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Item 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-2213-2021We 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.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 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-2213-2021To 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.Item 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-2213-2021Background 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.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 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-2213-2021Purpose: 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.Item 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-6910-2021Purpose. 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.Item 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-6910-2021Objectives. 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.Item 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-2213-2021Background. 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.Item Comparison of Involved Field Radiotherapy versus Elective Nodal Irradiation in Stage IIIB/C Non-Small-Cell Lung Carcinoma Patients Treated with Concurrent Chemoradiotherapy: A Propensity Score Matching Study(2020) Topkan, Erkan; Ozdemir, Yurday; Guler, Ozan Cem; Kucuk, Ahmet; Besen, Ali Ayberk; Mertsoylu, Huseyin; Sezen, Duygu; Akdemir, Eyub Yasar; Sezer, Ahmet; Bolukbasi, Yasemin; Pehlivan, Berrin; Selek, Ugur; 0000-0002-1932-9784; 0000-0001-6908-3412; 0000-0002-2218-2074; 0000-0002-6445-1439; 0000-0001-8120-7123; 0000-0002-7862-0192; 32952557; M-9530-2014; AAC-5654-2020; AAG-5629-2021; AAD-2667-2020; AAG-2213-2021; AAD-6910-2021Background. We retrospectively compared the incidence of isolated elective nodal failure (IENF) and toxicity rates and survival outcomes after elective nodal irradiation (ENI) versus involved-field RT (IFRT) by employing the propensity score matching (PSM) methodology in stage IIIB/C inoperable non-small-cell lung cancer (NSCLC) patients treated with definitive concurrent chemoradiotherapy (C-CRT).Methods. Our PSM examination included 1048 stage IIIB/C NSCLC patients treated with C-CRT from January 2007 to December 2016: a total dose of 66 Gy (2 Gy/fraction) radiotherapy and 1-3 cycles of platinum-based doublet chemotherapy concurrently. The primary and secondary endpoints were the IENF and toxicity rates and survival outcomes after ENI versus IFRT, respectively. Propensity scores were calculated for each group to adjust for confounding variables and facilitate well-balanced comparability by creating 1 : 1 matched study groups.Results. The median follow-up was 26.4 months for the whole study accomplice. The PSM analysis unveiled 1 : 1 matched 646 patients for the ENI (N = 323) and IFRT (N = 323) cohorts. Intergroup comparisons discovered that the 5-year isolated ENF incidence rates (3.4% versus 4.3%;P=0.52) and median overall survival (25.2 versus 24.6 months;P=0.69), locoregional progression-free survival (15.3 versus 15.1 months;P=0.52), and progression-free survival (11.7 versus 11.2 months;P=0.57) durations were similar between the ENI and IFRT cohorts, separately. However, acute grade 3-4 leukopenia (P=0.0012), grade 3 nausea-vomiting (P=0.006), esophagitis (P=0.003), pneumonitis (P=0.002), late grade 3-4 esophageal toxicity (P=0.038), and the need for hospitalization (P<0.001) were all significantly higher in the ENI than in the IFRT group, respectively.Conclusion. Results of the present large-scale PSM cohort established the absence of meaningful IENF or survival differences between the IFRT and ENI cohorts and, consequently, counseled the IFRT as the elected RT technique for such patients since ENI increased the toxicity rates.
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