Gendarme Sebastien, Irajizad Ehsan, Long James P, Fahrmann Johannes F, Dennison Jennifer B, Ghasemi Seyyed Mahmood, Dou Rongzhang, Volk Robert J, Meza Rafael, Toumazis Iakovos, Canoui-Poitrine Florence, Hanash Samir M, Ostrin Edwin J
Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, Texas; Université Paris-Est-Créteil, Inserm, IMRB, Créteil, France.
Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
J Thorac Oncol. 2025 May;20(5):565-576. doi: 10.1016/j.jtho.2025.01.003. Epub 2025 Jan 9.
To evaluate how comorbidities affect mortality benefits of lung cancer screening (LCS) with low-dose computed tomography.
We developed a comorbidity index (Prostate, Lung, Colorectal, and Ovarian comorbidity index [PLCO-ci]) using LCS-eligible participants' data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) trial (training set) and the National Lung Screening Trial (NLST) (validation set). PLCO-ci predicts five-year non-lung cancer (LC) mortality using a regularized Cox model; with performance evaluated using the area under the receiver operating characteristics curve. In NLST, LC mortality (per original publication) was compared between low-dose computed tomography and chest radiograph arms across the PLCO-ci quintile (Q1-5) using a cause-specific hazard ratio (csHR) with 95% confidence intervals (CIs).
Analyses included 34,690 PLCO and 53,452 NLST participants (mean age: 62 y [±5 y] and 61 y [±5 y], 58% and 59% male individuals, and 39% and 41% active smokers, respectively). PLCO-ci predicted five-year non-LC mortality with an area under the receiver operating characteristics curve of 0.72 (95% CI: 0.71-0.74) in PLCO and 0.69 (95% CI: 0.67-0.70) in NLST. In NLST, at a median follow-up of 6.5 years, LC mortality was significantly reduced for participants with intermediate comorbidity (Q2, Q3, and Q4): csHR 0.62 (95% CI: 0.41-0.95), 0.68 (95% CI: 0.48-0.96), and 0.72 (95% CI: 0.54-0.96) respectively, with a nonstatistically significant reduction for Q1 (csHR = 0.72, 95% CI: 0.45-1.17) and no reduction for Q5 participants (csHR = 0.99, 95% CI: 0.79-1.23). Participants in Q2, Q3, and Q4 (60%) accounted for 89% of LC deaths averted among all NLST participants. Q1 participants had low LC incidence, whereas Q5 had higher localized LC lethality, more squamous cell carcinomas, and untreated LC.
The PLCO-ci developed in this work shows that individuals with intermediate comorbidity benefited the most from LCS, highlighting the need of addressing comorbidities to achieve LC mortality benefits.
评估合并症如何影响低剂量计算机断层扫描肺癌筛查（LCS）的死亡率获益。
我们利用前列腺、肺癌、结直肠癌和卵巢癌（PLCO）试验（训练集）和国家肺癌筛查试验（NLST）（验证集）中符合LCS条件参与者的数据，开发了一种合并症指数（前列腺、肺、结直肠和卵巢合并症指数[PLCO-ci]）。PLCO-ci使用正则化Cox模型预测五年非肺癌（LC）死亡率；使用受试者工作特征曲线下面积评估其性能。在NLST中，使用特定病因风险比（csHR）及95%置信区间（CI），比较低剂量计算机断层扫描组和胸部X光检查组在PLCO-ci五分位数（Q1-5）中的LC死亡率（根据原始出版物）。
分析纳入了34,690名PLCO参与者和53,452名NLST参与者（平均年龄分别为62岁[±5岁]和61岁[±5岁]，男性分别占58%和59%，现吸烟者分别占39%和41%）。PLCO-ci在PLCO中预测五年非LC死亡率的受试者工作特征曲线下面积为0.72（95%CI：0.71-0.74），在NLST中为0.69（95%CI：0.67-0.70）。在NLST中，中位随访6.5年时，合并症中等（Q2、Q3和Q4）的参与者LC死亡率显著降低：csHR分别为0.62（95%CI：0.41-0.95）、0.68（95%CI：0.48-0.96）和0.72（95%CI：0.54-0.96），Q1参与者降低不显著（csHR = 0.72，95%CI：0.45-1.17），Q5参与者未降低（csHR = 0.99，95%CI：0.79-1.23）。Q2、Q3和Q4的参与者（占60%）占所有NLST参与者中避免的LC死亡的89%。Q1参与者的LC发病率低，而Q5的局部LC致死率更高，鳞状细胞癌更多，且LC未得到治疗。
本研究中开发的PLCO-ci表明，合并症中等的个体从LCS中获益最大，突出了处理合并症以实现LC死亡率获益的必要性。
