onc brain

Phase 2 open-label RCT (AIO-TRK-0320), 1:1, 20 sites in Germany/Austria. Planned 104 pts; halted early by the SMC after 68 randomized (34/arm) for excess fatal SAEs in the TRT arm. Recruited 2020-2022, last follow-up Sept 2024, post-hoc survival update April 2026.

ES-SCLC with at least stable disease after induction carboplatin-etoposide-atezolizumab. Baseline well balanced between arms and between pts with vs without SAEs. Unselected for lung function.

Consolidative TRT 30 Gy in 10 fractions added to atezolizumab maintenance (arm A) vs atezolizumab maintenance alone (arm B).

Primary: overall survival. Secondary included PFS and safety.

Primary OS not met: the TRT arm was numerically worse with no PFS difference and sharply higher serious and fatal toxicity (see table).

SAEs dominated by infection and respiratory disorders, linked to radiation-induced lymphocyte depletion; fatal-AE pts in arm A had lower baseline DLCO. No other risk factors identified.

CREST (pre-immunotherapy) showed a modest OS benefit from thoracic RT after chemo; TREASURE tested that strategy on an IMpower133-style IO-maintenance backbone and found harm, not benefit.

Open-label; small N (68) and early termination leave OS underpowered with a wide CI. Phase 2; efficacy conclusions provisional, though the safety signal is robust.

Randomised harm signal (SAEs 61% vs 18%, fatal 19% vs 3%) argues against adding consolidative TRT to IO maintenance, contesting emerging RT enthusiasm; OS worse but underpowered by early stop.

Phase 3 open-label RCT, 1:1, N=1607 ITT (808 CWI vs 799 no CWI) across 173 UK, European, and international sites. Median follow-up 9.6y, with 295 OS events (150 vs 145).

Intermediate-risk early breast: pT1N1, pT2N1, pT3N0, or pT2N0 with grade 3 and/or LVI. All had mastectomy, an axillary procedure, and adjuvant systemic therapy.

CWI 40-50 Gy to the chest wall. Supraclavicular fossa irradiated in only 97/808 CWI pts and IMC in 12/808 — this was chest-wall-only treatment, not comprehensive regional nodal RT.

Contemporary systemic backbone: 85% chemotherapy, 79% endocrine therapy, 19% trastuzumab.

OS, DFS, and DMFS were all null; the only endpoint favoring CWI was chest-wall recurrence (see table).

EBCTCG PMRT meta-analysis (Lancet 2014) showed reduced recurrence and breast-cancer mortality in node-positive disease; SUPREMO finds no OS benefit in the intermediate-risk 1-3 node group treated in a modern systemic era.

Open-label; SCF/IMC coverage was sparse and non-standardized, so it does not test comprehensive regional nodal RT. Enrolment 2006-2013 predates some contemporary systemic regimens.

Adequately powered phase 3, prespecified OS endpoint, 10-yr f/u; null result diverges from EBCTCG-based routine PMRT for intermediate-risk 1-3 node disease.

Phase 3 open-label RCT, 1:1, 193 randomized (177 eligible), stratified by performance status, liver function, degree of metastases, and macrovascular invasion. Accrual stopped early after first-line systemic SOC shifted.

Locally advanced HCC unsuitable for or refractory to standard locoregional therapy, fit for first-line systemic. 84.7% male, median age 66; macrovascular invasion in 74%.

Personalized SBRT, 27.5 to 50 Gy in 5 fractions, dose adapted to liver function, delivered before sorafenib.

Primary: overall survival. Secondary: progression-free survival, adverse events, quality of life.

Primary OS trend favored SBRT but missed the prespecified 1-sided threshold (P=.06); stratification-adjusted OS and the secondary PFS were both significant. See the endpoint table.

G3+ treatment-related AEs similar (47% vs 42%, P=.52). Treatment-related deaths: 2 with sorafenib (liver failure, death NOS), 1 with SBRT+sorafenib (lung infection). No excess RT-attributable toxicity.

Predates modern first-line combinations (atezolizumab-bevacizumab, durvalumab-tremelimumab); the sorafenib-alone comparator is now obsolete, leaving open whether SBRT adds over an IO backbone.

Open-label; accrual stopped early (underpowered); primary OS not significant unadjusted; comparator superseded; QoL assessed in small subsets (n=17-20).

Randomised phase 3 argues for adding SBRT to systemic in MVI-heavy HCC, but primary OS not significant (1-sided P=.06), stopped early, sorafenib comparator obsolete.

Phase 3 multicentre RCT, 1:1, N=153 (RT 77 / obs 76), enrolled 2016-2024, stratified by nodal stage (N0/N+) and chemotherapy. Median follow-up 47 mo. Underpowered: accrual fell short of the sample-size goal.

High-risk (T3-4, N1-3, or R+) non-metastatic urothelial MIBC after radical cystectomy. 62% pT3-4, 41% pN+, 28% variant-histology component; median age 57, median 20 nodes dissected, 4.6% positive margins, 2.6% neobladder.

50.4 Gy / 28 fx to cystectomy bed plus pelvic nodes (common / internal / external iliac, presacral, obturator). Stoma- and bowel-sparing IMRT with daily onboard image guidance.

Primary: 2-year locoregional failure-free survival. Secondary: bladder-cancer-specific survival, DFS, overall survival. Fine-Gray competing-risk analysis (distant mets, non-cancer death).

Primary met; the time-to-event secondaries (DFS, BCSS, OS) all favoured RT numerically but none reached significance.

Late grade 3+ toxicity comparable between arms; acute grade 2 GI higher with RT while grade 3 GI was lower, with no toxicity-related discontinuation.

Adjuvant RT after cystectomy is not routine (historic locoregional recurrence ~30% in high-risk pts); BART is the largest RCT in this space. A planned MERCY individual-patient-data meta-analysis will test the OS question.

Underpowered, OS not significant (HR 0.78, p=0.31) on a locoregional surrogate primary. 14/77 RT-arm pts never received RT, so the ITT HR (0.43) understates the per-protocol effect (HR 0.27). No immunotherapy used.

Randomised phase III, prespecified 2y LRFFS primary hit, diverging from the current no-adjuvant-RT norm. Underpowered and OS not significant, so short of practice-changing.

Multicentre non-inferiority phase 3 RCT, 7 Australian hospitals, N=660 biopsy-naive men, randomised 1:1, unmasked, stratified by site. Recruited Mar 2022 to Aug 2025; follow-up ongoing.

Clinical suspicion of significant prostate cancer with non-suspicious or equivocal MRI (PI-RADS 2 in 51%, PI-RADS 3 in 49%) plus high clinical risk (PSA density >0.1, abnormal DRE, family history, BRCA, PSA >10). PSA ≤20 ng/mL, ≤cT2; median age 61, median PSA 5.2.

Co-primary: proportion with clinically significant cancer (Gleason ≥3+4, ≥10% pattern 4; non-inferiority margin 10%) and proportion of the PET arm avoiding biopsy by 6 months (20% threshold), by intention-to-treat.

Both co-primary endpoints met: csPCa detection non-inferior with PET triage, and biopsy avoided in nearly half the PET arm. Post-biopsy AE rates similar between arms.

Open-label with no masking; follow-up ongoing, so long-term safety of avoided biopsies is unconfirmed. Single-country, single tracer ([68Ga]PSMA-11); health-economic and cross-radiopharmaceutical generalisability untested.

Phase 3 non-inferiority RCT met both co-primary endpoints; PSMA-PET biopsy triage diverges from biopsy-all standard. Open-label, single-country, follow-up ongoing.

Phase 2, open-label, randomised (1:1) screening trial, 21 hospitals in 6 countries. 196 randomised (MDT 99, ENRT 97), 190 evaluable, modified ITT. Median follow-up 50 mo (IQR 42-58).

Men with PET-detected pelvic nodal oligorecurrence (≤5 nodes) after radical local prostate treatment; WHO PS 0-1, histologically confirmed adenocarcinoma. All male.

ENRT: 45 Gy/25fx whole pelvis + SIB 65 Gy to PET-positive nodes (or salvage LND). MDT: SBRT 30 Gy/3fx every other day (or salvage LND). Both + 6 mo ADT. Stratified by tracer (choline vs PSMA) and MDT type.

Primary: metastasis-free survival (any M1 on PET or death), modified ITT. Reported with 80% CIs, a phase 2 screening threshold, not the conventional 95%.

Grade 3 events low in both arms and numerically higher with ENRT (urinary incontinence, diarrhoea). No treatment-related deaths.

First randomised ENRT-vs-MDT comparison for nodal oligorecurrence. Prior oligomet RCTs (STOMP, ORIOLE) tested MDT vs observation, not elective nodal RT, so this adds the missing head-to-head.

Open-label; primary endpoint p=0·063 did not clear conventional significance and rests on a phase 2 screening design. Authors position ENRT as a potential standard awaiting phase 3.

First randomised ENRT-vs-MDT comparison; ENRT's MFS edge diverges from MDT-favouring practice. Phase 2 screening design, p=0·063, awaits phase 3.

Phase 3 multicenter RCT with central RT quality assurance; 4004 women randomized 1996-2004 to added IM-MS nodal RT vs none. Prespecified for final analysis at 20yr on a delayed-benefit hypothesis; median follow-up 22.2yr.

Stage I-III breast adenocarcinoma, age ≤75. Eligible if central/medial primary (any nodal status) OR any-quadrant primary with axillary node involvement. Surgery was mastectomy or BCS plus ALND; median age 54.

Intervention added internal-mammary + medial-supraclavicular (levels 3-4) nodal irradiation on top of standard breast/chest-wall RT. 1996-2004 planning era (2D/3D, pre-DIBH/IMRT); dose and fractionation not specified in source text.

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

Primary OS was flatly null; the significant efficacy signals (lower breast cancer mortality, fewer breast recurrences) were offset in OS terms by excess non-breast-cancer deaths. Per-endpoint numbers in the table.

Excess late lung fibrosis, cardiac fibrosis, and cardiac disease with IM-MS-RT is the mechanism behind the competing non-breast-cancer mortality; severe grade 3-4 cardiac and lung events stayed rare in both arms (table).

Aligns with the 10-yr EORTC 22922 report (Poortmans, NEJM 2015) and MA.20 in showing regional nodal RT improves disease control more than OS. The new 20yr signal: late cardiopulmonary deaths neutralize the breast cancer mortality gain.

1996-2004 planning predates modern cardiac-sparing, so the non-breast-cancer-death penalty likely overstates contemporary risk. Systemic therapy followed era standards (tamoxifen era), not current regimens. OS as primary is a high bar a single nodal-RT field rarely clears.

Large randomized phase 3, OS-primary, 22yr f/u: internally valid to contest the IM-MS-RT survival rationale, which the mortality-toxicity tradeoff nullifies. Divergence is the headline.

Phase 3 multicenter RCT, 1:1, N=153 (RT=77 vs Obs=76); stratified by nodal involvement and chemotherapy timing (neoadjuvant/adjuvant/none). Median follow-up 47 mo.

High-risk nonmetastatic urothelial MIBC after radical cystectomy: any of pT3-4, N1-3, margin-positive, or ≤10 nodes dissected. Enrolled 62% pT3-4, 41% pN+.

Stoma-sparing IG-IMRT, 50.4Gy in 28 fractions to the cystectomy bed and pelvic nodes.

Over 90% received perioperative chemotherapy (71% neoadjuvant, 20% adjuvant). None received immunotherapy.

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

Primary LRFS met (HR 0.43, P=.04); DFS, BCSS, and OS all favored RT but none reached significance (see table).

No additional severe toxicity reported with adjuvant pelvic IMRT versus observation.

Reopens the adjuvant-RT-after-cystectomy question that prior Egyptian NCI trials raised for local control; first randomized test in the modern IG-IMRT era.

Small (N=153); primary endpoint is a locoregional-control surrogate, and survival endpoints were underpowered and nonsignificant. No immunotherapy-era comparator.

Randomised phase III hit prespecified primary LRFS endpoint favoring adjuvant RT (non-standard); but N=153 and DFS/BCSS/OS all NS. Field reopened, not settled.

Open-label phase 3 RCT at 16 Chinese public hospitals, randomised 1:1 (54Gy n=108, 45Gy n=116), N=224. Median follow-up 46 mo. DSMB stopped the trial early for benefit (Apr 2021).

LS-SCLC, age 18-70, ECOG 0-1, previously untreated or ≤1 course of platinum-etoposide. Median age 64 (IQR 58-68), 54% male. Stratified by ECOG, stage, prior chemo course and choice.

Both arms VMAT twice-daily, 10 fx/week, PTV 45Gy/30fx. Experimental arm adds a simultaneous integrated boost to 54Gy/30fx to the gross tumour volume. PCI 25Gy/10fx for responders.

Primary: overall survival in the ITT population. Safety analysed as-treated.

mOS 60.7 mo (95% CI 49.2-62.0) with 54Gy vs 39.5 mo (27.5-51.4) with 45Gy, HR 0.55 (0.37-0.72), p=0.003.

Grade 3-4 oesophagitis 13% vs 12% (p=0.84) and pneumonitis 5% vs 6% (p=0.663), no excess with dose escalation. One treatment-related death (MI) in the 54Gy arm.

Prior escalation via once-daily RT (CONVERT, CALGB 30610) did not beat 45Gy BID; this instead escalates the twice-daily schedule with a SIB and shows an OS gain.

Open-label; early DSMB termination for benefit can overestimate the effect. Single-country, modest N=224, and predates adjuvant durvalumab consolidation (ADRIATIC).

Randomised phase 3, primary OS hit (HR 0.55), diverges from the 20-yr 45Gy BID standard. Open-label and DSMB-stopped-early temper it, but design is valid for the divergence.