxel 100 mg/m2; 96.2% of chemo pts received a taxane. Tamoxifen premenopausal, aromatase inhibitor postmenopausal; trastuzumab concurrent with chemo and RT in HER2+ (13.5% overall).

48 Gy/24 Fx before Jan 2009 (26.2%), 50 Gy/25 Fx after (73.2%), 3D conformal wide tangents in free-breathing. IMN target was intercostal space 1-4; all pts had axilla level II-III plus interpectoral and level IV, with level I added for ≥6 positive nodes or <10 nodes removed. QA showed IMN CTV V90% 94.6% right vs 20.4% left.

Primary: overall survival. Secondary: breast cancer mortality and distant metastasis, both with non-breast-cancer death as a competing event. Cox models adjusted for age, menopausal status, histology, tumour size, and nodal count, stratified by IHC subtype and grade.

The OS point estimate sits on top of the EBCTCG regional-node meta-analysis rate ratio 0.90 (0.84-0.96) and of KROG 08-06's HR 0.87 (0.57-1.31), the only other 3D-based IMNI study, which was underpowered at n=735 and read as negative. It also reproduces DBCG IMN1's absolute OS gain of 4.7%, arguing the taxane/trastuzumab/AI era did not absorb the benefit.

Contamination runs both ways: 10.1% of left-sided pts (n=238) got IMNI and a quarter of right-sided pts had under 64.8% IMN coverage, so the observed gain likely understates a fully delivered one. Cardiac and lung toxicity were captured only as death, with no smoking, comorbidity, or cardiac-event data, and the era predates PET-CT staging and respiratory gating.

The ER-/HER2+ signal (HR 1.49, 0.98-2.25, interaction p=0.021) echoes Kyndi's DBCG 82b&c finding but conflicts with NSABP B-51, and the analysis was explorative without multiplicity correction, so it should not gate treatment. The medial/central plus ≥4 node cell (HR 0.98, 0.79-1.21) is the one group where benefit looks absent, matching IMN1's 0.91 (0.73-1.15).

Prospective nationwide cohort, prespecified primary endpoint, 13.7y follow-up; contradicts guidelines withholding IMNI at 1-3 nodes. Non-randomised laterality allocation keeps it below practice-changing.

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.

Open-label randomised phase 3, 16 public hospitals in China, 1:1, enrolled June 30 2017 to April 6 2021. Stratified by ECOG, stage, prior chemotherapy course, and platinum choice. Median follow-up 46 months (IQR 33-56); terminated early by the DSMB in April 2021 on interim benefit.

Aged 18-70, ECOG 0-1, VALSG limited-stage confirmed on whole-body FDG PET-CT and brain MRI, previously untreated or after one to two courses of platinum-etoposide. Median age 64, 46% female, 86% stage III, 79% current or former smokers. Age over 70 and ECOG 2 were excluded.

Four cycles of cisplatin 75 mg/m² (or carboplatin AUC 5) with etoposide 100 mg/m² days 1-3 every 3 weeks; 99% completed all four cycles in both arms. PCI 25 Gy in 10 fractions for responsive disease, given to 82% vs 81%.

VMAT, 6-MV, 30 twice-daily fractions over 3 weeks, minimum 6 h apart, starting 0-42 days after cycle 1. Experimental arm delivered a simultaneous integrated boost of 54 Gy to GTV/IGTV with the PTV at 45 Gy; the control arm had 45 Gy to both GTV and PTV. Target volumes were PET-positive lesions only, with elective nodal irradiation omitted and a 5 mm CTV margin.

Primary: overall survival in the ITT population, from the start of chemotherapy. Secondary: PFS, local PFS, metastatic-free survival, disease control rate, acute and late toxicity, and HRQOL (reported elsewhere).

No toxicity penalty for the boost: grade 3-4 oesophagitis 13% vs 12% (p=0.84) and pneumonitis 5% vs 6% (p=0.663). Grade 3-4 neutropenia 44% vs 41%. Late grade 3 pneumonitis in 2 vs 3 pts, no late grade 3 oesophagitis or pulmonary fibrosis in either arm. One treatment-related death (myocardial infarction, 54 Gy arm).

CONVERT (66 Gy in 33 once-daily fractions) and CALGB 30610/RTOG 0538 (70 Gy once daily) both failed to beat 45 Gy twice daily, with median OS 25 vs 30 mo and 28.5 vs 30.1 mo respectively. Neither escalated arm was hyperfractionated or accelerated. The Nordic phase 2 (60 Gy in 40 twice-daily fractions) did show a gain, 2-year OS 74.2% vs 48.1%, and this trial is the phase 3 counterpart of that signal.

Stopping at the interim analysis with 224 of a planned 326 pts inflates the observed effect, and the appendix-level subgroup analysis has not been done. There was no centralised QA of contouring or planning across the 16 centres, and prognostic variables that plausibly drive a dose effect (tumour volume, PTV size) were not balanced by design.

The 21.2-month OS gain is larger than the trial powered for (assumed HR 0.65, 37 vs 24 mo), and the control arm's 39.5 mo sits well above the 20.8-30 mo reported elsewhere for 45 Gy. That points to cohort selection (PET staging, VALSG limited stage, age and ECOG caps) rather than an underperforming control, which is reassuring for internal validity but limits transfer. Local PFS separating (HR 0.51) while MFS does not (HR 0.81) is the mechanistically coherent read for a dose escalation confined to the chest.

Randomised phase 3, prespecified OS primary hit at interim. Diverges from CONVERT/CALGB 30610 dose-escalation failures. Early stopping and single-country cohort temper it.

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.