Department of Global Pediatric Medicine, St Jude Children's Research Hospital, Memphis, TN, USA; Department of Epidemiology and Cancer Control, St Jude Children's Research Hospital, Memphis, TN, USA; Department of Oncology, St Jude Children's Research Hospital, Memphis, TN, USA.
School of Public Health, University of Alberta, Edmonton, AB, Canada.
Lancet. 2017 Dec 9;390(10112):2569-2582. doi: 10.1016/S0140-6736(17)31610-0. Epub 2017 Sep 8.
Survivors of childhood cancer develop early and severe chronic health conditions (CHCs). A quantitative landscape of morbidity of survivors, however, has not been described. We aimed to describe the cumulative burden of curative cancer therapy in a clinically assessed ageing population of long-term survivors of childhood cancer.
The St Jude Lifetime Cohort Study (SJLIFE) retrospectively collected data on CHCs in all patients treated for childhood cancer at the St Jude Children's Research Hospital who survived 10 years or longer from initial diagnosis and were 18 years or older as of June 30, 2015. Age-matched and sex-frequency-matched community controls were used for comparison. 21 treatment exposure variables were included in the analysis, with data abstracted from medical records. 168 CHCs for all participants were graded for severity using a modified Common Terminology Criteria of Adverse Events. Multiple imputation with predictive mean matching was used for missing occurrences and grades of CHCs in the survivors who were not clinically evaluable. Mean cumulative count was used for descriptive cumulative burden analysis and marked-point-process regression was used for inferential cumulative burden analysis.
Of 5522 patients treated for childhood cancer at St Jude Children's Research Hospital who had complete records, survived 10 years or longer, and were 18 years or older at time of study, 3010 (54·5%) were alive, had enrolled, and had had prospective clinical assessment. 2512 (45·5%) of the 5522 patients were not clinically evaluable. The cumulative incidence of CHCs at age 50 years was 99·9% (95% CI 99·9-99·9) for grade 1-5 CHCs and 96·0% (95% CI 95·3-96·8%) for grade 3-5 CHCs. By age 50 years, a survivor had experienced, on average, 17·1 (95% CI 16·2-18·1) CHCs of any grade, of which 4·7 (4·6-4·9) were CHCs of grade 3-5. The cumulative burden in matched community controls of grade 1-5 CHCs was 9·2 (95% CI 7·9-10·6; p<0·0001 vs total study population) and of grade 3-5 CHCs was 2·3 (1·9-2·7, p<0·0001 vs total study population). Second neoplasms, spinal disorders, and pulmonary disease were major contributors to the excess total cumulative burden. Notable heterogeneity in the distribution of CHC burden in survivors with differing primary cancer diagnoses was observed. The cumulative burden of grade 1-5 CHCs at age 50 years was highest in survivors of CNS malignancies (24·2 [95% CI 20·9-27·5]) and lowest in survivors of germ cell tumours (14·0 [11·5-16·6]). Multivariable analyses showed that older age at diagnosis, treatment era, and higher doses of brain and chest radiation are significantly associated with a greater cumulative burden and severity of CHCs.
The burden of CHCs in survivors of childhood cancer is substantial and highly variable. Our assessment of total cumulative burden in survivors of paediatric cancer, with detailed characterisation of long-term CHCs, provide data to better inform future clinical guidelines, research investigations, and health services planning for this vulnerable, medically complex population.
The US National Cancer Institute, St Baldrick's Foundation, and the American Lebanese Syrian Associated Charities.
儿童癌症幸存者会出现早期且严重的慢性健康问题（CHCs）。然而，目前尚未描述幸存者发病率的定量情况。本研究旨在描述在经过临床评估的长期儿童癌症幸存者老龄化人群中，通过根治性癌症治疗所产生的累积负担。
圣裘德儿童研究医院的圣裘德终身队列研究（SJLIFE）回顾性地收集了在圣裘德儿童研究医院接受治疗且生存时间超过 10 年、截至 2015 年 6 月 30 日年龄达到 18 岁或以上的所有儿童癌症幸存者的 CHC 数据。使用年龄匹配和性别频率匹配的社区对照进行比较。分析中纳入了 21 个治疗暴露变量，数据从病历中提取。使用改良的常见不良事件术语标准，对所有参与者的 168 个 CHC 进行严重程度分级。对于无法进行临床评估的幸存者，使用预测均值匹配的多重插补法来处理 CHC 发生次数和严重程度的缺失数据。使用累积计数平均值进行描述性累积负担分析，使用标记点过程回归进行推断性累积负担分析。
在圣裘德儿童研究医院接受治疗且完全记录、生存时间超过 10 年、研究时年龄达到 18 岁或以上的 5522 名儿童癌症患者中，有 3010 名（54.5%）患者存活、入组并接受了前瞻性临床评估。5522 名患者中有 2512 名（45.5%）无法进行临床评估。在 50 岁时，CHC 的累积发病率为 1 级-5 级 CHC 为 99.9%（95%CI 99.9-99.9），3 级-5 级 CHC 为 96.0%（95%CI 95.3-96.8）。到 50 岁时，幸存者平均经历了 17.1 次（95%CI 16.2-18.1）任何严重程度的 CHC，其中 4.7 次（4.6-4.9）为 3 级-5 级 CHC。1 级-5 级 CHC 的累积负担在匹配的社区对照组中为 9.2（95%CI 7.9-10.6；与总研究人群相比，p<0.0001），3 级-5 级 CHC 的累积负担为 2.3（1.9-2.7，与总研究人群相比，p<0.0001）。第二原发肿瘤、脊柱疾病和肺部疾病是导致总累积负担增加的主要原因。在不同原发癌诊断的幸存者中，CHC 负担的分布存在显著异质性。在中枢神经系统恶性肿瘤幸存者中，50 岁时 1 级-5 级 CHC 的累积负担最高（24.2 [95%CI 20.9-27.5]），而生殖细胞肿瘤幸存者的累积负担最低（14.0 [11.5-16.6]）。多变量分析显示，诊断时年龄较大、治疗时期以及更高剂量的脑部和胸部放疗与 CHC 的累积负担和严重程度显著相关。
儿童癌症幸存者的 CHC 负担是巨大的，且高度可变。我们对儿童癌症幸存者进行了全面的累积负担评估，并对长期 CHC 进行了详细描述，为更好地为这一脆弱、医疗复杂的人群提供未来的临床指南、研究调查和卫生服务规划提供了数据。
美国国家癌症研究所、圣巴多罗买会和美国黎巴嫩叙利亚裔慈善协会。
