Authors' Affiliations: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington; University of California San Diego & Rady Children's Hospital, San Diego, California; Children's Hospitals and Clinics of Minnesota; and Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota.
Cancer Epidemiol Biomarkers Prev. 2013 Nov;22(11):1954-63. doi: 10.1158/1055-9965.EPI-13-0610. Epub 2013 Sep 5.
Childhood cancer survivors (CCS) are more insulin resistant and have higher levels of several cardiovascular risk factors even while still children. This study examines specific treatment exposures associated with cardiovascular risk factors and insulin resistance.
CCS of ages 9 to 18 years at study entry and in remission 5 years or more from diagnosis (n = 319) and 208 sibling controls were recruited into this cross-sectional study that included physiologic assessment of insulin resistance (hyperinsulinemic euglycemic clamp) and assessment of cardiovascular risk factors. Regression and recursive tree modeling were used to ascertain treatment combinations associated with insulin resistance and cardiovascular risk.
Mean current age of CCS was 14.5 years and 54% were male (siblings 13.6 years, 54% male). Diagnoses included leukemia (35%), brain tumors (36%), solid tumors (33%), or lymphoma (6%). Among CCS, analysis of individual chemotherapy agents failed to find associations with cardiovascular risk factors or insulin resistance. Compared with siblings, insulin resistance was significantly higher in CCS who received platinum plus cranial radiotherapy (CRT, 92% brain tumors) and in those who received steroids but no platinum (majority leukemia). Insulin resistance did not differ between CCS who received surgery alone versus siblings. Within survivor comparisons failed to elucidate treatment combinations that increased insulin resistance compared with those who received surgery only.
Exposure to platinum, CRT, or steroids is associated with insulin resistance and cardiovascular risk factors and should be taken into consideration in the development of screening recommendations for cardiovascular risk.
Earlier identification of CCS who may benefit from targeted prevention efforts may reduce their future risk of cardiovascular disease.
儿童癌症幸存者（CCS）即使还是儿童，其胰岛素抵抗程度更高，且存在多种心血管危险因素。本研究旨在探讨与心血管危险因素和胰岛素抵抗相关的特定治疗暴露因素。
本横断面研究纳入了年龄在 9 至 18 岁且诊断后 5 年或以上无疾病（n=319）且无疾病的同胞对照组（n=208），对其进行了胰岛素抵抗的生理评估（高胰岛素-正葡萄糖钳夹）和心血管危险因素评估。采用回归和递归树模型来确定与胰岛素抵抗和心血管风险相关的治疗组合。
CCS 的平均当前年龄为 14.5 岁，54%为男性（同胞为 13.6 岁，54%为男性）。诊断包括白血病（35%）、脑肿瘤（36%）、实体瘤（33%）或淋巴瘤（6%）。在 CCS 中，对个别化疗药物的分析未能发现其与心血管危险因素或胰岛素抵抗之间存在关联。与同胞相比，接受铂类加颅放疗（CRT，92%为脑肿瘤）和接受类固醇但不接受铂类的 CCS（大多数为白血病）的胰岛素抵抗明显更高。接受单独手术的 CCS 与同胞相比，胰岛素抵抗无差异。在幸存者之间的比较中，未能阐明与仅接受手术相比增加胰岛素抵抗的治疗组合。
铂类、CRT 或类固醇的暴露与胰岛素抵抗和心血管危险因素相关，在制定心血管风险筛查建议时应考虑这些因素。
更早识别出可能受益于靶向预防措施的 CCS，可能会降低他们未来患心血管疾病的风险。
