Secondary Malignancies after Ewing Sarcoma—Epidemiological and Clinical Analysis of an International Trial Registry

Abstract

Ewing sarcoma (EwS) represents highly aggressive bone and soft tissue tumors that require intensive treatment by multi-chemotherapy, surgery and/or radiotherapy. While therapeutic regimens have increased survival rates, EwS survivors face long-term sequelae that include secondary malignant neoplasms (SMNs). Consequently, more knowledge about EwS patients who develop SMNs is needed to identify high-risk patients and adjust follow-up strategies. We retrospectively analyzed data from 4518 EwS patients treated in five consecutive EwS trials from the Cooperative Ewing Sarcoma Study (CESS) group. Ninety-six patients developed SMNs after primary EwS, including 53 (55.2%) with solid tumors. The latency period between EwS and the first SMN was significantly longer for the development of solid SMNs (median: 8.4 years) than for hematologic SMNs (median: 2.4 years) (p < 0.001). The cumulative incidence (CI) of SMNs in general increased over time from 0.04 at 10 years to 0.14 at 30 years; notably, the specific CI for hematologic SMNs remained stable over the different decades, whereas for solid SMNs it gradually increased over time and was higher for metastatic patients than in localized EwS patients (20 years: 0.14 vs. 0.06; p < 0.01). The clinical characteristics of primary EwS did not differ between patients with or without SMNs. All EwS patients received multi-chemotherapy with adjuvant radiotherapy in 77 of 96 (80.2%) patients, and the use of radiation doses ≥ 60 Gy correlated with the occurrence of SMNs. The survival rate after SMNs was 0.49, with a significantly better outcome for solid SMNs compared with hematologic SMNs (3 years: 0.70 vs. 0.24, respectively; p < 0.001). The occurrence of SMNs after EwS remains a rare event but requires a structured follow-up system because it is associated with high morbidity and mortality.

Osteosarcoma Arising After Ewing Sarcoma orVice Versa: A Report of 20 Affected Patients from the Cooperative Osteosarcoma Study Group (COSS)

“…However, our data confirms the overwhelming role of radiotherapy in this sequence of events. This has been previously observed by others (1)(2)(3). It may thus be wise to carefully analyze whether local Ewing sarcoma therapy truly requires irradiation or if the same quality of local control may be achieved by surgery.…”

“…To date, the low frequency of affected patients with both malignancies has limited analyses of epidemiological variables, apart from radiotherapy administered against the first cancer, and prognostic factors associated with better chances of survival of the second. The Cooperative Ewing Sarcoma Study Group CESS, like our group run under the auspices of the German Society of Pediatric Oncology and Hematology (GPOH), has very recently presented their experiences with both secondary malignancies arising after Ewing sarcomas (3) and secondary Ewing sarcomas (10), respectively. While there is considerable patient overlap between their group and ours, the clear focus on osteosarcomas, a detailed analysis of received therapies, and a presentation of long-term outcomes still make our analysis unique.…”

Research Progress of Multiple Primary Malignancies Associated With Esophageal Cancer

“…44 There is also evidence that second primary lung cancer, second primary gastrointestinal tumors, and Myelodysplastic syndrome are associated with the use of alkylating agents. [45][46][47] Therefore, in addition to considering the efficacy, the occurrence of chemotherapy related MPMs should be considered when selecting a chemotherapy regimen, especially for children.…”

Oncology

“…This analysis from Essen (Germany) looked at data from 4,518 patients treated for Ewing’s sarcoma included in the Cooperative Ewing’s Sarcoma Study. 6 Overall, 96 of these patients went on to develop secondary neoplasms. The latency to the development of these lesions was longer when these secondaries were solid tumours (8.4 years) when compared to haematologic lesions (2.4 years).…”