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.

IPD meta-analysis (PROSPERO CRD42023479078) of 7 phase 2 RCTs; the primary MDT-efficacy analysis pooled 6 trials randomizing 472 men to MDT+SOC (n=248) vs SOC (n=224). Median follow-up 40.7 mo (IQR 25.6-53.7).

Oligometastatic (up to 5 mets) prostate cancer; 65% castration-sensitive (n=375), ARTO entirely CRPC and EXTEND baskets CRPC-enriched. 85.5% (n=491) had prior definitive local therapy; median PSA 1.9 both arms.

MDT is delivered per each component trial (EXTEND, STOMP, ORIOLE, ARTO, COMET-SABR), predominantly SBRT-based. Dose, fractionation, target volume, and modality breakdown are not reported in this meta-analysis, so the technique-transfer question can't be answered from source.

Coprimary: PFS and OS. Secondary: rPFS and castration resistance-free survival (CRFS).

MDT plus SOC improved PFS, rPFS, and CRFS across both trial- and patient-level analyses; overall survival did not reach significance (effect sizes in the table above).

STOMP and ORIOLE (observation-controlled SBRT trials) drove the early MDT signal; this pooled IPD extends the PFS/CRFS benefit across 6 trials and shows it persists on a systemic-therapy backbone in the observation-excluded sensitivity analysis.

All 7 component trials are phase 2 with non-blinded randomization ('some concerns' RoB) and open-label PSA-driven endpoints. OS non-significant (p=0.051). SOC arm slightly older (71 vs 68) and more often on 2nd-gen ARPI (59.8% vs 50.4%).

IPD meta-analysis of 6 phase-2 non-blinded RCTs; PFS/rPFS/CRFS clearly hit but OS non-significant. Reinforces the emerging MDT-for-oligomet signal (STOMP, ORIOLE), doesn't establish survival.

Multicenter randomized phase II, 1:1, N=157, enrolled Jan 2019-Sep 2022. Primary: 6-month biochemical response.

Oligometastatic castration-resistant prostate cancer with ≤3 nonvisceral metastatic lesions, in the first-line abiraterone setting.

Both arms received abiraterone acetate + prednisone (AAP). The experimental arm added concomitant SBRT.

SBRT to all sites of disease, concomitant with AAP. Dose/fractionation not reported in source.

Primary: biochemical response (PSA drop ≥50% at 6mo). Secondary: complete BR (PSA <0.2 ng/mL), PFS.

Primary endpoint and PFS both met, favoring the SBRT arm (see results table).

Extends the metastasis-directed SBRT benefit seen in ORIOLE/STOMP (hormone-sensitive oligomet) into first-line CRPC.

Phase II, N=157. Primary endpoint is a PSA surrogate with no OS reported; dose/fractionation and long-term durability not in source.

Randomized phase II, primary hit, named comparator (AAP alone); primary is a PSA surrogate, so supportive of the emerging oligomet MDT paradigm rather than practice-setting.

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 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.