Fidler Miranda M, Reulen Raoul C, Winter David L, Kelly Julie, Jenkinson Helen C, Skinner Rod, Frobisher Clare, Hawkins Michael M
Centre for Childhood Cancer Survivor Studies, Institute of Applied Health Research, University of Birmingham, Birmingham B15 2TT, UK.
Department of Oncology, Birmingham Children's Hospital, NHS Foundation Trust, Birmingham, UK.
BMJ. 2016 Sep 1;354:i4351. doi: 10.1136/bmj.i4351.
To determine whether modern treatments for cancer are associated with a net increased or decreased risk of death from neoplastic and non-neoplastic causes among survivors of childhood cancer.
Population based cohort study.
British Childhood Cancer Survivor Study.
Nationwide population based cohort of 34 489 five year survivors of childhood cancer with a diagnosis from 1940 to 2006 and followed up until 28 February 2014.
Cause specific standardised mortality ratios and absolute excess risks are reported. Multivariable Poisson regression models were utilised to evaluate the simultaneous effect of risk factors. Likelihood ratio tests were used to test for heterogeneity or trend.
Overall, 4475 deaths were observed, which was 9.1 (95% confidence interval 8.9 to 9.4) times that expected in the general population, corresponding to 64.2 (95% confidence interval 62.1 to 66.3) excess deaths per 10 000 person years. The number of excess deaths from all causes declined among those treated more recently; those treated during 1990-2006 experienced 30% of the excess number of deaths experienced by those treated before 1970. The corresponding percentages for the decline in excess deaths from recurrence or progression and non-neoplastic causes were 30% and 60%, respectively. Among survivors aged 50-59 years, 41% and 22% of excess deaths were attributable to subsequent primary neoplasms and circulatory conditions, respectively, whereas the corresponding percentages among those aged 60 years or more were 31% and 37%.
The net effects of changes in cancer treatments, and surveillance and management for late effects, over the period 1940 to 2006 was to reduce the excess number of deaths from both recurrence or progression and non-neoplastic causes among those treated more recently. Among survivors aged 60 years or more, the excess number of deaths from circulatory causes exceeds the excess number of deaths from subsequent primary neoplasms. The important message for the evidence based surveillance aimed at preventing excess mortality and morbidity in survivors aged 60 years or more is that circulatory disease overtakes subsequent primary neoplasms as the leading cause of excess mortality.
确定现代癌症治疗方法是否与儿童癌症幸存者因肿瘤性和非肿瘤性原因导致的死亡风险净增加或减少相关。
基于人群的队列研究。
英国儿童癌症幸存者研究。
基于全国人群的队列,共34489名儿童癌症五年幸存者,诊断时间为1940年至2006年,随访至2014年2月28日。
报告特定病因的标准化死亡比和绝对超额风险。采用多变量泊松回归模型评估风险因素的同时作用。似然比检验用于检验异质性或趋势。
总体而言,观察到4475例死亡,是一般人群预期死亡数的9.1(95%置信区间8.9至9.4)倍,相当于每10000人年有64.2(95%置信区间62.1至66.3)例超额死亡。在最近接受治疗的人群中,所有原因导致的超额死亡人数有所下降;1990年至2006年期间接受治疗的人群经历的超额死亡人数是1970年之前接受治疗人群的30%。因复发或进展以及非肿瘤性原因导致的超额死亡人数下降的相应百分比分别为30%和60%。在50至59岁的幸存者中,分别有41%和22%的超额死亡归因于随后的原发性肿瘤和循环系统疾病,而在60岁及以上人群中,相应百分比分别为31%和37%。
1940年至2006年期间癌症治疗、晚期效应监测和管理变化的净效应是减少了最近接受治疗人群中因复发或进展以及非肿瘤性原因导致的超额死亡人数。在60岁及以上的幸存者中,循环系统疾病导致的超额死亡人数超过了随后原发性肿瘤导致的超额死亡人数。对于旨在预防年龄在60岁及以上幸存者的超额死亡率和发病率的循证监测而言,重要信息是循环系统疾病超过随后原发性肿瘤成为超额死亡的主要原因。