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    Systemic Inflammation Score for Predicting Radiation-Induced Trismus and Osteoradionecrosis of the Jaw Rates in Locally Advanced Nasopharyngeal Carcinoma Patients
    (2023) Somay, Efsun; Sezen, Duygu; Selek, Ugur; Besen, Ali Ayberk; Mertsoylu, Huseyin; Topkan, Erkan; 0000-0001-8120-7123; AAG-2213-2021
    We sought to determine the predictive value of the systemic inflammation score (SIS) for radiation-induced trismus (RIT) and osteora-dionecrosis of the jaw (ORNJ) in locally advanced nasopharyngeal carcinoma (LA-NPC) patients treated with concurrent chemoradio-therapy (C-CRT). LA-NPC patients (n= 188) who underwent C-CRT and pre-and post-C-CRT oral examinations from August 2010 to January 2022 were included. The three-tiered SIS groups were created using the serum albumin and lymphocyte-to-monocyte ratio (LMR) measures obtained on the first day of C-CRT: SIS-0: Albumin >= 40 g/dL and LMR >= 4.44); SIS-1: Albumin < 40 g/dL and LMR < 4.44 or albumin >= 0 g/dL and LMR >= 4.44; and SIS-2: Albumin < 40 g/dL and LMR <4.44. The primary objective was to ascertain whether there were irrefutable associations between pretreatment SIS groups and the respective post-C-CRT RIT and ORNJ rates. RIT and ORNJ were diagnosed in 33 (17.6%) and 21 (11.1%) patients, respectively. There were 12 (32.4%), 13 (12.7%), and 18 (45.0%) cases diagnosed with RIT in the respective SIS-0, SIS-1, and SIS-2 groups (p< 0.001). Similarly, there were 1 (2.7%), 11 (9.9%), and 9 (22.5%) cases with ORNJ diagnoses in the corresponding SIS groups (p< 0.001). The multivariate analysis's findings revealed that the SIS grouping was an independent predictor of RIT (p< 0.001) and ORNJ incidence rates (p< 0.001). Our study's findings indicate that the novel pretreatment SIS grouping is a dependable biomarker-based system, which can accurately predict the rates of RIT and ORNJ in LA-NPC patients who receive definitive C-CRT.
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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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    Predicting Teeth Extraction after Concurrent Chemoradiotherapy in Locally Advanced Nasopharyngeal Cancer Patients Using the Novel GLUCAR Index
    (2023) Somay, Efsun; Topkan, Erkan; Yilmaz, Busra; Besen, Ali Ayberk; Mertsoylu, Huseyin; Selek, Ugur; 0000-0001-8120-7123; 0000-0001-8251-6913; 38066835; AAG-2213-2021
    To evaluate the value of the newly created GLUCAR index in predicting tooth extraction rates after concurrent chemoradiotherapy (C-CRT) in locally advanced nasopharyngeal carcinomas (LA-NPCs). Methods: A total of 187 LA-NPC patients who received C-CRT were retrospectively analyzed. The GLUCAR index was defined as 'GLUCAR = (Fasting Glucose x CRP/Albumin Ratio) by utilizing measures of glucose, C-reactive protein (CRP), and albumin obtained on the first day of C-CRT. Results: The optimal GLUCAR cutoff was 31.8 (area under the curve: 78.1%; sensitivity: 70.5%; specificity: 70.7%, Youden: 0.412), dividing the study cohort into two groups: GLUCAR < 1.8 (N = 78) and GLUCAR >= 31.8 (N = 109) groups. A comparison between the two groups found that the tooth extraction rate was significantly higher in the group with a GLUCAR >= 31.8 (84.4% vs. 47.4% for GLUCAR < 31.8; odds ratio (OR):1.82; p < 0.001). In the univariate analysis, the mean mandibular dose >= 38.5 Gy group (76.5% vs. 54.9% for <38.5 Gy; OR: 1.45; p = 0.008), mandibular V55.2 Gy group >= 40.5% (80.3 vs. 63.5 for <40.5%, p = 0.004, OR; 1.30), and being diabetic (71.8% vs. 57.9% for nondiabetics; OR: 1.23; p = 0.007) appeared as the additional factors significantly associated with higher tooth extraction rates. All four characteristics remained independent predictors of higher tooth extraction rates after C-CRT in the multivariate analysis (p < 0.05 for each). Conclusions: The GLUCAR index, first introduced here, may serve as a robust new biomarker for predicting post-C-CRT tooth extraction rates and stratifying patients according to their tooth loss risk after treatment.
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    High Pre-Chemoradiotherapy Pan-Immune-Inflammation Value Levels Predict Worse Outcomes in Patients with Stage IIIB/C Non-Small-Cell Lung Cancer
    (2023) Topkan, Erkan; Kucuk, Ahmet; Ozkan, Emine Elif; Ozturk, Duriye; Besen, Ali Ayberk; Mertsoylu, Huseyin; Pehlivan, Berrin; Selek, Ugur; 0000-0001-8120-7123; 38091179; AAG-2213-2021
    Background and objectives We explored the prognostic usefulness of the pan-immune-inflammation value (PIV) in patients with stage IIIB/C non-small-cell lung cancer (NSCLC) who underwent concurrent chemoradiotherapy (CCRT).Methods and patients For all patients, the PIV was calculated using platelet (P), monocyte (M), neutrophil (N), and lymphocyte (L) measures obtained on the first day of CCRT: PIV = P x M x N divided by L. Using receiver operating characteristic (ROC) curve analysis, we searched for the existence of an ideal cutoff that may partition patients into two groups with unique progression-free- (PFS) and overall survival (OS) results. The primary endpoint of this retrospective cohort research was to determine whether there were any significant relationships between pretreatment PIV measures and post-CCRT OS outcomes.Results The present research included a total of 807 stage IIIB/C NSCLC patients. According to ROC curve analysis, the ideal PIV cutoff was 516 [area under the curve (AUC): 67.7%; sensitivity: 66.4%; specificity: 66.1%], which divided the whole cohort into two: low PIV (L-PIV: PIV < 516; N = 436) and high PIV (H-PIV: PIV >= 516; N = 371). The comparisons between the PIV groups indicated that either the median PFS (9.2 vs. 13.4 months; P < 0.001) or OS (16.7 vs. 32.7 months; P < 0.001) durations in the H-PIV group were substantially inferior to their L-PIV counterpart. Apart from the H-PIV (P < 0.001), the N-3 nodal stage (P = 0.006), IIIC disease stage (P < 0.001), and receiving only one cycle of concurrent chemotherapy (P = 0.005) were also determined to be significant predictors of poor PFS (P < 0.05, for each) and OS (P < 0.05, for each) outcomes in univariate analysis. The multivariate analysis findings revealed that all four variables had independent negative impacts on PFS (P < 0.05, for each) and OS (P < 0.05, for each).Conclusions The findings of this hypothesis-generating retrospective analysis claimed that the novel PIV was an independent and steadfast predictor of PFS and OS in stage IIIB/C NSCLC patients.
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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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    Definitive Chemoradiation Therapy Following Surgical Resection or Radiosurgery Plus Whole-Brain Radiation Therapy in Non-Small Cell Lung Cancer Patients With Synchronous Solitary Brain Metastasis: A Curative Approach
    (2014) Parlak, Cem; Mertsoylu, Huseyin; Guler, Ozan Cem; Onal, Cem; Topkan, Erkan; https://orcid.org/0000-0001-6170-0383; https://orcid.org/0000-0002-1932-9784; https://orcid.org/0000-0001-6908-3412; https://orcid.org/0000-0002-2742-9021; https://orcid.org/0000-0001-8120-7123; 24495594; B-3671-2014; M-9530-2014; AAC-5654-2020; HOC-5611-2023; AAG-2213-2021
    Purpose/Objectives: The aim of this study was to evaluate the impact of definitive thoracic chemoradiation therapy following surgery or stereotactic radiosurgery (SRS) and whole-brain radiation therapy (WBRT) on the outcomes of patients with non-small cell lung cancer (NSCLC) with synchronous solitary brain metastasis (SSBM). Methods and Materials: A total of 63 NSCLC patients with SSBM were retrospectively evaluated. Patients were staged using positron emission tomography-computed tomography in addition to conventional staging tools. Thoracic radiation therapy (TRT) with a total dose of 66 Gy in 2 Gy fractions was delivered along with 2 cycles of cisplatin-based chemotherapy following either surgery plus 30 Gy of WBRT (n = 33) or SRS plus 30 Gy of WBRT (n = 30) for BM. Results: Overall, the treatment was well tolerated. All patients received planned TRT, and 57 patients (90.5%) were also able to receive 2 cycles of chemotherapy. At a median follow-up of 25.3 months (7.1-52.1 months), the median months of overall, locoregional progression-free, neurological progression-free, and progression-free survival were 28.6, 17.7, 26.4, and 14.6, respectively. Both univariate and multivariate analyses revealed that patients with a T1-T2 thoracic disease burden (P = .001), a nodal stage of N0-N1 (P = .003), and no weight loss (P = .008) exhibited superior survival. Conclusions: In the present series, surgical and radiosurgical treatments directed toward SSBM in NSCLC patients were equally effective. The similarities between the present survival outcomes and those reported in other studies for locally advanced NSCLC patients indicate the potentially curative role of definitive chemoradiation therapy for highly selected patients with SSBM. (C) 2014 Elsevier Inc.
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    Patients with Distal Intestinal Gastric Cancer Have Superior Outcome with Addition of Taxanes to Combination Chemotherapy, While Proximal Intestinal and Diffuse Gastric Cancers do not: Does Biology and Location Predict Chemotherapy Benefit?
    (2015) Sedef, Ali Murat; Kose, Fatih; Sumbul, Ahmet Taner; Dogan, Ozlem; Besen, Ali Ayberk; Tatli, Ali Murat; Mertsoylu, Huseyin; Sezer, Ahmet; Muallaoglu, Sadik; Ozyilkan, Ozgur; Abali, Huseyin; 0000-0002-6445-1439; 0000-0002-6242-2802; 0000-0002-1932-9784; 0000-0002-7862-0192; 0000-0002-5573-906X; 0000-0001-8825-4918; 0000-0002-0156-5973; 25572818; AAD-2667-2020; IVU-7523-2023; -9530-2014; AAD-6910-2021; D-4793-2014; D-7660-2016; AAD-2817-2021; G-4827-2016; GZH-1913-2022
    Gastric cancer, with one million new cases observed annually, and its dismal prognosis, is one of the leading causes of cancer-related mortalities. Systemic chemotherapy is the main treatment modality in advanced gastric cancer patients. We aim to evaluate the predictive role of tumor localization and histopathology on choosing three or two-drug combination regimens. Consecutive 110 metastatic gastric adenocarcinoma patients who were admitted to the Baskent University Department of Medical Oncology and the Van Research and Training Hospital were included in the study. Data of patients were analyzed retrospectively. Median age of patients was 58 years (range 30-80). Proximal intestinal, distal intestinal, and diffuse gastric cancers were found in 35 (32 %), 64 (58 %), and 11 (10 %) patients, respectively. 5-fluoracil and platinum (PF) and PFtax were administered to 47 (43 %) and 63 (57 %) patients, respectively. Median progression-free survival (PFS) was 4.0 (95 % CI 2.5-5.6) and 7.4 months (95 % CI 6.0-8.7) for PF and PFtax groups, (p = 0.034). When we used tumor localization as strata in the PFS survival curve, PFtax produced significantly higher PFS rates only in distal intestinal-type gastric cancer, compared with PF (p = 0.03). Median overall survival (OS) was 9.0 (95 % CI 5.2-12.3) and 17.3 months (95 % CI 7.8-27) for PF and PFtax groups, (p = 0.010). When we used tumor localization as strata in the OS survival curve, PFtax produced significantly higher OS rates only in distal intestinal-type gastric cancer compared with PF (p = 0.015). Pathology and tumor location in gastric cancers may affect the outcome, the addition of taxanes as a third drug may significantly increase PFS and OS rate purely in distal intestinal-type gastric cancer but not in patients with proximal and diffuse-type gastric cancers.
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    Procalcitonin as A Biomarker for Infection-Related Mortality in Cancer Patients
    (2015) Sedef, Ali M.; Kose, Fatih; Mertsoylu, Huseyin; Ozyilkan, Ozgur; 0000-0002-0156-5973; 0000-0002-1932-9784; 0000-0001-8825-4918; 25872114; G-4827-2016; M-9530-2014; AAD-2817-2021
    Purpose of review Infectious diseases are the second leading cause of death following direct cancer-related complications in the field of oncology. Clinical studies using the classic inflammatory biomarkers, C-reactive protein, erythrocyte sedimentation rate, leukocytosis, and thrombocytosis fail to show a significant correlation between these biomarkers and infection-related mortality. It is therefore crucial to define new biomarkers that are not affected by the primary cancer and precisely show the severity of the infection to help in the decision-making process. Recent findings A significant increase in the number of cancer patients in the past decades has created an exponential increase in the number of immunocompromised patients. Preemptive and typically unnecessary usage of broad-spectrum antibiotics is common during the treatment of these patients and may result in an increase in multidrug-resistant microbial strains. Recent clinical studies suggest that a significant reduction in antibiotic consumption may be achieved by procalcitonin-guided algorithms without sacrificing the outcome of patients with severe infection. Summary In this article, we focus on procalcitonin and its potential role in differentiating cancer and infection-induced inflammation. Using this strategy may significantly reduce the usage of empirical broad-spectrum antibiotics and result in earlier discharge of patients.
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    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-2817-2021
    Purpose: 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.
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    Neutrophil-to-lymphocyte Ratio Predicts PSA Response, but not Outcomes in Patients with Castration-Resistant Prostate Cancer Treated with Docetaxel
    (2014) Sumbul, Ahmet Taner; Sezer, Ahmet; Abali, Huseyin; Kose, Fatih; Gultepe, Ilhami; Mertsoylu, Huseyin; Muallaoglu, Sadik; Ozyilkan, Ozgur; https://orcid.org/0000-0002-6445-1439; https://orcid.org/0000-0001-5596-0920; https://orcid.org/0000-0002-0156-5973; https://orcid.org/0000-0002-1932-9784; https://orcid.org/0000-0002-6242-2802; https://orcid.org/0000-0001-8825-4918; 24526335; AAD-2667-2020; D-7660-2016; G-4827-2016; M-9530-2014; IVU-7523-2023; AAD-2817-2021
    The neutrophil-to-lymphocyte ratio (NLR) is a marker of systemic inflammatory response and evidences for the relationship between NLR and the response to treatment gradually increases in cancer patients. In this study, we aimed to investigate the effect of the pretreatment NLR and other factors related to the patient on predicting the outcome of docetaxel + prednisone chemotherapy in prostate cancer patients who become castration resistant. Thirty-three metastatic castration-resistant prostate cancer patients those who were treated between 2009 and 2013 were included in our study. All data of the patients, including pathological, clinical, radiological, biochemical and hematological data, were assessed retrospectively using our database system. The median progression-free survival (PFS) was determined as 23.9 months (range 0.36-118.7) with androgen suppression therapy and 9.5 months (range 1.7-39.4) with docetaxel + prednisone therapy. NLR was found to be correlated with only posttreatment psa levels. In the NLR a parts per thousand currency sign3 group, the PSA levels were statistically significantly lower than the other group (r = 0.002). Furthermore, the relationships between the clinical response and PFS and the other pretreatment parameters of the patients were evaluated in order to predict which group would respond better to docetaxel + prednisone therapy after becoming androgen resistant. No relationship was found between any of the parameters and the response to therapy. Although NLR was found effective in predicting the PSA response in docetaxel + prednisone therapy, neither NLR nor any other clinical parameter was found effective in predicting the outcome and the role of NLR in the future of CRPC is questionable.