Colorectal Adenomas and Cancers After Childhood Cancer Treatment: A DCOG-LATER Record Linkage Study
Teepen, J C; Kok, Judith L; van Leeuwen, Flora E; Tissing, Wim J E; Dolsma, Wil V; van der Pal, Helena J; Loonen, Jacqueline J; Bresters, Dorine; Versluys, A B; van den Heuvel-Eibrink, Marry M; van Dulmen-den Broeder, Eline; van den Berg, Marleen H; van der Heiden-van der Loo, Margriet; Hauptmann, Michael; Jongmans, M C; Overbeek, L I; van de Vijver, M J; Kremer, L C M; Ronckers, C M; Aleman, B M P; van den Berg, M H; Caron, H N; Daniels, L A; Dolsma, W; van Dulmen-den Broeder, E; Grootenhuis, M A; Haasbeek, C J; den Hartogh, J G; Hauptmann, M; van der Heiden-van der Loo, M; van den Heuvel-Eibrink, Marry M; Hollema, N; Janssens, G O; Jongmans, M C; Jaspers, M W M; Kok, J L; van Leeuwen, F E; Loonen, J; Maduro, J H; Neggers, S J C M M; Oldenburger, F; van der Pal, H J; Postma, A; Ronckers, C M; Tersteeg, R J; Tissing, Wim J E; Versluys, A B; Zsíros, J; DCOG-LATER Study Group
(2018) Journal of the National Cancer Institute, volume 110, issue 7, pp. 758 - 767
(Article)
Abstract
Background: Although colorectal adenomas serve as prime target for colorectal cancer (CRC) surveillance in other high-risk groups, data on adenoma risk after childhood cancer are lacking. We evaluated the risk of histologically confirmed colorectal adenomas among childhood cancer survivors. A secondary aim was to assess CRC risk. Methods: The DCOG-LATER
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cohort study includes five-year Dutch childhood cancer survivors and a sibling comparison group (n = 883). Colorectal tumors were identified from the population-based Dutch Pathology Registry (PALGA). We calculated cumulative incidences of adenomas/CRCs for survivors and siblings. For adenomas, multivariable Cox regression models were used to evaluate potential risk factors. All statistical tests were two-sided. Results: Among 5843 five-year survivors (median follow-up = 24.9 years), 78 individuals developed an adenoma. Cumulative incidence by age 45 years was 3.6% (95% confidence interval [CI] = 2.2% to 5.6%) after abdominopelvic radiotherapy (AP-RT; 49 cases) vs 2.0% (95% CI = 1.3% to 2.8%) among survivors without AP-RT (28 cases; Pdifference = .07) and vs 1.0% (95% CI = 0.3% to 2.6%) among siblings (6 cases) (Pdifference = .03). Factors associated with adenoma risk were AP-RT (hazard ratio [HR] = 2.12, 95% CI = 1.24 to 3.60), total body irradiation (TBI; HR = 10.55, 95% CI = 5.20 to 21.42), cisplatin (HR = 2.13; 95% CI = 0.74 to 6.07 for <480 mg/m²; HR = 3.85, 95% CI = 1.45 to 10.26 for ≥480 mg/m²; Ptrend = .62), a hepatoblastoma diagnosis (HR = 27.12, 95% CI = 8.80 to 83.58), and family history of early-onset CRC (HR = 20.46, 95% CI = 8.10 to 51.70). Procarbazine was statistically significantly associated among survivors without AP-RT/TBI (HR = 2.71, 95% CI = 1.28 to 5.74). Thirteen CRCs occurred. Conclusion: We provide evidence for excess risk of colorectal adenomas and CRCs among childhood cancer survivors. Adenoma risk factors include AP-RT, TBI, cisplatin, and procarbazine. Hepatoblastoma (familial adenomatous polyposis-associated) and family history of early-onset CRC were confirmed as strong risk factors. A full benefit-vs-harm evaluation of CRC screening among high-risk childhood cancer survivors warrants consideration.
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Keywords: Adenoma/epidemiology, Adolescent, Adult, Age of Onset, Cancer Survivors/statistics & numerical data, Child, Child, Preschool, Colorectal Neoplasms/epidemiology, Female, Follow-Up Studies, Humans, Male, Medical Record Linkage/methods, Middle Aged, Neoplasms, Second Primary/epidemiology, Netherlands/epidemiology, Registries, Young Adult, Oncology, Cancer Research, Research Support, Non-U.S. Gov't, Journal Article
ISSN: 0027-8874
Publisher: Oxford University Press
Note: Funding Information: This work was supported by the Dutch Cancer Society (grant numbers DCOG2011-5027 and UVA2012-5517). Judith Kok was appointed on a Flexible Onderzoeker in Opleiding (OiO) grant awarded by the Academic Medical Center (AMC) Executive Board to C. M. Ronckers/L. C. Kremer in 2012. Publisher Copyright: © The Author(s) 2018. Published by Oxford University Press. All rights reserved. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
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