Characteristics and Predictors for Secondary Leukemia and Myelodysplastic Syndrome in Ewing and Osteosarcoma Survivors

Nina N. Sanford, Ruoyu Miao, Haotong Wang, Saveli Goldberg, Alex Jacobson, Andrew M. Brunner, Gregory M. Cote, Torunn I. Yock, David H. Ebb, Yi Bin Chen, Kyung Wook Jee, Francis Hornicek, Thomas F. DeLaney, Edwin Choy, Yen Lin Chen

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Purpose: Long-term survivors of Ewing sarcoma (ES) and osteosarcoma may be at risk for therapy-related acute leukemia or myelodysplastic syndrome (t-AL/MDS). Methods and Materials: We retrospectively reviewed the clinicopathologic characteristics of 1071 patients with osteosarcoma (n = 757) and ES (n = 314) who were 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. Results: 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 radiation therapy. Radiation therapy to ≥55.8 Gy was associated with development of t-AL/MDS (adjusted hazard ratio, 2.89; 95% confidence interval [CI], 1.23-6.80; P =.015), and there was a significant radiation dose × disease site interaction term (adjusted hazard ratio, 6.70; 95% CI, 2.71-16.53; Pinteraction <.001). The 5-year cumulative incidence of t-AL/MDS in patients receiving ≥55.8 Gy radiation therapy to the pelvis or spine was 5.0% (95% CI, 0.9-14.9) for osteosarcoma and 10.7% for ES (95% CI, 3.3-23.2). In our nested case-control study, cumulative doses of ifosfamide and etoposide were associated with development of t-AL/MDS. Conclusions: Patients with osteosarcoma and ES receiving ≥55.8 Gy of radiation therapy 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.

Original languageEnglish (US)
Pages (from-to)52-61
Number of pages10
JournalInternational Journal of Radiation Oncology Biology Physics
Volume103
Issue number1
DOIs
StatePublished - Jan 1 2019
Externally publishedYes

ASJC Scopus subject areas

  • Radiation
  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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    Sanford, N. N., Miao, R., Wang, H., Goldberg, S., Jacobson, A., Brunner, A. M., Cote, G. M., Yock, T. I., Ebb, D. H., Chen, Y. B., Jee, K. W., Hornicek, F., DeLaney, T. F., Choy, E., & Chen, Y. L. (2019). Characteristics and Predictors for Secondary Leukemia and Myelodysplastic Syndrome in Ewing and Osteosarcoma Survivors. International Journal of Radiation Oncology Biology Physics, 103(1), 52-61. https://doi.org/10.1016/j.ijrobp.2018.08.037