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    Pretreatment Pan-Immune-Inflammation Value Efficiently Predicts Survival Outcomes in Glioblastoma Multiforme Patients Receiving Radiotherapy and Temozolomide
    (2022) Topkan, Erkan; Kucuk, Ahmet; Selek, Ugur; https://orcid.org/0000-0001-8120-7123; 36479136; AAG-2213-2021
    Objectives. The purpose of this study was to determine the predictive significance of pretreatment pan-immune-inflammation value (PIV) in patients with newly diagnosed glioblastoma multiforme (GBM) who received postsurgical radiation (RT) and concurrent plus adjuvant temozolomide (TMZ). Methods. The outcomes of 204 newly diagnosed GBM patients were analyzed retrospectively. Each eligible patient's PIV was calculated using the findings of peripheral blood platelet (P), monocyte (M), neutrophil (N), and lymphocyte (L) counts obtained on the first day of therapy: PIV=PxMxN & DIVIDE;L. We used receiver operating characteristic (ROC) curve analysis to discover the ideal cutoff values for PIV concerning progression-free (PFS) and overall survival (OS) outcomes. The primary and secondary end-points were the OS and PFS divergences across the PIV groups. Results. In ROC curve analysis, the optimal PIV cutoff was 385, which substantially interacted with PFS and OS results and categorized patients into low PIV (L-PIV; N=75) and high PIV (H-PIV; N=129) groups. Comparative survival analyses showed that the patients in the H-PIV group had significantly shorter median PFS (6.0 vs. 16.6 months; P < 0.001) and OS (11.1 vs. 22.9 months; P < 0.001) durations than those in the L-PIV group. The results of multivariate Cox regression analysis indicated an independent and significant connection between an H-PIV measure and shorter PFS and OS outcomes. Conclusions. The novel PIV was able to independently stratify newly diagnosed GBM patients into two groups with fundamentally different PFS and OS outcomes following RT and concurrent plus adjuvant TMZ.
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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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    Postchemoradiotherapy Neutrophil-to-Lymphocyte Ratio Predicts Distant Metastasis and Survival Results in Locally Advanced Pancreatic Cancers
    (2022) Topkan, Erkan; Selek, Ugur; Haksoyler, Veysel; Kucuk, Ahmet; Durankus, Nulifer Kilic; Sezen, Duygu; Bolukbasi, Yasemin; Pehlivan, Berrin; https://orcid.org/0000-0001-8120-7123; 35685603; AAG-2213-2021
    Background and Objectives. In the absence of similar research, we endeavored to investigate the prognostic usefulness of posttreatment neutrophil-to-lymphocyte ratio (NLR) in patients treated with definitive concurrent chemoradiotherapy (CCRT) for locally advanced pancreatic adenocarcinoma (LAPAC). Materials and Methods. Our retrospective research included a sum of 126 LAPAC patients who received CCRT. The NLR was calculated for each patient based on the complete blood count test results obtained on the last day of the CCRT. The availability of optimal cutoff(s) that might dichotomize the whole cohort into two groups with significantly different clinical outcomes was searched using receiver operating characteristic (ROC) curve analysis. Primary and secondary endpoints were the potential association between the post-CCRT NLR measures and distant metastasis-free survival (DMFS) and overall survival (OS) outcomes. Results. The median follow-up duration was 14.7 months (range: 2.4-94.5). The median and 3-year OS and DMFS rates for the whole group were 15.3 months (95% confidence interval: 12.4-18.2) and 14.5%, and 8.7 months (95% CI: 6.7-10.7) and 6.3% separately. The ROC curve analysis findings separated the patients into two groups on a rounded NLR cutoff of 3.1 (area under the curve (AUC): 75.4%; sensitivity: 74.2%; specificity: 73.9%) for OS and DMFS: NLR < 3.1 (N = 62) and NLR >= 3.1 (N = 64), respectively. Comparisons between the NLR groups displayed that the median OS (11.4 vs. 21.4 months; P < 0.001) and DMFS (6.0 vs. 16.0 months; P < 0.001) lengths were significantly shorter in the NLR >= 3.1 group than its NLR < 3.1 counterparts, as well as the 3-year actuarial DM rate (79.7% vs. 50.0%; P=0.003). The N1-2 nodal stage, CA 19-9 > 90 U/mL, and NLR > 3.1 were found to be independent predictors of poor prognosis in the multivariate analysis. Conclusion. The present study found that the posttreatment NLR >= 3.1 was independently linked with a higher risk of DM and subsequent degraded survival outcomes in unresectable LAPAC patients managed with exclusive CCRT.
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    Role of Consolidative Thoracic Radiotherapy for Extensive-stage Small Cell Lung Cancer: Trod Thoracic Oncology Study Group 08-006 Multi-institutional Study
    (2022) Yavas, Guler; Kirakli, Esra Korkmaz; Dagdelen, Meltem; Topkan, Erkan; Saynak, Mert; Dincbas, Fazilet Oner; OzdemIr, Yurday; Yavas, Cagdas; Birgi, Sumerya Duru; Akyurek, Serap
    OBJECTIVE We aimed to evaluate the role of consolidative thoracic radiotherapy (TRT) in patients with extensive-stage small cell lung cancer (ES-SCLC). METHODS The clinical data for 151 patients with the diagnosis of ES-SCLC treated with consolidative TRT from six different hospitals from Turkey analyzed. RESULTS The median age of the patients was 61 years (range 36-83 years). The median dose of radiotherapy (RT) was 45 Gy (range: 30-66 Gy) applied in median 25 fractions (range 10-34 fractions). For 151 assessable patients, the median survival time (MST) was 14 months (range: 12.6-15.3). The patients who has complete response and partial response had 16 months, and 14 months of MST. In multivariate analyses prophylactic cranial irradiation (PCI) (p=0.011), female gender (p=0.017), and comorbidity (p=0.006) were found as significant parameters associated with survival. The MSTs were 12 months in patients without comorbidity, and 16 months for the patients with at least one comorbid disease. The patients who received PCI had improved MSTs when compared the ones without PCI (16 months vs. 12 months). There was a trend towards improved overall survival times in patients who received EQD2 >= 47 Gy RT doses (p=0.08). CONCLUSION Female gender, use of PCI, and unavailability of comorbid disease were associated with improved survival in ES-SLCL patients. There was a trend towards overall survival times in patients who received >= 47 Gy EQD2 doses; however, we believe that this statistical insignificance was related to our limited patient numbers.
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    Low Pre-Chemoradiotherapy Pan-Immune-Inflammation Value (PIV) Measures Predict Better Survival Outcomes in Locally Advanced Pancreatic Adenocarcinomas
    (2022) Topkan, Erkan; Selek, Ugur; Kucuk, Ahmet; Pehlivan, Berrin; 0000-0001-8120-7123; 0000-0001-8087-3140; 36158517; AAG-2213-2021
    Objective: This study sought to determine whether pretreatment pan-immune-inflammation value (PIV) could be used to predict prognosis in patients with locally advanced pancreatic adenocarcinoma (LA-PAC) following definitive concurrent chemoradiotherapy (C-CRT). Methods: The outcomes of 178 LA-PAC patients who received definitive C-CRT were analyzed retrospectively. For all patients, the PIV was calculated using the peripheral blood platelet (P), monocyte (M), neutrophil (N), and lymphocyte (L) counts obtained on the first day of C-CRT: PIV=PxMxN divided by L. The optimum cutoff values for PIV connected to progression-free (PFS) and overall survival (OS) results were sought using receiver operating characteristic (ROC) curve analysis. The OS and PFS differences between the PIV groups constituted the primary and secondary endpoints, respectively. Results: ROC curve analysis indicated that the ideal PIV cutoff was 464 (AUC: 75.9%, sensitivity: 74.1%, specificity: 71.9%), which categorized patients into two groups based on PFS and OS results: low PIV (L-PIV; N = 69) and high PIV (H-PIV; N = 109). According to comparative survival analyses, patients in the L-PIV group had significantly longer median PFS (14.3 vs 7.3 months; HR: 3.04; P < 0.001) and OS (25.9 vs 13.3 months; HR: 2.86; P < 0.001) than those in the H-PIV group. Although none of the H-PIV patients could survive beyond 5 years, the estimated 5-year OS rate was 29.7% in the L-PIV cohort. In multivariate analyses, besides the L-PIV, N0 nodal stage, and CA 19-9 <= 90 U/mL appeared to be the independent predictors of better PFS (P < 0.05 for each) and OS (P < 0.05 for each) results. Conclusion: The present results indicated that pre-C-CRT L-PIV measures were associated with favorable median and long-term PFS and OS results in LA-PAC patients, suggesting that the PIV is a potent and independent novel prognostic biomarker.
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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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    Prognostic Utility of Prechemoradiotherapy Albumin-to-Alkaline Phosphatase Ratio in Unresectable Locally Advanced Pancreatic Carcinoma Patients
    (2021) Haksoyler, Veysel; Topkan, Erkan; Prognostic Utility of Prechemoradiotherapy Albumin-to-Alkaline Phosphatase Ratio in Unresectable Locally Advanced Pancreatic Carcinoma Patients; 0000-0001-8120-7123; 33927759; AAG-2213-2021
    Background. We investigated the prognostic usefulness of prechemoradiotherapy (CRT) albumin-to-alkaline phosphatase ratio (AAPR) in unresectable locally advanced pancreatic adenocarcinoma (LAPAC) patients managed with definitive concurrent CRT (CCRT). Methods. A sum of 136 LAPAC patients who consecutively underwent definitive CCRT was retrospectively analyzed. The AAPR (serum albumin (g/dL)/serum alkaline phosphatase (IU/L)) was calculated by using the parameters obtained from the routine biochemistry tests on the first day of the CCRT. Ideal AAPR cutoff was sought by utilizing receiver operating characteristic (ROC) curve analysis. The primary and secondary endpoints were the impact of the AAPR on the overall survival (OS) and progression-free survival (PFS) results, respectively. Results. At a median follow-up of 14.8 months (range: 3.2-85.7), the median PFS and OS times were 7.5 (95% confidence interval (CI): 6.0-9.0) and 14.9 months (95% CI: 11.9-17.9), respectively. The ideal common AAPR cutoff was identified at the rounded 0.46 (area under the curve: 72.3%; sensitivity: 71.2%; specificity: 70.3%) point that dichotomized the patients into two groups: low AAPR (L-AAPR; N=71) and high AAPR (H-AAPR; N=65) groups, respectively. Comparative survival analyses showed that the L-AAPR cohort had significantly shorter median PFS (6.8 (95% CI: 5.7-7.9) versus 11.3 (95% CI: 9.9-12.7) months; P=0.005) and OS (12.8 (95% CI: 10.6-15.0) versus 19.2 (95% CI: 16.9-21.5) months; P=0.001) durations than their H-AAPR counterparts, separately. Albeit the N1-2 (P=0.004) and CA 19-9>90 U/mL (P=0.008) were also found to be associated with inferior outcomes, yet the results of the multivariate analyses ascertained the L-AAPR as an independent indicator of diminished PFS (P=0.003) and OS (P=0.002) results. Conclusion. The present results proposed that the pretreatment AAPR<0.46 was a novel independent indicator of adverse PFS and OS in unresectable LAPAC patients undergoing definitive CCRT.
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    High Pretreatment Platelet-to-Albumin Ratio Predicts Poor Survival Results in Locally Advanced Nasopharyngeal Cancers Treated with Chemoradiotherapy
    (2021) Haksoyler, Veysel; Topkan, Erkan; 0000-0001-8120-7123; 34262282; AAG-2213-2021
    Purpose: In a lack of similar research, we assessed the prognostic utility of pretreatment platelet-to-albumin ratio (PAR) in locally advanced nasopharyngeal carcinoma (LANPC) patients managed with concurrent chemoradiotherapy (CCRT). Patients and Methods: Present retrospective analysis included a sum of 128 consecutively treated LANPC patients who underwent cisplatinum-based radical CCRT. Availability of an ideal pretreatment PAR cutoff that may stratify the study population into two cohorts with significantly distinct survival outcomes was sought by utilizing the receiver operating characteristic (ROC) curve analysis. The primary and secondary endpoints were overall survival (OS) and progression-free survival (PFS), respectively. Results: A rounded 5.2 [area under the curve (AUC): 68.9%; sensitivity: 67.4%; and specificity: 65.2%] value was identified as the ideal PAR cutoff that grouped patients into two gatherings [PAR >= 5.2 (N=60) versus <5.2 (N=68)]. The median follow-up duration was 86.4 months (range: 9-147). Kaplan-Meier comparisons between the two PAR groups revealed significantly diminished median PFS (69.4 versus 106.8 months for PAR<5.2; P<0.012) and OS (88.3 versus not reached yet for PAR<5.2; P=0.023) for the PAR >= 5.2 group. The results of multivariate analyses affirmed the pretreatment PAR >= 5.2 as an independent prognostic factor that indicates diminished PFS (P=0.016) and OS (P=0.019) together with the respective N2-3 nodal stage (versus N0-1; P<0.05 for PFS and OS, respectively) and weight loss >5% at past six months (<= 5%; P<0.05 for PFS and OS, respectively). Conclusion: The results of the current retrospective analysis provided a robust and independent adverse prognostic value for pretreatment PAR >= 5.2 in terms of median and long-term PFS and OS outcomes in LA-NPC patients this patient group treated with conclusive CCRT.
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    The Prognostic Significance of Novel Pancreas Cancer Prognostic Index in Unresectable Locally Advanced Pancreas Cancers Treated with Definitive Concurrent Chemoradiotherapy
    (2021) Topkan, Erkan; Selek, Ugur; Pehlivan, Berrin; Kucuk, Ahmet; Haksoyler, Veysel; Durankus, Nulifer Kilic; Sezen, Duygu; Bolukbasi, Yasemin; 0000-0001-8087-3140; 0000-0001-8120-7123; 0000-0002-4505-2280; 34511977; O-5474-2014; AAG-2213-2021
    Purpose: We evaluated the prognostic quality of the novel pancreas cancer prognostic index (PCPI), a combination of CA 19-9 and systemic inflammation response index (SIRI), on the outcomes of locally advanced pancreas adenocarcinoma (LAPAC) patients who received concurrent chemoradiotherapy (C-CRT). Methods: This retrospective analysis covered 152 unresectable LAPAC patients treated from 2007 to 2019. Receiver operating characteristic (ROC) curve analysis was used to define ideal cutoff thresholds for the pretreatment CA 19-9 and SIRI measurements, indivi-dually. The associations between the PCPI groups and progression -free-(PFS) and overall survival (OS) comprised the respective primary and secondary endpoints. Results: The ROC curve analysis distinguished the respective rounded optimal cutoffs at 91 U/m/ L (< versus >= 90) and 1.8 (< versus >= 1.8) for CA 19-9 and SIRI, arranging the study cohort into two significantly different survival groups for each, with resultant four likely groups: Group-1: CA 19-9<90 U/m/L and SIRI<1.8, Group-2: CA 19-9<90 U/m/L but SIRI >= 1.8, Group-3: CA 19-9 >= 90 U/ m/L but SIRI<1.8, and Group-4: CA 19-9 >= 90 U/m/L and SIRI >= 1.8. Since the PFS (P=0.79) and OS (P=0.86) estimates of the groups 2 and 3 were statistically indistinct, we merged them as one group and created the novel three-tiered PCPI: PCPI-1: CA 19-9<90 U/m/L and SIRI<1.8, PCPI-2: CA 19-9<90 U/m/L but SIRI >= 1.8 or CA 19-9 >= 90 U/m/L but SIRI<1.8, and PCPI-3: CA 19-9 >= 90 U/m/L and SIRI >= 1.8, respectively. Comparative analyses unveiled that the PCPI-1 and PCPI-3 groups had the respective best and worst PFS (17.0 versus 7.5 versus 4.4 months; P<0.001) and OS (26.1 versus 15.1 versus 7.4 months; P<0.001) outcomes, while the PCPI-2 group posed in between. The multivariate analysis outcomes confirmed the novel three tired PCPI's independent prognostic significance on either of the PFS [HR: 5.38 (95% confidence interval (CI): 4.96-5.80); P<0.001)] and OS [HR: 5.67 (95% CI: 5.19-6.15); P<0.001] endpoints, separately. Conclusion: The new PCPI introduced here can be used as an independent and reliable prog-nostic indicator to divide LAPAC patients into three subgroups with discrete survival results.
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    Novel Clinically Weight-Optimized Dynamic Conformal Arcs (WO-DC A) for Liver SBRT: A Comparison with Volumetric Modulated Arc Therapy (VMAT)
    (2021) Topkan, Erkan; 0000-0001-8120-7123; 34611405; AAG-2213-2021
    Purpose: To evaluate the feasibility of shortening the duration of liver stereotactic radiotherapy (SBRT) without jeopardizing dosimetry or conformity by utilizing weight-optimized dynamic conformal arcs (WO-DCA) as opposed to volumetric modulated arc therapy (VMAT) for tumors away from critical structures. Methods: Nineteen patients with liver metastasis were included, previously treated with 50 Gy in 4 fractions with VMAT technique using two partial coplanar arcs of 6 MV beams delivered in high-definition multi-leaf collimator (HD-MLC). Two coplanar partial WODCA were generated on Pinnacle treatment planning system (TPS) for each patient; and MLC aperture around the planning target volume (PTV) was automatically generated at different margins for both arcs and maintained dynamically around the target during arc rotation. Weight of the two arcs using optimization method was adjusted between the arcs to maximize tumor coverage and protect organs at risk (OAR) based on the RTOG-0438 protocol. Results: The WO-DCA plans successfully "agreed" with the standard VMAT for OAR (liver, spinal cord, stomach, duodenum, small bowel, and heart) and PTV (D-mean, D-98%, D-2%, CI, and GI), with superior mean quality assurance (QA) pass rate (97.06 vs 93.00 for VMAT; P < 0.001 and t = 8.87). Similarly, the WO-DCA technique additionally reduced the beam-on time (3.26 vs 4.43; P < 0.001) and monitor unit (1860 vs 2705 for VMAT; P < 0.001) values significantly. Conclusion: The WO-DCA plans might minimize small-field dosimetry errors and defeat patient-specific VMAT QA requirements due to the omission of MLC beam modulation through the target volume. The WO-DCA plans may additionally enable faster treatment delivery times and lower OAR without sacrificing target doses in SBRT of liver tumors away from critical structures.