onc brain

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

International open-label phase 3 RCT, 1:1, 58 hospitals in 11 countries, stratified UK vs non-UK. N=157 randomised from 990 screened; median follow-up 64 mo.

Age ≥16, newly diagnosed atypical meningioma after surgeon-assessed GTR (Simpson I–III), WHO PS ≤2, able to start RT within 12 weeks. Excluded NF2, multiple or radiation-induced meningiomas, optic nerve sheath tumours.

IMRT 60 Gy in 30 fx over 6 weeks, median 2.50 mo from surgery. CTV 5–10 mm isotropic from GTV plus 3–5 mm PTV, with prospective central plan review before treatment.

Primary: DFS, surgery to MRI-confirmed recurrence or death. Secondary: HRQoL, neurocognition (UK/Ireland), time to second-line treatment, OS, cost-effectiveness.

Early RT-related AEs in 30 (45%), all G1-2; late in 17 (26%). G2 or 3 RT-related SAEs 5 (8%), including one G2 radiation necrosis and one G2 optic neuritis; no treatment-related deaths.

Before this, evidence was retrospective series and two non-randomised phase 2 cohorts reporting 3-yr PFS 88.7% (60 Gy/30 fx) and 93.8% (54 Gy/30 fx). NRG BN003 asks the same randomised question and will be the replication test.

No central pathology review (5 pts would now be grade 3) and no mandated early postop MRI. HRQoL data fell to 38% at 5 years and neurocognition was UK/Ireland-only with ~45% missing by 24 mo, so the null QoL and cognitive findings are weak.

With 70% of observed pts recurrence-free at 5 years, the result supports offering RT rather than mandating it. Methylation class stratifies risk but did not erase the RT effect, so it cannot yet select who to observe.

First randomised evidence and primary DFS met, but accrual closed at 41 of 46 planned events, CI upper bound 0.97, and recurrence was read locally without masking.

Randomised phase III, four-group intergroup trial (EORTC/NCIC-CTG/TROG/MRC-CTU), N=478, comparing two single-modality first-line strategies. This is the mature analysis; a post hoc reclassification to 2021 WHO criteria was possible in 73% (351/478) with analyzable tissue.

Clinical high-risk WHO grade 2 low-grade glioma, treatment-naive. Post hoc molecular strata: IDHmt/1p19q non-codeleted astrocytoma n=178, IDHmt/1p19q codeleted oligodendroglioma n=109, IDH wild-type n=64.

Standard fractionation, 28 × 1.8 Gy (50.4 Gy), delivered as the entire assigned treatment. No concurrent or adjuvant systemic therapy in the RT arm, which is the gap between this trial and how grade 2 glioma is treated now.

Dose-dense temozolomide 75 mg/m² once daily, 21 of 28 days, up to 12 cycles, given as sole first-line therapy with RT withheld.

progression-free survival. Overall survival and differential response by molecular marker were the mature-analysis questions.

No significant difference in PFS or OS between arms, and the null held across every molecular subtype except IDH wild-type, where OS favored TMZ.

RTOG 9802 established RT followed by PCV as the high-risk grade 2 benchmark, and combined-modality therapy is now standard for IDH-mutant astrocytoma. EORTC 22033 tested neither arm of that question: it asked which single modality to lead with, and answered that it does not matter.

Molecular strata are post hoc in 73% of the enrolled population, so subtype comparisons carry both selection and multiplicity risk. The IDH wild-type finding rests on n=64, and under 2021 criteria those tumors would not be enrolled as grade 2 at all.

The durable contribution is prognostic rather than therapeutic: median OS of 12.9-14.9 years in codeleted oligodendroglioma against 6.6-6.7 years in IDH-mutant astrocytoma quantifies how far molecular class outweighs modality choice. The finding that pts ≥40 fared better than <40 undercuts the age-40 cutoff that still gates high-risk definitions.

Mature randomised phase III, endpoint negative in both arms and across molecular subtypes; the IDHwt survival difference is post hoc, n=64.

Multi-arm prospective phase 2 trial (NCT00895622) of risk-adapted management, not randomised: each risk group followed its own assigned strategy. 244 consented, 165 eligible and treated per protocol. Original endpoint was 3-yr PFS, previously reported; this is the mature analysis with data cutoff 8/15/2023 and median follow-up 12.1, 12.0 and 11.1 years across the three cohorts.

Adults ≥18 with Zubrod 0-1 and histologically confirmed unifocal WHO grade 1-3 meningioma, newly diagnosed or recurrent, any resection extent, with centrally confirmed pathology. Median age 56, 62 in the high-risk group; 65.5% female overall. Recurrent disease made up 30.8% of the intermediate and 47.2% of the high-risk cohorts.

Group 1 (grade 1 post-GTR/STR) was observed only. Group 2 (recurrent grade 1, or newly diagnosed grade 2 post-GTR) received 54 Gy in 30 fractions. Group 3 (newly diagnosed grade 2 post-STR, newly diagnosed grade 3, or recurrent grade 2/3) received 60 Gy in 30 fractions.

The gradient tracks risk assignment cleanly at 10 years, and the two Cox covariates that survive adjustment are recurrent disease and subtotal resection, both for PFS and OS. See the cohort and covariate tables above.

Grade 3+ AEs attributed to radiotherapy occurred in 5 pts (9.6%) of the intermediate-risk and 8 pts (15.1%) of the high-risk cohorts. Newly reported late events in the intermediate group were auditory and neurologic grade 3 plus one grade 4 hemorrhage. Zubrod, MMSE and neurologic function score were stable over time.

This is the mature counterpart to the trial's own 3-yr landmark reports and now sits as the benchmark alongside the ongoing de-escalation questions in NRG BN003 (NCT03180268) and ROAM/EORTC 1308, both of which test whether grade 2 post-GTR needs RT at all. Until those read out, the 10-yr PFS 72.2% and OS 84.7% here are the reference numbers for treating that group.

Pathology was graded under the WHO criteria of the enrolment era, so some group 1 tumors would likely be reclassified today, which is the trial's own proposed explanation for the poor recurrent grade 1 outcomes. Subgroup estimates rest on very small denominators, with intervals such as 15.0% (0-42.0%) for recurrent grade 2 PFS that cannot support a practice decision on their own.

The trial settles the low-risk question (observe after GTR, 10-yr PFS 88.0%) and confirms that high-risk disease is not controlled by 60 Gy, with 10-yr PFS 42.5%. What it cannot settle is whether the intermediate-risk result reflects RT or favorable biology, since no group 2 patient went untreated.

Non-randomised risk-adapted phase 2 with mature 10+ yr follow-up; supports existing consensus (observe post-GTR grade 1, RT otherwise) rather than testing it against a control.