Hippisley-Cox Julia, Coupland Carol
Division of Primary Care, University Park, Nottingham NG2 7RD, UK
Division of Primary Care, University Park, Nottingham NG2 7RD, UK.
BMJ. 2017 Jun 15;357:j2497. doi: 10.1136/bmj.j2497.
To develop and externally validate risk prediction equations to estimate absolute and conditional survival in patients with colorectal cancer. Cohort study. General practices in England providing data for the QResearch database linked to the national cancer registry. 44 145 patients aged 15-99 with colorectal cancer from 947 practices to derive the equations. The equations were validated in 15 214 patients with colorectal cancer from 305 different QResearch practices and 437 821 patients with colorectal cancer from the national cancer registry. The primary outcome was all cause mortality and secondary outcome was colorectal cancer mortality. Cause specific hazards models were used to predict risks of colorectal cancer mortality and other cause mortality accounting for competing risks, and these risk estimates were combined to obtain risks of all cause mortality. Separate equations were derived for men and women. Several variables were tested: age, ethnicity, deprivation score, cancer stage, cancer grade, surgery, chemotherapy, radiotherapy, smoking status, alcohol consumption, body mass index, family history of bowel cancer, anaemia, liver function test result, comorbidities, use of statins, use of aspirin, clinical values for anaemia, and platelet count. Measures of calibration and discrimination were determined in both validation cohorts at 1, 5, and 10 years. The final models included the following variables in men and women: age, deprivation score, cancer stage, cancer grade, smoking status, colorectal surgery, chemotherapy, family history of bowel cancer, raised platelet count, abnormal liver function, cardiovascular disease, diabetes, chronic renal disease, chronic obstructive pulmonary disease, prescribed aspirin at diagnosis, and prescribed statins at diagnosis. Improved survival in women was associated with younger age, earlier stage of cancer, well or moderately differentiated cancer grade, colorectal cancer surgery (adjusted hazard ratio 0.50), family history of bowel cancer (0.62), and prescriptions for statins (0.77) and aspirin (0.83) at diagnosis, with comparable results for men. The risk equations were well calibrated, with predicted risks closely matching observed risks. Discrimination was good in men and women in both validation cohorts. For example, the five year survival equations on the QResearch validation cohort explained 45.3% of the variation in time to colorectal cancer death for women, the D statistic was 1.86, and Harrell's C statistic was 0.80 (both measures of discrimination, indicating that the scores are able to distinguish between people with different levels of risk). The corresponding results for all cause mortality were 42.6%, 1.77, and 0.79. Risk prediction equations were developed and validated to estimate overall and conditional survival of patients with colorectal cancer accounting for an individual's clinical and demographic characteristics. These equations can provide more individualised accurate information for patients with colorectal cancer to inform decision making and follow-up.
开发并外部验证风险预测方程,以估计结直肠癌患者的绝对生存和条件生存情况。队列研究。英格兰的全科医疗服务机构为与国家癌症登记处相关联的QResearch数据库提供数据。来自947家医疗机构的44145名年龄在15 - 99岁的结直肠癌患者用于推导方程。这些方程在来自305家不同QResearch医疗机构的15214名结直肠癌患者以及国家癌症登记处的437821名结直肠癌患者中进行了验证。主要结局是全因死亡率,次要结局是结直肠癌死亡率。使用特定病因风险模型来预测结直肠癌死亡率和其他病因死亡率的风险,并考虑竞争风险,将这些风险估计值合并以获得全因死亡率风险。为男性和女性分别推导了方程。测试了多个变量:年龄、种族、贫困得分、癌症分期、癌症分级、手术、化疗、放疗、吸烟状况、饮酒量、体重指数、肠癌家族史、贫血、肝功能检查结果、合并症、他汀类药物使用情况、阿司匹林使用情况、贫血的临床值以及血小板计数。在两个验证队列中分别在1年、5年和10年确定校准和区分度的指标。最终模型在男性和女性中纳入了以下变量:年龄、贫困得分、癌症分期、癌症分级、吸烟状况、结直肠手术、化疗、肠癌家族史、血小板计数升高、肝功能异常、心血管疾病、糖尿病、慢性肾病、慢性阻塞性肺疾病、诊断时开具的阿司匹林以及诊断时开具的他汀类药物。女性生存率的提高与年龄较小、癌症分期较早、癌症分级为高分化或中分化、结直肠癌手术(调整后风险比0.50)、肠癌家族史(0.62)以及诊断时开具他汀类药物(0.77)和阿司匹林(0.83)有关,男性的结果与之类似。风险方程校准良好,预测风险与观察到的风险紧密匹配。在两个验证队列中,男性和女性的区分度都很好。例如,QResearch验证队列中女性的五年生存方程解释了结直肠癌死亡时间变化的45.3%,D统计量为1.86,Harrell's C统计量为0.80(两者均为区分度指标,表明这些分数能够区分不同风险水平的人群)。全因死亡率的相应结果分别为42.6%、1.77和0.79。开发并验证了风险预测方程,以估计考虑个体临床和人口统计学特征的结直肠癌患者的总体生存和条件生存情况。这些方程可以为结直肠癌患者提供更个性化的准确信息,以指导决策和随访工作。