Tıp Fakültesi / Faculty of Medicine
Permanent URI for this collectionhttps://hdl.handle.net/11727/1403
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Item Pretreatment Masseter Muscle Volume Predicts Survival in Locally Advanced Nasopharyngeal Carcinoma Patients Treated with Concurrent Chemoradiotherapy(2023) Pehlivan, Umur Anil; Somay, Efsun; Yilmaz, Busra; Besen, Ali Ayberk; Mertsoylu, Huseyin; Selek, Ugur; Topkan, Erkan; 0000-0001-5871-0695; 0000-0001-8251-6913; 0000-0001-8120-7123; 37959329; AAG-2213-2021Background and purpose: Muscle loss is a significant indicator of cancer cachexia and is associated with a poor prognosis in cancer patients. Given the absence of comparable studies, the current retrospective study sought to examine the correlation between the total masseter muscle volume (TMMV) before treatment and the survival outcomes in locally advanced nasopharyngeal cancer (LA-NPC) patients who received definitive concurrent chemoradiotherapy (CCRT). Methods: A three-dimensional segmentation model was used to determine the TMMV for each patient by analyzing pre-CCRT magnetic resonance imaging. The optimal TMMV cutoff values were searched using receiver operating characteristic (ROC) curve analyses. The primary and secondary endpoints were the relationship between the pre-CCRT TMMV measures and overall survival (OS) and progression-free survival (PFS), respectively. Results: Ninety-seven patients were included in this study. ROC curve analyses revealed 38.0 cc as the optimal TMMV cutoff: <= 38.00 cc (n = 42) and >38.0 cc (n = 55). Comparisons between the two groups showed that the TMMV>38.0 cc group had significantly longer PFS [Not reached (NR) vs. 28; p < 0.01] and OS (NR vs. 71; p < 0.01) times, respectively. The results of the multivariate analysis demonstrated that the T-stage, N-stage, number of concurrent chemotherapy cycles, and TMMV were independent associates of PFS (p < 0.05 for each) and OS (p < 0.05 for each) outcomes, respectively. Conclusion: The findings of the current retrospective research suggest that pretreatment TMMV is a promising indicator for predicting survival outcomes in LA-NPC patients receiving definitive CCRT.Item Survival Associated with Extent of Radical Hysterectomy in Early-Stage Cervical Cancer: A Subanalysis of the Surveillance in Cervical Cancer (SCCAN) Collaborative Study(2023) Bizzarri, Nicolo; Querleu, Denis; Dostalek, Lukas; van Lonkhuijzen, Luc R. C. W.; Giannarelli, Diana; Lopez, Aldo; Salehi, Sahar; Ayhan, Ali; Kim, Sarah H.; Ortiz, David Isla; Klat, Jaroslav; Landoni, Fabio; Pareja, Rene; Manchanda, Ranjit; Kostun, Jan; Ramirez, Pedro T.; Meydanli, Mehmet M.; Odetto, Diego; Laky, Rene; Zapardiel, Ignacio; Weinberger, Vit; Dos Reis, Ricardo; Anchora, Luigi Pedone; Amaro, Karina; Akilli, Huseyin; Abu Rustum, Nadeem R.; Salcedo Hernandez, Rosa A.; Javurkova, Veronika; Mom, Constantijne H.; Scambia, Giovanni; Falconer, Henrik; Cibula, David; 37336255BACKGROUND: International guidelines recommend tailoring the radicality of hysterectomy according to the known preoperative tumor characteristics in patients with early-stage cervical cancer.OBJECTIVE: This study aimed to assess whether increased radicality had an effect on 5-year disease-free survival in patients with early-stage cervical cancer undergoing radical hysterectomy. The secondary aims were 5-year overall survival and pattern of recurrence.STUDY DESIGN: This was an international, multicenter, retrospective study from the Surveillance in Cervical CANcer (SCCAN) collaborative cohort. Patients with the International Federation of Gynecology and Obstetrics 2009 stage IB1 and IIA1 who underwent open type B/C1/C2 radical hysterectomy according to Querleu-Morrow classification between January 2007 and December 2016, who did not undergo neoadjuvant chemotherapy and who had negative lymph nodes and free surgical margins at final histology, were included. Descriptive statistics and survival analyses were performed. Patients were stratified according to pathologic tumor diameter. Propensity score match analysis was performed to balance baseline characteristics in patients undergoing nerve-sparing and non-nerve-sparing radical hysterectomy.RESULTS: A total of 1257 patients were included. Of note, 883 patients (70.2%) underwent nerve-sparing radical hysterectomy, and 374 patients (29.8%) underwent non-nerve-sparing radical hysterectomy. Baseline differences between the study groups were found for tumor stage and diameter (higher use of non-nerve-sparing radical hysterectomy for tumors >2 cm or with vaginal involvement; P<.0001). The use of adjuvant therapy in patients undergoing nerve-sparing and non-nerve-sparing radical hysterectomy was 27.3% vs 28.6%, respectively (P=.63). Five-year disease-free survival in patients undergoing nerve-sparing vs non-nerve-sparing radical hysterectomy was 90.1% (95% confidence interval, 87.9-92.2) vs 93.8% (95% confidence interval, 91.1-96.5), respectively (P=.047). Non-nerve-sparing radical hysterectomy was independently associated with better disease-free survival at multivariable analysis performed on the entire cohort (hazard ratio, 0.50; 95% confidence interval, 0.31-0.81; P=.004). Furthermore, 5-year overall survival in patients undergoing nerve-sparing vs non-nerve-sparing radical hysterectomy was 95.7% (95% confidence interval, 94.1-97.2) vs non-nerve-sparing 96.5% (95% confidence interval, 94.3-98.7), respectively (P=.78). In patients with a tumor diameter <= 20 mm, 5-year disease-free survival was 94.7% in nerve-sparing radical hysterectomy vs 96.2% in non-nerve-sparing radical hysterectomy (P=.22). In patients with tumors between 21 and 40 mm, 5-year disease-free survival was 90.3% in non-nerve-sparing radical hysterectomy vs 83.1% in nerve sparing radical hysterectomy (P=.016) (no significant difference in the rate of adjuvant treatment in this subgroup, P=.47). This was confirmed after propensity match score analysis (balancing the 2 study groups). The pattern of recurrence in the propensity-matched population did not demonstrate any difference (P=.70).CONCLUSION: For tumors <= 20 mm, no survival difference was found with more radical hysterectomy. For tumors between 21 and 40 mm, a more radical hysterectomy was associated with improved 5-year disease free survival. No difference in the pattern of recurrence according to the extent of radicality was observed. Non-nerve-sparing radical hysterectomy was associated with better 5-year disease-free survival than nerve sparing radical hysterectomy after propensity score match analysis.Item The Prognostic Value of the Novel Global Immune-Nutrition-Inflammation Index (GINI) in Stage IIIC Non-Small Cell Lung Cancer Patients Treated with Concurrent Chemoradiotherapy(2023) Topkan, Erkan; Selek, Ugur; Pehlivan, Berrin; Kucuk, Ahmet; Ozturk, Duriye; Ozdemir, Beyza Sirin; Besen, Ali Ayberk; Mertsoylu, Huseyin; 0000-0001-8120-7123; 37760482; AAG-2213-2021Simple Summary: We investigated the prognostic significance of the newly created Global Immune-Nutrition-Inflammation Index (GINI) in IIIC non-small cell lung cancer (NSCLC) patients who received definitive concurrent chemoradiotherapy (CCRT). A total of 802 newly diagnosed stage IIIC NSCLC patients were included. The optimal pre-CCRT GINI cutoff was 1562 (area under the curve: 76.1%; sensitivity: 72.4%; specificity: 68.2%; Youden index: 0.406). GINI >= 1562 was associated with significantly shorter median locoregional progression-free (p < 0.001), progression-free (p < 0.001), and overall survival (p < 0.001) than GINI < 1562. For each survival endpoint, the association between GINI and survival outcomes appeared independent of other confounding variables (p < 0.05 for each). The novel GINI index effectively stratified patients with stage IIIC NSCLSC into two distinct subgroups, demonstrating significant differences in both median and long-term survival rates. Background: We sought to determine the prognostic value of the newly developed Global Immune-Nutrition-Inflammation Index (GINI) in patients with stage IIIC non-small cell lung cancer (NSCLC) who underwent definitive concurrent chemoradiotherapy (CCRT). Methods: This study was conducted on a cohort of 802 newly diagnosed stage IIIC NSCLC patients who underwent CCRT. The novel GINI created first here was defined as follows: GINI = [C-reactive protein x Platelets x Monocytes x Neutrophils] divided by [Albumin x Lymphocytes]. The receiver operating characteristic (ROC) curve analysis was used to determine the optimal pre-CCRT GINI cut-off value that substantially interacts with the locoregional progression-free (LRPFS), progression-free (PFS), and overall survival (OS). Results: The optimal pre-CCRT GINI cutoff was 1562 (AUC: 76.1%; sensitivity: 72.4%; specificity: 68.2%; Youden index: 0.406). Patients presenting with a GINI >= 1562 had substantially shorter median LRPFS (13.3 vs. 18.4 months; p < 0.001), PFS (10.2 vs. 14.3 months; p < 0.001), and OS (19.1 vs. 37.8 months; p < 0.001) durations than those with a GINI < 1562. Results of the multivariate analysis revealed that the pre-CCRT GINI >= 1562 (vs. <1562), T4 tumor (vs. T3), and receiving only 1 cycle of concurrent chemotherapy (vs. 2-3 cycles) were the factors independently associated with poorer LRPS (p < 0.05 for each), PFS (p < 0.05 for each), and OS (p < 0.05 for each). Conclusion: The newly developed GINI index efficiently divided the stage IIIC NSCLSC patients into two subgroups with substantially different median and long-term survival outcomes.Item The Clinicopathological and Survival Differences Between Never and Ever Smokers with Non-Small Cell Lung Cancer(2014) Muallaoglu, Sadik; Karadeniz, Cemile; Mertsoylu, Huseyin; Besen, Ali Ayberk; Sezer, Ahmet; Sedef, Ali Murat; Kose, Fatih; Ozyilkan, Ozgur; https://orcid.org/0000-0002-6242-2802; https://orcid.org/0000-0002-1932-9784; https://orcid.org/0000-0002-6445-1439; https://orcid.org/0000-0002-0156-5973; https://orcid.org/0000-0001-8825-4918; 24965406; IVU-7523-2023; M-9530-2014; AAD-2667-2020; G-4827-2016; AAD-2817-2021Purpose: Cigarette smoking was regarded as the most important carcinogenic factor of lung cancer, yet in recent years lung cancer in never-smokers is an increasingly prominent public health issue. The aim of this study was to assess the epidemiological and clinicopathological characteristics of never-smoker patients with non small cell lung cancer (NSCLC), focusing on clinical risk factors and survival. Methods: We retrospectively analyzed 290 NSCLC patients who presented between 2006 and 2011. Differences in clinical features and survival between never- and ever-smoker patients were analyzed. Student's t-test and Mann-Whitney U-test were used to assess the significance of the variables between the groups. Survival curves were calculated using Kaplan-Meier method. Hazard ratio (HR) for death and its 95% confidence interval (CI) were calculated by Cox regression analysis. Results: There were 243 (83.8%) ever-smokers and 47 (16.2%) never-smokers. In never-smokers females predominated (80.9%) as well as patients with adenocarcinomas (78.7%). At the time of analysis 143 (49.3%) patients had died. The 5-year overall survival (OS) rates were not significantly different between never- and ever-smokers (p=0.410). The median OS of all patients was 26 months (95% CI: 16.8-35.2). The median OS was 23 months (95% CI: 11.8-34.2)for never-smokers and 30 months (95% CI: 19.7-40.3) forever-smokers (p=0.410). Never-smokers tended to present with more advanced disease than ever-smokers (p<0.004) and also with more advanced age (p<0.001). The HR for death increased with poorer Eastern Cooperative Oncology Group (ECOG) performance status (PS) (ECOG 2-3), advanced stage (stage 3-4) and untreated patients. Slightly lower risk for death was registered in patients with adenocarcinoma vs those with squamous cell carcinoma (S CC). Conclusion: Although no difference in survival was seen, definite epidemiologic differences do exist between never-smokers and ever-smokers patients with NSCLC. Future efforts should focus on the underlying biological differences, and on identifying potential non-tobacco related risk factors in order to improve treatment strategies for these two groups of NSCLC patients.Item Inhibition of the Notch Pathway Promotes Flap Survival by Inducing Functional Neoangiogenesis(2015) Abbas, Ozan Luay; Borman, Huseyin; Terzi, Yunus K.; Terzi, Aysen; Bayraktar, Nilufer; Ozkan, Burak; Yazici, Ayse C.; 0000-0002-7886-3688; 0000-0003-3093-8369; 0000-0002-1225-1320; 0000-0002-3132-242X; 0000-0001-5612-9696; 25180956; Y-8758-2018; AAI-5063-2020; F-7546-2013; AAS-6810-2021; B-4372-2018Objective The Notch pathway seems to function as an antiangiogenic factor, negatively regulating the sprouting effect of vascular endothelial growth factor (VEGF). This function is well defined in embryonic and tumor vasculature. However, little is known about its function in ischemia-induced angiogenesis. In the first part of this study, we investigated the role of Notch in reparative angiogenesis after ischemia. In the second part, we hypothesized that anti-Notch therapy will result in increased angiogenic sprouting. We analyzed the effect of Notch inhibition in the induction of angiogenic sprouting. Methods In the first part, we investigated the effect of ischemia on the Notch ligand delta-like ligand 4 (DLL4). Twenty rats were divided equally into 2 groups. In the surgery group, dorsal skin flap was used as model of ischemia. In the control group, no surgical procedure was performed. DLL4 and VEGF gene expressions were assessed. Immunohistochemical staining was used for detection of DLL4 in tissue materials. Plasma levels of VEGF and DLL4 were measured. In the second part, we investigated the effect of Notch inhibition using a gamma-secretase inhibitor (GSI) on inducing neoangiogenesis. Twenty rats were assigned to 2 equal groups. In all animals, dorsal skin flap was raised and sutured back into its bed. Animals in the GSI-treated group received GSI intravenously after surgery for 3 days. Saline was administered in the control group. Necrotic area measurements, microangiography, and histologic evaluations were performed to compare groups. Results In the first part, VEGF and DLL expressions increased in ischemic tissues (P < 0.01). Immunohistochemical analysis revealed that DLL4 expression was upregulated in capillary endothelial cells after ischemia. Plasma levels for VEGF and DLL4 were higher in the animals that underwent surgery (P < 0.01). In the second part, GSI treatment resulted in higher flap survival rates (P < 0.05). Microscopic analysis exhibited increase in the number of microvascular structures after GSI treatment (P < 0.05). Microangiographic evaluation showed that neovascularization increased in the GSI-applied flaps. Conclusions We present an evidence for the importance of the Notch pathway in the regulation of ischemia-induced angiogenesis. Notch inhibition promotes flap survival by creating a neovasculature that has an increase in vascular density.Item Influence of Creatinine Clearance on Survival Parameters in Small Cell Lung Cancer Treated with Cisplatin-Based Chemotherapy Regimen(2017) Gozel, Sedat; Sumbul, Ahmet; Sedef, Ali Murat; Besen, Ayberk; Mertsoylu, Huseyin; Batmaci, Celal; Kose, Fatih; 0000-0002-5573-906X; 0000-0002-7862-0192; 0000-0002-1932-9784; D-4793-2014; AAD-6910-2021; M-9530-2014Item Enhancement of Vascular Endothelial Growth Factor's Angiogenic Capacity by the Therapeutic Modulation of Notch Signalling Improves Tram Flap Survival in Rats Submitted to Nicotine(2017) Abbas, Ozan Luay; Terzi, Yunus Kasim; Ozatik, Orhan; Ozatik, Fikriye Yasemin; Turna, Gamze; Nar, Rukiye; Musmul, Ahmet; 0000-0001-5612-9696; 0000-0002-4662-6493; 0000-0002-8422-2975; 28277073; B-4372-2018; GXA-2381-2022; HOH-8201-2023Background: Smoke of cigarettes, and specifically nicotine, has been shown to diminish pedicled transverse rectus abdominis musculocutaneous (TRAM) flap survival. Considering that Notch signalling through its ligand Delta-like 4 (Dll4) functions as anti-angiogenic factor by inhibiting the pro-angiogenic effects of vascular endothelial growth factor (VEGF), it is hypothesised that inhibition of the Notch would promote angiogenesis and increase TRAM flap survival in rats submitted to nicotine. Methods: Twenty rats were treated with nicotine for 28 days preoperatively. Thereafter, a pedicled TRAM flap was created in all animals. The Notch inhibitor N-[N-(3,5-difluorophenacetyl)-1-alanyl]-S-phenylglycine-t-butyl-ester was administered in animals of the treatment group. Animals in the control group were given the same amount of solvent. Five days after the surgery, viable flap areas were determined. Skin samples were evaluated for VEGF and Dll4 mRNA levels. Immunohistochemical analysis was used for the assessment of endothelial Dll4 expression. Vascular density was determined histologically. Plasma levels of VEGF and Dll4 were measured. Results: A significant improvement in TRAM flap surviving area was observed in the treatment group (53.5014.25%) compared with the controls (32.20 +/- 9.15%). Immunohistochemical analysis revealed a significant increase in the number of Dll4 stained vessels in animals of the treatment group (9.2 +/- 1.6) in comparison with the controls (5.7 +/- 1.9). VEGF mRNA levels (0.22 +/- 0.08) in the treatment group were significantly lower than those in the control group (0.36 +/- 0.09). Conclusion: Notch inhibition significantly improved TRAM flap survival in animals exposed to nicotine by promoting VEGF-induced angiogenesis.Item Adding Taxane to Platin-5-Fluorouracil Combination Does Not Improve Survival Rate in Patients >= 65 Years of Age with Advanced Gastric Cancer: A Retrospective-Multicenter Study(2018) Gunaldi, Meral; Kose, Fatih; Demirci, Nebi Serkan; Gunduz, Seyda; Ozdemir, Nuriye; Kocoglu, Hakan; Okuturlar, Yildiz; Sedef, Ali Murat; Erdem, Dilek; Goksu, Sema Sezgin; https://orcid.org/0000-0002-0156-5973; 29745086; G-4827-2016Purpose: Advanced gastric cancer (AGC) has a dismal prognosis. Platin-5-fluorouracil (CF) combination chemotherapy is the most widely used protocol and addition of a taxane (TCF) seems to increase survival and toxicity rates. We aimed to evaluate efficacy and toxicity of TCF as compared to CF in patients older than 65 years and compare them with the patients younger than 65 years. Methods: A total of 341 patients with AGC have been treated at six different oncology centers in Turkey between 2010 and 2014 and evaluated retrospectively. The characteristics of the patients whose tumors were histologically confirmed and whose survival data were available were registered and analyzed. The study group consisted of 234 patients younger than 65 years (group 1) and 107 patients older than 65 years (group 2). All of the data obtained from the patients were statistically analyzed. Results: The median age of the patients was 58.2 years and the mean follow-up time 14.4 months. For the entire group, progression-free survival (PFS) and overall survival OS) were 9 and 13 months, respectively. Using TCF over CF regimen increased the OS by 4.2 months (i.e., group 1 and 2 together). For group 2, patients with liver metastases and without surgery of the primary tumor were treated with significantly more TCF as compared to CF, respectively. Although TCF yielded significantly higher PFS and OS in group 1 (p=0.0001 and p=0.017), there was no significant difference in group 2 as compared to CF. Also, grade 3-4 toxicity was statistically defined as one of the possible reasons of worsened OS in patients older than 65 years and receiving TCF. Conclusions: The addition of taxanes to CF backbone leads to a significant increase in both PFS and OS in patients younger than 65 years of age but the triplet regimen with taxanes does not provide superior survival in patients older than 65 years of age.Item Does Lymph Node Ratio (Metastasis/Total Lymph Node Count) Affect Survival And Prognosis In Gastric Cancer?(2022) Topcu, Ramazan; Sahiner, Ibrahim T.; Kendirci, Murat; Erkent, Murathan; Sezikli, Ismail; Tutan, Mehmet B.; https://orcid.org/0000-0002-3592-5092; 35110338; GVS-3968-2022; CAA-2756-2022Objectives: To investigate the influence of the metastatic lymph node/total lymph node ratio (N- ratio) on survival and prognosis in surgically treated gastric carcinomas. Methods: A retrospective review of 73 patients who underwent curative resection at the Department of General Surgery, Hitit University Faculty of Medicine, Turkey. Receiver operating characteristic analysis was used to calculate the cut-off value for the N-ratio of the patients. The N-ratio cut-off value was determined to be 0.32. Patients were divided into 2 groups: below 0.32 (Group 1) and 0.32 and above 0.32 (Group 2). Results: Group 2 patients had a total lymph node mean of 25.10 +/- 13.64 while Group 1 patients had a total lymph node mean of 18.77 +/- 9.36 (p=0.04). In Group 2, the mean of metastatic lymph node was 15.97 +/- 10.30 (p<0.001). The mortality rate of Group 1 was 18% while Group 2 was 51.7%, and were statistically significant (p=0.0039). The estimated survival duration of Group 2 was 24.22 months, and Group 1 was 48.01 months (p=0.001). The mean estimated survival time for the entire group was 40.92 months. We differentiated patients from the development of mortality cut-off value in ROC analysis with 65.2% sensitivity and 72% specificity. This ratio was found to be 0.32, which was statistically significant (p=0.003). Ratios greater than 0.32 raised the risk of mortality by 4.8 times, which was statistically significant (p=0.003). Conclusion: The N-ratio could be a new metric to evaluate prognosis following curative gastrectomy and improve the existing tumor lymph node metastasis staging system.Item Role of Consolidative Thoracic Radiotherapy for Extensive-stage Small Cell Lung Cancer: Trod Thoracic Oncology Study Group 08-006 Multi-institutional Study(2022) Yavas, Guler; Kirakli, Esra Korkmaz; Dagdelen, Meltem; Topkan, Erkan; Saynak, Mert; Dincbas, Fazilet Oner; OzdemIr, Yurday; Yavas, Cagdas; Birgi, Sumerya Duru; Akyurek, SerapOBJECTIVE We aimed to evaluate the role of consolidative thoracic radiotherapy (TRT) in patients with extensive-stage small cell lung cancer (ES-SCLC). METHODS The clinical data for 151 patients with the diagnosis of ES-SCLC treated with consolidative TRT from six different hospitals from Turkey analyzed. RESULTS The median age of the patients was 61 years (range 36-83 years). The median dose of radiotherapy (RT) was 45 Gy (range: 30-66 Gy) applied in median 25 fractions (range 10-34 fractions). For 151 assessable patients, the median survival time (MST) was 14 months (range: 12.6-15.3). The patients who has complete response and partial response had 16 months, and 14 months of MST. In multivariate analyses prophylactic cranial irradiation (PCI) (p=0.011), female gender (p=0.017), and comorbidity (p=0.006) were found as significant parameters associated with survival. The MSTs were 12 months in patients without comorbidity, and 16 months for the patients with at least one comorbid disease. The patients who received PCI had improved MSTs when compared the ones without PCI (16 months vs. 12 months). There was a trend towards improved overall survival times in patients who received EQD2 >= 47 Gy RT doses (p=0.08). CONCLUSION Female gender, use of PCI, and unavailability of comorbid disease were associated with improved survival in ES-SLCL patients. There was a trend towards overall survival times in patients who received >= 47 Gy EQD2 doses; however, we believe that this statistical insignificance was related to our limited patient numbers.
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