A long-term analysis of the DOREMY phase 2 nonrandomized clinical trial evaluated whether a reduced dose of preoperative radiotherapy can maintain oncologic safety while lowering treatment-related morbidity in patients with localized myxoid liposarcoma of the extremity or trunk.
The study is clinically relevant because the conventional preoperative radiotherapy regimen for soft-tissue sarcoma is often 50 Gy in 25 fractions, a schedule associated with late toxic effects such as edema, fibrosis, joint stiffness, and functional limitation. Myxoid liposarcoma appears to be more radiosensitive than many other soft-tissue sarcoma subtypes, raising the possibility that dose de-escalation may preserve local control while reducing toxicity.
In this prospective, multicenter, single-arm phase 2 trial, patients received 36 Gy in 18 once-daily fractions before surgical resection. The trial enrolled 90 adults with biopsy-proven, translocation-confirmed localized myxoid liposarcoma of the trunk or extremity. Patients were treated across 9 tertiary sarcoma centers in Europe and the United States. Median follow-up was more than 5 years, allowing assessment of long-term local control, survival outcomes, and late toxic effects.
Title: Dose Reduction of Preoperative Radiotherapy in Myxoid Liposarcoma: The Phase 2 DOREMY Nonrandomized Clinical Trial
Authors: Jules Lansu, Judith V. M. G. Bovée, Pètra M. Braam, Aisha B. Miah, Øyvind S. Bruland, Elizabeth H. Baldini, Astrid N. Scholten, Olga Hamming-Vrieze, Jolien Heukelom, Lisette M. Wiltink, Florine Foppele, Jan F. Ubbels, Vincent van der Noort, Rick L. Haas
Journal: JAMA Oncology
Year:2026
Study Design and Treatment Approach
The DOREMY trial was designed to test a de-escalated preoperative radiotherapy regimen in a rare sarcoma subtype with known radiosensitivity. All enrolled patients received preoperative radiotherapy according to protocol. Surgery was not performed in 3 patients because of intercurrent metastatic disease, leaving 87 patients who underwent resection and were evaluable for local recurrence and toxicity outcomes.
The reduced-dose regimen consisted of 36 Gy delivered in 18 fractions, followed by surgery after an interval of at least 4 weeks. The study used standardized target volume delineation and modern radiotherapy planning techniques. This approach aimed to reduce the late morbidity associated with standard-dose preoperative radiotherapy while preserving the local control benefit that radiotherapy provides in higher-risk soft-tissue sarcoma.
Local Control
The long-term local control results were strong. The 5-year local recurrence-free survival rate was 97.4%.
Only 2 local recurrences were observed among the 87 patients who underwent surgery. One recurrence occurred 10 months after treatment in a patient with a retroperitoneal tumor containing at least 5% round cell component, microscopically positive resection margins, and only 20% pathological response. This patient later died of disease progression.
The second local recurrence occurred 3.5 years after resection of a large 32-cm tumor in the proximal lower extremity. The initial surgical margin was close, and the tumor showed an 80% pathological response. Limb-sparing salvage surgery was performed. A solitary bone metastasis was later detected on whole-body MRI, and follow-up was ongoing.
These findings suggest that reduced-dose preoperative radiotherapy maintained excellent local control in carefully selected patients with myxoid liposarcoma, even with long-term follow-up.
Progression-Free and Survival Outcomes
The 5-year progression-free survival rate was 81.0%. Overall, 16 of the 90 enrolled patients experienced disease progression during follow-up.
Metastatic disease developed in 14 patients, and in more than half of these cases, more than one metastasis was detected at the initial presentation of metastatic disease. The first affected metastatic sites included bone, muscle, retroperitoneum or omentum, lung, pleura, liver, lymph nodes, subcutaneous tissue, and leptomeninges.
The metastatic pattern is notable because myxoid liposarcoma can spread outside the lungs, including to soft tissue, bone, and retroperitoneal sites. This supports the importance of careful systemic surveillance in this disease, beyond local control alone.
A total of 11 deaths were observed, 10 of which were associated with disease progression. At 5 years, disease-specific survival was 89.5%, and overall survival was 88.5%. One death was considered likely related to a second primary cancer rather than myxoid liposarcoma.
Toxicity and Wound Complications
The toxicity profile was favorable compared with the concerns typically associated with preoperative radiotherapy in soft-tissue sarcoma.
Among the 87 patients who underwent surgery, wound complications requiring intervention occurred in 14 patients, representing 16% of the surgical cohort. An additional 4 patients experienced minor wound complications. Overall, 18 patients had some form of wound complication.
Late toxic effects were also limited. The rate of any grade 2 or higher late toxic effect was 18%. Grade 3 toxic effects were observed in only 3 patients, all consisting of edema in patients with proximal lower extremity tumors.
Specific grade 2 or higher late toxic effects included fibrosis in 12%, joint stiffness in 5%, and edema in 7%. Other late toxic effects included fatigue, telangiectasia, and atrophy. Importantly, no fractures were reported, and there were no cases of severe fibrosis or severe joint stiffness.
These findings are important because late morbidity is a major reason to consider radiotherapy dose de-escalation in patients with extremity and trunk soft-tissue sarcoma, particularly younger patients who may live for many years after treatment.
Clinical Interpretation
This long-term analysis provides prospective evidence that a reduced preoperative radiotherapy dose can be oncologically safe in selected patients with myxoid liposarcoma. With a 5-year local recurrence-free survival rate of 97.4%, the study supports the view that this sarcoma subtype may not require the same preoperative radiotherapy dose used broadly across soft-tissue sarcomas.
The results are especially meaningful because myxoid liposarcoma is rare, making large randomized phase 3 trials difficult to conduct. In this context, a prospective multicenter phase 2 trial with long-term follow-up provides useful evidence for clinical practice.
The favorable toxicity profile also matters. A wound complication rate requiring intervention of 16%, grade 2 or higher late toxic effects in 18%, and grade 3 late toxic effects in only 3% suggest that dose reduction may reduce treatment burden without compromising local control for many patients.
How These Findings Fit With Prior Evidence
The findings align with other prospective evidence evaluating dose de-escalation in myxoid liposarcoma. Another single-arm phase 2 trial using 25 Gy in 5 fractions reported promising preliminary results, with no local recurrences among 27 evaluable patients after shorter follow-up.
Together, these studies suggest that dose-reduced preoperative radiotherapy may be a reasonable strategy in myxoid liposarcoma. The DOREMY regimen of 36 Gy in 18 fractions now has longer follow-up and provides stronger reassurance about durable local control.
Important Caveats
The study was single-arm, so it did not directly compare 36 Gy with the conventional 50 Gy regimen. Patient selection may also have influenced the favorable outcomes. Because local recurrence after myxoid liposarcoma can sometimes be difficult to salvage depending on tumor location, size, and relationship to critical structures, dose de-escalation should not be applied automatically to every patient.
The authors advised caution in cases where a local recurrence would be difficult to salvage without major morbidity. For example, a large thigh tumor broadly abutting the femur or sciatic nerve may still be safer to treat with a conventional 50 Gy regimen, because a local recurrence could place the patient at risk for fracture or loss of nerve function.
This means the reduced-dose approach should be used through careful shared decision-making, considering tumor anatomy, expected surgical margins, patient preferences, and the consequences of a possible local recurrence.
Takeaway
The long-term DOREMY trial analysis shows that 36 Gy in 18 fractions as preoperative radiotherapy for localized myxoid liposarcoma can provide excellent local control with a favorable toxicity profile.
At 5 years, local recurrence-free survival was 97.4%, progression-free survival was 81.0%, disease-specific survival was 89.5%, and overall survival was 88.5%. Wound complications requiring intervention occurred in 16% of surgically treated patients, while grade 2 or higher late toxic effects occurred in 18%.
These data support reduced-dose preoperative radiotherapy as an appropriate treatment option for selected patients with myxoid liposarcoma of the extremity or trunk. The decision should be individualized, with shared decision-making between the patient and multidisciplinary sarcoma team.
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