Tıp Fakültesi / Faculty of Medicine

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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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    Outcome of Elderly Nasopharyngeal Carcinoma Patients: A Single Center Study
    (2020) Basaran, Hamit; Cengiz, Mustafa; Yazici, Gozde; Ozdemir, Yurday; Suslu, Nilda; Gullu, Ibrahim H.; Ozyigit, Gokhan; 0000-0002-2218-2074; AAG-5629-2021
    Objective: This study aimed to assess the efficiency of radiotherapy and evaluate its outcomes for elderly (> 65 years) patients who have undergone treatment for nasopharyngeal carcinoma (NPC). Methods: Forty- five (male, 35; female, 10) elderly patients with a diagnosis of undifferentiated NPC who were treated at our institution between 1994 and 2012 were retrospectively evaluated. The primary endpoint was the relationship between the patients' characteristics and overall survival (OS); progression-free survival (PFS), locoregional progression-free survival (LR-PFS), and toxicity analysis were the secondary endpoints. Results: The patients had a median age of 74.2 years. At a median follow-up period of 64 months, the median OS, PFS, and LR-PFS were 45 (95% confidence interval [CI]: 5.887-84.113), 34 (95% CI: 0.0-70.504), and 45 (95% CI: 20.092-69908) months, respectively. The 2-, 3-, and 5-year OS rates were 61.5%, 53.1%, and 50.0%, respectively, and the 2-, 3-, and 5-year PFS rates were 57.6%, 46.8%, and 43.7%, respectively. Patients with T stage (T3-T4 vs.T1-T2) or N stage (N0-1 vs. N2) had significantly shorter OS (p<0.05), PFS (p<0.05), and LR-PFS (p<0.05) outcomes, respectively, which were also confirmed using a multivariate analysis (p<0.05). Conclusion: Our results demonstrated that the established prognostic factors, including T and N stages, were important prognostic indicators of NPC in elderly patients
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    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-6910-2021
    Background. 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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    Preliminary Simulation Study of Carotid Artery and Pharyngeal Constrictor Muscle Sparing-Radiotherapy in Glottic Carcinoma
    (2020) Ozdemir, Yurday; Acibuci, Ibrahim; Selek, Ugur; Topkan, Erkan; 0000-0002-2218-2074; 0000-0001-8120-7123; 33034277; AAG-5629-2021; AAG-2213-2021
    Background: This preliminary simulation study aimed to compare the dosimetric outcomes of carotid arteries (CAs) and pharyngeal constrictor muscle (PCM) in patients with T1N0M0 glottic carcinoma undergoing helical tomotherapy-intensity modulated radiotherapy (HT-IMRT) and 3-dimensional conformal radiotherapy (3D-CRT) plans. Methods: In addition to the clinical target volume (CTV) which was defined as the entire larynx, the CAs and PCM of 11 glottic carcinoma patients were delineated. The CTV was uniformly expanded 5 mm to create a planning target volume (PTV) relative to the PCM and at a distance of 2 mm from the CA. The dosimetric characteristics in HT-IMRT and lateral opposed fields-based 3D-CRT plans were analyzed. Results: Median D(95%)and V(100%)of PTV were significantly higher in HT-IMRT (p < 0.001) compared to 3D-CRT. The right/left CA dosimetric outcomes, including the mean doses (20.7/21.5 Gy versus 48.7/50.5 Gy), D-max(53.6/52.0 Gy versus 67.4/67.7 Gy), V-30(25.0/27.1% versus 77.6/80.3%), V-40(8.0/7.9% versus 74.6/71.9%), and V-50(2.0/1.2% versus 70.0/71.6%) were also significantly lower in HT-IMRT (p < 0.05), similar to the mean PCM doses (49.6 Gy versus 62.6 Gy for 3D-CRT;p < 0.001), respectively. Conclusions: Our present results demonstrated the feasibility of simultaneous sparing of the CAs and PCM in HT-IMRT- compared to 3D-CRT plans in glottic carcinoma patients undergoing definitive radiotherapy.
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    Low Advanced Lung Cancer Inflammation Index Predicts Poor Prognosis in Locally Advanced Nasopharyngeal Carcinoma Patients Treated with Definitive Concurrent Chemoradiotherapy
    (2020) Topkan, Erkan; Ozdemir, Yurday; Kucuk, Ahmet; Guler, Ozan Cem; Sezer, Ahmet; Besen, Ali Ayberk; Mertsoylu, Huseyin; Senyurek, Sukran; Kilic Durankus, Nulifer; Bolukbasi, Yasemin; Selek, Ugur; Pehlivan, Berrin; 0000-0001-8120-7123; 0000-0002-7862-0192; 0000-0002-2218-2074; 0000-0001-6908-3412; 0000-0002-1932-9784; 0000-0002-6445-1439; 0000-0002-5361-364X; 33082783; AAG-2213-2021; AAD-6910-2021; AAG-5629-2021; AAC-5654-2020; M-9530-2014; AAD-2667-2020
    Purpose. We aimed to retrospectively investigate the prognostic worth of pretreatment advanced lung cancer inflammation index (ALI) in locally advanced nasopharyngeal carcinoma (LA-NPC) patients treated with concurrent chemoradiotherapy (C-CRT).Patients and Methods. A total of 164 LA-NPC patients treated with cisplatinum-based definitive C-CRT were included in this retrospective cohort analysis. The convenience of ideal pre-C-CRT ALI cut-offs affecting survival results was searched by employing the receiver operating characteristic (ROC) curve analyses. The primary endpoint was the link between the ALI groups and overall survival (OS), while cancer-specific survival (CSS), locoregional progression-free survival [LR(PFS)], distant metastasis-free survival (DMFS), and PFS comprised the secondary endpoints.Results. The ROC curve analyses distinguished a rounded ALI cut-off score of 24.2 that arranged the patients into two cohorts [ALI >= 24.2 (N = 94) versus < 24.2 (N = 70)] with significantly distinct CSS, OS, DMFS, and PFS outcomes, except for the LRPFS. At a median follow-up time of 79.2 months (range: 6-141), the comparative analyses showed that ALI < 24.2 cohort had significantly shorter median CSS, OS, DMFS, and PFS time than the ALI >= 24.2 cohort (P<0.001for each), which retained significance at 5- (P<0.001) and 10-year (P<0.001) time points. In multivariate analyses, ALI < 24.2 was asserted to be an independent predictor of the worse prognosis for each endpoint (P<0.001for each) in addition to the tumor stage (T-stage) (P<0.05for all endpoints) and nodal stage (N-stage) (P<0.05for all endpoints).Conclusion. As a novel prognostic index, the pretreatment ALI < 24.2 appeared to be strongly associated with significantly diminished survival outcomes in LA-NPC patients treated with C-CRT independent of the universally recognized T- and N-stages.
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    Pretreatment Photopenia on F-18-Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography Scans Predicts Poor Prognosis in Nasopharyngeal Cancer Patients Undergoing Concurrent Chemoradiotherapy
    (2020) Topkan, Erkan; Selek, Ugur; Mertsoylu, Huseyin; Ozdemir, Yurday; Kucuk, Ahmet; Torun, Nese; Besen, Ali Ayberk; 0000-0002-2218-2074; 0000-0002-1932-9784; 0000-0001-8120-7123; 0000-0002-7862-0192; 0000-0002-5597-676X; 32075362; AAG-5629-2021; M-9530-2014; AAG-2213-2021; AAD-6910-2021; AAE-2718-2021
    Objectives. To investigate the influence of pretreatment primary tumor or nodal photopenia (PP) on F-18-fluorodeoxyglu- case positron emission tomography-computed tomography (FDG PET-CT), an indicator of tumor ischemia, on survival results of nasopharyngeal cancers (NPCs) treated with concurrent chemoradiotherapy (C-CRT). Methods. The pre-C-CRT FDG PET-CT scans of 104 patients with NPC (cT1-4 N0-3 M0) were retrospectively examined to determine the presence of PP (PP+). Our primary endpoint was the influence of PP+ on overall survival (OS), while the progression-free survival (PFS) and locoregional PFS (LRPFS) constituted the secondary endpoints. Results. The PP+ was detected in 29 (27.9%): nine (8.7%), seven (6.7%), and 13 (12.5%) in the primary tumor alone, primary tumor plus neck nodes, and neck nodes alone, respectively. Because the PP+ cases were small by count per location, all comparative analyses were performed according to overall PP+/PP- status instead of per detected site. At a median follow-up of 67.8 months (range, 9 to 130 months), the median survival times were not reached (NR) for the entire population. while 5-year OS, LRPFS, and PFS rates were 73.3%, 68.2%, and 63.4%, respectively. Comparatively the PP patients exhibited significantly poorer median OS (49.8 months vs. NR, P<0.001), LRPFS (40.7 months vs. NR, P=0.001), and PFS (31.8 months vs. NR, P=0.002) durations than their PP- counterparts. Furthermore, the PP+ retained its independent prognostic significance in multivariate analysis (P <0.001). Conclusion. Present results uncovered the pre-C-CRT PP as an independent predictor of poor prognosis for NPC patients, which underscore the requirement for the fortification of the local and systemic treatments in hypoxic NPCs.
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    Definitive concurrent chemoradiotherapy outcomes in Stage IIIB nonsmall cell lung cancer patients younger than 45 years: A retrospective analysis of 145 patients
    (2020) Topkan, Erkan; Guler, Ozan Cem; Ozdemir, Yurday; 0000-0001-6908-3412; 0000-0002-2218-2074; 0000-0001-8120-7123; 32930115; AAC-5654-2020; AAG-5629-2021; AAG-2213-2021
    Purpose: To assess the survival outcomes and prognostic factors of young (<= 45 years) Stage IIIB nonsmall cell lung cancer (NSCLC) patients treated with definitive concurrent chemoradiotherapy (C-CRT). Materials and Methods: Medical records of 145 Stage IIIB NSCLC patients (<= 45 years) who received 60-66 Gy thoracic radiotherapy and concurrent 1-3 cycles of cisplatin-based doublet chemotherapy were retrospectively evaluated. The primary endpoint was overall survival (OS), while locoregional progression-free survival (LRPFS), progression-free survival (PFS), and evaluation of potential prognostic factors constituted the secondary endpoints. Results: At median 21.6 months (range: 7.3-62.5) of follow-up, the median and 4-year survival estimates were 24.8 months and 24.2% for OS, 15.7 months and 18.9%, for LRPFS and 12.0 months and 11.2% for PFS, respectively. On univariate analyses, among all factors, the smaller tumor size (<= 7.0 cm; P = 0.03), lower T-stage (T1-T2; P = 0.02), lower N-stage (N2; P = 0.01), absence of anemia before C-CRT (hemoglobin [Hb] >= 12 g/dL; P < 0.001), and lower/no pretreatment weight loss (WL 5%; P < 0.001) were found to be associated significantly with longer median OS durations, which also retained their independent significance on multivariate analyses, except for tumor size category. Conclusions: The encouraging median 24.8 months OS duration observed here in young NSCLC patients accords well with the results of recent landmark locally advanced NSCLC series without age stratification. Other than the well-established T and N stages, extra exhibit of superior OS in patients with initial Hb 12 g/dL and <= 5% WL levels suggests a noteworthy prognostic role for these two latter variables in the stratification of such patients.
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    Systemic Inflammation Response Index Predicts Survival Outcomes in Glioblastoma Multiforme Patients Treated with Standard Stupp Protocol
    (2020) Topkan, Erkan; Kucuk, Ahmet; Ozdemir, Yurday; Mertsoylu, Huseyin; Besen, Ali Ayberk; Sezen, Duygu; Bolukbasi, Yasemin; Pehlivan, Berrin; Selek, Ugur; 0000-0002-7862-0192; 0000-0001-8120-7123; 0000-0002-2218-2074; 0000-0002-1932-9784; 33274245; AAD-6910-2021; AAG-2213-2021; AAG-5629-2021; M-9530-2014
    Objectives. We endeavored to retrospectively assess the prognostic merit of pretreatment systemic immune response index (SIRI) in glioblastoma multiforme (GBM) patients who underwent postoperative partial brain radiotherapy (RT) and concurrent plus adjuvant temozolomide (TMZ), namely, the Stupp protocol. Methods. The records of 181 newly diagnosed GBM patients who received the postoperative Stupp protocol were retrospectively analyzed. The SIRI value for each eligible patient was calculated by utilizing the platelet, neutrophil, and lymphocyte measures obtained on the first day of treatment: SIRI=NeutrophilsxMonocytes/Lymphocytes. The ideal cutoff values for SIRI connected with the progression-free- (PFS) and overall survival (OS) results were methodically searched through using the receiver operating characteristic (ROC) curve analysis. Primary and secondary end-points constituted the potential OS and PFS distinctions among the SIRI groups, respectively. Results. The ROC curve analysis labeled the ideal SIRI cutoffs at 1.74 (Area under the curve (AUC): 74.9%; sensitivity: 74.2%; specificity: 71.4%) and 1.78 (AUC: 73.6%; sensitivity: 73.1%; specificity: 70.8%) for PFS and OS status, individually. The SIRI cutoff of 1.78 of the OS status was chosen as the common cutoff for the stratification of the study population (Group 1: SIRI <= 1.78 (N=96) and SIRI>1.78 (N=85)) and further comparative PFS and OS analyses. Comparisons between the two SIRI cohorts manifested that the SIRI <= 1.78 cohort had altogether significantly superior median PFS (16.2 versus 6.6 months; P<0.001) and OS (22.9 versus 12.2 months; P<0.001) than its SIRI>1.78 counterparts. The results of multivariate Cox regression analyses ratified the independent and significant alliance between a low SIRI and longer PFS (P<0.001) and OS (P<0.001) durations, respectively. Conclusions. Present results firmly counseled the pretreatment SIRI as a novel, sound, and independent predictor of survival outcomes in newly diagnosed GBM patients intended to undergo postoperative Stupp protocol.