Abstract
Objectives: To identify a computed tomography (CT)-based radiomic signature for predicting progression-free survival (PFS) in stage IV anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC) patients treated with tyrosine kinase inhibitor (TKI) crizotinib.Materials and Methods: This retrospective proof-of-concept study included a cohort of 63 stage IV ALK-positive NSCLC patients who had received TKI crizotinib therapy for model construction and validation. Another independent cohort including 105 stage IV EGFR-positive NSCLC patients was also used for external validation in EGFR-TKI treatment. We initially extracted 481 quantitative three-dimensional features derived from manually segmented tumor volumes of interest. Pearson's correlation analysis along with the least absolute shrinkage and selection operator (LASSO) penalized Cox proportional hazards regression was successively performed to select critical radiomic features. A CT-based radiomic signature for PFS prediction was obtained using multivariate Cox regression. The performance evaluation of the radiomic signature was conducted using the concordance index (C-index), time-dependent receiver operating characteristic (ROC) analysis, and Kaplan–Meier survival analysis.Results: A radiomic signature containing three features showed significant prognostic performance for ALK-positive NSCLC patients in both the training cohort (C-index, 0.744; time-dependent AUC, 0.895) and the validation cohort (C-index, 0.717; time-dependent AUC, 0.824). The radiomic signature could significantly risk-stratify ALK-positive NSCLC patients (hazard ratio, 2.181; P < 0.001) and outperformed other prognostic factors. However, no significant association with PFS was captured for the radiomic signature in the EGFR-positive NSCLC cohort (log-rank tests, P = 0.41).Conclusions: The CT-based radiomic features can capture valuable information regarding the tumor phenotype. The proposed radiomic signature was found to be an effective prognostic factor in stage IV ALK mutated nonsynchronous nodules in NSCLC patients treated with a TKI.
Highlights
Non-small-cell lung cancer (NSCLC) accounts for 85% in lung cancer [1], making it the leading cause of cancer-related mortality across the globe [2]
Crizotinib, which is regarded as the first-line treatment for stage IV NSCLC patients with anaplastic lymphoma kinase (ALK) gene rearrangements according to the clinical practice guidelines given by the American Society of Clinical Oncology (ASCO) [4], has a proven therapeutical efficacy
In the ALK-mutant cohorts, a total of 63 patients who met the inclusion and exclusion requirements were enrolled, all of whom were stage IV ALK-mutant NSCLC treated with tyrosine kinase inhibitor (TKI) crizotinib
Summary
Non-small-cell lung cancer (NSCLC) accounts for 85% in lung cancer [1], making it the leading cause of cancer-related mortality across the globe [2]. An approximate estimate of 5% NSCLC patients are found to have rearrangements in the anaplastic lymphoma kinase (ALK) gene. Crizotinib, which is regarded as the first-line treatment for stage IV NSCLC patients with ALK gene rearrangements according to the clinical practice guidelines given by the American Society of Clinical Oncology (ASCO) [4], has a proven therapeutical efficacy. Those who respond to crizotinib may show rapid improvement in symptoms, including cough, dyspnea, and pain [5, 6]. At the genetic level, resistance to tyrosine kinase inhibitor (TKI) is hard to detect [14]
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