Abstract：
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.
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.
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.
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.
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.
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.
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.
摘要：
目的：对骨骼的辐射和烷化剂的暴露会增加儿童癌症幸存者患骨癌的风险，但骨组织放射剂量低于10Gy的风险以及特定类型化疗的剂量-反应关系存在不确定性.
方法：12个欧洲国家为一项巢式病例对照研究提供了228例病例和228名匹配对照，该研究由69,460名5年儿童癌症幸存者组成。计算了不同程度的累积辐射暴露和特定类型化疗的累积剂量下发展为骨癌的几率（OR）。计算过量OR以研究任何剂量-反应关系的形状和程度。
结果：与未暴露骨组织相比，暴露于1-4Gy的骨组织相关的OR为4.8倍（95％CI，1.2至19.6），而暴露于5-9Gy的骨组织相关的OR为9.6倍（95％CI，2.4至37.4）。对于≥40Gy的剂量，OR随着辐射剂量的增加而线性增加（Ptrend<.001），最高可达78倍（95％CI，9.2至669.9）。对于累积烷化剂剂量为10,000-19,999和≥20,000mg/m2，辐射调整的OR分别为7.1（95％CI，2.2至22.8）和8.3（95％CI，2.8至24.4），分别,每个人都有独立的贡献，异环磷酰胺,和环磷酰胺.其他细胞毒性与骨癌无关。
结论：据我们所知，我们首次证明,骨组织暴露于1~9Gy的累积辐射剂量后,患骨癌的风险增加了5~10倍.超过10,000mg/m2的烷基化剂将风险增加7至8倍，特别是在丙卡巴嗪之后，异环磷酰胺,和环磷酰胺.这些显著升高的风险应用于制定/更新临床随访指南和生存护理计划。
方法：12个欧洲国家为一项巢式病例对照研究提供了228例病例和228名匹配对照，该研究由69,460名5年儿童癌症幸存者组成。计算了不同程度的累积辐射暴露和特定类型化疗的累积剂量下发展为骨癌的几率（OR）。计算过量OR以研究任何剂量-反应关系的形状和程度。
结果：与未暴露骨组织相比，暴露于1-4Gy的骨组织相关的OR为4.8倍（95％CI，1.2至19.6），而暴露于5-9Gy的骨组织相关的OR为9.6倍（95％CI，2.4至37.4）。对于≥40Gy的剂量，OR随着辐射剂量的增加而线性增加（Ptrend<.001），最高可达78倍（95％CI，9.2至669.9）。对于累积烷化剂剂量为10,000-19,999和≥20,000mg/m2，辐射调整的OR分别为7.1（95％CI，2.2至22.8）和8.3（95％CI，2.8至24.4），分别,每个人都有独立的贡献，异环磷酰胺,和环磷酰胺.其他细胞毒性与骨癌无关。
结论：据我们所知，我们首次证明,骨组织暴露于1~9Gy的累积辐射剂量后,患骨癌的风险增加了5~10倍.超过10,000mg/m2的烷基化剂将风险增加7至8倍，特别是在丙卡巴嗪之后，异环磷酰胺,和环磷酰胺.这些显著升高的风险应用于制定/更新临床随访指南和生存护理计划。
