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Öğe Clinical and Pathologic Features of Patients with Rare Ovarian Tumors: Multi-Center Review of 167 Patients by the Anatolian Society of Medical Oncology(Asian Pacific Organization Cancer Prevention, 2013) Bilici, Ahmet; Inanc, Mevlude; Ulas, Arife; Akman, Tulay; Seker, Mesut; Babacan, Nalan Akgul; Inal, AliBackground: Non-epithelial malignant ovarian tumors and clear cell carcinomas, Brenner tumors, transitional cell tumors, and carcinoid tumors of the ovary are rare ovarian tumors (ROTs). In this study, our aim was to determine the clinicopathological features of ROT patients and prognostic factors associated with survival. Materials and Methods: A total of 167 patients with ROT who underwent initial surgery were retrospectively analyzed. Prognostic factors that may influence the survival of patients were evaluated by univariate and multivariate analyses. Results: Of 167 patients, 75 (44.9%) were diagnosed with germ-cell tumors (GCT) and 68 (40.7%) with sex cord-stromal tumors (SCST); the remaining 24 had other rare ovarian histologies. Significant differences were found between ROT groups with respect to age at diagnosis, tumor localization, initial surgery type, tumor size, tumor grade, and FIGO stage. Three-year progression-free survival (PFS) rates and median PFS intervals for patients with other ROT were worse than those of patients with GCT and SCST (41.8% vs 79.6% vs 77.1% and 30.2 vs 72 vs 150 months, respectively; p=0.01). Moreover, the 3-year overall survival (OS) rates and median OS times for patients with both GCT and SCST were better as compared to patients with other ROT, but these differences were not statistically significant (87.7% vs 88.8% vs 73.9% and 170 vs 122 vs 91 months, respectively; p=0.20). In the univariate analysis, tumor localization (p<0.001), FIGO stage (p<0.001), and tumor grade (p=0.04) were significant prognostic factors for PFS. For OS, the univariate analysis indicated that tumor localization (p=0.01), FIGO stage (p=0.001), and recurrence (p<0.001) were important prognostic indicators. Multivariate analysis showed that FIGO stage for PFS (p=0.001, HR: 0.11) and the presence of recurrence (p=0.02, HR: 0.54) for OS were independent prognostic factors. Conclusions: ROTs should be evaluated separately from epithelial ovarian cancers because of their different biological features and natural history. Due to the rarity of these tumors, determination of relevant prognostic factors as a group may help as a guide for more appropriate adjuvant or recurrent therapies for ROTs.Öğe Enhancing treatment decisions for advanced non-small cell lung cancer with epidermal growth factor receptor mutations: A Reinforcement learning approach(Mdpi, 2025) Bozcuk, Hakan Sat; Sert, Leyla; Kaplan, Muhammet Ali; Tatlı, Ali Murat; Karaca, Mustafa; Muğlu, Harun; Bilici, AhmetBackground: 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.Öğe Impact of adding pertuzumab to trastuzumab plus chemotherapy in neoadjuvant treatment of HER2 positive breast cancer patients: a multicenter real-life HER2PATH study(Taylor & Francis Ltd, 2023) Bilici, Ahmet; Olmez, Omer Fatih; Kaplan, Muhammed Ali; Oksuzoglu, Berna; Sezer, Ahmet; Karadurmus, Nuri; Cubukcu, ErdemAimTo investigate the pathological complete response (pCR) achieved after neoadjuvant therapy with versus without adding pertuzumab (P) to trastuzumab (H) plus neoadjuvant chemotherapy (NCT) in HER2+ breast cancer (BC) patients in a real-life setting.MethodsA total of 1528 female HER2+ BC patients who received NCT plus H with or without P were included in this retrospective real-life study. Primary endpoint was pCR rate (ypT0/Tis ypN0). Clinicopathological characteristics, event-free survival (EFS) time, and relapse rates were evaluated with respect to HER2 blockade (NCT-H vs. NCT-HP) and pCR.ResultsOverall, 62.2% of patients received NCT-H and 37.8% received NCT-HP. NCT-HP was associated with a significantly higher pCR rate (66.4 vs. 56.8%, p < 0.001) and lower relapse (4.5 vs. 12.2%, p < 0.001) in comparison to NCT-H. Patients with pCR had a significantly lower relapse (5.6 vs. 14.9%, p < 0.001) and longer EFS time (mean(SE) 111.2(1.9) vs. 93.9(2.7) months, p < 0.001) compared to patients with non-pCR. Patients in the NCT-HP group were more likely to receive docetaxel (75.0 vs. 40.6%, p < 0.001), while those with pCR were more likely to receive paclitaxel (50.2 vs. 40.7%, p < 0.001) and NCT-HP (41.5 vs. 32.1%, p < 0.001). Hormone receptor status and breast conservation rates were similar in NCT-HP vs. NCT-H groups and in patients with vs. without pCR. Invasive ductal carcinoma (OR, 2.669, 95% CI 1.596 to 4.464, p < 0.001), lower histological grade of the tumor (OR, 4.052, 95% CI 2.446 to 6.713, p < 0.001 for grade 2 and OR, 3.496, 95% CI 2.020 to 6.053, p < 0.001 for grade 3), lower T stage (OR, 1.959, 95% CI 1.411 to 2.720, p < 0.001) and paclitaxel (vs. docetaxel, OR, 1.571, 95% CI 1.127 to 2.190, p = 0.008) significantly predicted the pCR.ConclusionsThis real-life study indicates that adding P to NCT-H enables higher pCR than NCT-H in HER2+ BC, while pCR was associated with lower relapse and better EFS time.Öğe Outcomes of surveillance versus adjuvant chemotherapy for patients with stage IA and IB nonseminomatous testicular germ cell tumors(Springer, 2017) Gumus, Mahmut; Bilici, Ahmet; Odabas, Hatice; Ustaalioglu, Bala Basak Oven; Kandemir, Nurten; Demirci, Umut; Cihan, SenerBackground Currently, it is accepted that risk assessment of clinical stage I (CS I) nonseminomatous germ cell tumors (NSGCT) patient is mainly dependent on the presence of lymphovascular invasion (LVI). Initial active surveillance, adjuvant chemotherapy and retroperitoneal lymph node dissection (RPLND) are acceptable treatment options for these patients, but there is no uniform consensus. The purpose of this study was to compare outcomes of active surveillance with adjuvant chemotherapy. Methods A total of 201 patients with CS I NSGCT after orchiectomy were included. Outcomes of active surveillance and adjuvant chemotherapy were retrospectively analyzed. The prognostic significance of risk factors for survival and relapse was evaluated. Results Of the 201 patients, 110 (54.7%) received adjuvant chemotherapy, while the remaining 91 patients (45.3%) underwent surveillance. Relapses were significantly higher for patients underwent surveillance compared to adjuvant chemotherapy group (18.3 vs. 1.2%, p < 0.001). The 5-year relapse-free survival (RFS) rate for patients who were treated with adjuvant chemotherapy was significantly better than those of patients underwent surveillance (97.6 vs. 80.8%, respectively; p < 0.001). Univariate analysis showed that the presence of LVI (p = 0.01) and treatment option (p < 0.001) were prognostic factors for RFS and pT stage (p = 0.004) and invasion of rete testis (p = 0.004) and the presence of relapse (p < 0.001) were significant prognostic factors for OS. Multivariate analysis revealed that the treatment strategy was an independent prognostic factor for RFS (p < 0.001, HR 0.54). A logistic regression analysis demonstrated that treatment options (p = 0.031), embryonal carcinoma (EC) > 50% (p = 0.013) and tumor diameter (p = 0.016) were found to be independent factors for predicting relapse. Conclusion Our results indicate that adjuvant chemotherapy is associated with improved RFS compared with surveillance for CS I NSGCT patients. Moreover, the treatment strategy is an important prognostic indicator for RFS and a predictive factor for relapse. Although adjuvant chemotherapy seems to be a suitable treatment for patients with risk factors for relapse, surveillance is still preferred management option.Öğe Outcomes of surveillance VS. adjuvant chemotherapy for patients with STAGE IA and IB NON-seminomatous testicular germ-cell tumors.(Amer Soc Clinical Oncology, 2016) Bilici, Ahmet; Gumus, Mahmut; Odabas, Hatice; Kandemir, Nurten; Demirci, Umut; Cihan, Sener; Bayoglu, Ibrahim Vedat[Abstract Not Available]Öğe Prognostic Factors for Lymph Node Negative Stage I and IIA Non-small Cell Lung Cancer: Multicenter Experiences(Asian Pacific Organization Cancer Prevention, 2013) Ustaalioglu, Bala Basak Oven; Unal, Olcun Umit; Turan, Nedim; Bilici, Ahmet; Kaya, Serap; Eren, Tulay; Ulas, ArifeBackground: Surgery is the only curative treatment for operable non-small lung cancer (NSCLC) and the importance of adjuvant chemotherapy for stage IB patients is unclear. Herein, we evaluated prognostic factors for survival and factors related with adjuvant treatment decisions for stage I and IIA NSCLC patients without lymph node metastasis. Materials and Methods: We retrospectively analyzed 302 patients who had undergone curative surgery for prognostic factors regarding survival and clinicopathological factors related to adjuvant chemotherapy. Results: Nearly 90% of the patients underwent lobectomy or pneumonectomy with mediastinal lymph node resection. For the others, wedge resection were performed. The patients were diagnosed as stage IA in 35%, IB in 49% and IIA in 17%. Histopathological type (p=0.02), tumor diameter (p=0.01) and stage (p<0.001) were found to be related to adjuvant chemotherapy decisions, while operation type, lypmhovascular invasion (LVI), grade and the presence of recurrence were important factors in predicting overall survival (OS), and operation type, tumor size greater than 4 cm, T stage, LVI, and visceral pleural invasion were related with disease free survival (DFS). Multivariate analysis showed operation type (p<0.001, hazard ratio (HR):1.91) and the presence of recurrence (p<0.001, HR:0.007) were independent prognostic factors for OS, as well visceral pleural invasion (p=0.01, HR:0.57) and LVI (p=0.004, HR:0.57) for DFS. Conclusions: Although adjuvant chemotherapy is standard for early stage lymph node positive NSCLC, it has less clear importance in stage I and IIA patients without lymph node metastasis.Öğe Prognostic factors for survival in metastatic renal cell carcinoma patients with brain metastases receiving targeted therapy(Sage Publications Ltd, 2018) Yildiz, Ibrahim; Bilici, Ahmet; Karadurmus, Nuri; Ozer, Leyla; Tural, Deniz; Kaplan, Mehmet A.; Akman, TulayBackground: The primary objective of our study was to examine the clinical outcomes and prognosis of patients with metastatic renal cell carcinoma (mRCC) with brain metastases (BMs) receiving targeted therapy. Patients and methods: Fifty-eight patients from 16 oncology centers for whom complete clinical data were available were retrospectively reviewed. Results: The median age was 57 years (range 30-80). Most patients underwent a nephrectomy (n = 41; 70.7%), were male (n = 42; 72.4%) and had clear-cell (CC) RCC (n = 51; 87.9%). Patients were treated with first-line suni-tinib (n = 45; 77.6%) or pazopanib (n = 13; 22.4%). The median time from the initial RCC diagnosis to the diagnosis of BMs was 9 months. The median time from the first occurrence of metastasis to the development of BMs was 7 months. The median overall survival (OS) of mRCC patients with BMs was 13 months. Time from the initial diagnosis of systemic metastasis to the development of BMs (<12 months; p = 0.001), histological subtype (non-CC; p<0.05) and number of BMs (>2; p<0.05) were significantly associated with OS in multivariate analysis. There were no cases of toxic death. One mRCC patient with BMs (1.7%) experienced treatment-related cerebral necrosis. All other toxicities included those commonly observed with VEGF-TKI therapy. Conclusions: The time from the initial diagnosis of systemic metastasis to the development of BMs (<12 months), a non-CC histological subtype, and a greater number of BMs (>2) were independent risk factors for a poor prognosis.Öğe Real-life analysis of efficacy and safety of everolimus plus exemestane in hormone receptor-positive, human epidermal growth factor receptor-2-negative metastatic breast cancer patients: A Turkish Oncology Group (TOG) study(Taylor & Francis, 2022) Bilici, Ahmet; Uysal, Mükremin; Menekşe, Serkan; Akın, Semih; Yıldız, Fatih; Turan, Merve; Kaplan, Muhammet AliPurpose This study evaluated the efficacy and safety of everolimus (EVE) plus exemestane (EXE) in hormone-receptor positive (HR+), human epidermal growth factor receptor-2-negative (HER2-) metastatic breast cancer (MBC) patients in real-life settings. Methods Overall, 204 HR+, HER2- MBC patients treated with EVE + EXE after progressing following prior endocrine treatment were included. Overall survival (OS) and progression-free survival (PFS) and safety data were analyzed. Results The objective response rate, median PFS, and median OS were 33.4%, 8.9 months, and 23.4 months, respectively. Multivariate analysis revealed that negative progesterone receptor status was a significant determinant of poor treatment response (p = 0.035) and PFS (p = 0.024). The presence of bone-only metastasis was associated with better treatment response (p = 0.002), PFS (p < 0.001), and OS (p = 0.001). Conclusion We confirmed the favorable efficacy and safety profile of EVE + EXE for HR+, HER - MBC patients.Öğe Real-life analysis of pathologic complete response with neoadjuvant trastuzumab plus taxane with or without pertuzumab therapy in HER2 positive locally-advanced breast cancer (HER2PATH Study).(Lippincott Williams & Wilkins, 2022) Bilici, Ahmet; Olmez, Omer Fatih; Sezer, Ahmet; Oksuzoglu, Berna; Kaplan, Muhammet Ali; Karadurmus, Nuri; Cubukcu, Erdem[Abstract Not Available]Öğe Real-world outcomes of pazopanib in metastatic soft tissue sarcoma: a retrospective Turkish oncology group (TOG) study(Springer Science and Business Media, 2023) Bilici, Ahmet; Koca, Sinan; Karaaǧaç, Mustafa; Aydın, Sabin Göktaş; Eraslan, Emrah; Kaplan, Muhammed AliAim: Description of patient characteristics, effectiveness and safety in Turkish patients treated with pazopanib for metastatic soft tissue sarcoma (STS). Patients and methods: This multicenter study is based on retrospective review of hospital medical records of patients (≥ 18 years) treated with pazopanib for non-adipocytic metastatic STS at 37 Oncology clinics across Turkey. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS) were evaluated with further analysis of data on the three most common histological subtypes (leiomyosarcoma [LMS], undifferentiated pleomorphic sarcoma [UPS], synovial sarcoma [SS]) in the cohort. Results: Data of 552 adults (57.6% women, median age: 52 years) were analyzed. DCR and ORR were 43.1% and 30.8%, respectively. Median PFS was 6.7 months and OS was 13.8 months. For LMS, UPS and SS, median PFSs were 6.1, 5.9 and 7.53 months and median OSs were 15.03, 12.87 and 12.27 months, respectively. ECOG ≥ 2 was associated with poor PFS and OS. Liver metastasis was only a factor for progression. Second-line use of pazopanib (vs. front-line) was associated with better PFS, its use beyond third line predicted worse OS. Adverse events (AE) occurred in 82.7% of patients. Most common AEs were fatigue (58.3%) and anorexia (52.3%) which were graded as ≥ 3 in 8.2% and 7.4% of patients, respectively. Conclusion: Pazopanib is effective and well-tolerated in treatment of non-adipocytic metastatic STS. Its earlier use (at second-line), good performance status may result in better outcomes. Worldwide scientific collaborations are important to gain knowledge on rarer STS subtypes by conducting studies in larger patient populations.Öğe Tissue levels of adiponectin in breast cancer patients(Humana Press Inc, 2007) Karaduman, Mehmet; Bilici, Ahmet; Ozet, Ahmet; Sengul, Ali; Musabak, Ugur; Alomeroglu, MelihBackground Adiponectin is a new adipocyte- secreted protein and associated with insulin-resistant status, such as type 2 diabetes mellitus and obesity. The inverse correlation between serum adiponectin levels and breast cancer risk was recently documented. On the other hand, the association of tissue adiponectin levels with breast cancer has not been previously reported. Thus, in the present study, the relationship between tissue adiponectin levels and breast cancer was evaluated. Methods We analyzed the correlation between tissue adiponectin levels and the occurrence of breast cancer in a case-control study comprising 27 women with diagnosed and histologically confirmed breast cancer and 33 women with fibroadenoma. In addition, the association of tissue adiponectin levels with the various classical risk factors, such as body mass index, menopausal status and, tumor size, stage, lymph node status, hormonal status were also studied. Results Tissue adiponectin levels in patients with breast cancer (0.75 +/- 0.06) were significantly higher than those in controls (0.68 +/- 0.1) (P = 0.02). The high tissue adiponectin levels were associated with significantly (P = 0.001) an increased risk for breast cancer compared with those in the low tissue adiponectin levels (OR, 1.34; 95% Cl, 1.12-1.84) in breast cancer patients. In addition, postmenopausal women with the high tissue adiponectin levels showed a significantly (P = 0.003) an increased risk for breast cancer compared with women in low tissue adiponectin levels (OR, 1.63; 95% Cl, 1.23-1.90). The correlation between BMI and breast cancer was not found (P > 0.05). Furthermore, the status of estrogen receptor, progesteron receptor, HER-2/neu receptor and lymph nodes involvement were established, no effect on the tissue adiponectin levels in patients with breast cancer and no correlations were detected among tumor stage; tumor size and the levels of tissue adiponectin (P > 0.05). Conclusion Our results suggest that the high tissue adiponectin levels significantly detected in breast cancer patients and associated with an increased risk for breast cancer.Öğe Treatment preferences in stage IA and IB testicular seminoma: multicenter study of Anatolian Society of Medical Oncology(Springer, 2015) Bilici, Ahmet; Ozturk, Turkan; Turkmen, Esma; Odabas, Hatice; Cihan, Sener; Selcukbiricik, Fatih; Erdogan, BulentApproximately 75 % of patients with testicular seminoma present with stage I disease, and the probability of long-term survival approaches 100 %. However, the standard adjuvant treatment for stage I seminoma patients remains controversial, and there is no uniform consensus in the literature. The present study was performed to evaluate treatment preference and outcomes for men with stage I testicular seminoma. From 1997 to 2013, 282 patients with histologically confirmed stage IA and IB testicular seminoma who underwent orchiectomy were included. The outcomes of three management options and survivals were retrospectively analyzed. The prognostic significance of risk factors for relapse on survival was evaluated by univariate and multivariate analysis; in addition, the factors predicting relapse were also evaluated by logistic regression analysis. Of the 282 patients with stage I seminoma, 130 (46.1) received adjuvant radiotherapy (RT), 80 (28.4 %) were treated with adjuvant carboplatin, while the remaining 72 patients (25.5 %) underwent surveillance. At the time of analysis, the median follow-up period of 38.5 months; relapses were observed in 16 patients (22.3 %) on surveillance, in one patient (1.2 %) treated with adjuvant carboplatin and in ten patients (%7.7) who received adjuvant RT. The 5-year disease-free survival (DFS) rate for patients who underwent surveillance was worse than those of patients treated with adjuvant carboplatin and RT (64.2 vs. 97.7 vs. 91.9 %, respectively; p < 0.001). However, the 5-year overall survival (OS) rate for patients on surveillance was similar compared with the adjuvant treatment groups (100 vs. 92.3 vs. 97.4 %, respectively; p = 0.44). Univariate analysis showed that only the treatment approach (surveillance vs. adjuvant carboplatin vs. adjuvant RT) for DFS (p < 0.001), invasion of the rete testis (p = 0.041) and the presence of relapse (p < 0.001) for OS were important prognostic indicators. Multivariate analysis indicated that the treatment strategy for DFS (p < 0.001, HR 0.34) was an independent prognostic factor. Furthermore, a logistic regression analysis showed that adjuvant treatment was found to be an independent factor for predicting relapse (p = 0.004, odds ratio: 0.39). Our results indicate that adjuvant treatment with carboplatin or RT is associated with improved DFS compared with surveillance for men with stage I testicular seminoma after orchiectomy. Moreover, the treatment strategy is an important prognostic indicator for DFS and a predictive factor for relapse. Although adjuvant treatment, especially carboplatin, seems to be a suitable treatment for patients with risk factors for relapse, surveillance is still feasible and the preferred management option after radical orchiectomy in men with stage I seminoma. More reliable predictive factors are needed to make treatment decisions.
