{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T10:21:05Z","timestamp":1784974865415,"version":"3.55.0"},"reference-count":50,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"31","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["J Clin Oncol"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>Among childhood cancer survivors, we evaluated not previously explored relationships between colorectal subsequent malignant neoplasm (SMN) incidence and colorectum-specific radiation dose metrics currently used in radiation therapy (RT) planning and expanded upon previously reported chemotherapy associations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      The Childhood Cancer Survivor Study (CCSS) includes 5-year survivors of childhood cancer diagnosed between 1970 and 1999. RT was assessed as mean colorectal dose (MCD) and the percent volume (V\n                      <jats:sub>X Gy<\/jats:sub>\n                      ) receiving \u22655, 10, 20, 30, and 40 Gy. Chemotherapy was assessed as cumulative doses for procarbazine and platinum agents, cyclophosphamide-equivalent doses for alkylating agents, and doxorubicin-equivalent doses for anthracyclines. Piecewise-exponential models and excess rate ratio (ERR) models evaluated dose-response relationships for the incidence of colorectal SMNs. Reference groups were those not receiving the assessed treatment(s).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Among 25,723 survivors (median follow-up = 28.5 years; range = 5.0-48.9), 104 colorectal SMNs were identified. A dose-response relationship was observed between MCD and colorectal SMN rates; incidence rate ratios (IRRs) for 10 to &lt;20 Gy and \u226520 Gy were 3.6 (95% CI, 1.9 to 6.9) and 8.3 (95% CI, 3.9 to 17.8), respectively. When \u226520% of the colorectum volume was irradiated, IRRs increased with increasing volume. The V\n                      <jats:sub>20 Gy<\/jats:sub>\n                      IRRs were 3.8 (95% CI, 1.9 to 7.6), 4.9 (95% CI, 2.0 to 12.0), and 8.7 (95% CI, 3.5 to 21.6) for irradiated volumes of 20% to &lt;40%, 40% to &lt;80%, and \u226580%, respectively. The IRR was 1.8 (95% CI, 1.0 to 3.0) for doxorubicin-equivalent dose \u2265250 mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      , 3.7 (95% CI, 2.2 to 6.4) for cyclophosphamide-equivalent dose \u22656,000 mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      , and 4.5 (95% CI, 2.0 to 10.1) for platinum dose \u2265450 mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      . For procarbazine dose, the IRR was 6.3 (95% CI, 3.0 to 13.2) for 4,200 to &lt;7,036 mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      and 9.0 (95% CI, 4.3 to 18.9) for \u22657,036 mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      . In the absence of RT, colorectal SMN rates increased with exposure to any platinum-based agent (IRR, 3.8 [95% CI, 1.1 to 12.7]), alkylator (IRR, 4.8 [95% CI, 1.6 to 14.4]), or procarbazine (IRR, 16.9 [95% CI, 5.9 to 48.8]). Colorectal SMN rates increased linearly with procarbazine dose (ERR per 1,000 mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      = 73.0 [95% CI, 26.4% to 119.6%]) and MCD (ERR per 1 Gy = 20.8 [95% CI, 9.0% to 32.5%]). Quadratic ERR models did not improve data fit compared with linear ERR models.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>These RT and chemotherapy dose-response relationships can better inform contemporary RT planning for pediatric patients and surveillance guidelines for high-risk survivors.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco-25-00531","type":"journal-article","created":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T19:59:07Z","timestamp":1759348747000},"page":"3403-3421","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":6,"title":["Colorectal-Specific Radiation Dose and Chemotherapy Risk for Subsequent Colorectal Malignancies in Childhood Cancer Survivors: A Childhood Cancer Survivor Study (CCSS) 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