In a Childhood Cancer Survivor Study analysis reported in the Journal of Clinical Oncology, Owens et al identified the risks of colorectal subsequent malignant neoplasms (SMNs) associated with colorectal-specific radiotherapy (RT) doses and chemotherapy doses among 5-year survivors of childhood cancer.
Study Details
The study included data from survivors of childhood cancer diagnosed between 1970 and 1999. RT was analyzed as mean colorectal dose (MCD) and percent volume (V X Gy) receiving ≥ 5, 10, 20, 30, and 40 Gy. Chemotherapy was analyzed as cumulative doses for procarbazine and platinum agents, cyclophosphamide-equivalent doses for alkylating agents, and doxorubicin-equivalent doses for anthracyclines. Reference groups were those survivors who did not receive the assessed treatment(s).
Key Findings
Among 25,723 survivors, 104 colorectal SMNs were identified over a median follow-up of 28.5 years (range = 5.0–48.9 years). A dose-response relationship was observed between MCD and colorectal SMN rates: incidence rate ratios (IRRs) were 3.6 (95% confidence interval [CI] = 1.9–6.9) for 10 to < 20 Gy and 8.3 (95% CI = 3.9–17.8) for ≥ 20 Gy. In cases in which ≥ 20% of the colorectum volume was irradiated, IRRs increased with increasing volume: V 20 Gy IRRs per irradiated volumes were 3.8 (95% CI = 1.9–7.6) for 20% to < 40%, 4.9 (95% CI = 2.0–12.0) for 40% to < 80%, and 8.7 (95% CI = 3.5–21.6) for ≥ 80%.
For chemotherapy exposures, IRRs were 1.8 (95% CI = 1.0–3.0) for a doxorubicin-equivalent dose of ≥ 250 mg/m2, 3.7 (95% CI = 2.2–6.4) for a cyclophosphamide-equivalent dose of ≥ 6,000 mg/m2, 4.5 (95% CI = 2.0–10.1) for a platinum dose of ≥ 450 mg/m2, and 6.3 (95% CI = 3.0–13.2) and 9.0 (95% CI = 4.3–18.9) for a procarbazine dose of 4,200 to < 7,036 mg/m2 and ≥ 7,036 mg/m2, respectively. For chemotherapy exposure without RT exposure, IRRs increased with exposure to any platinum-based agent (3.8, 95% CI = 1.1–12.7), alkylator (4.8, 95% CI = 1.6–14.4), or procarbazine (16.9, 95% CI = 5.9–48.8).
Colorectal SMN rates increased linearly with the procarbazine dose (excess rate ratio [ERR] per 1,000 mg/m2 = 73.0%, 95% CI = 26.4%–119.6%) and MCD (ERR per 1 Gy = 20.8%, 95% CI = 9.0%–32.5%).
The investigators concluded: “These RT and chemotherapy dose-response relationships can better inform contemporary RT planning for pediatric patients and surveillance guidelines for high-risk survivors.”
Rebecca M. Howell, PhD, of the Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, is the corresponding author of the Journal of Clinical Oncology article.
Disclosure: The study was supported by the National Cancer Institute and American Lebanese-Syrian Associated Charities. For full disclosures of all study authors, visit ascopubs.org.
