(P 433) A 20-YEAR MONOCENTER EXPERIENCE ON CLINICAL CHARACTERISTICS AND OUTCOME OF EXTRASKELETAL EWING SARCOMA.

Objective: Extraskeletal Ewing sarcoma (EES) represents a rare entity, historically described as the soft tissue counterpart of the classical bone Ewing Sarcoma (ES), including Askin tumors and peripheral primitive neuroectodermic tumor (pPNET). Morphologically, they belong to the small round blue cells sarcoma family.
Compared to the ES, EES is more common in adults and young adult (AYA) patients (pts) rather than paediatric population. Besides incidence and clinical presentation, the outcome and the molecular/biological characteristics markedly differ among the two ES groups. So far, the
available data on this topic originate from multicenter, paediatric ES studies, and the treatments have replayed the therapeutic approaches generally adopted for the ES.
Furthermore, for both EES and ES, the molecular pattern prognostic impact is still debated.
This retrospective analysis aimed to describe the clinical features, the peculiar behaviour and the outcomes of a monocenter EES population. Beside the classical fusion-transcript, new entities have been identified (CIC-DUX and BCOR), which requires a further personalized
approach.

Methods: We collected and analysed the data (demographic, clinical, pathological and radiologic data) of all subsequent EES treated in a tertiary cancer center between 1997 to 2023. Based on the clinical presentation at diagnosis (extremities vs axial site, tumour volume and stage) and according to the previous published bone ES data, we identified three risk categories: 1) standard risk (localized disease, susceptible to radical surgery), 2) high risk (locally advanced, usually axial site and over than 5 cm, and pulmonary metastasis and 3)very high risk (presence of extrapulmonary metastatic patients).   Each available pathological specimen has been review by a sarcoma-dedicated team of pathologists, with the molecular
assessment still ongoing for the final data. The retrospective analysis was approved by our Etic Committee.

Results: We identified 76 pts, 47 males (62%), with a median age at diagnosis of 26 (15-70). 3 (4%) were categorized into standard risk, 58 (76%) high risk and 15 (20%) very high risk; 14 pts had an Askin tumour (18%) and they all were categorized as high risk sarcoma.
27 pts presented with metastatic disease at diagnosis. Among the 41 pts with available molecular data, 35/41 (85%) presented an ets-related fusion transcript. At the staging, the bone marrow biopsy was performed on 55 patients (72%), with only 3 pts positive. 14/49 localized/locally advanced disease pts had surgery upfront, due to the clinical presentation. The remaining had chemotherapy upfront as indicated in ES therapeutic management. 40 (53%) received high dose chemotherapy after standard treatment based on the risk category. In terms of local treatment, 11 pts had radical surgery (upfront or after induction chemotherapy), 10 received definitive radiotherapy, 24 pts have been treated with both local treatment (49%) due to soft tissue involvement. The whole 5-years event-free survival (PFS) and overall survival (OS) were 35% and 41%, respectively.
We stratified the outcomes pts based on stage (metastatic diseases vs localized/locally advanced disease) and on risk category (very high risk vs standard/High risk), suggesting a statistical difference between the groups. Furthermore, with this analysis (Table 1) we also demonstrated the impact of non pulmonary metastases on EES pts prognosis. An updated analysis will be provided at the time of the meeting.

Conclusion: According to our knowledge, this analysis is the largest monocentric study on EES and represents a useful instrument to better understand this rare entity, affecting both adolescent & young adult (AYA) and adult patients. We showed the prognostic impact of non-pulmonary metastatic disease (classified as the very high risk category )on EES pts, suggesting an comparable survival rate for patients with pulmonary metastatic disease and those with locally-advanced disease. Further prospective studies are needed to explore and demonstrate this hypothesis.