Noninvasive Computed Tomography-based Risk Stratification of Lung Adenocarcinomas in the National Lung Screening Trial

Abstract

Rationale: Screening for lung cancer using low-dose computed tomography (CT) reduces lung cancer mortality. However, in addition to a high rate of benign nodules, lung cancer screening detects a large number of indolent cancers that generally belong to the adenocarcinoma spectrum. Individualized management of screen-detected adenocarcinomas would be facilitated by noninvasive risk stratification.

Objectives: To validate that Computer-Aided Nodule Assessment and Risk Yield (CANARY), a novel image analysis software, successfully risk stratifies screen-detected lung adenocarcinomas based on clinical disease outcomes.

Methods: We identified retrospective 294 eligible patients diagnosed with lung adenocarcinoma spectrum lesions in the low-dose CT arm of the National Lung Screening Trial. The last low-dose CT scan before the diagnosis of lung adenocarcinoma was analyzed using CANARY blinded to clinical data. Based on their parametric CANARY signatures, all the lung adenocarcinoma nodules were risk stratified into three groups. CANARY risk groups were compared using survival analysis for progression-free survival.

Measurements and main results: A total of 294 patients were included in the analysis. Kaplan-Meier analysis of all the 294 adenocarcinoma nodules stratified into the Good, Intermediate, and Poor CANARY risk groups yielded distinct progression-free survival curves (P < 0.0001). This observation was confirmed in the unadjusted and adjusted (age, sex, race, and smoking status) progression-free survival analysis of all stage I cases.

Conclusions: CANARY allows the noninvasive risk stratification of lung adenocarcinomas into three groups with distinct post-treatment progression-free survival. Our results suggest that CANARY could ultimately facilitate individualized management of incidentally or screen-detected lung adenocarcinomas.

Keywords: image analysis; individualized medicine; lung adenocarcinoma; risk stratification.

Figure 1.

Consolidated Standards of Reporting Trials–style diagram outlining the cases included into the Computer-Aided Nodule Assessment and Risk Yield analysis. CT = computed tomography.

Figure 2.

The distribution of the Computer-Aided Nodule Assessment and Risk Yield (CANARY) patterns and parametric signature. Representative adenocarcinoma nodules quantitatively characterized using CANARY are shown for the three CANARY risk groups, Good (G), Intermediate (I), and Poor (P). (A) Raw computed tomography axial sections illustrating the nodule. (B) The computed tomography sections overlaid with CANARY pattern colors. (C) The three-dimensional rendering of the nodule. (D) Glyphs of the analyzed nodules.

Figure 3.

Montage of Computer-Aided Nodule Assessment and Risk Yield glyphs of the adenocarcinoma nodules stratified based on the identified three risk groups: Good (G), Intermediate (I), and Poor (P).

Figure 4.

Progression-free survival based on Computer-Aided Nodule Assessment and Risk Yield Good, Intermediate, and Poor groups using low-dose computed tomography for patients diagnosed with adenocarcinoma during the National Lung Screening Trial. (A) All 294 cases. (B) All 218 pathologic stage I cases.