Temporal Trends in Treatment and Subsequent Neoplasm Risk Among 5-Year Survivors of Childhood Cancer, 1970-2015.
Temporal Trends in Treatment and Subsequent Neoplasm Risk Among 5-Year Survivors of Childhood Cancer, 1970-2015.
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DOI：
10.1001/jama.2017.0693
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发表时间：
2017-02-28
期刊：
影响因子：
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通讯作者：
Neglia JP
中科院分区：
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作者：
Turcotte LM;Liu Q;Yasui Y;Arnold MA;Hammond S;Howell RM;Smith SA;Weathers RE;Henderson TO;Gibson TM;Leisenring W;Armstrong GT;Robison LL;Neglia JP
癌症治疗与儿童癌症幸存者的后续肿瘤相关。目前尚不清楚治疗的时间变化是否与后续肿瘤风险的变化相关。量化治疗剂量变化与后续肿瘤风险之间的相关性。回顾性、多中心队列研究，研究对象为1970-1999年间在美国和加拿大三级儿科医院诊断为21岁之前癌症的5年存活者，随访至2015年12月。放疗和化疗剂量随时间变化。随后的肿瘤15年累积发病率，累积负担，和标准化发病率比（SIR）的后续恶性肿瘤进行了比较治疗十年。多变量模型通过5年增量评估后续肿瘤的相对发生率（RR），并根据人口统计学和临床特征进行调整。中介分析评估了后续肿瘤发生率随时间的变化是否由治疗变量调整介导。在23，603名儿童癌症幸存者（平均诊断年龄为7.7岁; 46%为女性）中，最常见的初始诊断为急性淋巴细胞白血病，霍奇金淋巴瘤和星形细胞瘤。在平均20.5年的随访期间（374，638人-年的风险），1，639名幸存者经历了3，115例后续肿瘤，包括1，026例恶性肿瘤，233例良性脑膜瘤和1，856例非黑色素瘤皮肤癌。最常见的后续恶性肿瘤是乳腺癌和甲状腺癌。接受辐射的个体减少（1970年代，77% vs. 1990年代，33%），中位剂量也减少（1970年代，30戈伊[IQR 24-44] vs. 1990年代，26戈伊[IQR 18-45]）。随后恶性肿瘤的15年累积发病率随着诊断的10年而降低（1990年代：1.3%，95%CI 1.1-1.5; 1980年代：1.7%，95%CI 1.5-2.0; 1970年代：2.1%，95%CI 1.7-2.4）。后续恶性肿瘤、脑膜瘤和非黑色素瘤皮肤癌的参考绝对发生率为1.12/1000人年（95%CI 0.84-1.57），0.16（95%CI 0.06-0.41）和1.71（95%CI 0.88-3.33）。随着年龄的增长，治疗数十年后恶性肿瘤的SIR下降。随后的恶性肿瘤（RR=0.87，95%CI 0.82-0.93，p<0.001）、脑膜瘤（RR=0.85，95%CI 0.75-0.97，p=0.034）和非黑色素瘤皮肤癌（RR=0.75，95%CI 0.67-0.84，p<0.001）的相对发病率随着每5年的增加而下降。辐射剂量的改变与随后的恶性肿瘤、脑膜瘤和非黑色素瘤皮肤癌的风险降低有关。在儿童癌症幸存者中，20世纪90年代诊断的儿童在初次癌症诊断后15年发生后续恶性肿瘤的风险仍然增加，尽管与20世纪70年代诊断的儿童相比，风险较低。这种较低的风险与治疗辐射剂量的减少有关。
Cancer treatments are associated with subsequent neoplasms in childhood cancer survivors. It is unknown whether temporal changes in therapy are associated with changes in subsequent neoplasm risk. Quantify the association between temporal treatment dosing changes and subsequent neoplasm risk. Retrospective, multicenter cohort of five-year cancer survivors diagnosed before age 21 years from pediatric tertiary hospitals in the United States and Canada between 1970-1999, with follow-up through December 2015. Radiation and chemotherapy dose changes over time. Subsequent neoplasm 15-year cumulative incidence, cumulative burden, and standardized incidence ratios (SIRs) for subsequent malignancies were compared by treatment decade. Multivariable models assessed relative rates (RRs) of subsequent neoplasms by 5-year increments, adjusting for demographic and clinical characteristics. Mediation analyses assessed whether changes in subsequent neoplasm rates over time were mediated by treatment variable modifications. Among 23,603 childhood cancer survivors (mean age at diagnosis, 7.7 years; 46% female) the most common initial diagnoses were acute lymphoblastic leukemia, Hodgkin lymphoma and astrocytoma. During a mean follow up of 20.5 years (374,638 person-years at risk), 1,639 survivors experienced 3,115 subsequent neoplasms, including 1,026 malignancies, 233 benign meningiomas, and 1,856 non-melanoma skin cancers. The most common subsequent malignancies were breast and thyroid cancers. Individuals receiving radiation decreased (1970s, 77% vs. 1990s, 33%), as did median dose (1970s, 30 Gy [IQR 24-44] vs. 1990s, 26 Gy [IQR 18-45]). Fifteen-year cumulative incidence of subsequent malignancies decreased by decade of diagnosis (1990s: 1.3%, 95%CI 1.1-1.5, 1980s: 1.7%, 95%CI 1.5-2.0, 1970s: 2.1%, 95%CI 1.7-2.4). Reference absolute rates per 1,000 person-years for subsequent malignancies, meningiomas and non-melanoma skin cancers were 1.12 (95%CI 0.84-1.57), 0.16 (95%CI 0.06-0.41), and 1.71 (95%CI 0.88-3.33), respectively, for survivors with reference characteristics (no chemotherapy, splenectomy or radiation therapy, male, attained age of 28). SIRs declined for subsequent malignancies over treatment decades, with advancing attained age. Relative rates declined with each 5-year increment for subsequent malignancies (RR=0.87, 95%CI 0.82-0.93, p<0.001), meningiomas (RR=0.85, 95%CI 0.75-0.97, p=0.034), and non-melanoma skin cancers (RR=0.75, 95%CI 0.67-0.84, p<0.001). Radiation dose changes were associated with reduced risk for subsequent malignancies, meningiomas, and non-melanoma skin cancers. Among childhood cancer survivors, the risk of subsequent malignancies at 15 years after initial cancer diagnosis remained increased for those diagnosed in the 1990s, although the risk was lower compared with those diagnosed in the 1970s. This lower risk was associated with reduction in therapeutic radiation dose.