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Updated: Oct 4, 2025

Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
Machine Learning-Based Analysis of Treatment Sequences Typology in Advanced Non-Small-Cell Lung Cancer Long-Term
Christos Chouaïd1, Valentine Grumberg2, Alexandre Batisse3
1Service de pneumologie, Centre Hospitalier Intercommunal de Créteil, Créteil, France.
Purpose:
Immune checkpoint inhibitors substantially changed advanced non-small-cell lung cancer (aNSCLC) management and can lead to long-term survival. The aims of this study were (1) to use a machine learning method to establish a typology of treatment sequences on patients with aNSCLC who were alive 2 years after initiating a treatment with anti-programmed death-ligand 1 monoclonal antibody nivolumab and (2) to describe the patients' characteristics according to the typology of treatment sequences.
Materials And Methods:
This retrospective observational study was based on data from the comprehensive French hospital discharge database for all patients with lung cancer with at least one line of platinum-based chemotherapy, starting nivolumab between January 1, 2015, and December 31, 2016, and alive 2 years after nivolumab treatment initiation. Patients were followed until December 31, 2018. A typology of most common treatment sequences was established using hierarchical clustering with time sequence analysis.
Results:
Two thousand two hundred twelve study patients were, on average, 63.0 years old, 69.9% of them were men, and 61.9% had a nonsquamous cell carcinoma. During the 2 years after nivolumab treatment initiation, clusters of patients with four basic types of treatment sequences were identified: (1) almost continuous nivolumab treatment (44% of patients); (2) nivolumab most of the time followed by a treatment-free interval or a chemotherapy (15% of patients); and a short or medium nivolumab treatment, followed by (3) a long systemic treatment-free interval (17% of patients) or (4) a long chemotherapy (23% of patients).
Conclusion:
This machine learning approach enabled the identification of a typology of four representative treatment sequences observed in long-term survival. It was noted that most long-term survivors were treated with nivolumab for well over 1 year.
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