Risk Factors for Primary Bone Cancer After Childhood Cancer: A PanCare Childhood and Adolescent Cancer Survivor Care and Follow-Up Studies Nested Case-Control Study

Autor: Raoul C. Reulen, David L. Winter, Ibrahim Diallo, Cristina Veres, Damien Llanas, Rodrigue S. Allodji, Francesca Bagnasco, Edit Bárdi, Elizabeth A.M. Feijen, Daniela Alessi, Miranda M. Fidler-Benaoudia, Stine Høgsholt, Jop C. Teepen, Helena Linge, Nadia Haddy, Julianne Byrne, Ghazi Debiche, Desiree Grabow, Thorgerdur Gudmundsdottir, Romain Fauchery, Wael Zrafi, Gisela Michel, Hilde Øfstaas, Peter Kaatsch, Giao Vu-Bezin, Helen Jenkinson, Melanie Kaiser, Roderick Skinner, Trevor Cole, Nicolas Waespe, Grit Sommer, Susanne Nordenfelt, Momcilo Jankovic, Tuomas Lähteenmäki Taalas, Milena M. Maule, Helena J.H. van der Pal, Cécile M. Ronckers, Flora E. van Leeuwen, Judith L. Kok, Monica Terenziani, Maria Winther Gunnes, Thomas Wiebe, Carlotta Sacerdote, Zsuzsanna Jakab, Riccardo Haupt, Päivi M. Lähteenmäki, Lorna Zadravec Zaletel, Claudia E. Kuehni, Jeanette Falck Winther, Leontien C.M. Kremer, Lars Hjorth, Florent de Vathaire, Michael M. Hawkins
Rok vydání: 2023
Předmět:
Zdroj: Journal of Clinical Oncology.
ISSN: 1527-7755
0732-183X
Popis: PURPOSE Radiation to the bone and exposure to alkylating agents increases the risk of bone cancer among survivors of childhood cancer, but there is uncertainty regarding the risks of bone tissue radiation doses below 10 Gy and the dose-response relationship for specific types of chemotherapy. METHODS Twelve European countries contributed 228 cases and 228 matched controls to a nested case-control study within a cohort of 69,460 5-year survivors of childhood cancer. Odds ratios (ORs) of developing bone cancer for different levels of cumulative radiation exposure and cumulative doses of specific types of chemotherapy were calculated. Excess ORs were calculated to investigate the shape and extent of any dose-response relationship. RESULTS The OR associated with bone tissue exposed to 1-4 Gy was 4.8-fold (95% CI, 1.2 to 19.6) and to 5-9 Gy was 9.6-fold (95% CI, 2.4 to 37.4) compared with unexposed bone tissue. The OR increased linearly with increasing dose of radiation ( Ptrend < .001) up to 78-fold (95% CI, 9.2 to 669.9) for doses of ≥40 Gy. For cumulative alkylating agent doses of 10,000-19,999 and ≥20,000 mg/m2, the radiation-adjusted ORs were 7.1 (95% CI, 2.2 to 22.8) and 8.3 (95% CI, 2.8 to 24.4), respectively, with independent contributions from each of procarbazine, ifosfamide, and cyclophosphamide. Other cytotoxics were not associated with bone cancer. CONCLUSION To our knowledge, we demonstrate—for the first time—that the risk of bone cancer is increased 5- to 10-fold after exposure of bone tissue to cumulative radiation doses of 1-9 Gy. Alkylating agents exceeding 10,000 mg/m2 increase the risk 7- to 8-fold, particularly following procarbazine, ifosfamide, and cyclophosphamide. These substantially elevated risks should be used to develop/update clinical follow-up guidelines and survivorship care plans.
Databáze: OpenAIRE
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