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    Effectiveness of bendamustine in relapsed or refractory lymphoma cases: a Turkish Oncology Group study
    (2021) Karadurmus, Nuri; Paydas, Semra; Esin, Ece; Surmeli, Zeki Gokhan; Yildiz, Birol; Erturk, Ismail; Nayir, Erdinc; Dogan, Mutlu; Sumbul, Ahmet Taner; Barista, Ibrahim; Gurkan, Emel; Ocal, Ramazan; Ferhanoglu, Burhan; Ozgur, Gokhan; Karakas, Yusuf; Lacin, Sahin; Ozaydin, Sukru; Petekkaya, Halil İbrahim; Uskent, Necdet; 34336021
    Introduction: We aimed to investigate the efficacy and side effects of bendamustine in relapsed/refractory lymphoma patients in Turkey. Material and methods: In this retrospective study, we included relapsed/refractory Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) patients who underwent multiple lines of chemotherapy. The primary endpoint was to determine the objective response and toxicity. Results: Ninety-nine patients with a median age of 59.8 years were included in the study. Eighty-one patients had NHL (follicular lymphoma: 10, diffuse large B- cell lymphoma: 27, mantle-cell lymphoma: 18, marginal zone lymphoma: 9, small lymphocytic lymphoma/chronic lymphocytic leukemia: 17) and 18 patients had HL. The patients had previously received a median of three lines of chemotherapy (range: 2-8) except autologous stem cell transplantation (ASCT); 19 patients (HL: 11, NHL: 8) had undergone ASCT. The objective response rate (ORR) was 74.3%, the complete response rate was 57% (= 53), and the partial response rate was 16.6% (= 19). The overall survival (OS) rate at 1 year was 74.6%. The progression-free survival (PFS) rate at 1 year was 62.5%. The most common side effects were lymphopenia, anemia and neutropenia. Side effects which were observed as grade 3 and higher levels were lymphopenia (14.1%), neutropenia (10.1%) and fatigue (7.1%). Conclusions: Objective response rate of bendamustine was found to be 74.3% in relapsed/refractory HL and NHL patients. It appears to be an effective option as a salvage treatment for patients who have previously received multiple lines of therapy.
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    Response to first-line chemotherapy regimen is associated with efficacy of immune checkpoint blockade therapies in patients with metastatic urothelial carcinoma
    (2021) Sumbul, Ahmet Taner; 34762201
    Background Atezolizumab (ATZ) has demonstrated antitumor activity in previous studies in patients with metastatic platinum-resistant urothelial carcinoma. However, the response rate of ATZ was modest. Therefore, finding biologic or clinical biomarkers that could help to select patients who respond to the immune checkpoint blockade remains important. Patients and methods In this study, we present the retrospective analysis of 105 patients with urothelial cancer treated with ATZ after progression on first-line chemotherapy. Data of patients were obtained from patient files and hospital records. The association between response to first-line chemotherapy and ATZ was using Fisher's exact test. Median follow-up was calculated using the reverse Kaplan-Meier method. OS was estimated by using the Kaplan-Meier method. Results The median follow-up time was 23.5 months. Forty (74.1%) of patients who experienced clinical benefit after firs-line chemotherapy also had clinical benefit after atezolizumab, while only 14 (25.9%) of patients with initial PD after first-line chemotherapy subsequently experienced clinical benefit with ATZ (p = 0.001). The median OS on ATZ of 14.8 and 3.4 months for patients with clinical benefit and progressive disease in response to first-line chemotherapy, respectively (p = 0.001). Three of the adverse prognostic factors according to the Bellmunt criteria were independent factors of short survival: liver metastases {Hazard ratio [HR] = 1.9; p = 0.04}, ECOG PS >= 1 (HR = 2.7; p = 0.001), and Hemoglobin level below 10 mg/dl (HR = 2.8; p < 0.001). In addition, patients with clinical benefit from first-line chemotherapy (HR = 0.39; p < 0.001) maintained a significant association with OS in multivariate analysis. Conclusions Our study demonstrated that clinical benefit from first-line chemotherapy was independent prognostic factors on OS in patients' use of ATZ as second-line treatment in metastatic bladder cancer. Furthermore, these findings are important for stratification factors for future immunotherapy study design in patients with bladder cancer who have progressed after first-line chemotherapy.
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    Cardiotoxicity of Trastuzumab Emtansine (T-DM1): A Single-center Experience
    (2021) Acibuca, Aynur; Sezer, Ahmet; Yilmaz, Mustafa; Sumbul, Ahmet Taner; Demircan, Senol; Muderrisoglu, Ibrahim Haldun; Ozyilkan, Ozgur; 0000-0002-3444-8845; 34898302; ABG-4047-2020
    Objective New anti-cancer drugs promise to increased survival benefits and reduce adverse events. Trastuzumab emtansine (T-DM1) is a novel anti-human epidermal growth factor receptor 2 agent that has shown minimal cardiotoxicity in clinical trials. However, data on real-life outcomes are required. Methods A retrospective review of our center's medical records was performed, including female patients aged >= 18 years with a diagnosis of metastatic breast cancer who were treated with T-DM1. Descriptive statistics were used to investigate clinical features that could increase the risk of cardiotoxicity. Cardiotoxicity was determined by comparing pre and post-T-DM1 echocardiogram results and was defined as a decrease in the left ventricular ejection fraction (LVEF) >10% to below 55%. Results Data from 41 female patients with a mean age of 52 +/- 11.5 years were evaluated. A significant LVEF decrease (from 59% to 33%) was observed in one patient during T-DM1 treatment. Further investigation showed that this decrease was due to underlying coronary artery disease, and LVEF recovered to the baseline value after coronary revascularization. Conclusion T-DM1 seems to be safe in terms of cardiotoxicity. Real-life data with a larger sample size are still needed to confirm the cardiac safety of T-DM1.
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    The Prognostic Significance of Complete Response Rates in Patients with Extensive Stage Small Cell Lung Cancer
    (2019) Sedef, Ali Murat; Calikusu, Zuleyha; Bahceci, Aykut; Gokcay, Serkan; Sumbul, Ahmet Taner; D-4793-2014
    OBJECTIVE Small cell lung cancer (SCLC) is the most aggressive type of lung cancer. Platinum-etoposide chemotherapy combination is used as first line treatment. The aim of this trial is evaluate the effect of complete response rates and clinical features in patients with extensive stage (ES) SCLC. METHODS In this retrospective study, a total of 117 patients from four different oncology centers in Turkey between 2011 and 2017 were divided into 2 groups, namely, patients with complete response (group 1) and those with no complete response (group 2) after platin-etoposide combination therapy. RESULTS The median age of the patients was 61 (range 38-81) years. The median follow-up time was 12 months and 95 (81%) patients died. Progression-free survival (PFS) and overall survival (OS) were estimated, respectively, as 8 and 13 months. Overall survival of group 1 patients was statistically significantly better than the group 2 (16 versus 10 months respectively and p=0.00). The overall survival of patients who had late recurrent disease (>6 mo.) was statistically significantly better than the early ones (<6 mo) (19 versus 14 months respectively and p=0,008). CONCLUSION Complete response and recurrent free time were the prognostic factors for ES SCLC patients in our study
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    Can serial monitoring of serum Vascular Endothelial Growth Factor (VEGF), Nitric Oxide (NO), and Angiotensin II (ANGII) levels have predictive role during Bevacizumab treatment?
    (2014) Sumbul, Ahmet Taner; Disel, Umut; Sezgin, Nurzen; Sezer, Ahmet; Kose, Fatih; Besen, Ali Ayberk; Sumbul, Zehra; Abali, Huseyin; Ozyilkan, Ozgur
    Background: Standard treatment of colorectal cancer includes both cytostatic chemotherapy and targeted therapies. Bevacizumab, targeting the VEGF receptor, is one of the primary targeted therapies that achieve better response rate and survival rate as compared to combination chemotherapy. To the best of our knowledge, there is no established single marker that can be used as a predictive marker in bevacizumab therapy. Material/Methods: We enrolled 24 patients with the diagnosis of metastatic colorectal cancer in our study. During the study, 2 blood samples were drawn from patients before the first cycle and after the sixth cycle of bevacizumab therapy. Serum levels of VEGF, ANG II, and NO were recorded. Results: While the change across VEGF levels was found to be a statistically significant decreasing trend (p=0.009), this decrease was not found to be correlated with treatment response and hypertension development. Additionally, no statistically significant difference was found in terms of NO and ANG II levels. Conclusions: This study showed a significant decrease in serum VEGF, but failed to show a significant change in NO and ANG II levels during bevacizumab treatment. Although no significant correlation was found between the presence of hypertension and markers, most patients (83%) had an increase in their blood pressure. Our results suggest that dynamic monitoring of NO and ANG II, along with VEGF, may not be useful as predictive markers for bevacizumab treatment in colorectal cancer.
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    Can Low Molecular Weight Heparins Circumvent the Problem of Coumadine and Chemotherapy Interaction in Cancer Patients with Prosthetic Heart Valves?
    (2014) Sezer, Ahmet; Sumbul, Ahmet Taner; Abali, Gulcan; Sumbul, Zehra; Mualloglu, Sadik; Abali, Huseyin
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    Malignant pleural mesothelioma: A single-center experience in Turkey
    (2014) Sezer, Ahmet; Sumbul, Ahmet Taner; Abali, Huseyin; Mertsoylu, Huseyin; Ozyilkan, Ozgur
    Background: Malignant pleural mesothelioma is a rare lethal malignancy caused by asbestos exposure. It is more frequently seen in certain regions in Turkey. In this retrospective study, we aimed to analyse demographic, clinical, and pathological data and treatment-related features in 54 patients. Material/ Methods: The study included 54 patients diagnosed with malignant mesothelioma that were followed and treated. Results: Of the 54 patients, 34 (55.6%) were male. The median age in men and women were 60.3 (38.2-77.2) and 65.8 (37.7-77.5) years, respectively. In 35 (64.8%), exposure to asbestosis was present. Epithelial type was found in 27 (50.0%), followed by mixed type in 7 (13.0%) patients, and in 20 (37.0%) patients the subtype could not be determined. The disease was staged as IV in 37 (68.5%) patients. In 28 patients (51.9%), it was right-sided and in 1 (1.9%) it was bilateral. The most frequent metastatic sites (in decreasing order) were lungs, mediastinum, diaphragm, liver, and thoracal wall. Of the 54 patients, 36 (66.6%) received 1st-line chemotherapy and 20 (37%) 2nd-line chemotherapy. Eighteen patients (33.3%) received radiotherapy; 11 (20.3%) with palliative intention and 7 (12.9%) with curative intention. Median overall survival (OS) was 12.03 months (95% CI 7.2-16.8). OS was not affected by sex (p=0.32), smoking history (p=0.51), alcohol consumption (p=0.36), family history (p=0.67), pleural effusion presence (p=0.80), operation (p=0.14), clinical stage (p=0.072), symptom at presentation (p=0.66), having mixed type histology (p=0.079), asbestos exposure (p= 0.06), and type of 1st-line chemotherapy (p=0.161). On the contrary, it may be positively affected by good ECOG PS (0-1) (p<0.01), age below 65 (p=0.03), left-sided disease (p=0.01), receiving chemotherapy (p<0.01), having unilateral pleural effusion (p=0.018), and type of 2nd-line chemotherapy (p=0.025). Conclusions: OS of our patients was better than that found in the literature, seeming to be positively affected by early stages, better ECOG PS, age below 65 years, left side involvement, and having second-line chemotherapy with cisplatin- gemcitabine or 3M. Overall treatment success seems to be comparable to what is currently expected.
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    Concurrent Chemoradiotherapy with Vinorelbine plus Split-Dose Cisplatin may be an Option in Inoperable Stage III Non-Small Cell Lung Cancer: A Single-Center Experience
    (2015) Mertsoylu, Huseyin; Kose, Fatih; Sumbul, Ahmet Taner; Sedef, Ali Murat; Dogan, Ozlem; Besen, Ali Ayberk; Parlak, Cem; Findikcioglu, Alper; Muallaoglu, Sadik; Sezer, Ahmet; Sakalli, Hakan; Ozyilkan, Ozgur; 25731741
    Background: Concurrent chemoradiotherapy is the current standard treatment for inoperable stage III non-small cell lung cancer (NSCLC). In this study we aimed to investigate the efficacy and toxicity of CCRT with split dose of cisplatin (30 mg/m(2)) and vinorelbine (20 mg/m(2)) in patients with inoperable stage III NSCLC followed in our oncology clinic. Material/Methods: Medical records of 97 patients with inoperable stage III NSCLC treated with concurrent chemoradiotherapy with cisplatin-vinorelbine were retrospectively analyzed. Cisplatin (30 mg/m(2)) and vinorelbine (20 mg/m(2)) were administered on days 1, 8, 22, and 29 during radiotherapy. Two cycles of consolidation chemotherapy were given. All patient data, including pathological, clinical, radiological, biochemical, and hematological data, were assessed retrospectively using our database system. Results: Our study included 97 unresectable stage III NSCLC patients who were treated with CCRT. Median age was 58 years old (range 39-75) and 87 (89.7%) of the patients were men. ECOG performance score was 0-1 in 93 patients (95.9%). Squamous histology, the most common histology, was diagnosed in 46 patients (47.4%). Median follow-up time was 23.8 months. Median progression-free survival (PFS) and median overall survival time (OS) were 10.3 months and 17.8 months, respectively. Objective response rate and clinical benefit rate were 75.3% and 83.5%, respectively. Distant and local relapse rate were 57.1% and 42.9%, respectively. Hematological and non-hematological grade 3-4 toxicities were seen in 13 (13.4%) and 16 (16.5%) patients, respectively. Six (6.1%) patients died due to toxicity. Conclusions: The results of this study suggest that split-dose cisplatin may offer fewer grade III-IV toxicities without sacrificing efficacy and could be an option in patients with inoperable stage III NSCLC during CCRT. Similar to past studies, despite high response rate during CCRT, distant relapse is the major parameter that influences patient survival in long-term in NSCLC.
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    Ductal Adenocarcinoma: A Rare Entity of Prostate Gland in a Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Patient
    (2015) Ozgur, Tumay; Rifaioglu, Murat Mehmet; Sumbul, Ahmet Taner; Aydogan, Fusun; Atci, Nesrin
    Prostate cancer is the most common malignancy in men and ductal adenocarcinoma is a pathologic subtype with specific histological and clinical features. Seventy-six year-old male patient with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) admitted to our hospital with lower urinary tract symptoms. The last prostate specific antigen (PSA) level was 26 ng/ml and serial transrectal ultrasound guided biopsies were administered and benign prostate hyperplasia and non-specific prostatitis were the results of pathology reports. Due to the persistence of the symptoms transurethral resection of the prostate was performed. In the pathologic evaluation of the material adenocarcinoma focuses without stroma has been observed between the hyperplasic prostate tissues. The tumor has been diagnosed as ductal adenocarcinoma with 4 + 4 Gleason pattern score. Bone scintigraphy was revealed activity uptake on lomber vertebral column due to metastasis. Computerized tomography was revealed previous bilateral inguinal and right iliac lymphadenopathy due to CLL/SLL. Total androgen deprivation therapy and bilateral orchiectomy was applied. After three mounts according to biochemical and imaging results, radiotherapy cure began. Ductal adenocarcinoma is a rare subtype of prostate carcinoma with clinical behavior from that seen in conventional adenocarcinoma. On the other hand it is worth to point out the occurence of this entity as second malignancy during follow-up of CLL/SLL.
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    An old enemy not to be forgotten during PET CT scanning of cancer patients: tuberculosis
    (2016) Sumbul, Ahmet Taner; Sezer, Ahmet; Abali, Huseyin; Gultepe, Bilge; Kocer, Emrah; Reyhan, Mehmet; Tonyali, Onder; Ozyilkan, Ozgur; 27358601
    Aim of the study: Positron emission tomography-computed tomography (PET CT) scan is commonly used in current medical oncology practice as an imaging method. In this study we present data from cancer patients who were followed at our clinic and suspected of having tuberculosis during PET CT scanning. After the biopsy, they were diagnosed with concomitant tuberculosis. Material and methods: In this study, 14 patients who applied to our clinic and followed up due to cancer, and had PET CT scanning for the preliminary staging or further evaluation, were included. The patients were diagnosed with metastatic or recurrent disease, and their biopsy results revealed tuberculosis. Results: The mean age was 57.8 years with SD (standard deviation) 13.1 years and gender distribution of 78.6% (n = 11) females and 21.4% (n = 3) males. None of the patients had tuberculosis in their personal history (0%). Among the patients, 5 (35.7%) were diagnosed with tuberculosis during the preliminary staging, whereas 9 (64.3%) were diagnosed during the follow-up after the treatment. The median time to tuberculosis diagnosis was 11 months (min-max: 3-24 months) after the treatment. The most commonly involved lymph nodes during PET CT scanning were mediastinal in 8 (64.3%), axillary in 3 (21.4%) and para-aortic in 3 (21.4%) patients. The mean SUVmax (maximum standardised uptake value) of lymph node involved by PET CT scanning was defined as 8.5 (SD 2.6). Conclusions: Despite all improvements in modern medicine, tuberculosis is still a serious public health problem. It should always be considered in differential diagnosis while evaluating PET CT scanning results of cancer patients, because it may cause false positive results.