Publications by authors named "Osman Kostek"

67 Publications

The Relationship between Nutritional Parameters and Thrombosis Risk in Cancer Patients.

Nutr Cancer 2021 Jul 26:1-6. Epub 2021 Jul 26.

Department of Medical Oncology, Faculty of Medicine, Akdeniz University, Antalya, Turkey.

Venous thromboembolism which consists of pulmonary embolism and deep venous thrombosis is one of the most important problems in cancer patients. The mechanisms of cancer-associated thrombosis are multi-factorial and still unclear. Nutrition is an important factor in the treatment and prognosis of cancer. Assessment of the nutritional status of cancer patients is multifactorial and it should be performed at each visit. We aimed to assess the relationship between nutritional status and thrombosis risk in various cancer types. It was a cross-sectional and single-center study and 582 cancer patients were included. Patients nutritional status was evaluated with their height, weight, BMI, triceps skinfold thickness, waist circumference, and upper arm circumference. It was found that there was a statistically significant relationship between the thrombosis risk and nutritional parameters such as weight, BMI, and waist circumference which are important anthropometric measurements. As a result, thrombosis is an important cause of morbidity and mortality in cancer patients. Obesity and cachexia are both important conditions in cancer patients and should be well evaluated. It has been shown that increased weight, BMI, and waist circumference indicating obesity are important risk factors for thrombosis risk in cancer patients.
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http://dx.doi.org/10.1080/01635581.2021.1952631DOI Listing
July 2021

Prognostic Factors for Survival in Transverse Colon Cancers.

J Gastrointest Cancer 2021 Jul 24. Epub 2021 Jul 24.

Division of Medical Oncology, Department of Internal Medicine, Trakya University School of Medicine, Edirne, Turkey.

Background: Transverse colon cancer (TCC) is a rare condition that accounts for 10% of all colon cancers. TCC was accepted more likely right-sided colon cancers. We aimed to investigate whether TCC differs from other colon tumors by using clinical, pathological, and molecular prognostic factors known to be important in colon cancer and if it differs in its own anatomical structure.

Patients And Methods: We evaluated local and locally advanced TCC patients between 2007 and 2020 years for demographics data, symptoms, treatment status, and histopathological and molecular features.

Results: Overall, 107 TCC patients were included in this study. According to the molecular data analysis of 44, 35, and 23 patients for MSI, RAS, and BRAF status, respectively, 7 (15.9%) were MSI-H, 13 (37.1%) were RAS mutant, and 11 (47.8%) had BRAF V600E mutation. The median follow-up time was 31.5 months. Median disease-free survival (DFS) was 5.19 months, and median OS was 88.3 months for the whole study population. The tumor stage was the most significant prognostic factor for DFS and OS. Although BRAF mutation was not a significant marker for DFS, it was an independent prognostic marker for OS (HR 3.90 95% CI 1.42-10.7). There were no statistically significant differences between proximal two-thirds and distal one-third tumor location.

Conclusion: TCC has molecular features and prognostic factors more likely RCC and no differences between proximal and distal sub-parts. BRAF V600E mutation status is an independent predictor of survival even in the early stages of TCC.
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http://dx.doi.org/10.1007/s12029-021-00675-1DOI Listing
July 2021

The relation between tissue galectin-3 level and platinum resistance in neoadjuvant bladder cancer treatment.

J BUON 2021 May-Jun;26(3):1034-1039

Trakya University School of Medicine, Department of Internal Medicine, Division of Medical Oncology, Edirne, Turkey.

Purpose: This study aimed to reveal the relationship between the level of galectin-3 expression and the depth of response to neoadjuvant therapy in bladder tumor tissue with muscle invasion revealed by transurethral biopsy.

Methods: The percentage of galectin-3 staining in transurethral biopsy tissue with muscle invasion was determined by immunohistochemistry. The patients were divided into two groups: the down-staging (+) group consisting of patients with pathological complete response or non-invasive bladder cancer, and the down-staging (-) group consisting of patients with stage 2 and above.

Results: There were 11 patients in the down-staging (+) group and 12 patients in the down-staging (-) group. There was no significant difference between the two groups in terms of median age, gender, smoking, clinical stage at the time of diagnosis, distribution of carboplatin or cisplatin used as a platinum agent. Galectin-3 was positive in 2 patients (18.2%) in the group where down-staging was achieved with neoadjuvant therapy, while it was positive in 9 patients (75%) in the other group (p = 0.01). The median follow-up period of the patients was 31.6 months (95% CI 25.1-39.3). Overall survival was 43.4 months in the down-staging (+) group (95% CI 25.1-61.6) and 31.6 months in the down-staging (-) group (95% CI 12.7-50.6). Although there was a numerical difference, it did not reach statistical significance (p=0.37).

Conclusion: The rate of down-staging after platinum-based neoadjuvant chemotherapy is significantly higher in patients with low galectin-3 staining in transurethral bladder biopsy tissue.
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July 2021

Skeletal muscle loss during anti-epidermal growth factor receptor therapy is an independent prognostic factor on non-small cell lung cancer patients survival.

J BUON 2021 May-Jun;26(3):853-860

1Division of Medical Oncology, Department of Internal Medicine, Trakya University School of Medicine, Edirne, Turkey.

Purpose: We aimed to assess whether skeletal muscle loss during EGFR thyrosine kinase inhibitor therapy of advance non-small cell lung cancer patients is an independent prognostic factor for progression-free survival (PFS) and overal survival (OS).

Methods: A total of 45 patients who had computed tomography images were retrospectively evaluated at the diagnosis and during the treatment period before progression occurs.

Results: During treatment 19 patients (42.2%) had skeletal muscle loss. Objective response rates in muscle loss group and muscle stable group were 36.8% and 73.0%, respectively (p<0.01). Median follow-up time was 18.9 months (14.8-32.1). Median PFS was 14.7 months (95% CI 12.1-17.3) in muscle stable group and 7.6 months (95% CI 6.7-8.5) in muscle loss group (p<0.01). Median OS was 18.3 months (95% CI 16.5-20.2) in muscle loss group while it was 30.1 months (95% CI 22.1-38.2) in muscle stable group (p<0.01). In multivariate analysis for both PFS and OS, skeletal muscle loss was an independent prognostic factor. Hazard ratios (HR) for PFS and OS were 12.2 (95% CI 4.3-34.4) and 3.51 (95% CI 1.41-8.73) respectively.

Conclusion: On CT imaging skeletal muscle loss before progression is an independent prognostic factor for both PFS and OS in advance non-small cell lung cancer patients who received EGFR tyrosine kinase inhibitor therapy.
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July 2021

Factors affecting the mortality rate of patients with cancer hospitalized with COVID-19: a single center's experience.

J Chemother 2021 May 25:1-10. Epub 2021 May 25.

Department of Medical Oncology, Health Science University Kartal Dr. Lütfi Kırdar Training and Research Hospital, İstanbul, Turkey.

The main objective is to define the mortality of patients with cancer admitted to our hospital, their clinical and demographic characteristics, investigate the risk of COVID-19 for patients with cancer, and determine factors that affect the mortality rates of patients with cancer dying of COVID-19. A total of 2401 patients were admitted to our hospital with the diagnosis of COVID-19 from March 11th, 2020, to May 31st, 2020. Ninety-two out of a total of 112 cancer patients were included in this study based on the planned inclusion/exclusion criteria. The clinical, demographic, and laboratory features and treatments provided were studied, and their effect on mortality rates was analyzed. In our study the median age of the patients was 67 years, and 55.4% were male. More than half (56.5%) of our patients had metastasis. The mortality rate was 6.2% in the overall population with COVID-19, whereas it was 23.9% in patients with cancer. The mortality rate in patients with metastasis was statistically significantly higher compared with those without metastasis (34.0% vs. 10.3%  0.008). The mortality rate in patients still smoking was statistically significantly higher than in non-smokers (37.5% vs. 12.5%  0.033). The mortality rates of patients with high average C-reactive protein (CRP), ferritin, lactate dehydrogenase (LDH), and D-dimer levels were statistically significantly higher than in those without, and the mortality rates of patients with lower average albumin and hemoglobin levels were statistically significantly higher than those without ( 0.001,  0.006,  0.041,  0.001,  0.001, and  0.028, respectively). Having metastases concurrent with COVID-19 was a statistically significant factor predictive of prognosis. Also, high CRP, ferritin, LDH, and D-dimer, and low albumin and hemoglobin were related to increased mortality rates. The predictive and prognostic role of possible factors related to prognosis is still unknown and further large, multicenter prospective studies are needed to confirm these results.
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http://dx.doi.org/10.1080/1120009X.2021.1923153DOI Listing
May 2021

Prognostic factors in patients with metastatic urothelial carcinoma who have treated with Atezolizumab.

Int J Clin Oncol 2021 Aug 23;26(8):1506-1513. Epub 2021 May 23.

Medical Oncology, Istanbul Kartal Dr. Lutfi Kirdar Training and Research Hospital, Istanbul, Turkey.

Background: Atezolizumab (ATZ) has demonstrated antitumor activity and manageable safety in previous studies of patients with metastatic platinum-resistant urothelial carcinoma. However, the response rate of Atezolizumab was modest. In the current study, we evaluated the pretreatment prognostic factors for overall survival in patients with metastatic urothelial carcinoma who have progressed after first-line chemotherapy in the Expanded-Access Program of Atezolizumab.

Patients And Methods: In this study, we present a retrospective analysis of 113 patients with urothelial cancer treated with ATZ after progression on first-line chemotherapy. Data of the patients was obtained from patient files and hospital records. Eligible patients included metastatic urothelial carcinoma patients treated with at least one course of ATZ. Univariate analysis was used to identify clinical and laboratory factors that significantly impact OS. Variables were retained for multivariate analysis if they had a statistical relationship with OS (p  < 0.1), and then included a final model of p  < 0.05.

Results: The median follow-up duration was 23.5 months. Of the patients, 98 (86.7%) were male and 13.3% were female. The median age was 65 years of age (37-86). In univariate analysis, primary tumor location in the upper tract, increasing absolute neutrophil count (ANC), increasing absolute lymphocyte count, neutrophil-to-lymphocyte ratio (NLR) > 3, liver metastases, baseline creatinine clearance less (GFR) than 60 ml/min, Eastern Cooperative Oncology Group (ECOG) performance status (1 ≥), and hemoglobin levels below 10 mg/dl were all the significantly associated with OS. Three of the five adverse prognostic factors according to the Bellmunt criteria were independent of short survival: liver metastases HR 3.105; 95% CI 1.673-5.761; p < (0.001), ECOG PS (1 ≥) HR 2.184; 95% CI 1.120-4.256; p = 0.022, and Hemoglobin level below 10 mg/dl HR 2.680; 95% CI 1.558-4.608; p < (0.001). In addition, NLR > 3 hazard ratio [HR] 2.092; 95% CI 1.031-4.243; p = 0.041 and GFR less than 60 ml/min HR 1.829; 95% CI 1.1-3.041; p = 0.02, maintained a significant association with OS in multivariate analysis.

Conclusions: This model confirms the Bellmunt model with the addition of NLR > 3 and GFR less than 60 ml/min and can be associated with clinical trials that use immunotherapy in patients with bladder cancer.
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http://dx.doi.org/10.1007/s10147-021-01936-6DOI Listing
August 2021

Efficacy and Safety of Trastuzumab Emtansine in Her2 Positive Metastatic Breast Cancer: Real-World Experience.

Cancer Invest 2021 Jul-Aug;39(6-7):473-481. Epub 2021 Jun 7.

Department of Medical Oncology, Selçuk University, Konya, Turkey.

Aim: The aim of this study is to evaluate the efficacy and toxicity of trastuzumab emtansine (T-DM1) in cases with metastatic breast cancer (mBC) in different lines of treatment.

Method: Retrospective analysis of T-DM1 results of human epidermal growth factor receptor 2 (Her2) positive 414 cases with mBC from 31 centers in Turkey.

Findings: Except 2, all of the cases were female with a median age of 47. T-DM1 had been used as second-line therapy in 37.7% of the cases and the median number of T-DM1 cycles was 9. Progression-free survival (PFS) and overall survival (OS) times were different according to the line of treatment. The median OS was found as 43, 41, 46, 23 and 17 months for 1st, 2nd, 3rd, 4th and 5th line, respectively ( = 0.032) while the median PFS was found as 37, 12, 8, 8 and 8 months, respectively ( = 0.0001). Treatment was well tolerated by the patients. The most common grade 3-4 adverse effects were thrombocytopenia (2.7%) and increased serum gamma-glutamyl transferase (2%).

Discussion: The best of our knowledge this is the largest real-life experience about the safety and efficacy of T-DM1 use in cases with mBC after progression of Her2 targeted treatment. This study suggests and supports that T-DM1 is more effective in earlier lines of treatment and is a reliable option for mBC.
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http://dx.doi.org/10.1080/07357907.2021.1933011DOI Listing
July 2021

Comparative assessment of three different second-line regimens in chemotherapy resistant / refractory small-cell lung cancer.

J BUON 2021 Jan-Feb;26(1):79-86

Department of Medical Oncology, Sakarya University / Faculty of Medicine, Sakarya, Turkey.

Purpose: Small cell lung cancer (SCLC) patients unresponsive or relapsing within 90 days following frontline chemotherapy have poor prognosis and they should be treated with different chemotherapy regimens other than those used in the first-line regimen. Currently there is no globally accepted standard chemotherapeutic regimen for the treatment of these patients. This retrospective study was designed to compare CAV (Cyclophosphamide, Doxorubicin, Vincristine), weekly topotecan and weekly irinotecan regimens and to evaluate the efficacy of the three regimens in patients with chemotherapy resistant/refractory (CRR) SCLC.

Methods: A total of 67 CRR-SCLC patients, who were treated with CAV, weekly topotecan and weekly irinotecan were reviewed for weekly irinotecan (27 for 60 mg/m2 intravenously on days 1, 8 and 15 of a 28-day cycle,24 for CAV (Cyclophosphamide 750 mg/m² on day 1, Doxorubicin 50 mg/m² on day 1 and Vincristine 1.4mg/m2 on day 1 every 3 weeks), 16 for weekly topotecan (4 mg/m2 intravenously on days 1, 8 and 15 of a 28-day cycle).

Results: The median follow-up time was 12.45 months, there was no difference about disease control rates (DCR) between three chemotherapy regimens (DCR; 25.9% with irinotecan, 29.2% with CAV and 31.3% with topotecan, p=0.92). Objective response rates (ORR) for irinotecan, CAV and topotecan groups were 3,7%, 8,8%, and 0%, respectively (p=0.63). Median progression free survival (PFS) and overall survival (OS) were similar according to irinotecan, CAV, and topotecan (PFS: 1.93 months, 2.30 months and 3.45 months; OS: 2.89 months, 4.79 months and 5.81 months, respectively). The adverse events were generally mild and manageable for both hematological and nonhematological toxicities in all three arms.

Conclusions: Weekly irinotecan, CAV and weekly topotecan are similarly effective and safe chemotherapy protocols for the treatment of CRR-SCLC patients.
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March 2021

Comparison of real-life data from patients with NGS panel negative and mutation positive metastatic lung adenocarcinoma.

Tumori 2021 Feb 24:300891621996448. Epub 2021 Feb 24.

Department of Internal Medicine, Division of Medical Oncology, Trakya University School of Medicine, Edirne, Turkey.

Objective: To evaluate clinical and demographic characteristics and the results of cytotoxic treatments of , , and next-generation sequencing (NGS) panel negative patients.

Methods: NGS data of 1264 patients with non-small cell lung cancer were retrospectively evaluated. Among these patients, the mutation distributions of 1081 patients with metastatic lung adenocarcinoma were analyzed. A total of 150 patients with negative NGS panel or mutant followed up in our clinic were included. Clinical features, overall survival, first-line chemotherapy responses, and progression-free survival of NGS panel negative, , and groups were compared.

Results: In 1081 patients who underwent NGS from tumor tissue with the diagnosis of metastatic lung adenocarcinoma, 296 (27%) NGS panel negative and 276 (26%) mutant patients were detected. Among these patients, 150 patients whose data were available were 71 (47.3%) NGS panel negative, 54 (36%) , and 25 (16.7%) . Clinical features, brain metastasis, and first-line chemotherapy response were similar among groups. Bone metastases were detected more often in the NGS panel negative group ( = 0.03). The median follow-up was 8.4 months. Overall, 107 deaths had occurred at the time of analysis. There was no difference in overall survival ( = 0.56) or progression-free survival ( = 0.71) among NGS panel negative, , and patients.

Conclusion: There is no difference in overall survival, first-line chemotherapy response, or progression-free survival among patients with NGS panel negative, , or metastatic lung adenocarcinoma. Bone metastases were observed more frequently in the NGS panel negative group.
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http://dx.doi.org/10.1177/0300891621996448DOI Listing
February 2021

Perioperative myocardial damage and the incidence of type 2 myocardial infarction in patients with intermediate and high cardiovascular risk.

Anatol J Cardiol 2021 02;25(2):89-95

Department of Internal Medicine, Medeniyet University Göztepe Education and Research Hospital, Istanbul Turkey.

Objective: Perioperative myocardial infarction is a major cause of morbidity and mortality in patients undergoing surgical operations. We aimed to determine the incidence of perioperative myocardial infarction in patients with intermediate- or high-risk Framingham scores.

Methods: One hundred and one patients (62 males, 39 females) over 40 years of age (mean age 72±11 years) median 73 (65-81), min- max (46-96), with Framingham risk scores of 10% or higher, and scheduled for surgical interventions in the orthopedics and urology departments of our hospital were included in the study. Patient demographics, comorbidities, blood pressures, and biochemical data were recorded. Troponin values and electrocardiographic findings were obtained during the immediate preoperative period and on postoperative day 2 and then compared. Perioperative myocardial injury and infarction were diagnosed using the third universal definition of myocardial infarction.

Results: In 44 (43%) patients, postoperative troponin values were compared with the preoperative values. In 26 (25%) patients, the changes were consistent with myocardial ischemia or damage. Alterations in troponin values with significant electrocardiogram (ECG) changes were found in 6 patients (6%).

Conclusion: The risk of postoperative myocardial damage was high in our patients with intermediate or high-risk Framingham scores. This im-plies that close follow-up of these patients with abnormal ECG and troponin values during the pre- and postoperative period is required.
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http://dx.doi.org/10.14744/AnatolJCardiol.2020.45752DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8114639PMC
February 2021

Comparing Late-line Treatment Sequence of Regorafenib and Reduced-intensity FOLFOXIRI for Refractory Metastatic Colorectal Cancer.

Authors:
Osman Köstek

Am J Clin Oncol 2020 12;43(12):905-906

Edirne Sultan I. Murat State Hospital, Clinic of Medical Oncology, Edirne, Turkey.

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http://dx.doi.org/10.1097/COC.0000000000000759DOI Listing
December 2020

Does the efficacy of regorafenib differ in chemotherapy refractory metastatic colorectal cancer patients who had mucinous pathology compared to those who had non-mucinous pathology?

Curr Probl Cancer 2021 Jun 22;45(3):100670. Epub 2020 Oct 22.

Department of Medical Oncology, Health Science University Kartal Dr. LütfiKırdar Training and Research Hospital, İstanbul, Turkey.

Purpose: To investigate the importance of mucinous histopathology on the assessment of tumor response in patients with metastatic colorectal cancer (mCRC) receiving regorafenib.

Materials And Method: All patients diagnosed with histologically confirmed mCRC in 2 oncology centers between 2013 and 2018 were retrospectively analyzed. Among 678 patients diagnosed with mCRC, 103 patients were treated with regorafenib. Ninety-four of these patients who had used at least 2 cycles of regorafenib and evaluable for treatment response were included in the analysis. Histopathologically, 18 patients with mucinous adenocarcinoma and 76 patients with nonmucinous adenocarcinoma were compared in terms of response rate and survival durations.

Results: Median follow-up duration of 6 months, median age of the patients was 61 (34-77) years. While 19.1% of the patients had mucinous histology, 80.9% had nonmucinous histology. The overall response rate was significantly lower in the mucinous subgroup than the nonmucinous subgroup (5.6% vs 43.4%, respectively, P = 0.003). Similarly, both progression-free survival (3.0 vs 4.0 months, respectively, P = 0.011) and overall survival duration were shorter in the mucinous subgroup (3.0 vs 7.0 months, P = 0.016, respectively) compared with the nonmucinous subgroup.

Conclusion: The histological subgroup may predict tumor response in mCRC patients receiving regorafenib. Its efficacy on nonmucinous histology had significantly more favorable than mucinous subtype.
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http://dx.doi.org/10.1016/j.currproblcancer.2020.100670DOI Listing
June 2021

Introduction of a novel quantitative scoring system for acanthosis nigricans and its validation in a pilot study.

Dermatol Ther 2020 11 7;33(6):e14450. Epub 2020 Nov 7.

Department of Dermatology and Allergy, Technical University of Munich, Munich, Germany.

Inconsistent data exist regarding the diagnostic value of acanthosis nigricans (AN) or skin tags as clinical markers for obesity or diabetes. In an outpatient department-based prospective study, we designed a scoring for AN severity (SCANS) to evaluate AN and skin tags, their correlation with obesity or diabetes. Quantification of AN in six anatomic sites, in consideration of the affected skin surface areas, texture changes, number of skin tags, leads to a total severity score between 0 and 46. Among 336 adult patients (aged ≥18 years) with AN, a higher BMI was associated with AN (r = 0.299, P < .001), but not with diabetes (P = .43), as compared with 243 age- and sex-matched controls without AN. Among nondiabetics, AN scores were significantly correlated with waist circumference (r = 0.131, P = .024) and total cholesterol levels (r = 0.155, P = .04). Skin tags alone in the absence of AN were not associated with obesity (P = .333) or diabetes (P = .164). The total AN scores were positively correlated with the presence of skin tags (r = 0.132, P < .001), and the involvement of anterior neck (r = 0.668, P < .001) and axilla (r = 0.793, P < .001). Knuckles and groins were unaffected in our series. Our results indicate that combination of AN with skin tags can be used as clinical marker for obesity, but not for diabetes. Large-scale studies on patients of different ethnic background are required to further validate our proposed scoring.
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http://dx.doi.org/10.1111/dth.14450DOI Listing
November 2020

Efficacy of regorafenib in the second-and third-line setting for patients with advanced hepatocellular carcinoma: A real life data of multicenter study from Turkey.

J BUON 2020 Jul-Aug;25(4):1897-1903

Department of Medical Oncology, Trakya University, Medicine Faculty, Edirne, Turkey.

Purpose: After failure of the first-line sorafenib treatment in advanced or metastatic stage hepatocellular carcinoma (HCC), regorafenib is one of the newly-approved targeted agents. We aimed to evaluate the efficacy of regorafenib in patients with advanced HCC treated in the second- or third-line setting.

Methods: In this retrospective and multicenter study, advanced HCC patients not eligible for local therapies, who received a second- or third-line regorafenib therapy after progression on the first-line sorafenib or sequential therapy with chemotherapy (CT) followed by sorafenib, were included.

Results: In the first-line setting, 28 (28.9%) patients received CT and 69 (71.1%) patients received sorafenib. There were 24 (24.7%) patients who were intolerant to sorafenib. Disease control rate (DCR) was 53.6% for all patients treated with regorafenib, 62.3% in patients who received regorafenib in the second-line, and 32.1% for those receiving regorafenib in the third-line (p=0.007). Median progression-free survival (PFS) and overall survival (OS) were 5.6 (range; 4.3-6.9) and 8.8 (range, 6.3-11.3) months for all patients treated with regorafenib vs. 7.1 months and 10.3 months for patients who received regorafenib in the second-line vs. 5.1 and 8.7 months for patients who received regorafenib in the third-line, respectively; however, there was no statistically significant difference (pPFS=0.22 and pOS=0.85).

Conclusion: Although receiving CT as a first-line therapy in advanced HCC patients did not affect the survival rates of subsequent regorafenib therapy, it might diminish the DCR of regorafenib.
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July 2021

Sunitinib or Pazopanib: Is There Any Difference Between Tyrosine Kinase Inhibitors in the Pre-Nivolumab Setting in Metastatic Renal Cell Carcinoma?

Cureus 2020 Sep 18;12(9):e10525. Epub 2020 Sep 18.

Medical Oncology, Health of Science Ankara City Hospital, Ankara, TUR.

Introduction Treatment options for metastatic renal cell carcinoma disease have been improved in recent years. However, there is still no optimal treatment sequence or combination for metastatic disease. We aimed to investigate whether patients differed in terms of disease outcomes regarding pre-nivolumab tyrosine kinase inhibitors (TKIs). Material and methods The analysis of patients was performed after all cohorts were sub-grouped into two groups according to pre-nivolumab TKIs as following the sunitinib arm and the pazopanib arm. Result A total of 75 patients were included in this study. The median follow-up time was eight months for all cohorts. The objective response rate was statistically significantly higher in the pazopanib arm as compared to the sunitinib arm (56% vs 30%, p=0.02). Progression-free survival was significantly higher in pazopanib than sunitinib (10.3 months vs 5.3 months, p=0.02). Multivariate analysis revealed that pazopanib treatment was associated with better progression-free survival (HR: 0.44, 95 CI; 0.22-0.91, p=0.02). While the median overall survival for patients who had received sunitinib was 11.0 months, it has not been reached the median in the pazopanib arm (11.0 months vs NR, p=0.051). Discussion We demonstrated significantly better progression-free survival and a higher objective response rate with nivolumab treatment in patients who had received pazopanib as compared with patients who received sunitinib in the pre-nivolumab period.
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http://dx.doi.org/10.7759/cureus.10525DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7574822PMC
September 2020

Atezolizumab in Patients with Metastatic Urothelial Carcinoma Who Have Progressed After First-line Chemotherapy: Results of Real-life Experiences.

Eur Urol Focus 2020 Sep 30. Epub 2020 Sep 30.

Medical Faculty, Ankara University, Ankara, Turkey.

Background: Atezolizumab (ATZ) has demonstrated antitumor activity and manageable safety in previous studies in patients with locally advanced or metastatic platinum-resistant urothelial carcinoma.

Objective: To compare the real-life experience and data of clinical trials on ATZ treatment in metastatic urothelial carcinoma.

Design, Setting, And Participants: Patients with urothelial cancer treated with ATZ after progression on first-line chemotherapy from an expanded access program were retrospectively studied. Data of patients were obtained from their files and hospital records. Safety was evaluated for patients treated with at least one cycle of ATZ.

Outcome Measurements And Statistical Analysis: The primary endpoint was objective response rate (ORR). The secondary endpoints are overall survival (OS), progression-free survival (PFS), duration of response, and safety profile of patients. Kaplan-Meier methods were used to calculate median follow-up and estimate PFS and OS.

Results And Limitations: Data of 115 enrolled patients were analyzed. Most of the patients (92.3%, n = 106) had received chemotherapy regimen only once prior to ATZ. The median follow-up duration was 23.5 mo. The complete response rate, partial response rate, and ORR were 8.7% (n = 10), 20.0% (n = 23), and 28.7% (n = 33), respectively. The median duration of response was 20.4 mo (95% confidence interval [CI], 6.47-28.8). Of the 33 patients who responded to treatment, 60% (n = 20) had an ongoing response at the time of the analysis. PFS and OS with ATZ were 3.8 mo (95% CI, 2.25-5.49) and 9.8 mo (95% CI, 6.7-12.9), respectively. All-cause and any-grade adverse events were observed in 113 (98%) patients. Of the patients, 64% experienced a treatment-related adverse event of any grade and 24 (21.2%) had a grade 3-4 treatment-related adverse event. Limitations of the study included its retrospective design, and determination of treatment response based on clinical notes and local radiographic studies.

Conclusions: In these real-life data, ATZ was effective and well tolerated in patients with metastatic urothelial carcinoma who have progressed with platinum-based first-line chemotherapy. ATZ is an effective and tolerable treatment for patients with locally advanced or metastatic platinum-resistant urothelial carcinoma in our study, similar to previously reported trials.

Patient Summary: Atezolizumab is effective and well-tolerated in patients with metastatic urothelial cancer who progressed with first-line chemotherapy, consistent with the outcomes of the previous clinical trials in this setting.
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http://dx.doi.org/10.1016/j.euf.2020.09.010DOI Listing
September 2020

Is lymph node dissection necessary for staging while undergoing nephrectomy in patients with renal cell carcinoma?

Curr Probl Cancer 2021 02 6;45(1):100619. Epub 2020 Aug 6.

Bezmialem Vakif University, School of Medicine Hospital, Department of Medical Oncology, Istanbul, Turkey.

Objective: The essential treatment for patients with renal cell carcinoma is nephrectomy. As no lymph node dissection (LND) could be performed in the majority of these patients, healthy staging could not be carried out. In this study, we investigated the impact of LND during nephrectomy on patient survival.

Methods: A total of 181 patients-58 (32%) were female and 123 (68%) were male-were included in the study. Median follow-up period was 48 months. The patients were separated into 4 groups according to their stage during diagnosis; group 1 (T1-3N0M0), group 2 (T1-3NXM0), group 3 (T1-3N1M0), and group 4 (T1-4N0/XM1). The disease-free survival of nonmetastatic patients and the overall survival of all groups were calculated.

Results: Mean age was 58.4 ± 12.0 years. Median survival for Group 1 could not be reached. Median survival was 89 months in Group 2, 50 months in Group 3, and 39 months in Group 4 (P <0.001). There was no statistically significant difference between the N1 and M1 groups (P = 0.297). For the NX patient group without LND, median survival was 89 months, which is worse than the N0 group and better than the N1 group (P = 0.002).

Conclusions: Our study presumes that the patients without LND are not staged sufficiently, NX patients have worse survival rates when compared with N0 patients, node-positive patients have poor survival rates as do the metastatic patients, and it should be defined as TNM stage4.
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http://dx.doi.org/10.1016/j.currproblcancer.2020.100619DOI Listing
February 2021

The relationship between FDG PET/CT-defined metabolic parameters and the histopathological subtype of oesophageal carcinomas.

Pol J Radiol 2020 15;85:e254-e260. Epub 2020 May 15.

Department of Nuclear Medicine, Faculty of Medicine, Trakya University, Edirne, Turkey.

Purpose: 18F-fluorodeoxyglucose (F-FDG) positron emission tomography (PET) combined with computed tomography (CT) scan is accepted as a standard tool in the staging of oesophageal cancer (OC). Histological subtype of tumour is known to be a major determinant of prognosis and metabolic behaviour. In this study, we aimed to evaluate the effect of histological subtypes of OC on standard uptake value (SUV), metabolic tumour volume (MTV), and total lesion glycolysis (TLG) obtained by PET/CT, and also to compare this effect with prognosis.

Material And Methods: Images and clinical course data of 57 patients who were diagnosed with EC and treated in our hospital between 2009 and 2016 were evaluated in a retrospective manner. PET/CT images were re-analysed in terms of metabolic parameters, and observations were compared with histological subtypes.

Results: No significant difference was observed between histological subtypes with SUV, overall survival (OS), or progression-free survival (PFS). Thus, MTV was observed to be related with histological subtype; MTV values of adenocancer patients were significantly higher than those of squamous cell cancer patients.

Conclusions: Metabolic tumour volume was related with histological subtype of OC, but clinical staging, TLG, and SUV values were not related with histological subtype, which may suggest the use of MTV as a routine parameter for OC and inclusion of MTV observations in prognostic scoring.
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http://dx.doi.org/10.5114/pjr.2020.95945DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7315051PMC
May 2020

Contrast nephropathy in cancer patients receiving anti-VEGF therapy: a prospective study.

Int J Clin Oncol 2020 Oct 26;25(10):1757-1762. Epub 2020 Jun 26.

Division of Medical Oncology, Department of Internal Medicine, Trakya University School of Medicine, 22030, Edirne, Turkey.

Objectives: Contrast nephropathy risk has been increasing in cancer patients. Nephrotoxic side effects of anti-vascular endothelial growth factor/receptor (anti-VEGF/R) drugs used in oncologic treatment are also prominent. The purpose of this study was to identify the possible association among anti-VEGF/R drugs use and development of the contrast-induced nephropathy (CIN) in patients with cancers.

Methods: A total of 92 patients were included in this prospective cross-sectional study. Patients whose glomerular filtration rate (GFR) of < 50 ml/min, hemoglobin of < 10 g/dl, and eastern cooperative oncology group (ECOG) score of ≥ 2 and had received nephrotoxic drugs were not included in the study. Blood samples were collected baseline at pre computed tomography (CT) and day 2, day 3 and day 7 later CT imaging. CIN was defined as either an increased serum creatinine value of 0.5 mg/dl or increased 25% to baseline. CIN frequency between groups receivingand not receiving anti-VEGF/R was compared using the chi-squared test. CIN frequency between bevacizumab and other anti-VEGF/R was also analyzed.

Results: There were 39 patients in the anti-VEGF/R (+) group and 53 patients in the anti-VEGF/R (-) group. Eleven patients (28%) in the anti-VEGF/R (+) group and 3 patients (5.6%) in the anti-VEGF/R (-) group had CIN (p = 0.006). In the anti-VEGF/R (+) group, 23 patients received bevacizumab (combined with FOLFOX/FOLFIRI), while 16 patients received other anti-VEGF/R (sunitinib, axitinib, regorafenib, aflibercept) effective treatments. CIN ratio in patients who received bevacizumab or other anti-VEGFR therapy was similar (p = 0 = 50). Of the patients, one patient had acute kidney injury leading to death.

Conclusion: CIN was significantly more frequent in cancer patients who receiving anti-VEGF/R drugs than those not receiving anti-VEGF/R drugs.
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http://dx.doi.org/10.1007/s10147-020-01729-3DOI Listing
October 2020

Sarcopenia and Inflammation with Immunotherapy.

Oncologist 2020 05 19;25(5):e875. Epub 2020 Mar 19.

Haydarpaşa Numune Training and Research Hospital, Clinic of Medical Oncology, İstanbul, Turkey.

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http://dx.doi.org/10.1634/theoncologist.2019-1005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7216466PMC
May 2020

Assessment of Duodenal Diverticula: Computed Tomography Findings.

Curr Med Imaging Rev 2019;15(10):948-955

Department of Radiology, School of Medicine, Trakya University, Edirne, Turkey.

Aims: To demonstrate the prevalence, accompanying pathologies, imaging and follow up findings of Duodenal Diverticula (DD) with Multidetector Computed Tomography (MDCT).

Materials And Methods: Consecutive 2910 abdominal MDCTs were retrospectively reviewed on axial, coronal and sagittal planes. DD were evaluated for prevalence, location, number, size, contents, diverticular neck, accompanying pancreaticobiliary pathologies, jejunal and colonic diverticula, respectively.

Results: DD were diagnosed in 157 cases (5.4%) and found mostly in the second part of the duodenum. Juxta-ampullary DD was the most common type (78.3%) and mostly located ventral (n:86, 69.9%) to the ampulla of Vater. DD was solitary in 123 patients (78.3%) and more than one in 34 patients (21.7%). The median diameter of DD was 2.5 cm (range 1.5-3.6 cm) in the long-axis. The lumen of DD contains air and contrast agent (n:96, 61.1%); air, contrast agent and debris (n:42, 26.7%) in most cases. Colonic diverticula (n:36, 22.9%), cholelithiasis (n:32, 20.4%), choledocholithiasis (n:7, 4.4%), and biliary dilatation (n:8, 5.1%) were the most common additional findings. Median follow-up time was 23 months (range 11 to 41 months). In three cases, new findings (cholelithiasis, n:3, choledocholithiasis, n:1) were detected.

Conclusion: Accompanying pathologies with DD diagnosis are valuable for physicians in order to manage the patients. Following clinical and radiological features of well-diagnosed DD might reduce the possible complications.
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http://dx.doi.org/10.2174/1573405614666180904123526DOI Listing
October 2020

Does celiac disease impair coronary microvascular circulation: Coronary flow velocity reserve of patients with celiac disease.

Echocardiography 2020 01 9;37(1):34-40. Epub 2019 Dec 9.

Cardiology, Istanbul Medeniyet University Goztepe Training and Research Hospital, Istanbul, Turkey.

Background: Celiac disease (CD) is an enteropathy characterized with immune reaction to gliadin protein.

Aim: In this study, we aimed to assess effect of CD on coronary microvascular circulation and the association between coronary flow velocity reserve (CFVR) and hs-CRP/Albumin ratio.

Material And Methods: Study was conducted between March 2017 and November 2018 with CD at Umraniye Training and Research Hospital Gastroenterology Clinic. CFVR was defined as the ratio of hyperemic to baseline diastolic peak velocities. CFVR ≥ 2.0 was considered normal. C-reactive protein/albumin ratio (CAR) was calculated as hs-CRP/albumin.

Results: Serum albumin (4.27 ± 0.56 vs 4.50 ± 0.34; P value: .04) level was significantly lower in celiac group but higher Hs-CRP (2.44 ± 1.24 vs 1.82 ± 1.29; P value < .01), hs-CRP/albumin ratio (0.57 ± 0.30 vs 0.41 ± 0.31; P value: .03) were recorded in celiac group. Both hyperemic flow and CFVR substantially lower in the celiac group compared to controls. In univariate analysis; age, hs-CRP, and hs-CRP/albumin ratio were associated with low CFVR and hs-CRP/albumin level was an accurate predictor of low CFVR at the ROC curve.

Conclusion: In this study, we found that in patients with CD, coronary flow reserve is impaired.
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http://dx.doi.org/10.1111/echo.14554DOI Listing
January 2020

Comparison of skeletal muscle mass loss in patients with metastatic colorectal cancer treated with regorafenib or TAS-102.

J BUON 2019 Sep-Oct;24(5):2198-2204

Department of Medical Oncology, Trakya University Faculty of Medicine, Edirne, Turkey.

Purpose: To assess whether regorafenib and TAS-102 treatments are associated with a change in Skeletal Muscle Area (SMA) as well as to compare Skeletal Muscle Mass (SMM) loss levels between regorafenib and TAS-102 treatments and prognostic significance in the patients with metastatic colorectal cancer (mCRC).

Methods: A total of 36 mCRC patients, who received regorafenib or TAS-102 in the third-line and subsequent settings were assessed in the analysis. SMM changes were assessed with CT scans findings, and they were categorized into two groups as SMM-loss (SMM decrease ≥2%) and SMM-stable (SMM change <2%).

Results: The SMM change after regorafenib therapy was significantly worse compared with TAS-102 therapy (p=0.001). The median overall survival (OS) was longer in SMM-stable group than in SMM-loss group (12.8 months; 95%CI:9.8-15.7) vs. 6.4 months; 95%CI:5.2-7.7, respectively;p=0.04). Cox regression analysis showed that SMM loss was independent prognostic indicator for OS (HR, 2.87; 95%CI: 1.07-7.42, p=0.03).

Conclusion: Although patients who received regorafenib had more SMM loss than those who received TAS-102, there was no difference in OS between drugs.
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April 2020

Lipid profile, atherogenic indices, and their relationship with epicardial fat thickness and carotid intima-media thickness in celiac disease.

North Clin Istanb 2019 2;6(3):242-247. Epub 2019 Sep 2.

Department of Cardiology and Internal Medicine, Istanbul Medeniyet University, Goztepe Training and Reaserch Hospital, Istanbul, Turkey.

Objective: In this study, we aimed to investigate the presence of subclinical atherosclerosis by measuring epicardial fat thickness (EFT) and carotid intima-media thickness (cIMT), evaluate low-level inflammation with high-sensitivity C-reactive protein (hsCRP), and evaluate whether there is a relationship among lipid profile, atherogenic indices, and hsCRP with these subclinical atherosclerosis markers in patients with celiac disease (CD).

Methods: After exclusion and inclusion criteria were applied, 31 patients with CD (24 female, mean age: 39.4±12.3 years) and 32 healthy controls (21 female, mean age: 39.5±4.4 years), totally 63 cases, were recruited. Subclinical atherosclerosis was evaluated with EFT by transthoracic echocardiography and cIMT by ultrasonography. Inflammatory markers including erythrocyte sedimentation rate (ESR), hsCRP, and lipid profile were recorded. Also, atherogenic indices were calculated: Castelli risk index I and II (TG/HDL-c and LDL-c/HDL-c, respectively), atherogenic index of plasma (AIP; logarithm TG/HDL-c), non-HDL-c (TG-HDL-c), and atherogenic coefficient (AC; non-HDL-c/HDL-c).

Results: EFT was significantly higher in the CD group (0.49±0.10 vs. 0.49±0.09; p-value: 0.02). Although cIMT was higher in the patient group, it did not reach statistical significance (0.51±0.08, 0.47±0.08; p-value: 0.10). HDL cholesterol level was found to be significantly lower (42.0±8.8 vs. 50.0±13.7; p-value: 0.01), and the plasma atherogenic index was found to be significantly higher in the patient group (0.98±0.50 vs. 0.62±0.64; p-value: 0.02). hsCRP (3.51±3.18 vs. 1.92±1.40; p-value: 0.02) and ESR (17.2±12.8 with 9.7±3.1; p-value: 0.01) were found to be significantly higher in the CD group. Although there was a significant positive correlation between EFT and hsCRP (r: 0.453; p-value: 0.01), there was a significant negative correlation between cIMT and HDL-cholesterol (-0.339; p-value: 0.05), and a significant positive correlation with the other components of the atherogenic index was found.

Conclusion: The risk of atherosclerosis has been increased in patients with CD. Chronic inflammation may be responsible for this increase along with atherogenic indices.
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http://dx.doi.org/10.14744/nci.2019.54936DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6790920PMC
September 2019

Is the prognostic nutritional index a prognostic and predictive factor in metastatic non-small cell lung cancer patients treated with first-line chemotherapy?

Support Care Cancer 2020 May 30;28(5):2273-2282. Epub 2019 Aug 30.

Department of Medical Oncology, SBÜ Bakırköy Dr. Sadi Konuk Education and Research Hospital, İstanbul, Turkey.

Purpose: We aimed to assess the prognostic and predictive significance of pretreatment Onodera's prognostic nutritional index (OPNI) in metastatic non-small cell lung cancer patients (NSCLC) treated with first-line chemotherapy.

Materials And Methods: Patients with metastatic NSCLC who attended five different medical oncology clinics between December 2008 and January 2018 were retrospectively analyzed. The optimal cut-off point for OPNI was performed by a receiver operating characteristic (ROC) curve analysis. Patients were assigned to either the low OPNI group or high OPNI group.

Results: A total of 333 patients were included in the study. Significant differences between the low and high OPNI groups were found regarding the rates of response to chemotherapy, sex, and hemoglobin level (p < 0.05). The patients in high OPNI group had a longer overall survival (OS) (15.3 vs. 10.6 months, p < 0.001) and progression-free survival (PFS) (6.7 vs. 5.3 months, p < 0.001) compared to the patients in low OPNI group. A multivariate analysis using Cox regression model revealed that a high OPNI score was an independent prognostic factor of OS (HR = 1.535, p = 0.002) and PFS (HR = 1.336, p = 0.014), but failed to demonstrate a statistical significance of pretreatment OPNI scores in predicting treatment response (p = 0.56).

Conclusions: Pretreatment OPNI is an independent prognostic factor for OS and PFS in metastatic NSCLC patients treated with first-line chemotherapy. Thus, it may be used as easily calculated and low-cost prognostic tool in the routine clinical practice in this patient group.
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http://dx.doi.org/10.1007/s00520-019-05055-xDOI Listing
May 2020

Is the Charlson Comorbidity Index a Prognostic Indicator for Toxicity and Mortality in Elderly Patients with Locally Advanced Rectal Cancer?

Arch Iran Med 2019 05 1;22(5):236-241. Epub 2019 May 1.

Ankara Numune Training and Research Hospital, Clinic of Medical Oncology, Ankara, Turkey.

Background: Aging is significantly related to multiple comorbidities. Even with a good performance score, some elderly patients may have poor survival outcomes. We aimed to evaluate the prognostic value of the Charlson comorbidity index (CCI) for mortality and toxicity in elderly patients with locally advanced rectal cancer (LARC).

Methods: Seventy-two elderly patients with LARC who were treated with neoadjuvant chemoradiotherapy (CRT) were included. Based on their CCI score, severity of the comorbidity was categorized into 2 groups: CCI<7 and CCI≥7.

Results: The overall survival (OS) at 5 years was 54.4 percent in patients treated with neoadjuvant CRT. Median OS was not reached for all patients as well as patients with CCI score <7, but median OS was 25 (95% CI 1.0-62.1) months in patients with CCI≥7 (P=0.002). The OS at 2 years was 79.1 percent in the patients with CCI <7 and 50.0 percent in the patients with CCI score ≥7 (P=0.002). Moreover, there was a trend toward, patients with higher CCI score who had more treatment related to grade 3 or 4 toxicity compared to those with CCI score <7 (33.3% vs 13.3%, respectively, P=0.09). Multivariable analysis indicated that the CCI score ≥7, presence of down-staging after therapy and clinical stage (III) independently predict mortality (HR 6.14, 95%CI 2.45-15.35, P<0.001) in patients with LARC.

Conclusion: Although CCI score was not significantly associated with both toxicity and disease-free survival (DFS), we suggest that baseline CCI score might be a valuable prognostic indicator for physicians to evaluate elderly patiens with LARC for optimal treatment.
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May 2019

Changes in skeletal muscle area and lean body mass during pazopanib vs sunitinib therapy for metastatic renal cancer.

Cancer Chemother Pharmacol 2019 04 24;83(4):735-742. Epub 2019 Jan 24.

Division of Medical Oncology, Department of Internal Medicine, Trakya University School of Medicine, 22030, Edirne, Turkey.

Purpose: To evaluate whether sunitinib and pazopanib treatments are associated with change in skeletal muscle area (SMA) and total lean body mass (LBM) as well as to compare their efficacies and safety profiles in patients with metastatic renal cell cancer (mRCC).

Methods: Thirty-six patients treated with a tyrosine kinase inhibitor were included. Eighteen of them received sunitinib and the rest/remaining received pazopanib in the first line of mRCC treatment. Baseline and follow-up computed tomography studies of the patients were performed to measure cross-sectional areas (cm) of muscle tissues.

Results: About 69% of patients were male and median age was 60 (49-68) years. Median time interval between two CT imagings was 6.1 (3.1-7.7) months and it was similar between the two groups (for sunitinib, 4.9 (2.5-6.9) months vs for pazopanib, 7.3 (3.2-9.5) months, p = 0.16, respectively). Disease control rate was 77.7% in all patients. Of these, 66.6% in sunitinib group was consisted of four partial responses and eight stable diseases. In addition, 88.8% in pazopanib group was consisted of three partial responses and 13 stable diseases. A significant decrease in SMA and LBM was observed after sunitinib therapy, whereas SMA and LBM values of pazopanib group did not change significantly (p = 0.02 and p = 0.70, respectively). No significant differences were observed between patients with sunitinib, and pazopanib group median PFS [11.9 (95% CI 6.1-17.6) vs 8.1 months (95% CI 7.2-9.1), respectively; p = 0.28] and median OS [28.6 (95% CI 24.3-32.9) vs 25.5 months (95% CI 18.9-52.7), respectively; p = 0.42]. Dose-limiting toxicities were significantly more frequent in sunitinib group than in pazopanib group (66.7% vs 22.2%, p = 0.02, respectively).

Conclusions: Loss of SMA and LBM with sunitinib was more substantial than with pazopanib. Treatment efficacies of both drugs were similar, but dose-limiting toxicity was more frequent in sunitinib group. Loss of SMA had no significant association with prognosis. Further studies are needed to clarify the possible association between SMA and prognosis in mRCC patients who receive sunitinib or pazopanib.
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http://dx.doi.org/10.1007/s00280-019-03779-5DOI Listing
April 2019

The Impact of Prognostic Nutritional Index on Coronary Flow Reserve in Patients with Inflammatory Bowel Disease.

Medeni Med J 2019 27;34(3):271-277. Epub 2019 Sep 27.

Istanbul Medeniyet University Faculty of Medicine, Department of Cardiology, Istanbul, Turkey.

Objective: The recurring inflammation of mucosal layer of intestines is known as inflammatory bowel disease (IBD), which can be accompanied by nutritional deficiencies. The association between inflammation and coronary artery disease has been established. Coronary flow reserve (CFR), which is an established method to evaluate combined microvascular and epicardial flow of coronary arteries, can be assessed by using transthoracic echocardiography. The aim of this study was to evaluate the association of Prognostic Nutritional Index (PNI) with CFR in IBD patients.

Method: This prospective study included 101 patients with IBD. These patients were compared to control group (n=32). PNI was calculated by using serum albumin level and lymphocyte count. CFR was assessed by using Doppler echocardiography.

Results: Multivariate regression analysis indicated that the presence of IBD, age (>40 years) and decreased PNI (<53.8) independently predict impairment of CFR. The area under the curve (AUC) was 75.1% (95% CI:0.664-0.838), and PNI levels were significant predictor of low CFR (p<0.001).

Conclusion: This study showed that PNI, which is calculated using the serum level of albumin and lymphocyte count, is a strong predictor of decreased CFR in IBD patients in remission. Our findings support previous studies showing the relationship between PNI and coronary artery disease. This immunonutritional index has only two components and is easy to calculate, and inexpensive.
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http://dx.doi.org/10.5222/MMJ.2019.47108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7433735PMC
September 2019

Regorafenib or rechallenge chemotherapy: which is more effective in the third-line treatment of metastatic colorectal cancer?

Cancer Chemother Pharmacol 2019 01 29;83(1):115-122. Epub 2018 Oct 29.

Department of Medical Oncology, Trakya University, Edirne, Turkey.

Purpose: To assess the efficacy and safety of regorafenib versus rechallenge chemotherapy in previously treated mCRC patients in third-line setting.

Materials And Methods: The data of 104 patients diagnosed with mCRC enrolled from 2010 to 2017 in six oncology centers were analyzed. Tumor treatment options were obtained from follow-up and treatment files. Rechallenge chemotherapy was identified as the re-use of the regimen which was previously administered to patients in one of the therapy lines and obtained disease control, these were the patients whose disease did not progress within 3 months.

Results: A total of 104 patients had received previously two lines of chemotherapy regimens for mCRC. Of these, 73 patients with mCRC who received regorafenib and 31 those who received rechallenge chemotherapy in third-line therapy were analyzed. Overall survival was better with rechallenge than it was with regorafenib (HR 0.29 95% CI 0.16-0.54, p < 0.001). Median OS was 12.0 months (95% CI 8.1-15.9) in rechallenge versus 6.6 months (95% CI 6.0-7.3) in regorafenib group (p < 0.001). Progression-free survival in the rechallenge group showed a higher median value of 9.16 months (95% CI 7.15-11.18) versus with that recorded in the regorafenib group of 3.41 months (95% CI 3.01-3.82), in favor of rechallenge chemotherapy. The most common adverse events of regorafenib was liver function test abnormality and hand-foot syndrome. Although grade 3 or 4 adverse events were similar, non-hematologic toxicities were more common than those of rechallenge.

Conclusions: Rechallenge is still a valuable option against regorafenib in patients who achieved disease control in one of the first two lines of therapy. Even though mCRC patients treated with regorafenib benefited clinically from this treatment, we revealed that chemotherapy rechallenge compared to regorafenib was more effective in the third-line treatment for mCRC patients.
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http://dx.doi.org/10.1007/s00280-018-3713-6DOI Listing
January 2019

Value of MRI apparent diffusion coefficient for assessment of response to sorafenib in hepatocellular carcinoma.

J BUON 2018 Jul-Aug;23(4):979-984

Trakya University, School of Medicine, Department of Medical Oncology, Edirne, Turkey.

Purpose: Efficient and adequate evaluation of therapeutic response in hepatocellular carcinoma (HCC) is an evolving field. We aimed to evaluate apparent diffusion coefficient (ADC) values in the prediction of response to sorafenib and prognosis in patients with advanced HCC.

Methods: Baseline magnetic resonance (MR) imaging was performed before treatment. After sorafenib started, clinical and radiological response were evaluated at approximately 3 months later. ADC measurements were performed by a 12- year experienced radiologist who evaluated MR before and after sorafenib therapy.

Results: A total of 17 patients (median age 60 years, range 51-66 and M/F ratio=3.25/1) were analyzed. A significant increase in ADC levels in responders was observed 3 months after sorafenib therapy. Baseline and post-sorafenib ADC values were not significantly associated with mortality (hazard ratio/HR baseline ADC=1.003, p=0.98) and after sorafenib (HR 0.480, p=0.48, respectively).

Conclusion: Advanced HCC patients with a favorable response to sorafenib had a significant increase in ADC value at the first radiological evaluation. The predictive and prognostic role of ADC for overall survival is still unknown and further research is needed to investigate any possible association.
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November 2019
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