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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    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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    High Measures of Pre-Chemoradiotherapy Platelet-to-Albumin Ratio Indicates Poor Prognosis in Locally Advanced Pancreatic Cancer Patients
    (2022) Kucuk, Ahmet; Topkan, Erkan; Selek, Ugur; Haksoyler, Veysel; Mertsoylu, Huseyin; Besen, Ali Ayberk; Pehlivan, Berrin; https://orcid.org/0000-0001-8120-7123; 35444422; AAG-2213-2021
    Purpose: In a lack of similar research, we meant to retrospectively investigate the prognostic significance of pre-chemoradiotherapy (C-CRT) platelet-to-albumin ratio (PAR) on the survival results of locally advanced unresectable pancreatic adenocarcinoma (LAPC) patients. Patients and Methods: The present analysis included 139 LAPC patients who received C-CRT in total. The utility of pre-C-CRT cutoff(s) reshaping survival data was explored using receiver operating characteristic (ROC) curve analysis. The primary and secondary objectives were the associations between PAR levels and overall survival (OS) and progression-free survival (PFS) outcomes. Results: At a median follow-up of 15.7 months (95% CI: 11.6-19.8), the overall cohort's median and 5-year OS rates were 14.4 months (95% CI: 11.8-17) and 14.7%, respectively, while the corresponding PFS rates were 7.8 months (95% CI: 6.5-9.1) and 11.2%. Because the ROC curve analysis found 4.9 as the optimal PAR cutoff for both OS and PFS [area under the curve (AUC): 75.4%; sensitivity: 72.4%; specificity: 70.3%], we divided the patients into two PAR cohorts: PAR<4.9 (N=60) and PAR>4.9 (N=79). Comparative analysis per PAR group exhibited significantly worse OS (11.2 vs 18.6 months, and 9.8% vs 20.9% at 5 years, P=0.003) and DFS (7 vs 14.3 months, and 7.6% vs 16.2% at 5 years, P=0.001) with PAR>4.9 versus PAR<4.9, respectively. In multivariate analysis, the N0 nodal status, CA 19-9 <= 90 U/mL, and PAR<4.9 were found to be independent predictors of improved OS and PFS. Conclusion: The pre-C-CRT high PAR (>4.9) robustly and independently prognosticated significantly worse OS and PFS results in inoperable LAPC patients who underwent definitive C-CRT.
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    Prechemoradiotherapy Systemic Inflammation Response Index Stratifies Stage IIIB/C Non-Small-Cell Lung Cancer Patients into Three Prognostic Groups: A Propensity Score-Matching Analysis
    (2021) Topkan, Erkan; Selek, Ugur; Kucuk, Ahmet; Haksoyler, Veysel; Ozdemir, Yurday; Sezen, Duygu; Mertsoylu, Huseyin; Besen, Ali Ayberk; Bolukbasi, Yasemin; Ozyilkan, Ozgur; Pehlivan, Berrin; 0000-0001-8120-7123; 0000-0002-2218-2074; 0000-0002-7862-0192; 33552158; AAG-2213-2021; AAG-5629-2021; AAD-6910-2021
    Purpose. We explored the prognostic influence of the systemic inflammation response index (SIRI) on the survival outcomes of stage IIIB/C non-small-cell lung cancer (NSCLC) patients who underwent concurrent chemoradiotherapy. Methods. Present propensity score-matching (PSM) analysis comprised 876 stage IIIB/C NSCLC patients who received 1-3 cycles of platinum-based doublets concurrent with thoracic radiotherapy from 2007 to 2017. The primary and secondary objectives were the relationships between the SIRI values and overall (OS) and progression-free survival, respectively. Propensity scores were calculated for SIRI groups to adjust for confounders and to facilitate well-balanced comparability between the SIRI groups by creating 1 : 1 matched study groups. Results. The receiver operating characteristic curve analysis identified an optimal SIRI cutoff at 1.9 for OS (AUC: 78.8%; sensitivity: 73.7%; specificity: 70.7%) and PFS (AUC: 80.5%; sensitivity: 75.8%; specificity: 72.9%) and we grouped the patients into two PSM cohorts: SIRI < 1.9 (N = 304) and SIRI >= 1.9 (N = 304), respectively. The SIRI >= 1.9 cohort had significantly worse median OS (P<0.001) and PFS (P<0.001) than their SIRI < 1.9 companions. The further combination of SIRI with disease stage exhibited that the SIRI-1 (IIIB and SIRI < 1.9) and SIRI-3 (IIIC and SIRI >= 1.9) cohorts had the best and worst outcomes, respectively, with SIRI-2 cohort (IIIB and SIRI >= 1.9 or IIIC and SIRI < 1.9) being remained in between (P<0.001 for OS and PFS, separately). In multivariate analysis, the two- and three-laddered stratifications per the 1.9 cutoffs and SIRI groups retained their independent significance, individually. Conclusions. The SIRI >= 1.9 independently prognosticated significantly worse OS and PFS results and plated the stage IIIB/C patients into three fundamentally distinct prognostic groups.
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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 Value of Pretreatment Systemic Immune-Inflammation Index in Glioblastoma Multiforme Patients Undergoing Postneurosurgical Radiotherapy Plus Concurrent and Adjuvant Temozolomide
    (2020) Topkan, Erkan; Besen, Ali Ayberk; Ozdemir, Yurday; Kucuk, Ahmet; Mertsoylu, Huseyin; Pehlivan, Berrin; Selek, Ugur; 0000-0002-1932-9784; 0000-0002-2218-2074; 0000-0001-8120-7123; 0000-0002-7862-0192; 32565725; M-9530-2014; AAG-5629-2021; AAG-2213-2021; AAD-6910-2021
    Objectives. To evaluate the potential prognostic utility of pretreatment systemic immune-inflammation index (SII) in newly diagnosed glioblastoma multiforme (GBM) patients who underwent postneurosurgical radiotherapy and concurrent plus adjuvant temozolomide. Methods. The retrospective data of GBM patients who underwent postneurosurgical radiotherapy and concurrent plus adjuvant temozolomide were analyzed. For each patient, SII was calculated using the platelet, neutrophil, and lymphocyte measures obtained on the first day of treatment: SII=plateletsxneutrophils/lymphocytes. The receiver operating characteristic (ROC) curve analysis was utilized for the evaluation of optimal cut-off values for SII those linked with the outcomes. Primary and secondary endpoints constituted the overall (OS) and progression-free survival (PFS) per conveyance SII group. Results. A total of 167 patients were included. The ROC curve analysis identified the optimum SII cut-off at a rounded 565 value that significantly interacted with the PFS and OS and stratified patients into two groups: low-SII (SII<565; n=71) and high-SII (SII >= 565; n=96), respectively. Comparative survival analyses exhibited that the high-SII cohort had significantly shorter median PFS (6.0 versus 16.6 months; P<0.001) and OS (11.1 versus 22.9 months; P<0.001) than the low-SII cohort. The relationship between the high-SII and poorer PFS (P<0.001) and OS (P<0.001) further retained its independent significance in multivariate analysis, as well. Conclusions. The outcomes displayed here qualified the pretreatment SII as a novel independent prognostic index for predicting survival outcomes of newly diagnosed GBM patients undergoing postneurosurgical radiotherapy and concurrent plus adjuvant temozolomide.
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    Prognostic Value of C-Reactive Protein to Albumin Ratio in Glioblastoma Multiforme Patients Treated with Concurrent Radiotherapy and Temozolomide
    (2020) Topkan, Erkan; Besen, Ali A.; Mertsoylu, Huseyin; Kucuk, Ahmet; Pehlivan, Berrin; Selek, Ugur; 0000-0002-7862-0192; 0000-0002-1932-9784; 0000-0001-8120-7123; 32566124; AAD-6910-2021; M-9530-2014; AAG-2213-2021
    Objective. We investigated the prognostic impact of C-reactive protein to albumin ratio (CRP/Alb) on the survival outcomes of newly diagnosed glioblastoma multiforme (GBM) patients treated with radiotherapy (RT) and concurrent plus adjuvant temozolomide (TMZ).Methods. The pretreatment CRP and Alb records of GBM patients who underwent RT and concurrent plus adjuvant TMZ were retrospectively analyzed. The CRP/Alb was calculated by dividing serum CRP level by serum Alb level obtained prior to RT. The availability of significant cutoff value for CRP/Alb that interacts with survival was assessed with the receiver-operating characteristic (ROC) curve analysis. The primary endpoint was the association between the CRP/Alb and the overall survival (OS).Results. A total of 153 patients were analyzed. At a median follow-up of 14.7 months, median and 5-year OS rates were 16.2 months (95% CI: 12.5-19.7) and 9.5%, respectively, for the entire cohort. The ROC curve analysis identified a significant cutoff value at 0.75 point (area under the curve: 74.9%; sensitivity: 70.9%; specificity: 67.7%;P<0.001) for CRP/Alb that interacts with OS and grouped the patients into two: CRP/Alb <0.75 (n = 61) and >= 0.75 (n = 92), respectively. Survival comparisons revealed that the CRP/Alb <0.75 was associated with a significantly superior median (22.5 versus 15.7 months;P<0.001) and 5-year (20% versus 0%) rates than the CRP/Alb >= 0.75, which retained its independent significance in multivariate analysis (P<0.001).Conclusion. Present results suggested the pretreatment CRP/Alb as a significant and independent inflammation-based index which can be utilized for further prognostic lamination of GBM patients.
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    Low Systemic Inflammation Response Index Predicts Good Prognosis in Locally Advanced Pancreatic Carcinoma Patients Treated with Concurrent Chemoradiotherapy
    (2020) Topkan, Erkan; Mertsoylu, Huseyin; Kucuk, Ahmet; Besen, Ali Ayberk; Sezer, Ahmet; Sezen, Duygu; Bolukbasi, Yasemin; Selek, Ugur; Pehlivan, Berrin; 0000-0002-7862-0192; 0000-0002-6445-1439; 0000-0002-1932-9784; 0000-0001-8120-7123; AAD-6910-2021; AAD-2667-2020; M-9530-2014; AAG-2213-2021
    Background. We investigated the prognostic significance of pretreatment systemic inflammation response index (SIRI) in locally advanced pancreatic carcinoma (LAPC) patients treated with concurrent chemoradiotherapy (CRT). Methods. Present retrospective cohort analysis investigated consecutive 154 LAPC patients who received radical CRT. The SIRI was defined as:SIRI=neutrophilxmonocyte/lymphocyte counts. Ideal SIRI cutoff(s) influencing overall survival (OS) and progression-free survival (PFS) results were sought by using receiver operating characteristic (ROC) curve analysis. The primary endpoint was the interaction between the SIRI and OS results. Results. The median follow-up, PFS, and OS durations were 14.3 (range: 2.9-74.6), 7.9 [%95 confidence interval (CI): 5.7-10.1), and 14.7 months (%95 CI: 11.4-18.0) for the entire cohort, respectively. ROC curve analyses determined the ideal SIRI cutoff that exhibiting a significant link with OS and PFS outcomes at the rounded 1.6 point (AUC: 74.3%; sensitivity: 73.8%; specificity: 70.1%).The SIRI <1.6 patients (N=58) had significantly superior median PFS (13.8 versus 6.7 months; P<0.001) and OS (28.6 versus 12.6 months; P<0.001) lengths than SIRI >= 1.6 patients (N=96), respectively. Although the N0 (versus N1; P<0.05) and CA 19-9 <= 90 U/mL (versus >90 U/mL) appeared as the other significant associates of better OS and PFS in univariate analyses, yet the results of multivariate analyses confirmed the SIRI <1.6 as the independent indicator of superior OS and PFS (P<0.001 for each). Conclusion. Pretreatment SIRI is a novel independent prognosticator that may further enhance the conventional tumor-node-metastases staging system in a more precise prediction of the OS and PFS outcomes of LAPC patients after radical CRT.