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    Enhancing Treatment Decisions for Advanced Non-Small Cell Lung Cancer with Epidermal Growth Factor Receptor Mutations: A Reinforcement Learning Approach †
    (Multidisciplinary Digital Publishing Institute (MDPI), 2025) Bozcuk, Hakan Şat; Sert, Leyla; Kaplan, Muhammet Ali; Tatlı, Ali Murat; Karaca, Mustafa; Muğlu, Harun; Bilici, Ahmet; Kılıçtaş, Bilge Şah; Artaç, Mehmet; Erel, Pınar; Yumuk, Perran Fulden; Bilgin, Burak; Şendur, Mehmet Ali Nahit; Kılıçkap, Saadettin; Taban, Hakan; Ballı, Sevinç; Demirkazık, Ahmet; Akdağ, Fatma; Hacıbekiroğlu, İlhan; Güzel, Halil Göksel; Koçer, Murat; Gürsoy, Pınar; Köylü, Bahadır; Selçukbiricik, Fatih; Karakaya, Gökhan; Alemdar, Mustafa Serkan
    Background: Although higher-generation TKIs are associated with improved progression-free survival in advanced NSCLC patients with EGFR mutations, the optimal selection of TKI treatment remains uncertain. To address this gap, we developed a web application powered by a reinforcement learning (RL) algorithm to assist in guiding initial TKI treatment decisions. Methods: Clinical and mutational data from advanced NSCLC patients were retrospectively collected from 14 medical centers. Only patients with complete data and sufficient follow-up were included. Multiple supervised machine learning models were tested, with the Extra Trees Classifier (ETC) identified as the most effective for predicting progression-free survival. Feature importance scores were calculated by the ETC, and features were then integrated into a Deep Q-Network (DQN) RL algorithm. The RL model was designed to select optimal TKI generation and a treatment line for each patient and was embedded into an open-source web application for experimental clinical use. Results: In total, 318 cases of EGFR-mutant advanced NSCLC were analyzed, with a median patient age of 63. A total of 52.2% of patients were female, and 83.3% had ECOG scores of 0 or 1. The top three most influential features identified were neutrophil-to-lymphocyte ratio (log-transformed), age (log-transformed), and the treatment line of TKI administration, as tested by the ETC algorithm, with an area under curve (AUC) value of 0.73, whereas the DQN RL algorithm achieved a higher AUC value of 0.80, assigning distinct Q-values across four TKI treatment categories. This supports the decision-making process in the web-based ‘EGFR Mutant NSCLC Treatment Advisory System’, where clinicians can input patient-specific data to receive tailored recommendations. Conclusions: The RL-based web application shows promise in assisting TKI treatment selection for EGFR-mutant advanced NSCLC patients, underscoring the potential for reinforcement learning to enhance decision-making in oncology care. © 2025 by the authors.