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 - Inserm - Institut national de la santé et de la recherche médicale Accéder directement au contenu
Article Dans Une Revue Journal of Clinical Oncology Année : 2023

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

1 University of Birmingham [Birmingham]
2 CESP - Centre de recherche en épidémiologie et santé des populations
3 IGR - Institut Gustave Roussy
4 IRCCS Istituto Giannina Gaslini [Genoa, Italy]
5 JKU - University of Linz - Johannes Kepler Universität Linz
6 Kepler University Hospital
7 Princess Máxima Center for Pediatric Oncology
8 UNITO - Università degli studi di Torino = University of Turin
9 A.O.U - Città della Salute e della Scienza di Torino
10 University of Calgary
11 Lund University
12 Skane University Hospital [Lund]
13 BRI - Boyne Research Institute [Drogheda, Irlande]
14 JGU - Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University
15 Institute for Medical Biostatistics, Epidemiology and Informatics (IMBEI)
16 Landspitali National University Hospital of Iceland
17 UNILU - Université de Lucerne = Universität Luzern
18 Cancer Registry of Norway
19 University Medical Center [Mainz]
20 Birmingham Children’s Hospital
21 Newcastle Upon Tyne Hospitals NHS Foundation Trust
22 Great North Children’s Hospital [Newcastle Upon Tyne, UK]
23 Newcastle University [Newcastle]
24 Birmingham Women's and Children's NHS Foundation Trust
25 Inselspital - Bern University Hospital [Berne]
26 UNIBE - Universität Bern / University of Bern
27 UNIMIB - Università degli Studi di Milano-Bicocca = University of Milano-Bicocca
28 SGH - San Gerardo Hospital [Monza, Italy]
29 TYKS - Turku University Hospital
30 University of Turku
31 NKI - Netherlands Cancer Institute
32 IRCCS Istituto Nazionale dei Tumori [Milano]
33 Oslo University Hospital [Oslo]
34 Semmelweis University [Budapest]
35 Institute of Oncology [Ljubljana]
36 Aarhus University [Aarhus]
37 Aarhus University Hospital
38 Academic Medical Center - Emma Children's Hospital [Amsterdam, Netherlands]
39 Amsterdam UMC - Amsterdam University Medical Center
Raoul Reulen
David Winter
Grit Sommer
Flora van Leeuwen
Zsuzsanna Jakab
Michael Hawkins

Résumé

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 ( P trend < .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/m 2 , 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/m 2 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.
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Dates et versions

inserm-04438098 , version 1 (05-02-2024)

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Raoul Reulen, David Winter, Ibrahim Diallo, Cristina Veres, Damien Llanas, et al.. 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. Journal of Clinical Oncology, 2023, 41 (21), pp.3735-3746. ⟨10.1200/JCO.22.02045⟩. ⟨inserm-04438098⟩
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