In the phase II DOREMY trial reported in JAMA Oncology, Lansu et al found that a reduction in preoperative radiotherapy dose was effective and associated with reduced morbidity in patients with myxoid liposarcoma.

A stated by the investigators, “Currently, preoperative radiotherapy for all soft-tissue sarcomas is identical at a 50-Gy dose level, which can be associated with morbidity, particularly wound complications. The observed clinical radiosensitivity of the myxoid liposarcoma subtype might offer the possibility to reduce morbidity.”

Study Details

The study included 79 patients with nonmetastatic, biopsy-proven, and translocation-confirmed myxoid liposarcoma of the extremity or trunk enrolled between November 2010 and August 2019 at nine centers in Europe and the United States. Patients received preoperative radiotherapy at 36 Gy in once-daily 2-Gy fractions, with subsequent definitive surgical resection after an interval of ≥ 4 weeks.

The primary endpoint was centrally reviewed pathologic treatment response, with the regimen considered a success if ≥ 70% of resection specimens showed treatment response (defined as ≥ 50% of tumor volume containing treatment effects). Morbidity outcomes were wound complications and late toxic effects.

Treatment Response

Among the 79 patients, 2 did not undergo surgery due to intercurrent metastatic disease. Among 77 patients undergoing surgical resection, extensive pathologic treatment response was observed in 70 patients (91%; posterior mean of success probability = 90.4%, 95% highest probability density interval = 83.8%–96.4%). Local control was achieved in all patients. Surgical margins were negative in 72 patients (94%) and microscopically positive in 5 (6%).  

For survival outcomes, 1- and 3-year rates were 97% and 93% for progression-free survival, 99% and 96% for disease-specific survival, and 99% and 95% for overall survival.

Morbidity

Wound complications of any severity were observed in 17 (22%) of 77 patients, with minor, moderate, and major complications observed in 5%, 10%, and 6%, respectively. Complications requiring intervention occurred in 13 patients (17%).

Grade 1 late toxic effects were observed in 28 (40%) of 70 evaluable patients, grade 2 effects were observed in 8 (11%), and grade 3 effects were observed in 2 (3%; edema in both patients); no grade 4 or 5 effects were observed. Among patients with at least 2 years of follow-up, grade ≥ 2 toxic effects consisted of fibrosis in 7%, edema in 5%, and joint stiffness in 0%.

The investigators concluded, “The findings of the DOREMY nonrandomized clinical trial suggest that de-intensification of preoperative radiotherapy dose is effective and oncologically safe and is associated with less morbidity than historical controls, although differences in radiotherapy techniques and follow-up should be considered. A 36-Gy dose delivered in once-daily 2-Gy fractions is proposed as a dose-fractionation approach for myxoid liposarcoma, given that phase III trials are logistically impossible to execute in rare cancers.”

Rick L. Haas, PhD, of the Sarcoma Unit, Netherlands Cancer Institute, Amsterdam, is the corresponding author for the JAMA Oncology article.

Disclosure: This study was by Nanobiotix, Honderdduizend Keer een Tientje Foundation, EORTC-Soft Tissue and Bone Sarcoma Group, UK Institute of Cancer Research, and others. For full disclosures of the study authors, visit jamanetwork.com.