Late mortality and chronic health conditions in long-term survivors of early-adolescent and young adult cancers: a retrospective cohort analysis from the Childhood Cancer Survivor Study.,The Lancet Oncology

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Late mortality and chronic health conditions in long-term survivors of early-adolescent and young adult cancers: a retrospective cohort analysis from the Childhood Cancer Survivor Study.
The Lancet Oncology ( IF 41.6 ) Pub Date : 2020-02-14 , DOI: 10.1016/s1470-2045(19)30800-9
Eugene Suh ₁ , Kayla L Stratton ₂ , Wendy M Leisenring ₂ , Paul C Nathan ₃ , Jennifer S Ford ₄ , David R Freyer ₅ , Jennifer L McNeer ₆ , Wendy Stock ₇ , Marilyn Stovall ₈ , Kevin R Krull ₉ , Charles A Sklar ₁₀ , Joseph P Neglia ₁₁ , Gregory T Armstrong ₉ , Kevin C Oeffinger ₁₂ , Leslie L Robison ₉ , Tara O Henderson ₆

Affiliation

Loyola University Chicago Health Sciences, Maywood, IL, USA.
Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
Hunter College and The Graduate Center, City University of New York, New York, NY, USA.
Children's Hospital Los Angeles, Los Angeles, CA, USA.
Department of Pediatrics, University of Chicago, Chicago, IL, USA.
Department of Medicine, University of Chicago, Chicago, IL, USA.
The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
St Jude Children's Research Hospital, Memphis, TN, USA.
Memorial Sloan Kettering Cancer Center, New York, NY, USA.
University of Minnesota, Minneapolis, MN, USA.
Duke University School of Medicine, Durham, NC, USA.

BACKGROUND Treatment outcomes among survivors of cancer diagnosed during adolescence and early young adulthood have not been characterised independently of survivors of cancers diagnosed during childhood. We aimed to describe chronic health conditions and all-cause and cause-specific mortality among survivors of early-adolescent and young adult cancer. METHODS The Childhood Cancer Survivor Study (CCSS) is a retrospective cohort study with longitudinal follow-up of 5-year survivors diagnosed with cancer before the age of 21 years at 27 academic institutions in the USA and Canada between 1970 and 1999. We evaluated outcomes among survivors of early-adolescent and young adult cancer (aged 15-20 years at diagnosis) and survivors diagnosed at age younger than 15 years (matched on primary cancer diagnosis, including leukaemia, lymphoma, CNS tumours, neuroblastoma, Wilms tumour, soft-tissue sarcomas, and bone cancer) by comparing both groups to siblings of the same age. Mortality was ascertained with the National Death Index. Chronic health conditions were classified with the Common Terminology Criteria for Adverse Events. Standardised mortality ratios (SMRs) were estimated with age-specific, sex-specific, and calendar year-specific US rates. Cox proportional hazard models estimated hazard ratios (HRs) for chronic health conditions and 95% CIs. FINDINGS Among 5804 early-adolescent and young adult survivors (median age 42 years, IQR 34-50) the SMR compared to the general population for all-cause mortality was 5·9 (95% CI 5·5-6·2) and among 5804 childhood cancer survivors (median age 34 years; 27-42), it was 6·2 (5·8-6·6). Early-adolescent and young adult survivors had lower SMRs for death from health-related causes (ie, conditions that exclude recurrence or progression of the primary cancer and external causes, but include the late effects of cancer therapy) than did childhood cancer survivors (SMR 4·8 [95% CI 4·4-5·1] vs 6·8 [6·2-7·4]), which was primarily evident more than 20 years after cancer diagnosis. Early-adolescent and young adult cancer survivors and childhood cancer survivors were both at greater risk of developing severe and disabling, life-threatening, or fatal (grade 3-5) health conditions than siblings of the same age (HR 4·2 [95% CI 3·7-4·8] for early adolescent and young adult cancer survivors and 5·6 [4·9-6·3] for childhood cancer survivors), and at increased risk of developing grade 3-5 cardiac (4·3 [3·5-5·4] and 5·6 [4·5-7·1]), endocrine (3·9 [2·9-5·1] and 6·4 [5·1-8·0]), and musculoskeletal conditions (6·5 [3·9-11·1] and 8·0 [4·6-14·0]) when compared with siblings of the same age, although all these risks were lower for early-adolescent and young adult survivors than for childhood cancer survivors. INTERPRETATION Early-adolescent and young adult cancer survivors had higher risks of mortality and severe and life threatening chronic health conditions than the general population. However, early-adolescent and young adult cancer survivors had lower non-recurrent, health-related SMRs and relative risks of developing grade 3-5 chronic health conditions than childhood cancer survivors, by comparison with siblings of the same age, which were most notable more than 20 years after their original cancer. These results highlight the need for long-term screening of both childhood and early-adolescent and young adult cancer survivors. FUNDING National Cancer Institute and American Lebanese-Syrian Associated Charities.

中文翻译：

早期青春期和年轻成人癌症长期存活者的晚期死亡率和慢性健康状况：儿童癌症幸存者研究的回顾性队列分析。

背景技术在青春期和成年早期诊断出的癌症幸存者中，治疗结果尚未独立于儿童期诊断出的癌症幸存者的特征。我们旨在描述慢性健康状况以及早期青春期和年轻成人癌症幸存者之间的全因病因和特定病因死亡率。方法儿童癌症幸存者研究（CCSS）是一项回顾性队列研究，对1970年至1999年间在美国和加拿大的27个学术机构中21岁之前被诊断出患有癌症的5年幸存者进行了纵向随访。我们评估了结局在青春期和年轻成人癌症的幸存者中（诊断时年龄为15-20岁）和在15岁以下被诊断出的幸存者中（与初次癌症诊断者相匹配，包括白血病，淋巴瘤，中枢神经系统肿瘤，神经母细胞瘤，威尔姆斯瘤，软组织肉瘤和骨癌），方法是将两组与同龄的兄弟姐妹进行比较。死亡率通过国家死亡指数确定。慢性健康状况根据不良事件通用术语标准进行分类。使用特定年龄，特定性别和特定日历年的美国比率来估算标准死亡率（SMR）。Cox比例风险模型估计了慢性健康状况和95％CI的风险比（HRs）。结果在5804名早期和年轻成年幸存者（中位年龄42岁，IQR 34-50）中，与一般人群相比，SMR的全因死亡率为5·9（95％CI 5·5-6·2），并且在5804名儿童癌症幸存者（中位年龄34岁； 27-42岁）中，这一比例为6·2（5·8-6·6）。与儿童癌症幸存者（SMR）相比，早期和成年幸存者因健康相关原因死亡的SMR较低（即，排除原发癌复发或进展和外部原因，但包括癌症治疗的晚期影响的疾病）。 4·8 [95％CI 4·4-5·1]和6·8 [6·2-7·4]），这在癌症诊断后20多年中最为明显。与同龄的同胞相比，早期和青年癌症幸存者和儿童癌症幸存者患严重和致残，威胁生命或致命（3-5级）健康状况的风险更高（HR 4·2 [95] ％CI 3·7-4·8]对于早期的青少年和年轻成人癌症幸存者，而5·6 [4·9-6·3]对于儿童癌症幸存者），发展为3-5级心脏的风险更高（4 ·3 [3·5-5·4]和5·6 [4·5-7·1]），内分泌（3·9 [2·9-5·1]和6·4 [5·1-8·0]）和肌肉骨骼疾病（6·5 [3·9-11·1]和8·0 [ [4·6-14·0]）与同龄的兄弟姐妹相比，尽管所有这些风险对于早期和年轻成年幸存者而言都比儿童癌症幸存者要低。解释与一般人群相比，早期癌症和年轻的成年癌症幸存者具有更高的死亡风险，严重的生命危险和威胁生命的慢性健康状况。然而，与同龄的同胞相比，与儿童同龄的同胞相比，早期和年轻的成年癌症幸存者与儿童癌症幸存者相比，与健康相关的非复发性SMR较低，发生3-5级慢性疾病的相对风险较低。在他们最初的癌症发生20多年后。这些结果凸显了对儿童，青少年，年轻成人癌症幸存者进行长期筛查的必要性。资助国家癌症研究所和美国黎巴嫩叙利亚联合慈善组织。

更新日期：2020-03-03

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