Differences in Patient Outcomes of Prevalence, Interval, and Screen-Detected Lung Cancers in the CT Arm of the National Lung Screening Trial
Differences in Patient Outcomes of Prevalence, Interval, and Screen-Detected Lung Cancers in the CT Arm of the National Lung Screening Trial
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DOI：
10.1371/journal.pone.0159880
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发表时间：
2016-08-10
期刊：
影响因子：
3.7
通讯作者：
Gillies, Robert J.
中科院分区：
文献类型：
--
作者：
Schabath, Matthew B.;Massion, Pierre P.;Gillies, Robert J.
肺癌筛查可识别具有异质性行为的癌症。一些肺癌将在先前CT筛查阴性的患者中被发现，并在后续扫描中发展为新生结节，被确定为癌症。其他肺癌将在先前有一次或多次稳定阳性扫描但未被确定为肺癌(不确定的肺结节)，但在后续扫描中被诊断为肺癌的患者中识别。使用来自国家肺筛查试验的CT ARM的数据，这项分析调查了根据筛查结果的顺序，在患病率、间隔期和筛查检测到的肺癌之间患者特征和生存终点的差异。肺癌在阳性基线(T0)之后和T1筛查之前立即形成流行队列。在下一轮筛查之前的任何时间点，都会在阴性筛查后诊断出间歇性癌症。两组筛查发现的肺癌(SDLC)的基线阳性筛查未被确定为肺癌(即不确定的肺结节)，但在随访扫描中被诊断为12个月(SDLC 1)或24个月(SDLC 2)的肺癌发病率。另外两个发病队列进行了基线阴性筛查发现的肺癌，在随访扫描后，12个月(SDLC 3)或24个月(SDLC 4)出现了一个新生结节，被确定为癌症。评估患者特征、无进展生存期(PFS)和总生存期(OS)的差异。SDLC3/SDLC4的肺癌特定死亡率高于SDLC1/SDLC2肺癌(136.6/1,000人年vs.71.3/1,000人年，P<；0.001)。此外，与SDLC 1/SDLC 2相比，SDLC 3/SDLC 4的PFS和OS显著降低(P<；0.004；P<；0.002)。当按分期和组织学分层时，这些发现是一致的。多变量COX比例模型显示，SDLC3/SDLC4病例组的PFS(HR=1.89；95%CI 1.31~2.74)和OS(HR=1.80；95%CI 1.21~2.67)显著低于SDLC1/SDLC2肺癌(HR=1.00)。与癌症诊断前至少有一次阳性筛查的患者相比，出现新生结节并被确定为癌症(即在癌症诊断前至少有一次CT阴性筛查)的肺癌患者的生存结果较差。因此，观察到新发现的筛查与较差的存活率相关，可能归因于生长更快、更具侵袭性的癌症，这些癌症发生在以前缺乏局灶性异常的肺部环境中。
Lung cancer screening identifies cancers with heterogeneous behaviors. Some lung cancers will be identified among patients who had prior negative CT screens and upon follow-up scans develop a de novo nodule that was determined to be cancerous. Other lung cancers will be identified among patients who had one or more prior stable positive scans that were not determined to be lung cancer (indeterminate pulmonary nodules), but in follow-up scans was diagnosed with an incidence lung cancer. Using data from the CT arm of the National Lung Screening Trial, this analysis investigated differences in patient characteristics and survival endpoints between prevalence-, interval-, and screen-detected lung cancers, characterized based on sequence of screening results. Lung cancers immediately following a positive baseline (T0), and prior to the T1 screen, formed the prevalence cohort. Interval cancers were diagnosed following a negative screen at any time point prior to the next screening round. Two cohorts of screen-detected lung cancers (SDLC) were identified that had a baseline positive screen that was that was not determined to be lung cancer (i.e., an indeterminate pulmonary nodule), but in follow-up scans was diagnosed with an incidence lung cancer 12 (SDLC1) or 24 (SDLC2) months later. Two other incidence cohorts had screen-detected lung cancers that had baseline negative screen and upon follow-up scans developed a de novo nodule determined to be cancerous at 12 (SDLC3) or 24 (SDLC4) months later. Differences in patient characteristics, progression-free survival (PFS), and overall survival (OS) were assessed. The lung cancer-specific death rate was higher for SDLC3/SDLC4 compared to SDLC1/SDLC2 lung cancers (136.6/1,000 person-years vs. 71.3/1,000 person-years, P < 0.001). Moreover, PFS and OS were significantly lower for SDLC3/SDLC4 compared to SDLC1/SDLC2 (P < 0.004; P < 0.002, respectively). The findings were consistent when stratified by stage and histology. Multivariable Cox proportional models revealed that the SDLC3/SDLC4 case groups were associated with significantly poorer PFS (HR = 1.89; 95% CI 1.31-2.74) and OS (HR = 1.80; 95% CI 1.21-2.67) compared to SDLC1/SDLC2 lung cancers (HR = 1.00). Lung cancer patients who develop a de novo nodule that determined to be cancerous (i.e., at least one negative CT screen prior to cancer diagnosis) had poorer survival outcomes compared to patients who had at least one positive screen prior to cancer diagnosis. As such, the observation that de novo screen-detected are associated with poorer survival could be attributed to faster growing, more aggressive cancers that arose from a lung environment previously lacking focal abnormalities.