TY - JOUR
T1 - Risk Factors for Primary Bone Cancer After Childhood Cancer
T2 - A PanCare Childhood and Adolescent Cancer Survivor Care and Follow-Up Studies Nested Case-Control Study
AU - Reulen, Raoul C
AU - Winter, David L
AU - Diallo, Ibrahim
AU - Veres, Cristina
AU - Llanas, Damien
AU - Allodji, Rodrigue S
AU - Bagnasco, Francesca
AU - Bárdi, Edit
AU - Feijen, Elizabeth A M
AU - Alessi, Daniela
AU - Fidler-Benaoudia, Miranda M
AU - Høgsholt, Stine
AU - Teepen, Jop C
AU - Linge, Helena
AU - Haddy, Nadia
AU - Byrne, Julianne
AU - Debiche, Ghazi
AU - Grabow, Desiree
AU - Gudmundsdottir, Thorgerdur
AU - Fauchery, Romain
AU - Zrafi, Wael
AU - Michel, Gisela
AU - Øfstaas, Hilde
AU - Kaatsch, Peter
AU - Vu-Bezin, Giao
AU - Jenkinson, Helen
AU - Kaiser, Melanie
AU - Skinner, Roderick
AU - Cole, Trevor
AU - Waespe, Nicolas
AU - Sommer, Grit
AU - Nordenfelt, Susanne
AU - Jankovic, Momcilo
AU - Lähteenmäki Taalas, Tuomas
AU - Maule, Milena M
AU - van der Pal, Helena J H
AU - Ronckers, Cécile M
AU - van Leeuwen, Flora E
AU - Kok, Judith L
AU - Terenziani, Monica
AU - Winther Gunnes, Maria
AU - Wiebe, Thomas
AU - Sacerdote, Carlotta
AU - Jakab, Zsuzsanna
AU - Haupt, Riccardo
AU - Lähteenmäki, Päivi M
AU - Zadravec Zaletel, Lorna
AU - Kuehni, Claudia E
AU - Falck Winther, Jeanette
AU - Kremer, Leontien C M
AU - Hjorth, Lars
AU - de Vathaire, Florent
AU - Hawkins, Michael M
PY - 2023/5/26
Y1 - 2023/5/26
N2 - 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.
AB - 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.
M3 - Article
C2 - 37235821
SN - 0732-183X
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
ER -
