Ewing Sarcoma Survivors At Increased Risk for Subsequent Malignancies

Survivors of childhood Ewing sarcoma have substantial risk for late mortality and subsequent neoplasms, according to a long-term follow-up study. The results support the idea that lifelong follow-up is beneficial in this survivor population.

Though treatment for Ewing sarcoma has improved, allowing for good long-term survival rates, these treatments still generally involve high-dose chemotherapy and aggressive local control measures. “Though effective, these strategies place survivors at risk for long-term medical complications, including anthracycline-induced cardiomyopathy and subsequent neoplasms,” wrote study authors led by Neyssa M. Marina, MD, MS, of Stanford University in Palo Alto, California.

This analysis extends previous work based on the Childhood Cancer Survivor Study; a retrospective study, it included 404 5-year survivors of Ewing sarcoma who were treated between 1970 and 1986, with a median age at last follow-up of 34.8 years. The results were published in Cancer.

Among the 5-year survivors, the 35-year survival rate was 70%. The most common cause of death was recurrent disease in 15.1% of patients, followed by treatment-related causes in 11.2%. The standardized mortality ratio, calculated based on expected deaths from US mortality data, was 8.5 for all causes.

A total of 53 survivors developed subsequent neoplasms, 38 of which were malignant; the cumulative incidence rate of subsequent neoplasms at 35 years from diagnosis was 14.3%, and the standardized incidence ratio (SIR) was 7.8. Breast cancer and osteosarcoma were frequent subsequent neoplasms; the SIR for breast cancer was 14.9, and for osteosarcoma it was 377.1. Acute myeloid leukemia (SIR of 28.9) and lymphoid leukemia (SIR of 15.5) were also substantially more likely in these survivors. The authors noted that nearly all survivors who developed malignant subsequent neoplasms were previously exposed to alkylating agents, anthracyclines, and radiotherapy.

The relative risk of certain chronic conditions was also elevated in Ewing sarcoma survivors. For musculoskeletal conditions, the relative risk was 18.1, while for cardiac complications it was 1.8. The cumulative incidence rates of any chronic conditions and two or more such conditions 35 years after diagnosis were 84.6% and 73.8%, respectively.

“The development and assessment of interventions designed to improve the long-term health of Ewing sarcoma survivors should be a priority,” concluded the authors.