Are Rogerofenib and Nilotinib Effective for Advanced Gastrointestinal Stromal Tumor (GIST) Patients who have Already been Given Main Treatments?

Ozaslan, Ersin,Ozkan, Metin,Bozkurt, Oktay,Duran, Ayse Ocak,Ucar, Mahmut,Eker, Baki,Berk, Veli,Karaca, Halit Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.11

Effectiveness of Palatal Mucosa Graft in Surgical Treatment of Sub-Glottic Stenosis

Umit Aydogmus,Adem Topkara,Metin Akbulut,Adem Ozkan,Figen Turk,Barbaros Sahin,Gokhan Yuncu 대한이비인후과학회 2016 Clinical and Experimental Otorhinolaryngology Vol.9 No.4

Objectives. Mucosal free grafts may be successfully applied in many surgical interventions. This study aims at investigating the feasibility of palatal mucosa graft in sub-glottic field in an animal model. Methods. This randomized prospective controlled study was conducted with an animal model. Sub-glottic inflammation was created in 15 adult rabbits in each group and sub-glottic stenosis surgery was applied thereafter. The rabbits in group 1 (control group) underwent segmental resection, partial cricoidectomy, and trachea-thyroid cartilage anastomosis; the rabbits in group 2 underwent segmental resection, cricoplasty, and crico-tracheal anastomosis using free buccal mucosa graft; and the rabbits in group 3 underwent segmental resection, cricoplasty, and crico-tracheal anastomosis using free palatal mucosa graft. Re-stenosis was evaluated after 42 days. Results. The percentages of stenosis were 27%±20%, 40%±20%, and 34%±23% for group 1, 2, and 3, respectively and the difference was not statistically significant (P=0.29). Intensive and tight fibrosis was observed in 2 rabbits (13%) in group 1, in 5 rabbits (33%) in group 2, and in 3 rabbits (20%) in group 3. There was not a statistically significant difference between groups (P=0.41). Excessive inflammation was observed in 3 rabbits (20%) in group 1, in 7 rabbits (47%) in group 2, and 3 rabbits (20%) in group 3. There was no a statistically significant difference between groups although inflammation rate was higher in the rabbits which underwent buccal mucosa graft (P=0.18). Conclusion. The surgical treatments applied with free mucosa graft reduced anastomosis tension through enabling anastomosis to the distal of cricoid instead of thyroid cartilage. Free palatal mucosa grafts may be used in sub-glottic field, one of the most challenging fields of trachea surgery, due to ease of application and rapid vascularization.

Cyclin D1 Gene G870A Variants and Primary Brain Tumors

Zeybek, Umit,Yaylim, Ilhan,Ozkan, Nazli Ezgi,Korkmaz, Gurbet,Turan, Saime,Kafadar, Didem,Cacina, Canan,Kafadar, Ali Metin Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.7

Alterations of cyclin D1, one of the main regulators of the cell cycle, are known to be involved in various cancers. The CCDN1 G870A polymorphism causes production of a truncated variant with a shorter half-life and thus thought to impact the regulatory effect of CCDN1. The aim of the present study was to contribute to existing results to help to determine the prognostic value of this specific gene variant and evaluate the role of CCDN1 G870A polymorphism in brain cancer susceptibility. A Turkish study group including 99 patients with primary brain tumors and 155 healthy controls were examined. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism analysis. The CCDN1 genotype frequencies in meningioma, glioma and control cases were not significantly different (p>0.05). No significant association was detected according to clinical parameters or tumor characteristics; however, a higher frequency of AG genotype was recorded within patients with astrocytic or oligoastrocytic tumors. A significant association between AG genotype and gliobilastoma multiforme (GBM) was recorded within the patients with glial tumors (p value=0.048 OR: 1.87 CI% 1.010-3.463). According to tumor characteristics, no statistically significant difference was detected within astrocytic, oligoasltrocytic tumors and oligodentrioglias. However, patients with astrocytic astrocytic or oligoastrocytic tumors showed a higher frequency of AG genotype (50%) when compared to those with oligodendrioglial tumors (27.3%). Our results indicate a possible relation between GBM formation and CCDN1 genotype.

Gemcitabine Plus Paclitaxel as Second-line Chemotherapy in Patients with Advanced Non-Small Cell Lung Cancer

Baykara, Meltem,Coskun, Ugur,Berk, Veli,Ozkan, Metin,Kaplan, Muhammet Ali,Benekli, Mustafa,Karaca, Halit,Inanc, Mevlude,Isikdogan, Abdurrahman,Sevinc, Alper,Elkiran, Emin Tamer,Demirci, Umut,Buyukberb Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.10

Purpose: The aim of this retrospective study was to determine response rates, progression-free survival (PFS), overall survival (OS) and toxicity of gemcitabine and paclitaxel combinations with advanced or metastatic non-small cell lung cancer patients (NSCLC) who have progressive disease after platinum-based first-line chemotherapy. Methods: We retrospectively evaluated the file records of patients treated with gemcitabine plus paclitaxel in advanced or metastatic NSCLC cases in a second-line setting. The chemotherapy schedule was as follows: gemcitabine $1500mg/m^2$ and paclitaxel 150 mg/m2 administered every two weeks. Results: Forty-eight patients (45 male, 3 female) were evaluated; stage IIIB/IV 6/42; PS0, 8.3%, PS1, 72.9%, PS2, 18.8%; median age, 56 years old (range 38-76). Six (12.5%) patients showed a partial response (PR), 13 (27.1%) stable disease (SD), and 27 (56.3%) progressive disease (PD). The median OS was 6.63 months (95% CI 4.0-9.2); the median PFS was 2.7 months (95% CI 1.8-3.6). Grade 3 and 4 hematologic toxicities, including neutropenia (n=4, 8.4%), and anemia (n=3, 6.3%) were encountered, but no grade 3 or 4 thrombocytopenia. One patient developed febrile neutropenia. There were no interruption for reasons of toxicity and no exitus related to therapy. Conclusion: The combination of two-weekly gemcitabine plus paclitaxel was an effective and well-tolerated second-line chemotherapy regimen for advanced or metastatic NSCLC patients previously treated with platinum-containing chemotherapy. Although the most common and dose limiting toxicities were neutropenia and neuropathy, this regimen was tolerated well by the patients.

Efficacy and Toxicity of Gemcitabine Plus Docetaxel Combination as a Second Line Therapy for Patients with Advanced Stage Soft Tissue Sarcoma

Ali Osman, Kaya,Suleyman, Buyukberber,Metin, Ozkan,Necati, Alkis,Alper, Sevinc,Nuriye Yildirim, Ozdemir,Suleyman, Alici,Onur, Esbah,Veli, Berk,Celalettin, Camci,Arife, Ulas,Ugur, Coskun,Mustafa, Benek Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.2

Purpose: To assess the safety and efficacy of a gemcitabine plus docetaxel regimen as a second line therapy for patients with advanced soft tissue sarcoma (STS) resistant to doxorubicin and ifosfamide-based therapy. Patients and Methods: Medical records of 64 patients with advanced STS who received gemcitabine plus docetaxel regimen as a second line treatment between May 2006 and June 2011 were examined. All patients had been previously treated with doxorubicin plus ifosfamide-based regimen at first line setting. Patients received gemcitabine 900 $mg/m^2$ on days one and eight intravenously over 90 minutes, followed by docetaxel 75 $mg/m^2$ on day eight intravenously over one hour. Cycles were repeated every 3 weeks. Results: The male-to-female ratio was 37/27 and the median age was 44 years (range; 19-67 years). Objective responses were observed in 13 (20.3 %) patients (2 CR, 11 PR) and stable disease in 21 (32.8 %). Total clinical benefit (CR+PR+SD) was observed in 34 (53.1 %). Median overall survival (OS) was 18 months (95% confidence interval (CI):12.1-23.9) and Median time to progression (TTP) was 4.8 months (95% CI: 3.6-6). A total of 243 cycles of chemotherapy were administered. The median number of cycle was 3 (range;1-11). The most common grade 3-4 hematologic toxicity was neutropenia (35.9 %). The most common nonhematologic toxicities consisted of nausea/vomiting (37.5 %), mucositis (32.8 %), peripheral neuropathy (29.7%), and fatigue (26 %). There was no toxicity-related death. Conclusion: The combination of gemcitabine plus docetaxel is an active and tolerable regimen as a second line therapy for patients with advanced soft tissue sarcoma who have failed doxorubicin and ifosfamide-based therapy.

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.

Association of Human Epidermal Growth Factor Receptor-2 Expression and Clinicopathological Findings in Patients with Colorectal Cancer

Karaca, Halit,Deniz, Kemal,Berk, Veli,Inanc, Mevlude,Ozkan, Metin Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.12

Background: To determine the frequency of HER-2 overexpression in colorectal cancer (CRC) patients, and to explore the relationship between clinicopathological prognostic factors and their effects on survival, based on immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) analysis. Materials and Methods: The study included 80 patients with a histologically proven diagnosis of CRC that received adjuvant FOLFOX-4 chemotherapy at our department between March 2006 and September 2010. Patient data were analyzed retrospectively. Results: The median follow-up period and age of the patients were 24 months and 59 years, respectively. In immunohistochemical staining, 3+ staining was found in 2 patients (2.5%) while 2+ was in 13 (16%). FISH for HER-2 was performed for all of these 15 patients; samples which were 3+ showed positivity but the ones with 2+ were negative. There was no significant correlation between HER-2 expression and age, gender, tumor localization, histological subtype, grade, lymphovascular and perineural invasion, or pTN stage (P>0.05), even when the patients with HER-2 overexpression were analyzed separately. There was also no significant relationship between progression-free survival (PFS) and overall survival (OS), and HER-2 expression, gender, tumor localization, obstruction-perforation, bleeding, histological type, grade, lymphovascular and perineural invasion, or pT staging (P>0.05); however, there was a significant relationship between lymph node involvement, and PFS and OS (P<0.05). Conclusions: Evaluation of HER-2 overexpression in a more comprehensive, multi-center, prospective trial with standardized methods will be an appropriate approach.

Albumin-globulin Ratio for Prediction of Long-term Mortality in Lung Adenocarcinoma Patients

Duran, Ayse Ocak,Inanc, Mevlude,Karaca, Halit,Dogan, Imran,Berk, Veli,Bozkurt, Oktay,Ozaslan, Ersin,Ucar, Mahmut,Eroglu, Celalettin,Ozkan, Metin Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.15

Background: Prior studies showed a relationship between serum albumin and the albumin to globulin ratio with different types of cancer. We aimed to evaluate the predictive value of the albumin-globulin ratio (AGR) for survival of patients with lung adenocarcinoma. Materials and Methods: This retrospective study included 240 lung adenocarcinoma patients. Biochemical parameters before chemotherapy were collected and survival status was obtained from the hospital registry. The AGR was calculated using the equation AGR=albumin/(total protein-albumin) and ranked from lowest to highest, the total number of patients being divided into three equal tertiles according to the AGR values. Furthermore, AGR was divided into two groups (low and high tertiles) for ROC curve analysis. Cox model analysis was used to evaluate the prognostic value of AGR and AGR tertiles. Results: The mean survival time for each tertile was: for the $1^{st}$ 9.8 months (95%CI:7.765-11.848), $2^{nd}$ 15.4 months (95%CI:12.685-18.186), and $3^{rd}$ 19.9 months (95%CI:16.495-23.455) (p<0.001). Kaplan-Meier curves showed significantly higher survival rates with the third and high tertiles of AGR in comparison with the first and low tertiles, respectively. At multivariate analysis low levels of albumin and AGR, low tertile of AGR and high performance status remained an independent predictors of mortality. Conclusions: Low AGR was a significant predictor of long-term mortality in patients with lung adenocarcinoma. Serum albumin measurement and calculation of AGR are easily accessible and cheap to use for predicting mortality in patients with lung adenocarcinoma.

Prognostic Factors for Overall Survival in Patients With Metastatic Colorectal Carcinoma Treated With Vascular Endothelial Growth Factor-Targeting Agents

Cetin, Bulent,Kaplan, Mehmet Ali,Berk, Veli,Ozturk, Selcuk Cemil,Benekli, Mustafa,Isikdogan, Abdurrahman,Ozkan, Metin,Coskun, Ugur,Buyukberber, Suleyman Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.3

Objective: Angiogenesis represents a key element in the pathogenesis of malignancy. There are no robust data on prognostic factors for overall survival (OS) in patients with metastatic colorectal cancer treated with vascular endothelial growth factor (VEGF)-targeted therapy. The present study was conducted to establish a prognostic model for patients using an oxaliplatin-based or irinotecan-based chemotherapy plus bevacizumab in metastatic colorectal cancer. Methods: Baseline characteristics and outcomes on 170 patients treated with FOLFIRI or XELOX plus anti-VEGF therapy-naive metastatic colorectal cancer were collected from three Turkey cancer centers. Cox proportional hazards regression was used to identify independent prognostic factors for OS. Results: The median OS for the whole cohort was 19 months (95% CI, 14.3 to 23.6 months). Three of the seven adverse prognostic factors according to the Anatolian Society of Medical Oncology (ASMO) were independent predictors of short survival: serum lactate dehydrogenase (LDH) greater than the upper limit of normal (ULN; p<0.001); neutrophils greater than the ULN (p<0.0014); and progression free survival (PFS) less than 6 months (p =0.001). Conclusion: Serum LDH and neutrophil levels were the main prognostic factors in predicting survival, followed by PFS. This model validates incorporation of components of the ASMO model into patient care and clinical trials that use VEGF-targeting agents.

Analyses of Multiple Factors for Determination of "Selected Patients" Who Should Receive Rechallenge Treatment in Metastatic Colorectal Cancer: a Retrospective Study from Turkey

Ozaslan, Ersin,Duran, Ayse Ocak,Bozkurt, Oktay,Inanc, Mevlude,Ucar, Mahmut,Berk, Veli,Karaca, Halit,Elmali, Ferhan,Ozkan, Metin Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.7

Background: Repeating a prior chemotherapy (rechallenge therapy) is an option for selected patients with metastatic colorectal cancer, but there is very little evidence in the literature for this approach. Thus, we reviewed our registry to evaluate prognostic factors and survival of patients who received irinotecan and oxaliplatin-based regimens as rechallenge third and fourth-line therapy. Materials and Methods: Patients who received irinotecan-based or oxaliplatin-base regimen as first-line had been rechallenged with third-line or fourth-line therapy. These patients were selected from the database of Turkish mCRC registry archives between October 2006 and June 2013 and evaluated retrospectively for factors effecting progression free survival (PFS) and overall survival (OS) by the Kaplan-Meire and Cox-regression methods. Results: Thirty-nine patients were enrolled. The median duration of follow-up was 36 months (14-68 months). Thirty-one patients (76%) died during follow-up. In terms of rechallenge treatments, 29 patients had received third-line and 10 patients had received fourth-line. Response rate (RR) was found to be 12.9%, with stable disease in 19 (48.7%) patients. The median PFS was 6 months (95%CI=4.64-7.35 months) and the median OS was 11 months (95%CI=8.31-13.68 months). The factors effecting survival (PFS and OS) were only being PFS after first-line chemotherapy ${\geq}12months$ (p=0.007, 95% CI=1.75-35.22 and p=0.004, 95%CI=1.44-7.11), both in univariate and multivariate analyses. Conclusions: This study indicates that rechallenge treatment could be a good option as a third or later line therapy in patients who had ${\geq}12months$ PFS onreceiving first line therapy.