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    Clinical outcomes of concomitant use of proton pump inhibitors and regorafenib in patients with metastatic colorectal cancer: A multicenter study
    (LIPPINCOTT WILLIAMS & WILKINS, 2022) Yekedüz, Emre; Özbay, Mehmet Fatih; Çağlayan, Dilek; Yıldırım, Atila; Erol, Cihan; Yıldırım, Hasan Çağrı; Tunç, Sezai; Özyurt, Neslihan; Özdemir, Feyyaz; Şendur, Mehmet Ali Nahit; Kılıçkap, Saadettin
    Clinical outcomes of concomitant use of proton pump inhibitors and regorafenib in patients with metastatic colorectal cancer: A multicenter study
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    Crizotinib efficacy and safety in patients with advanced NSCLC harboring MET alterations: a real-life data of Turkish oncology group
    (Lippincott Williams and Wilkins, 2022) Gürbüz, Mustafa; Bilici, Ahmet; Karadurmuş, Nuri; Sezer, Ahmet; Şendur, Mehmet Ali Nahit; Paydaş, Semra; Artaç, Mehmet; Fulden Yumuk, Perran; Gürsoy, Pınar; Uysal, Mükremin; Şenol Coşkun, Hasan; Kılıçkap, Saadettin
    Crizotinib is a multikinase inhibitor, effective in non-small cell lung cancer (NSCLC) harboring mesenchymal-epidermal transition (MET) alterations. Although small prospective studies showed efficacy and safety of crizotinib in NSCLC with MET alterations, there is limited real-life data. Aim of this study is to investigate real-life efficacy and safety of crizotinib in patients with advanced NSCLC harboring MET alterations. This was a retrospective, multicenter (17 centers) study of Turkish Oncology Group. Patients’ demographic, histological data, treatment, response rates, survival outcomes, and toxicity data were collected. Outcomes were presented for the study population and compared between MET alteration types. Total of 62 patients were included with a median age of 58.5 (range, 26–78). Major histological type was adenocarcinoma, and 3 patients (4.8%) had sarcomatoid component. The most common MET analyzing method was next generation sequencing (90.3%). MET amplification and mutation frequencies were 53.2% (n = 33) and 46.8% (n = 29), respectively. Overall response rate and disease control rate were 56.5% and 74.2% in whole study population, respectively. Median progression free survival (PFS) was 7.2 months (95% confidence interval [CI]: 3.8–10.5), and median overall survival (OS) was 18.7 months (95% CI: 13.7–23.7), regardless of treatment line. Median PFS was 6.1 months (95% CI: 5.6–6.4) for patients with MET amplification, whereas 14.3 months (95% CI: 6.7–21.7) for patients with MET mutation (P = .217). Median PFS was significantly longer in patients who have never smoked (P = .040), have good performance score (P < .001), and responded to the treatment (P < .001). OS was significantly longer in patients with MET mutation (25.6 months, 95% CI: 15.9–35.3) compared to the patients with MET amplification (11.0 months; 95% CI: 5.2–16.8) (P = .049). In never-smokers, median OS was longer than smoker patients (25.6 months [95% CI: 11.8–39.3] vs 16.5 months [95% CI: 9.3–23.6]; P = .049). The most common adverse effects were fatigue (50%), peripheral edema (21%), nausea (29%) and diarrhea (19.4%). Grade 3 or 4 adverse effects were observed in 6.5% of the patients. This real-life data confirms efficacy and safety of crizotinib in the treatment of advanced NSCLC harboring MET alteration.
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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.
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    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, Saadettin
    ObjectiveTo 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.
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    Treatment patterns and attrition in metastatic renal cell carcinoma: real-life experience from the Turkish oncology group kidney cancer consortium (TKCC) database
    (CIG media group, 2024) Bölek, Hatice; Sertesen, Elif; Kuzu, Ömer Faruk; Tural, Deniz; Sim, Saadet; Şendur, Mehmet Ali Nahit; Uçar, Gökhan; Işık, Selver; Hacıoğlu, Bekir; Çiçin, İrfan; Arslan, Çağatay; Göksu, Sema Sezgin; Sever, Özlem Nuray; Karaçin, Cengiz; Karadurmuş, Nuri; Özgüroğlu, Mustafa; Yekedüz, Emre; Ürün, Yüksel
    The inclusion of patients with more favorable prognoses in clinical trials imits generalizability to broader and more diverse patient group. This study examines treatment patterns and attrition rates in Turkish oncology clinics for metastatic renal cell carcinoma. The percentages of patients receiving treatment in the second, third, and fourth lines of therapy were 62.8%, 27.4%, and 8.9%, respectively. Disease progression was the primary cause of attrition, followed by toxicity. Introduction: Despite the rapid evolution in management of metastatic renal cell carcinoma (mRCC) over the past decade, challenges remain in accessing new therapies in some parts of the world. Despite therapeutic advancements, attrition rates remain persistently high. This study aims to assess the treatment patterns and attrition rates of patients with mRCC in oncology clinics across Turkey. Patients and Methods: Patients diagnosed with mRCC between January 1, 2008, and December 31, 2022, with first-line systemic treatment data, were retrospectively evaluated using the Turkish Oncology Group Kidney Cancer Consortium (TKCC) Database. Results: The final analysis included a total of 1126 patients. The percentages of patients treated in the 2nd, 3rd, 4th, and 5th lines of therapy were 62.8%, 27.4%, 8.9%, and 2.1%, respectively. The drugs that were most commonly used in the groups were tyrosine kinase inhibitors (TKIs) (52.2%) and interferon (IFN)-alpha (43.3%) for the first line, TKIs (66.3%) and immunotherapy (IO) monotherapy (25.9%) for the second line, TKI (41.4%) and mTOR inhibitors (28.8%) for the third line, TKI (44.4%) and mTOR inhibitors (29%) for the fourth line, and IO monotherapy (37.5%) and TKI (25%) for the fifth line. For the first-line treatment, the primary cause of attrition was disease progression (66.4%), followed by toxicity (16.5%), death (11.2%), and patient preference (5.9%). The primary reason for attrition across all treatment lines was disease progression. Over time, the use of TKIs in first-line treatment increased, while IFN-alpha usage declined. IOs began to be utilized in earlier lines, predominantly in second-line treatment, though use of IO-based combination therapies remains limited. Conclusion: This study underscores that despite significant progress in therapeutic options, the adoption of novel agents remains slow, and attrition rates are still high. These findings indicate a disparity in systemic therapy compared to developed countries.