Long-term survivors of Ewing sarcoma (ES) and osteosarcoma may be at risk for therapy-related acute leukemia or myelodysplastic syndrome (t-AL/MDS).
We retrospectively reviewed the clinicopathologic characteristics of 1,071 patients with osteosarcoma (n=757) and ES (n=314) treated between 1985 and 2014. Multivariable competing risk analysis was used to analyze predictors of t-AL/MDS including a radiation dose (>55.8 Gy vs. <55.8 Gy) * disease site (pelvis/spine vs. other) interaction term. A supplemental nested case control study was conducted to assess the association between cumulative chemotherapy dose and t-AL/MDS.
The median follow-up for surviving patients was 97 months (range 0.03-380). Twenty patients developed t-AL/MDS, all of whom received chemotherapy and 15 of whom were treated with radiotherapy. Radiotherapy to >55.8 Gy was associated with development of t-AL/MDS (AHR 2.89, 95% CI 1.23-6.80, p=0.015) and there was a significant radiation dose * disease site interaction term (AHR 6.70, 95% CI 2.71-16.53, Pinteraction <0.001). For osteosarcoma and ES, the 5-year cumulative incidence of t-AL/MDS in patients receiving >55.8 Gy radiotherapy to the pelvis or spine was 5.0% (95% CI 0.9-14.9) and 10.7% (95% CI 3.3-23.2), respectively. In our nested case control study, cumulative doses of ifosfamide and etoposide were associated with development of t-AL/MDS.
Osteosarcoma and ES patients receiving >55.8 Gy of radiotherapy to the pelvis or spine appear to be at increased risk for t-AL/MDS. Treatment with high cumulative doses of chemotherapy may further augment this risk.
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