Neglia Joseph P, Robison Leslie L, Stovall Marilyn, Liu Yan, Packer Roger J, Hammond Sue, Yasui Yutaka, Kasper Catherine E, Mertens Ann C, Donaldson Sarah S, Meadows Anna T, Inskip Peter D
Department of Pediatrics, University of Minnesota School of Medicine, Minneapolis, MN, USA.
J Natl Cancer Inst. 2006 Nov 1;98(21):1528-37. doi: 10.1093/jnci/djj411.
Subsequent primary neoplasms of the central nervous system (CNS) have frequently been described as late events following childhood leukemia and brain tumors. However, the details of the dose-response relationships, the expression of excess risk over time, and the modifying effects of other host and treatment factors have not been well defined.
Subsequent primary neoplasms of the CNS occurring within a cohort of 14,361 5-year survivors of childhood cancers were ascertained. Each patient was matched with four control subjects by age, sex, and time since original cancer diagnosis. Tumor site-specific radiation dosimetry was performed, and chemotherapy information was abstracted from medical records. Conditional logistic regression was used to estimate odds ratios (ORs), to calculate 95% confidence intervals (CIs), and to model the excess relative risk (ERR) as a function of radiation dose and host factors. For subsequent gliomas, standardized incidence ratios (SIRs) and excess absolute risks (EARs) were calculated based on Surveillance, Epidemiology, and End Results data.
Subsequent CNS primary neoplasms were identified in 116 individuals. Gliomas (n = 40) occurred a median of 9 years from original diagnosis; for meningiomas (n = 66), it was 17 years. Radiation exposure was associated with increased risk of subsequent glioma (OR = 6.78, 95% CI = 1.54 to 29.7) and meningioma (OR = 9.94, 95% CI = 2.17 to 45.6). The dose response for the excess relative risk was linear (for glioma, slope = 0.33 [95% CI = 0.07 to 1.71] per Gy, and for meningioma, slope = 1.06 [95% CI = 0.21 to 8.15] per Gy). For glioma, the ERR/Gy was highest among children exposed at less than 5 years of age. After adjustment for radiation dose, neither original cancer diagnosis nor chemotherapy was associated with risk. The overall SIR for glioma was 8.7, and the EAR was 19.3 per 10,000 person-years.
Exposure to radiation therapy is the most important risk factor for the development of a new CNS tumor in survivors of childhood cancers. The higher risk of subsequent glioma in children irradiated at a very young age may reflect greater susceptibility of the developing brain to radiation.
中枢神经系统（CNS）的后续原发性肿瘤常被描述为儿童白血病和脑肿瘤后的晚期事件。然而，剂量反应关系的细节、随时间的超额风险表达以及其他宿主和治疗因素的修饰作用尚未明确界定。
确定了14361名儿童癌症5年幸存者队列中发生的CNS后续原发性肿瘤。根据年龄、性别和自最初癌症诊断后的时间，为每位患者匹配4名对照对象。进行肿瘤部位特异性放射剂量测定，并从病历中提取化疗信息。使用条件逻辑回归估计比值比（OR），计算95%置信区间（CI），并将超额相对风险（ERR）建模为放射剂量和宿主因素的函数。对于后续胶质瘤，根据监测、流行病学和最终结果数据计算标准化发病比（SIR）和超额绝对风险（EAR）。
在116名个体中发现了CNS后续原发性肿瘤。胶质瘤（n = 40）自最初诊断起的中位发病时间为9年；脑膜瘤（n = 66）为17年。放射暴露与后续胶质瘤（OR = 6.78，95%CI = 1.54至29.7）和脑膜瘤（OR = 9.94，95%CI = 2.17至45.6）的风险增加相关。超额相对风险的剂量反应呈线性（对于胶质瘤，斜率 = 0.33 [95%CI = 0.07至1.71] 每Gy，对于脑膜瘤，斜率 = 1.06 [95%CI = 0.21至8.15] 每Gy）。对于胶质瘤，在5岁前暴露的儿童中ERR/Gy最高。在调整放射剂量后，最初的癌症诊断和化疗均与风险无关。胶质瘤的总体SIR为8.7，EAR为每10000人年19.3。
放射治疗暴露是儿童癌症幸存者发生新的CNS肿瘤的最重要危险因素。幼年接受放疗的儿童后续患胶质瘤的风险较高，这可能反映出发育中的大脑对辐射更易感性。
