Publications by authors named "Ozan C Guler"

17 Publications

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Stereotactic body radiotherapy for oligoprogressive lesions in metastatic castration-resistant prostate cancer patients during abiraterone/enzalutamide treatment.

Prostate 2021 Jun 27;81(9):543-552. Epub 2021 Apr 27.

Department of Radiation Oncology, Faculty of Medicine, Hacettepe University, Ankara, Turkey.

Background: Metastasis-directed therapy (MDT) utilizing stereotactic body radiotherapy (SBRT) for oligoprogressive lesions could provide a delay in next-line systemic treatment (NEST) change while undergoing androgen receptor-targeted agents (ARTA) treatment. We evaluated prognostic factors for prostate cancer-specific survival (PCSS) and progression-free survival (PFS) to characterize patients receiving treatment with ARTA who may benefit from MDT for oligoprogressive lesions. The impact of MDT on delaying NEST and the predictive factors for NEST-free survival (NEST-FS) were also assessed.

Materials And Methods: The clinical data of 54 metastatic castration-resistant prostate cancer patients with 126 oligoprogressive lesions receiving abiraterone (1 g/day) or enzalutamide (160 mg/day) before or after systemic chemotherapy were analyzed. A median of three lesions (range: 1-5) were treated with MDT. The primary endpoints were PCSS and PFS. The secondary endpoints were time to switch to NEST and NEST-FS.

Results: The median follow-up time was 19.1 months. Univariate analysis showed that the number of oligoprogressive lesions treated with SBRT and the time between the start of ARTA treatment and oligoprogression were significant prognostic factors for PCSS, and the timing of ARTA treatment (before or after chemotherapy) and the prostate-specific antigen (PSA) response after MDT were significant prognostic factors for PFS. Multivariate analysis showed that early MDT for oligoprogressive lesions delivered less than 6 months after the beginning of ARTA and higher PSA levels after MDT were significant predictors of worse PCSS and PFS. The median total duration of ARTA treatment was 13.8 months. The median time between the start of ARTA treatment and the start of MDT for oligoprogressive lesions was 5.2 months, and MDT extended the ARTA treatment by 8.6 months on average. Thirty-two (59.3%) patients continued ARTA treatment after MDT. ARTA treatment after chemotherapy, early oligoprogression requiring MDT, and lower radiation doses for MDT were independent predictors of NEST-FS in multivariate analysis.

Conclusions: MDT for oligoprogressive lesions is effective and may provide several benefits compared to switching from ARTA treatment to NEST. Patients with early progression while on ARTAs and inadequate PSA responses after MDT have a greater risk of rapid disease progression and poor survival, which necessitates intensified treatment.
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http://dx.doi.org/10.1002/pros.24132DOI Listing
June 2021

Retrospective correlation of ga-psma uptake with clinical parameters in prostate cancer patients undergoing definitive radiotherapy.

Ann Nucl Med 2020 Jun 27;34(6):388-396. Epub 2020 Mar 27.

Faculty of Medicine, Department of Nuclear Medicine, Adana Dr Turgut Noyan Research and Treatment Center, Başkent University, Adana, Turkey.

Objective: The aim of the study is to investigate the correlation between the intensity of prostate-specific membrane antigen (PSMA) uptake in primary tumor and clinico-pathological characteristics of non-metastatic prostate cancer patients treated with definitive radiotherapy (RT).

Methods: Using the clinical data of 201 prostate cancer patients who were referred for  Ga-PSMA-positron emission tomography (PET/CT) for staging and RT planning, we analyzed the correlations among intermediate- or high-risk disease based on Gleason score (GS), prostate-specific antigen (PSA) level, D'Amico risk group classification, and maximum standardized uptake (SUV) of primary tumor.

Results: Primary tumor was visualized via  Ga-PSMA-PET/CT scan in 192 patients (95.5%). The median SUV of primary tumor and metastatic lymph node were 13.2 (range 3.3-83.7) and 11.4 (range 3.6-64.5), respectively. A significant moderate correlation was observed between PSA level and median tumor SUV as measured by  Ga-PSMA-PET/CT (Spearman = 0.425; p < 0.001). Patients with serum PSA > 10 ng/mL, GS > 7, D'Amico high-risk group classification, and pelvic lymph node metastasis had significantly higher tracer uptake in primary tumor than their counterparts. The median SUV of primary tumor was highest in patients with GS 9. The primary tumor detection rates of  Ga-PSMA-PET/CT were 83%, 92%, and 99% for patients with serum PSA ≤ 5.0 ng/mL (14 patients, 7%), PSA 5.1-10.0 ng/mL (45 patients, 22%), and PSA > 10 ng/mL (142 patients, 71%), respectively.

Conclusions: We demonstrated a correlation between prostate tumor characteristics and PSMA tracer uptake. Patients with serum PSA > 10 ng/mL, GS > 7, D'Amico high-risk group classification, and pelvic lymph node metastasis had significantly higher SUV than their counterparts. In addition, the primary tumor detection rate was higher in patients with serum PSA > 10 ng/mL and GS > 7.
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http://dx.doi.org/10.1007/s12149-020-01462-xDOI Listing
June 2020

Dosimetric Comparison of Sequential Simultaneous-integrated Boost in Early-stage Breast Cancer Patients Treated With Breast-conserving Surgery.

In Vivo 2019 Nov-Dec;33(6):2181-2189

Department of Radiation Oncology, Baskent University Faculty of Medicine, Adana, Turkey.

Background/aim: To compare simultaneous-integrated boost (SIB) versus sequential-boost (SB) delivered in the context of whole-breast irradiation (WBI) via volumetric-modulated arc therapy (VMAT) and helical-tomotherapy (HT).

Materials And Methods: Planning target-volume (PTV) dosimetric parameters and organs at risk (OAR) were analyzed for SB plan (50 Gy plus 16 Gy boost) and SIB plan (50.4 Gy WBI and 64.4 Gy tumor bed boost) in VMAT and HT techniques.

Results: Conformity and homogeneity for target-volume doses were better in HT plans compared to VMAT plans. There were no significant differences in ipsilateral lung doses between VMAT and HT plans for SB/SIB techniques, except for a significantly higher lung V5 value with VMAT-SB, and lung V13 value with HT-SIB technique. HT provided a statistically significant decrease in contralateral lung mean V5.

Conclusion: The SIB technique showed better target-volume dose distribution in both HT and VMAT plans, and better sparing heart in HT compared to the SB technique.
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http://dx.doi.org/10.21873/invivo.11720DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6899153PMC
March 2020

Risk Factors for Fatal Pulmonary Hemorrhage following Concurrent Chemoradiotherapy in Stage 3B/C Squamous-Cell Lung Carcinoma Patients.

J Oncol 2018 1;2018:4518935. Epub 2018 Nov 1.

Bahcesehir University Medical Faculty, Department of Radiation Oncology, Istanbul, Turkey.

We aimed to identify the fatal pulmonary hemorrhage- (FPH-) related risk factors in stage 3B/C squamous-cell lung carcinoma (SqCLC) patients treated with definitive concurrent chemoradiotherapy (C-CRT). Medical records of 505 stage 3B/C SqCLC patients who underwent 66 Gy radiotherapy plus 1-3 cycles of concurrent chemotherapy with available pretreatment thoracic computerized tomography scans were retrospectively analyzed. Primary end-point was the identification of FPH-related risk factors. Examined factors included the basal patient and tumor characteristics with specific emphasis on the tumor cavitation (TC) status, tumor size (TS) and cavitation size (CS), tumor volume and cavitation volume (TV and CV), relative cavitation size (RCS = CS/TS), and relative cavitation volume (RCV=CV/TV). FPH emerged in 13 (2.6%) patients, with 12 (92.3%) of them being diagnosed ≤12 months of C-CRT. All FPHs were diagnosed in patients with TC (N=60): group-specific FPH incidence: 21.6%. TC (P<0.001) was the unique independent factor associated with higher FPH risk in multivariate analysis. Further analysis limited to TC patients exhibited the RCV>0.14 (37.5% versus 11.1% for RCV≤0.14; P<0.001), major RCS group [31.0% versus 19.0% for minor versus 0% for minimum RCS; P=0.008), and baseline hemoptysis (26.3% versus 13.6% for no hemoptysis; P=0.009) as the independent risk factors for higher FPH incidence. FPH was an infrequent (2.6%) complication of C-CRT in stage 3B/C SqCLC patients, but its incidence increased to 37.5% in patients presenting with TC and RCV>0.14. Diagnosis of >90% FPHs ≤12 months of C-CRT stresses the importance of close and careful follow-up of high-risk patients after C-CRT for multidisciplinary discussion of possible invasive preventive measures.
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http://dx.doi.org/10.1155/2018/4518935DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6236701PMC
November 2018

Incidence and Impact of Pretreatment Tumor Cavitation on Survival Outcomes of Stage III Squamous Cell Lung Cancer Patients Treated With Radical Concurrent Chemoradiation Therapy.

Int J Radiat Oncol Biol Phys 2018 08 26;101(5):1123-1132. Epub 2018 Apr 26.

Baskent University Medical Faculty, Department of Medical Oncology, Adana, Turkey.

Purpose: To investigate the incidence and influence of tumor cavitation (TC) on survival outcomes of locally advanced squamous cell lung cancer (LA-SqCLC) patients treated with concurrent chemoradiation therapy (C-CRT).

Methods And Materials: Records of 789 stages IIIA/B squamous cell lung cancer (SqCLC) patients treated with C-CRT who received 1 to 3 cycles of platinum-based doublet chemotherapy during 60 to 66 Gy radiation therapy (RT) were analyzed retrospectively. Primary endpoint was the association between overall survival (OS) and pretreatment TC status. Secondary endpoints included locoregional progression-free survival (LRPFS), progression-free survival (PFS), and incidence of TC and correlated factors.

Results: Pretreatment TC occurred in 95 patients (12%), being significantly more common in those patients with ever-smoking history (12.6% vs 3.9%; P < .001), weight loss >5% (20.9% vs 7.1%; P < .001), and hemoptysis (27.1% vs 6.4%; P < .001). Rates of acute and late toxicities were similar in patients who presented with and without TC (P > .05 for each). For the whole cohort, at a median follow-up of 22.9 months (range: 2.4-71.1), the respective median OS, LRPFS, and PFS estimates were 23.7, 14.7, and 10.7 months. In multivariate analysis, stage IIIB disease (P < .001; hazard ratio [HR]: 1.33; 95% CI: 1.21-1.45), weight loss >5% (P < .001; HR: 2.10; 95% CI: 1.85-2.35), anemia (P < .001; HR: 1.82; 95% CI: 1.67-1.97), and presence of TC (P < .001; HR: 1.54; 95% CI: 1.37-1.71) appeared to be independently associated with poorer OS durations, likewise the LRPFS (P < .001 for each of these covariates), and PFS (P < .001 for each of these covariates), respectively.

Conclusions: Present results showed that the TC occurred in 12% of LA-SqCLC patients, which was strongly associated with poorer PFS, LRPFS, and OS outcomes after definitive C-CRT.
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http://dx.doi.org/10.1016/j.ijrobp.2018.04.053DOI Listing
August 2018

Chemoradiotherapy-induced hemoglobin nadir values and survival in patients with stage III non-small cell lung cancer.

Lung Cancer 2018 07 21;121:30-36. Epub 2018 Apr 21.

Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Purpose: We investigated the influence of change in hemoglobin (Hgb) levels during concurrent chemoradiotherapy (C-CRT) on outcomes of non-anemic patients with stage IIIA/B non-small cell lung cancer (NSCLC).

Methods: We identified 722 patients with stage IIIA/B NSCLC without anemia at baseline [hemoglobin (Hgb) <12 g/dL for women or <13 g/dL for men], either nonsmokers or ex-smokers, who received C-CRT between 2007 and 2012. All patients had received 1-3 cycles of platinum-based doublet chemotherapy during radiotherapy to 60-66 Gy and had documented Hgb measurements before treatment and at weekly intervals for 6 weeks during the C-CRT. Potential associations were assessed between baseline, nadir, extent of change in Hgb level, and anemia and overall survival (OS), locoregional progression-free survival (LRPFS), and PFS.

Results: The median baseline Hgb level was 13.9 g/dL (range 12.0-16.8) and declined to a median 12.4 g/dL (range 7.9-16.1) during treatment. Anemia appeared in 237 patients (32.8%) and was more common among women (44.8% vs. 26.5%, P < 0.001). Neither baseline Hgb level nor change during treatment nor anemia emergence influenced any survival endpoint. Receiver operating curve analysis revealed an Hgb nadir of 11.1 g/dL to be associated with outcomes, in that a nadir Hgb <11.1 g/dL (in 156 patients) was linked with shorter median OS time (P < 0.001), LRPFS time (P < 0.001), and PFS time (P < 0.001); retained significance for all three endpoints in multivariate analyses; and was more strongly associated with OS in squamous cell carcinoma (P < 0.001) than in adenocarcinoma (P = 0.009).

Conclusion: Nadir Hgb <11.1 g/dL levels during C-CRT were associated with significantly poorer survival times in initially non-anemic patients presenting with locally advanced NSCLC.
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http://dx.doi.org/10.1016/j.lungcan.2018.04.016DOI Listing
July 2018

Prognostic value of the Glasgow Prognostic Score for glioblastoma multiforme patients treated with radiotherapy and temozolomide.

J Neurooncol 2018 Sep 25;139(2):411-419. Epub 2018 Apr 25.

Department of Neurosurgery, Baskent University Medical Faculty, Adana, Turkey.

Introduction: To evaluate the prognostic value of the Glasgow Prognostic Score (GPS), the combination of C-reactive protein (CRP) and albumin, in glioblastoma multiforme (GBM) patients treated with radiotherapy (RT) and concurrent plus adjuvant temozolomide (GPS).

Methods: Data of newly diagnosed GBM patients treated with partial brain RT and concurrent and adjuvant TMZ were retrospectively analyzed. The patients were grouped into three according to the GPS criteria: GPS-0: CRP < 10 mg/L and albumin > 35 g/L; GPS-1: CRP < 10 mg/L and albumin < 35 g/L or CRP > 10 mg/L and albumin > 35 g/L; and GPS-2: CRP > 10 mg/L and albumin < 35 g/L. Primary end-point was the association between the GPS groups and the overall survival (OS) outcomes.

Results: A total of 142 patients were analyzed (median age: 58 years, 66.2% male). There were 64 (45.1%), 40 (28.2%), and 38 (26.7%) patients in GPS-0, GPS-1, and GPS-2 groups, respectively. At median 15.7 months follow-up, the respective median and 5-year OS rates for the whole cohort were 16.2 months (95% CI 12.7-19.7) and 9.5%. In multivariate analyses GPS grouping emerged independently associated with the median OS (P < 0.001) in addition to the extent of surgery (P = 0.032), Karnofsky performance status (P = 0.009), and the Radiation Therapy Oncology Group recursive partitioning analysis (RTOG RPA) classification (P < 0.001). The GPS grouping and the RTOG RPA classification were found to be strongly correlated in prognostic stratification of GBM patients (correlation coefficient: 0.42; P < 0.001).

Conclusions: The GPS appeared to be useful in prognostic stratification of GBM patients into three groups with significantly different survival durations resembling the RTOG RPA classification.
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http://dx.doi.org/10.1007/s11060-018-2879-4DOI Listing
September 2018

Prognostic value of metabolic tumor volume and total lesion glycolysis in esophageal carcinoma patients treated with definitive chemoradiotherapy.

Nucl Med Commun 2018 Jun;39(6):553-563

Departments of Radiation Oncology.

Purpose: The aim of this study was to evaluate the prognostic importance metabolic tumor volume (MTV), total lesion glycolysis (TLG), and standardized uptake value (SUV) in patients with esophageal cancer treated with definitive chemoradiotherapy.

Patients And Methods: Seventy-two esophageal cancer patients treated with definitive chemoradiotherapy [57 (79%) patients] or definitive radiotherapy [15 (21%) patients] were retrospectively analyzed. The regions equal to or greater than SUV of 2.5 were selected to delineate MTV and TLG was calculated by multiplying the mean SUV by the MTV of the primary lesions. The overall survival (OS) and disease-free survival (DFS) were evaluated for all patients and also patients with squamous cell carcinoma.

Results: The median survival time was 13.4 months (range: 1.8-119.3 months) for all patients. Maximum SUV, mean SUV, MTV, and TLG values were significantly higher in patients with extensive T-stage (T3-T4) compared with patients with T1-T2 disease. Patients with regional lymph node metastasis had significantly higher MTV and TLG values compared with patients with no lymph node metastasis. On multivariate analysis, MTV, TLG, presence of lymph node metastasis, and lack of concurrent chemotherapy were negative significant prognostic factors for OS and DFS for the entire cohort and for patients with squamous cell carcinoma esophageal cancer.

Conclusion: Metabolic volumes (MTV and TLG), regional lymph node metastasis, and concurrent chemotherapy are major prognostic factors for DFS and OS in patients with esophageal carcinoma. In addition, MTV and TLG are important in predicting nodal metastasis, and together with metabolic volumes, SUV are associated significantly with local tumor invasion.
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http://dx.doi.org/10.1097/MNM.0000000000000837DOI Listing
June 2018

Adjuvant Small Pelvic Radiotherapy in Patients with Cervical Cancer Having Intermediate Risk Factors Only - Is It Sufficient?

Oncol Res Treat 2017 21;40(9):523-527. Epub 2017 Aug 21.

Background: We sought to determine the outcomes of adjuvant small pelvic external beam radiotherapy (EBRT) and prognostic factors for survival and disease control.

Patients And Methods: We retrospectively evaluated 113 cervical cancer patients treated with postoperative median 50.4-Gy small pelvic EBRT. We treated the surgical bed, bilateral parametria, paravaginal soft tissues, upper third of the vagina, and presacral lymphatics.

Results: Median follow-up of all patients and survivors was 58 and 67 months, respectively. The 2- and 5-year overall survival (OS) and disease-free survival rates were 91 and 82%, and 85 and 74%, respectively. The locoregional failure rate was 10%. Age was a significant predictor for OS and distant metastasis-free survival (DMFS) on univariate analysis. The number of dissected lymph nodes being < 30 negatively affected the pelvic recurrence-free survival. The only independent predictor on multivariate analysis was older age for DMFS. Although no severe acute toxicity was observed, late grade ≥ 3 toxicity developed in 8 patients.

Conclusion: Small pelvic EBRT produces satisfactory survival and locoregional control with acceptable toxicity, and can be an alternative to whole pelvic EBRT in selected cervical cancer patients.
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http://dx.doi.org/10.1159/000476037DOI Listing
September 2018

The role of delineation education programs for improving interobserver variability in target volume delineation in gastric cancer.

Br J Radiol 2017 May 24;90(1073):20160826. Epub 2017 Mar 24.

3 Department of Radiation Oncology, Faculty of Medicine, Ege University, Izmir, Turkey.

Objective: To assess whether delineation courses for radiation oncologists improve interobserver variability in target volume delineation for post-operative gastric cancer radiotherapy planning.

Methods: 29 radiation oncologists delineated target volumes in a gastric cancer patient. An experienced radiation oncologist lectured about delineation based on contouring atlas and delineation recommendations. After the course, the radiation oncologists, blinded to the previous delineation, provided delineation for the same patient.

Results: The difference between delineated volumes and reference volumes for pre- and post-course clinical target volume (CTV) were 19.8% (-42.4 to 70.6%) and 12.3% (-12.0 to 27.3%) (p = 0.26), respectively. The planning target volume (PTV) differences pre- and post-course according to the reference volume were 20.5% (-40.7 to 93.7%) and 13.1% (-10.6 to 29.5%) (p = 0.30), respectively. The concordance volumes between the pre- and post-course CTVs and PTVs were 467.1 ± 89.2 vs 597.7 ± 54.6 cm (p < 0.001) and 738.6 ± 135.1 vs 893.2 ± 144.6 cm (p < 0.001), respectively. Minimum and maximum observer variations were seen at the cranial part and splenic hilus and at the caudal part of the CTV. The kappa indices compared with the reference contouring at pre- and post-course delineations were 0.68 and 0.82, respectively.

Conclusion: The delineation course improved interobserver variability for gastric cancer. However, impact of target volume changes on toxicity and local control should be evaluated for further studies. Advances in knowledge: This study demonstrated that a delineation course based on current recommendations helped physicians delineate smaller and more homogeneous target volumes. Better target volume delineation allows proper target volume irradiation and preventing unnecessary normal tissue irradiation.
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http://dx.doi.org/10.1259/bjr.20160826DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5605107PMC
May 2017

Prognostic value of metabolic response measured by 18F-FDG-PET in oesophageal cancer patients treated with definitive chemoradiotherapy.

Nucl Med Commun 2016 Dec;37(12):1282-1289

Departments of aRadiation Oncology bNuclear Medicine, Faculty of Medicine, Baskent University, Ankara, Turkey.

Background: This study aimed to assess the efficacy of fluorine-18 fluorodeoxyglucose (F-FDG)-PET for predicting overall survival (OS) and disease-free survival (DFS) in oesophageal cancer patients after definitive chemoradiotherapy (CRT) and prognostic importance of metabolic response detected by post-treatment PET at least 3 months after completing CRT.

Materials And Methods: Data from 58 oesophageal cancer patients receiving definitive CRT were retrospectively analysed. Post-treatment F-FDG-PET was delivered at a median of 3.2 (range, 3.0-6.4) months after CRT. The impact of metabolic response determined by post-treatment F-FDG-PET, maximum post-treatment standardized uptake value (SUVmax) and percent SUV change (pretreatment to post-treatment) on survival was analysed.

Results: The median follow-up was 19.7 (range, 4.2-91.9) months for all patients and 28.2 (range, 13.7-91.9) months for survivors. The mean pretreatment and post-treatment SUVmax and the median percent SUV decrease were 18.6±6.4, 6.2±4.6 and -73% (+13 to -100%). Pretreatment SUVmax was higher in patients with locoregional or distant failure than in those without (P<0.001). Pretreatment SUVmax was lower in patients with a complete response (CR) than in those without a CR (P=0.006). Two-year OS and DFS were higher in patients with CR compared with those without CR (P<0.001). CR rates detected by post-treatment F-FDG-PET were lower in patients with lymph node metastases or longer tumours than in those with shorter tumours or no metastases. During multivariate analysis, post-treatment SUVmax was a significant predictor for OS, and post-treatment SUVmax, percent SUV decrease and tumour length were significant prognostic factors for DFS.

Conclusion: Metabolic response assessed by post-treatment F-FDG-PET at least 3 months after CRT showed that post-treatment SUVmax and percent SUV change were important survival predictors.
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http://dx.doi.org/10.1097/MNM.0000000000000594DOI Listing
December 2016

Predicting tumor recurrence in patients with cervical carcinoma treated with definitive chemoradiotherapy: value of quantitative histogram analysis on diffusion-weighted MR images.

Acta Radiol 2017 Apr 28;58(4):481-488. Epub 2016 Jul 28.

1 Department of Radiology, Baskent University Faculty of Medicine, Ankara, Turkey.

Background Further research is required for evaluating the use of ADC histogram analysis in more advanced stages of cervical cancer treated with definitive chemoradiotherapy (CRT). Purpose To investigate the utility of apparent diffusion coefficient (ADC) histogram derived from diffusion-weighted magnetic resonance images in cervical cancer patients treated with definitive CRT. Material and Methods The clinical and radiological data of 50 patients with histologically proven cervical squamous cell carcinoma treated with definitive CRT were retrospectively analyzed. The impact of clinicopathological factors and ADC histogram parameters on prognostic factors and treatment outcomes was assessed. Results The mean and median ADC values for the cohort were 1.043 ± 0.135 × 10 mm/s and 1.018 × 10 mm/s (range, 0.787-1.443 × 10 mm/s). The mean ADC was significantly lower for patients with advanced stage (≥IIB) or lymph node metastasis compared with patients with stage
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http://dx.doi.org/10.1177/0284185116656492DOI Listing
April 2017

Prognostic Use of Pretreatment Hematologic Parameters in Patients Receiving Definitive Chemoradiotherapy for Cervical Cancer.

Int J Gynecol Cancer 2016 07;26(6):1169-75

Department of Radiation Oncology, Faculty of Medicine, Baskent University, Adana, Turkey.

Objectives: The aim of this work was to evaluate the prognostic role of pretreatment neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in recipients of definitive chemoradiotherapy (ChRT) for cervical cancer.

Methods: In 235 patients given definitive ChRT for histologically confirmed cervical cancer, clinical data and pretreatment complete blood cell counts were analyzed. Prognostic and therapeutic ramifications of NLR and PLR were assessed.

Results: Median pretreatment NLR and PLR were 3.03 (range, 1.04-13.03) and 133.02 (range, 36.3-518.16), respectively. Both NLR and PLR correlated significantly with tumor size, lymph node metastasis, and treatment response. In addition to NLR and PLR, tumor stage, size, and nodal metastasis were identified by univariate analysis as significant predictors of overall survival (OS) and progression-free survival (PFS). By multivariate analysis, independent predictors of OS and PFS were NLR (OS: hazard ratio [HR], 3.322; 95% confidence interval [CI], 1.905-5.790; PFS: HR, 3.579; 95% CI, 2.106-6.082; both P < 0.001) and lymph node metastasis (OS: HR, 2.620; 95% CI, 1.706-4.023; PFS: HR, 2.989; 95% CI, 1.918-4.378; both P < 0.001), although patients' age (HR, 1.019; 95% CI, 1.003-1.035; P = 0.02) was also significantly predictive of OS.

Conclusions: Pretreatment NLR and PLR were associated with larger tumors, lymph node metastasis, and poorer therapeutic responses to definitive ChRT. By multivariate analysis, pretreatment NLR and lymph node metastasis were found independently predictive of OS and PFS, whereas patients' age was significantly predictive of OS only. In patients with advanced cervical cancer, NLR is a potential biomarker, serving to guide systemic therapy and predict treatment outcomes.
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http://dx.doi.org/10.1097/IGC.0000000000000741DOI Listing
July 2016

Treatment response evaluation using the mean apparent diffusion coefficient in cervical cancer patients treated with definitive chemoradiotherapy.

J Magn Reson Imaging 2016 10 27;44(4):1010-9. Epub 2016 Feb 27.

Department of Radiation Oncology, Baskent University Faculty of Medicine, Adana, Turkey.

Purpose: To investigate the pre- and posttreatment mean apparent diffusion coefficient (ADCmean ) of cervical cancer tumors treated with definitive chemoradiotherapy (CRT) and evaluate their correlation with recurrence and survival rates.

Materials And Methods: Forty-four patients with cervical squamous cell carcinoma were retrospectively evaluated. All patients underwent multiparametric 1.5T magnetic resonance imaging (MRI) including T2 -weighted, fat-saturated T2 -weighted, dynamic contrast-enhanced (DCE), and diffusion-weighted imaging (DWI) sequences before and after treatment. Posttreatment MR images were acquired within a median of 3.2 months (range, 2.8-4.1 months) after completing CRT. We assessed the impact of primary tumor pre- and posttreatment ADC values on prognostic factors and treatment outcomes.

Results: The pre- and posttreatment ADCmean values were 0.882 ± 0.096 × 10(-3) mm(2) /sec and 1.159 ± 0.168 × 10(-3) mm(2) /sec, respectively, and the difference was statistically significant (P < 0.001). The median percent ADC change was 33.7% (range, 5.0-70.0%). Patients with disease recurrence had lower ADC values, both pretreatment (0.822 ± 0.096 × 10(-3) mm(2) /sec vs. 0.936 ± 0.058 × 10(-3) mm(2) /sec; P < 0.001) and posttreatment (1.060 ± 0.116 × 10(-3) mm(2) /sec vs. 1.248 ± 0.160 × 10(-3) mm(2) /sec; P < 0.001). The ADC change was lower in patients with recurrence (25.7% ± 13.0% vs. 42.8% ± 15.7; P < 0.001) than in patients without recurrence. In multivariate analysis, pelvic lymph node metastasis and pretreatment ADCmean were prognostic factors for overall survival (OS) and disease-free survival (DFS). ADC change between pre- and posttreatment DW-MRI was a prognostic factor for OS.

Conclusion: DWI parameters, measured before and after treatment, may be useful prognostic biomarkers for tumor burden, recurrence, and survival in cervical cancer patients treated with CRT. The primary tumor pretreatment ADCmean is an independent prognostic factor for DFS and OS. J. MAGN. RESON. IMAGING 2016;44:1010-1019.
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http://dx.doi.org/10.1002/jmri.25215DOI Listing
October 2016

Effects of bladder distension on dose distribution of vaginal vault brachytherapy in patients with endometrial cancer.

J Contemp Brachytherapy 2015 Jan 31;6(4):371-6. Epub 2014 Dec 31.

Department of Radiation Oncology, Baskent University Faculty of Medicine, Adana, Turkey.

Purpose: To investigate dosimetric effects of bladder distention on organs at risk (OARs) during treatment of endometrial cancer using 3D image-based planning of postoperative vaginal vault brachytherapy (BRT).

Material And Methods: Fifteen patients with early-stage endometrial cancer were studied, each undergoing adjuvant BRT of vaginal vault via 3.5 cm diameter cylinder. As treatment, 25 Gy in 5 fractions were delivered to 5 mm depth of the vaginal mucosa. Dose-volume histograms of OARs were generated individually with bladder empty and with bladder inflated by sterile saline (180 ml), to compare doses received.

Results: Bladder distention appreciably impacted dosimetry of bladder, sigmoid colon, and small bowel, but dosimetry of rectum was unaffected. With bladder inflated, mean cylinder-to-bowel distance increased significantly (1.69 cm vs. 1.20 cm; p = 0.006). Mean minimum dose to most exposed 2 cc (D2cc) volume also rose significantly at bladder (5.40 Gy vs. 4.55 Gy [18.7%]; p < 0.001), as opposed to near-significant reductions in D2cc at sigmoid colon (15.1%; p = 0.11) and at small bowel (10.5%; p = 0.14). A full bladder had no effect on dose to 50% volume (D50%) of bladder or rectum, and declines seen in mean D50% values of sigmoid colon (22.7%; p = 0.12) and small bowel (19.0%; p = 0.13) again fell short of statistical significance.

Conclusions: The combination of a full bladder and an empty rectum may cause significant unwanted increases in BRT dosing of bladder, without significantly impacting sigmoid colon and small bowel exposures. These findings should be validated through further clinical studies.
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http://dx.doi.org/10.5114/jcb.2014.47868DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4300363PMC
January 2015

Prognostic value of 18F-fluorodeoxyglucose uptake in pelvic lymph nodes in patients with cervical cancer treated with definitive chemoradiotherapy.

Gynecol Oncol 2015 Apr 29;137(1):40-6. Epub 2015 Jan 29.

Department of Nuclear Medicine, Baskent University Faculty of Medicine, Ankara, Turkey.

Purpose: To evaluate the prognostic significance of the maximum standardized uptake (SUVmax) value for pelvic lymph nodes in patients with cervical cancer and its impact on treatment response, disease control, and survival.

Methods: Ninety-three patients with pelvic or para-aortic metastasis detected by PET/CT and treated with definitive chemoradiotherapy were evaluated. The impact of pelvic lymph node SUVmax on prognostic factors and treatment outcomes was assessed.

Results: The size and SUVmax of pelvic lymph nodes were significantly correlated (r=0.859; p<0.001). Patients with pelvic and para-aortic lymph node metastases had significantly higher SUVmax values for both primary tumor (23.4±9.2 vs. 18.5±7.3; p=0.01) and pelvic lymph nodes (11.4±4.6 vs. 7.4±3.8; p=0.001). Patients with pelvic lymph node SUVmax≥7.5 had significantly higher primary tumor SUVmax, larger pelvic lymph nodes, higher rates of para-aortic lymph node metastasis, and lower post-therapy complete response rates. Overall survival (OS) and disease-free survival (DFS) rates were significantly higher in patients with SUVmax<7.5 compared to patients with SUVmax≥7.5. In a multivariate analysis, pelvic lymph node SUVmax and post-therapy metabolic response were significant prognostic factors for both OS and DFS for all patients, but no significant prognostic factors were found in pelvic lymph node metastasis only.

Conclusions: Patients with highly FDG-avid pelvic lymph nodes have a higher risk of disease recurrence with worse survival. Identification of these patients may assist in the evaluation of the clinical benefits of additional treatments.
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http://dx.doi.org/10.1016/j.ygyno.2015.01.542DOI Listing
April 2015

Treatment outcomes of patients with cervical cancer with complete metabolic responses after definitive chemoradiotherapy.

Eur J Nucl Med Mol Imaging 2014 Jul 22;41(7):1336-42. Epub 2014 Feb 22.

Department of Radiation Oncology, Baskent University Faculty of Medicine, Adana, Turkey,

Purpose: We sought to evaluate failure patterns and prognostic factors predictive of recurrences and survival in cervical cancer patients who are treated with definitive chemoradiotherapy (ChRT), who have a subsequent complete metabolic response (CMR) with (18) F-fluorodeoxyglucose positron-emission tomography (FDG-PET) after treatment.

Methods: The records of 152 cervical cancer patients who were treated with definitive chemoradiotherapy were evaluated. All patients underwent pre-treatment positron emission tomography (PET-CT), and post-treatment PET-CT was performed within a median of 3.9 months (range, 3.0-9.8 months) after the completion of ChRT. The prognoses of partial response/progressive disease (PR/PD) cases (30 patients, 18 %) and CMR cases (122 patients, %82) were evaluated. Univariate and multivariate analysis effecting the treatment outcome was performed in CMR cases.

Results: The median follow-ups for all patients and surviving patients were 28.7 (range, 3.3-78.7 months) and 33.2 months (range, 6.23-78.7 months), respectively. Four-year overall survival (OS) rate was significantly better in patients with CMR compared to patients with PR/PD (66.9 % vs. 12.4 %, p < 0.001, respectively). Patients with PR/PD had higher maximum standardized uptake value (SUVmax) of primary cervical tumor (26.4 ± 10.1 vs. 15.9 ± 6.3; p < 0.001) and larger tumor (6.4 cm ± 2.3 cm vs. 5.0 cm ± 1.4 cm; p < 0.001) compared to patients with CMR. Of the 122 patients with post-treatment CMRs, 25 (21 %) developed local, locoregional, or distant failure. In univariate analysis, tumor size ≥ 5 cm, 'International Federation of Obstetricians and Gynecologists' (FIGO) stage ≥ IIB, and pelvic and/or para-aortic lymph node metastasis were predictive of both overall survival (OS) and disease-free survival (DFS), while histology was predictive of only OS. In multivariate analysis, tumor size, stage and lymph node metastasis were predictive of OS and DFS.

Conclusion: Although CMR is associated with better outcomes, relapses remain problematic, especially in patients with bulky tumors (≥ 5 cm), extensive stage (≥ IIB) or pelvic and/or para-aortic lymph node metastasis. These findings could support the need for more aggressive treatment or adjuvant chemotherapy regimens.
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http://dx.doi.org/10.1007/s00259-014-2719-5DOI Listing
July 2014