儿童癌症幸存者的长期皮肤癌风险：DCOG-LATER 队列研究。
Long-Term Risk of Skin Cancer Among Childhood Cancer Survivors: A DCOG-LATER Cohort Study.
机构信息
See the Notes section for the full list of authors' affiliations.
出版信息
J Natl Cancer Inst. 2019 Aug 1;111(8):845-853. doi: 10.1093/jnci/djy212.
BACKGROUND
Skin cancer is common after radiotherapy among childhood cancer survivors (CCSs). We studied risks and risk factors for subsequent skin cancers, with emphasis on radiation dose, exposed skin surface area, and chemotherapeutic agents.
METHODS
The DCOG-LATER cohort study includes 5-year Dutch CCSs diagnosed 1963-2001. Subsequent skin cancers were identified from record linkages with the Netherlands Cancer Registry and Dutch Pathology Registry. Incidence rates were compared with general population rates. Multivariable Cox regression models were used, applying a novel method of case-control sampling enabling use of tumor location in cohort analyses. All statistical tests were two-sided.
RESULTS
Among 5843 CCSs, 259 developed 1061 basal cell carcinomas (BCCs) (standardized incidence ratio [SIR] = 29.8, 95% confidence interval [CI] = 26.3 to 33.6; excess absolute risk per 10 000 person-years (EAR) = 24.6), 20 had melanoma (SIR = 2.3, 95% CI = 1.4 to 3.5; EAR = 1.1), and 10 had squamous cell carcinoma (SIR = 7.5, 95% CI = 3.6 to 13.8; EAR = 0.8). Cumulative incidence of BCC 40 years after childhood cancer was 19.1% (95% CI = 16.6 to 21.8%) after radiotherapy vs 0.6% expected based on general population rates. After a first BCC, 46.7% had more BCCs later. BCC risk was associated with any radiotherapy to the skin compartment of interest (hazard ratio [HR] = 14.32, 95% CI = 10.10 to 20.29) and with estimated percentage in-field skin surface area (26-75%: HR = 1.99, 95% CI = 1.24 to 3.20; 76-100%: HR = 2.16, 95% CI = 1.33 to 3.53, vs 1-25% exposed; Ptrend among exposed = .002), but not with prescribed radiation dose and likelihood of sun-exposed skin-area. Of all chemotherapy groups examined, only vinca alkaloids increased BCC risk (HR = 1.54, 95% CI = 1.04 to 2.27).
CONCLUSION
CCSs have a strongly, 30-fold increased BCC risk. BCC risk appears to increase with increasing skin surface area exposed. This knowledge underscores the need for awareness by survivors and their health care providers.
背景
儿童癌症幸存者（CCS）在接受放疗后常见皮肤癌。我们研究了随后发生皮肤癌的风险和危险因素，重点关注辐射剂量、暴露皮肤表面积和化疗药物。
方法
DCOG-LATER 队列研究包括 1963-2001 年诊断的 5 年荷兰 CCS。通过与荷兰癌症登记处和荷兰病理登记处的记录链接来识别随后发生的皮肤癌。通过与普通人群的发病率进行比较来确定发病率。采用多变量 Cox 回归模型，应用一种新的病例对照抽样方法，可在队列分析中使用肿瘤位置。所有统计检验均为双侧。
结果
在 5843 例 CCS 中，有 259 例发生 1061 例基底细胞癌（BCC）（标准化发病比[SIR] = 29.8，95%置信区间[CI] = 26.3 至 33.6；每 10000 人年的超额绝对风险[EAR] = 24.6），20 例发生黑色素瘤（SIR = 2.3，95%CI = 1.4 至 3.5；EAR = 1.1），10 例发生鳞状细胞癌（SIR = 7.5，95%CI = 3.6 至 13.8；EAR = 0.8）。儿童癌症后 40 年 BCC 的累积发病率为 19.1%（95%CI = 16.6%至 21.8%），而基于普通人群发病率的预期发病率为 0.6%。在首次发生 BCC 后，46.7%的患者后来发生了更多的 BCC。BCC 风险与感兴趣的皮肤部位的任何放疗（风险比[HR] = 14.32，95%CI = 10.10 至 20.29）和估计的照射野皮肤表面积百分比（26-75%：HR = 1.99，95%CI = 1.24 至 3.20；76-100%：HR = 2.16，95%CI = 1.33 至 3.53，与 1-25%暴露相比；P 趋势在暴露人群中 =.002）相关，但与规定的辐射剂量和阳光照射皮肤面积的可能性无关。在所检查的所有化疗组中，只有长春碱类药物增加了 BCC 的风险（HR = 1.54，95%CI = 1.04 至 2.27）。
结论
CCS 的 BCC 风险高 30 倍。BCC 风险似乎随着暴露皮肤表面积的增加而增加。这一知识强调了幸存者及其医疗保健提供者需要提高认识。
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