Tayfun Toptas

Predictive Value of the CA-125 Elimination Rate Constant K (KELIM) in Predicting Progression-Free Survival and Overall Survival in Epithelial Ovarian Cancer

Background: It is crucial to predict the response to chemotherapy and identify prognostic markers for recurrence and survival in patients with epithelial ovarian cancer (EOC), in order to effectively manage patient care. The CA-125 elimination rate constant K (KELIM) has recently been developed as a means of assessing the chemotherapy response and has been tested mainly in patients enrolled in randomized controlled trials. The objective of this study was to investigate whether the KELIM score is a prognostic marker for progression-free survival (PFS) and overall survival (OS) in EOC, utilizing its role in predicting the chemotherapy response in real-life settings. Method: Demographic, surgical, and survival data of patients with EOC operated on in Antalya Training and Research Hospital between January 2015 and December 2021 were obtained from the electronic gynecological oncology clinic database system and analyzed retrospectively. Results: A total of 102 patients with EOC were included; 30 patients (29.4%) had a KELIM score ≥ 1 and 72 (70.6%) patients had a KELIM score < 1. In the group with a KELIM score < 1, recurrence and refractory disease occurred in 49 patients, while it was 11 patients in the group with a KELIM score ≥ 1 (p = 0.004). PFS was 12 months and 32 months in the groups with KELIM scores of <1 and ≥1, respectively (p = 0.012). There was no difference between groups regarding OS (p = 0.139). In the whole group, KELIM score (<1 vs. ≥1) and type of surgery (IDS vs. PDS) were found to be independent prognostic factors for PFS (RR = 0.44; 95%CI: 0.22–0.88; p = 0.021 and RR = 2.97; 95%CI: 1.76–5.01; p < 0.001, respectively). Conclusion: We found that a favorable KELIM score was associated with better PFS in all groups of patients undergoing surgery for EOC in a real-life setting. With the increasing number of studies, the KELIM score will play an important role in providing better guidance to clinicians at the initial presentation of patients and in subsequent treatment planning.

Prediction of Clavien Dindo Classification ≥ Grade III Complications After Epithelial Ovarian Cancer Surgery Using Machine Learning Methods

Background and Objectives: Ovarian cancer surgery requires multiple radical resections with a high risk of complications. The aim of this single-centre, retrospective study was to determine the best method for predicting Clavien–Dindo grade ≥ III complications using machine learning techniques. Material and Methods: The study included 179 patients who underwent surgery at the gynaecological oncology department of Antalya Training and Research Hospital between January 2015 and December 2020. The data were randomly split into training set n = 134 (75%) and test set n = 45 (25%). We used 49 predictors to develop the best algorithm. Mean absolute error, root mean squared error, correlation coefficients, Mathew’s correlation coefficient, and F1 score were used to determine the best performing algorithm. Cohens’ kappa value was evaluated to analyse the consistency of the model with real data. The relationship between these predicted values and the actual values were then summarised using a confusion matrix. True positive (TP) rate, False positive (FP) rate, precision, recall, and Area under the curve (AUC) values were evaluated to demonstrate clinical usability and classification skills. Results: 139 patients (77.65%) had no morbidity or grade I-II CDC morbidity, while 40 patients (22.35%) had grade III or higher CDC morbidity. BayesNet was found to be the most effective prediction model. No dominant parameter was observed in the Bayesian net importance matrix plot. The true positive (TP) rate was 76%, false positive (FP) rate was 15.6%, recall rate (sensitivity) was 76.9%, and overall accuracy was 82.2% A receiver operating characteristic (ROC) analysis was performed to estimate CDC grade ≥ III. AUC was 0.863 with a statistical significance of p < 0.001, indicating a high degree of accuracy. Conclusions: The Bayesian network model achieved the highest accuracy compared to all other models in predicting CDC Grade ≥ III complications following epithelial ovarian cancer surgery.

High-grade endometrial stromal sarcoma versus undifferentiated uterine sarcoma: a Turkish uterine sarcoma group study-001

Prognostic factors associated with high-grade endometrial stromal sarcoma (HGESS) and undifferentiated uterine sarcoma (UUS) have not been distinctly determined due to the repetitive changes in the World Health Organization (WHO) classification. We aimed to compare clinicopathologic features and outcomes of patients with HGESS with those of patients with UUS. A multi-institutional, retrospective, cohort study was conducted including 71 patients, who underwent surgery at 13 centers from 2008 to 2017. An experienced gynecopathologist from each institution re-evaluated the slides of their own cases according to the WHO The median disease-free survival (DFS) for HGESS and UUS was 12 months and 6 months, respectively. While the median overall survival was not reached in HGESS group, it was 22 months in the UUS group. Kaplan-Meier analyses revealed that patients with UUS had a significantly poorer DFS than those with HGESS (p = 0.016), although OS did not differ between the groups (p = 0.135). Lymphovascular-space involvement (LVSI) was the sole significant factor associated with progression, recurrence or death for HGESS (Hazard ratio: 9.353, 95% confidence interval: 2.539-34.457, p = 0.001), whereas no significant independent factor was found for UUS. UUS has a more aggressive behavior than HGESS. While no significant predictor of prognosis was found for UUS, LVSI is the sole independent prognostic factor for HGESS, with patients 9.3 times more likely to experience refractory/progressive disease, recurrence or death.

Neoadjuvant chemotherapy in patients with stage IVB uterine serous carcinoma: a Turkish multicentric study

The aim of this study was to evaluate the prognostic factors for and determine the effect of neoadjuvant chemotherapy (NACT) on oncologic outcome in stage IVB pure serous endometrial carcinoma patients who received taxane and platinum. Forty-two patients with 2009 International Federation of Gynecology and Obstetrics (FIGO) stage IVB uterine serous carcinoma were enrolled from six gynecologic oncology centers and a study group was created. The study group had a 2-year disease-free survival (DFS) of 32% and 2-year disease-specific survival (DSS) of 73%. On univariate analysis; lymphadenectomy (not performed vs. performed), paraaortic lymph node metastasis (positive vs. negative) and number of metastatic lymph node count (≤5 vs. >5) were found to have statistical significance for DFS (

Radical hysterectomy in early cervical cancer in Europe: characteristics, outcomes and evaluation of ESGO quality indicators

Comprehensive updated information on cervical cancer surgical treatment in Europe is scarce. To evaluate baseline characteristics of women with early cervical cancer and to analyze the outcomes of the ESGO quality indicators after radical hysterectomy in the SUCCOR database. The SUCCOR database consisted of 1272 patients who underwent radical hysterectomy for stage IB1 cervical cancer (FIGO 2009) between January 2013 and December 2014. After exclusion criteria, the final sample included 1156 patients. This study first described the clinical, surgical, pathological, and follow-up variables of this population and then analyzed the outcomes (disease-free survival and overall survival) after radical hysterectomy. Surgical-related ESGO quality indicators were assessed and the accomplishment of the stated recommendations was verified. The mean age of the patients was 47.1 years (SD 10.8), with a mean body mass index of 25.4 kg/m In this European cohort, the rate of adjuvant therapy after radical hysterectomy is higher than for most similar patients reported in the literature. The majority of centers were already following the European recommendations even 5 years prior to the ESGO quality indicator implementations.

SUCCOR quality: validation of ESGO quality indicators for surgical treatment of cervical cancer

To evaluate whether compliance with European Society of Gynaecological Oncology (ESGO) surgery quality indicators impacts disease-free survival in patients undergoing radical hysterectomy for cervical cancer. In this retrospective cohort study, 15 ESGO quality indicators were assessed in the SUCCOR database (patients who underwent radical hysterectomy for International Federation of Gynecology and Obstetrics (FIGO) stage 2009 IB1, FIGO 2018 IB1, and IB2 cervical cancer between January 2013 and December 2014), and the final score ranged between 0 and 16 points. Centers with more than 13 points were classified as high-quality indicator compliance centers. We constructed a weighted cohort using inverse probability weighting to adjust for the variables. We compared disease-free survival and overall survival using Cox proportional hazards regression analysis in the weighted cohort. A total of 838 patients were included in the study. The mean number of quality indicators compliance in this cohort was 13.6 (SD 1.45). A total of 479 (57.2%) patients were operated on at high compliance centers and 359 (42.8%) patients at low compliance centers. High compliance centers performed more open surgeries (58.4% vs 36.7%, p<0.01). Women who were operated on at centers with high compliance with quality indicators had a significantly lower risk of relapse (HR=0.39; 95% CI 0.25 to 0.61; p<0.001). The association was reduced, but remained significant, after further adjustment for conization, surgical approach, and use of manipulator surgery (HR=0.48; 95% CI 0.30 to 0.75; p=0.001) and adjustment for adjuvant therapy (HR=0.47; 95% CI 0.30 to 0.74; p=0.001). Risk of death from disease was significantly lower in women operated on at centers with high adherence to quality indicators (HR=0.43; 95% CI 0.19 to 0.97; p=0.041). However, the association was not significant after adjustment for conization, surgical approach, use of manipulator surgery, and adjuvant therapy. Patients with early cervical cancer who underwent radical hysterectomy in centers with high compliance with ESGO quality indicators had a lower risk of recurrence and death.

SUCCOR cone study: conization before radical hysterectomy

To evaluate disease-free survival of cervical conization prior to radical hysterectomy in patients with stage IB1 cervical cancer (International Federation of Gynecology and Obstetrics (FIGO) 2009). A multicenter retrospective observational cohort study was conducted including patients from the Surgery in Cervical Cancer Comparing Different Surgical Aproaches in Stage IB1 Cervical Cancer (SUCCOR) database with FIGO 2009 IB1 cervical carcinoma treated with radical hysterectomy between January 1, 2013, and December 31, 2014. We used propensity score matching to minimize the potential allocation biases arising from the retrospective design. Patients who underwent conization but were similar for other measured characteristics were matched 1:1 to patients from the non-cone group using a caliper width ≤0.2 standard deviations of the logit odds of the estimated propensity score. We obtained a weighted cohort of 374 patients (187 patients with prior conization and 187 non-conization patients). We found a 65% reduction in the risk of relapse for patients who had cervical conization prior to radical hysterectomy (hazard ratio (HR) 0.35, 95% confidence interval (CI) 0.16 to 0.75, p=0.007) and a 75% reduction in the risk of death for the same sample (HR 0.25, 95% CI 0.07 to 0.90, p=0.033). In addition, patients who underwent minimally invasive surgery without prior conization had a 5.63 times higher chance of relapse compared with those who had an open approach and previous conization (HR 5.63, 95% CI 1.64 to 19.3, p=0.006). Patients who underwent minimally invasive surgery with prior conization and those who underwent open surgery without prior conization showed no differences in relapse rates compared with those who underwent open surgery with prior cone biopsy (reference) (HR 1.94, 95% CI 0.49 to 7.76, p=0.349 and HR 2.94, 95% CI 0.80 to 10.86, p=0.106 respectively). In this retrospective study, patients undergoing cervical conization before radical hysterectomy had a significantly lower risk of relapse and death.

Assessment of the differences in oncologic outcomes between patients with high‐grade serous ovarian carcinoma and uterine serous carcinoma

AbstractAimTo evaluate whether the recurrence rates, recurrence patterns, and survival outcomes differed according to the primary site of the tumor in patients with high‐grade serous ovarian carcinoma (HGSOC) and uterine serous carcinoma (USC).MethodsThe population of this multicenter retrospective study consisted of patients who had USC or HGSOC. Progression‐free survival (PFS) and disease‐specific survival (DSS) estimates were determined using the Kaplan–Meier method. Survival curves were compared using the log‐rank test.ResultsThe study cohort consisted of 247 patients with HGSOC and 34 with USC. Recurrence developed in 118 (51.1%) in the HGSOC group and 14 (42.4%) in the USC group (p = 0.352). The median time to recurrence was 23.5 (range, 4–144) and 17 (range, 4–43) months in the HGSOC and USC groups, respectively (p = 0.055). The 3‐year PFS was 52% in the HGSOC group and 47% in the USC group (p = 0.450). Additionally, 3‐year DSS was 92% and 82% in the HGSOC and USC groups, respectively (p = 0.060).ConclusionsHGSOC and USC are aggressive tumors with high recurrence and mortality rates in advanced stages. These two carcinomas, which are similar in molecular features and clinical management, may also have similar recurrence patterns, disease failure, and survival rates.

Perceived social support, fatigue, and sleep quality in women treated for gynecological cancer: a cross-sectional study

Abstract Aim The study aims to determine the levels of perceived social support, fatigue, and sleep quality among women undergoing treatment for gynecological cancer. Methods This cross-sectional and descriptive study included 217 women. Participants completed the personal information form, the multidimensional perceived social support scale, the Pittsburgh Sleep Quality Index, and the brief fatigue questionnaire. This study was conducted with patients who received treatment at the Gynaecological Oncology Clinic of a Training and Research Hospital and met the inclusion criteria. Data were collected between April and September 2023 after obtaining approval from the ethics committee and the relevant institution. Results The mean total score for perceived social support was 59.85 ± 17.04, the median total score on the fatigue scale was 63.00 (IQR = 16.50), and the mean total score on the PSQI was 6.91 ± 2.60. Most of the participants (67.4%) had poor sleep quality. There was a weak negative correlation between the daytime dysfunction subdimension and the total PSQI score and both the subdimensions and total score of the social support scale, as well as a weak positive correlation with the fatigue scale (p &lt; 0.05). Conclusion In our study, perceived social support and fatigue scores among patients with gynecological cancer were found to be above the moderate level, while their sleep quality was poor.

Nicotinamide Phosphoribosyltransferase (NAMPT) as a New Marker in Cervical Preinvasive Lesions

Objective To examine the relationship between cervical dysplasia and tissue levels of nicotinamide phosphoribosyltransferase (NAMPT). Materials and Methods Patients who underwent colposcopic biopsy due to human papilloma virus positivity were classified as normal tissue and cervical intraepithelial neoplasia (CIN) 1, CIN 2-3. These were stained with NAMPT antibodies using streptavidin-biotin peroxidase method (Invitrogen, 85-9043, CA, USA). The staining intensity was scored as: 0, 1, 2, and 3 for no, mild, moderate, and intense staining, respectively. The percentage score was classified as: 1, 2, and 3 for 1% to 33%, 34% to 66%, and 67% to 100% positivity, respectively. The product score was calculated. Totally, 86 patients were included in the study. Results The NAMPT staining scores were significantly higher in the CIN 2-3 group compared to the group with CIN 1/normal (90% vs 9%; respectively, P  &lt; .000). No intense NAMPT staining was observed in any of the specimens with CIN 1 or normal results. The percentage score of 2 to 3 was seen in 83% and 12% for patients with and without CIN 2-3, respectively ( P  &lt; .000). Using a cutoff value for product score of 2, the test demonstrated a sensitivity, a negative-predictive value, a specificity, and a positive-predictive value of 96%, 98%, 80%, and 71%, respectively. Although the product score was 2 and higher for 96% of CIN 2-3 specimens, 78% of those with CIN 1 or normal results had that below 2. Conclusion The NAMPT staining differs significantly among groups and may be a useful marker for distinguishing CIN 2-3 from normal tissue and CIN 1. That has potential to improve the sensitivity–specificity of diagnosing and treating cervical premalignant lesions.

Defining the relationship between ovarian adult granulosa cell tumors and synchronous endometrial pathology: Does ovarian tumor size correlate with endometrial cancer?

Abstract Objective The main feature of adult granulosa cell tumors (AGCT) is their capacity to secrete hormones, with nearly all of them capable of synthesizing oestradiol. The primary goal of this study is to identify synchronized endometrial pathologies, particularly endometrial cancer, in AGCT patients who had undergone a hysterectomy. Materials and Methods The study cohort comprised retrospectively of 316 AGCT patients from 10 tertiary gynecological oncology centers. AGCT surgery consisted of bilateral salpingo‐oophorectomy, hysterectomy, peritoneal cytology, omentectomy, and the excision of any suspicious lesion. The median tumor size value was used to define the relationship between tumor size and endometrial cancer. The relationship between each value and endometrial cancer was evaluated. Results Endometrial intraepithelial neoplasia, or hyperplasia with complex atypia, was detected in 7.3% of patients, and endometrial cancer in 3.1% of patients. Age, menopausal status, tumor size, International Federation of Gynecology and Obstetrics stage, ascites, and CA‐125 level were not statistically significant factors to predict endometrial cancer. There was no endometrial cancer under the age of 40, and 97.8% of women diagnosed with endometrial hyperplasia were over the age of 40. During the menopausal period, the endometrial cancer risk was 4.5%. Developing endometrial cancer increased to 12.1% from 3.2% when the size of the tumor was &gt;150 mm in menopausal patients ( p  = 0.036). Conclusion Endometrial hyperplasia, or cancer, occurs in approximately 30% of AGCT patients. Patients diagnosed with AGCT, especially those older than 40 years, should be evaluated for endometrial pathologies. There may be a relationship between tumor size and endometrial cancer, especially in menopausal patients.

Prognostic factors of adult granulosa cell tumors of the ovary: a Turkish retrospective multicenter study

To define the clinical, histopathological features and the prognostic factors affecting survival in patients with adult granulosa cell tumors of the ovary (AGCT). A 322 patients whose final pathologic outcome was AGCT treated at nine tertiary oncology centers between 1988 and 2021 participated in the study. The mean age of the patients was 51.3±11.8 years and ranged from 21 to 82 years. According to the International Federation of Gynecology and Obstetrics 2014, 250 (77.6%) patients were stage I, 24 (7.5%) patients were stage II, 20 (6.2%) patients were stage III, and 3 (7.8%) were stage IV. Lymphadenectomy was added to the surgical procedure in 210 (65.2%) patients. Lymph node involvement was noted in seven (3.3%) patients. Peritoneal cytology was positive in 19 (5.9%) patients, and 13 (4%) had metastases in the omentum. Of 285 patients who underwent hysterectomy, 19 (6.7%) had complex hyperplasia with atypia/endometrial intraepithelial neoplasia, and 8 (2.8%) had grade 1 endometrioid endometrial carcinoma. It was found that 93 (28.9%) patients in the study group received adjuvant treatment. Bleomycin, etoposide, cisplatin was the most commonly used chemotherapy protocol. The median follow-up time of the study group was 41 months (range, 1-276 months). It was noted that 34 (10.6%) patients relapsed during this period, and 9 (2.8%) patients died because of the disease. The entire cohort had a 5-year disease-free survival (DFS) of 86% and a 5-year disease-specific survival of 98%. Recurrences were observed only in the pelvis in 13 patients and the extra-abdominal region in 7 patients. The recurrence rate increased 6.168-fold in patients with positive peritoneal cytology (95% confidence interval [CI]=1.914-19.878; p=0.002), 3.755-fold in stage II-IV (95% CI=1.275-11.063; p=0.016), and 2.517-fold in postmenopausal women (95% CI=1.017-6.233; p=0.046) increased. In this study, lymph node involvement was detected in 3.3% of patients with AGCT. Therefore, it was concluded that lymphadenectomy can be avoided in primary surgical treatment. Positive peritoneal cytology, stage, and menopausal status were independent prognostic predictors of DFS.

Prognostic Value of Conization and Negative HPV After Conization in AIS and Early Stage Cervical Cancer

In women with cervical cancer -Squamous cell carcinoma, Adeno carcinoma, Adeno-squamous carcinoma or AIS we want to examine prospectively: 1. Examine if negative HR-HPV after conization to the HR-HPV the women had before conization has a high prognostic value for no residual tumor in the final pathology. 2. To examine if conization in women with cervical tumor up to Stage I B 2 (FIGO 2018) is corelated with better prognosis.