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Öğe Blood based biomarkers as predictive factors for hyperprogressive disease(MDPI, 2022) Yıldırım, Hasan Çağrı; Güven, Deniz Can; Aktepe, Oktay Halit; Taban, Hakan; Yılmaz, Feride; Yasar, Serkan; Aksoy, Sercan; Erman, Mustafa; Kılıçkap, Saadettin; Yalçın, SuayibPurpose: With the widespread use of immunotherapy agents, we encounter treatment responses such as hyperprogression disease (HPD) that we have not seen with previous standard chemotherapy and targeted therapies. It is known that survival in patients with HPD is shorter than in patients without HPD. Therefore, it is important to know the factors that will predict HPD. We aimed to identify HPD-related factors in patients treated with immunotherapy. Methods: A total of 121 adult metastatic cancer patients treated with immunotherapy for any cancer were included. Baseline demographics, the ECOG performance status, type of tumors and baseline blood count parameters were recorded. Possible predisposing factors were evaluated with univariate and multivariate analyses. Results: The median age was 62.28 (interquartile range (IQR) 54.02-67.63) years, and the median follow-up was 12.26 (IQR 5.6-24.36) months. Renal cell carcinoma (33%) and melanoma (33.8%) were the most common diagnoses. Twenty patients (16.5%) had HPD. A high LDH level (p: 0.001), hypoalbuminemia (p: 0.016) and an NLR > 5 (p: 0.007) were found to be associated with hyperprogression. Sex (female vs. male, p: 0.114), age (>65 vs. <65, p: 0.772), ECOG (0 vs. 1-4, p: 0.480) and the line of treatment (1-5, p: 0.112) were not found to be associated with hyperprogression. Conclusions: In this study, we observed HPD in 16.5% of immunotherapy-treated patients and increased HPD risk in patients with a high LDH level (p: 0.001), hypoalbuminemia (p: 0.016) and an NLR > 5 (p: 0.007).Öğe Crizotinib efficacy after progression with entrectinib in ROS1-Positive lung cancer: a case report(CUREUS INC, 2022) Taban, Hakan; Güven, Deniz Can; Kılıçkap, SaadettinCrizotinib and entrectinib are approved tyrosine kinase inhibitors by the FDA to treat advanced-stage ROS1-positive non-small cell lung cancer (NSCLC). Although, entrectinib could be used after crizotinib, it is unknown whether crizotinib is effective after entrectinib. We report a case of NSCLC with ROS1 rearrangement that achieved a nearly complete response with crizotinib in the second-line treatment after progression with entrectinib. A 22-year-old Caucasian non-smoker female patient was diagnosed with stage IV non-squamous lung cancer with ROS1 positivity. We started on entrectinib as first-line therapy. Due to progression in the 10th month of treatment, entrectinib was stopped and crizotinib was started as a second -line treatment. At the end of the third month of the treatment, a nearly complete response was obtained in the follow-up imaging. The patient is still being followed up with crizotinib and is in the 15th month of treatment. Based on our experience, crizotinib can be an option as second-line therapy in patients who are treated with entrectinib in the first line, especially in patients without brain metastasis.Öğe Differences between hyperprogressive disease and progressive disease in patients receiving immunotherapy(Kare Publishing, 2022) Yıldırım, Hasan Çağrı; Güven, Deniz Can; Aktepe, Oktay Halit; Taban, Hakan; Yılmaz, Feride; Yaşar, Serkan; Aktaş, Burak Yasin; Güner, Gürkan; Dizdar, Ömer; Aksoy, Sercan; Erman, Mustafa; Yalçın, Suayib; Kılıçkap, SaadettinObjectives: Although immune checkpoint inhibitors (ICIs) became a vital part of cancer care, many patients do not respond to treatment. In this group, a few of the patients with a hyperprogressive disease (HPD) have shorter overall survival (OS) compared with those having a progressive disease (PD). Therefore, biomarkers are needed to differentiate HPD and PD. Methods: Ninety-five patients treated with ICIs with progression according to response evaluation criteria ın solid tumors criteria in the first control imaging were included. HPD was defined according to Russo's work. The PILE scoring system, which includes pan-immune-inflammation value, lactate dehydrogenase, and Eastern Cooperative Oncology Group PS, was followed. The relationship between PILE score and HPD was analyzed. Results: The median OS of all cohorts was 11.18 months. The patients in the HPD group had decreased OS (4.77 vs. 13.94 months, p<0.001) and progression-free survival (PFS) (1.89 vs. 3.16 months, p<0.001) compared with those in the PD group. The risk of HPD was higher than the risk of PD in patients with a high PILE score (p=0.001). Conclusion: In this study, we showed that patients treated with ICI with a higher PILE score are at greater risk for HPD. The PILE score may be a biomarker to differentiate HPD from PD. © 2022 by Eurasian Journal of Medicine and Oncology.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 Lower prognostic nutritional index is associated with poorer survival in patients receiving ımmune-checkpoint ınhibitors(Future Medicine, 2021) Güven, Deniz C.; Aktepe, Oktay H.; Taban, Hakan; Aktaş, Burak Y.; Güner, Gürkan; Yıldırım, Hasan C.; Kılıçkap, SaadettinAim: Blood-based biomarkers like prognostic nutritional index (PNI) are readily available biomarkers for immunotherapy efficacy, although the data are limited. So, we aimed to evaluate the association between PNI and overall survival (OS) in immunotherapy-treated patients. Materials & methods: For this retrospective cohort study, data of 150 immunotherapy-treated advanced cancer patients were evaluated. The association between clinical factors and OS was evaluated with multivariate Cox-regression analyses. Results: After a median follow-up of 8.5 months, 94 patients died. The median OS was 11.07 months. The low PNI (hazard ratio [HR]: 2.065; p = 0.001), high lactate dehydrogenase (HR: 2.515; p = 0.001) and poor Eastern Cooperative Oncology Group (ECOG) status (HR: 2.164; p = 0.009) was associated with poorer OS in multivariate analyses. Conclusion: In our experience, survival with immunotherapy was impaired in patients with lower PNI and higher lactate dehydrogenase levels and poorer ECOG status.
