Ewing's sarcoma and the development of secondary malignancies

The multimodality treatment approach for patients with Ewing's sarcoma during the last decades has dramatically improved patient long-term survival. With improved survival, late consequences and morbidity associated with treatment have become apparent. Among the morbidity associated with treatment is the increased risk of development of secondary malignancies. Therefore, the purpose of the current study was to define the outcome of patients who had secondary malignancy develop subsequent to the diagnosis and treatment of Ewing's sarcoma. Of the 397 patients treated for Ewing's sarcoma at our institution during the past 25 years, 26 patients (6.5%) had 29 secondary malignancies develop. The mean age of the 13 males and 13 females averaged 16 years (range, 6-51 years), and the interval from the diagnosis of the Ewing's sarcoma to the development of the secondary malignancy averaged 9.5 years (range, 1-32.5 years). The secondary malignancies included eight hematopoietic cancers, 12 sarcomas, and nine carcinomas. Although carcinomas most likely represent the general risk of developing cancer in the healthy population, the sarcomas were caused by radiation therapy and the hematopoietic tumors caused by chemotherapy. The latter occurred at a mean latent period of 4.8 years (range, 1.7-12.9 years), and the sarcomas occurred after a mean of 10.9 years (range, 1.5-32.5 years). At the mean followup of 15 years (range, 2-33 years) from diagnosis of Ewing's sarcoma and at a mean followup of 5 years (range, 0.5-28 years) from diagnosis of the second malignancy, 14 patients are alive (43%); however, patients with either sarcomas or hematopoietic secondary malignancies had not only a significantly shorter interval from secondary malignancy to followup (3.3 and 1.2 years, respectively, versus 7.3 years), but also a more dismal prognosis (eight of 12 or six of eight patients died, respectively, versus one of nine). Although the risk of having secondary malignancy develop after the treatment of a Ewing's sarcoma may be only slightly greater than the risk compared with other childhood cancers, patients with hematopoietic and radiation-induced secondary malignancies have a detrimental prognosis. Patients with Ewing's sarcoma need to be followed up carefully and frequently.