Jop C Teepen1,2, Judith L Kok1, Flora E van Leeuwen3, Wim J E Tissing4, Wil V Dolsma5, Helena J van der Pal1,2, Jacqueline J Loonen6, Dorine Bresters7, Birgitta Versluys8, Marry M van den Heuvel-Eibrink2,9, Eline van Dulmen-den Broeder10, Marleen H van den Berg10, Margriet van der Heiden-van der Loo11, Michael Hauptmann3, Marjolijn C Jongmans2,12,13,14, Lucy I Overbeek15,14, Marc J van de Vijver14, Leontien C M Kremer1,2, Cécile M Ronckers1. 1. Department of Pediatric Oncology, Emma Children's Hospital/Academic Medical Center, Amsterdam, the Netherlands. 2. Princess Maxima Center for Pediatric Oncology, Utrecht, the Netherlands. 3. Department of Epidemiology and Biostatistics, The Netherlands Cancer Institute, Amsterdam, the Netherlands. 4. Department of Pediatric Oncology/Hematology, Beatrix Children's Hospital/University of Groningen/University Medical Center Groningen, Groningen, the Netherlands. 5. Department of Radiation Oncology, University of Groningen/University Medical Center Groningen, Groningen, the Netherlands. 6. Department of Hematology, Radboud University Medical Center, Nijmegen, the Netherlands. 7. Department of Pediatric Stem Cell Transplantation, Willem-Alexander Children's Hospital/Leiden University Medical Center, Leiden, the Netherlands. 8. Department of Pediatric Oncology and Hematology, Wilhelmina Children's Hospital/University Medical Center Utrecht, Utrecht, the Netherlands. 9. Department of Pediatric Oncology/Hematology, Sophia Children's Hospital/Erasmus Medical Center, Rotterdam, the Netherlands. 10. Department of Pediatric Oncology/Hematology, VU University Medical Center, Amsterdam, the Netherlands. 11. Dutch Childhood Oncology Group, The Hague, the Netherlands. 12. Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands. 13. Department of Medical Genetics, University Medical Center Utrecht, Utrecht, the Netherlands. 14. Department of Pathology, Academic Medical Center, Amsterdam, the Netherlands. 15. Foundation PALGA (The Nationwide Network and Registry of Histo- and Cytopathology in the Netherlands), Houten, the Netherlands.
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 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.
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 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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