Wu Dongfeng, Rai Shesh N, Seow Albert
Department of Bioinformatics and Biostatistics, University of Louisville, USA.
Department of Radiology, University of Louisville, USA.
Stat Interface. 2022;15(3):349-358. doi: 10.4310/21-sii696.
Estimation of the three key parameters: onset age of the preclinical state, sojourn time and screening sensitivity is critical in cancer screening, since all other terms are functions of the three. A novel link function to connect sensitivity with time in the preclinical state and the likelihood method were used in this project; since sensitivity depends on how long one has entered the preclinical state relative to the total sojourn time. Simulations using Markov Chain Monte Carlo and maximum likelihood estimate were carried out to estimate the key parameters for male and female heavy smokers separately in the low-dose computed tomography group of the National Lung Screening Trial. Sensitivity for male and female heavy smokers were 0.883 and 0.915 respectively at the onset of the preclinical state, and increased to 0.972 and 0.981 at the end. The mean age to make the transition into the preclinical state was 70.94 or 71.15 for male and female heavy smokers respectively, and 90% of heavy smokers at risk for lung cancer would enter the preclinical state in age interval (55.7, 85.8) for males and (54.2, 87.7) for females, and the transition peaked around age 69 for both genders. The mean sojourn time in the preclinical state was 1.43 and 1.49 years, and the 99% credible intervals for the sojourn time were (0.21, 2.96) and (0.37, 2.69) years for male and female heavy smokers correspondingly. Based on the result, low-dose CT should be started at age 55 and ended before 85 for heavy smokers. This provided important information to policy makers.
临床前状态的起始年龄、停留时间和筛查敏感性在癌症筛查中至关重要，因为所有其他项都是这三个参数的函数。本项目使用了一种新颖的链接函数来连接临床前状态下的敏感性与时间，并采用了似然方法；因为敏感性取决于相对于总停留时间进入临床前状态的时长。使用马尔可夫链蒙特卡罗方法和最大似然估计进行了模拟，以分别估计国家肺癌筛查试验低剂量计算机断层扫描组中男性和女性重度吸烟者的关键参数。男性和女性重度吸烟者在临床前状态开始时的敏感性分别为0.883和0.915，结束时分别增至0.972和0.981。男性和女性重度吸烟者进入临床前状态的平均年龄分别为70.94岁或71.15岁，90%有肺癌风险的重度吸烟者将在男性年龄区间(55.7, 85.8)和女性年龄区间(54.2, 87.7)进入临床前状态，且两性的转变在69岁左右达到峰值。临床前状态的平均停留时间为1.43年和1.49年，男性和女性重度吸烟者停留时间的99%可信区间分别为(0.21, 2.96)年和(0.37, 2.69)年。基于该结果，重度吸烟者应在55岁开始进行低剂量CT检查，并在85岁之前结束。这为政策制定者提供了重要信息。
