onc brain

Multicentre stepped-wedge cluster-randomised non-inferiority trial, 2017-2021, Netherlands Trial Register NTR-6803. This report covers 5y outcomes at median f/u 76 mo (IQR 67-86).

Locally advanced oesophageal cancer with a complete clinical response after nCRT, defined as no tumour on endoscopic biopsies, endoscopic ultrasound, or PET-CT. N=309: 198 active surveillance, 111 standard surgery.

nCRT was the common backbone. The regimen, dose and fractionation are not stated in source, so whether the result transfers to a given chemoRT protocol cannot be judged from this abstract.

The earlier report showed non-inferiority on two-year OS with improved QoL under surveillance. This analysis compares 5y OS and DFS by Cox regression and estimates distant metastasis incidence with competing-risk analysis.

OS and DFS were not significantly different, but distant mets were higher under surveillance (P<.01). 85/198 (43%) were spared non-beneficial oesophagectomy.

This extends SANO's own 2y non-inferiority result and follows the preSANO cCR-assessment framework. It parallels the watch-and-wait paradigm in rectal cancer (OPRA). The randomised definitive-CRT question is being tested separately in NEEDS.

The 43% spared figure counts pts with distant mets within 6 mo of nCRT, which inflates the organ-preservation benefit. At 5y, no NI margin is reported, and an OS HR upper bound of 1.77 cannot exclude clinically relevant harm.

Survival parity holds at 5y, but the distant-mets excess is the signal to explain. It could reflect micrometastatic seeding during delayed resection, or disease surfacing on surveillance imaging that resection would have found later. The abstract cannot separate the two.

Long-term f/u of a cluster-randomised NI trial supporting emerging organ preservation; wide OS CI and a significant distant-mets excess stop short of practice-changing.

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.

Randomized, double-blind, placebo-controlled NRG/RTOG trial; 840 randomized 1998-2003, 760 eligible analyzed (384 vs 376). Median follow-up 13 years among survivors.

Post-RP with lymphadenectomy, pT2 with positive margin or pT3, pN0, detectable PSA 0.2-4.0 ng/ml at least 8 weeks after surgery. No prior RT or chemo; prior hormones limited to short preoperative courses (6.4%). Staging by CT and bone scan.

Bicalutamide 150 mg daily for 24 months vs placebo, starting with RT. Adherence ≥18 months was 69.8% vs 74.7%.

64.8 Gy in 36 fractions of 1.8 Gy to the prostatic bed and membranous urethra, 6-10 MV photons, 2D or 3D planning. Pelvic nodes omitted because all dissections were negative. QA: 64.8% per protocol, 4.4% unacceptable variation.

Primary: overall survival. Secondary: disease-specific death, distant metastases, local progression, non-disease-specific death, second biochemical recurrence, AEs.

Primary met; every disease-control endpoint favored bicalutamide (table). The OS gain is concentrated at entry PSA ≥0.7 ng/ml in post hoc subgroups.

Gynecomastia 69.7% vs 10.9%. Late GU G3 7.0% vs 6.0%; no excess early bladder, bowel or hematologic toxicity, and no excess non-disease-specific death.

SPPORT and RADICALS-HD tested GnRH-based ADT with salvage RT, but neither used a placebo-controlled OS design. The Early Prostate Cancer Program trials of the same drug and dose reported a matching gynecomastia signal (68% vs 8%).

Post-randomization exclusion of 79 ineligible pts departs from strict ITT. Cardiac events were captured only as reported AEs, which risks ascertainment bias. Pre-PSMA staging leaves occult extra-field disease in the cohort.

OS benefit is real but risk-adapted: below PSA 0.7 the subgroup trended the other way. The open questions are whether a modern GnRH agonist reproduces the effect and which duration is enough.

Double-blind placebo-controlled RCT, OS primary met at 13y median f/u. Benefit concentrated at PSA ≥0.7 (post hoc); bicalutamide 150mg since superseded by GnRH agonists.

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.

Exploratory individual-patient-data pooled analysis of 9 prospective GBG/AGO-B neoadjuvant trials (GeparDuo through GeparSepto, PREPARE, TECHNO), 1998-2013. N=10,075; median follow-up 67 mo. Pathologic response was analysed with landmarking (multivariate set N=9552).

Histologically confirmed primary invasive breast cancer, tumour mostly ≥2 cm; locally advanced cT4a-c and inflammatory cT4d eligible in all trials except GeparDuo. 63.6% HR-positive, 28.1% HER2-positive; pCR (ypT0 ypN0) in 20.4%.

Anthracycline/taxane-based NACT in all trials. Anti-HER2 therapy varied by trial (trastuzumab, lapatinib, pertuzumab in later trials; none in GeparDuo, GeparTrio, PREPARE). Endocrine therapy ≥5 years for ER/PgR-positive pts.

Protocols recommended adjuvant RT per national guidelines, with RNI indicated mainly by nodal stage. No patient-level RT data were available, so receipt, fields and dose are unknown.

LRR as first event (breast/chest wall, axillary, infra/supraclavicular nodes) measured from surgery; distant recurrence, second malignancy and death were competing events.

5-yr LRR 7.8% BCS vs 11.3% mastectomy, but surgery type was not an independent predictor in multivariate analysis. Age, cN, grade, subtype and pCR were independent; non-pCR HR 3.33 and TNBC HR 2.72.

The authors place this alongside the EBCTCG meta-analysis, which found higher local recurrence after NACT than after adjuvant chemotherapy, especially with suboptimal local therapy. The NSABP B-51 question (RNI after nodal pCR) is the RT decision these data frame but cannot answer.

Anti-HER2 therapy was inconsistent across eras, which the authors use to explain the lower LRR in HR+/HER2+ disease. gBRCA status incomplete; the univariate surgery effect is likely confounded by selection.

Biology and response drive LRR after NACT more than surgery type. The non-pCR TNBC and HR-/HER2+ groups are where locoregional escalation has the most room to show benefit. With RT unrecorded, the low post-pCR rates are not evidence that RT can be omitted.

Large mature IPD pool of prospective trials confirming known LRR predictors after NACT. Exploratory, prognostic only, and blind to RT delivery, so it cannot test an RT decision.

EBCTCG individual patient data meta-analysis of 88 trials. Kaplan-Meier and Cox regression, stratified by trial and treatment, from year 5 to year 20.

62,923 women with ER-positive T1-T2 disease, 0-9 positive nodes, diagnosed before age 75, scheduled to stop endocrine therapy at 5 years and event-free at year 5. 63% tamoxifen, 17% AI, 20% a tamoxifen-AI sequence; all had lymph-node dissection.

Distant recurrence, any breast-cancer event (distant, locoregional, contralateral), and death from breast cancer by log-rank subtraction.

Recurrences continued at a steady rate from year 5 to 20 in every TN category. Given TN status, grade and Ki-67 carried only moderate independent value after year 5; PR and HER2 status were not predictive.

The source restates EBCTCG data that 5y tamoxifen cut recurrence by about 30% in years 5-10 versus no therapy. Extension trials such as ATLAS and MA.17 test the intervention; this analysis supplies the untreated baseline risk that their proportional benefit acts on.

Grade and Ki-67 were often locally assessed, and Ki-67 was available in only 7692 pts. Few pts received trastuzumab (2%), and treatment eras predate modern staging and systemic therapy.

No TN subgroup had a late risk low enough to dismiss extension outright, even low-grade T1N0 at 10% distant recurrence. Whether extension actually lowers mortality, and in whom it outweighs toxicity, is left to randomised data.

Large multi-trial IPD prognostic analysis, not a randomised test of extension. Quantifies baseline late risk; extended-therapy benefit must come from separate randomised trials.

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.

Unblinded 2-arm randomized noninferiority trial, 1:1, 209 US and Canadian sites, enrolled 2018-2021. N=898 enrolled, 825 evaluable (38 withdrew before RT, 35 ineligible). Median f/u 3.9 yr.

T0N1-2a, T1N1-2a, T2N1-2a or T3N0-2a, M0 after mastectomy, ECOG 0-1, with completed, ongoing or intended reconstruction. Excluded T4, N3, positive margins, collagen vascular disease, bilateral or prior ipsilateral cancer, prior thoracic RT. Median age 49, N1 76%, 51% neoadjuvant chemo.

50 Gy/25 fx over 5 wk vs 42.56 Gy/16 fx over 3 wk. IROC plan QA: 90% per-protocol or acceptable, 4% unacceptable. Target volumes and boost not stated in source excerpt.

Primary: composite reconstruction complications at 24 mo (wound healing, readmission, capsular contracture, unplanned reoperation, failure). NI margin 10%. Secondary: local/locoregional recurrence, acute and late toxicity.

NI met in ITT and in the 631 pts who completed reconstruction within 18 mo. Fractionation effect did not appear to differ by reconstruction type or timing.

Acute G3+ non-reconstruction toxicity 5.0% vs 7.7% (p=0.11). RT-attributed toxicity similar except dermatitis, less frequent with hypofractionation. Late toxicity not statistically different.

Extends the hypofractionation evidence from post-lumpectomy trials (START, FAST-Forward) and post-mastectomy without reconstruction to the reconstructed chest wall, the setting where adoption lagged. Sits alongside FABREC, which tested the same 16-fraction schedule in implant reconstruction; RT CHARM adds autologous and delayed reconstructions.

Margin of 10% was powered on an assumed 25% control rate, but control ran 10.2%, so the margin is relatively generous. Unblinded assessment of complications; 35 pts lacked reconstruction forms at freeze. Late contracture and failure need longer f/u.

Reconstruction timing (delayed OR 2.96) moved complication risk far more than fractionation. The remaining questions are long-term reconstruction durability and whether shorter schedules (5 fx) hold up in this setting.

Randomized NI met across 209 sites with low LRR; wide 10% absolute margin against a 10.2% control rate and 3.9-yr f/u keep it short of practice-changing.

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.

Randomized phase II/III; this is the phase II acute toxicity report for the p16-negative cohort. 234 randomized (118 Q3, 116 Q1) between Oct 2021 and Sept 2025; 91% completed all follow-up up to 6 months. QA modality reviews were done on a random sample of cases.

p16-negative locoregionally advanced SCCHN. Median age 60; 76% male; 58% Zubrod 0; 87% former or current smokers, 70% >10 pack-years. 57% larynx, 28% oropharynx, 15% hypopharynx; 83% T1-3 and 74% node-positive.

Cisplatin 100 mg/m2 Q3 weeks (Q3) vs cisplatin 40 mg/m2 weekly (Q1), each with RT. Chemotherapy delivery scored per protocol or acceptable variation in 80% on Q3 vs 98% on Q1. Cumulative cisplatin dose delivered is not reported in source.

70 Gy in both arms; fractionation, technique and target volumes are not reported in source. RT reviews were completed for 91% of sampled pts, scored per protocol or acceptable variation in 81% on Q3 vs 94% on Q1.

acute toxicity by T-score, the number of all treatment-related grade 3-4 AEs during treatment or within six months. To proceed to phase III, the mean T-score ratio (Q1/Q3) had to be below 1 at 1-sided p<0.1, together with a 6-month locoregional failure difference criterion (printed as '= 8%' absolute in the portal text).

The cohort did not meet criteria for continuing to phase III; arm-level values are in the tables.

Total G3-4 burden was similar, but the profile differed by schedule. Q3 carried more G3-4 nausea (12% vs 4%), dehydration (9% vs 1%) and acute kidney injury (11% vs 3%); weekly carried more WBC decrease (28% vs 14%) and hypomagnesemia (8% vs 2%). Late toxicity is not reported in source.

The Tata Memorial randomized trial (Noronha et al.) favored Q3 over a lower weekly dose for locoregional control in a mostly postoperative population, while JCOG1008 supported weekly dosing after surgery. This cohort tests the schedule question with 70 Gy RT in p16-negative disease and gives no toxicity support for weekly; the source draws no comparison to either trial.

The T-score weighs every G3-4 event equally, so marrow and renal events are interchangeable in the primary. QA was scored on a random sample, not all cases, and per-arm cumulative cisplatin dose is missing. The portal text has lost the inequality in the LRF criterion, so the abstract alone does not show whether that half of the rule passed.

The tolerability premise for weekly cisplatin did not hold here: toxicity was redistributed, not reduced. The LRF difference favors Q3 but rests on a 6-month read in a toxicity-driven phase II, so it is a direction, not an efficacy result. Pooled results for all 475 pts were deferred to the presentation.

Randomized, prespecified phase II go/no-go analysis; weekly failed its toxicity criterion, leaving Q3 as the reference schedule. Abstract only; 6-month LRF is immature and not an efficacy test.

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.

Individual patient data meta-analysis from the MARCAP Consortium, 12 eligible trials, 10,853 patients, median follow-up 11.4 years (IQR 9.0-15.0). Three intensification questions analyzed separately: ADT use, neoadjuvant ADT prolongation, adjuvant ADT prolongation.

Localized prostate cancer treated with definitive radiotherapy, stratified by NCCN prognostic risk group. The RT ± ADT comparison ran 2,557 control vs 2,579 experimental (NCCN high 32.6% vs 32.8%, intermediate 47.6% vs 48.7%); the adjuvant-prolongation comparison was high-risk enriched at 71.5% vs 71.1% NCCN high across 1,900 vs 1,874 pts.

Dose was analyzed as a binary ≥74 Gy vs <74 Gy split, with the companion HEAT analysis using 64 to <74 Gy vs ≥74 Gy and escalation up to 79.2 Gy. Brachytherapy boost is discussed as an escalation route alongside external-beam dose.

ADT addition improved MFS HR 0.83 (0.77-0.89) and OS HR 0.86 (0.80-0.92). Adjuvant prolongation improved MFS HR 0.84 (0.78-0.91) and OS HR 0.85 (0.78-0.94); neoadjuvant prolongation did neither (MFS HR 0.95, OS HR 0.95). 10-yr MFS 61% (59-63) with ADT vs 52% (50-54) without; 10-yr OS 65% (63-67) vs 57% (55-59).

The 2022 HEAT network meta-analysis (13 trials, 11,862 pts) found dose escalation improved biochemical RFS but not MFS or OS, and named high-dose RT plus long-term ADT the best strategy. PROG 05/09 and GETUG-18 are invoked to explain the gap: a 21% 5-year biochemical benefit in low risk where metastasis is rare, versus 3% in high risk where it is not.

The pooled trials span 30+ years of practice, so the RT technique behind the <74 Gy stratum is not the technique a reader delivers today. The stated optimal durations (closer to 12 months high risk, 24+ months very high risk) come from DHARMA, accepted but unpublished, so that specific number is not yet auditable.

The framing claim is that dose escalation and ADT are not interchangeable levers: escalation buys biochemical control, ADT buys metastasis-free and overall survival, and the two do not substitute. The dogma that dose escalation obviates ADT is named as widely repeated and never demonstrated.

IPD meta-analysis of randomised trials, large N, long f/u. Reinforces ADT intensification over dose escalation; no new randomisation, and duration guidance rests on unpublished DHARMA.

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.

Phase 3 international randomised trial, 1:1 central allocation by ICR-CTSU with permuted blocks, stratified by centre and NCCN risk group. Treatment allocation was open-label. Of 874 randomised, 844 formed the analysis population (SBRT=414, CRT=430), median follow-up 85.7 and 85.6 mo.

Men with low-/intermediate-risk localised prostate cancer. Baseline characteristics balanced; baseline PROM data pooled across arms given equivalent pretreatment function.

SBRT 36.25 Gy in five fractions versus CRT 78 Gy in 39 fractions or 62 Gy in 20 fractions. Image-guidance method was not analysed as a variable, and rectal spacer use is not reported in this analysis.

Primary comparison: SBRT vs CRT at 5 yr for each PROM endpoint, using EPIC-26 urinary incontinence, sexual and bowel domains plus the Vaizey faecal incontinence score at baseline, 1, 2 and 5 yr. Binary outcomes by chi-squared with Wilson 95% CIs; continuous by Mann-Whitney.

All predefined between-group differences were nonsignificant. Sexual domain median score fell from 48.7 (IQR 22.2-77.8) to 26.3 (IQR 16.7-57) for SBRT and 54.2 (IQR 27.8-75.0) to 24.3 (IQR 16.7-52.8) for CRT, p=0.89.

Moderate or big urinary leakage problems reached 6% (15/250) SBRT and 4% (9/244) CRT; bowel problems 5% in both arms. Solid stool incontinence never/rarely in 94% (232/248) SBRT and 90% (217/241) CRT; liquid stool 92% in both.

PACE-B previously showed SBRT non-inferior to conventional and moderately hypofractionated RT for efficacy but with higher cumulative GU adverse events; these PROMs argue that excess did not persist to 5 yr. Against TrueNTH's robotic prostatectomy benchmark at 1 yr (42% leak- and pad-free, 6% of baseline-potent men retaining intercourse-adequate erections), the RT curves sit far better, and PACE-A reported pad use of 4.6% after SBRT versus 46.9% after prostatectomy.

The EPIC-26 irritative/obstructive domain was not included, removing the symptom cluster most often attributed to SBRT, though the authors note no 5-yr difference was seen in prior reporting. There is no untreated control arm, so age-related decline is unseparated from treatment effect, and no analysis by image-guidance method.

The clinically useful claim is narrow and real: five fractions buys convenience without a late functional cost relative to 20 or 39 fractions. The cross-modality framing against surgery is the weaker half, comparing separate cohorts at different timepoints with a shared instrument rather than a randomised contrast.

Prespecified 5-yr PROM analysis of a phase 3 RCT; all between-group differences nonsignificant, supporting five-fraction SBRT already in guideline use. Attrition to ~60% limits precision.

Protocol-planned secondary analysis of the TROG 08.03 RAVES phase 3 noninferiority RCT, 166 aRT vs 167 sRT. Median follow-up 6 yr (IQR 4 to 7.1) in both arms. Complete-case analysis, no imputation, chi-square per timepoint.

High-risk features after RP: positive margins, extraprostatic extension, or seminal vesicle invasion. 82% Gleason 7, 3% Gleason 8, 12% Gleason 9. Median age 63.8 vs 63.9 yr (p = 0.9).

64 Gy in 32 fractions to the prostate fossa in both arms, mostly 3D-CRT rather than IMRT. aRT within 6 mo of RP; sRT triggered at PSA 0.20 ng/ml and delivered within 4 mo. Concurrent ADT and pelvic nodal treatment were not permitted.

Primary: proportion with a minimal clinically important change, defined as a >0.5 SD decline from baseline on each QLQ-PR25 domain. MCIC thresholds were 7 points urinary, 2 points bowel, 14 sexual activity, 12 sexual functioning. Global QOL by QLQ-C30.

The RP-to-RT interval regression is the cleanest read: no coefficient approached significance at 3, 4, or 5 yr in any domain, with the largest estimate 0.20 (95% CI -0.29 to 0.70, p = 0.4).

GETUG-AFU 17 and RADICALS reported the same directional late GU penalty for adjuvant RT, though cross-trial comparison is blocked by differing urinary grading. Prior clinician-rated series put CTCAE grade 2 incontinence at 10 to 20%, bracketing the 16% seen here.

The aRT versus never-irradiated comparison is not randomized: those 87 men were selected by not recurring, so comorbidity and baseline continence are unbalanced by construction. The sRT-received group's worse sexual activity at 3 and 4 yr is confounded by higher-risk disease and likely more ADT off-protocol, and the 5-yr sexual functioning cells are as small as n = 10.

The patient-reported bowel signal is invisible on CTCAE (RAVES showed no clinician-rated GI difference), and the patient-reported urinary trend never reached consistent significance despite a 70% vs 54% clinician-rated G2+ GU gap. The two instruments are measuring different things, and neither alone describes what a man experiences.

Protocol-planned secondary analysis of a randomized trial; supports the established early-salvage standard. Exploratory, unadjusted for multiple testing, 3D-CRT era.

IPD meta-analysis of randomised phase 3 CFRT vs MHFRT trials via the MARCAP consortium. Searches on Dec 15, 2023 and re-run Jan 8, 2025 screened 1696 records down to 7 eligible trials. Three separate analyses: efficacy, physician-scored late toxicity, and patient-reported outcomes.

Localised prostate cancer on trials that published patient-level efficacy AND late toxicity data. 3454 pts across three isodose trials, 2426 pts across four dose-escalated trials. Trials whose CFRT arm fell below modern dose were excluded.

The intervention split is the whole point: isodose MHFRT (same equivalent dose in fewer fractions, eg 60 Gy in 20 fractions) versus dose-escalated MHFRT. The CFRT comparator had to deliver ≥70 Gy in 2 Gy equivalents.

Primary (efficacy): progression-free survival. Co-primary toxicity endpoints: late grade 2 or higher GU and GI. Co-primary PRO endpoints: clinically-significant decrement in urinary or bowel quality of life.

The GI signal sits entirely in the dose-escalated stratum and shows up on both physician grading and patient report; the isodose stratum carries neither. GU odds ran above 1 in both comparisons with intervals crossing unity.

CHHiP and PROFIT established 60 Gy in 20 fractions as non-inferior to conventional fractionation. The escalated schedules were built on the premise that a higher equivalent dose in fewer fractions would improve control; pooled here that premise fails on PFS while adding bowel toxicity.

Toxicity scales and PRO instruments were not uniform across the seven trials, and the dose-escalated stratum pools four schedules that are not interchangeable, so the OR describes escalation as a class, not one regimen. Follow-up also differs between strata (5.4 vs 7.1 yrs).

With efficacy answered as a null, the schedule decision turns entirely on toxicity, and the toxicity difference runs one way. Escalating per-fraction dose beyond isodose buys no measurable PFS while adding bowel morbidity that pts themselves report, which leaves little argument for an escalated MHFRT schedule in intact localised disease.

Pooled IPD from seven randomised phase 3 trials, aligned with existing moderate-hypofractionation practice; refines which regimen rather than establishing a new modality or population.

Randomized, non-blinded phase III, 1:1, N=698 (MH-IMRT 345, SBRT 353), stratified by Gleason score, PSA, and rectal manipulation. The trial's oncologic primary endpoint sits elsewhere; this analysis reports the patient-reported secondary endpoints.

Localized intermediate-risk prostate cancer, median age 68 (IMRT) and 69 (SBRT). Two patients were ineligible (one high-risk, one PSA out of window). Baseline EPIC domains were balanced across arms, all p≥0.093.

SBRT 36.25 Gy in 5 fractions delivered 2-3 per week, PTV expansion 5mm except 3mm posteriorly and anteriorly, PTV max capped at 38.78 Gy unless the urethra was visualized and contoured (acceptable variation 43.5 Gy). MH-IMRT 70 Gy/28 fx or 60 Gy/20 fx, PTV expansion 8mm except 5mm posteriorly. CTV was prostate ± 1cm proximal seminal vesicles. Rectal manipulation was common: SpaceOAR in 55% overall.

EPIC-26 at baseline, 12 and 24 months. MCID thresholds: >5 points urinary irritative/obstructive, >6 urinary incontinence, >10 sexual, >4 bowel and hormonal. Individual MCID rather than group mean scores was the analytic unit, with an exploratory longitudinal linear model adjusted for baseline score, arm, stratification factors, T-stage, age, and race.

The arm-level MCID and toxicity comparisons are tabulated above. Longitudinal modeling of urinary incontinence gave a least square mean difference of 2.91 (95% CI 0.85-4.97, p=0.0058) favoring SBRT, while sexual and hormonal domains showed no significant treatment effect.

Investigator-reported toxicity favored SBRT across the board: grade ≥3 GU 0.6% vs 2.5% (p=0.04), any-grade rectal hemorrhage 10.5% vs 17.3% (p=0.01), any-grade fatigue 39.2% vs 50.8% (p=0.0025). The GU finding is the one that most often runs the other way in ultrahypofractionation series, so it is worth reading as the trial's own answer to the pre-trial toxicity concern.

PACE-B is the other large randomized SBRT vs moderate hypofractionation comparison, and both trials show lower urinary incontinence decline with SBRT despite differing MCID definitions. Prior patient-level meta-analysis had suggested less clinically meaningful bowel and urinary irritative/obstructive decline at two years with SBRT, and the 1-year bowel result here is directionally consistent.

Differential attrition ran against the IMRT arm: 22 IMRT patients (6.4%) died or withdrew before year 1 versus 4 SBRT patients (1.1%), and 22 IMRT patients never received the assigned RT after withdrawal versus 1 in the SBRT arm. Completion was 79.9% (IMRT) and 84.0% (SBRT) at year 1. The domain-by-timepoint pattern (bowel and sexual at 1yr, incontinence at 2yr) is the kind of scattered significance that multiplicity should temper.

The trial was designed when the open question was whether five fractions cost the patient something. The PRO answer is that it does not, and the investigator-reported toxicity answer is that it may cost less. What the QoL data cannot do is settle whether SBRT is oncologically non-inferior, which is the primary endpoint and is not reported in this source.

Prespecified PRO secondary analysis of a phase III trial, non-blinded with patient-reported endpoints; aligns with PACE-B rather than establishing a new position. Oncologic primary endpoint not reported here.

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.

International investigator-initiated phase 3, N=802 from 8 countries, accrued March 2014 to June 2018, median follow-up 8 years. Powered at 80% for an HR 0.67. Primary was changed from OS to MFS during the trial because deaths ran below projection.

High-risk clinically localized or locally-advanced disease suitable for EBRT: 90% Gleason 8-10, 36% PSA >20 ng/ml, 12% cN1 by conventional imaging. 40% planned for pelvic RT and 8% for a brachytherapy boost.

Experimental: enzalutamide 160 mg daily x 24 months plus LHRH agonist x24 months. Control: conventional NSAA x6 months plus LHRH agonist x24 months. The control is an active antiandrogen, not ADT alone.

Prostate to 78Gy, or 46Gy plus brachytherapy boost, starting 16 weeks after hormonal therapy. Pelvic nodal RT required for cN1 (46Gy elective nodes plus boost to gross nodes) and optional for cN0 but declared before randomization. QA was unusually tight: credentialing, benchmarking, real-time review of the first 5 plans per site, then 20% random sampling.

Primary: MFS. Secondary: OS, CSS, PSA PFS, clinical PFS, castration resistance, HRQoL, adverse events, cost-effectiveness. Main effects by unstratified log-rank at alpha=0.05, Cox HRs, all p-values nominal without multiplicity adjustment, five prespecified subgroups tested by interaction.

Primary MFS not met. PFS favored enzalutamide at a nominal p=0.044 and OS was flat; the subgroup detail sits in the table above.

STAMPEDE's abiraterone-based intensification in non-metastatic high-risk disease produced an MFS HR 0.53 against ENZARAD's 0.88, and the ENZARAD cN1 subgroup HR mirrors the STAMPEDE result. The gap plausibly reflects population, not drug: cN1 11% vs 39%, median PSA 14 vs 35 ng/ml, cT3-4 47% vs 92%.

The pelvic-RT subgroup is not a clean randomized comparison of pelvic coverage: it carried 28% N1 and 62% Gleason 9/10 against 0% N1 and 49% Gleason 9/10 in the no-pelvic-RT group, so risk enrichment and biological interaction are entangled. The presenter named both explanations and could separate neither.

Two prespecified subgroups moving together on MFS and OS, with OS HRs tracking MFS HRs as ICECaP surrogacy predicts, is more internally consistent than a lone subgroup blip. It still does not establish that enzalutamide works only when the pelvis is treated.

Adequately powered phase 3 missed its primary MFS endpoint against an active NSAA control; benefit rests on two prespecified subgroups with overlapping risk composition.

Systematic review and individual patient data meta-analysis (X-MET collaboration), PROSPERO CRD42023479078. Searched Embase, PubMed, CENTRAL, MEDLINE and ClinicalTrials.gov to Nov 3 2023, updated May 4 2025; dual independent screening in Covidence, Cochrane RoB 2.0. Of 2975 studies screened, 7 phase 2 trials randomising 574 men were included.

Published randomised prospective trials in oligometastatic (up to five metastases) prostate cancer with data sufficient for PFS and OS. Most patients were castration-sensitive (n=375, 65%); ARTO enrolled entirely CRPC and the two EXTEND baskets a CRPC subset. The primary tumour had received prior definitive local therapy in 491 patients (85.5%), required in every trial except the EXTEND baskets and ARTO.

Co-primary: progression-free survival and overall survival. Secondary: radiographic PFS and castration resistance-free survival. Primary analysis restricted to the six trials randomising MDT plus SOC versus SOC, with both a random-effects trial-level analysis and a patient-level analysis stratified by trial.

Effect sizes are in the endpoint table. Trial- and patient-level estimates agreed closely on all four endpoints, and OS showed HR<1 in every individual trial without reaching significance in aggregate.

The constituent trials are the ones that currently drive MDT practice: STOMP and ORIOLE (small randomised phase 2, ADT-free intervals and progression), ARTO (MDT added to abiraterone in CRPC), the two EXTEND hormone baskets, and the prostate subgroup of SABR-COMET (16 men). Pooling them raises precision on PFS but cannot add the phase 3 evidence none of them supply, and the ongoing randomised phase 3 programmes remain the gate.

The SOC arm was not one thing: observation in all or part of STOMP, ORIOLE and COMET-SABR, and second-generation ARPI use differed between arms (59.8%, n=134 in SOC vs 50.4%, n=125 in MDT), which cuts against MDT rather than for it. Four abstract-only randomised primary analyses could not supply IPD and were excluded, and the prostate contribution from SABR-COMET is 16 men.

PFS is where the estimate is tight and consistent; OS is where the question stays open, and at p=0.051 the honest read is an underpowered signal, not a negative result. The endpoint most likely to matter to practice is CRFS (HR 0.58) in castration-sensitive disease, because deferring castration resistance is the outcome MDT is being asked to deliver.

Pools only phase 2 trials with non-blinded randomisation and mixed SOC; co-primary OS missed (p=0.051). Supports existing MDT practice rather than establishing level 1 evidence.

Single-centre randomised open-label phase 2 at the European Institute of Oncology, Milan. 105 pts assigned 1:1 between Aug 1, 2019 and April 30, 2023; median follow-up 31 months (IQR 16-36). Modified intention-to-treat analysis, 3 pts lost to follow-up.

Metachronous oligorecurrent hormone-sensitive disease: biochemical progression after radical local treatment with ≤3 lesions (pelvic nodal, extra-regional nodal, or bone) on next-generation imaging, ECOG 0-1. Median age 70 (IQR 65-75). Stratified by doubling time (≤3 vs >3 mo), node vs bone, and PET vs MRI.

30 Gy in 3 fractions every other day to all oligometastatic sites, or equivalent regimens by site. Stated EQD2 98.6 Gy (α/β 1.5 Gy) and BED >100 Gy, an ablative prescription rather than a symptomatic one, which is the dose the control-arm result belongs to.

6 months of ADT with an LHRH analogue in the combination arm, begun within 1 week before SBRT; no ADT in the control arm. The RT backbone is fixed across arms, so the randomised variable is the short systemic course alone.

Primary: clinical progression-free survival, assessed in 51 pts per group. No overall survival, ADT-free survival, or castration-resistance readout is reported in source.

Radiation contributed one G1 GI event; the only G3 was a left ureter stenosis in the combination arm, with no late toxicity in either group. The 22 G1 events were ADT-attributed and had resolved by last follow-up, so the harm ledger sits with the systemic course, not the RT.

STOMP and ORIOLE established MDT against observation in metachronous oligorecurrence, partly on the strength of keeping men off systemic therapy. EXTEND tested the mirror-image addition, MDT layered onto hormone therapy. This is the first randomised trial in this setting to report improved cPFS for the combination.

Progression was assessed unmasked, and PSA suppression from the randomised ADT gates the restaging that defines the event. Median follow-up sits below the combination arm's median cPFS of 32.2 mo, so the tail after testosterone recovery is thin. No biomarker separates the pts who would do well on SBRT alone.

Local and systemic therapy read as additive here rather than redundant, but the trade is priced in cPFS only. Whether 6 months is the right duration, and for whom SBRT alone suffices, is exactly what the investigators leave to future biomarker work.

Randomised, prespecified primary cPFS hit (HR 0.43). Single-centre, N=105, surrogate composite endpoint, so it supports adding short ADT to MDT rather than establishing it.

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.

Multicenter, open-label, phase III RCT from India, 1:1, stratified by oral cavity subsite, PNI/LVE and differentiation. N=392 (191 RT, 201 observation); median follow-up 47.2 mo (IQR 30-59.4). Powered at 80% to detect HR 0.6256, assuming 3-yr LRFS 70% with observation.

pT1-T2, pN0 OSCC after adequate surgery: clear margins ≥5mm and at least ipsilateral level I-III neck dissection with ≥16 nodes. Required ≥1 intermediate risk factor: DOI ≥5 to ≤10mm, PNI, LVE, or poor differentiation.

60Gy in 30 fractions over 6 weeks to the resected tumor bed and at-risk neck nodal region. Technique and nodal volume definitions not stated in source; no concurrent systemic therapy described.

Primary: loco-regional recurrence-free survival, from randomization to first local and/or regional recurrence. Also reported: cumulative incidence of loco-regional failure with death as competing event, DFS, OS.

LRFS benefit held on PP and competing-risk analyses; DFS and OS not significantly different, with no survival HRs in source.

The abstract describes the evidence for adjuvant RT in this setting as largely retrospective; AREST is the randomised test of that practice. The RTOG and EORTC postoperative trials tested adding concurrent chemo to RT in high-risk resected disease and did not randomise RT itself against observation.

Control arm beat its design assumption (3-yr LRFS 80.9% vs 70% assumed), so the absolute gain sits against a lower-risk baseline than planned. Oral tongue vs buccal mucosa is an exploratory subgroup with no HR in source, and no result is given per risk factor. Salvage treatment at recurrence is not described, which bears on the OS read.

Loco-regional control improved without DFS or OS separation; one explanation is effective salvage of isolated recurrences in observed pts, which the abstract cannot confirm. The decision it moves is adjuvant RT vs observation after adequate resection, weighed against RT morbidity the abstract does not report.

Randomised phase III hit LRFS primary at 47.2 mo median f/u; DFS/OS not significantly different and no toxicity data in abstract, so supports rather than mandates adjuvant RT.

Randomized phase III SWOG/NRG cooperative-group trial, accrual 8/13/20 to 9/6/24, 417 randomized / 403 eligible (201 SBRT alone, 202 atezolizumab + SBRT) against an accrual goal of 432. Closed at the first interim analysis for futility on both OS and PFS. Median follow-up in living pts was 12 months (range 0.03-49).