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

Background

Myxoid liposarcoma (MLS) is a rare soft-tissue sarcoma that most often develops in the limbs or trunk. Like other sarcomas, it is usually treated with a combination of surgery and radiation therapy, especially when the tumor is localized and can be removed with curative intent. Preoperative radiotherapy is commonly used to shrink the tumor, improve surgical margins, and reduce the risk of local recurrence. However, standard preoperative doses can increase the chance of wound-healing problems after surgery.

Because MLS appears to be highly sensitive to radiation, researchers asked whether a lower preoperative dose might still provide excellent tumor control while reducing side effects. Earlier phase 2 studies suggested that this approach could be safe and effective, but long-term outcomes had not yet been clearly established.

Why this trial mattered

The DOREMY trial was designed to test a reduced-dose preoperative radiotherapy strategy in patients with localized MLS. The question was clinically important because MLS is uncommon, making large randomized phase 3 trials difficult to perform. If a lower dose works well, it could spare patients unnecessary toxicity without compromising cure rates.

This long-term report provides a more complete picture of whether dose reduction remains effective over time, not just in the short period after treatment.

Study design

DOREMY was a prospective, single-group, phase 2 nonrandomized clinical trial conducted at 9 tertiary sarcoma centers in Europe and the United States. Adults with biopsy-proven, translocation-confirmed localized MLS of the trunk or extremity were eligible. Patients were enrolled between November 24, 2010, and May 14, 2020.

All participants received preoperative radiotherapy to a reduced total dose of 36 Gy, delivered as once-daily 2-Gy fractions, followed by surgical resection when feasible. The analysis reported here includes long-term follow-up data analyzed from January to December 2025.

Who participated

Ninety patients were included in the study. The mean age was 47 years, and 56% were male. The median follow-up was 66.4 months, or a little over 5 and a half years, which is long enough to assess durable local control and later toxic effects.

Importantly, preoperative radiotherapy was delivered according to protocol in all patients. Surgery was not performed in 3 patients because metastatic disease developed before the planned operation.

Main findings

The results were strong and reassuring. At 5 years, the local recurrence-free survival rate was 97.4%, meaning very few patients had the tumor return in the treated area. The progression-free survival rate was 81.0%, the disease-specific survival rate was 89.5%, and overall survival was 88.5%.

These numbers indicate that reduced-dose preoperative radiotherapy maintained excellent local control while preserving favorable longer-term outcomes. In a disease where local recurrence can significantly affect treatment burden and quality of life, this is a major finding.

Safety and toxicity

One of the main goals of lowering the radiation dose was to reduce treatment-related complications, especially problems with wound healing after surgery. In the trial, 18 patients (21%) experienced a wound complication, and 14 patients (16%) required some form of intervention.

Late toxic effects were generally limited. Any grade 2 late toxicity was observed in 13 patients (15%), and grade 3 late toxicity in 3 patients (3%). These findings suggest that the reduced-dose approach may lower the risk of serious long-term harm while still delivering excellent cancer control.

What the results mean

This long-term analysis supports the idea that MLS is particularly radiosensitive and that a preoperative dose of 36 Gy may be sufficient for many patients with localized disease. The data suggest that it is possible to balance efficacy and safety more favorably than with conventional dosing.

For patients, this may mean a shorter or less intensive radiotherapy course with a lower chance of late side effects, while still keeping the risk of local recurrence very low. For clinicians, the findings offer evidence-based support for tailoring treatment rather than using a one-size-fits-all dose.

Clinical implications

In rare cancers like MLS, treatment decisions often rely on phase 2 evidence, expert consensus, and shared decision-making rather than large randomized trials. The authors note that conducting a phase 3 trial would be difficult and likely impractical because of the rarity of the disease.

As a result, these compelling phase 2 data may reasonably support adoption of this reduced-dose regimen in appropriate patients, especially when discussed carefully with the patient and multidisciplinary sarcoma team. Treatment decisions should still consider tumor size, location, resectability, surgical risk, and patient preferences.

Limitations

As with any nonrandomized single-group study, the findings should be interpreted in context. Without a direct comparison group, it is not possible to prove that the reduced dose is superior to standard-dose radiotherapy. The study also reflects care delivered at specialized sarcoma centers, which may not fully represent all treatment settings.

Even so, the long follow-up, multicenter design, and consistent protocol delivery make the results highly informative and clinically meaningful.

Conclusion

The DOREMY trial shows that reduced-dose preoperative radiotherapy for localized myxoid liposarcoma can achieve excellent long-term local control with a favorable toxicity profile. Five-year outcomes were strong, wound complications were acceptable, and late serious toxic effects were uncommon.

For this rare cancer, the evidence supports reduced-dose preoperative radiotherapy as a reasonable treatment option. In practice, it can be considered through shared decision-making between patients and their sarcoma specialists, with the goal of maintaining cure rates while minimizing treatment burden.

Trial registration

ClinicalTrials.gov Identifier: NCT02106312.