Ewing Sarcoma as Secondary Malignant Neoplasm—Epidemiological and Clinical Analysis of an International Trial Registry

SIMPLE SUMMARY: Ewing sarcoma (EwS) is a malignant bone and soft-tissue cancer that primarily affects adolescents and young adults. In rare cases, EwS develops as a secondary cancer; that is, after a previous cancer other than EwS. We collected information on all patients with EwS as a secondary cancer from three past international EwS studies to better understand affected patients and to identify potential at-risk patients. Forty-two patients with secondary EwS were identified, representing approximately 1.1% of all EwS cases. As primary cancers, patients suffered mainly from cancers of the blood-forming system, such as leukemia and lymphoma. We could not identify any risk factors for the development of EwS as a secondary cancer. Survival from a second cancer diagnosis with EwS is comparable to EwS as a first cancer diagnosis; therefore, patients with secondary EwS should also be offered complete therapy with the goal of cure, especially if the tumor is localized to only one site. ABSTRACT: Ewing sarcoma (EwS) is the second most common bone and soft tissue tumor, affecting primarily adolescents and young adults. Patients with secondary EwS are excluded from risk stratification in several studies and therefore do not benefit from new therapies. More knowledge about patients with EwS as secondary malignant neoplasms (SMN) is needed to identify at-risk patients and adapt follow-up strategies. Epidemiology, clinical characteristics, and survival analyses of EwS as SMN were analyzed in 3844 patients treated in the last three consecutive international EwS trials, EICESS 92, Euro-E.W.I.N.G. 99, and EWING 2008. Forty-two cases of EwS as SMN (approximately 1.1% of all patients) were reported, preceded by a heterogeneous group of malignancies, mainly acute lymphoblastic leukemias (n = 7) and lymphomas (n = 7). Three cases of EwS as SMN occurred in the presumed radiation field of the primary tumor. The median age at diagnosis of EwS as SMN was 19.4 years (range, 5.9–72) compared with 10.8 years (range, 0.9–51.2) for primary EwS. The median interval between first malignancy and EwS diagnosis was 7.4 years. The 3-year overall survival (OS)/event-free survival (EFS) was 0.69 (SE = 0.09)/0.53 (SE = 0.10) for localized patients and 0.36 (SE = 0.13)/0.29 (SE = 0.12) for metastatic patients (OS: p = 0.02; EFS: p = 0.03). Survival in patients with EwS as SMN did not differ between hematologic or solid primary malignancies. EwS as SMN is rare; however, survival is similar to that of primary EwS, and its risk-adjusted treatment should be curative, especially in localized patients.