Advances in the Management of Unresectable or Metastatic Pancreatic Neuroendocrine Tumors: Chemotherapy, Targeted Therapy, Hormonal Treatment, and Future Directions

Bilici, Ahmet Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.6

Pancreatic neuroendocrine tumors (pNETs) are rare and heterogenous tumors and surgery to remove the primary tumor is the mainstay of treatment for resectable disease. However, curative surgery is often not feasible, because half of patients with pNET have metastases at the time of diagnosis. Palliative dubulking surgery and liver-directed therapies are appropriate options for these patients. Streptozocin-based regimens are standard, although temozolamide-based treatments are rapidly gaining wide clinical application. Somatostatin analogs are mainly indicated in hormonally active tumors to ameliorate symptoms. In addition, anti-tumoral activity has been proven in well-differentiated NETs. Recently, there has been tremendous progress in the molecular biology of pNETs; thereby, the efficacy of sunitinib and everolimus in the treatment of patients with metastatic pNETs has been proven by large placebo-controlled phase III trials. Currently, there are no definitively proven predictive biomarkers to evaluate response to medical therapies in patients with pNET. Therefore, further studies are needed to individualize and optimize their management. This article reviews systemic chemotherapy, targeted therapies, and anti-secretory treatments for the management of patients with unresectable or metastatic pNETs, summarized in the light of recent advances.

Modified Docetaxel and Cisplatin in Combination with Capecitabine (DCX) as a First-Line Treatment in HER2-Negative Advanced Gastric Cancer

Bilici, Ahmet,Selcukbiricik, Fatih,Demir, Nazan,Ustaalioglu, Bala Basak Oven,Dikilitas, Mustafa,Yildiz, Ozcan Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.20

Background: Docetaxel and cisplatin in combination with fluorouracil (DCF) regimen is accepted to be one of the standard regimens in the treatment of advanced gastric cancer. However, substantial toxicity has limited its use in daily clinical practice. Therefore, modification of DCF regimens, including introduction of capecitabine has been investigated to improve the safety profiles. In the present study, the efficacy and toxicity of a regimen with a modified dose of docetaxel and cisplatin in combination with oral capecitabine (DCX) was evaluated in untreated patients with HER2-negative advanced gastric cancer. Materials and Methods: Fifty-four patients with HER2-negative locally advanced or metastatic gastric cancer were included in this cohort. Patients received docetaxel $60mg/m^2$ plus cisplatin $60mg/m^2$ (day 1) combined with capecitabine $1650mg/m^2$ (days 1-14) every 3 weeks. Treatment response, survival, and toxicity were retrospectively analyzed. Results: The median age was 54 years (range: 24-76). The majority of patients (70%) had metastatic disease, while 11 patients (21%) had recurrent disease and underwent curative gastrectomy, and 5 patients (9%) had locally advanced disease (LAD). The median number of DCX cycles was 4. There were 28 partial responses and 11 complete responses, with an overall response rate of 72%. Curative surgery could be performed in four patients among five with LAD. At the median follow-up of 10 months, the median progression-free survival (PFS) and overall survival (OS) of the entire cohort of patients were 7.4 and 12.1 months, respectively. Dose modification was done in 12 patients due to toxicity in 8 and noncompliance in 4 patients. The most common hematological toxicity was neutropenia, which occurred at grade 3-4 intensity in 10 of 54 patients (27.7%). Febrile neutropenia was diagnosed only in two cases. Conclusions: DCX regimen offers prominent anti-tumor activity and considered to be effective first-line treatment with manageable toxicity for patients with HER2-negative advanced gastric cancer.

Clinical and Pathologic Features of Patients with Rare Ovarian Tumors: Multi-Center Review of 167 Patients by the Anatolian Society of Medical Oncology

Bilici, Ahmet,Inanc, Mevlude,Ulas, Arife,Akman, Tulay,Seker, Mesut,Babacan, Nalan Akgul,Inal, Ali,Bal, Oznur,Koral, Lokman,Sevinc, Alper,Tufan, Gulnihal,Elkiran, Emin Tamer,Ustaalioglu, Bala Basak Ove Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.11

Background: 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.

Pulmonary BALT Lymphoma Successfully Treated with Eight Cycles Weekly Rituximab: Report of First Case and F-18 FDG PET/CT Images

Ahmet Bilici,Mesut Seker,Bala Basak Oven Ustaalioglu,Nesrin Canpolat,Taflan Salepci,Mahmut Gumus 대한의학회 2011 Journal of Korean medical science Vol.26 No.4

Extra marginal-zone lymphomas of the lung is a very rare tumor and it originates from bronchial-associated lymphoid tissue. A 68-yr-old woman presented with productive cough and dyspnea. A thorax computed tomography scan showed a 9 × 10 cm in size mass in the left lung and pleural effusion in the lower lobe of left lung. Positron emission tomography/computed tomography (PET/CT) revealed intense uptake foci at the upper and middle sites of left lung and slight uptake foci at the mediastinal lymph nodes which showed malignant involvement. After bronchoscopic biopsy, the diagnosis of pulmonary bronchial-associated lymphoid tissue (BALT) lymphoma was confirmed. At the end of the eight cycles weekly rituximab treatment, complete response was obtained by PET/CT findings. It is concluded that extended rituximab schedule is more effective and it would be beneficial to investigate the use of PET/CT in the diagnosis and evaluating of the treatment response of pulmonary BALT lymphoma.

Temperature dependence of elastic and shear modulus, poisson ratio and ultrasonic wave velocity of electroless nickel-coated composites

Ahmet Yönetkena,Vildan Özkan Bilici,Ayhan Erol 한양대학교 청정에너지연구소 2023 Journal of Ceramic Processing Research Vol.24 No.5

There are many factors affecting the production process depending on the raw materials, equipment and technology used inthe production of composite materials. Reaching the desired density and strength of the product to be obtained is possible withappropriate arrangements and reinforcements to be made at every stage. Composite materials that combine more than onefeature are produced in material groups. In this study, composite production was made with nickel-based (0.4% BN ceramic+ 27.07% Astaloy CrM metallic) + 72.53%Ni powders by applying electroless nickel plating process, and these metallic andceramic powders were used for reinforcement. After these samples were shaped circularly in a uniaxial cold press, they weresintered in an argon atmosphere conventional furnace at 1000, 1100, 1200, 1300 and 1400 °C for two hours. The mechanicaland ultrasonic properties of the composite samples obtained with the addition of nickel-coated ceramic and metallic powderwithout electric current were determined. The effect of changing the sintering temperatures of Ni-based composite samples onultrasonic properties was measured by ultrasonic pulse echo method. The sintering temperature was found to be one of themost effective factors on the propagation velocity of ultrasonic waves, Young's modulus and shear modulus, Poisson ratio. Atthe same time, Young's modulus and shear modulus and Poisson ratios changed depending on the propagation velocity of theultrasonic waves. In addition, the results obtained by XRD analysis and SEM (Scanning Electron Microscopy) metallographicevaluation on the composite samples were supported.

Xeliri Plus Bevacizumab Compared with Folfiri Plus Bevacizumab as First-Line Setting in Patients with Metastatic Colorectal Cancer: Experiences at Two-Institutions

Uygun, Kazim,Bilici, Ahmet,Kaya, Serap,Ustaalioglu, Bala Basak Oven,Yildiz, Ramazan,Temiz, Suleyman,Seker, Mesut,Aksu, Gorkem,Cabuk, Devrim,Gumus, Mahmut Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.4

Background: Efficacy of chemotherapy plus bevacizumab has been shown in patients with metastatic colorectal cancer (mCRC) compared with chemotherapy alone. The aim of the present study was to evaluate the efficacy and safety of FOLFIRI or XELIRI regimens in combination with bevacizumab for mCRC patients in a first-line setting. Materials and Methods: A total of 132 patients with previously untreated and histologically confirmed mCRC were included. They were treated with either FOLFIRI-Bevacizumab (Bev) or XELIRI-Bev according to physician preference. The efficacy and safety of the two regimens were compared. Results: Between 2006 and 2010, 68 patients were treated with the XELIRI-Bev regimen, while the remaining 64 patients received the FOLFIRI-Bev regimen. The median age was 58.5 years (53.6 years in the FOLFIRI-Bev and 59.7 years in the XELIRI-Bev arm, p=0.01). Objective response rate was 51.6% for FOLFIRI-Bev versus 41.2% for XELIRI-Bev (p=0.38). At the median follow-up of 24.5 months, the median progression-free survival (PFS) was not different between two groups (14.2 months in FOLFIRI-Bev vs. not reached in the XELIRI-Bev, p=0.30). However, median overall survival time for the FOLFIRI-Bev arm was better than that for patients treated with XELIRIBev, but these differences was not statistically significant (37.8 months vs. 28.7 months, respectively, p=0.58). Most commonly reported grade 3-4 toxicities (FOLFIRI-Bev vs XELIRI-Bev) were nausea/vomiting (7.8% vs. 14.7%, p=0.27), diarrhea (10.9% vs 22.1%, p=0.10), hand-foot syndrome (0% vs 8.8%, p=0.02) and neutropenia (18.7% vs 27.9%, p=0.22). Conclusion: Our results showed that FOLFIRI-Bev and XELIRI-Bev regimens were similarly effective treatments in a first-line setting for patients with untreated mCRC, with manageable adverse event profiles.

A Particle Swarm Optimization for Multiobjective Sustainable Maritime Shipping

Saowanit Lekhavat,Nursen Aydin,Ahmet Bilici,Habin Lee 동중앙아시아경상학회 2015 한몽경상학회 학술대회 Vol.2015 No.07

Clinicopathological Features and Localization of Gastric Cancers and their Effects on Survival in Turkey

Selcukbiricik, Fatih,Tural, Deniz,Bilici, Ahmet,Uzel, Esengul Kocak,Ozguroglu, Mustafa,Demirelli, Fuat,Buyukunal, Evin,Serdengecti, Suheyla Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.1

Background: This study was designed to examine changing trends in localization of gastric cancer in Turkey in recent years. Materials and Methods: A total of 796 adult patients with newly diagnosed, histologically proven adenocarcinomas, treated and followed up at our oncology center between 2000-2011, were examined retrospectively. In all cases tumor localization were identified and recorded with clinicopathological features. Results: The median age was 58 with a range between 22-90 for the 552 men and 244 women. Median follow up was 12 months (1-276) and median overall survival was also 12 months (11.5-12.4). There was a trend for a change in tumor localization from distal to proximal. Survival of patients was low with advanced T and N stage tumours. Positive surgical margins, lymphovascular invasion, perineural invasion, cardioesophageal localization were predisposition factors for metastatic disease in gastric cancer. There was no relation between age or sex and histopathological type of gastric cancer. Conclusions: There is a trend in our country for a change in gastric tumour localization from distal to proximal, with clear significance for treatment choices.

Prognostic Factors for Lymph Node Negative Stage I and IIA Non-small Cell Lung Cancer: Multicenter Experiences

Ustaalioglu, Bala Basak Oven,Unal, Olcun Umit,Turan, Nedim,Bilici, Ahmet,Kaya, Serap,Eren, Tulay,Ulas, Arife,Inal, Ali,Berk, Veli,Demirci, Umut,Alici, Suleyman,Bal, Oznur,Benekli, Mustafa,Gumus, Mahmu Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.11

Background: 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.

Efficiency and Side Effects of Sorafenib Therapy for Advanced Hepatocellular Carcinoma: A Retrospective Study by the Anatolian Society of Medical Oncology

Berk, Veli,Kaplan, Mehmet Ali,Tonyali, Onder,Buyukberber, Suleyman,Balakan, Ozan,Ozkan, Metin,Demirci, Umut,Ozturk, Turkan,Bilici, Ahmet,Tastekin, Didem,Ozdemir, Nuriye,Unal, Olcun Umit,Oflazoglu, Utk Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.12

Background: Inoperable and metastatic hepatocellular carcinoma (HCC) is associated with a poor prognosis and low chemotherapeutic efficiency. Sorafenib is an oral multi-kinase inhibitor exerting its effects via the RAF/MEK/ERK pathway, vascular endothelial growth factor receptor (VEGFR) and platelet derived growth factor receptor beta (PDGFR-${\beta}$) tyrosine kinases. Randomized studies have shown a significant contribution of sorafenib to life expectancy and quality of life of cancer patients. The aim of the present study is to evaluate the efficacy and side effects of sorafenib therapy in Turkey. Materials and Methods: Data for 103 patients (82 males, 21 females) receiving sorafenib therapy in 13 centers from February 2008 to December 2012 were evaluated. Median age was 61 years and median ECOG performance status was 1 (range: 0-2). 60 patients (58%) had hepatitis B, 15 patients (15%) had hepatitis C infection and 12 patients (12%) had a history of alcohol consumption. All of the patients had Child scores meeting the utilization permit of the drug in our country (Child A). Results: A total of 571 cycles of sorafenib therapy were administered with a median of four per patient. Among the evaluable cases, there was partial response in 15 (15%), stable disease in 52 (50%), and progressive disease in 36 (35%). Median progression-free survival was 18 weeks and median overall survival was 48 weeks. The dose was reduced only in 6 patients and discontinued in 2 patients due to grade 3-4 toxicity, 18 patients (17%) suffering hand-foot syndrome, 7 (7%) diarrhea, and 2 (2%) vomiting. Conclusions: This retrospective study demonstrated better efficacy of sorafenib therapy in patients with advanced HCC compared to the literature while progression-free survival and overall survival findings were comparable. The side effect rates indicate that the drug was tolerated well. In conclusion, among the available treatment options, sorafenib is an efficient and tolerable agent in patients with inoperable or metastatic HCC.