Long-term inpatient disease burden in the Adult Life after Childhood Cancer in Scandinavia (ALiCCS) study: A cohort study of 21,297 childhood cancer survivors.
Long-term inpatient disease burden in the Adult Life after Childhood Cancer in Scandinavia (ALiCCS) study: A cohort study of 21,297 childhood cancer survivors.
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DOI：
10.1371/journal.pmed.1002296
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发表时间：
2017-05
期刊：
影响因子：
15.8
通讯作者：
ALiCCS study group
中科院分区：
文献类型：
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作者：
de Fine Licht S;Rugbjerg K;Gudmundsdottir T;Bonnesen TG;Asdahl PH;Holmqvist AS;Madanat-Harjuoja L;Tryggvadottir L;Wesenberg F;Hasle H;Winther JF;Olsen JH;ALiCCS study group
儿童期癌症的幸存者受到各种晚期影响的风险增加。然而，目前还没有大规模的以人群为基础的研究涵盖了包括亚组诊断和所有主要类型的儿童癌症在内的整个躯体诊断范围。因此，我们的目的是提供儿童癌症幸存者长期住院风险的最详细概述。从丹麦、芬兰、冰岛和瑞典的国家癌症登记处中，我们确定了21297名20岁前被诊断为癌症的5年儿童癌症幸存者，时间分别为1943年至2008年丹麦、1971年至2008年芬兰、1955年至2008年冰岛和1958年至2008年瑞典。我们从全国人口登记册中随机选择152231个按年龄、性别、年份和国家（或瑞典的城市）匹配的人口比较个体。采用队列设计，研究参与者在1977-2010年期间在丹麦国家医院登记；芬兰,1975 - 2012;冰岛,1999 - 2008;瑞典，1968-2009年。使用幸存者和比较个体的疾病特异性住院率来计算基于住院时间的幸存者标准化住院率比（rr）、绝对超额风险（AERs）和标准化床位日比（SBDRs）。我们通过间接标准化调整了性别、年龄和年份。在336,554人年的随访期间（平均16年，范围0-42年），儿童癌症幸存者因120种疾病中的一种或多种疾病（不包括癌症复发）首次住院的人数为21,325人，而预期为10,999人，总体RR为1.94（95%置信区间[95% CI] 1.91-1.97）。AER为每100,000人年3,068人（2,980-3,156人），这意味着每增加一年的随访，100名幸存者中平均有3人因超出背景率的新疾病住院。大约50%的超额住院治疗是神经系统疾病（占所有超额住院治疗的19.1%）、内分泌系统疾病（11.1%）、消化器官疾病（10.5%）和呼吸系统疾病（10.0%）。所有类型儿童癌症的幸存者随后住院的风险都增加了，风险最高的是神经母细胞瘤（RR: 2.6 [2.4 - 2.8]; n = 876）、肝脏肿瘤（RR: 2.5 [2.0-3.1]; n = 92）、中枢神经系统肿瘤（RR: 2.4 [2.3-2.5]; n = 6175）和霍奇金淋巴瘤（RR: 2.4 [2.3-2.5]; n = 2027）的幸存者。幸存者的平均住院天数是对照组的5倍（SBDR: 4.96 [4.94-4.98]; n = 422,218）。住院天数的分析包括新的原发癌症和复发。在幸存者住院的422218天中，47%（197596个床日）用于治疗新发原发癌症和复发。我们的研究可能低估了幸存者所经历的绝对总体疾病负担，因为如果他们在门诊环境或初级卫生保健系统中得到充分治疗，就会错过不那么严重的晚期影响。儿童癌症幸存者患需要住院治疗的疾病的长期风险增加，甚至在他们最初患癌症的几十年后也是如此。不从事后期影响领域工作的卫生保健提供者，特别是初级卫生保健提供者，应该认识到这一极具挑战性的患者群体，以便通过预防、早期发现和适当治疗来避免或推迟住院。在丹麦、芬兰、冰岛和瑞典的一项基于人群的队列研究中，Sofie de Fine light及其同事发现儿童癌症幸存者的长期疾病负担增加，严重到需要住院治疗。今天，五分之四的儿童癌症患者成为长期幸存者。然而，由于毒性治疗（通常是联合治疗）是在以生长和器官成熟为特征的年龄进行的，许多儿童癌症幸存者面临着显著的、通常是无特征的晚期躯体疾病。以前没有研究能够检查儿童癌症幸存者的长期住院发病率，包括几乎所有儿童癌症类型和疾病特定结果的组合。我们利用北欧国家独特的健康登记处，包括120种疾病实体和所有主要的儿童癌症诊断组，探讨了21,297名5年儿童癌症幸存者的终生躯体发病率模式。我们发现，与年龄和性别相似的人群相比，幸存者住院的总体风险为2倍，住院时间更长。癌症幸存者住院的主要原因是神经系统疾病（占所有超额住院的19.1%）、内分泌系统疾病（11.1%）、消化器官疾病（10.5%）和呼吸系统疾病（10.0%）。这四类疾病加起来占癌症幸存者因特定原因过度住院的51%。发病率模式高度依赖于儿童癌症的类型，神经母细胞瘤、肝脏和中枢神经系统（CNS）肿瘤和霍奇金淋巴瘤的幸存者的风险最高。这项研究提供了一个全面的概述终身，复杂的，往往严重的疾病模式，儿童癌症患者在结束治疗后遇到。由于我们使用诊断住院患者信息作为结果的衡量标准，我们的研究显示了最严重的躯体疾病负担，与先前描述的认知和其他心理不良影响相结合，可能对儿童癌症幸存者的生活质量和总体死亡率产生重大影响。初级和二级卫生保健的临床医生应该意识到这一弱势患者群体，以便更好地发现、预防和管理治疗引起的晚期效应。我们建议在专门的环境中对儿童癌症幸存者的高风险亚群进行长期随访。
Survivors of childhood cancer are at increased risk for a wide range of late effects. However, no large population-based studies have included the whole range of somatic diagnoses including subgroup diagnoses and all main types of childhood cancers. Therefore, we aimed to provide the most detailed overview of the long-term risk of hospitalisation in survivors of childhood cancer. From the national cancer registers of Denmark, Finland, Iceland, and Sweden, we identified 21,297 5-year survivors of childhood cancer diagnosed with cancer before the age of 20 years in the periods 1943–2008 in Denmark, 1971–2008 in Finland, 1955–2008 in Iceland, and 1958–2008 in Sweden. We randomly selected 152,231 population comparison individuals matched by age, sex, year, and country (or municipality in Sweden) from the national population registers. Using a cohort design, study participants were followed in the national hospital registers in Denmark, 1977–2010; Finland, 1975–2012; Iceland, 1999–2008; and Sweden, 1968–2009. Disease-specific hospitalisation rates in survivors and comparison individuals were used to calculate survivors’ standardised hospitalisation rate ratios (RRs), absolute excess risks (AERs), and standardised bed day ratios (SBDRs) based on length of stay in hospital. We adjusted for sex, age, and year by indirect standardisation. During 336,554 person-years of follow-up (mean: 16 years; range: 0–42 years), childhood cancer survivors experienced 21,325 first hospitalisations for diseases in one or more of 120 disease categories (cancer recurrence not included), when 10,999 were expected, yielding an overall RR of 1.94 (95% confidence interval [95% CI] 1.91–1.97). The AER was 3,068 (2,980–3,156) per 100,000 person-years, meaning that for each additional year of follow-up, an average of 3 of 100 survivors were hospitalised for a new excess disease beyond the background rates. Approximately 50% of the excess hospitalisations were for diseases of the nervous system (19.1% of all excess hospitalisations), endocrine system (11.1%), digestive organs (10.5%), and respiratory system (10.0%). Survivors of all types of childhood cancer were at increased, persistent risk for subsequent hospitalisation, the highest risks being those of survivors of neuroblastoma (RR: 2.6 [2.4–2.8]; n = 876), hepatic tumours (RR: 2.5 [2.0–3.1]; n = 92), central nervous system tumours (RR: 2.4 [2.3–2.5]; n = 6,175), and Hodgkin lymphoma (RR: 2.4 [2.3–2.5]; n = 2,027). Survivors spent on average five times as many days in hospital as comparison individuals (SBDR: 4.96 [4.94–4.98]; n = 422,218). The analyses of bed days in hospital included new primary cancers and recurrences. Of the total 422,218 days survivors spent in hospital, 47% (197,596 bed days) were for new primary cancers and recurrences. Our study is likely to underestimate the absolute overall disease burden experienced by survivors, as less severe late effects are missed if they are treated sufficiently in the outpatient setting or in the primary health care system. Childhood cancer survivors were at increased long-term risk for diseases requiring inpatient treatment even decades after their initial cancer. Health care providers who do not work in the area of late effects, especially those in primary health care, should be aware of this highly challenged group of patients in order to avoid or postpone hospitalisations by prevention, early detection, and appropriate treatments. In this population-based cohort study in Denmark, Finland, Iceland, and Sweden, Sofie de Fine Licht and colleagues present the increased long-term burden of disease serious enough to require hospitalization in survivors of childhood cancer. Today, four out of five children with cancer become long-term survivors. However, as toxic treatments, often in combination, are given at an age distinguished by growth and organ maturation, many childhood cancer survivors face significant and often uncharacterised late somatic morbidities. No previous study has been able to examine the long-term inpatient morbidity in childhood cancer survivors including virtually all combinations of type of childhood cancer and disease-specific outcome. We explored the lifetime somatic morbidity pattern in 21,297 5-year survivors of childhood cancer using the unique health registries of the Nordic countries, including 120 disease entities and all main diagnostic groups of childhood cancer. We found that survivors had an overall 2-fold risk of being hospitalised and experienced longer stays in hospital than population comparisons of similar age and sex. Major reasons for hospitalisation among cancer survivors were diseases of the nervous system (19.1% of all excess hospitalisations), endocrine system (11.1%), digestive organs (10.5%), and respiratory system (10.0%). Together, these four groups of diseases accounted for 51% of the excess cause-specific hospitalisations among cancer survivors. The morbidity pattern was highly dependent on the type of childhood cancer, with highest risks seen for survivors of neuroblastoma, hepatic and central nervous system (CNS) tumours, and Hodgkin lymphoma. This study provides a comprehensive overview of the lifelong, complex, and often serious disease pattern that childhood cancer patients encounter after ended treatment. As we have used diagnostic inpatient information as measure of outcomes, our study presents the most serious somatic disease burden, which, in combination with previously described cognitive and other psychological adverse effects, may have significant impact on the quality of life and overall mortality of childhood cancer survivors. Clinicians in primary and secondary health care should be aware of this vulnerable group of patients for better detection, prevention, and management of treatment-induced late effects. We recommend long-term follow-up of high-risk subsets of childhood cancer survivors in a specialised setting.