Tıp Fakültesi / Faculty of Medicine

Permanent URI for this collectionhttps://hdl.handle.net/11727/1403

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    Uterine Perforation During 3-Dimensional Image-Guided Brachytherapy in Patients With Cervical Cancer Baskent University Experience
    (2014) Onal, Cem; Guler, Ozan Cem; Dolek, Yemliha; Erbay, Gurcan; https://orcid.org/0000-0002-2742-9021; https://orcid.org/0000-0001-6908-3412; https://orcid.org/0000-0002-1706-8680; 24407583; HOC-5611-2023; AAC-5654-2020; AAK-5370-2021
    Objectives This study aimed to determine the incidence and characteristics of uterine perforation at our department using 3-dimensional computed tomography (CT)-based brachytherapy (BRT). The characteristics of the patients presenting with perforation and impact of the perforation on the treatment course were also analyzed. Materials and Methods The clinical and radiologic data of 200 patients with biopsy-proven cervical cancer treated using CT-based BRT were retrospectively evaluated. All patients had undergone tandem-based intracavitary BRT, and 67 patients had undergone magnetic resonance imaging (MRI) before BRT. Results Of the 200 patients, 17 (8.5%) had uterine perforation. Of the 626 applications with CT images, 30 (4.8%) resulted in uterine perforation. The median age of patients with perforation was higher (68 years; range, 44-89 years) than that of the patients without perforation (59 years; range, 21-87 years), and the mean (SD) tumor size at diagnosis was larger in patients with perforation (7.0 [1.5] cm) than in patients without perforation (5.0 [1.5] cm). The most frequent perforation site was the posterior uterine wall (8 patients), followed by the fundus (5 patients) and anterior wall (4 patients). Of the 7 patients with a retroverted uterus, 4 had uterine perforation during BRT. In 67 patients with MRI delivered before BRT, only 3 (4%) had uterine perforation, and 2 of the 3 patients with uterine perforation had a retroverted uterus. However, of the 133 patients with no MRI evaluation before BRT, 14 (11%) had uterine perforation. No life-threatening complications or signs of intraperitoneal tumor cell seeding were observed. Conclusions Older age, larger tumors, a retroverted uterus, and a stenotic cervical os were all predisposing factors for uterine perforation during BRT. Preoperative MRI is a feasible and safe method to decrease the risks of uterine perforation and could be used preoperatively in centers where intraoperative ultrasonography is not used in routine practice.
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    Prognostic Value of 18F-Fluorodeoxyglucose Uptake in Pelvic Lymph Nodes in Patients with Cervical Cancer Treated with Definitive Chemoradiotherapy
    (2015) Onal, Cem; Guler, Ozan C.; Reyhan, Mehmet; Yapar, Ali Fuat; 0000-0001-6908-3412; 0000-0003-1715-4180; 0000-0002-2742-9021; 0000-0001-8550-3368; 25641567; AAC-5654-2020; AAI-8973-2021; D-5195-2014; AAJ-5242-2021; HOC-5611-2023
    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 +/- 73; 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. (C) 2015 Elsevier Inc. All rights reserved.
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    Treatment Outcomes of Patients with Cervical Cancer with Complete Metabolic Responses After Definitive Chemoradiotherapy
    (2014) Onal, Cem; Reyhan, Mehmet; Guler, Ozan C.; Yapar, Ali Fuat; https://orcid.org/0000-0002-2742-9021; https://orcid.org/0000-0001-8550-3368; https://orcid.org/0000-0001-6908-3412; https://orcid.org/0000-0003-1715-4180; 24562649; HOC-5611-2023; AAJ-5242-2021; AAC-5654-2020; AAI-8973-2021
    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 a parts per thousand yen 5 cm, 'International Federation of Obstetricians and Gynecologists' (FIGO) stage a parts per thousand yenaEuro parts per thousand 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 (a parts per thousand yen 5 cm), extensive stage (a parts per thousand yen 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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    Restaging of Cervical Cancer Patients Treated with Adjuvant Radiotherapy According to FIGO 2018 and Suggestions for the Next Staging: Turkish Society for Radiation Oncology Gynecologic Group Study (TROD 04-004)
    (2022) Alanyali, Senem; Balci, Beril; Esen, Caglayan Selenge Beduk; Gultekin, Melis; Yildirim, Berna Akkus; Ozkurt, Selnur; Ergen, Sefika Arzu; Gursel, Sukriye Bilge; Cetin, Ilknur Alsan; Sert, Fatma; Sari, Sezin Yuce; Ibis, Kamuran; Onal, Cem; Sahinler, Ismet; Yildiz, Ferah; Ozsaran, Zeynep
    OBJECTIVE The objective of this study was to compare Federation of Gynecology and Obstetrics (FIGO) 2009 and 2018 staging systems in patients with uterine cervical cancer. METHODS Medical records of 571 patients who were treated with adjuvant radiotherapy or radiochemotherapy between 2001 and 2018 were retrospectively reviewed. Differences in overall survival (OS) and progression-free survival (PFS) rates according to FIGO 2009 and FIGO 2018 staging systems were compared using the log-rank test. Cox regression model was used to identify independent prognostic factors for survival. RESULTS The median follow-up was 59 months. Five-year OS and PFS rates were 81.1% and 77.7%, respectively. Stage migration was recorded in 401 patients (70.2%) and the most remarkable stage migration was detected in stage I patients (60%). A total of 157 (27.5%) patients upstaged to stage IIIC disease. According to FIGO 2009, 5-year OS rates were 87.3%, 80.5% (p=0.076), and PFS rates were 82.8%, 77.5% (p=0.036) for stage IB1 and IB2, respectively. According to FIGO 2018, the 5-year OS rates for stage IB1, IB2, and IB3 were 89.8%, 87.1%, and 81.4% (p=0.310), and PFS rates were 90.2%, 80.5%, and 80.1% (p=0.189), respectively. Patients with >= 2 pelvic lymph node (LN) metastases had worse 5-year OS and PFS rates than patients with one metastasis (p=0.015 and p=0.006). Number of para-aortic LN metastasis and metastatic LN ratio (MLNR) were also correlated with 5-year OS and PFS. CONCLUSION Current FIGO staging system better discriminates patients with cervical cancer. However, integration of metastatic LN number and/or MLNR to the upcoming FIGO staging system may improve the prognostic value of the staging.
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    Prognostic Use of Pretreatment Hematologic Parameters in Patients Receiving Definitive Chemoradiotherapy for Cervical Cancer
    (2016) Onal, Cem; Guler, Ozan C.; Yildirim, Berna A.; 0000-0002-2742-9021; 0000-0001-6661-4185; 0000-0001-6908-3412; 27206286; D-5195-2014; V-5717-2017; AAC-5654-2020
    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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    Predicting Tumor Recurrence in Patients with Cervical Carcinoma Treated with Definitive Chemoradiotherapy: Value Of Quantitative Histogram Analysis On Diffusion-Weighted MR Images
    (2017) Erbay, Gurcan; Onal, Cem; Karadeli, Elif; Guler, Ozan C.; Arica, Sami; Koc, Zafer; https://orcid.org/0000-0002-1706-8680; https://orcid.org/0000-0002-0352-8818; https://orcid.org/0000-0001-6908-3412; https://orcid.org/0000-0003-0987-1980; 27445314; AAK-5370-2021; HOC-5611-2023; AAK-5399-2021; AAC-5654-2020; S-8384-2016
    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 x 10(-3) mm(2)/s and 1.018 x 10(-3) mm(2)/s (range, 0.787-1.443 x 10(-3) mm(2)/s). The mean ADC was significantly lower for patients with advanced stage (>= IIB) or lymph node metastasis compared with patients with stage < IIB or no lymph node metastasis. The mean ADC, 75th percentile ADC (ADC75), 90th percentile ADC (ADC90), and 95th percentile ADC (ADC95) were significantly lower in patients with tumor recurrence compared with patients without recurrence. In multivariate analysis, tumor size, ADC75 and ADC95 were independent prognostic factors for both overall survival and disease-free survival. Conclusion: ADC histogram parameters could be markers for disease recurrence and for predicting survival outcomes. ADC75, ADC90, and ADC95 of the primary tumor were significant predictors of disease recurrence in cervical cancer patients treated with definitive CRT.
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    Definitive Chemoradiotherapy in Elderly Cervical Cancer Patients: A Multiinstitutional Analysis
    (2017) Guler, Ozan Cem; Sari, Sezin Yuce; Birgi, Sumerya Duru; Gultekin, Melis; Yildiz, Ferah; Onal, Cem; https://orcid.org/0000-0002-2742-9021; 28604459; D-5195-2014
    Objective The aim of the study was to investigate the prognostic factors for survival and treatment-related toxicities in older (65 years) cervical cancer patients treated with definitive chemoradiotherapy. In addition, we sought to compare the outcomes between the older elderly (75 years) and their younger old counterparts (age, 65-74 years). Materials and Methods We retrospectively reviewed medical records from 269 biopsy-proven nonmetastatic cervical cancer patients treated with external radiotherapy and intracavitary brachytherapy at the departments of radiation oncology in 2 different universities. The prognostic factors for survival, local control, and distant metastasis (DM) were analyzed. Results The median follow-up time was 38.8 months (range, 1.5-175.5 months) for the entire cohort and 70.0 months (range, 6.1-175.7 months) for survivors. The 2- and 5-year overall survival (OS), disease-free survival (DFS), and cause-specific survival rates were 66% and 42%, 63% and 39%, and 72% and 55%, respectively. Patients 75 years or older showed significantly worse OS compared with patients aged 65 to 74 years but showed no significant difference in DFS. The 2- and 5-year local control rates were 86% and 71%, respectively. The incidences of DMs at 2 and 5 years were 22% and 30%, respectively. In multivariate analysis, vaginal infiltration and lymph node metastasis were predictive of OS, DFS, local recurrence, and DM. Concomitant chemotherapy was predictive of OS, DFS, and local recurrence, and larger tumor (>4 cm) was a significant prognostic factor for local recurrence. None of the patients had toxicity that necessitated the discontinuation of radiotherapy. All patients were evaluable for acute toxicity, and no grade higher than 3 adverse events occurred during external beam radiation therapy or brachytherapy. Conclusions Although age limited the delivery of aggressive treatment, concurrent chemoradiotherapy in elderly patients associated with improved outcomes similar as in younger counterparts without increasing serious acute and late toxicities.
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    The Utility of Pretreatment and Posttreatment Lymphopenia in Cervical Squamous Cell Carcinoma Patients Treated With Definitive Chemoradiotherapy
    (2018) Onal, Cem; Yildirim, Berna Akkus; Guler, Ozan Cem; Mertsoylu, Huseyin; 0000-0002-2742-9021; 0000-0001-6661-4185; 0000-0002-1932-9784; 30247248; D-5195-2014; V-5717-2017; M-9530-2014
    Objective: The aim of this study was to investigate the prognostic significance of pretreatment and posttreatment lymphopenia in locally advanced squamous cell carcinoma (SCC) cervical cancer patients treated with definitive chemoradiotherapy (ChRT). Methods: Data from 95 patients with SCC were retrospectively analyzed. Relationships between pretreatment or posttreatment lymphopenia and patient or tumor characteristics, and overall survival (OS) and disease-free survival (DFS) were evaluated. Results: Median follow-ups for the entire cohort and survivors were 68 months (range, 3-133 months) and 88 months (range, 22-133 months), respectively. Ten patients (11%) exhibited pretreatment lymphopenia, whereas 58 patients (61%) exhibited posttreatment lymphopenia. Median pretreatment total lymphocyte counts decreased from 2029 cells/mu L to 506 cells/mu L 2 months after ChRT (P < 0.001). The 5-year OS and DFS rates were significantly higher in patients without pretreatment lymphopenia compared with patients with pre-retreatment lymphopenia (61% vs 20% [P < 0.001], 55% vs 20% [P < 0.001]). Patients without posttreatment lymphopenia had significantly higher 5-year OS and DFS rates than their counterparts (70% vs 46% [P = 0.02], 70% vs 39% [P = 0.004]). Complete response (CR) was observed in significantly fewer patients with pretreatment lymphopenia than in those without, after ChRT. Patients with posttreatment lymphopenia had higher rates of lymph node metastasis (P = 0.001) and lower posttreatment CR rates (P = 0.01) versus patients without posttreatment lymphopenia. In univariate analysis, International Federation of Gynecology and Obstetrics stage, tumor size, lymph node metastasis, and treatment response were prognostic for OS and DFS. In multivariate analysis, pretreatment lymphopenia, lymph node metastasis, and treatment response were independent predictors of OS and DFS. Age was predictive of OS. Tumor size was prognostic for DFS. Conclusions: Pretreatment lymphopenia and posttreatment lymphopenia are associated with worse treatment response in patients given ChRT for cervical SCC. Pretreatment lymphopenia is predictive for OS and DFS. Therapeutic strategies including pretreatment or posttreatment immune preservation or modulation may improve response rates and survival in women with cervical SCC.
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    The Impact Of Serum Albumin-To-Alkaline Phosphatase Ratio In Cervical Cancer Patients Treated With Definitive Chemoradiotherapy
    (2022) Onal, Cem; Gultekin, Melis; Yavas, Guler; Oymak, Ezgi; Sari, Sezin Yuce; Guler, Ozan Cem; Yigit, Ecem; Yildiz, Ferah; 35653776
    We retrospectively analysed the prognostic significance of serum albumin, alkaline phosphatase (ALP) and albumin to ALP ratio (AAPR) and other prognostic factors affecting the overall survival (OS) and progression-free survival (PFS) in 200 cervical cancer patients treated with definitive chemoradiotherapy (CRT). The prognostic factors for OS and DFS, in addition to the predictive factors of albumin, ALP and AAPR, were investigated. Older age, lymph node metastasis, non-complete response (CR) to treatment and low serum albumin levels emerged as predictors of poor OS and PFS in multivariate analysis. However, with a cut-off value of 0.51, AAPR was not a significant prognostic factor of survival in multivariable analysis. There were no significant differences in clinicopathological factors between patients with low and high AAPR, except for lymph node metastasis, where lymph node metastasis rate was significantly higher in patients with a low AAPR compared to those with a high AAPR. Patients with CR had a significantly higher serum albumin level and AAPR compared to patients without CR. The pre-treatment serum albumin level was independent predictive for survival; therefore, it could be a suitable biomarker to guide systemic therapy and predict patient outcomes. Impact Statement What is already known on this subject? Two major determinants of tumour progression are nutritional status and inflammation. The albumin-to-alkaline phosphatase ratio (AAPR), which was originally proposed as a marker for nutritional status and immune response, was recently discovered to be a prognostic factor for various cancer types. However, its utility in the treatment of cervical cancer has not been established. What do the results of this study add? Low serum albumin levels were associated with a significantly shorter OS and PFS in cervical cancer patients treated definitively with CRT. AAPR, on the other hand, was not a significant prognostic factor for survival with a cut-off value of 0.51. Regional lymph node metastasis was significantly more common in patients with a low AAPR than in those with a high AAPR. What are the implications of these findings for clinical practice and/or further research? Patients with multiple clinicopathological risk factors and low serum albumin levels had an increased risk of disease recurrence and a poorer prognosis, highlighting the importance of additional adjuvant treatment strategies in these patients. Due to the preliminary nature of our findings, additional research is required to corroborate them.
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    Prognostic values of ADC(mean) and SUVmax of the primary tumour in cervical cancer patients treated with definitive chemoradiotherapy
    (2019) Yildirim, Berna Akkus; Onal, Cem; Erbay, Gurcan; Guler, Ozan Cem; Karadeli, Elif; Reyhan, Mehmet; Koc, Zafer; 0000-0002-2742-9021; 0000-0003-0987-1980; 30354907; D-5195-2014; S-8384-2016
    We analysed the correlation of F-18-fluorodeoxyglucose uptake into primary tumours using the maximum standardised uptake value (SUVmax) and the mean apparent diffusion coefficient (ADC(mean)) values in magnetic resonance imaging (MRI) with the clinical and pathological factors in patients with cervical cancer who were treated with concurrent chemoradiotherapy. The patients were stratified according to the primary tumour pre-treatment ADC(mean) and SUVmax cut-off values. There were significant correlations between the SUVmax of the primary tumour and tumour size, and the treatment response. The correlation between the ADC(mean) and FIGO stage, tumour size, and the lymph node metastasis was significant. The SUVmax was significantly and inversely correlated with the ADC(mean) for cervical cancer (r = -0.44, p <.001). In the multivariate analysis, the primary tumour ADC(mean), treatment response and the lymph node metastasis emerged as significant independent predictors of both OS and DFS, and of the primary tumour SUVmax for DFS. Tumour size has a borderline significance for OS. High SUVmax and low ADC(mean) of the primary tumour are important predictive factors for identifying high-risk patients with cervical cancer who are treated with definitive chemoradiotherapy. These results point to a future role for the diffusion-weighted MRI and for F-18-fluorodeoxyglucose positron emission tomography, not only in the staging of cervical cancer but as an aid in the selection of an adjuvant treatment regimen after chemoradiotherapy for individual patients.