Tıp Fakültesi / Faculty of Medicine

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    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-2213-2021
    Background 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.
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    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-2213-2021
    Simple 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.
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    Prognostic Value of Metabolic Tumor Volume and Total Lesion Glycolysis in Esophageal Carcinoma Patients Treated with Definitive Chemoradiotherapy
    (2018) Yildirim, Berna A.; Torun, Nese; Guler, Ozan C.; Onal, Cem; 0000-0001-6908-3412; 0000-0001-6661-4185; 0000-0002-2742-9021; 0000-0002-5597-676X; 29668513; AAC-5654-2020; V-5717-2017; D-5195-2014; AAE-2718-2021
    PurposeThe aim of this study was to evaluate the prognostic importance metabolic tumor volume (MTV), total lesion glycolysis (TLG), and standardized uptake value (SUV) in patients with esophageal cancer treated with definitive chemoradiotherapy.Patients and methodsSeventy-two esophageal cancer patients treated with definitive chemoradiotherapy [57 (79%) patients] or definitive radiotherapy [15 (21%) patients] were retrospectively analyzed. The regions equal to or greater than SUV of 2.5 were selected to delineate MTV and TLG was calculated by multiplying the mean SUV by the MTV of the primary lesions. The overall survival (OS) and disease-free survival (DFS) were evaluated for all patients and also patients with squamous cell carcinoma.ResultsThe median survival time was 13.4 months (range: 1.8-119.3 months) for all patients. Maximum SUV, mean SUV, MTV, and TLG values were significantly higher in patients with extensive T-stage (T3-T4) compared with patients with T1-T2 disease. Patients with regional lymph node metastasis had significantly higher MTV and TLG values compared with patients with no lymph node metastasis. On multivariate analysis, MTV, TLG, presence of lymph node metastasis, and lack of concurrent chemotherapy were negative significant prognostic factors for OS and DFS for the entire cohort and for patients with squamous cell carcinoma esophageal cancer.ConclusionMetabolic volumes (MTV and TLG), regional lymph node metastasis, and concurrent chemotherapy are major prognostic factors for DFS and OS in patients with esophageal carcinoma. In addition, MTV and TLG are important in predicting nodal metastasis, and together with metabolic volumes, SUV are associated significantly with local tumor invasion.
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    Prognostic Value of Metabolic Response Measured by F-18-FDG-PET in Oesophageal Cancer Patients Treated with Definitive Chemoradiotherapy
    (2016) Onal, Cem; Torun, Nese; Guler, Ozan C.; Yildirim, Berna A.; 0000-0002-2742-9021; 0000-0001-6661-4185; 0000-0002-5597-676X; 0000-0001-6908-3412; 27612030; D-5195-2014; V-5717-2017; AAE-2718-2021; AAC-5654-2020
    BackgroundThis study aimed to assess the efficacy of fluorine-18 fluorodeoxyglucose (F-18-FDG)-PET for predicting overall survival (OS) and disease-free survival (DFS) in oesophageal cancer patients after definitive chemoradiotherapy (CRT) and prognostic importance of metabolic response detected by post-treatment PET at least 3 months after completing CRT.Materials and methodsData from 58 oesophageal cancer patients receiving definitive CRT were retrospectively analysed. Post-treatment F-18-FDG-PET was delivered at a median of 3.2 (range, 3.0-6.4) months after CRT. The impact of metabolic response determined by post-treatment F-18-FDG-PET, maximum post-treatment standardized uptake value (SUVmax) and percent SUV change (pretreatment to post-treatment) on survival was analysed.ResultsThe median follow-up was 19.7 (range, 4.2-91.9) months for all patients and 28.2 (range, 13.7-91.9) months for survivors. The mean pretreatment and post-treatment SUVmax and the median percent SUV decrease were 18.66.4, 6.2 +/- 4.6 and -73% (+13 to -100%). Pretreatment SUVmax was higher in patients with locoregional or distant failure than in those without (P<0.001). Pretreatment SUVmax was lower in patients with a complete response (CR) than in those without a CR (P=0.006). Two-year OS and DFS were higher in patients with CR compared with those without CR (P<0.001). CR rates detected by post-treatment F-18-FDG-PET were lower in patients with lymph node metastases or longer tumours than in those with shorter tumours or no metastases. During multivariate analysis, post-treatment SUVmax was a significant predictor for OS, and post-treatment SUVmax, percent SUV decrease and tumour length were significant prognostic factors for DFS.ConclusionMetabolic response assessed by post-treatment F-18-FDG-PET at least 3 months after CRT showed that post-treatment SUVmax and percent SUV change were important survival predictors.
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    Prognostic Role of Pretreatment Level Hemoglobin Levels in Patients with Local Advanced Rectum Cancer Treated with Preoperative Chemotherapy
    (2018) Yildirim, Berna Akkus; Sumbul, Ahmet Taner; Guler, Ozan Cem; Sedef, Ali Murat; Onal, Cem; Topkan, Erkan; https://orcid.org/0000-0001-6661-4185; https://orcid.org/0000-0002-5573-906X; https://orcid.org/0000-0001-6908-3412; https://orcid.org/0000-0001-8120-7123; V-5717-2017; D-4793-2014; AAC-5654-2020; HOC-5611-2023; AAG-2213-2021
    Purpose: This study aims to systematically evaluate the relationship between baseline blood count levels, simply and basically initiated, and treatment response in locally advanced rectal cancer patients treated with neoadjuvant chemoradiotherapy. Materials and Methods: This retrospective study included 123 locally advanced rectal cancer patients who were treated with neoadjuvant chemoradiotherapy followed by surgery. Pretreatment Hb level was assessed as an independent variable for the whole study sample. The primary endpoint was the impact of pre-treatment Hb levels on overall survival. Results: At a median follow-up of 40,3 months (1,4-92 months). A Hb cut-off value of 12.5 g/dl (AUC=0.673, %95 0.564-0.781) was identified by using ROC analysis. Following the stratification of patients at this cut-off point into two groups: normal-Hb (nHb; Hb>12) and low-Hb (dHb <= 12), the comparative survival analysis demonstrated that the patients in the nHb group had significantly increased OS than those in the dHb group, and retained its independent significant association with survival outcomes in the multivariate analysis. Conclusion: Knowledge of pretreatment hematological parameters appears to be an important prognostic factor in patients with rectal carcinoma.
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    The Impact Of Serum Albumin-To-Alkaline Phosphatase Ratio In Cervical Cancer Patients Treated With Definitive Chemoradiotherapy
    (2022) Onal, Cem; Gultekin, Melis; Yavas, Guler; Oymak, Ezgi; Sari, Sezin Yuce; Guler, Ozan Cem; Yigit, Ecem; Yildiz, Ferah; 35653776
    We retrospectively analysed the prognostic significance of serum albumin, alkaline phosphatase (ALP) and albumin to ALP ratio (AAPR) and other prognostic factors affecting the overall survival (OS) and progression-free survival (PFS) in 200 cervical cancer patients treated with definitive chemoradiotherapy (CRT). The prognostic factors for OS and DFS, in addition to the predictive factors of albumin, ALP and AAPR, were investigated. Older age, lymph node metastasis, non-complete response (CR) to treatment and low serum albumin levels emerged as predictors of poor OS and PFS in multivariate analysis. However, with a cut-off value of 0.51, AAPR was not a significant prognostic factor of survival in multivariable analysis. There were no significant differences in clinicopathological factors between patients with low and high AAPR, except for lymph node metastasis, where lymph node metastasis rate was significantly higher in patients with a low AAPR compared to those with a high AAPR. Patients with CR had a significantly higher serum albumin level and AAPR compared to patients without CR. The pre-treatment serum albumin level was independent predictive for survival; therefore, it could be a suitable biomarker to guide systemic therapy and predict patient outcomes. Impact Statement What is already known on this subject? Two major determinants of tumour progression are nutritional status and inflammation. The albumin-to-alkaline phosphatase ratio (AAPR), which was originally proposed as a marker for nutritional status and immune response, was recently discovered to be a prognostic factor for various cancer types. However, its utility in the treatment of cervical cancer has not been established. What do the results of this study add? Low serum albumin levels were associated with a significantly shorter OS and PFS in cervical cancer patients treated definitively with CRT. AAPR, on the other hand, was not a significant prognostic factor for survival with a cut-off value of 0.51. Regional lymph node metastasis was significantly more common in patients with a low AAPR than in those with a high AAPR. What are the implications of these findings for clinical practice and/or further research? Patients with multiple clinicopathological risk factors and low serum albumin levels had an increased risk of disease recurrence and a poorer prognosis, highlighting the importance of additional adjuvant treatment strategies in these patients. Due to the preliminary nature of our findings, additional research is required to corroborate them.
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    Low Prognostic Nutritional Index Predicts Poor Clinical Outcomes in Patients with Stage IIIB Non-small-cell Lung Carcinoma Undergoing Chemoradiotherapy
    (2020) Ozdemir, Yurday; Topkan, Erkan; Mertsoylu, Huseyin; Selek, Ugur; 0000-0002-1932-9784; 0000-0001-8120-7123; 0000-0002-2218-2074; 32214853; M-9530-2014; AAG-2213-2021; AAG-5629-2021
    Purpose: To investigate the prognostic utility of the prognostic nutritional index (PNI) in stage IIIB non-small-cell lung carcinoma (NSCLC) patients undergoing concurrent chemoradiotherapy (CRT). Methods: A total of 358 stage IIIB NSCLC patients who received a total dose of 60-66 Gy (2 Gy/fraction) radiotherapy and >= 1 cycle(s) of platinum-based chemotherapy were analyzed. The receiver operating curve analysis was utilized to identify the optimal PNI cut-off value demonstrating a significant connection with the overall survival (OS), locoregional progression-free survival (LRPFS), and progression-free survival (PFS). Results: At a median follow-up time of 22.5 months (range: 2.4-123.5), 30.2% and 14% of the patients were still alive and free of disease progression, respectively.The median OS, LRPFS, and PFS were 25.2 [95% confidence interval (CI): 36.3-46.6 months], 15.4 (95% CI: 26.6-35.3 months), and 10.7 (95% CI: 36.8-69.9 months), individually, for the whole study accomplice. The ROC analysis revealed an optimum rounded cut-off that associated meaningfully with each of the OS [area under the curve (AUC): 84.1%; sensitivity: 75.9%;72.4% specificity], LRPFS (AUC: 92.4%; sensitivity: 87.9%; 85.1% specificity), and PFS (AUC: 80.1%; sensitivity: 73.7%; 71.6% specificity) at a value of 40.5. Comparative analyses revealed that the patients presenting with PNI <= 40.5 had significantly inferior OS (16.8 vs 36.7; P<0.001), LRPFS (11.5 vs 19.5; P<0.001), and PFS (8.6 vs 13.6; P<0.001) outcomes compared to patients with PNI>40.5. In univariate analyses, lower T-stage (1-2 vs 3-4; P< 0.001), lower N-stage (N2 vs N3; P< 0.001), anemia status (absent vs present; P< 0.001), weight loss status (<5% vs >= 5%; P< 0.001), and PM group (<= 40.5 vs >40.5; P<0.001) were the factors found to be associated with OS, LRPFS and PFS results. The results of multivariate analysis exhibited that the PM was independently associated with each of the OS (P<0.001), LRPFS (P<0.001), and PFS (P<0.001) outcomes. Conclusion: The pretreatment PNI appears to be a robust novel prognostic factor that stratifies patients with stage IIIB NSCLC into two significantly distinct survival groups after CRT.
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    Prognostic values of ADC(mean) and SUVmax of the primary tumour in cervical cancer patients treated with definitive chemoradiotherapy
    (2019) Yildirim, Berna Akkus; Onal, Cem; Erbay, Gurcan; Guler, Ozan Cem; Karadeli, Elif; Reyhan, Mehmet; Koc, Zafer; 0000-0002-2742-9021; 0000-0003-0987-1980; 30354907; D-5195-2014; S-8384-2016
    We analysed the correlation of F-18-fluorodeoxyglucose uptake into primary tumours using the maximum standardised uptake value (SUVmax) and the mean apparent diffusion coefficient (ADC(mean)) values in magnetic resonance imaging (MRI) with the clinical and pathological factors in patients with cervical cancer who were treated with concurrent chemoradiotherapy. The patients were stratified according to the primary tumour pre-treatment ADC(mean) and SUVmax cut-off values. There were significant correlations between the SUVmax of the primary tumour and tumour size, and the treatment response. The correlation between the ADC(mean) and FIGO stage, tumour size, and the lymph node metastasis was significant. The SUVmax was significantly and inversely correlated with the ADC(mean) for cervical cancer (r = -0.44, p <.001). In the multivariate analysis, the primary tumour ADC(mean), treatment response and the lymph node metastasis emerged as significant independent predictors of both OS and DFS, and of the primary tumour SUVmax for DFS. Tumour size has a borderline significance for OS. High SUVmax and low ADC(mean) of the primary tumour are important predictive factors for identifying high-risk patients with cervical cancer who are treated with definitive chemoradiotherapy. These results point to a future role for the diffusion-weighted MRI and for F-18-fluorodeoxyglucose positron emission tomography, not only in the staging of cervical cancer but as an aid in the selection of an adjuvant treatment regimen after chemoradiotherapy for individual patients.
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    Concurrent chemoradiotherapy with weekly carboplatin and paclitaxel may be a feasible option in inoperable stage III non-small cell lung cancer: a single center experience
    (2019) Calikusu, Zuleyha; Sedef, Ali Murat; Saltaoglu, Pinar
    Purpose: Concurrent chemoradiotherapy (CCRT) is a standard treatment for patients with unresectable stage III non-small cell lung cancer (NSCLC). An optimal chemotherapy regimen with concurrent thoracic radiotherapy is not known. In this study, we investigated the efficacy and toxicity of CCRT with carboplatin [area under curve (AUC) 2] and paclitaxel (80 mg/m(2)) during CCRT. Materials and Methods: We performed a retrospective survival analysis using medical records of 40 patients with inoperable stage III NSCLC that were treated with concurrent chemoradiotherapy with carboplatin-paclitaxel (AUC 2, 60 mg/m2). Results: The most common histopathology was adenocarcinoma, which was diagnosed in 18 patients (45%). There were 12 stage IIIA patients (30%) and 28 stage IIIB patients (70%). The median follow-up time was 22.5 months [95% confidence interval (CI), 2.9-72.2]. Median disease-free survival (DFS) and overall survival (OS) were 22.5 months (95% CI, 18.1-27.0) and 53.5 months (95% CI, 23.5-82.8). Grade 3-4 hematological and non-hematological toxicities were seen in 8 (20%) and 5 (12.5%) patients, respectively. Conclusion: This study showed that CCRT with weekly carboplatin-paclitaxel provides similar outcomes to cases in the literature and the regimen seems to be feasible with a low rate of grade 3-4 toxicity during CCRT of non operable stage III NSCLC. Keywords: Carboplatin, non-small cell lung cancer, chemoradiotherapy, paclitaxel
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    The prognostic value of haematologic parameter changes during treatment in cervical cancer patients treated with definitive chemoradiotherapy
    (2019) Yildirim, Berna A.; Guler, Ozan Cem; Kose, Fatih; Onal, Cem; 0000-0001-6908-3412; 0000-0002-0156-5973; 31023114; AAC-5654-2020
    We retrospectively analysed the prognostic significance of changes in absolute neutrophil count (ANC), absolute lymphocyte count (ALC) and neutrophil/lymphocyte ratio (NLR) during treatment with definitive chemoradiotherapy (CRT) in 104 cervical cancer patients. The absolute white blood cell, ANC and ALC decrease during treatment, NLR increased throughout treatment and reached to a plateau at fifth week. The ANC and NLR after 3rd week of definitive CRT were significantly higher and ALC after 3rd week of treatment was significantly lower in patients with progressive disease compared patients with no evidence of disease. Patients in low-haematological risk (LHR) group had significantly higher number of patients with smaller tumour size, early stage disease and without lymph node metastasis. In multivariate analysis, high-haematological risk (HHR) group and lymph node metastasis were negative prognosticators of overall and disease-free survival (DFS). The presence of lymph node metastasis and HHR could serve as a predicative factor of poor prognosis for cervical cancer patients.IMPACT STATEMENTWhat is already known on this subject? The ANC and NLR after 3rd week of definitive CRT were significantly higher and ALC after 3rd week of treatment was significantly lower in patients with progressive disease compared patients with no evidence of disease. Patients in LHR group had significantly higher number of patients with smaller tumour size, early stage disease and without lymph node metastasis. Lymph node metastasis and HHR and were negative prognosticators of overall and disease-free survival (DFS). The presence of lymph node metastasis and HHR could serve as a predicative factor of poor prognosis for cervical cancer patients.What the results of this study add? Weekly changes in ANC, ALC, and NLR, especially after 3rd week of treatment are predictive factors of disease progression, not the high-risk features of disease. Furthermore, in HHR group more patients with extensive stage disease, larger tumour and lymph node metastasis were observed compared to LHR group.What the implications are of these findings for clinical practice and/or further research? The patients may be stratified according to risk factors. The treatment intensification maybe required for HHR patients compared to LHR patients. Since our findings are preliminary, further studies are required to support these findings.