2026-06-16

digest generated 2026-07-19

DOREMY: 5yr LRFS 97.4% after de-escalated 36Gy/18fx preop RT in myxoid liposarcoma, supports dropping below the 50Gy STS standard.

TL;DR

Sarcoma and prostate carry the day, both RT-actionable. DOREMY backs preop de-escalation to 36Gy/18fx in myxoid liposarcoma (5yr LRFS 97.4%, wound complications 21%), likely the evidence ceiling for a rare histology. REVELUTION favors relugolix over leuprolide on coronary plaque progression (68.9 mm³) for men on RT+ADT, though the endpoint is an imaging surrogate, not MACE.

Sarcoma

Rare radiosensitive histology tests whether preop dose can safely drop below the 50Gy STS standard.

Early signal

DOREMY NCT02106312

ForLocalized translocation-confirmed myxoid liposarcoma, trunk/extremity

TL;DR5yr local recurrence-free survival 97.4% after de-escalated 36Gy/18fx preop RT in myxoid liposarcoma; wound complications 21%.

Why it mattersRadiation oncology

The RT read is dose de-escalation: 36Gy/18fx (vs the standard 50Gy/25fx) held 5yr LRFS at 97.4% in translocation-confirmed MLS, with wound complications 21% and G3 late toxicity 3%. Exploiting MLS radiosensitivity trims ~14Gy without a local-control cost, moving the preop-dose decision for this histology specifically.

7 details 4 trials watching

Design

Phase 2 single-group nonrandomized trial, N=90, 9 tertiary sarcoma centers (Europe + US), enrolled 2010-2020. Median follow-up 66.4 mo (IQR 48.8-87.5).

Population & inclusion

Adults with biopsy-proven, translocation-confirmed localized MLS of trunk or extremity. Mean age 47, 56% male.

Radiotherapy

36 Gy in once-daily 2-Gy fractions (18 fx) preoperatively, against the standard 50 Gy/25 fx for soft-tissue sarcoma. Delivered per protocol in all 90 pts, then resection.

Results

5yr LRFS 97.4% (95% CI 93.9-100) is the standout; PFS 81.0%, DSS 89.5%, OS 88.5% (full set in table). 3 pts (3%) progressed to metastasis before surgery.

Endpoint (5yr)	Rate	95% CI
Local recurrence-free survival	97.4%	93.9-100
Progression-free survival	81.0%	72.6-89.4
Disease-specific survival	89.5%	82.6-96.4
Overall survival	88.5%	81.2-95.8

Safety

Wound complications in 18 pts (21%), 14 (16%) needing intervention. Late toxicity: G2 in 13 (15%), G3 in only 3 (3%).

vs leading data

Standard preoperative dose for soft-tissue sarcoma is 50 Gy/25 fx. MLS is highly radiosensitive, which motivates cutting ~14 Gy to 36 Gy while preserving local control.

Applies to

localized, translocation-confirmed myxoid liposarcoma of trunk or extremity

Does not represent other soft-tissue sarcoma histologies or non-translocation-confirmed disease.

Limitations

Single-arm, no randomized comparator vs 50 Gy; equivalence inferred, not proven. Rare cancer makes a phase 3 impractical (authors' argument).

Rationale

Single-arm nonrandomized phase 2; no randomized comparator vs standard 50Gy. Long follow-up, but efficacy equivalence is inferred, not tested. Single-arm design caps the read.

Monday clinic

In localized, translocation-confirmed myxoid liposarcoma of the trunk or extremity, this supports reduced-dose 36Gy preop RT as an option; it does not extend to other soft-tissue sarcoma histologies that lack this radiosensitivity.

Open questions

Non-inferiority vs standard 50Gy preop RT unproven

recruiting International Prospective Registry on Local Treatment Approaches in MLS

n=300 · primary completion 2031-01 · prospective MLS registry: 36Gy vs 50Gy preop RT
Generalizability to non-myxoid soft-tissue sarcoma histologies

active Pre-operative RadiothErapy for Soft Tissue SarcOmas Phase NA

n=15 · primary completion 2027-05 · hypofrac preop RT in mixed extremity/trunk STS

recruiting Short Course of Radiotherapy Prior to Surgery of Soft Tissue Sarcomas Phase NA

n=150 · primary completion 2028-11 · 14x3Gy hypofrac preop RT across STS histologies

recruiting Assessment of the Long-term Efficacy of Moderately Hypofractionated Neoadjuvant Radiotherapy Soft Tissue Sarcoma in the Limbs or Trunk Wall Phase 2

n=135 · primary completion 2032-06 · mod-hypofrac neoadj RT, all STS grades, LC endpoint

Sourced from Lansu et al.

📚 Sources · 📄 1 paper

📄 PAPER Lansu; Bovée; Braam et al. · JAMA oncology (2026-05)

Dose Reduction of Preoperative Radiotherapy in Myxoid Liposarcoma: The Phase 2 DOREMY Nonrandomized Clinical Trial.

PMID 42141895 → doi full text (PMC)

Abstract

IMPORTANCE: Prospective data from 2 phase 2 trials showed favorable wound complication rates and promising local control after a reduced preoperative radiotherapy dose for myxoid liposarcoma (MLS). However, long-term follow-up data are currently lacking. OBJECTIVE: To determine the efficacy and toxicity profile of a reduced preoperative radiotherapy dose in patients with MLS with long-term follow-up. DESIGN, SETTING, AND PARTICIPANTS: The Dose Reduction of Preoperative Radiotherapy in Myxoid Liposarcoma (DOREMY) trial is a prospective, single-group, phase 2 nonrandomized clinical trial conducted in 9 tertiary sarcoma centers in Europe and the US. Eligible patients were adults with biopsy-proven and translocation-confirmed localized MLS of the trunk or extremity who were enrolled from November 24, 2010, to May 14, 2020. Data were analyzed from January to December 2025. INTERVENTION: Preoperative radiotherapy to a reduced dose of 36 Gy in once-daily 2-Gy fractions followed by resection. MAIN OUTCOMES AND MEASURES: Long-term local recurrence-free survival, progression-free survival, disease-specific survival, overall survival, and late toxic effects. RESULTS: Ninety patients (mean [SD] age, 47 [13.1] years; 50 [56%] male) were included and followed up for a median (IQR) of 66.4 (48.8-87.5) months. Preoperative radiotherapy was delivered according to protocol in all patients. Surgery was not performed in 3 patients (3%) due to intercurrent metastatic disease. Local recurrence-free survival, progression-free survival, disease-specific survival, and overall survival rates at 5 years were 97.4% (95% CI, 93.9%-100%), 81.0% (95% CI, 72.6%-89.4%), 89.5% (95% CI, 82.6%-96.4%), and 88.5% (95% CI, 81.2%-95.8%), respectively. In total, 18 patients (21%) experienced a wound complication, and 14 (16%) required intervention. Any grade 2 or grade 3 late toxic effects were seen among 13 patients (15%) and 3 patients (3%), respectively. CONCLUSIONS AND RELEVANCE: This long-term analysis of the DOREMY nonrandomized clinical trial demonstrated excellent local control and a favorable toxicity profile following dose reduction of preoperative radiotherapy in patients with MLS. These compelling phase 2 findings support adoption of this regimen as an appropriate treatment option through shared decision-making with the patient, given the impracticality of conducting a phase 3 trial for a rare cancer. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02106312.

📝 42141895

Radiation Curative Phase 2 trial Early signal

Prostate

GnRH antagonist vs agonist choice reframed as a coronary-plaque question for men on RT + ADT.

Early signal

REVELUTION

ForIntermediate/high-risk non-metastatic prostate on definitive RT + ADT

Total coronary plaque volume change safety

68.9 mm³ more plaque with leuprolide vs relugolix

Adjusted for age, statin, baseline plaque; crude 56 vs 25 mm³

TL;DR68.9 mm³ greater total coronary plaque progression with leuprolide vs relugolix at 12mo (adjusted), non-metastatic prostate on RT + ADT.

Reported via UroToday →

Why it mattersRadiation oncology

The signal is non-calcified plaque: leuprolide added 68.9 mm³ more total plaque than relugolix at 12mo (adjusted), and that gap tracked the non-calcified subtype, with no significant difference in calcified or low-attenuation plaque. For a radonc co-prescribing ADT with definitive RT, it strengthens the mechanistic case for relugolix in cardiovascular-risk pts.

8 details 3 trials watching

Design

Single-institution, open-label, parallel-cohort randomized trial (4 Emory-affiliated centers, Jun 2020-2024). ADT-eligible pts randomized 1:1 relugolix vs leuprolide, stratified by ASCVD 10-yr risk; a lower-risk radiotherapy-alone cohort ran in parallel as a no-ADT control. N=94.

Population & inclusion

Non-metastatic intermediate/high-risk prostate cancer, all receiving pelvic RT (± pelvic nodes). ADT arms received ≥6 months hormone therapy; the control cohort was lower-risk, RT-alone, with no planned ADT.

Regimen

Relugolix 360mg load then 120mg daily vs leuprolide 3-month depot. Serial coronary CTA at baseline and 12mo, blinded to arm, quantified by the HeartFlow automated tool.

Endpoints

Primary: 12-month change in total plaque volume. Secondary: non-calcified, calcified, and low-attenuation plaque subtypes.

Results

Adjusted mean total-plaque difference 68.9 mm³ favoring relugolix; crude 12-mo change 56 vs 25 mm³ (leuprolide vs relugolix). Excess driven by non-calcified plaque; calcified and low-attenuation subtypes showed no significant difference.

vs leading data

Offers a coronary-atherosclerosis mechanism for HERO (2020), where relugolix showed lower MACE than leuprolide despite similar testosterone suppression and metabolic effects.

Applies to

intermediate/high-risk non-metastatic prostate pts receiving definitive RT plus ADT

Does not represent metastatic disease or ADT-free lower-risk management.

Limitations

Surrogate imaging endpoint (plaque volume), not clinical MACE; small single-institution N=94, 12-month follow-up. Open-label, with a non-randomized RT-alone control cohort.

Rationale

Small single-institution randomized trial, surrogate coronary-plaque imaging endpoint (not clinical MACE), 12-mo f/u; mechanistically supports HERO but doesn't independently establish clinical benefit.

Monday clinic

In an intermediate or high-risk non-metastatic prostate pt getting definitive RT plus ADT with elevated cardiovascular risk, this supports favoring relugolix over leuprolide on a coronary-plaque basis; it does not extend to ADT-free lower-risk pts or to hard cardiovascular-event rates.

Open questions

Do plaque-volume differences translate to fewer clinical cardiovascular events?

recruiting Effects of Relugolix vs Leuprolide on Cardiac Function in Patients With Prostate Cancer Phase 2

n=70 · primary completion 2027-12 · phase 2 relugolix vs leuprolide cardiac function MRI

recruiting REVELUTION-2: Relugolix+Abiraterone Acetate (AA) Versus Leuprolide+AA Cardiac Trial Phase 3

n=72 · primary completion 2029-07 · phase 3 relugolix vs leuprolide cardiac head-to-head
Durability of plaque effect beyond 12 months

recruiting REVELUTION-2: Relugolix+Abiraterone Acetate (AA) Versus Leuprolide+AA Cardiac Trial Phase 3

n=72 · primary completion 2029-07 · up to 24-mo combination arm, cardiac readout to 2029
Generalizability beyond single-institution N=94

📚 Sources · 📄 1 paper

📄 PAPER · UroToday

REVELUTION Trial: A Comparative Study of GnRH Agonist and Antagonist on Coronary Plaque in Prostate Cancer - Sagar Patel

article →

Abstract

UroToday - GU OncToday brings coverage of the clinically relevant content needed to stay at the forefront of the dynamic field of GU oncology and urology.

📝 https://www.urotoday.com/video-lectures/prostate-cancer/video/5353-revelution-trial-a-comparative-study-of-gnrh-agonist-and-antagonist-on-coronary-plaque-in-prostate-cancer-sagar-patel.html?mtm_campaign=Patel_SocialVideo_ID5353

Systemic Curative Phase 2 trial Early signal