onc brain

International phase 3, randomized 1:1, double-blind, placebo-controlled, multicenter; N=703. Results are from the second interim analysis (IA2), after which the study was stopped. Median follow-up 47.1 mo.

Previously untreated locally advanced unresectable ESCC, EAC or GEJ cancer (cTX N+ M0 or cT2-T4a NX M0), or cervical/upper thoracic EC with supraclavicular nodal M1 only. ECOG 0-1, ineligible for curative surgery but suitable for dCRT.

Pembro 200 mg or placebo Q3W for 8 cycles, then 400 mg or placebo Q6W for 5 cycles, concurrent with dCRT. Chemo backbone FP or FOLFOX by site choice.

50 Gy or 60 Gy with FP, or 50 Gy with FOLFOX, by site choice. Fractionation, technique and target volume not reported in source.

Dual primary: investigator-assessed EFS and OS, tested hierarchically in PD-L1 CPS ≥10, CPS ≥1, then all pts.

EFS not improved in CPS ≥10 (arm-level numbers in table), so every downstream comparison went untested and the study was stopped.

Grade ≥3 AEs in 100% of both arms. Grade 5 AEs 44 (13%) vs 37 (10%), AE discontinuation 117 (34%) vs 97 (27%). Authors report no new safety signals.

Joins KUNLUN (durvalumab + dCRT) as a negative concurrent IO-dCRT trial in esophageal cancer. Adjuvant nivolumab per CheckMate 577 belongs to the resected trimodality setting and is untouched by this result.

RT dose and chemo backbone by site choice with no outcome breakdown, pooled histologies, and no local control or failure-pattern data in source to show whether IO changed in-field control.

A flat EFS and OS in the PD-L1-enriched group argues against a hidden benefit in the untested CPS ≥1 or all-comer groups. Whether timing (consolidation vs concurrent) or histology matters stays open.

Double-blind phase 3 stopped at IA2 after the gatekeeper EFS endpoint failed in the enriched CPS ≥10 group; reaffirms dCRT alone as standard. Downstream populations formally untested.

Open-label, international, randomised phase 3 at 103 centres across six GCIG groups; 1:1 by biased-coin minimisation, stratified by centre, lymphadenectomy, stage and histology. 686 enrolled, 660 in the ITT analysis; median follow-up 60.2 mo.

High-risk endometrial cancer, FIGO 2009: stage IA EEC grade 3 with LVSI, IB EEC grade 3, EEC stage II or III, or serous / clear cell stage IA (with invasion) to III. WHO PS 0-2, no upper age limit; median age 62, stage III in 46% vs 43%.

Experimental arm added cisplatin 50 mg/m² x2 concurrent, then 4 cycles carboplatin AUC5 + paclitaxel 175 mg/m². Both cisplatin cycles completed by 92%; all 4 carboplatin and paclitaxel cycles by 79% and 71%.

Pelvic EBRT 48.6 Gy in 1.8 Gy fractions in both arms; 45.0-50.4 Gy delivered in 100% vs 98%. Vaginal brachy boost for cervical invasion, given in 46% vs 48%.

Co-primary: overall survival and failure-free survival, ITT, Cox-adjusted for stratification factors.

G3+ AEs during treatment 60% vs 12% (p<0.0001). G2+ neuropathy persisted at 3y in 8% vs 1%.

Direction matches the pooled NSGO-EC-9501/EORTC-55991 + ManGO Iliade analysis (PFS 78% vs 69%, OS trend 82% vs 75%), here in a larger trial with concurrent plus adjuvant chemo. GOG-249 found chemo + VBT no better than pelvic EBRT in stage I-II with more pelvic and para-aortic recurrence; the GOG-258 abstract reported no OS/RFS gain for CRT over chemo alone but more vaginal and nodal failures without RT.

Final analysis was time-based, with OS events at 69% of the number required, so a 5% OS difference was below what the trial could detect. RT plan QA outside ANZGOG was still pending, and the stage and age subgroup reads are exploratory.

CRT buys FFS, not OS, at 5y, at the price of a fivefold G3+ toxicity rate and persistent neuropathy. The authors read the stage I-II FFS gain as not outweighing toxicity, so the combined regimen fits individual counselling, mainly in stage III.

Randomised phase 3 met co-primary FFS but missed OS with only 69% of required OS events; direction matches pooled NSGO-EC-9501/ManGO data. Toxicity cost tempers adoption.

Open-label randomised phase 3 non-inferiority trial, 1:1, 12 centres in Sweden and Denmark, N=1200 randomised 2005-2015. Median follow-up 5.0 yr (IQR 3.1-7.0).

Men up to 75 with intermediate-to-high-risk, T1c-T3a N0M0 prostate cancer, PSA ≤20, WHO PS 0-2. No ADT allowed. 89% intermediate risk, 11% high risk.

42.7 Gy/7 fx (3 d/wk, 2.5 wk) vs 78.0 Gy/39 fx (5 d/wk, 8 wk), prescribed as mean PTV dose and designed equi-effective for late effects at α/β = 3 Gy. CTV prostate only, no seminal vesicles; 7 mm isotropic margin with fiducials; 80% 3DCRT.

Primary: failure-free survival (Phoenix nadir+2 biochemical or clinical failure), per-protocol, NI margin 4% at 5yr (critical HR 1.338). Secondary: OS, PCSS, RTOG toxicity, erectile function.

Efficacy and toxicity by arm are tabulated above; the primary met NI with a point estimate of essentially no difference.

UHF carries a higher acute and 1yr GU burden (G2+ at 1yr 6% vs 2%, p=0.0037) that converges by 5yr (5% vs 5%). Late bowel toxicity no different; patient-reported acute urinary and bowel symptoms higher with UHF.

CHHiP, RTOG 0415, PROFIT and HYPRO established moderate hypofractionation against conventional fractionation. HYPO-RT-PC is the first randomised test of ultra-hypofractionation, the evidence the 2018 ASTRO/ASCO/AUA guideline said it was waiting for.

The upper CI bound (1.325) clears the 1.338 limit narrowly. 80% 3DCRT and a 7 mm margin predate modern SBRT delivery, and 7 fx every other weekday is not the 5 fx schedule most programs use. Five-year median follow-up is short for late intermediate-risk failures.

The trial settles disease-control equivalence of UHF for prostate-only, ADT-free treatment. It leaves open UHF with ADT, with SV or nodal coverage, and against moderate hypofractionation.

Randomised phase 3, NI primary met at 5yr median f/u; open-label, per-protocol primary, redesigned from superiority mid-trial. Backs guideline-conditional UHF rather than redefining SOC alone.

Phase III randomized, central telephone randomization at SAKK, stratified by menopausal status, adjuvant chemo and axillary nodes at diagnosis. 178 randomized, 11 ineligible (6%). Median f/u 11.6 yr for surviving pts.

Good-risk ILRR after mastectomy: first recurrence in the ipsilateral chest wall, shoulder, neck or upper arm, or in regional nodes. Eligibility required an ER+ recurrence, or ER unknown with DFI >12 mo and <4 nodules ≤3 cm. Pts with prior adjuvant TAM were excluded.

Every pt had radical excision, then 5000 cGy at 200 cGy/fx, 5 days a week, to the involved region. RT was fixed across arms, so the trial tests systemic therapy added to full local therapy.

Tamoxifen 20 mg/d orally until progression vs observation.

DFS favored TAM (log-rank P=0.053, Gehan-Wilcoxon P=0.008), with no OS difference (P=0.79). The benefit was confined to postmenopausal pts (5-yr DFS 61% vs 33%, P=0.006). In the multivariate model, TAM and DFI >12 mo predicted longer DFS.

No deaths from pulmonary embolism or endometrial cancer attributable to TAM in either menopausal group.

The authors describe this as the only randomized trial of systemic therapy for ILRR to reach its accrual goal. IBCSG Trial 27 was opened to test chemotherapy vs local treatment alone in LRR, a question this trial does not address.

The early-weighted test carries the DFS result while log-rank misses 0.05. The menopausal split rests on small subgroups. Receptor status was not determined in about a third of pts.

The DFS benefit has persisted since the first analysis, but OS is unchanged, possibly because there were few events and competing mortality in postmenopausal pts. The premenopausal OS deficit with TAM is unexplained and nonsignificant, so it reads as noise more than harm.

Mature phase III, but small, 1980s accrual, borderline log-rank DFS and no OS gain. Backs current endocrine therapy after resected ILRR without defining it for TAM-pretreated pts.

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.

Phase 3 trial, 296 men randomized (152 COPORT, 144 HYPORT). This is the 5-year report; median follow-up 7 years (range: 0 to 8). Blinding, stratification and site count are not stated in source.

Postprostatectomy men with either a detectable post-op PSA (source prints "=0.1 ng/mL") and pT2/3 pNX/0 disease, or an undetectable PSA (<0.1 ng/mL) with pT3 disease or pT2 with a positive surgical margin. The split between these two groups is not reported in source.

HYPORT: 62.5 Gy to the prostate bed in 25 fractions of 2.5 Gy. COPORT: 66.6 Gy in 37 fractions of 1.8 Gy, 48% more fractions. Pelvic nodal RT, technique and ADT use are not reported in source.

Primary (reported at 2 years): patient-reported GU and GI toxicity by EPIC, where HYPORT was noninferior. Secondary, reported here: EQ-5D quality of life, AEs, overall survival, prostate-cancer specific survival, and biochemical failure (PSA 0.4 ng/mL and rising; source prints the operator as "=").

Arm-level figures are in the table. No difference in 5-yr EPIC bowel or urinary change scores, EQ-5D change, or 5-yr BF; 31 deaths, 4 (13%) due to prostate cancer.

Grade 3 AEs 16% (23 men) HYPORT vs 7% (11 men) COPORT, p=0.02, driven by grade 3 renal and urinary disorders, 13% vs 3% (p=0.003): noninfective cystitis 7% vs 0%, hematuria 6% vs 0.7%. No grade 4-5 RT-related AEs, one grade 3 stricture (COPORT), and time to grade 3 AEs did not differ (p=0.4).

Moderate hypofractionation for the intact prostate rests on large randomized trials such as CHHiP and PROFIT; the postoperative bed has lacked comparable randomized data. The authors state the grade 3 GU rates, including the excess with HYPORT, were consistent with contemporary series, which the source does not name.

The patient-reported reassurance rests on 56% EPIC and 51% EQ-5D compliance at 5 years, with no account of who dropped out. BF is a secondary endpoint with no stated noninferiority margin, and p-values for the cystitis and hematuria differences are not given.

HYPORT buys a shorter course at the cost of a physician-reported grade 3 cystitis/hematuria excess that patient-reported scores do not register. Biochemical control looks comparable (5-yr BF 21% vs 18%, p=0.3) but the trial was built around toxicity, so equivalence of disease control is suggested, not established.

Phase 3 RCT with its primary PRO noninferiority endpoint met at 2 yr; 5-yr update agrees on PROs and BF but adds a physician-reported G3 GU excess. Abstract only.

Open-label, phase 3, randomized, non-inferiority trial at a single national cancer center in China, 1:1. 820 enrolled (June 2008 to June 2016), 810 in mITT (409 conventional, 401 hypofractionated). Median follow-up 11.5 yr (IQR 9.6 to 13.8).

Women with high-risk breast cancer after mastectomy and axillary dissection. Stage, nodal burden, receptor status, systemic therapy and reconstruction status are not given in the source.

43.5 Gy in 15 fractions over 3 weeks vs 50 Gy in 25 fractions over 5 weeks, to the chest wall and supraclavicular region. Technique, IMN or axillary coverage, bolus and boost are not described in the source.

Primary: 5-year cumulative incidence of locoregional recurrence. Secondary: DFS, OS, late radiation-related toxicity. Outcomes through 10 years were analyzed descriptively.

LRR and fibrosis by arm are in the table. 10-yr DFS (65.2% vs 69.9%) and OS (72.9% vs 77.5%) showed no significant difference; the source does not make the arm order explicit for these two.

No G4-5 late toxicity and no brachial plexopathy in either arm. G1-2 pulmonary fibrosis was more frequent with hypofractionation: 19.7% vs 11.7%, p=0.008. Other late endpoints (lymphedema, skin, cardiac) are not reported in the source.

The START trials established moderate hypofractionation mainly for whole-breast RT after breast conservation, with few mastectomy pts and limited nodal irradiation. This trial fills that PMRT plus supraclavicular gap with long follow-up. DBCG Skagen and HypoG-01 address hypofractionated nodal RT, and RT CHARM and FABREC address the reconstructed chest wall.

The source does not restate the non-inferiority margin, and the 10-yr 95% CI reaches 1.82. Fibrosis ascertainment method is not stated, and grading was unblinded. Accrual ran 2008 to 2016 with RT technique undescribed, so transfer to modern planning is uncertain.

The 10-yr data show no late divergence in locoregional control and no plexus injury after a hypofractionated supraclavicular field. What it leaves open is whether the low-grade fibrosis excess is specific to this schedule and era, and whether the result holds with IMN coverage or reconstruction.

Randomized phase 3 with non-inferiority already shown at 5 yr per source; 10-yr read is descriptive, single-center, open-label. Aligns with the field's adoption of hypofractionated PMRT.

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.

Phase 3, multicentre, open-label RCT at 20 UK NHS hospitals, 2:1 by minimisation, N=205 (136 IMPT, 69 IMRT). IMPT delivered at two proton centres, IMRT at the local referring centre. Median follow-up 28.3 mo (IQR 26.5 to 39.3).

Newly diagnosed locally advanced oropharyngeal SCC suitable for concurrent CRT including bilateral neck treatment; 197/205 (96%) p16-positive, 99 (48%) T3 or T4. Excluded: N3, upfront neck dissection, induction chemo, prior H&N RT, or a feeding tube needed before treatment.

70 Gy to the therapeutic target and 56 Gy to lower-risk volumes in 33 daily fractions over 6.5 weeks, RBE 1.1 for IMPT, same OAR planning priorities in both arms. IMPT plans checked against 3-mm setup and 3.5% range uncertainty, with daily CBCT and a week-3 repeat planning CT in both arms.

Concurrent cisplatin 100 mg/m² every 3 weeks x2. 138 (69%) of 199 received both cisplatin cycles; 49 (25%) received cisplatin then carboplatin.

Co-primary at 12 mo: gastrostomy-tube dependence or severe (≥20%) weight loss, and UW-QoL physical composite score; either reaching significance counted as success (α=0.025 each). LRC and OS were exploratory.

Neither co-primary met. Composite events were driven by weight loss (20/110 vs 3/53); G-tube dependence was 2% in both arms.

14 serious AEs in 12 pts, treatment-related in one IMPT vs four IMRT; no treatment-related deaths. Grade 3 weight loss persisted at 24 mo in 12 (13%) of 95 IMPT pts vs none on IMRT.

PARSPORT made parotid-sparing IMRT the photon benchmark. TORPEdO asks whether IMPT adds function over IMRT planned to the same OAR targets; at 12 mo it did not.

Feeding-tube policy was set per centre and prophylactic placement was lower on IMPT (26% vs 38%), confounding tube and weight endpoints. IMPT delivery was more disrupted (replanning 61% vs 30%, cyclotron-driven interruptions), so a mature proton service may perform differently.

The composite leaned against IMPT on weight loss (18% vs 6% at 12 mo), opposite to the dosimetric hypothesis, though p=0.079 does not establish harm. With OAR doses lower on IMPT for most structures and no functional gain, the gap between dosimetric advantage and patient-reported benefit is now the open question.

Randomised phase 3, both co-primaries null, source concludes IMRT remains SOC. Open-label, N=205, 2:1 allocation: wide CIs cannot exclude a meaningful difference either way.

Subset analysis of the phase 3 HERO trial, which randomized 934 men with advanced prostate cancer 2:1 to relugolix or leuprolide for 48 weeks. This report covers a 90-day recovery period after treatment discontinuation.

184 men who completed 48 weeks of assigned therapy and had no plan to start alternative ADT within the next 12 weeks (24 weeks after a last leuprolide 3-month depot). 137 had received relugolix, 47 leuprolide.

Relugolix 120 mg orally once daily after a single 360 mg loading dose on Day 1, versus leuprolide injections every 12 weeks, each for 48 weeks.

Time to testosterone recovery to ≥280 ng/dL by Kaplan-Meier, PSA during the recovery phase, and adverse events during recovery. No oncologic efficacy endpoint in this analysis.

During recovery, 96% of men had at least one adverse event and 15% had a grade ≥3 event, similar in both groups.

The 90-day window sits inside the pharmacologic tail of a 3-month leuprolide depot, so part of the 53.9% vs 3.2% gap is measurement timing rather than a durable biologic difference. The leuprolide median of 112.0 days derives from 2 recovery events.

Consistent in direction with the parent HERO result, where relugolix gave deeper sustained castration (96.7% vs 88.8%, difference 7.9%, 95% CI 4.1 to 11.8, P<0.001). The trade the two readings define is depth of suppression on-treatment against speed of recovery off-treatment, both favoring the oral antagonist.

This settles a kinetic question, not a clinical one: no recurrence, quality-of-life, or cardiometabolic endpoint is tied to the faster recovery here. Whether restoring normal testosterone months earlier translates into measurable benefit, or into a PSA that reflects recovering physiology rather than disease, remains untested.

Post-hoc subset of a phase 3 trial, non-randomised entry criterion, 137 vs 47 arms; recovery kinetics are a pharmacologic expectation, not a new clinical outcome.

Multicenter open-label randomized phase III noninferiority trial, 16 hospitals across 11 provinces of China, accrual August 2015 to August 2018, N=599 randomly assigned 1:1 (TNT 302, CRT 297). Stratified by tumor location, clinical stage and MRF status; median follow-up 35.0 months (range 8.3-63.9).

Age 18-70, ECOG 0-1, rectal adenocarcinoma of the distal or middle third (0-10cm from anal verge), cT3-4 and/or node-positive, no distant metastases, no prior anticancer treatment. Arms were balanced: cT4 15.9% v 12.8%, MRF involvement 56.3% v 56.2%, clinical stage III 85.8% v 83.5%.

TNT arm received 25Gy in 5 fractions over one week; CRT arm 50Gy in 25 fractions over 5 weeks with concurrent capecitabine 825mg/m2 twice daily. All patients received IMRT, a departure from RAPIDO, Polish II and PRODIGE 23. CTV covered mesorectum, presacral space, internal iliac, obturator nodes and ischiorectal fossa; superior border at the sacral promontory, inferior 2-3cm distal to the tumor, external iliacs added only for cT4b; CTV-to-PTV expansion 0.5-1.0cm.

TNT arm: 4 cycles CAPOX (oxaliplatin 130mg/m2 day 1, capecitabine 1,000mg/m2 twice daily days 1-14) starting 7-14 days after radiotherapy, then TME, then 2 further cycles. CRT arm: concurrent capecitabine during radiotherapy, then TME, then 6 cycles CAPOX. Total mesorectal excision was scheduled 6-8 weeks after preoperative treatment in both arms; a watch-and-wait pathway was permitted for clinical complete responders.

Primary: 3-year disease-free survival, noninferiority claimed if the upper bound of the 95% CI of the HR was at or below 1.43 (an 11% absolute margin against an assumed 65% CRT rate). Secondary endpoints were overall survival, metastasis-free survival, locoregional recurrence and surgical complications. Target accrual 600 with at least 194 DFS events for 80% power at one-sided alpha 0.05.

Acute grade III-V toxicity during preoperative treatment was 26.5% with TNT versus 12.6% with CRT (P<.001), driven almost entirely by hematologic events (grade 3-4 15.8% v 2.0%, P<.001) rather than by anything the radiotherapy added. Radiotherapy delivery itself was cleaner in the short-course arm, with no dose reductions at all, and grade III+ surgical complications were comparable (14.0% v 15.7%, P=.625). Grade III-IV toxicity during adjuvant chemotherapy ran lower after TNT (3.3% v 11.8%, P=.003).

STELLAR is the third randomized trial of short-course radiotherapy plus neoadjuvant chemotherapy against long-course CRT, after Polish II and RAPIDO, with PRODIGE 23 addressing the adjacent question of chemotherapy sequencing around long-course CRT. Its 3-year LRR of 8.4% with TNT sits alongside RAPIDO and PRODIGE 23 (4%-8.3%) and well below Polish II (21%-22%), which enrolled a heavier fixed cT3/cT4 population. Unlike RAPIDO and PRODIGE 23, STELLAR showed no reduction in distant metastasis (3-year DM 22.8% v 24.7%), and its OS advantage mirrors the early Polish II signal that later disappeared at 8 years.

The 11% noninferiority margin is wide, and the authors concede in retrospect that a narrower margin or larger sample would have been defensible given how close the arms proved. Distant metastasis, the endpoint short-course TNT was designed to move, did not separate at all (22.8% v 24.7%), which weakens the mechanistic case for the OS difference. Adjuvant chemotherapy completion also differed between arms (60.0% v 48.3%, P=.009), so postoperative treatment intensity is not held constant across the comparison.

The defensible read is the primary endpoint: 25Gy in 5 fractions followed by CAPOX delivers the same 3-year DFS and the same locoregional control as 50Gy in 25 fractions, in one week of radiotherapy instead of five. The 11.4-point OS separation is the number that will be quoted and the one least supported, since neither MFS nor LRR moved and the same pattern in Polish II did not survive longer follow-up. What transfers most reliably is the technique: full elective pelvic coverage with IMRT at 5x5Gy, delivered without a single dose reduction.

Prespecified noninferiority met on 3yr DFS with adequate accrual, but open-label, 35mo follow-up only, and the OS gain is a secondary endpoint unsupported by MFS or LRR.

Multicenter randomized phase III, N=458, accrual June 6, 2017 to December 27, 2023, median follow-up 51 months. Primary endpoint: DFS. Blinding is not reported and the two regimens are not maskable.

Stage II/III LARC aged 18 to 70 with at least one MRI high-risk feature (cT4a-b, cN2, mesorectal fascia involvement, or cT3c-d with EMVI). Baseline burden was heavy: cT4 47.82%, cN2 75.98%, threatened MRF 70.96%, EMVI 54.80%.

Experimental: one cycle induction CAPOX, LCRT with two cycles concurrent CAPOX, three cycles consolidation CAPOX, then surgery, so all cytotoxic therapy precedes resection. Control: LCRT with concurrent capecitabine, surgery, then six cycles adjuvant CAPOX at 4 to 8 weeks.

Long-course RT in both arms, so RT is the fixed element and the randomized variable is chemotherapy timing plus oxaliplatin exposure. Dose, fractionation, technique and target volume are not reported in the source text, nor is whether concurrent doublet chemotherapy altered RT delivery.

Primary: DFS. Secondary results reported here: MFS, pCR, locoregional failure, overall survival, grade ≥3 adverse events, major postoperative complications.

Primary endpoint met, with MFS moving in step and pCR strongly favoring the experimental arm, while locoregional failure and 3-year OS did not separate. See the efficacy table.

Grade ≥3 toxicity front-loads into the neoadjuvant phase with the doublet, but severe toxicity across the entire treatment course and major postoperative complications were comparable. Total mesorectal excision was performed in approximately 87% (TNT) and 90% (nCRT).

Sits alongside RAPIDO, PRODIGE-23 and STELLAR, the trials that established TNT, but keeps long-course chemoradiation as the RT backbone rather than short-course RT. Unlike RAPIDO's longer follow-up, intensification here did not increase locoregional failure.

Control-arm adjuvant CAPOX delivery and completion are not reported, and a TNT advantage partly reflects therapy planned but not received when postoperative chemotherapy under-delivers. Accrual spanned 2017 to 2023, during which TNT became routine, so control-arm contemporaneity drifted. Age was capped at 70.

The gain is distant, not local: MFS tracks DFS while locoregional failure is flat and low in both arms, which says long-course chemoradiation with a fluoropyrimidine is near its local ceiling in this population and the remaining room is systemic. The pCR tripling is the organ-preservation lever, but pCR is a resection-specimen endpoint and this trial did not test nonoperative management.

Randomized phase III, primary DFS met at 51mo median f/u, but TNT is already established by RAPIDO, PRODIGE-23, STELLAR; this refines regimen rather than the paradigm.