Chemoradiotherapy vs Radiotherapy Alone Linked to Increased Risk of Subsequent Malignancies in Long-Term Survivors of Hereditary Retinoblastoma
Increased risk of subsequent malignant neoplasms has been reported in hereditary retinoblastoma survivors after radiotherapy. In a study reported in Journal of Clinical Oncology, Wong et al found that chemotherapy plus radiotherapy was associated with increased risk of subsequent malignant neoplasms vs radiotherapy alone in 5-year survivors of hereditary retinoblastoma, including increased risk of bone tumors and leiomyosarcoma.
Study Details
The study included 906 5-year hereditary retinoblastoma survivors diagnosed from 1914 to 1996 and followed through 2009. Totals of 90% received radiotherapy (53% radiotherapy alone, 37% radiotherapy plus chemotherapy) and 39% received chemotherapy (37% with radiotherapy, 2% alone).
Among 336 patients receiving chemotherapy plus radiotherapy, 64% received alkylating chemotherapy with triethylenemelamine alone and 31% received alkylating therapy with or without triethylenemelamine; among 13 patients receiving chemotherapy alone, 15% received triethylenemelamine alone and 85% received alkylating therapy with or without triethylenemelamine. Among the 813 survivors treated with radiotherapy alone or chemotherapy plus radiotherapy, 265 (33%) developed at least one subsequent malignant neoplasm. Median duration to first subsequent malignant neoplasm diagnosis was 26.3 years.
Chemotherapy/Radiotherapy vs Radiotherapy
Overall, risk of subsequent malignant neoplasms was significantly increased for chemotherapy plus radiotherapy vs radiotherapy alone (hazard ratio [HR] = 1.31, 95% confidence interval [CI] = 1.02–1.68), including increased risk for bone tumors (HR = 1.73, 95% CI = 1.13–2.67) and leiomyosarcoma (HR = 2.61, 95% CI = 1.19–5.70), but not for other soft tissue sarcoma (HR = 0.99), melanoma (HR = 0.72), or epithelial tumors (HR = 0.94).
Alkylating Chemotherapy/Radiotherapy vs Radiotherapy
Overall, risk of subsequent malignant neoplasms was not significantly increased for alkylating chemotherapy plus radiotherapy vs radiotherapy alone (HR = 1.27, 95% CI = 0.99–1.63), although significant increases were found for bone tumors (HR = 1.60, 95% CI = 1.03–2.49) and leiomyosarcoma (HR = 2.67, 95% CI = 1.22–5.85). No significant difference in risk was found for other soft tissue sarcomas (HR = 0.97), melanoma (HR = 0.83), or epithelial tumors (HR = 0.89).
Effect of Age
Leiomyosarcoma risk was significantly increased with alkylating chemotherapy at age < 1 year (HR = 5.17, 95% CI = 1.76–15.17) but not at age ≥ 1 year (HR = 1.75, 95% CI = 0.68–4.51). Risk of other soft tissue sarcomas, bone tumors, melanoma, and epithelial tumors were similar regardless of age at alkylating chemotherapy. Only the cumulative incidence of leiomyosarcoma was significantly higher for alkylating chemotherapy plus radiotherapy vs radiotherapy (5.8% vs 1.6%, P = .01, at age 40 years).
The investigators concluded: “This comprehensive quantification of [subsequent malignant neoplasm] risk after chemotherapy and [radiotherapy] among hereditary [retinoblastoma] survivors also demonstrates an [alkylating agent]-related contribution to risk. Although triethylenemelamine is no longer prescribed, our findings warrant further follow-up to investigate potential [subsequent malignant neoplasm] risks associated with current chemotherapies used for [retinoblastoma].”
Ruth A. Kleinerman, MPH, of the National Cancer Institute, is the corresponding author for the Journal of Clinical Oncology article.
The study was supported by the National Cancer Institute and National Institutes of Health. The authors indicated no conflicts of interest.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
