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Öğe Adjuvant Chemoradiation for Gastric Cancer: Multicentric Study of the Anatolian Society of Medical Oncology(H G E Update Medical Publishing S A, 2012) Kucukoner, Mehmet; Isikdogan, Abdurrahman; Arpaci, Erkan; Bilici, Mehmet; Uncu, Dogan; Cetin, Bulent; Dane, FaysalBackground/Aims: The aims of this study were to report the clinical outcomes of adjuvant chemo-radiotherapy after curative resection in 637 patients with gastric cancer. Methodology: The retrospective analysis included 637 patients with resectable gastric cancer and stage IB-IV (MO) from 8 medical centers between 2003 and 2010. The patients were treated with 5FU-leucovorin and radiotherapy according to Schema for INT-0116. Results: Of the 637 patients, the median of overall survival (OS) was 43.7 months and relapse free survival (RFS) was 36.6 months. OS rates were 84%, 45%, 40% while RFS rates were 81%, 45% and 35% at 1, 3 and 5-years, respectively. Hematological and gastro-intestinal toxicities (grade 1-4) were observed in 35% and 36.5% of patients, respectively. In univariate analysis, according to the Lauren classification, tumor grade, T stage, N stage, type of operation (total gastrectomy or subtotal) and surgery resection margin (R0 or R1) were found as prognostic factors on RFS and OS (p<0.05). In multivariate analysis, T stage, N stage and surgical margins were found as effective factors on OS. T stage, N stage and Lauren classification were factors affecting RFS. Conclusions: Adjuvant chemo-radiotherapy after curative resection of gastric cancer was feasible, with acceptable toxicities in the Turkish population.Öğe Bevacizumab-containing Chemotherapy is Safe in Patients with Unresectable Metastatic Colorectal Cancer and a Synchronous Asymptomatic Primary Tumor(Oxford Univ Press, 2013) Cetin, Bulent; Kaplan, Mehmet Ali; Berk, Veli; Tufan, Gulnihal; Benekli, Mustafa; Isikdogan, Abdurrahman; Ozkan, MetinSurgical resection of asymptomatic primary colorectal cancer in patients presenting with synchronous unresectable metastatic disease is controversial. Concerns and controversies remain over combining cytotoxic chemotherapy with bevacizumab in this patient population. We identified medical records of 99 patients with synchronous metastatic primary colorectal cancer who received chemotherapy with bevacizumab as their initial treatment. The incidence of subsequent use of surgery and surgical outcomes were recorded. Patients were also assessed for overall survival. Patients who received bevacizumab-containing chemotherapy for synchronous metastatic primary colorectal cancer were divided into the non-surgery and surgery groups according to the resection status of their asymptomatic primary tumor. In the non-surgery group, two patients (4.4) underwent additional surgery, while three patients (5.7) required surgery for rectovesical fistula in the surgery group. The median overall survival was 17 months for the non-surgery group (95 CI: 10.623.3 months) and 23 months for the surgery group (95 CI: 21.324.6 months; P 0.322). This study utilizing chemotherapy with bevacizumab did not result in an increased rate of morbidity related to the unresected primary tumor. Survival is not compromised by leaving the primary colon tumor intact.Öğe Dynamic multidetector computed tomography findings of hepatocellular carcinoma of hepatitis B virus-positive and -negative patients(E-Med, 2014) Senturk, Senem; Cetin, Bulent; Cengiz, Mustafa; Bilici, Aslan; Ozekinci, SelverBackground: The objective of this study was to retrospectively investigate and compare multidetector computed tomography findings of hepatocellular carcinoma (HCC) in hepatitis B virus (HBV)-positive and -negative patients. Methods: Triphasic (arterial, portal venous, and delayed phases) dynamic multidetector computed tomography (CT) was performed in 83 patients with HCC, 48 of whom were HBV-positive. The diagnosis of HCC was established with typical CT imaging findings (68 patients) or histopathological evaluation (15 patients). Distribution of solitary, multiple, and diffuse HCC, portal/hepatic vein thrombosis, metastasis, and patients with high alpha-fetoprotein levels in the HBV-positive and -negative groups were compared using the Kolmogorov-Smirnov test. Lesion size, alpha-fetoprotein levels, arterial, portal, delayed enhancement, and washout of lesions were compared using the Student's t-test. Results: Hypervascular tumors were observed in 72 (87%) patients, and hypovascular tumors were found in 11 (13%) patients. The mean alpha-fetoprotein value of HBV-positive patients with HCC was significantly higher than the mean alpha-fetoprotein value of HBV-negative patients (P < 0.05). Portal/hepatic vein thrombosis and metastasis were more frequently observed in HBV-positive patients (P < 0.05). The frequencies of solitary, multiple, and diffuse lesions in HBV-positive and -negative patients were not significantly different (P > 0.05). The mean diameters, arterial, portal, and delayed phase attenuations, and washout of HCC were not significantly different (P > 0.05). Conclusions: Multidetector CT imaging findings of HCC in HBV-positive and -negative patients are alike. Portal/hepatic vein thrombosis and metastasis are more frequently observed in HBV-positive patients. Alpha-fetoprotein levels are higher in HBV-positive patients.Öğe Is the Pretreatment Neutrophil to Lymphocyte Ratio an Important Prognostic Parameter in Patients with Metastatic Renal Cell Carcinoma?(Cig Media Group, Lp, 2013) Cetin, Bulent; Berk, Veli; Kaplan, Mehmet Ali; Afsar, Baris; Tufan, Gulnihal; Ozkan, Metin; Isikdogan, AbdurahmanIn this study, we have undertaken a retrospective review of 100 patient charts to investigate whether neutrophil to lymphocyte ratio (NLR) is associated with progression-free survival (PFS) in metastatic renal cell carcinoma (mRCC) patients treated with second-line vascular endothelial growth factor (VEGF) targeted tyrosine kinase inhibitors (TKIs) after failure of interferon-alpha. We have shown that NLR at diagnosis is an independent predictor of survival in mRCC patients. Investigation of therapies which harness the immune response are warranted in this disease. Background: Tyrosine kinase inhibitor is a standard treatment for mRCC. The NLR, an index of systemic inflammation, is associated with outcome in several cancer types. To study the association of pretreatment NLR with PFS and overall survival (OS) of patients treated with VEGF-targeted therapy. Patients and Methods: We retrospectively studied an unselected cohort of patients with mRCC, who were treated with TKIs. Kaplan-Meier and log-rank analyses were employed on PFS and OS and multivariate Cox proportional hazard model analyzed clinical parameters for their prognostic relevance. Results: A total of 100 patients with mRCC who had early progressed after first-line therapy with interferon-alpha were included in this retrospective multicenter study conducted at 4 centers between February 2008 and December 2011. The median of the NLR was 3.04 and patients were divided into 2 higher and lower NLR groups according to median of NLR. Median PFS was 9 versus 11 months in patients with baseline NLR > 3.04 versus <= 3.04 (P = .009). The median OS was 16 months versus 29 months, in patients with NLR > 3.04 versus <= 3.04, respectively (P = .004). In the whole group OS was independently associated with higher NLR (hazard ratio [HR], 2.406; P = .004), PFS more than 6 months (HR, 4.081; P = .0001), and sex (HR, 2.342; P = .040). On the other hand in the higher NLR group (HR, 1.107; P = .009) Memorial Sloan-Kettering Cancer Center score (HR, 3.398; P = .0001) was associated with PFS. Conclusion: In patients with mRCC treated with VEGF-targeted therapy, pretreatment NLR, the duration of PFS might be associated with OS. This should be investigated prospectively. (C) 2013 Elsevier Inc. All rights reserved.Öğe Ischemic colitis after capecitabine plus cisplatin treatment in advanced gastric cancer(Springer, 2011) Cetin, Bulent; Buyukberber, Suleyman; Senturk, Senem; Guzel, Evrim; Coskun, Ugur; Benekli, MustafaSystemic chemotherapy can be complicated by colonic toxicity, which usually determines the onset of pseudomembranous colitis and, rarely, of ischemic colitis in patients with cancer. This report describes the case of a 45-year-old man with advanced gastric cancer who developed severe ischemic colitis after chemotherapy with cisplatin and capecitabine. The patient developed symptoms of gastrointestinal toxicity with abdominal pain and bloody diarrhea. He had a normal white blood cell count throughout his illness; the assay of stool specimens for Clostridium difficile toxins and the stool cultures were both negative. An endoscopy showed a mild, transient ischemic colitis. Although cisplatin is related to severe colonic cytotoxicity, it has not been previously reported that capecitabine induces arterial thrombosis and necrosis of the gastrointestinal mucosa and inhibits angiogenesis. Pseudomembranous colitis is the most frequent complication in patients with cancer who undergo capecitabine-based chemotherapy and develop gastrointestinal toxicity. Once Clostridium difficile infection has been excluded, a diagnosis of ischemic colitis should be considered, especially in patients with cancer who have normal white blood cell counts.Öğe Lack of Prognostic Value of Mean Corpuscular Volume with Capecitabine Therapy in Metastatic Breast Cancer(Asian Pacific Organization Cancer Prevention, 2014) Bozkurt, Oktay; Berk, Veli; Kaplan, Muhammed Ali; Cetin, Bulent; Ozaslan, Ersin; Karaca, Halit; Inanc, MevludeCapecitabine is an oral fluoropyrimidine derivative which is frequently used alone or in combination regimens for the treatment of metastatic breast cancer. Although overall and progression free survivals have increased in recent years with the use of new generation drugs, predictive factors that would further improve the outcomes are needed. Previous studies have demonstrated the relation between post-treatment increase in mean corpuscular volume (MCV) and predicting therapy response as well as survival. The present study investigated the clinical impact of MCV elevation in metastatic breast cancer patients treated with capecitabine. Materials and Methods: The data of a total of 82 patients from three centers followed between June 2005 and June 2013 were retrospectively analyzed. The demographic data and hormone receptor status of the patients, as well as initial examination before and after treatment and data concerning progression were recorded. MCV >= 100 fl was considered as macrocytosis. Capecitabine was given at a dose of 2500 mg/m(2) daily for 14 days every three weeks. Pre-treatment and post-treatment MCV and other parameters of complete blood count were recorded. Post-treatment initial evaluation was performed after 2 cycles of therapy. Results: The median age of the patients was 46.5 years (range 26-72 years) and 54% were premenopausal. Performance status was ECOG 0 and 1 in 81 (99%) patients. The median number of cycles for capecitabine therapy was 5 (min-max: 2-18). The median Delta MCV level (post-treatment values at sixth week - baseline) was 6.4. Whilst Delta MCV was >= 6.4 in 42 patients, it was <6.4 in 40 patients. Clinical benefit (complete response+partial response+stable disease) was observed in 37 (88%) of 42 patients with a median Delta MCV >= 6.4 and in 30 (75%) of 40 patients with Delta MCV <6.4 with no statistically significant difference (p=0.158). No significant difference was determined between the group with Delta MCV >= 6.4 and the group with Delta MCV <6.4 in terms of progression-free survival (11 vs 12 months) (p=0.55) and overall survival (20 months vs. 24 months) (p=0.11). Conclusions: The identification of new predictive markers in metastatic breast cancer is very important. In some recent studies, increase in MCV has been suggested as a marker in tumor response. In the present study, however, no significant difference was determined between tumor response and increase in MCV. Further studies including higher numbers of patients are needed to determine whether increase in MCV is a predictive marker or not.Öğe Lapatinib plus Capecitabine for Brain Metastases in Patients with Human Epidermal Growth Factor Receptor 2-Positive Advanced Breast Cancer: A Review of the Anatolian Society of Medical Oncology (ASMO) Experience(Karger, 2012) Cetin, Bulent; Benekli, Mustafa; Oksuzoglu, Berna; Koral, Lokman; Ulas, Arife; Dane, Faysal; Turker, IbrahimBackground: We investigated the clinical outcome of patients with brain metastases (BMs) from human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (MBC) treated with lapatinib and capecitabine (LC). Patients and Methods: A total of 203 patients with HER2+ MBC, who had progressed after trastuzumab-containing chemotherapy, were retrospectively evaluated in 11 centers between September 2009 and May 2011. 85 patients who had developed BMs before the initiation of treatment with LC were included. All patients had received prior cranial radiotherapy. All patients were treated with the combination of lapatinib (1,250 mg/day continuously) and capecitabine (2,000 mg/m(2) on days 1-14 of a 21-day cycle). Results: The median follow-up was 10.5 months (range 1-38 months). An overall response rate of 27.1% was achieved, including complete response in 2 (2.4%) and partial response in 21 (24.7%) patients. Median progression-free survival was 7 months (95% confidence interval (CI) 5-9), with a median overall survival of 13 months (95% Cl 9-17). The most common side effects were hand-foot syndrome (58.8%), nausea (55.3%), fatigue (48.9%), anorexia (45.9%), rash (36.5%), and diarrhea (35.4%). Grade 3-4 toxicities were hand-foot syndrome (9.4%), diarrhea (8.3%), fatigue (5.9%), and rash (4.7%). There were no symptomatic cardiac events. Conclusion: LC combination therapy was effective and well-tolerated in patients with HER2+ MBC with BMs, who had progressive disease after trastuzumab-containing therapy.Öğe Lapatinib plus capecitabine for HER2-positive advanced breast cancer: a multicentre study of Anatolian Society of Medical Oncology (ASMO)(Taylor & Francis Ltd, 2014) Cetin, Bulent; Benekli, Mustafa; Turker, Ibrahim; Koral, Lokman; Ulas, Arife; Dane, Faysal; Oksuzoglu, BernaLapatinib is the first dual tyrosine kinase inhibitor of human epidermal growth factor receptor type 2 (HER2/neu) and epidermal growth factor receptor (EGFR). The present study evaluated the efficacy and tolerability of the combination of lapatinib and capecitabine in patients with metastatic breast cancer (MBC) who progressed after therapy with trastuzumab, a taxane and/or anthracycline. A total of 203 patients with a median age of 48 years (range: 25-82 years) were evaluated retrospectively in 11 centres between September 2007 and May 2011. All the patients had HER2-positive MBC progressing after trastuzumab and chemotherapy including an anthracycline and/or taxane. All patients were treated with the combination of lapatinib (1250 mg/day, continuously) and capecitabine (2000 mg/m(2) on days 1 through 14 of a 21-day cycle). Data on demographics, clinical outcome, and toxicity were collected for descriptive analyses. The median follow-up was 10.7 months (range: 1-40 months). An overall response rate (ORR) of 33.4% was achieved including 7 complete responses (CR, 3.4%), 61 partial responses (PR, 30.0%), and 44 stable disease (37.9%). Clinical benefit rate of 71.3% was achieved. Median progression-free survival (PFS) was 7 months (95% CI: 6-10 months), with a median overall survival (OS) of 15 months (95% CI: 12-18 months). The most common side effects were hand-foot syndrome (46.8%), nausea (42.3%), fatigue (42.2%), anorexia (38.5%), diarrhea (31.5%), and rash (29.6%). Grade 3-4 toxicities were identified as hand foot syndrome (7.9%), diarrhea (6.9%), fatigue (5.9%), and rash (5.4%). There were no symptomatic cardiac events. Lapatinib and capecitabine combination therapy is effective and well tolerated in patients with MBC who had progressive disease after trastuzumab, taxane, and/or anthracycline therapy, as evidenced by this retrospective evaluation. Toxicity was mild to moderate with low grade 3-4 toxicity.Öğe Lapatinib plus Capecitabine for HER2-Positive Advanced-Stage Breast Cancer in Elderly Women: Review of the Anatolian Society of Medical Oncology (ASMO) Experience(Karger, 2013) Cetin, Bulent; Benekli, Mustafa; Dane, Faysal; Boruban, Cem; Gumus, Mahmut; Oksuzoglu, Berna; Kaplan, Mehmet A.Background: The efficacy and safety of the lapatinib and capecitabine combination remain elusive in elderly patients with metastatic breast cancer (MBC), who progress after trastuzumab-based therapy. Patients and Methods: A total of 26 patients with HER2-positive MBC were included in this retrospective multicenter study. Median age was 69 years (range 65-82 years). All patients were treated with the combination of lapatinib (1,250 mg/day, continuously) and capecitabine (2,000 mg/m(2) on days 1-14 of a 21-day cycle). Data on demographics, clinical outcome, and toxicity were collected for descriptive analyses. Results: The median follow-up was 10 months (range 2-31 months). An overall response rate of 33.4% was achieved, including 1 complete response (3.8%), and 8 partial responses (30.8%). Median progression-free survival was 7 months (95% confidence interval (CI) 5-8), and the median overall survival was 15 months (95% CI 11-19). Most common side effects were fatigue (53.8%), diarrhea (46%), vomiting (36.3%), hand-foot syndrome (34.5%), and anorexia (34.6%). Grade 3-4 toxicities were identified as hand-foot syndrome (3.8%), diarrhea (7.6%), and fatigue (11.5%). There were no symptomatic cardiac events. Conclusion: Lapatinib and capecitabine combination therapy was effective and well tolerated in elderly patients with MBC, who had progressive disease after trastuzunnab-based therapy.Öğe Prognostic analysis of the patients with operable gastric cancer and the importance of tolerability of therapy: Study of Anatolian Society of Medical Oncology(Amer Soc Clinical Oncology, 2012) Kucukoner, Mehmet; Arpaci, Erkan; Isikdogan, Abdurrahman; Bilici, Mehmet; Uncu, Dogan; Cetin, Bulent; Dane, Faysal[Abstract Not Available]Öğe Prognostic Factors for Overall Survival in Patients With Metastatic Colorectal Carcinoma Treated With Vascular Endothelial Growth Factor-Targeting Agents(Asian Pacific Organization Cancer Prevention, 2012) Cetin, Bulent; Kaplan, Mehmet Ali; Berk, Veli; Ozturk, Selcuk Cemil; Benekli, Mustafa; Isikdogan, Abdurrahman; Ozkan, MetinObjective: 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.Öğe Results of Adjuvant FOLFOX Regimens in Stage III Colorectal Cancer Patients: Retrospective Analysis of 667 Patients(Karger, 2013) Uncu, Dogan; Aksoy, Sercan; Cetin, Bulent; Yetisyigit, Tarkan; Ozdemir, Nuriye; Berk, Veli; Dane, FaysalObjective: The aim of this study was to assess the use of 5-fluorouracil (5-FU), leucovorin and oxaliplatin (FOLFOX) regimens in clinical practice according to their efficacy and toxicity. Methods: Patients who received oxaliplatin-containing regimens after curative resection for colorectal carcinoma from 10 different oncology centers between May 2004 and December 2009 were included in the study. All patients were treated with FOLFOX regimens. Patients with rectal carcinoma were also treated with chemoradiotherapy with 5-FU after 2 cycles of a FOLFOX regimen. Results: The median age of the patients was 56 years (range 17-78). Of the total 667 patients, 326 were given FOLFOX-4, 232 were given modified FOLFOX-4 and 109 were given FOLFOX-6. The distribution according to disease stage was 33 patients with stage IIIA colorectal cancer, 382 patients with stage IIIB and 252 patients with stage IIIC. The most common adverse events were neutropenia (54%), nausea (36.9%), neuropathy (38.2%) and anemia (33.1%) for all grades. The median follow-up time was 23 months (range 1-79). Three-year disease-free survival and overall survival were 65 and 85.7%, respectively. Conclusion: The different oxaliplatin-containing 5-FU-based adjuvant chemotherapy regimens in patients with stage III colorectal cancer seemed to be at least equal in terms of efficacy regardless of the method of 5-FU administration or oxaliplatin dose. Copyright (C) 2012 S. Karger AG, BaselÖğe Sonographic assessment of fatty liver: intraobserver and interobserver variability(E-Century Publishing Corp, 2014) Cengiz, Mustafa; Senturk, Senem; Cetin, Bulent; Bayrak, Aylin Hasanefendioglu; Bilek, Senem UysalNon-alcoholic fatty liver disease (NAFLD) is a common liver disease worldwide and ultrasonography is widely used in the diagnosis and the follow-up we purposed to assess intraobserver and interobserver variability in the sonographic evaluation of the existence and steatosis grades of NAFLD. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and AST to ALT (AST/ALT) ratio were compared between the grades of hepatosteatosis. Hepatic ultrasonography (US) examinations consisted of 5-10 static images of 113 successive adult patients, whose records were in the picture archiving and communication system (PACS) of our hospital were retrospectively evaluated by two experienced radiologists. Hepatic images were graded into 4 groups; as normal, mild, moderate or severe hepatic steatosis. Evaluation of hepatic steatosis of the same set of images was repeated after one month under the same conditions. Interobserver and intraobserver agreement was assessed by using kappa (kappa) statistics. In each group, the percentage of individuals with high ALT and/or AST, or AST/ALT ratio over 1 was calculated. The intraobserver agreement was 51%, fair kappa (kappa=0.356) for observer 1; and 68%, moderate (kappa=0.591) for observer 2. The interobserver agreements in the initial and second readings were 39% and 40%, fair (kappa=0.208) and (kappa=0.225), respectively. Elevations of ALT and/or AST levels were similar between groups depending on the degree of hepatosteatosis among the patients. Visual assessment of NAFLD by ultrasonography has substantial interobserver variability, and reproducibility of results is limited. More objective imaging modalities are needed to evaluate the degree of hepatosteatosis.
