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Öğe The Efficacy and Safety of Treatment Regimens Used in the First-Line Setting in Metastatic Pancreatic Cancer Patients A Multicenter Real-Life Study(Lippincott Williams & Wilkins, 2022) Akdeniz, Nadiye; Kaplan, Muhammet Ali; Inanc, Mevlude; Uncu, Dogan; Ergun, Yakup; Kucukoner, Mehmet; Demirci, AyseObjectiveThe aim of the study is to compare the efficacy and safety of 3 chemotherapy regimens used as first-line treatments in the real-life management of metastatic pancreatic cancer.MethodsA total of 218 patients were included in this multicenter study. Gemcitabine (Gem, n = 71), gemcitabine-cisplatin (Gem-Cis, n = 91), and FOLFIRINOX (a combination of leucovorin, 5-fluorouracil, irinotecan, and oxaliplatin [FFX], n = 56) treatments were compared.ResultsOverall response rate was significantly higher in the FFX group (50.0%) than in the Gem (28.2%) and Gem-Cis (27.5%) groups (P = 0.010). Median progression-free survival (8.4 vs 4.6 and 5.5 months, respectively, P < 0.001) and overall survival (16.4 vs 8.1 and 8.7 months, respectively, P = 0.002) were significantly longer in the FFX group than in the Gem and Gem-Cis groups. Toxicity of any grade was noted in 46 (64.8%), 56 (61.5%), and 49 (87.5%) patients in the Gem, Gem-Cis, and FFX groups, respectively (P = 0.003).ConclusionsIn our study, FFX regimen provides a significant advantage over the other treatment regimens in terms of response rates and survival. Treatment toxicity was more frequent but manageable with the FFX regimen.Öğe 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 SerkanBackground: 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.Öğe Established and new treatment roadmaps for pleural mesothelioma: opinions of the Turkish Collaborative Group(Mosby-Elsevier, 2023) Kaplan, Muhammet Ali; Sendur, Mehmet Ali Nahit; Cangir, Ayten Kayi; Firat, Pinar; Goker, Erdem; Kilickap, Saadettin; Oyan, BasakPleural mesothelioma (PM) is a cancer of the pleural surface, which is aggressive and may be rapidly fa-tal. PM is a rare cancer worldwide, but is a relatively common disease in Turkey. Asbestos exposure is the main risk factor and the most common underlying cause of the disease. There have been significant im-provements in diagnoses and treatments of many malignancies; however, there are still therapeutic chal-lenges in PM. In this review, we aimed to increase the awareness of health care professionals, oncolo-gists, and pulmonologists by underlining the unmet needs of patients with PM and by emphasizing the need for a multidisciplinary treatment and management of PM. After reviewing the general information about PM, we further discuss the treatment options for patients with PM using immunotherapy and offer evidence for improvements in the clinical outcomes of these patients because of these newer treatment modalities.(c) 2023 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )Öğe Evaluation of the efficacy and safety of nivolumab in the second- or later-line treatment of patients with locally advanced/metastatic non-small cell lung cancer in Türkiye: a retrospective multicenter non-interventional registry study(Taylor & francis LTD, 2024) Karadurmuş, Nuri; Kaplan, Muhammet Ali; Şendur, Mehmet Ali Nahit; Urun, Yuksel; Demirci, Umut; Karaca, Şaziye Burçak; Aydın, Sabin Göktaş; Aykan, Musa Barış; Bilici, Ahmet; Sezer, Ahmet; Yılmaz, Ülkü; Abalı, Hüseyin; Yumuk, Perran Fulden; Değirmencioğlu, Serkan; Demirkazık, Ahmet; Paydaş, Semra; Mirili, Cem; Turna, Hande; Kargı, Ayşegül; Özdoğan, Mustafa; Güven, Deniz Can; Özgüroğlu, Mustafa; Kılıçkap, SaadettinObjectiveTo evaluate the efficacy and safety of nivolumab in the second-line (2L) or later-line (LL) treatment of patients with locally advanced/metastatic non-small cell lung cancer (NSCLC) in real-life setting in T & uuml;rkiye.MethodsThis study was designed as a national, multi-center, retrospective study. The study population was evaluated in two groups for the line of nivolumab therapy: those receiving nivolumab in the 2L (Group 2L) and third-line (3L) or LL (Group 3L/LL). Efficacy was evaluated based on one-year overall survival (OS) and progression-free survival (PFS). Safety was evaluated based on treatment-related adverse events (AEs) and nivolumab discontinuation rate.ResultsOf 244 patients, 52.9% were in Group 2L and 47.1% were in Group 3L/LL. Demographic and clinical characteristics did not differ between the groups. In Group 2L and Group 3L/LL, one-year OS and PFS rates were 60.8% and 61.4% (p = 0.592) and 31.2% and 21.3% (p = 0.078), respectively. The objective response rate (ORR) was 34.7% in Group 2L and 27.3% in Group 3L/LL (p = 0.262). The percentage of patients reporting at least one AE in Groups 2L and 3L/LL was 34.9% and 43.5%, respectively (p = 0.169). Fatigue was the most common (16.4%) treatment-related AE in each group. The groups were comparable regarding the AE frequency. Nivolumab was discontinued in 61 patients in Group 2L and 53 patients in Group 3L/LL, with the most common reason being disease progression (57.4% and 66.0%, respectively).ConclusionNivolumab is safe and effective in the 2L or 3L/LL treatment of locally advanced/metastatic NSCLC and associated with acceptable AEs in real-life setting. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer (around 85% of all lung cancers). Patients with NSCLC are usually diagnosed at advanced or metastatic stages. When cancer cells spread to other areas from where they first formed, it is called metastatic cancer. Surgery may not be a treatment option for such patients. Currently, immunotherapeutic agents are used in the treatment of NSCLC. Nivolumab is one of the approved immunotherapeutic agents in the treatment of patients with metastatic NSCLC, who have failed after receiving chemotherapy. Our study explored the efficacy and safety of nivolumab in real-life setting in T & uuml;rkiye. Nivolumab effectiveness was evaluated by overall survival (OS) and progression-free survival (PFS) rates. OS indicates the proportion of patients who are still alive at a given time after diagnosis or treatment initiation. PFS refers to "the length of time during and after cancer treatment that a person lives with the disease but does not get worse." In the present study, one-year OS for 244 patients who received nivolumab was 61.1% and one-year PFS was 26.4%. Nivolumab safety was evaluated based on the frequency of adverse events observed during nivolumab therapy. Of the patients 38.9% had at least one side effect, with fatigue being the most common (16.4%). Our results support the earlier studies and showed that nivolumab was a safe and effective agent and is associated with acceptable side effects.
