As reported in the Journal of Clinical Oncology by Turcotte et al, analysis of the Childhood Cancer Survivor Study Cohort showed that childhood cancer survivors treated with chemotherapy alone—particularly higher cumulative doses of platinum and alkylating agents—are at an increased risk of subsequent malignant neoplasms.
Study Details
The study identified subsequent malignant neoplasms (excluding nonmelanoma skin cancers) occurring more than 5 years after diagnosis in cancer survivors diagnosed at less than 21 years of age between 1970 to 1999 in the Childhood Cancer Survivor Study. Patients had a median age at diagnosis of 7.0 years, and median age at last follow-up was 31.8 years. The analysis included 7,448 patients who received chemotherapy only, 10,485 who received chemotherapy plus radiation, 2,063 who received radiation only, and 2,158 who received neither.
“Childhood cancer survivors treated with chemotherapy only, particularly higher cumulative doses of platinum and alkylating agents, face increased subsequent malignant neoplasm risk. Linear dose responses were seen between alkylating agents and subsequent malignant neoplasm rates and between anthracyclines and breast cancer rates. Limiting cumulative doses and consideration of alternate chemotherapies may reduce subsequent malignant neoplasm risk.”— Turcotte et al
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Key Findings
A total of 1,498 subsequent malignant neoplasms were identified among 1,344 survivors; of these, 229 occurred among 206 treated with chemotherapy only.
The 30-year cumulative incidence of subsequent malignant neoplasms was 3.9%, 9.0%, 10.8%, and 3.4% for the chemotherapy-only, chemotherapy plus radiation, radiation-only, and neither-treatment groups, respectively.
Survivors treated with chemotherapy only had a 2.8-fold increased subsequent malignant neoplasm risk compared with the general population (standardized incidence ratio [SIR] = 2.8, 95% confidence interval [CI] =2.5–3.2); SIRs were increased for subsequent leukemia/lymphoma (1.9, 95% CI = 1.3–2.7), breast cancer (4.6, 95% CI = 3.5–6.0), soft-tissue sarcoma (3.4, 95% CI = 1.9–5.7), thyroid cancer (3.8, 95% CI = 2.7–5.1), and melanoma (2.3, 95% CI = 1.5–3.5).
Increased risk of subsequent malignant neoplasm was associated with a > 750 mg/m2 cumulative platinum dose (relative rate [RR] = 2.7, 95% CI = 1.1–6.5) and increasing cumulative doses of alkylating agents (RR = 1.2 per 5,000 mg/m2, 95% CI = 1.1–1.3). A linear dose response was also found between anthracyclines and risk of breast cancer as a subsequent malignant neoplasm (RR = 1.3 per 100 mg/m2, 95% CI = 1.2–1.6).
The investigators concluded, “Childhood cancer survivors treated with chemotherapy only, particularly higher cumulative doses of platinum and alkylating agents, face increased subsequent malignant neoplasm risk. Linear dose responses were seen between alkylating agents and subsequent malignant neoplasm rates and between anthracyclines and breast cancer rates. Limiting cumulative doses and consideration of alternate chemotherapies may reduce subsequent malignant neoplasm risk.”
Lucie M. Turcotte, MD, of the Division of Pediatric Hematology/Oncology, University of Minnesota Medical School, Minneapolis, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by the National Cancer Institute. For full disclosures of the study authors, visit jco.ascopubs.org.
