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
Reulen, Raoul C. ✉; Winter, David L.; Diallo, Ibrahim; Veres, Cristina; Llanas, Damien; Allodji, Rodrigue S.; Bagnasco, Francesca; Bardi, Edit; Feijen, Elizabeth A. M.; Alessi, Daniela; Fidler-Benaoudia, Miranda M.; Hogsholt, Stine; Teepen, Jop C.; Linge, Helena; Haddy, Nadia; Byrne, Julianne; Debiche, Ghazi; Grabow, Desiree; Gudmundsdottir, Thorgerdur; Fauchery, Romain; Zrafi, Wael; Michel, Gisela; ofstaas, Hilde; Kaatsch, Peter; Vu-Bezin, Giao; Jenkinson, Helen; Kaiser, Melanie; Skinner, Roderick; Cole, Trevor; Waespe, Nicolas; Sommer, Grit; Nordenfelt, Susanne; Jankovic, Momcilo; Taalas, Tuomas Lahteenmaki; Maule, Milena M.; van, der Pal Helena J. H.; Ronckers, Cecile M.; van, Leeuwen Flora E.; Kok, Judith L.; Terenziani, Monica; Gunnes, Maria Winther; Wiebe, Thomas; Sacerdote, Carlotta; Jakab, Zsuzsanna [Jakab, Zsuzsanna (Gyermekgyógyászat...), szerző] II. Sz. Gyermekgyógyászati
Klinika (SE / AOK / K); Haupt, Riccardo; Lahteenmaki, Paivi M.; Zaletel, Lorna Zadravec; Kuehni, Claudia E.; Winther, Jeanette Falck; Kremer, Leontien C. M.; Hjorth, Lars; de, Vathaire Florent; Hawkins, Michael M.
Angol nyelvű Sokszerzős vagy csoportos szerzőségű szakcikk (Folyóiratcikk) Tudományos
PURPOSERadiation 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.METHODSTwelve 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.RESULTSThe 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 & GE;40 Gy. For cumulative alkylating agent doses of 10,000-19,999 and
& GE;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.CONCLUSIONTo 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.
