Excess morbidity and mortality in long term survivors of childhood Ewing sarcoma

2 Sep 2010

By Dr Sharan Sharma

Ewing sarcoma (ES) is the second most common primary osseous malignancy in childhood and adolescence with the estimated annual incidence of 2.93 per million children in USA. For the last few decades, we have seen the improvement in the survival of patients with ES with 5-year survival rate for localized ES of 75% at present. These tumours are aggressive, and multimodality therapy is always required, involving the use of chemotherapy and some form of local therapy (surgery and/or radiation). Therapy-related morbidities include outcomes such as second (and subsequent) malignant neoplasms, cardiac toxicity and infertility. There have been very few studies to understand the long-term outcomes among childhood survivors of ES. The small number of patients diagnosed with ES, and an even smaller number of survivors, complicates the study of disease-specific late effects. To expand the current understanding, researchers from USA designed a study that aimed to assess selected key outcomes (late mortality, subsequent malignant neoplasms, chronic health conditions, fertility, and health status) among long-term ES survivors from the Childhood Cancer Survivor Study (CCSS). They have reported their findings in Journal of the National Cancer Institute that was first published online on July 23, 2010.

They compared cause-specific mortality and health status of a cohort of long-term (5 years) survivors of childhood ES from the US Childhood Cancer Survivor Study (CCSS) with those of sibling control subjects and the US population. Evaluation was made in eligible survivors of 568 and it was compared with US population and sibling control subjects of 3899. According to the analysis, overall survival at 20 years from diagnosis was 78.5% for all ES survivors (95% CI = 74.9 to 81.8). The all-cause standardized mortality ratio, including recurrence, was 13.3 (95% CI = 11.2 to 15.8) overall, 23.1 for women and 10.0 for men. Disease recurrence/progression of the primary ES accounted for 82 (60.3%) deaths. Other causes of death included subsequent malignant neoplasms (n = 19; SMR = 20.0, 95% CI = 12.0 to 31.6), cardiac disease (n = 8; SMR = 12.0, 95% CI = 5.2 to 23.6), other medical causes (n = 10; SMR = 4.0, 95% CI = 1.9 to 7.3), and pulmonary disease (n = 1). With respect to subsequent malignant neoplasms, for those patients who received radiation therapy and those who did not, the standardized mortality ratios were 26.4 (95% CI = 14.4 to 44.7) and 10.0 (95% CI = 0.1 to 55.9), respectively.

In summary the authors of the study indicate clear evidence of long-term negative sequelae in ES survivors. "In addition to increased mortality following ES, survivors are at substantially higher risk of morbidity because of second malignancies, chronic health conditions, and functional impairment, all of which require extensive clinical management. Enrolment and long-term follow-up in late effect programs is clearly indicated in this cohort" they add.