(P 423) COMPARISON OF CLINICAL COURSE AND FEATURES BETWEEN SCLEROSING EPITHELOID FIBROSARCOMA AND LOW-GRADE FIBROMYXOID SARCOMA

Objective: Sclerosing epithelioid fibrosarcoma (SEF) and low-grade fibromyxoid sarcoma (LGFMS) are ultra-rare sarcomas that share similar genetic translocations. Despite this, the natural history, demographics, and therapy response can vary widely. Herein, we describe in detail differences and similarities between these two histologies to gain a better understanding of where they align and diverge.

Methods: We conducted a single-institution retrospective study of patients (pts) with biopsy proven SEF or LGFMS, who were identified using a free text medical record search engine. Clinical data collected included demographics (age, sex, race/ethnicity), presenting symptoms, tumor extent, and therapies. Overall survival was defined as time from initial diagnosis to death, censored at date of last contact. Analysis of overall survival was conducted using the Kaplan-Meier method with differences in survival curves between LGFMS and SEF evaluated using the log-rank test.

Results: Seventy-eight pts were identified from 1998 to 2024. The majority of participants identified as non-Hispanic white (83%, n=65). The median age of diagnosis was 38 and 53 years for LGFMS and SEF, respectively. We found that LGFMS and SEF had similar male to female ratios (LGFMS 48% female, n=24; SEF 46% female, n=13). At diagnosis, 4 pts (8%) with LGFMS and 9 pts (32%) with SEF had metastatic disease (p=0.017). In both histologies, palpation of a mass was the most common symptom (LGFMS 80%, n=40; SEF 68%, n=19) followed by pain (LGFMS 14%, n=7; SEF 32%, n=9). LGFMS pts had a median interval of 7 months (IQR 2.7-33.8) from symptom onset to diagnosis compared to SEF pt’s interval of 5 months (IQR 1.6-11.9). The most common primary site was the extremities in LGFMS (62%, n=31) and the abdomen in SEF (29%, n=8). All pts whose MUC4 status was reported were positive (LGFMS n=20, SEF n=9). Fusion testing was reported in 13 pts with 12 having the EWSR1-CREB3L1 translocation (LGFMS n=6, SEF n=6) and a single LGFMS pt having the FUS-CREB3L2 translocation. Full analysis of available histologic and molecular data is forthcoming. Therapies rendered for LGFMS and SEF patients, regardless of extent of disease, included surgery (92% vs 89%), radiation therapy (52% vs 36%), and systemic therapy (4% vs 29%), respectively in pts with available data. Amongst pts presenting with localized disease, LGFMS pts were less likely to develop subsequent metastasis as compared to SEF pts (7% vs 52%, p=0.002). Amongst the localized patients, the median time to development was longer in LGFMS as compared to SEF pts (NA vs 3. 9 years). Overall survival was found to be 17.5 years (SD +/- 1.6 years). When stratified by diagnosis, the survival difference between LGFMS and SEF pts reached statistical significance (p < 0.0001).

Conclusion: Despite their genetic similarities, LGFMS and SEF have different demographics and natural histories. LGFMS pts are younger and more likely to present with localized disease. SEF pts have a more aggressive course and are more likely to develop metastatic disease and shorter median overall survival. Detailed pathologic and treatment response comparison data will be presented. Comprehensive genomic studies evaluating molecular changes beyond the characteristic oncofusion are ongoing in order to identify potential therapeutic options.