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    Initial neutrophil-to-lymphocyte ratio predicts radiation-induced trismus in parotid gland cancer
    (2023) Somay, Efsun; Yilmaz, Busra; Topkan, Erkan; Kucuk, Ahmet; Pehlivan, Berrin; Selek, Ugur; 0000-0001-8120-7123; 36349491; AAG-2213-2021
    ObjectiveTo investigate the link between pretreatment neutrophil-to-lymphocyte ratio(NLR) and the incidence of radiation-induced trismus(RIT) in parotid gland cancers(PGC) patients after postoperative radiotherapy(PORT). MethodData of PGC patients who had oral examinations before and after PORT were reviewed retrospectively. We comprised patients who had maximum mouth opening (MMO) assessments before and after PORT and complete blood count test on the first day of PORT. MMO of <= 35 mm was considered as RIT. The receiver operating characteristic (ROC) curve analysis was used to search for an ideal NLR threshold value that might be linked to RIT rates. ResultsFifty-one patients were included, with a RIT incidence of 15.7%. The NLR cutoff that showed a link with the prevalence of RIT in the ROC curve analysis was 2.7[Area under the curve (AUC):82.0%; sensitivity:87.5%; specificity:74.4%]. The patients were divided into groups based on this value:Group 1: NLR <= 2.7 (N = 34) and;NLR >2.7 (N = 17). In comparative analysis, the incidence of RIT was found to be statistically higher in the NLR >2.7 than counterpart (35.2%vs.5.8%;r(s):0.79; p < .001). Also, a mean temporomandibular joint dose >= 51.0Gy was linked to increased RIT rates (p < .001). ConclusionThis study showed that high pre-PORT NLR levels were a robust and independent predictor of significantly elevated rates of RIT.
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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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    Hemoglobin-to-platelet ratio in predicting the incidence of trismus after concurrent chemoradiotherapy
    (2023) Somay, Efsun; Yilmaz, Busra; Topkan, Erkan; Kucuk, Ahmet; Haksoyler, Veysel; Pehlivan, Berrin; Selek, Ugur; Araz, Kenan; 0000-0003-0633-5648; 0000-0001-8120-7123; 36038508; AAG-2213-2021
    Objective The significance of pre-hemoglobin-to-platelet ratio (HPR) in predicting the occurrence of radiation-induced trismus (RIT) in locally advanced nasopharyngeal carcinoma patients (LA-NPC) who received concurrent chemoradiotherapy (C-CRT). Methods The records of LA-NPC patients with oral examination before and after C-CRT were analyzed. Maximum mouth openings (MMO) were measured before and after C-CRT to confirm RIT status, with an MMO of <= 35 mm defined as RIT. HPR values were calculated on the first day of C-CRT. The relationship between the HPR values and RIT status was discovered using the receiver operating characteristic curve analysis. Results A total of 43 patients RIT cases among 198 individuals were diagnosed. The optimal HPR cutoff that stratified the patients into two groups was 0.54. RIT incidence was found to be significantly higher in the HPR <= 0.54 group than its HPR >0.54 counterpart(p < 0.001). Univariately T3-4 stage, mean masticator apparatus dose>57.2Gy, and pre-C-CRT MMO <= 40.7 mm were found as the other significant correlates of increased RIT rates(p < 0.05). All four variables seemed to be independently connected to greater RIT incidence in multivariate analysis (p < 0.05, for each). Conclusion The risk of post-C-CRT RIT may be significantly increased when pre-treatment HPR levels are low.
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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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    Vaginal cuff brachytherapy practice in endometrial cancer patients: a report from the Turkish Oncology Group
    (2021) Bolukbasi, Yasemin; Onal, Cem; Ozsaran, Zeynep; Senyurek, Sukran; Akdemir, Eyub Yasar; Selek, Ugur; Yildiz, Ferah; 33897788
    Purpose: The American Brachytherapy Association is attempting to develop standards for delivering brachytherapy, although differences in practice have been reported in the literature. This study evaluated vaginal cuff brachytherapy (VBT) practice and quality of life-related recommendations among Turkish radiation oncologists. Material and methods: A nationwide web-based 17-item survey was distributed to the members of the Turkish Society for Radiation Oncology. These members received e-mail notifications, and a link was posted on the Turkish Society for Radiation Oncology internet site to solicit voluntary responses The survey addressed the simulation processes, target volume, prescribed dose, delivery schedules, and recommendations related to vaginal side effects. Results: Fifty-seven radiation oncologists responded to the survey. The most used dose fraction schemes for adjuvant VBT were 7 Gy x 3 fractions (30%), 5.5 Gy x 5 fractions (26%), and 6 Gy x 5 fractions (28%). The preferred VBT scheme was 5 Gy x 3 fractions (50%) when the external beam radiotherapy (EBRT) dose was 45 Gy external radiotherapy, while the preferred schemes were 6 Gy x 3 fractions (30%) or 5 Gy x 3 fractions (32%) when the external radiotherapy dose was increased to 50.4 Gy. One-half of the respondents delivered VBT twice a week, and the dose was prescribed to 0.5 cm from vaginal mucosa by 86% of the respondents. There was no common definition for the dose prescription length, which was defined as 3 cm from the vaginal cuff in 33% of responses and as 4 cm in 35% of responses. For serous and clear cell histological types, 38% of the respondents targeted "full cylinder length". To prevent vaginal side effects, 78% of the respondents recommended using a vaginal dilator and/or sexual intercourse after VBT. Conclusions: This survey revealed variations in the clinical practice of VBT among Turkish radiation oncologists, which suggests that standardization is necessary.
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    Oligometastatic Bone Disease in Castration-Sensitive Prostate Cancer Patients Treated With Stereotactic Body Radiotherapy Using Ga-68-PSMA PET/CT TROD 09-004 Study
    (2021) Onal, Cem; Ozyigit, Gokhan; Akgun, Zuleyha; Atalar, Banu; Igdem, Sefik; Oymak, Ezgi; Agaoglu, Fulya; Selek, Ugur; Guler, Ozan Cem; Hurmuz, Pervin; 33661210
    Purpose To evaluate the outcomes of metastasis-directed treatment (MDT) using stereotactic body radiotherapy (SBRT) for bone-only oligometastasis (OM) detected with gallium prostate-specific membrane antigen (Ga-68-PSMA) PET/CT in castration-sensitive prostate cancer (PC) patients. Methods In this multi-institutional study, clinical data of 74 PC patients with 153 bone lesions who were undergoing MDT were retrospectively evaluated. Twenty-seven patients (36.5%) had synchronous, and 47 (63.5%) had metachronous OM. All patients had PC with 5 metastases or fewer detected by Ga-68-PSMA PET/CT and treated using SBRT with a median dose of 20 Gy. The prognostic factors for PC-specific survival (PCSS) and progression-free survival (PFS) were analyzed. Results The median follow-up was 27.3 months. Patients with synchronous OM were older and received higher rates of androgen deprivation therapy after SBRT compared with patients with metachronous OM. The 2-year PCSS and PFS rates were 92.0% and 72.0%, respectively. A prostate-specific antigen (PSA) decline was observed in 56 patients (75.7%), and 48 (64.9%) had a PSA response defined as at least 25% decrease of PSA after MDT. The 2-year local control rate per lesion was 95.4%. In multivariate analysis, single OM and PSA response after MDT were significant predictors for better PCSS and PFS. In-field recurrence was observed in 4 patients (6.5%) with 10 lesions at a median of 13.1 months after MDT completion. No serious late toxicity was observed. Conclusions We demonstrated that SBRT is an efficient and well-tolerated treatment option for PC patients with 5 bone-only oligometastases or fewer detected with Ga-68-PSMA PET/CT.
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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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    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.