Secondary gastrointestinal cancer in childhood cancer survivors: A cohort study

Tara O. Henderson, Kevin C. Oeffinger, John Whitton, Wendy Leisenring, Joseph Neglia, Anna Meadows, Catherine Crotty, David T. Rubin, Lisa Diller, Peter Inskip, Susan A. Smith, Marilyn Stovall, Louis S. Constine, Sue Hammond, Greg T. Armstrong, Leslie L. Robison, Paul C. Nathan

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Abstract

Background: Childhood cancer survivors develop gastrointestinal cancer more frequently and at a younger age than the general population, but the risk factors have not been well-characterized. Objective: To determine the risk and associated risk factors for gastrointestinal subsequent malignant neoplasms (SMNs) in childhood cancer survivors. Design: Retrospective cohort study. Setting: The Childhood Cancer Survivor Study, a multicenter study of childhood cancer survivors diagnosed between 1970 and 1986. Patients: 14 358 survivors of cancer diagnosed when they were younger than 21 years of age who survived for 5 or more years after the initial diagnosis. Measurements: Standardized incidence ratios (SIRs) for gastrointestinal SMNs were calculated by using age-specific population data. Multivariate Cox regression models identified associations between risk factors and gastrointestinal SMN development. Results: At median follow-up of 22.8 years (range, 5.5 to 30.2 years), 45 cases of gastrointestinal cancer were identified. The risk for gastrointestinal SMNs was 4.6-fold higher in childhood cancer survivors than in the general population (95% CI, 3.4 to 6.1). The SIR for colorectal cancer was 4.2 (CI, 2.8 to 6.3). The highest risk for gastrointestinal SMNs was associated with abdominal radiation (SIR, 11.2 [CI, 7.6 to 16.4]). However, survivors not exposed to radiation had a significantly increased risk (SIR, 2.4 [CI, 1.4 to 3.9]). In addition to abdominal radiation, high-dose procarbazine (relative risk, 3.2 [CI, 1.1 to 9.4]) and platinum drugs (relative risk, 7.6 [CI, 2.3 to 25.5]) independently increased the risk for gastrointestinal SMNs. Limitation: This cohort has not yet attained an age at which risk for gastrointestinal cancer is greatest. Conclusion: Childhood cancer survivors, particularly those exposed to abdominal radiation, are at increased risk for gastrointestinal SMNs. These findings suggest that surveillance of at-risk childhood cancer survivors should begin at a younger age than that recommended for the general population. Primary Funding Source: National Cancer Institute.

Original languageEnglish (US)
Pages (from-to)757-766
Number of pages10
JournalAnnals of internal medicine
Volume156
Issue number11
DOIs
StatePublished - 2012

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Henderson, T. O., Oeffinger, K. C., Whitton, J., Leisenring, W., Neglia, J., Meadows, A., Crotty, C., Rubin, D. T., Diller, L., Inskip, P., Smith, S. A., Stovall, M., Constine, L. S., Hammond, S., Armstrong, G. T., Robison, L. L., & Nathan, P. C. (2012). Secondary gastrointestinal cancer in childhood cancer survivors: A cohort study. Annals of internal medicine, 156(11), 757-766. https://doi.org/10.7326/0003-4819-156-11-201206050-00002