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Open-label, international, multicentre, parallel-group, superiority phase 2/3 trial at 37 hospitals in the UK, Netherlands, Sweden, Denmark, and Belgium. Phase 2 randomised 1:1:1 (LCCRT-OP, SCRT-OP, TME); phase 3 used a partially randomised patient-preference design, with those choosing organ preservation randomised 1:1 between the two RT schedules, stratified by country and MRI T category.

Biopsy-confirmed rectal adenocarcinoma <40 mm staged mrT1-T3bN0, ECOG 0-1, aged ≥16 (UK) or ≥18 elsewhere. Excluded: diameter >40 mm, metastatic disease, MRI-defined nodal involvement or extramural venous invasion, tumour within 1 mm of mesorectal fascia, anterior tumours above the peritoneal reflection, mucinous histology. Median age 67, 72% male, 80% below the peritoneal reflection.

LCCRT-OP: 50 Gy in 25 fractions with oral capecitabine 825 mg/m² twice daily. SCRT-OP: 25 Gy in five fractions. Completion was high in both groups: 159 (99%) of 161 LCCRT participants and 168 (100%) SCRT. 18 (11%) of 161 receiving LCCRT needed at least one capecitabine dose modification for toxicity.

Phase 3 primary: organ preservation 30 months after treatment initiation (absence of TME, stoma, or local recurrence), assessed in the mITT population and not reported in this analysis. This report gives the 12-month implementation outcomes: TME-free survival, clinical complete response at the second response assessment, and serious adverse events. Bayesian framework with Cox models for time-to-event outcomes.

Response-adapted decision-making at 16-20 weeks explains the divergence: cCR 64% vs 36% favoured LCCRT-OP while TAE for near-complete response was commoner after SCRT-OP (23% vs 40%), and the resulting TME-free survival gap was 78.5% vs 60.6%.

Grade 3-4 serious adverse events were most often gastrointestinal (2% LCCRT vs 4% SCRT vs 8% TME) and procedural complications (2% vs 3% vs 6%). Grade ≥3 SAEs within four weeks of finishing RT were 9 (6%) LCCRT-OP vs 2 (1%) SCRT-OP. In the TME group, grade ≥3 SAEs occurred in 14 (18%) of 78, with one postoperative death from sepsis after anastomotic leakage and intraperitoneal perforation from anastomotic leak in 12 (15%).

The phase 2 effect (HR 3.7, 1.7-8.0) was far larger than the pooled 12-month estimate (HR 1.90), and the authors ran exploratory post-hoc analyses of stratification variables, tumour length, and centre organ-preservation volume to explain the phase difference. Baseline MRI excluded nodal disease, yet 17 (22%) of TME specimens carried positive nodes, so occult nodal disease is present in the preserved cohort too and is not captured by a 12-month TME-free endpoint. The primary TME comparator in phase 3 was self-selected, not randomised.

TME-free survival at 12 months is an implementation readout, not durable organ preservation: it counts who has avoided surgery so far, not who stays disease-free without it. The clinically load-bearing question, whether the higher cCR rate after 50 Gy/25 fx converts into sustained preservation without a local-recurrence penalty, waits on the 30-month endpoint.

Interim 12-month implementation analysis; prespecified 30-month organ-preservation primary endpoint unreported. Phase 3 TME arm by patient preference, not randomisation.

Retrospective review of a departmental re-RT database, single institution (Porto), treated 2017-2021. Thirteen identified, two excluded (different fractionation; T4 treated with WBI), leaving N = 11. Median follow-up 41 months (27-62), Kaplan-Meier estimates with two-sided log-rank comparisons.

Isolated ipsilateral breast tumor recurrence after BCS plus whole-breast irradiation, all T1-2, clinically node negative, no metastatic disease before second BCS. Inclusion required age ≥ 50, unifocal disease on ultrasound, mammography and MRI, size < 2-3 cm, and an interval of ≥ 48 months from primary treatment. Median age at recurrence 63 (41-81), ECOG 0-1 in all.

Initial course was whole-breast irradiation at 2 Gy/fraction in all 11, with a 10 Gy / 5 fraction boost in 2. Re-RT was partial breast, 40 Gy at 2.67 Gy daily, direct-planning IMRT, supine, without DIBH. Median interval between courses 107 months (27-239).

No registered primary. LR-FS, DR-FS and OS by Kaplan-Meier from the day of re-RT completion, with adverse events graded by CTCAE v5.0 (acute < 90 days, late > 90 days) and cosmesis by the Harris scale.

At 3 years, 9/11 free from local recurrence, 10/11 from distant recurrence, 9/11 alive, each 86%. Two local recurrences, at 11 and 15 months. TAM-stratified LR-FS was 100% low risk, 80% intermediate, 100% in the single high-risk patient; the OS difference between low and intermediate risk was not significant (p = 0.75).

No grade 3 or higher late reactions. Acute events were skin-limited, most commonly grade 1-2 dermatitis (8 grade 1 erythema, 2 grade 1 pigmentation, 1 pruritus). At 1 year, grade 1 fibrosis in 9 and grade 1-2 oedema in 5, breast pain grade 1 in 2. No cardiopulmonary events, no rib fractures. Cosmesis good in 6, fair in 2, poor in 3.

RTOG 1014 (45 Gy / 1.5 Gy BID, 3D-CRT, n = 66) reported 7% late grade 3 and no grade 4-5 at 5.5 years; Janssen 2018 (n = 83, 45 Gy / 1.8 Gy daily) reported a 15% LR rate at 35 months. Brachytherapy series sit at 94-100% third-IBTR-free survival with 8-11% grade 3-4 complications. This cohort's toxicity is at or below all of them, on a fraction of the patient numbers and follow-up.

The first course's dose distribution was unavailable, so no composite plan sum could be produced and cumulative OAR dose stays uncharacterized, which is the number that actually gates re-RT safety. Cosmesis was scored unblinded by the treating radiation oncologist, and the reported confidence intervals (46-62%, 52-65%, 47-63%) do not contain their own 86% point estimates as printed.

The contribution is schedule feasibility, not efficacy: a once-daily 15-fraction re-RT plan met every published constraint with wide margin, which is what a department needs before abandoning BID. Whether 40 Gy in 15 fractions matches 45 Gy BID for in-breast control remains untested; two events in 11 patients cannot answer it.

Retrospective single-arm series, N=11, 2 events, median f/u 41 months. No comparator vs mastectomy or vs the established BID re-RT schedules.

Prospective observational natural history cohort at the NCI, presented at GU-ASCO 2026. Baseline data on the first 130 pts; the cohort is ongoing at a median follow-up of about 2 years with interim outcome data pending.

Men with biochemical recurrence after definitive therapy, all of whom had already received salvage radiation or declined it. PSA ≥ 0.5 required for a baseline PET. Deliberately framed as PSMA-positive BCR, a state that would not have been detectable in the historical trials these pts map onto and that excluded them from metastatic trials.

The presented analysis is cross-sectional: PSMA PET findings at baseline against PSA doubling time, the field's working predictor of metastasis in BCR. Imaging cadence is protocolized at annual if the baseline PET is negative, every 6 months if anything is seen, including equivocal findings.

Among pts with slow kinetics (PSADT > 9mo and > 12mo), the majority still had PSMA PET findings once PSA was above 5: nodal disease, prostate bed recurrence, and small equivocal bone lesions. Only about a third have started any therapy. A companion poster found 5 of the first ~150 pts progressed on conventional imaging at roughly 1.5yr, and over 95% showed no abrupt PET change out of step with PSA.

The counts are reported conversationally in an interview ("about 130", "the first 150 or so", "that number's five"), with no stratum denominators and no CIs, so the PSADT-by-PET relationship cannot be quantified from this source. Allowing any therapy under 6 months, including SBRT and intermittent ADT, means the observed group is not an untreated comparator.

The claim being staked is that PSMA PET positivity in BCR is near-ubiquitous above PSA 5 and therefore weakly discriminating, so it should not by itself trigger treatment. What the cohort has not yet shown is whether PET burden or its change over time adds anything to PSA doubling time for predicting the outcomes that matter.

Baseline cross-sectional read of an ongoing single-institution cohort, median f/u ~2yr, no outcome analysis yet. Numbers reported conversationally, not tabulated.

Prospective randomized phase 2, 1:1, N=106 (55 SIB-CRT, 51 CRT), accrued August 2013 to February 2015. Median follow-up 116.6 months, which is the study's real asset.

Stage II/III rectal adenocarcinoma. Radical surgery planned 6 to 8 weeks after chemoradiotherapy. Perioperative chemotherapy was not randomized, and its receipt defines the subgroup that carries the result.

Both arms received 50 Gy/25 fx to the pelvis. The experimental arm added a simultaneous integrated boost of 56 Gy to PGTV and 60 Gy to lateral metastatic nodes where present, so the escalation targets gross primary and involved lateral nodes rather than the elective volume.

Primary: pCR rate. Secondary: DFS, OS, MFS, LC, CSS and toxicity. Every result the conclusion rests on is secondary.

Acute grade 3 toxicity 14.5% (SIB-CRT) vs 19.6% (CRT), primarily radiation dermatitis. Late toxicity is not reported in the source, which matters most for a boost delivered near bowel and for pts followed nearly a decade.

Neoadjuvant dose escalation in LARC has repeatedly raised pCR without translating to survival; this trial reports the mirror image, a null pCR (15.2% vs 18.4%) with survival separation. The result also sits against the TNT era, where systemic intensification rather than RT dose is the current lever, and the chemo-receiving subgroup here showed no additional benefit.

The survival claim is a secondary-endpoint result from 51 vs 55 pts, so a handful of events moves each HR, and no confidence intervals are reported in the source. The driving subgroup is defined by non-randomized chemotherapy receipt, and the higher rate of curative treatment in the SIB arm (89.1% vs 78.4%) is itself a plausible route to the OS difference independent of dose.

A pelvic boost has a defensible mechanism for LC 87.1% vs 70.1% and essentially none for MFS 70.8% vs 47.2%. The authors attribute the distant benefit to intensified control of micrometastases; the simpler reading is that a small trial with a large curative-treatment imbalance produced correlated secondary endpoints.

Randomized phase 2, N=106, primary endpoint (pCR) missed; survival gains are secondary endpoints with wide implied precision and a non-randomized chemo subgroup driving them.

Multicentre retrospective cohort across three centres, March 2015 to May 2025, chosen to capture the daily-CBCT image-guidance era. N=107 (39 dose-escalated, 68 standard), median follow-up 23 months (range 3 to 104).

MIBC after TURBT treated with curative intent, with or without concurrent chemotherapy; node-positive pts eligible if non-metastatic. Metastatic or palliative-intent pts excluded. T2 86%, ECOG 2-3 in half the cohort, hypofractionation in 91%.

Standard cohort received 55Gy/20fx or 64Gy/32fx to the whole bladder. Escalated cohort received a simultaneous integrated boost to the primary lesion, up to 60Gy/20fx or 70Gy/32fx. CT simulation with empty bladder; MRI and FDG PET fused for target delineation in selected pts; daily CBCT in all but one pt.

2-year local control for invasive and non-invasive disease, metastasis-free survival, overall survival, bladder preservation, and toxicity. Local control analysed by Fine-Gray competing-risk models, univariable then multivariable adjusted for T stage.

Dose escalation was associated with lower invasive local recurrence; non-invasive recurrence, metastasis, and survival did not differ. Numbers are in the outcomes table above.

No difference in G2+ GU (17.9% vs 22.1%, p=0.8) or G2+ GI toxicity (5.1% vs 7.4%, p=0.9). Grade 3 toxicity in 2 pts (2.9%), both in the standard-dose arm. No pt required early cessation of treatment for toxicity.

The direction matches BC2001 and BCON, which established chemoradiation and hypoxic modification as ways to improve local control within bladder preservation but never randomised the RT dose itself. The open question these left, whether escalating the primary lesion adds control on top of a modern image-guided plan, is what this cohort probes, at retrospective strength rather than randomised.

The escalated cohort was systematically more favourable: 100% single-focus disease vs 65%, hydronephrosis in 10% vs 28%, T3 in 8% vs 16%. Only T stage entered the multivariable model, and with 18 invasive events total the model could not have supported more. Recurrence ascertainment differed by arm: 3 standard-dose recurrences were presumed invasive on CT and MDT consensus while every escalated-cohort recurrence was confirmed cystoscopically.

The local-control signal is real in this dataset but its magnitude is not transferable: an SHR of 0.20 resting on 2 events versus 16, in cohorts that differ on tumour focality, is an effect size that would be expected to shrink under randomisation. What survives the caveats is a tolerability finding, that an integrated boost to the primary did not raise G2+ GU or GI toxicity.

Retrospective, N=107, 18 total invasive events driving the SHR; boost cohort had single-focus disease and less hydronephrosis, with only T stage adjusted.

Phase II randomized trial, 1:1, unmasked, single institution, accrual February 2020 to April 2023, database lock June 2024. 55 randomized, 4 withdrew or were ineligible, 51 analyzed (25 optimized, 26 standard). Randomization used permuted blocks of 2 and 4, stratified by tumor location.

Early-stage NSCLC, pathologically or imaging-confirmed, unable or unwilling to undergo surgery; ECOG 0-2; pre-RT ALC > 0.5 x 10^9 cells/L. Prior-recurrence pts eligible. Excluded prior thoracic RT within 2 years and systemic therapy within the prior year or planned within 6 months post-SBRT. Median age 74 both arms; cT1 in 100% optimized vs 88.5% standard.

SBRT 45-60 Gy in 5 fractions (BED 85.5-132 Gy) by IMRT or VMAT, 6X-FFF, 4DCT-based ITV, PTV margin 5mm radial and 8mm superior-inferior, daily CBCT. Both arms met RTOG 0813/0915 constraints; the optimized arm added heart, great vessels, thoracic spine and lymph-node-stations (Chapet atlas) contoured to a 40 cGy per fraction threshold as competing OARs.

Primary: in vivo lymphocyte depletion (ALC change) at end-of-treatment, 4 weeks and 6 months, plus safety/toxicity comparison. OS and EFS were unplanned subgroup analyses, descriptive only.

Two grade 3 events (lung infection) in the optimized arm vs four in the standard arm (dyspnea, hypoxia, lung infection); all recovered. Grade 2 events in 6 (24%) optimized vs 9 (35%) standard. No grade 2+ pneumonitis and no grade 4+ toxicity in either arm.

The premise rests on the observed link between post-RT lymphopenia and worse outcomes rather than on any prior trial that randomized immune-organ sparing, so there is no comparator trial to place this against. The authors cite lung SBRT plus immunotherapy improving 4-year EFS from 53% to 77% as the alternative route to the same immune endpoint, which is an add-a-drug strategy rather than a planning one.

Chance imbalance runs against the optimized arm on some axes (fewer treatment-naive: 64.0% vs 88.5%) and toward it on others (more central tumors: 36.0% vs 23.1%), and with 51 pts neither is correctable by adjustment. The LN V5 35.4cc OS split is a post-hoc median dichotomy on the same small cohort, so it cannot be read as an independent confirmation of the ALC result. Only 15 central tumors carried the largest effect estimate.

The trial establishes that the dose can be moved, and that ALC follows it, in a setting where the target dose was held fixed. What it does not establish is that the lymphocyte curve translates into disease control, and the OS and EFS signals here are explicitly underpowered and unplanned.

Preprint, single-institution phase II, N=51, endpoint is a lymphocyte surrogate not a clinical outcome; survival analyses unplanned and underpowered.

Investigator-initiated phase 2 nonrandomized trial across 21 centers (community, regional, academic), enrolling Jan 2008 to Apr 2010. 310 evaluable pts, median age 68, median follow-up 9 yr. Kaplan-Meier estimation with log-rank comparison of LR vs IR.

172 low-risk (T1b-T2a, Gleason 6, PSA under 10) and 138 intermediate-risk (T1b-T2b, Gleason 7 or Gleason 6 with PSA 10-20), all confirmed by central pathologic review. IR pts subclassified favorable vs unfavorable by MSK criteria. Prostate volume up to 100 cc allowed; prior TURP and baseline AUA score were not exclusions.

40 Gy in 5 fractions (8 Gy x 5, equivalent to ~100 Gy at 2 Gy/fx assuming a/b = 2) on a noncoplanar robotic platform. Fiducial tracking with translational and rotational intrafractional motion correction was mandatory. Androgen suppression was not allowed, so the outcomes are RT-attributable.

Relapse defined as biochemical failure (nadir + 2), clinical failure, or administration of any salvage, antiandrogen, or systemic therapy. Late toxicity was physician-reported, CTCAE v3, events beyond 3 mo. Day 0 was the last day of treatment.

10-yr OS 84% (76-91). Freedom from local failure 96% (93-99) overall. The separation that matters is within IR: favorable 92% vs unfavorable 77%, p = 0.002, whereas LR vs IR overall was not significant (p = 0.19).

Four pts had five grade 3 events, all GU, and no grade 4-5 events occurred. Cumulative 10-yr grade 3 rates were 1.4% LR and 1.5% IR, far below the 10% rate the trial deemed acceptable. Grade 2+ GU 14% exceeds grade 2+ GI 2.1% by roughly sevenfold; no new late grade 3+ events after year 5.

IR relapse-free survival (86%) sits above the 74-78% 10-yr RFS of dose-escalated EBRT in RTOG 0126, and the authors note an updated HYPO-RT-PC now shows superior 10-yr RFS in the 6.1 Gy x 7 arm. Toxicity matched Fuller's CyberKnife trial but was lower than the PACE-B SBRT arm and PATRIOT, both of which treated substantial fractions on a conventional linac.

The toxicity advantage over PACE-B and PATRIOT is confounded by platform, and the sponsor makes that platform, so the comparison cannot separate tracking from delivery-era and case-mix differences. Toxicity is physician-reported CTCAE only, with no patient-reported instrument, which understates GU bother relative to the EPIC-based comparators. Comparator EBRT series (RTOG 0126) predate modern IGRT.

The durability question, not the toxicity question, is what 10 yr answers here: two-thirds of relapses occurred between 5 and 10 yr, in this trial and in Fuller's. That timing means a 5-yr non-inferiority readout is structurally optimistic for both arms, and it reframes what PACE-B's 5-yr result can and cannot settle.

Single-arm nonrandomized phase 2, no concurrent comparator; sponsor-funded with device-specific delivery. Extends existing 5-yr SBRT data rather than testing a new question.

Multicentre phase 2 randomised open-label trial, 16 academic and community centres in Italy, 1:1 by random permuted blocks, stratified by centre, ECOG PS and number of metastases. Enrolment Jan 2, 2019 to Sept 7, 2022; median follow-up 53 months (IQR 43-60). ITT analysis.

Age ≥18 with prostate adenocarcinoma and metastatic castrate-resistant disease, no more than three metastatic sites, and no previous systemic therapy for the mCRPC state. N=157 (control 82, experimental 75). No race or ethnicity data collected.

Both arms received ADT plus oral abiraterone acetate 1000 mg daily. The experimental arm added SBRT; the systemic backbone was identical, so the contrast isolates the radiotherapy.

SBRT delivered to all sites of metastatic disease in one to five fractions at a biologically effective dose ≥100 Gy. Comprehensive ablative intent, not treatment of an index lesion.

Primary: 6-month biochemical response (PSA decline ≥50% from baseline), reported previously. After the primary was met the power calculation was updated post-hoc for overall survival, finalised before unmasking; this report is an unplanned long-term OS analysis.

Most common grade 3-4 events were infectious complications (five control, zero experimental) and cardiovascular disorders (three each). One treatment-related death, in the control group, from myocardial failure. No excess grade 3-4 toxicity attributable to SBRT in the reported events.

STOMP and ORIOLE established MDT in hormone-sensitive oligometastatic disease without a systemic backbone, and SABR-COMET tested SABR across mixed histologies. ARTO is the randomised test in castrate-resistant disease with an ARSI given to both arms, which is the setting those trials leave open.

Open-label with no sham, and the OS power calculation was revised after the primary read, so the alpha spent on this comparison is not the trial's original design. The experimental median is not reached, meaning the reported HR rests on a control-arm curve that is itself only partly mature at 53 months.

A survival signal from comprehensive ablation on top of a modern ARSI backbone is the strongest randomised argument yet that MDT in CRPC is doing more than delaying PSA progression. What it does not settle is whether the benefit tracks the ablative dose, the completeness of coverage, or simply the favourable biology of pts whose disease stayed oligometastatic into castration resistance.

See the OS figures above; per-arm event counts beyond the medians and HR are not reported in source.

Randomised phase 2, but the OS analysis is unplanned with post-hoc power revision and the primary endpoint was 6-month PSA response. N=157.

Single-arm bladder-preservation study of induction ipilimumab plus nivolumab followed by chemoradiation. Phase, N, number of sites and median follow-up are not reported in the source tweet; results are read out at 2 years.

Stage II/III muscle-invasive bladder cancer, cT2-4aN0-2. That range admits both node-positive and cT4a disease, a broader population than many bladder-preservation series. No further eligibility, performance status or baseline detail in source.

Induction ipilimumab + nivolumab, then chemoradiation. Dosing, number of induction cycles, and the concurrent radiosensitizer are not reported in source.

The chemoradiation component is named but not specified: no total dose, fractionation, technique, or target volume. Whether the cT4a and N1-2 pts received elective pelvic nodal coverage is unstated, which is the parameter that most gates transfer to another practice.

Primary read: 2yr bladder-intact event-free survival, 78% (0.67-0.9). 2yr OS 96% (0.91-1). Whether the trial prespecified bladder-intact EFS as its primary endpoint is not stated in source.

The 96% 2yr OS sits well above what an unselected cT2-4aN0-2 population would predict, which points at selection; the source reports no eligibility filter to judge that against. With no cystectomy or pathologic-response denominator reported, bladder-intact EFS cannot be separated into pts who never needed salvage vs pts who declined it.

The claim on offer is that adding induction ipi/nivo raises the ceiling of trimodality therapy, but a single arm cannot isolate the immunotherapy's contribution from the chemoradiation backbone. What it does establish is feasibility: pts got through induction dual checkpoint blockade and still completed CRT, with 2yr OS 96%.

Single-arm induction immunotherapy plus CRT with 2yr follow-up and wide CI; no randomised comparator against standard chemoradiation or cystectomy.

Prospective, single-group, phase 2 nonrandomized trial across 9 tertiary sarcoma centers in Europe and the US. Enrollment ran November 2010 to May 2020; data analyzed January to December 2025. Median follow-up 66.4 months (IQR 48.8-87.5).

Adults with biopsy-proven and translocation-confirmed localized myxoid liposarcoma of the trunk or extremity. N=90, mean age 47 (SD 13.1), 50 (56%) male.

Preoperative RT to a reduced dose of 36 Gy in once-daily 2-Gy fractions, followed by resection. Delivered per protocol in all patients. Three pts (3%) did not proceed to surgery because of intercurrent metastatic disease.

Long-term local recurrence-free survival, progression-free survival, disease-specific survival, overall survival, and late toxic effects. No single stated primary endpoint for this long-term analysis.

Wound complications in 18 pts (21%), with 14 (16%) requiring intervention. Late toxic effects were grade 2 in 13 pts (15%) and grade 3 in 3 pts (3%).

The authors argue the long-term data support adopting 36 Gy as an option through shared decision-making, explicitly on the grounds that a phase 3 trial is impractical in a rare cancer. That is an argument about feasibility, not about evidence level, and the reader should price it as such.

Fourteen-year accrual window spans changing surgical and imaging practice, so the wound complication rate reflects a long era rather than current technique. Late toxicity is reported only as pooled grade counts, without organ or site attribution, which limits comparison against 50 Gy series.

Single-arm phase 2, no randomised 50 Gy comparator; authors concede phase 3 impractical in a rare histology. Long f/u strengthens but does not replace randomisation.

Single-institution, parallel-cohort, open-label randomized trial across four Emory-affiliated centers, enrolling June 2020 to 2024. ADT-eligible pts randomized 1:1 relugolix vs leuprolide, stratified by ASCVD 10-year risk score; a parallel prospective RT-alone cohort was enrolled as control.

94 men with non-metastatic prostate cancer, intermediate and high risk, all treated with pelvic radiotherapy to the prostate with or without pelvic nodes. Lower-risk men eligible for definitive RT alone without planned ADT formed the parallel arm.

Relugolix 360 mg day 1, then 120 mg daily; leuprolide in 3-month depots. ADT given for at least six months, longer by cancer risk tier.

All pts received pelvic radiotherapy to the prostate with or without the pelvic lymph nodes. Dose, fractionation and technique are not reported in source.

Primary: change in total plaque volume. Secondary: changes in plaque subtypes (non-calcified, calcified, low-attenuation). Serial CCTA at baseline (within 7 days of treatment start) and 12 months, blinded to arm, quantified by the automated HeartFlow tool; 12-month mean difference by ANCOVA adjusted for age, statin use and baseline plaque volume.

The adjusted total-plaque-volume difference of 68.9 mm³ favouring relugolix was driven mainly by non-calcified plaque; calcified and low-attenuation plaque showed no significant difference with low absolute change. Per-arm CIs and p-values are not reported in source.

HERO (2020) showed a lower MACE rate with relugolix vs leuprolide and drove the FDA approval, but offered no mechanism, since both agents suppress testosterone comparably and share the hypogonadal metabolic profile. REVELUTION supplies the candidate mechanism, accelerated coronary atherosclerosis under GnRH agonism, consistent with the 2010s observational signal that agonists carry higher cardiovascular risk than orchiectomy.

The imaging endpoint is validated as a predictor of MACE, not a substitute for it, and 12 months is short for plaque trajectories. The parallel RT-alone cohort was not randomized against either ADT arm, so the no-hormone comparison is observational and cannot isolate radiotherapy's own contribution to plaque change.

If the agonist-antagonist difference is real and mechanistic, the decision it moves is which ADT agent accompanies definitive RT in a man with baseline cardiovascular risk, not whether to give ADT at all. It does not establish that changing agent prevents events; that inference still rests on HERO.

Small single-institution randomized trial with an imaging surrogate (plaque volume), not clinical MACE. Supplies a mechanism for HERO rather than independent outcome evidence.

Multicenter randomized phase 2, 1:1 allocation, N=157 enrolled January 2019 to September 2022. Median follow-up not reported in source.

Oligometastatic castrate-resistant prostate cancer, defined as three or fewer nonvisceral metastatic lesions. Visceral disease excluded by definition.

Both arms received abiraterone acetate and prednisone (AAP). The experimental arm added concomitant SBRT, so AAP is a fixed backbone and the randomized contrast is radiotherapy alone.

SBRT to all sites of disease, delivered concomitantly with AAP. Dose, fractionation and target-volume detail are not reported in the source text, which gates how directly the result transfers to a given SBRT practice.

Primary: biochemical response, PSA decrease ≥50% from baseline at 6 months. Secondary: complete biochemical response (PSA <0.2 ng/mL at 6 months) and progression-free survival. No survival endpoint reported.

No toxicity reported in source, so the added burden of ablating up to three lesions is unquantified. PSA endpoints are mechanically sensitive to removing PSA-producing deposits, and the 6-month timepoint precedes any durability read.

STOMP and ORIOLE established the randomized signal for metastasis-directed therapy in hormone-sensitive oligometastatic disease. ARTO's addition is that the signal persists on an ARSI backbone in castration-resistant disease, a setting those trials did not test.

The PFS HR 0.35 is the more meaningful of the two results, since it is less mechanically coupled to ablating PSA-producing lesions than the primary endpoint. What remains unsettled is whether deferring progression on an ARSI translates into anything durable, which a phase 2 sized for a 6-month PSA readout cannot answer.

Randomized phase 2 with a 6-month PSA surrogate primary endpoint; no OS, no reported toxicity, and phase 3 confirmation in CRPC is absent.

Phase 2, 2-arm randomized trial across 3 US radiation facilities affiliated with one university hospital. 80 men screened, 54 randomized 2:1 to SABR or observation, accrual May 2016 to March 2018, data cutoff May 20 2019. Median follow-up 18.8 months (range 5.8-35.0).

Recurrent hormone-sensitive prostate cancer with 1 to 3 metastases detected on conventional imaging (CT, MRI, or bone scan), asymptomatic, arisen within the prior 6 months, no larger than 5.0 cm. Prior definitive treatment of the primary required; salvage prostate-bed or pelvic RT allowed. No ADT within 6 months of enrollment or 3 or more years total. Median age 68 in both arms; Gleason grade ran higher in the observation arm (mean 8 vs 7).

SABR to metastatic sites, with treatment planning blinded to PSMA-PET, so PET-avid lesions outside the conventional-imaging map were left untreated in 16 of 36 SABR pts. Dose and fractionation are not reported in the source text. Local control 98.9% at 6 months.

Primary: progression at 6 months, a composite of PSA rise, radiographic progression on conventional imaging, symptomatic progression, ADT initiation for any reason, or death. Secondary: SABR toxicity, 6-month local control, PFS, Brief Pain Inventory QoL, and concordance between conventional imaging and PSMA-PET.

No grade 3 or higher adverse events in either arm. No differences in Brief Pain Inventory scores between arms or within either arm over time.

Sits alongside STOMP, the other randomized trial of metastasis-directed therapy versus surveillance in oligorecurrent hormone-sensitive disease, and reaches the same directional conclusion from an independent population. What ORIOLE adds is the PSMA-PET consolidation question, which STOMP's choline-PET-selected design could not isolate.

The composite primary is driven partly by ADT initiation for any reason, a clinician decision made without blinding in an open trial, so the treating team's knowledge of arm allocation can move the endpoint directly. The PET-untreated-lesion comparison is a within-arm post-randomization subgroup (19 vs 16 men), not a randomized contrast, and the men whose conventional imaging missed more disease plausibly had more disease to begin with.

The trial makes two distinct claims and they carry different weight. That SABR beats observation on a 6-month composite in a 54-man phase 2 is a signal, not a standard; that leaving PSMA-avid disease untreated tracks with earlier and more distant failure is the finding that changed how the field plans these treatments, even though it rests on an observational contrast inside one arm.

Phase 2, N=54, 6-month composite primary including ADT initiation, median f/u 18.8mo. Hypothesis-generating for MDT; no OS or definitive endpoint.

Prospective multicentre cohort, N=848 across 17 Dutch centres, accrued 2011-2015, presented at EBCC15 with 10-year follow-up; 838 completed follow-up. Not randomised: every patient received the RT volume their risk group assigned.

Breast tumour under 5 cm with 1 to 3 involved lymph nodes at presentation, treated with neoadjuvant chemotherapy then surgery (BCS or mastectomy). Most underwent axillary lymph node dissection.

Volume was set by post-chemotherapy nodal status. ypN0: breast RT after BCS, none after mastectomy. ypN1: breast or chest wall only, regional nodes omitted. ypN2+: breast or chest wall plus regional nodal irradiation. Dose and fractionation are not reported in source.

24 of 838 (2.9%) had a locoregional recurrence without distant spread at 10 years. Per-group counts appear in the detail table; the rates do not separate across strata.

The randomised test of this exact question is NSABP B-51/RTOG 1304 (NCT01872975), which the investigators expect in about 3 years; until then no trial has randomised ypN0 pts to nodal RT versus omission. Prior nodal-RT evidence (MA.20, EORTC 22922) was built in upfront-surgery populations, so it cannot arbitrate a post-chemotherapy response-adapted rule.

The 2.9% rate is uninterpretable without a comparator: a low event count in a de-escalated cohort is equally consistent with the omitted RT having been unnecessary and with the cohort being low-risk to begin with. ALND staging also means the ypN0 label carries more information than a modern sentinel-node ypN0 does.

The finding that recurrence is flat at 2.4% / 3.2% / 2.8% across escalating risk is the intended signal: the added RT in the higher strata may be doing the work that keeps them level with the low-risk group. It does not settle whether the low-risk group needed any RT, only that the allocation rule did not produce a visible failure.

Single-arm prospective cohort with no randomised comparator; allocation used ALND-era nodal staging. Confirmatory randomised answer (NSABP B-51) still pending.

Territory-wide retrospective cohort (OCEANUS) using the Hong Kong Hospital Authority CDARS, covering more than 90% of the population. Propensity score overlap weighting was the primary method with IPTW for sensitivity; analysis ran December 2024 to April 2025. Landmark analysis was applied, and refractory pts had to survive at least 90 days.

NSCLC diagnosed January 1, 2010 to December 31, 2021 who subsequently received iRT for advanced or refractory disease. Of 3522 pts who received ICIs, 335 received RT: 155 newly diagnosed advanced and 180 refractory. 247 (73.7%) male, median age 64 (range 34-90).

The exposure is RT timing relative to ICI, sequential vs concurrent, in newly diagnosed disease, and RT with vs without ICI maintenance in refractory disease. Dose, fractionation, modality, target volume and irradiated site are not reported in the source, which is the gap that limits transfer to a specific plan.

Primary: real-world OS after landmark, estimated with weighted Kaplan-Meier and Cox models. Where proportional hazards were violated per Schoenfeld residuals, effects were summarized with restricted mean survival time.

Sequential iRT carried longer OS than concurrent in newly diagnosed advanced disease, aHR 0.68 (0.47-0.99), P=.045. In refractory disease the ICI-maintenance difference was not significant (P=.20), and added chemotherapy showed no significant OS association there.

PACIFIC established consolidation durvalumab after concurrent chemoRT in stage III unresectable disease, and PEMBRO-RT and MDACC randomized data tested RT added to pembrolizumab in metastatic disease, but none of these randomize sequential against concurrent iRT in advanced NSCLC. That question has no randomized answer, which is why a 155-pt weighted cohort is currently among the larger reads on it.

Timing was clinician-assigned, so pts pushed to concurrent RT plausibly had more urgent, symptomatic or bulky disease, an indication bias that overlap weighting on recorded covariates cannot remove. The 2010-2021 window also mixes ICI eras, agents and lines, and the source reports no toxicity, so the pneumonitis risk that motivates avoiding concurrency is unmeasured here.

The result argues that separating RT from ICI administration does not cost survival and may favor it, which is the opposite of the abscopal-synergy rationale often used to justify concurrency. It does not establish causality, define an interval, or identify which pts the timing matters for.

Retrospective propensity-weighted registry cohort, 155 pts in the primary comparison, P=.045 with CI touching 1.0. Authors themselves call it hypothesis generating.

Phase 2, open-label, randomised 1:1, investigator-initiated, 21 hospitals across Australia, Belgium, Italy, Norway, Spain and Switzerland. Recruited June 11, 2018 to April 30, 2021; median follow-up 50 months (IQR 42-58). Stratified by PET tracer (choline vs PSMA) and MDT type (sLND vs SBRT); participants and investigators unmasked.

Biochemical relapse after radical prostatectomy, postoperative RT, or definitive RT, with up to five PET-detected pelvic nodes (pelvis defined up to the aortic bifurcation, common iliac included). Bone, visceral, or above-bifurcation nodal disease excluded, as was previous RT overlapping current fields. Median age 70-71, median PSA at inclusion 1·00 vs 0·85 ng/mL, 91% and 86% EAU high-risk BCR, and 55-62% had a single positive node.

MDT arm: SBRT 30 Gy in 3 fractions every other day to 90% of the PTV with a 3 mm margin, or salvage lymph node dissection. ENRT arm: 45 Gy in 25 fractions to the whole pelvis on a modified RTOG 2009 template (upper limit L4-L5) with a simultaneous integrated boost to 65 Gy on PET-positive nodes; IMRT or rotational technique mandatory, with a benchmark-case QA programme. Prostate bed RT (≥66 Gy/33 fx) was advised for pT3-4, Gleason ≥8, or positive margins and given to 25% of MDT and 41% of ENRT pts.

Both groups received 6 months of LHRH agonist or antagonist, started no later than the first fraction (or day 1-10 postoperatively after sLND). Every patient who started intended local therapy plus ADT completed it. Physicians were instructed not to restart ADT absent clinical progression.

Primary: metastasis-free survival (any M1 on PET or death), with local or pelvic nodal relapse explicitly NOT counted as an event. Secondary: biochemical RFS, locoregional RFS, ADT-free survival, and late grade 2+ GU/GI toxicity to 48 months. OS, prostate cancer-specific survival, and time to castration resistance had insufficient events and are deferred.

Grade 2+ GU events above baseline at 4 years were 28% MDT vs 31% ENRT (absolute difference 3%, p=0·73) and grade 2+ GI 7% vs 9% (difference 2%, p=0·93). Most common grade 3 events were urinary incontinence (6% vs 10%) and diarrhoea (1% vs 2%). In post-hoc analysis the driver of toxicity was the prostate bed, not the pelvic volume: GI OR 4·6 (95% CI 1·5-15·8), p=0·0085 and GU OR 1·85 (0·95-3·60), p=0·068 with bed inclusion. No treatment-related deaths.

The single-arm GETUG-P07 OLIGOPELVIS reported 3-year bRFS of 45% for ENRT against 57% at 4 years here, though its median PSA was 3-4 ng/mL and staging was choline-based, so the populations differ. Against the ADT-intensification trials, EMBARK and PRESTO enrolled the PSA-doubling-time population that simulations put at up to 40% pelvic nodal relapse on PET, and this trial's median time off ADT exceeded 48 months in MDT and was not reached in ENRT, versus 13-18 months with RT alone and 16-17 months with ADT alone across earlier series.

No central PET review at baseline or follow-up, so the primary endpoint depends on local reads (authors cite κ 0·74 for pelvic nodes). Curves did not separate in year 1 because of the shared 6 months of ADT, which strains the proportional hazards assumption the HR summarises. The open-label design plausibly biased adverse-event attribution in both directions, and prostate bed RT was left to physician discretion, so a treatment that materially changed both toxicity and local recurrence was not randomised.

The result reads as a field-size question answered on pattern of failure rather than on distant control: relapse after MDT was predominantly locoregional, meaning PSMA PET missed nodal disease in at least half of pts treated to visible targets only. That reframes ENRT less as escalation than as compensation for imaging sensitivity that has not caught up with the treatment paradigm it enabled.

Phase 2 powered at α=0·20; primary MFS p=0·063 would not clear conventional significance, and the authors themselves await a phase 3 (POINTER-PC).

Non-randomised phase 2, eight hospitals in Australia and the Netherlands, run by TROG and ANZUP. Enrolment July 28 2016 to Feb 27 2020; 71 enrolled, one withdrew consent before treatment. This report is the pre-planned final follow-up at a median of 62 months (IQR 60-72).

Histologically confirmed primary RCC, medically inoperable, high risk, or declined surgery, ECOG ≤2, tumours ≤10 cm, N0-N1. Median age 77 years (70-82), 49 (70%) male. Median tumour size 46 mm (37-55), with 39 (56%) T1b, six (9%) T2a and one (1%) T3a.

Size-adapted prescription: 26 Gy in a single fraction for tumours ≤4 cm, 42 Gy in three fractions 48 h apart for tumours >4 cm. Histological confirmation was required before treatment, so this is a biopsy-proven cohort rather than a radiographic-diagnosis one.

Primary: freedom from local progression by RECIST, assessed in the intention-to-treat population, as was safety.

100% local control at 36, 60 and 84 months, with no local recurrences and no cancer-related deaths reported in the cohort.

Seven (10%) patients had at least one treatment-related grade 3 event within 9 months: pain in four (6%), nausea and vomiting in three (4%), colonic obstruction in two (3%), diarrhoea in one (1%). No grade 4 events and no treatment-related deaths; no new long-term safety signals emerged with extended follow-up.

A 100% point estimate in 70 pts carries a wide confidence bound that the headline hides, and RECIST is an imperfect local-control instrument after ablative RT, where a treated mass commonly persists without viable tumour. Renal function trajectory, the endpoint that actually competes with nephrectomy, is not reported in this source.

Prior SABR evidence in primary RCC was retrospective and pooled, so a prospective multicentre dataset at 84 months is the new contribution rather than the effect size itself. Comparison to partial nephrectomy and thermal ablation remains indirect: no randomised trial has run, and this cohort was selected against surgery by definition.

The finding that transfers is durability at a tumour size where thermal ablation performs worst, with a median of 46 mm and 65% at least T1b. What it does not settle is whether SABR is a choice rather than a fallback, which needs a randomised or matched comparison in operable pts, with renal function as a co-primary.

Single-arm phase 2, N=70, inoperable or surgery-declining pts only. No randomised comparator vs partial nephrectomy or thermal ablation. Maturity gate holds despite 62mo f/u.