Dose Reduction of Preoperative Radiotherapy in Myxoid Liposarcoma: Long-Term Results from the Phase 2 DOREMY Trial

Background

Myxoid liposarcoma (MLS) is a rare type of soft tissue sarcoma, most often arising in the trunk or extremities. Unlike many other sarcomas, MLS is known to be relatively sensitive to radiotherapy. That characteristic has led researchers to ask an important question: can the usual preoperative radiation dose be safely reduced without sacrificing tumor control?

For most soft tissue sarcomas, standard preoperative radiotherapy is typically delivered to a total dose of 50 Gy. In MLS, however, earlier prospective studies suggested that lower doses might still achieve excellent local control while potentially reducing treatment-related harm, especially wound complications after surgery. The DOREMY trial was designed to test that idea. This long-term follow-up report provides a more complete picture of both benefit and safety.

Study Design

The Dose Reduction of Preoperative Radiotherapy in Myxoid Liposarcoma (DOREMY) trial was a prospective, single-group, phase 2 nonrandomized clinical trial conducted at 9 tertiary sarcoma centers in Europe and the United States. Adults were eligible if they had localized MLS of the trunk or an extremity that was confirmed by biopsy and molecular testing for the characteristic translocation associated with this tumor.

Patients were enrolled between November 24, 2010, and May 14, 2020. The analysis for this long-term report was performed from January to December 2025. Because this was a rare cancer, a randomized phase 3 trial was considered difficult to complete in a practical timeframe, which is one reason phase 2 evidence is especially important in this setting.

Treatment Approach

Participants received preoperative radiotherapy at a reduced total dose of 36 Gy, delivered in once-daily 2-Gy fractions. After radiotherapy, the standard plan was surgical resection of the tumor.

The rationale for this approach was straightforward: if MLS responds well enough to a lower dose, patients may avoid some of the toxicity associated with higher-dose radiation while still receiving effective local treatment before surgery. Preoperative radiation can help shrink or sterilize part of the tumor, potentially making surgery easier and improving local disease control, but it can also increase the risk of wound-healing problems. Reducing the dose could therefore offer a meaningful quality-of-care advantage if cancer control remains strong.

Who Took Part

A total of 90 patients were included. The mean age was 47 years, and 56% were men. The median follow-up was 66.4 months, or a little over 5 and a half years, which is long enough to evaluate whether local recurrence or late treatment-related toxicity emerged over time.

Preoperative radiotherapy was delivered exactly as planned in all patients. Surgery was not performed in 3 patients because they developed metastatic disease during the treatment course, which changed the clinical situation before the operation could take place.

Main Results

The long-term outcomes were encouraging.

At 5 years, local recurrence-free survival was 97.4%. This means that nearly all patients remained free of the cancer returning in the original area. Progression-free survival was 81.0%, disease-specific survival was 89.5%, and overall survival was 88.5%.

These results are particularly notable because they were achieved with a reduced radiotherapy dose rather than the conventional higher dose. In practical terms, the study suggests that for many patients with localized MLS, 36 Gy before surgery may be enough to maintain excellent local control.

Safety and Toxicity

A key goal of dose reduction is lowering harm, and the safety findings in DOREMY support that goal.

Wound complications occurred in 18 patients, or 21% of the cohort. Of these, 14 patients, or 16%, required some form of intervention. In sarcoma care, wound complications matter because they can delay recovery, require additional procedures, and affect the timing of other treatments.

Late toxic effects were also relatively limited. Any grade 2 late toxicity was seen in 13 patients (15%), and grade 3 late toxicity in 3 patients (3%). Grade 2 toxic effects represent moderate symptoms or functional changes, while grade 3 toxic effects are more severe and often require medical attention or intervention. The low rate of serious late toxicity is a favorable sign for long-term tolerability.

What the Findings Mean

These results strengthen the case for reduced-dose preoperative radiotherapy in MLS. The trial demonstrates that excellent local control can be achieved with 36 Gy, while keeping wound and late toxicity at acceptable levels.

This is important because treatment decisions in rare cancers often rely on limited evidence. In MLS, the biological sensitivity of the tumor appears to justify a tailored approach rather than automatically applying the standard dose used for other soft tissue sarcomas. The DOREMY trial provides prospective long-term evidence that a lower dose can work well in carefully selected patients with localized disease.

There are also practical advantages. Lower radiation exposure may reduce the burden on patients and healthcare systems, and it may help preserve function and recovery after surgery. For patients, that can translate into a more manageable treatment journey without compromising the main goal of curing localized disease.

Clinical Context

Although the results are very strong, they should be interpreted in the context of the study design. This was a single-group phase 2 trial, not a randomized comparison against standard-dose radiotherapy. That means we cannot say with absolute certainty how the reduced-dose regimen would compare head-to-head with conventional dosing in every situation.

Still, in rare tumors like MLS, randomized phase 3 trials may be unrealistic because of slow patient accrual and the limited number of cases. In such settings, carefully designed phase 2 studies with long follow-up can provide enough evidence to support practice change, especially when the treatment effect is large and consistent.

Practical Takeaway

For adults with localized myxoid liposarcoma of the trunk or extremity, preoperative radiotherapy to 36 Gy followed by surgery appears to offer excellent long-term local control with an acceptable toxicity profile. The findings support discussing this approach as a treatment option through shared decision-making between clinicians and patients.

Shared decision-making is particularly important here because treatment choice depends on tumor location, planned surgery, patient priorities, functional concerns, and the balance between maximizing local control and minimizing treatment-related side effects.

Conclusion

The long-term DOREMY trial results show that dose-reduced preoperative radiotherapy can be a highly effective and reasonably safe strategy for localized myxoid liposarcoma. Five-year local recurrence-free survival was outstanding, and serious late toxicity was uncommon. For a rare cancer where a large randomized trial is unlikely, these data provide meaningful support for incorporating reduced-dose preoperative radiotherapy into routine discussion and care planning.

Trial Registration

ClinicalTrials.gov Identifier: NCT02106312.