Oral Cyclophosphamide and Etoposide in Treatment of Malignant Pleural Mesothelioma

Gunduz, Seyda,Mutlu, Hasan,Goksu, Sema Sezgin,Arslan, Deniz,Tatli, Ali Murat,Uysal, Mukremin,Coskun, Hasan Senol,Bozcuk, Hakan,Ozdogan, Mustafa,Savas, Burhan Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.20

Background: Malignant mesothelioma (MM) is almost always fatal and few treatment options are available. The aim of this study was to evaluate the efficacy of oral cyclophosphamide and etoposide for patients who underwent standard treatment for advanced MM. Materials and Methods: This study included 22 malignant pleural mesothelioma patients who were treated with oral cyclophosphamide and etoposide (EE). Results: The average follow-up period of the patients was 39.1 months. Under the treatment of oral EE, median progression-free survival was 7.7 months [95%CI HR (4.3-11.1)] and median overall survival was 28.1 months [95%CI HR (5.8-50.3)]. The treatment response rates were as follows: 4 patients (27.3%) had a partial response (PR), 12 (54.5%) had stable disease (SD), and progressive disease (PD) was observed in 6 (35.9%). Conclusions: Oral EE can be administered effectively to patients with inoperable malignant mesothelioma who had previously received standard treatments.

Prognostic Value of Hematologic Parameters in Patients with Metastatic Renal Cell Carcinoma Using Tyrosine Kinase Inhibitors

Gunduz, Seyda,Mutlu, Hasan,Uysal, Mukremin,Coskun, Hasan Senol,Bozcuk, Hakan Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.8

Background: The prognostic significance of the neutrophil-to-lymphocyte ratio for progression free survival in patients with metastatic renal cell carcinoma is unclear. Materials and Methods: We retrospectively reviewed 45 patients diagnosed with metastatic RCC previously treated with tyrosine kinase inhibitors from two centers, Akdeniz University Hospital and Afyon Kocatepe University. The prognostic value of the pretreatment neutrophil-tolymphocyte ratio, and other clinical and laboratory parameters were assessed by univariate and multivariate analysis. Results: Median progression free survival (PFS) was 13.9 months [95% CI for HR (6.88-20.91)] and overall survival figure of 16.6 months [95% CI for HR (7.23-26.03)] Univariate analysis revealed that PFS was significantly affected by hemoglobin level [p=0.013 (95% CI for HR (0.71-0.96))], eosinophil count [p=0.031 (95% CI for HR (0.20-0.92))], ratio of neutrophil lymphocytes (NLR) [p=0.007 (95% CI for HR (1.47-11.74))] and calcium level [p=0.006 (95% CI for HR (0.15-0.73))]. However, only NLR [p=0.031 (95% CI for HR (1.15-18.1))] and calcium levels [p=0.018 (95% CI for HR (0.20-18.1))] retained significance with multivariate analysis. Median PFS was 23.9 vs 8.6 months in patients with NLR ${\leq}2$ vs NLR >2 (Log rank; p= 0.040). Conclusions: This study showed that increased pretreatment NLR is an independent prognostic factor for patients with metastatic RCC using tyrosine kinase inhibitors.

Use of Blood Transfusion at the End of Life: Does it Have Any Effects on Survival of Cancer Patients?

Goksu, Sema Sezgin,Gunduz, Seyda,Unal, Dilek,Uysal, Mukremin,Arslan, Deniz,Tatli, Ali Murat,Bozcuk, Hakan,Ozdogan, Mustafa,Coskun, Hasan Senol Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.10

Background: Treatment of anemia is an important issue in the palliative care setting. Blood transfusion is generally used for this purpose in supportive care. However the place of blood transfusion in terminally ill cancer cases is less far established. Objective: We aimed to outline the use of transfusions and to find the impact of blood transfusion on survival in patients with advanced cancer and very near to death. Design: Patients dying in 2010-2011 with advanced cancer were included in the study. We retrospectively collected the data including age, type of cancer, the duration of last hospitalisation, ECOG performance status, Hb levels, transfusion history of erythrocytes and platelets, cause and the amount of transfusion. The anaemic patients who had transfusion at admission were compared with the group who were not transfused. Survival was defined as the time between the admission of last hospitalisation period and death. Results: Three hundred and ninety eight people with solid tumours died in 2010-2011 in our clinic. Ninety percent of the patients had anemia at the time of last hospitalisation. One hundred fifty three patients had erythrocyte transfusion at admission during the last hospitalisation period (38.4%). In the anaemic population the duration of last hospitalisation was longer in patients who had erythrocyte transfusion (15 days vs 8 days, p<0.001). Conclusions: Patients who had blood transfusion at the end of life lived significantly longer than the anaemic patients who were not transfused. This study remarks that blood transfusions should not be withheld from terminal cancer patients in palliative care.

Expression Pattern and Prognostic Significance of Claudin 1, 4 and 7 in Pancreatic Cancer

Alikanoglu, Arsenal Sezgin,Gunduz, Seyda,Demirpence, Ozlem,Suren, Dinc,Gunduz, Umut Riza,Sezer, Cem,Yildiz, Mustafa,Yildirim, Mustafa Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.10

Background: Tight junctions (TJs) organise paracellular permeability and they have an important role in epithelial and endothelial cell polarity and permanence of barrier function. It has been demonstrated that the Claudin family constitutes an important component of them. In this study, we assessed expression patterns of of Claudin1, 4 and 7 and whether they have any relation with prognosis in patients with pancreatic cancer. Materials and Methods: Expression patterns of Claudin 1,4 and 7 were examined by immunohistochemistry in 25 patients with a histopathological diagnosis of pancreatic cancer using a semiquantitative scoring of the extent and intensity of staining. After grouping the staining scores as low (final score 0-2) and high (final score 3-9) the relation between expression of Claudin 1,4 and 7 and survival was evaluated. Results: There was no significant relation between expression of Claudin 1,4 and 7 and gender and stage. No statistically significant relation was found between Claudin 1 and 4 expression and survival whereas a statistically significant relation was found between decrease in Claudin 7 expression and decrease in survival. Conclusions: Claudins have important functions other than their popular function known as adhesion. Supporting this hypothesis, we found a statistically significant relationship between increased Claudin 7 expression and increased survival time, and this suggests that Claudin 7 may exert different tumorigenic effects in pancreatic cancer other than its well-known adhesion effect.

Survival Results and Prognostic Factors in T4 N0-3 Non-small Cell Lung Cancer Patients According to the AJCC 7^th Edition Staging System

Arslan, Deniz,Bozcuk, Hakan,Gunduz, Seyda,Tural, Deniz,Tattli, Ali Murat,Uysal, Mukremin,Goksu, Sema Sezgin,Bassorgun, Cumhur Ibrahim,Koral, Lokman,Coskun, Hasan Senol,Ozdogan, Mustafa,Savas, Burhan Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.6

Background: The American Joint Committee on Cancer (AJCC) published a new staging system ($7^{th}$ edition) in 2009. In our study, we evaluated the survival results and prognostic factors among T4 local advanced non-small cell lung cancer (LA-NSCLC) patients in a large heterogeneous group, in accordance with this new system. Materials and Methods: We retrospectively evaluated the files of 122 T4 N0-3 M0 LA-NSCLC patients, identified according to the new staging system, treated at two centers between November 2003 and June 2012. Variables correlating with univariate survival at p<0.20 were later included in multivariate Cox regression analysis. Here, selection of relevant predictors of survival was carried out in accordance with the likelihood ratio formula with p<0.05 regarded as significant. Results: The median age was 60 and the median follow-up period was 17.4 months. Median overall survival (OS) was 18.3 months, the 1 year overall survival (OS) rate was 72%, and the 5 year OS rate was 28%. Statistically significant predictors of survival were (p<0.20) ECOG-PS (Eastern Cooperative Oncology Group Performance Status), age, T4 factor subgroup, stage and primary treatment in OS univariate analysis. On multivariate analysis for OS ECOG-PS (p=0.001), diagnostic stage (p=0.021), and primary treatment (p=0.004) were significant. In the group receiving non-curative treatment, the median OS was 11.0 months, while it was 19.0 months in the definitive RT group and 26.6 months in the curative treatment group. There was a significant difference between the non-curative group and the groups which had definitive RT and curative operations (respectively p<0.001 and p=0.001) in terms of OS, but not between the groups which had definitive RT and curative operations. The median event free survival (EFS) rate was 9.9 months, with rates of 46% and 19% at 3 and 5 years, respectively. On univariate analysis of EFS rate with ECOG-PS, weight loss and staging, statistical significance was found only for thorax computerized tomography (CT)+18F-fluorodeoxy-glucose positron emission tomography-CT (PET-CT) use, stage and primary treatment (p<0.20). In multivariate analysis with EFS, only the primary treatment was statistically significant (p=0.001). In the group receiving non-curative treatment, the median EFS was 10.5 months while in the curative operation group it was 14.7 months. When all the primary treatment groups were taken into consideration, grade III/IV side effect swas observed in 57 patients (46.6%). Esophagitis was most prominent among those that received definitive radiotherapy. Conclusions: Independent prognostic factors among these 122 heterogeneous LA-NSCLC T4 N0-3 M0 patients were age at diagnosis, ECOG-PS, stage and primary treatment, the last also being a significant prognostic indicator of EFS. Our findings point to the importance of appropriate staging and a multidisciplinary approach with modern imaging methods in this patient group. In those with T4 lesions, treatment selection and the effective use of curative potential should be the most important goal of clinical care.

Clinicopathologic Features and Molecular Subtypes of Breast Cancer in Young Women (Age ≤35)

Goksu, Sema Sezgin,Tastekin, Didem,Arslan, Deniz,Gunduz, Seyda,Tatli, Ali Murat,Unal, Dilek,Salim, Derya,Guler, Tunc,Coskun, Hasan Senol Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.16

Introduction: Breast cancer in young women is a relatively rare disease; however it tends to be more aggressive and is the leading cause of cancer death in this population. The aim of this study is to investigate the clinical and biological features of breast cancer arising in young Turkish breast cancer patients. Materials and Methods: Patients with breast cancer aged 35 or less (${\leq}35$ years) were selected for the study. In total 211 cases were included. Pathologic features; histologic subtypes, grade, lymphovascular invasion, axillary involvement, and stage were recorded for each. Results: The most common subtype was luminal B (36.5%), followed by luminal A (30.8%), triple negative (23.2%) and HER2+(9.5%) subtypes. Twelve percent of the patients had stage 4, 32.7% had stage 3, 46.4% had stage 2, and 6.2% had stage 1 disease at the time of diagnosis. Mean tumour diameter was 3.87 cm (range 0.3-13 cm). The axillary lymph nodes were positive in 74.4% of the patients, while lympho-vascular invasion was seen in 56.4%. Some 9.5% of patients had grade 1, 51.2% had grade 2, and 31.8% had grade 3 tumors. Conclusions: Young women with breast cancer in Turkey are more likely to present with luminal B subtype. Tumors in young women are more likely to present with advanced disease, to be high grade and and to have more lymphovascular invasion. Further research should focus on whether we need new treatment strategies for young patients with breast carcinoma.

Prognostic Significance of p53 in Gastric Cancer: a Meta-Analysis

Yildirim, Mustafa,Kaya, Vildan,Demirpence, Ozlem,Gunduz, Seyda,Bozcuk, Hakan Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.1

Background: Gastric cancer is one of the frequently seen cancers in the world and it is the second most common reason for death due to cancer. The prognostic role of expression of p53 detected by immunohistochemistry in gastric cancer remains controversial. This meta-analysis aimed to explore any association between overexpression and survival outcomes. Materials and Methods: We systematically searched for studies investigating the relationships between expression of p53 detected by immunohistochemistry and prognosis of gastric cancer patients. Study quality was assessed using the Newcastle-Ottawa Scale. After careful review, survival data were extracted from eligible studies. A meta-analysis was performed to generate combined hazard ratios for overall survival and disease-free survival. Results: A total of 4.330 patients from 21 studies were included in the analysis. Our results showed tissue p53 overexpression in patients with gastric cancer to be associated with poor prognosis in terms of overall survival (HR, 1.610; 95% CI, 1.394 -5.235; p:<0.001). Pooled hazard ratio for disease free survival showed that p53 positivity or negativity were not statitistically significant (HR, 1.219; 95%CI, 0.782-1.899; p:0.382). Conclusions: The present meta-analysis indicated overexpression of p53 detected by immunohistochemistry to be associated with a poor prognosis in patients with gastric cancer.

Effects of Definitive Chemoradiotherapy on Respiratory Function Tests and Quality of Life Scores During Treatment of Lung Cancer

Duman, Evrim,Yildirim, Mustafa,Kaya, Vildan,Ozturk, Duriye,Inal, Aysun,Akarsu, Zeynep,Gunduz, Seyda,Yildiz, Mustafa Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.15

Background: Chemoradiotherapy is an important treatment modality for lung cancers. The aim of this study was to investigate alterations in, as well as the interrelationship between, lung function and quality of life of patients receiving chemoradiotherapy due to locally advanced non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) limited to the thorax. Materials and Methods: The study included patients receiving definitive chemoradiotherapy for lung carcinoma. The respiratory function of the patients was assessed by measuring forced expiratory volume in 1 s per unit (FEV1) and forced expiratory volume in 1s per unit of vital capacity (FEV1/VC) before, in the middle of and after treatment. During the study, EORTC QLQ C30 and LC13 questionnaires developed by the Committee of the European Organization for Research and Treatment of Cancer (EORTC) were employed to evaluate the quality of life on the same day as respiratory function tests (RFT). Findings: The study included 23 patients in total: 19 (82.6%) diagnosed with NSCLC and 4 (17.4%) with SCLC. The average percentage FEV1 was $55.6{\pm}21.8%$ in the pre-treatment period, $56.2{\pm}19.2%$ in the middle of treatment and $60.4{\pm}22%$ at the end of treatment. The improvement in functional scores, symptom scores and general health scores during treatment was not statistically significant (P= 0.568, P= 0.734, P= 0.680, P=0.757 respectively). Conclusions: Although this study showed an improvement in respiratory function and quality of life of patients during treatment with thoracic chemoradiotherapy, no statistically significant results were obtained. While evaluating the effectiveness of treatments for lung carcinoma, the effects of treatment on respiratory function and quality of life should be considered.

Esophageal Cancer, Gastric Cancer and the use of Pesticides in the Southwestern of Turkey

Yildirim, Mustafa,Kaya, Vildan,Yildiz, Mustafa,Demirpence, Ozlem,Gunduz, Seyda,Dilli, Utku Donem Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.6

Background: Esophageal and gastric cancer generally have a poor prognosis and may share common risk factors. It has been demonstrated that the pesticide usage may contribute to development of many cancer types. In this study, the relation between amount of pesticides used in agriculture and esophageal and gastric cancer incidence was researched. Materials and Methods: Findings from the data bank of the Ministry of Health Provincial Health Directorate Cancer Records Center between the years of 1998-2010 were used. All patients who were diagnosed with gastric and esophageal cancer histopathologically were included. Data for annual pesticide usage were obtained from Provincial Agriculture Directorate for the same time period. Statistical analysis was performed using the Spearman test. Results: One thousand eight hundred and ninety-six patients were involved in the study, 1,233 males (65%) and 663 females (35%), 230 with esophageal cancer (12.1%) and 1,666 with gastric cancer (87.9%). No statistically significant relation was apparent between pesticide amount used and esophageal cancer (p: 0.87). Conclusions: In our study, there was no relationship between pesticide usage and esophageal or gastric cancer. However, the time between pesticide usage and cancer development was not known, qualifying the comparison.

Mean Platelet Volume as an Independent Predictive Marker for Pathologic Complete Response after Neoadjuvant Chemotherapy in Patients with Locally Advanced Breast Cancer

Mutlu, Hasan,Eryilmaz, Melek Karakurt,Musri, Fatma Yalccn,Gunduz, Seyda,Salim, Derya Kivrak,Coskun, Hasan Senol Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.4

Background: The impact of mean platelet volume (MPV) on prognosis, diagnosis and response to therapy in cancer patients has been widely investigated. In the present study, we evaluated whether MPV at diagnosis has predictive value for pathologic complete response (pCR) after neoadjuvant chemotherapy in patients with locally advanced breast cancer (LABC). Materials and Methods: A total of 109 patients with LABC from Akdeniz University and Antalya Research and Training Hospital were evaluated retrospectively. Results: ROC curve analysis suggested that the optimum MPV cut-off point for LABC patients with pCR (+) was 8.15 (AUC:0.378, 95%CI [0.256-0.499], p=0.077). The patients with MPV <8.15 had higher pCR rates (29.2% vs. 13.1%, p=0.038). After binary logistic regression analysis, MPV and estrogen receptor absence were independent predictors for pCR. Conclusions: MPV has an independent predictive value for pCR after neoadjuvant chemotherapy in patients with LABC.