onc brain

Multicenter phase IIR/III, two-step RCT. Step 1: gemcitabine vs gemcitabine + erlotinib. Step 2 (reported here): random assignment to a sixth chemo cycle ± CXRT after 5 progression-free cycles. N=354 (180 CXRT, 174 chemo).

Curative-intent resected pancreatic head adenocarcinoma, progression-free on adjuvant chemo. Median age 63, 55% male, 56% PS 1.

Fluoropyrimidine-sensitized CXRT added to the sixth cycle. Dose, fractionation, and target volume not stated in the source excerpt.

Primary: overall survival. Secondary: DFS. Powered for HR 0.76 (316 events, 80% power, 1-sided α=.05).

Primary OS not met (HR 0.96). The one positive signal was the treatment-by-nodal-status interaction (OS P=.0063, DFS P=.014) favoring CXRT in node-negative pts; subgroup effect size not in source.

No increase in grade 4/5 toxicity. Grade 3 toxicity higher with CXRT: 38% vs 19% (P<.001).

ESPAC-1's older 5-FU-based CXRT suggested inferior outcomes; here modern CXRT shows no OS harm but no all-comer benefit. Backbone predates FOLFIRINOX-type adjuvant chemo, named in the source as current SOC.

Node-negative benefit rests on a subgroup interaction, not the prespecified primary. Trial underwent multiple mid-course modifications (LAP07, accrual, slow event rate), and no local-control or pattern-of-failure endpoint is reported despite RT's locoregional rationale.

Clean negative primary OS (HR 0.96) reinforces no routine adjuvant CXRT; node-negative benefit is a subgroup interaction needing confirmation; gemcitabine backbone predates FOLFIRINOX.

Planned secondary analysis of the TROG 08.03 RAVES randomised trial comparing adjuvant RT with salvage RT delivered at PSA >0.2 ng/ml after radical prostatectomy. Patient-reported QOL collected prospectively across multiple Australian and New Zealand sites.

EORTC QLQ-C30 and QLQ-PR25. The unit of analysis is a minimal clinically important change (MCIC), a decline of >0.5 SD from baseline, in bowel symptoms, urinary symptoms, sexual activity, and sexual functioning.

The aRT arm (n=166) reported more bowel-symptom MCIC at 1-5 yr than sRT pts who never required RT. Against pts in the sRT group who did receive RT, no consistent differences in urinary, bowel, or sexual domains emerged.

Dose, fractionation, and target volume are not reported in the source text. Median follow-up from RT was 2.6 yr in the salvage group who received RT (IQR 1.2-5.2), and aRT pts started RT younger (63.9 vs 66.8 yr, p=0.01).

Self-reported QOL in an unblinded trial, so expectancy cuts toward the arm that knows it was irradiated. Denominators thin sharply by 5 yr (23 sRT pts post-RT; 8 in the no-RT sexual-functioning group), and the scattered significant timepoints in the aRT-vs-sRT comparison are fragile at that N.

Reframes the early-salvage rationale: the QOL dividend is sparing roughly the share of men who never trigger RT, not delaying exposure. That matters because delay was the intuitive mechanism, and the regression data do not support it.

Prespecified secondary QOL analysis of a randomised trial; supports the already-guideline-endorsed early-salvage strategy. Small late-timepoint denominators and unblinded self-report temper it.

IPD meta-analysis of 7 phase 3 RCTs (MARCAP consortium) of CFRT vs MHFRT. Primary efficacy endpoint PFS; co-primary toxicity late G2+ GU and G2+ GI; co-primary PRO urinary/bowel QoL decrement. Two prespecified strata: isodose vs dose-escalated MHFRT.

Localised prostate cancer. CFRT arm required modern dose (≥70 Gy in 2 Gy equivalents); trials lacking published IPD efficacy or late-toxicity data excluded. 3454 pts across 3 isodose trials, 2426 pts across 4 dose-escalated trials.

Isodose MHFRT exemplified by 60 Gy in 20 fractions; dose-escalated MHFRT schedules pooled (specific fractionations not given in source). Median follow-up 5.4 y (isodose) and 7.1 y (dose-escalated).

Efficacy equivalent to CFRT for both strata. The only toxicity separations were in the dose-escalated arm, late G2+ GI and bowel QoL, not isodose (see table).

Reinforces isodose 60/20 (CHHiP-type) as the standard MHFRT regimen and argues against dose-escalating hypofractionated schedules, which buy no efficacy but cost bowel toxicity.

Physician-scored late toxicity carries grading subjectivity, though PRO data corroborate the bowel signal. Dose-escalated stratum pools heterogeneous fractionation; longer follow-up needed to confirm late-toxicity divergence.

IPD meta-analysis of 7 phase 3 RCTs consolidating isodose 60/20 as standard MHFRT; reinforces current practice, no efficacy gained by dose-escalating.

Phase 3, randomized, non-blinded, international; N=698 (SBRT 353 / MH-IMRT 345). Co-primary: disease-free survival (superiority) and EPIC-26 bowel + urinary-irritation QoL at 24 mo. Interim futility analyses prespecified.

Localized intermediate-risk prostate cancer, median age 68. Stratified by Gleason score, PSA, and rectal manipulation (SpaceOAR in ~55%).

SBRT 36.25 Gy/5 fx (7.25 Gy/fx, 2-3×/wk) vs MH-IMRT 70 Gy/28 fx or 60 Gy/20 fx. CTV = prostate ±1 cm proximal SV; SBRT PTV margin 5 mm radial / 3 mm AP. Fiducials, MRI fusion, daily IGRT mandated.

Co-primary DFS powered for a 38% relative improvement (target HR 0.62). Co-primary QoL: absolute reduction in MCID for EPIC bowel (≥4) and urinary irritation/obstruction (≥5) at 24 mo.

DFS superiority not met (futility bound crossed); QoL split, bowel favored SBRT while urinary irritation did not. Effect sizes in the tables above.

Investigator-reported toxicity favored SBRT: fewer G≥3 GU events, less rectal hemorrhage, less fatigue (all p<0.05). Table above.

Consistent with PACE-B: both show lower urinary-incontinence decline with SBRT vs MH-IMRT. MH-IMRT SOC anchored by RTOG 0415.

Non-blinded, so patient-reported QoL endpoints are unblinded. SBRT was designed to prove superiority and failed it; 3y biochemical failure ran numerically higher with SBRT.

Prespecified phase III; SBRT failed DFS superiority (futility crossed) and did not beat MH-IMRT on the urinary-irritation co-primary. Confirms SBRT as a safe equivalent option, not an upgrade.

Phase 3 RCT (EORTC 22033-26033 with NCIC-CTG/TROG/MRC-CTU), N=478 clinical high-risk WHO grade 2 LGG, randomized to RT vs dose-dense TMZ. Mature results, with post-hoc 2021 WHO molecular reclassification in 73% (351/478).

RT 28 × 1.8 Gy, standard fractionation, as the single-modality comparator arm.

Dose-dense TMZ 75 mg/m² once daily, 21 of 28 days, up to 12 cycles.

Primary: progression-free survival; overall survival co-reported. No significant difference in PFS or OS between arms.

Neither PFS nor OS differed by arm overall; molecular-subgroup OS is in the detail table, with only IDH-wildtype favoring TMZ.

Combined-modality (RT + chemo) was not tested here but has since become standard for IDH-mutant astrocytoma (e.g. RTOG 9802, RT+PCV).

Molecular subtypes are post-hoc reclassification (tissue in 73%); the IDH-wildtype subgroup is small (n=64). Combined-modality untested.

Mature phase 3; the null modality comparison confirms combined-modality's rise as SOC. Molecular subgroups reclassified post-hoc, so no single-modality practice change lands.

Phase 3 open-label RCT, N=802 across 8 countries (2014-2018), median follow-up 8 years. Primary: metastasis-free survival (switched from OS mid-trial for fewer-than-expected deaths). Enzalutamide 160mg × 24mo vs conventional NSAA × 6mo, both on 24mo LHRH agonist + EBRT.

High-risk clinically-localized or locally-advanced prostate, EBRT-suitable. 90% Gleason 8-10, 36% PSA >20, 12% cN1 by conventional imaging. 40% planned pelvic RT, 8% brachytherapy boost.

Prostate to 78Gy, or 46Gy + brachy boost. Pelvic nodal RT 46Gy elective + boost to gross nodes, required for cN1, optional (pre-declared) for cN0. Intensive QA: credentialing, real-time review of first 5 plans per site, 20% sampling thereafter.

Primary MFS not met; PFS positive, OS neutral; benefit isolated to the cN1 and pelvic-RT-planned subgroups (see tables).

The cN1 MFS benefit mirrors STAMPEDE abiraterone; the weaker overall effect reflects ENZARAD's more favorable baseline risk (lower cN1 fraction, lower PSA, less cT3-4).

Active NSAA control (not placebo) narrows the measured enzalutamide effect. Subgroup benefits are prespecified but hypothesis-generating, and the pelvic-RT arm is confounded by nodal enrichment. Primary endpoint switched from OS to MFS mid-trial.

Phase 3, prespecified MFS primary, 8yr f/u, active-NSAA control; negative overall reinforces restrained intensification, cN1/pelvic-RT benefit mirrors STAMPEDE. Subgroups prespecified, not practice-defining alone.

RT randomization of NRG/RTOG 0848 phase 3. After curative-intent resection and adjuvant gemcitabine-based chemo without progression, N=354 randomized to no further therapy (n=174) vs fluoropyrimidine-sensitized CXRT (n=180). Primary: overall survival.

Resected pancreatic head adenocarcinoma; mix of N0 (n=91) and N1 (n=263), predominantly T3 (n=288 vs T1/T2 n=66), mostly negative margins (n=295). Only pts completing adjuvant chemo without progression.

Adjuvant systemic backbone gemcitabine-based: gemcitabine alone (n=236), non-oxaliplatin gemcitabine combinations (n=18), gemcitabine+erlotinib (n=100). Added arm was fluoropyrimidine-sensitized CXRT.

CXRT was fluoropyrimidine-sensitized chemoradiotherapy delivered after completion of adjuvant chemo. RT dose, fractionation, and target volume not reported in source text.

Primary: overall survival. Prespecified 5-yr OS subgroup estimates with interaction tests by nodal status, T stage, margins, CA19-9, sex, age, and systemic regimen.

Primary OS negative: HR 0.96 (90% CI 0.79-1.18), p=0.38; median OS 2.6 vs 2.3 yr. Nodal-status interaction p=0.022 with a node-negative gain (see table).

Gemcitabine backbone predates FOLFIRINOX-era adjuvant standard; authors note the node-negative signal needs confirmation in trials using FOLFIRINOX/FOLFOXIRI.

Node-negative OS benefit is a subgroup finding (n=91, interaction p=0.022), hypothesis-generating. Dated gemcitabine backbone; RT technique not reported in source.

Prospective phase III, primary OS endpoint not met (HR 0.96); reinforces omitting adjuvant CXRT. Node-negative benefit is subgroup-only (interaction p=0.022), needs independent confirmation.

Prospective phase 2, multi-institutional (NRG/RTOG), risk-adapted by WHO grade, extent of resection, and recurrence status. 244 consented, 165 protocol-treated. Central pathology review; data cutoff 8/15/2023.

Adults ≥18, Zubrod 0-1, histologically confirmed unifocal WHO grade 1-3 meningioma, any resection extent. Low-risk n=60, intermediate n=52, high-risk n=53.

Intermediate-risk 54 Gy and high-risk 60 Gy, both in 30 fractions, adjuvant. Low-risk received no RT (observation). No hypofractionation or SRS arm.

Primary (3-yr PFS) reported previously. This analysis reports long-term PFS, OS, and cumulative incidence of progression (competing-risk) at ~12-yr median follow-up.

Per-cohort 10-yr PFS, OS, and cumulative-incidence values are in the table above. Median PFS not reached for low- and intermediate-risk.

RT-attributable grade 3+ toxicity 9.6% (intermediate, 5/52) and 15.1% (high-risk, 8/53). The observed low-risk cohort carried no RT toxicity.

No randomised RT-vs-observation trial in grade 2 meningioma has reported. ROAM/EORTC-1308 and NRG-BN003 (GTR grade 2) remain open; RTOG 0539 is the prospective benchmark.

Each risk cohort is single-arm, no randomised RT-vs-observation comparison; modest per-cohort N (~50-60); grading predates molecular integration into WHO CNS grading.

Prospective multi-institutional risk-adapted phase 2, 12-yr mature f/u, sets RT patient-selection benchmark. Each cohort single-arm; no randomised RT-vs-observation comparison.

Prospective practice-pattern study within the Michigan Radiation Oncology Quality Consortium (MROQC), a statewide RT registry. 553 pts across 26 centers, Jun 2020–Nov 2024. Facility modeled as a random intercept (mixed-effects).

Intact, high-risk M0/N0-1 prostate cancer on definitive RT. GG4-5 75.0%, PSA ≥20 40.0%, cN1 19.9%, cT3/4 13.3%. 27.9% met STAMPEDE M0 intensification criteria.

Primary: intended guideline-concordant ADT (≥18mo). Also assessed: ARPI adoption before vs after STAMPEDE M0 publication, facility-level variability, and multivariable predictors of concordance.

91.3% recommended any ADT, 67.0% guideline-concordant. ARPI intensification among STAMPEDE-eligible rose 0% → 23.2% post-publication. Facility variability persisted on MVA (P<.0001).

Benchmarks real practice against the 2022 AUA/ASTRO guideline (18-36mo ADT) and STAMPEDE M0 (ARPI for high-burden high-risk). Documents a persistent adoption gap, not a treatment effect.

Captures intended ADT duration and recommendations, not delivered therapy or adherence. Single-state consortium limits generalizability, and there is no efficacy or outcome endpoint.

Descriptive practice-pattern audit (no efficacy endpoint); reinforces AUA/ASTRO ADT guideline and STAMPEDE M0 as benchmark, documenting under-adoption rather than testing a new effect.

Phase 3 noninferiority RCT, 1:1, N=2766 enrolled (2540 per-protocol), 67 sites across 5 countries; median follow-up 46.8 mo. Reports the prespecified secondary RFS; primary OS not yet reported.

cN0 T1-T3 breast cancer with 1-2 sentinel-node macrometastases (>2mm). Extends eligibility beyond Z0011 to mastectomy, T3, extracapsular extension, and men.

Nodal RT including nodal target volumes reached 89.9% (SNB-only) and 88.4% (cALND). ALND omission was therefore tested within regional nodal irradiation, not as omission of axillary treatment.

Primary: overall survival (not reported in source). This analysis: prespecified secondary recurrence-free survival, per-protocol and modified ITT.

Noninferiority met: the upper confidence bound stayed below the prespecified 1.44 margin (P<0.001) across 191 recurrence-or-death events.

Consistent with Z0011 (breast-conserving + whole-breast RT) and AMAROS (axillary RT replacing ALND), both null for ALND benefit at 10 yr. SENOMAC adds the macromet-only, mastectomy/T3/ECE/male groups in a larger cohort.

This is the secondary RFS endpoint, not the OS primary, at a 46.8-mo median follow-up short for ER+ biology. The HR 1.44 noninferiority margin is generous, and ~90% nodal RT confounds attribution to surgical omission alone.

Randomised phase 3 noninferiority; prespecified secondary RFS met, extends Z0011/AMAROS de-escalation to mastectomy/T3/ECE/men. Primary OS not yet reported.

Phase 3 open-label RCT, 1:1, SWOG/NRG; N=403 eligible (201 S / 202 AS). Stopped at first interim for futility on OS and PFS. Median follow-up 12 mo (0.03-49).

T1-3N0M0 NSCLC ≤7cm, medically inoperable or declined surgery, ≥1 recurrence risk factor (diameter ≥2cm, SUV ≥6.2, moderate/poor/undifferentiated). Median age 73, median tumor 2.3cm, 89% ECOG 0-1.

SBRT both arms (SoC backbone): 3-8 fractions, BED ≥100 Gy. Stratified by central vs peripheral, <4 vs ≥4cm, PS 0-1 vs 2.

Atezolizumab 1200mg IV Q3wk ×8 (neoadjuvant, concurrent, adjuvant); SBRT initiated at cycle 3.

Primary: overall survival. Secondary: PFS, failure patterns, toxicity, QoL. 1-sided stratified log-rank at 2.5%.

G≥3 AEs 12% AS (21 G3, 1 G4, 1 G5 respiratory-failure death) vs 2% S. Excess toxicity with no efficacy gain.

Prior randomized phase 2 (**PMID 37478883, I-SABR, nivolumab+SBRT) suggested benefit adding IO; S1914 with atezolizumab does not confirm** and shows harm signals.

Open-label; stopped early at interim (median f/u 12mo, only 49 deaths). Former/never-smoker harm is an exploratory subgroup; central review of local recurrence ongoing.

Phase 3 stopped for futility; adding IO to SBRT gave no OS/PFS benefit and excess toxicity, reaffirming SBRT-alone SOC and not confirming the prior phase 2 signal.

Prospective nationwide population-based cohort, N=4541, 6 RT centres, treated 2007-14. IMNI assigned by tumour laterality: right-sided → IMNI, left-sided → no IMNI. Median follow-up 13.7 yr.

Node-positive breast cancer, including the 1-3 positive-node low-burden group. Excluded prior malignancy, bilateral cancer, neoadjuvant systemic therapy, pre-RT recurrence, non-standard RT.

Modern systemic backbone: taxane chemotherapy, trastuzumab, aromatase inhibitors, the era hypothesized to shrink absolute IMNI gain.

3D-based RT. IMNI delivered to right-sided tumours only; laterality allocation balances cardiac dose. Dose/fractionation not reported in source.

Primary: overall survival. Secondary: breast cancer mortality, distant metastasis.

IMNI improved all three endpoints (see table). Absolute 15yr OS gain 4.2% (65.0% vs 60.8%).

Confirms DBCG IMN1 (+4.7% abs OS at 14.8 yr) and the EBCTCG meta-analysis (+3% abs 15yr survival, regional node RT); contradicts the negative Korean KROG 06-08 in the modern-therapy era.

Non-randomized: IMNI assigned by tumour laterality rather than randomization, so residual confounding is possible despite balanced baseline characteristics.

Large prospective laterality-allocated cohort, not randomized; confirms IMN1 + EBCTCG that IMNI benefit persists with modern systemic therapy. Non-random design caps it below practice-changing.