Section Structure
Highlights
Background and Clinical Rationale
Study Design and Methods
Key Efficacy Results
Safety and Late Toxic Effects
Clinical Interpretation
Strengths and Limitations
Implications for Practice
Conclusion
Funding and Trial Registration
References
Highlights
In the phase 2 DOREMY trial, preoperative radiotherapy reduced to 36 Gy in 18 fractions was associated with a 5-year local recurrence-free survival of 97.4% in patients with localized myxoid liposarcoma of the trunk or extremity.
Long-term disease outcomes remained favorable after a median follow-up of 66.4 months, with 5-year progression-free survival of 81.0%, disease-specific survival of 89.5%, and overall survival of 88.5%.
Wound complications occurred in 21% of patients, with 16% requiring intervention, and grade 2 to 3 late toxic effects were uncommon, supporting a favorable toxicity profile compared with historical expectations for standard-dose preoperative radiotherapy in soft tissue sarcoma.
For a rare and notably radiosensitive sarcoma subtype, these data strengthen the argument that de-escalated preoperative radiotherapy is a reasonable standard option when discussed through shared decision-making.
Background and Clinical Rationale
Myxoid liposarcoma is a biologically distinctive subtype of soft tissue sarcoma characterized by recurrent chromosomal translocations, most commonly involving FUS::DDIT3. Clinically, it differs from many other sarcomas in several important ways: it tends to arise in the extremities, often in younger adults, and is unusually sensitive to radiotherapy. This radiosensitivity has long made myxoid liposarcoma an attractive candidate for treatment de-escalation.
Standard preoperative radiotherapy for localized soft tissue sarcoma has generally been 50 Gy in 25 fractions. That approach is supported by broad sarcoma experience, but myxoid liposarcoma may not require the same dose to achieve durable local control. If lower-dose radiotherapy can preserve efficacy, the potential advantages are clinically meaningful: less acute toxicity, fewer postoperative wound complications, reduced fibrosis, edema, stiffness, pain, and better long-term limb function.
This question matters because preoperative radiotherapy creates a tradeoff. Compared with postoperative radiotherapy, it typically allows smaller treatment volumes and lower total dose, which may improve late effects, but it also increases postoperative wound complications. In myxoid liposarcoma, where tumors often shrink substantially and undergo marked histologic response after irradiation, reducing the dose further may improve the therapeutic ratio.
The DOREMY trial was designed to test that premise prospectively. Earlier reports from phase 2 experience suggested promising short-term outcomes with reduced-dose preoperative radiotherapy, but long-term oncologic durability remained essential before practice could move decisively. The current report addresses that evidence gap.
Study Design and Methods
DOREMY was a prospective, single-group, phase 2 nonrandomized clinical trial conducted across 9 tertiary sarcoma centers in Europe and the United States. Patients were enrolled from November 24, 2010, to May 14, 2020. Data analysis was performed from January to December 2025.
Eligible participants were adults with biopsy-proven, translocation-confirmed, localized myxoid liposarcoma of the trunk or extremity. The requirement for molecular confirmation is important, because the biological rationale for dose de-escalation rests on the specific radiosensitivity of true myxoid liposarcoma rather than on soft tissue sarcoma as a broad category.
The intervention consisted of preoperative radiotherapy delivered to 36 Gy in once-daily 2-Gy fractions, followed by surgical resection. This regimen represents a substantial reduction from the conventional 50 Gy preoperative standard used for unselected soft tissue sarcomas.
The main outcomes for this long-term analysis were local recurrence-free survival, progression-free survival, disease-specific survival, overall survival, and late toxic effects. Wound complications were also reported, as these remain one of the most clinically relevant downsides of preoperative treatment.
Ninety patients were included. The mean age was 47 years, and 56% were male. Preoperative radiotherapy was delivered according to protocol in all patients, underscoring the feasibility of the regimen across multiple high-volume referral centers. Surgery was not performed in 3 patients because of intercurrent metastatic disease, a reminder that even in a highly local-treatment-responsive sarcoma subtype, systemic relapse still shapes outcomes.
Key Efficacy Results
The central finding is the excellent local control achieved with dose-reduced radiotherapy. At 5 years, local recurrence-free survival was 97.4%, with a 95% confidence interval of 93.9% to 100%. For clinicians managing localized sarcoma, this is the most practice-changing result. Local control after preoperative treatment is the benchmark that cannot be compromised by de-escalation, and the DOREMY results suggest that, in myxoid liposarcoma, it was not.
This magnitude of local control is especially compelling because it was achieved in a multicenter prospective setting rather than a small, single-institution retrospective series. It supports the biological premise that myxoid liposarcoma requires less radiation dose than other soft tissue sarcomas to sterilize microscopic residual disease and support limb-sparing surgery.
The broader disease outcomes were also favorable, although, as expected, not quite as striking as local control. Five-year progression-free survival was 81.0% (95% CI, 72.6% to 89.4%). Five-year disease-specific survival was 89.5% (95% CI, 82.6% to 96.4%), and overall survival was 88.5% (95% CI, 81.2% to 95.8%). These outcomes indicate that the excellent local results did not come at the cost of compromised long-term disease control.
It is also important to interpret these endpoints in light of myxoid liposarcoma biology. Patients may develop metastatic disease despite excellent local management, and this subtype has a somewhat distinctive metastatic pattern, sometimes involving extrapulmonary soft tissue sites. Therefore, progression-free and overall survival are not determined solely by the success of local therapy. The DOREMY findings are reassuring because systemic outcomes appear consistent with what would be expected for localized myxoid liposarcoma managed at expert centers, rather than suggesting any adverse effect of lower local radiation dose.
Although the study was nonrandomized and lacked a direct 50-Gy comparator arm, the long-term local recurrence-free survival estimate compares favorably with historical outcomes from standard-dose preoperative radiotherapy and surgery in soft tissue sarcoma, and arguably exceeds what many clinicians would consider necessary to justify de-escalation in such a rare disease.
Safety and Late Toxic Effects
Toxicity is where dose de-escalation is expected to deliver its clinical value. In DOREMY, 18 patients, or 21%, experienced a wound complication, and 14 patients, or 16%, required intervention. For sarcoma specialists, these figures are notable because wound morbidity after preoperative radiotherapy has historically been a major practical concern, especially for lower-extremity tumors.
While cross-trial comparisons should be made cautiously, these wound complication rates appear favorable relative to historical experiences with standard-dose preoperative radiotherapy for soft tissue sarcoma, where wound complication rates near one-third have often been cited. A lower rate of wound intervention is particularly meaningful for patient counseling, because this is the aspect of toxicity patients most immediately experience after limb-sparing surgery.
Late toxic effects were uncommon. Grade 2 late toxic effects occurred in 13 patients (15%), and grade 3 late toxic effects in 3 patients (3%). The abstract does not enumerate each specific late effect, but in sarcoma practice these events commonly include fibrosis, edema, joint stiffness, pain, or functional impairment. The low rate of higher-grade late toxicity is consistent with the theoretical benefit of reducing dose in a disease highly responsive to radiotherapy.
From a survivorship perspective, this matters greatly. Many patients with localized myxoid liposarcoma are relatively young and may live for years after treatment. In that setting, even modest reductions in fibrosis, stiffness, and chronic soft-tissue damage may translate into substantial gains in mobility, work capacity, and quality of life. Therefore, the favorable late-toxicity profile is not merely supportive information; it is part of the main clinical value proposition of the regimen.
Clinical Interpretation
The DOREMY trial adds a persuasive layer of evidence to an evolving treatment concept: histology-specific radiotherapy dosing in soft tissue sarcoma. Rather than treating all sarcomas with a single preoperative dose standard, DOREMY supports tailoring dose to tumor biology. Myxoid liposarcoma is precisely the kind of subtype in which this strategy makes sense, because radiosensitivity is well recognized and measurable both radiographically and pathologically.
There are several reasons these results are likely to influence practice. First, randomized phase 3 trials are often unrealistic in rare sarcoma subtypes because of low incidence, slow accrual, biological heterogeneity, and limited funding. The investigators explicitly acknowledge this practical barrier. Second, the study enrolled patients across multiple expert centers, increasing confidence that the findings are not idiosyncratic to a single institution. Third, the follow-up is now long enough to address the chief concern surrounding de-escalation: whether early favorable local control would endure.
For multidisciplinary sarcoma teams, the regimen may be particularly attractive in patients for whom postoperative function is a high priority, such as younger adults with lower-extremity disease. It may also be helpful when the anticipated wound risk with standard preoperative treatment is a major concern. However, the decision still requires individualized discussion involving surgical oncology, radiation oncology, pathology, radiology, and the patient.
Shared decision-making remains important because dose de-escalation, even with strong prospective support, is not identical to proof from randomized comparison. Some clinicians may still favor conventional-dose treatment in unusual clinical scenarios, such as borderline resectability, concern for adverse histologic features, or uncertainty about diagnosis. Yet for a molecularly confirmed localized myxoid liposarcoma treated in an experienced center, DOREMY makes a convincing case that 36 Gy preoperative radiotherapy is an appropriate treatment option.
Strengths and Limitations
The trial has several strengths. It was prospective, multicenter, and focused on a biologically defined sarcoma subtype. Treatment delivery was protocol compliant in all patients, and follow-up was long, with a median of 66.4 months. The endpoints were clinically relevant and included both oncologic outcomes and toxicity.
Its limitations are equally important to acknowledge. The study was single-group and nonrandomized, so all efficacy and toxicity interpretation depends on comparison with historical controls rather than a concurrent control arm. The sample size, although appropriate for a rare tumor, remains modest at 90 patients. Management in tertiary sarcoma centers may limit generalizability to lower-volume settings. In addition, the abstract does not provide granular detail on surgical margin status, tumor size distribution, functional outcomes, or patient-reported quality-of-life measures, all of which would help refine patient selection and counseling.
Another limitation is that excellent local control in myxoid liposarcoma may partly reflect expert surgery and imaging-based planning rather than dose reduction alone. That does not weaken the clinical usefulness of the regimen, but it does mean that replication outside specialized teams should proceed thoughtfully.
Implications for Practice
For current clinical practice, the main message is straightforward: for adults with biopsy-proven, translocation-confirmed, localized myxoid liposarcoma of the trunk or extremity, preoperative radiotherapy to 36 Gy in 18 fractions followed by resection appears to provide durable local control with a favorable toxicity profile.
This does not necessarily imply that every patient with myxoid liposarcoma should automatically receive this exact approach. Rather, it supports making 36 Gy preoperative radiotherapy part of the standard discussion in sarcoma boards and patient consultations. In many cases, it may reasonably replace the historical 50-Gy strategy.
The study also reinforces a broader oncology principle: de-escalation should be driven by tumor biology and prospective evidence, not by convenience alone. Myxoid liposarcoma may become a model for subtype-specific radiotherapy adaptation in other rare tumors, provided the biological rationale is strong and long-term follow-up confirms safety.
Conclusion
The long-term DOREMY results provide some of the strongest prospective evidence to date that reduced-dose preoperative radiotherapy is sufficient for localized myxoid liposarcoma. A regimen of 36 Gy in 18 fractions achieved a 5-year local recurrence-free survival of 97.4%, with encouraging progression-free and survival outcomes and relatively low rates of wound morbidity and late toxicity.
In a rare cancer where a definitive phase 3 trial is unlikely to be feasible, these data are clinically consequential. They support a shift from one-size-fits-all sarcoma radiotherapy toward a more histology-informed strategy. For appropriately selected patients treated in experienced centers, reduced-dose preoperative radiotherapy should now be considered a legitimate and evidence-based option.
Funding and Trial Registration
Trial registration: ClinicalTrials.gov Identifier NCT02106312.
The abstract provided does not specify funding details. Readers should consult the full JAMA Oncology publication for complete funding and conflict-of-interest disclosures.
References
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