Machine learning models for identifying predictors of clinical outcomes with first-line immune checkpoint inhibitor therapy in advanced non-small cell lung cancer.

TitleMachine learning models for identifying predictors of clinical outcomes with first-line immune checkpoint inhibitor therapy in advanced non-small cell lung cancer.
Publication TypeJournal Article
Year of Publication2022
AuthorsLi Y, Brendel M, Wu N, Ge W, Zhang H, Rietschel P, Quek RGW, Pouliot J-F, Wang F, Harnett J
JournalSci Rep
Volume12
Issue1
Pagination17670
Date Published2022 Oct 21
ISSN2045-2322
KeywordsCarcinoma, Non-Small-Cell Lung, Clinical Trials as Topic, Humans, Immune Checkpoint Inhibitors, Ligands, Lung Neoplasms, Machine Learning, Prospective Studies, Retrospective Studies, Serum Albumin
Abstract

Immune checkpoint inhibitors (ICIs) are standard-of-care as first-line (1L) therapy for advanced non-small cell lung cancer (aNSCLC) without actionable oncogenic driver mutations. While clinical trials demonstrated benefits of ICIs over chemotherapy, variation in outcomes across patients has been observed and trial populations may not be representative of clinical practice. Predictive models can help understand heterogeneity of treatment effects, identify predictors of meaningful clinical outcomes, and may inform treatment decisions. We applied machine learning (ML)-based survival models to a real-world cohort of patients with aNSCLC who received 1L ICI therapy extracted from a US-based electronic health record database. Model performance was evaluated using metrics including concordance index (c-index), and we used explainability techniques to identify significant predictors of overall survival (OS) and progression-free survival (PFS). The ML model achieved c-indices of 0.672 and 0.612 for OS and PFS, respectively, and Kaplan-Meier survival curves showed significant differences between low- and high-risk groups for OS and PFS (both log-rank test pā€‰<ā€‰0.0001). Identified predictors were mostly consistent with the published literature and/or clinical expectations and largely overlapped for OS and PFS; Eastern Cooperative Oncology Group performance status, programmed cell death-ligand 1 expression levels, and serum albumin were among the top 5 predictors for both outcomes. Prospective and independent data set evaluation is required to confirm these results.

DOI10.1038/s41598-022-20061-6
Alternate JournalSci Rep
PubMed ID36271096
PubMed Central IDPMC9586943
Division: 
Institute of Artificial Intelligence for Digital Health
Category: 
Faculty Publication