Clinicopathological and Survival Characteristics of Mismatch Repair Status and PD-1 Expression in Serous Ovarian Cancer.

OBJECTIVE: To evaluate the clinicopathological characteristics of mismatch repair (MMR) deficiency and its clinical outcomes by performing immunohistochemistry (IHC) for MMR genes in the serous ovarian cancer (SOC) tumour sections. STUDY DESIGN: A retrospective case-control study. Place and Duration of the Study: Gynecology Department of Kanuni Sultan Süleyman Training and Research Hospital, and Department of Medical Oncology of Medipol University, between March 2001 and January 2020. METHODOLOGY: IHC was carried out for MLH1, MSH2, MSH6, and PMS2 on full-section slides from 127 SOCs to evaluate the MMR status. MMR-negative and MMR-low groups together were defined as MMR deficient and called microsatellite instability-high (MSI-H). The MSI status and expression of programmed cell death-1 (PD-1) were compared in SOCs with different MMR statuses. RESULTS: A significantly higher frequency of MMR-deficient SOCs was diagnosed at early stages compared with the patients in the MSS group (38.6% and 20.6%, respectively, p=0.022). The frequency of cases with PD-1 expression was significantly higher in the MSI-H group (76.2%) than in the MSS counterparts (58.8%, p=0.028). Patients in the MSI-H group had significantly longer DFS (25.6 months) and OS (not reached) than those in the MSS group (16 months and 48.9 months, p=0.039 and p=0.026, respectively). CONCLUSION: MSI-H SOCs were diagnosed at an earlier stage as compared to MMR proficient cases. The presence of PD-1 expression was significantly higher in cases presenting MMR deficiency compared with MMR-proficient cases. MSI status was significantly associated with DFS and OS. KEY WORDS: Serous ovarian cancer, Microsatellite instability, Mismatch repair deficiency.

Preoperative prediction of retroperitoneal lymph node involvement in clinical stage IB and IIA cervical cancer.

Objective: Lymph node metastasis (LNM) is the most important factor affecting survival in early-stage cervical cancer (CC). International Federation of Gynecology and Obstetrics revised the staging of CC in 2018 and reported LNM as a staging criterion. We investigated the preoperatively assessable risk factors associated with LNM in surgically treated stage IB1-IIA2 CC patients. Materials and Methods: This was a retrospective cohort study of women who underwent radical hysterectomy and pelvic lymphadenectomy with or without para-aortic lymphadenectomy for CC stage IB1-IIA2 from 2004 to 2019. All patients included in this study were examined with speculum inspection, parametrial assessment by rectovaginal palpation under general anesthesia, transvaginal ultrasonography, magnetic resonance imaging (MRI), and chest radiography. Clinical staging was done according to the preoperative findings. MRI was used to measure tumor and lymph node dimensions. Results: Out of the 149 women included in the study, 29 (19.4%) had LNM. Univariate analysis revealed that larger tumor size (≥30 mm), lymphovascular space invasion (LVSI) detected with diagnostic biopsy, parametrial involvement, and deep stromal invasion status were significantly different between the group with LNM and the group without LNM. In multivariate analysis, specific preoperative risk factors such as MRI based tumor diameter ≥30 mm and LVSI (+) on the diagnostic biopsy were found to be independent risk factors for LNM in the multivariate analysis. Conclusion: The rate of LNM is high in patients with CC with a tumor size ≥30 mm and preoperative biopsy LVSI status even if they are clinically in early stages. Surgeons can take this into account while deciding between primary surgery and chemoradiotherapy in the treatment of CC.

High expression of CD8 in the tumor microenvironment is associated with PD-1 expression and patient survival in high-grade serous ovarian cancer.

Objective: The current study assesses programmed death-1 (PD-1) receptor expression and CD3, CD4, and CD8 tumor-infiltrating lymphocytes (TILs) in high-grade serous ovarian cancer (HGSOC) and associates our results with neoadjuvant chemotherapy history and disease prognosis. Materials and Methods: We included cases diagnosed with primary HGSOC with biopsy or surgical resection materials in this study. The immunoreactivity of CD3, CD4, CD8, and PD1 was assessed immunohistochemically in tumor tissue. We analyzed TILs in two predetermined groups of high and low TIL. The relationships between clinical characteristics, PD-1, and TIL were assessed. by the χ(2) test or Fisher's Exact test. We used Kaplan-Meier survival analysis and Cox proportional hazards regression model to the connection between survival and the amounts of TIL, and PD1. Results: Univariate analysis demonstrated that optimal debulking (p<0.001), early International Federation of Gynecology and Obstetrics stage (p=0.046), and higher scores of stromal CD8+ TIL expression (p=0.028) in tumor cells were all substantially correlated with longer disease-free survival (DFS), whereas the remaining variables analyzed, including PD-1 positivity, stromal CD3+, and CD4+ TILs, and intraepithelial CD3+, CD4+, and CD8+ TILs, were not correlated with DFS. Also, univariate analysis revealed that optimal debulking (p=0.010), and higher scores of stromal CD8+ TIL expression (p=0.021) in tumor cells were all substantially correlated with longer overall survival (OS). Conclusion: Higher scores of stromal CD8+ TILs are substantially correlated with DFS and OS in univariate analyses, whereas scores of stromal CD3+ and CD4+ TILs, and intraepithelial CD3+, CD4+, and CD8+ TILs are not correlated with DFS and OS in both univariate and multivariate analyses. Also, we found a significant association between PD-1 positivity and the scores of stromal CD3+ TILs and intraepithelial CD8+ TILs. However, no remarkable relationship was revealed between PD-1 positivity and the survival of HGSOC cases.

Open abdomen technique used in complications of major gynecological oncology surgery.

OBJECTIVE: To evaluate the open abdomen technique (laparostomy) used in complications of major gynecological oncology surgery. METHODS: We analyzed retrospectively the surgical database of all patients who had undergone major open surgery by the same gynecologic oncologist over a 5-year period. All patients who had had open abdomen procedure were identified; demographic data and indications of primary surgery, temporary abdominal closure procedure details, fascia closure and morbidity, mortality rates were evaluated. Intraabdominal infection and intraoperative massive hemorrhage were the major indications for all open abdomen cases. Mannheim Peritonitis Index was used perioperatively to determine open abdomen decision in intraabdominal infections. Vacuum Assisted Abdominal Closure system and Bogota Bag were used for temporary abdominal closure techniques. RESULTS: Out of the total 560 patients who had undergone major oncological surgery, 19 patients (3.3%) had open abdomen procedure due to surgical complications. Eleven patients had intraabdominal infection, six patients had hemodynamic instability due to peri and postoperative hemorrhage, two patients had gross fecal contamination during posterior pelvic exenteration surgery. The fascia was closed totally in 15 (78%), partially in 3 (15%) and could not be closed in 1 patient who had died secondary to multiorgan failure. Total morbidity and mortality rates were 26% (5/19) (two intrabdominal abscess, one pulmonary embolism, one skin necrosis, one enteroatmospheric fistula) and 5.2% (1/19) respectively. CONCLUSION: Open abdomen is a life-saving procedure when applied with correct indications and timing. Gynecological oncologic surgeries are candidates to serious complications and gynecologic oncologists dealing with such surgery should be as experienced as general surgeons in this regard.

OPEC study: An international multicenter study of ovarian preservation in endometrial cancers.

OBJECTIVE: To evaluate the feasibility and oncological safety of ovarian preservation in early stage endometrial adenocarcinoma (EC) patients aged 40 and below. METHODS: A total of 11 institutions from eight countries participated in the study. 169 of 5898 patients aged ≤40 years were eligible for the study. Patients with EC treated between March 2007 and January 2019 were retrospectively assessed. RESULTS: The median duration of follow-up after EC diagnosis was 59 months (4-187). Among 169 participants, ovarian preservation surgery (OPS) was performed in 54 (31.9%), and BSO was performed in 115 (68.1%) patients. Although patients younger than 30 years of age were more likely to have OPS than patients aged 30 to 40 years (20.4% vs. 9.6%, P = 0.021), there was no significant difference by the mean age. There were no other relevant baseline differences between OPS and BSO groups. The Kaplan-Meier analysis revealed no difference in either the overall survival (P = 0.955) or recurrence-free survival (P = 0.068) among patients who underwent OPS, and BSO. CONCLUSION: OPS appears to be safe without having any adverse impact on survival in women aged ≤40 years with FIGO Stage I EC.

Factors associated with the involvement of lymph nodes in low-grade serous ovarian cancer.

BACKGROUND AND OBJECTIVES: Evaluating nodal metastases in low-grade serous ovarian cancer (LGSOC) patients. METHODS: Women with LGSOC who had undergone primary cytoreductive surgery comprising systematic pelvic-paraaortic lymphadenectomy were included. Data were obtained retrospectively from 12 oncology centers. RESULTS: One hundred and forty-eight women with LGSOC who had undergone comprehensive surgical staging were included. Seventy-one (48.0%) patients had metastatic lymph nodes. Preoperative serum CA-125 levels of ≥170 U/ml (odds ratio [OR]: 3.84; 95% confidence interval [CI]: 1.22-12.07; p = 0.021) and presence of lymphovascular space invasion (LVSI) (OR: 13.72; 95% CI: 3.36-55.93; p < 0.001) were independent predictors of nodal metastasis in LGSOC. Sixty (40.5%) patients were classified to have apparently limited disease to the ovary/ovaries. Twenty (33.3%) of them were upstaged after surgical staging. Twelve (20.0%) had metastatic lymph nodes. Presence of LVSI (OR: 12.96; 95% CI: 1.14-146.43; p = 0.038) and preoperative serum CA-125 of ≥180 U/ml (OR: 7.19; 95% CI: 1.35-38.12; p = 0.02) were independent predictors of lymph node metastases in apparent Stage Ⅰ disease. CONCLUSIONS: Clinicians may consider to perform a reoperation comprising systematic lymphadenectomy in patients who had apparently limited disease to the ovary/ovaries and had not undergone lymphadenectomy initially. Reoperation may be considered particularly in patients whose preoperative serum CA-125 is ≥180 U/ml and/or whose pathological assessment reported the presence of LVSI.

Prognostic factors and survival outcomes of women with uterine leiomyosarcoma: A Turkish Uterine Sarcoma Group Study-003.

To assess the clinicopathological features, prognostic factors, and survival rates associated with uterine leiomyosarcoma (uLMS). Databases from 15 participating gynecological oncology centers in Turkey were searched retrospectively for women who had been treated for stage I-IV uLMS between 1996 and 2018. Of 302 consecutive women with uLMS, there were 234 patients with Federation of Gynecology and Obstetrics (FIGO) stage I disease and 68 with FIGO stage II-IV disease. All patients underwent total hysterectomy. Lymphadenectomy was performed in 161 (54.5%) cases. A total of 195 patients received adjuvant treatment. The 5-year disease-free survival (DFS) and overall survival (OS) rates were 42% and 54%, respectively. Presence of lymphovascular space invasion (LVSI), higher degree of nuclear atypia, and absence of lymphadenectomy were negatively correlated with DFS, while LVSI, mitotic count, higher degree of nuclear atypia, FIGO stage II-IV disease, and suboptimal surgery significantly decreased OS. LVSI and higher degree of nuclear atypia appear to be prognostic indicators for uLMS. Lymphadenectomy seems to have a significant effect on DFS but not on OS.

Impact of cytoreductive surgery on survival of patients with low-grade serous ovarian carcinoma: A multicentric study of Turkish Society of Gynecologic Oncology (TRSGO-OvCa-001).

BACKGROUND AND OBJECTIVES: The aim of this study was to analyze the factors affecting recurrence-free (RFS) and overall survival (OS) rates of women diagnosed with low-grade serous ovarian cancer (LGSOC). METHODS: Databases from 13 participating centers in Turkey were searched retrospectively for women who had been treated for stage I-IV LGSOC between 1997 and 2018. RESULTS: Overall 191 eligible women were included. The median age at diagnosis was 49 years (range, 21-84 years). One hundred seventy-five (92%) patients underwent primary cytoreductive surgery. Complete and optimal cytoreduction was achieved in 148 (77.5%) and 33 (17.3%) patients, respectively. The median follow-up period was 44 months (range, 2-208 months). Multivariate analysis showed the presence of endometriosis (p = .012), lymphovascular space invasion (LVSI) (p = .022), any residual disease (p = .023), and the International Federation of Gynecology and Obstetrics (FIGO) stage II-IV disease (p = .045) were negatively correlated with RFS while the only presence of residual disease (p = .002) and FIGO stage II-IV disease (p = .003) significantly decreased OS. CONCLUSIONS: The maximal surgical effort is warranted for complete cytoreduction as achieving no residual disease is the single most important variable affecting the survival of patients with LGSOC. The prognostic role of LVSI and endometriosis should be evaluated by further studies as both of these parameters significantly affected RFS.

Comparison of stage III mucinous and serous ovarian cancer: a case-control study.

BACKGROUND: The purpose of this case-control study was to compare the prognoses of women with stage III mucinous ovarian carcinoma (MOC) who received maximal or optimal cytoreduction followed by paclitaxel plus carboplatin chemotherapy to those of women with stage III serous epithelial ovarian cancer (EOC) treated in the similar manner. METHODS: We performed a multicenter, retrospective review to identify patients with stage III MOC at seven gynecologic oncology departments in Turkey. Eighty-one women with MOC were included. Each case was matched to two women with stage III serous EOC in terms of age, tumor grade, substage of disease, and extent of residual disease. Survival estimates were measured using Kaplan-Meier plots. Variables predictive of outcome were analyzed using Cox regression models. RESULTS: With a median follow-up of 54 months, the median progression-free survival (PFS) for women with stage III MOC was 18.0 months (95% CI; 13.8-22.1, SE: 2.13) compared to 29.0 months (95% CI; 24.04-33.95, SE: 2.52) in the serous group (p = 0.19). The 5-year overall survival rate of the MOC group was significantly lower than that of the serous EOC group (44.9% vs. 66.3%, respectively; p < 0.001). For the entire cohort, presence of multiple peritoneal implants (Hazard ratio [HR] 2.39; 95% confidence interval [CI], 1.38-4.14, p = 0.002) and mucinous histology (HR 2.28; 95% CI, 1.53-3.40, p < 0.001) were identified as independent predictors of decreased OS. CONCLUSION: Patients with MOC seem to be 2.3 times more likely to die of their tumors when compared to women with serous EOC.

Risk Factors for Recurrence in Low-Risk Endometrial Cancer: A Case-Control Study.

AIM: The aim of this study was to investigate the risk factors for recurrence in patients with low-risk endometrial cancer (EC). PATIENTS AND METHODS: This retrospective study was performed using 10 gynecological oncology department databases. Patients who met the following criteria were included in the study: (a) endometrioid-type histology, (b) histological grade 1 or 2, (c) no or < 50% myometrial invasion, (d) no intraoperative evidence of extrauterine spread, and (e) the patient underwent at least a pelvic lymphadenectomy. Recurrence was detected in 56 patients who were histologically diagnosed with low-risk EC, and these patients made up the case group. A total of 224 patients with low-risk EC without recurrence were selected (control group) using a dependent random sampling method. The case and control groups were match-paired in terms of grade, stage, and operative technique. RESULTS: Lymphovascular space invasion (LVSI) (odds ratio (OR) 5.8, 95% confidence interval (CI) 2.0-16.9; p = 0.001) and primary tumor diameter (PTD) ≥ 20 mm (OR 6.6, 95% CI 2.7-15.8; p < 0.001) were found to be independent risk factors for recurrence in women with low-risk EC. CONCLUSION: The presence of LVSI and PTD ≥ 20 mm seem to be significant risk factors for recurrence in women with low-risk EC.

Evaluation of Factors Affecting Lymph Node Metastasis in Clinical Stage I-II Epithelial Ovarian Cancer.

BACKGROUND: Systematic lymphadenectomy is useful for accurate staging of early-stage ovarian cancer and has obvious prognostic value. Accurate staging may prevent unnecessary postoperative chemotherapy. The aim of this study was to evaluate the rate of lymph node involvement and factors affecting it in clinically early-stage epithelial ovarian cancer (EOC; stages I, II). PATIENTS AND METHODS: The study included 163 patients who underwent surgery at our hospital between January 2004 and April 2017 and who were diagnosed with early-stage EOC based on preoperative and intraoperative examination. Patient data were retrospectively analyzed. The rate of lymph node involvement and factors affecting it were analyzed. RESULTS: Of 163 patients, 21 (12.9%) had lymph node metastasis, whereas 16 (16.3%) of 98 patients who underwent comprehensive lymphadenectomy had lymph node metastasis. According to the univariate results for patients undergoing any type of lymphadenectomy, the rate of positive lymph nodes was significantly higher (37.1%) in those with bilateral ovarian involvement (p < 0.001). The rate was significantly higher in patients with positive intraabdominal fluid cytology (25.9%; p < 0.001), serous histology (20.5%; p = 0.02), and grade 3 disease (33.3%; p < 0.001). In multivariate logistic regression analysis, the rate was significantly higher in patients with bilateral adnexal involvement (p = 0.012). The risk of positive lymph nodes was significantly higher in patients with grade 3 disease (p = 0.016). CONCLUSION: Comprehensive lymphadenectomy increases the detection rate for metastatic lymph nodes in patients with clinically early-stage EOC. The rate of lymph node involvement is significantly higher in grade 3 tumors, serous cytology, bilateral adnexal involvement, and positive intraabdominal fluid cytology.

Prognostic factors for maximally or optimally cytoreduced stage III nonserous epithelial ovarian carcinoma treated with carboplatin/paclitaxel chemotherapy.

OBJECTIVE: To identify factors predictive of poor prognosis in women with stage III nonserous epithelial ovarian cancer (EOC) who had undergone maximal or optimal primary cytoreductive surgery (CRS) followed by six cycles of intravenous carboplatin/paclitaxel chemotherapy. METHODS: A multicenter, retrospective department database review was performed to identify patients with stage III nonserous EOC who had undergone maximal or optimal primary CRS followed by six cycles of carboplatin/paclitaxel chemotherapy at seven gynecological oncology centers in Turkey. Demographic, clinicopathological and survival data were collected. RESULTS: A total of 218 women met the inclusion criteria. Of these, 64 (29.4%) patients had endometrioid, 61 (28%) had mucinous, 54 (24.8%) had clear-cell and 39 (17.9%) had mixed epithelial tumors. Fifty-five (25.2%) patients underwent maximal CRS, whereas 163 (74.8%) had optimal debulking. With a median follow-up of 31.5 months, the 5-year progression-free survival (PFS) and overall survival (OS) rates were 34.8% and 44.2%, respectively. Bilaterality (hazard ratio [HR] 1.44, 95% CI 1.01-2.056; P = 0.04), age (HR 2.25, 95% CI 1.176-4.323; P = 0.014) and maximal cytoreduction (HR 0.34, 95% CI 0.202-0.58; P < 0.001) were found to be independent prognostic factors for PFS. However, age (HR 2.6, 95% CI 1.215-5.591; P = 0.014) and maximal cytoreduction (HR 0.31, 95% CI 0.166-0.615; P < 0.001) were defined as independent prognostic factors for OS. CONCLUSION: The extent of CRS seems to be the only modifiable prognostic factor associated with stage III nonserous EOC. Complete cytoreduction to no gross residual disease should be the main goal of management in these women.

Impact of lymph node ratio on survival in stage IIIC endometrioid endometrial cancer: a Turkish Gynecologic Oncology Group study.

OBJECTIVE: The purpose of this study was to investigate the prognostic value of lymph node ratio (LNR) in women with stage IIIC endometrioid endometrial cancer (EC). METHODS: A multicenter, retrospective department database review was performed to identify patients with stage IIIC pure endometrioid EC at 6 gynecologic oncology centers in Turkey. A total of 207 women were included. LNR, defined as the percentage of positive lymph nodes (LNs) to total nodes recovered, was stratified into 2 groups: LNR1 (≤0.15), and LNR2 (>0.15). Kaplan-Meier method was used to generate survival data. Factors predictive of outcome were analyzed using Cox proportional hazards models. RESULTS: One hundred and one (48.8%) were classified as stage IIIC1 and 106 (51.2%) as stage IIIC2. The median age at diagnosis was 58 (range, 30-82) and the median duration of follow-up was 40 months (range, 1-228 months). There were 167 (80.7%) women with LNR ≤0.15, and 40 (19.3%) women with LNR >0.15. The 5-year progression-free survival (PFS) rates for LNR ≤0.15 and LNR >0.15 were 76.1%, and 58.5%, respectively (p=0.045). An increased LNR was associated with a decrease in 5-year overall survival (OS) from 87.0% for LNR ≤0.15 to 62.3% for LNR >0.15 (p=0.005). LNR >0.15 was found to be an independent prognostic factor for both PFS (hazard ratio [HR]=2.05; 95% confidence interval [CI]=1.07-3.93; p=0.03) and OS (HR=3.35; 95% CI=1.57-7.19; p=0.002). CONCLUSION: LNR seems to be an independent prognostic factor for decreased PFS and OS in stage IIIC pure endometrioid EC.

Can concurrent high-risk endometrial carcinoma occur with atypical endometrial hyperplasia?

BACKGROUND: This study investigated the frequency of high-risk cancer types in hysterectomy material obtained from patients who were diagnosed with atypical endometrial hyperplasia (AEH) by endometrial sampling. MATERIALS AND METHODS: A total of 227 patients with AEH were retrospectively included in the study. Hysterectomy material was examined as both perioperative frozen section (FS) and paraffin-embedded permanent section (PS). Grade III tumors, grade II tumors larger than 2 cm, over 50% myometrial invasion, cervical involvement, and serous or clear cell histology were considered high-risk. RESULTS: In final pathology, 57 (25.1%) patients had endometrial cancer and 7 (3%) patients had high-risk cancer. Overall analysis of FS/PS agreement yielded a Cohen's Kappa (K) coefficient of 0.420 (moderate agreement). There was moderate (K = 0.526) agreement between FS and PS in detecting tumor grade, and good agreement (K = 0.653) in evaluation of myometrial invasion. CONCLUSION: High-risk endometrial cancer can coexist with AEH. It should be remembered that despite preoperative and FS examinations, these high-risk tumors can be overlooked until final pathology.

Does the primary route of spread have a prognostic significance in stage III non-serous epithelial ovarian cancer?

BACKGROUND: The purpose of this retrospective study was to determine the prognosis of non-serous epithelial ovarian cancer (EOC) patients with exclusively retroperitoneal lymph node (LN) metastases, and to compare the prognosis of these women to that of patients who had abdominal peritoneal involvement. METHODS: A multicenter, retrospective department database review was performed to identify patients with stage III non-serous EOC at 7 gynecologic oncology centers in Turkey. Demographic, clinicopathological and survival data were collected. The patients were divided into three groups based on the initial sites of disease: 1) the retroperitoneal (RP) group included patients who had positive pelvic and /or para-aortic LNs only. 2) The intraperitoneal (IP) group included patients with > 2 cm IP dissemination outside of the pelvis. These patients all had a negative LN status, 3) The IP / RP group included patients with > 2 cm IP dissemination outside of the pelvis as well as positive LN status. Survival data were compared with regard to the groups. RESULTS: We identified 179 women with stage III non-serous EOC who were treated at 7 participating centers during the study period. The median age of the patients was 53 years, and the median duration of follow-up was 39 months. There were 35 (19.6%) patients in the RP group, 72 (40.2%) in the IP group and 72 (40.2%) in the IP/RP group. The 5-year disease-free survival (DFS) rates for the RP, the IP, and IP/RP groups were 66.4%, 37.6%, and 25.5%, respectively (p = 0.002). The 5-year overall survival (OS) rate for the RP group was significantly longer when compared to those of the IP, and the IP/RP groups (74.4% vs. 54%, and 36%, respectively; p = 0.011). However, we were not able to define "RP only disease" as an independent prognostic factor for increased DFS or OS. CONCLUSIONS: Primary non-serous EOC patients with node-positive-only disease seem to have better survival when compared to those with extra-pelvic peritoneal involvement.

Prognostic factors and patterns of recurrence in lymphovascular space invasion positive women with stage IIIC endometriod endometrial cancer.

AIM: The purpose of this study was to determine the prognostic factors and patterns of failure in lymphovascular space invasion (LVSI)-positive women with stage IIIC endometrioid endometrial cancer (EC). METHODS: A multicenter, retrospective, department database review was performed to identify LVSI-positive patients with stage IIIC endometrioid EC at five gynecological oncology centers in Turkey. Demographic, clinicopathological and survival data were collected. RESULTS: We identified 172 LVSI-positive women with stage IIIC endometrioid EC during the study period; 75 (43.6%) were classified as Stage IIIC1 and 97 (56.4%) as Stage IIIC2 . The median age at diagnosis was 59 years, and the median duration of follow up was 34.5 months. The total number of recurrences was 46 (26.7%). We observed 14 (8.1%) locoregional recurrences, 12 (7.0%) retroperitoneal failures and 20 (11.6%) distant relapses. For the entire study cohort, 5-year progression-free survival (PFS) was 67.4%, while the 5-year overall survival (OS) rate was 75.1%. Grade 3 histology (hazard ratio [HR] 2.62, 95% confidence interval [CI] 1.34-5.12; P = 0.005), cervical stromal invasion (HR 2.33, 95% CI 1.09-4.99; P = 0.028) and myometrial invasion (MMI) ≥50% (HR 4.0, 95% CI 1.16-13.69; P = 0.028) were found to be independent prognostic factors for decreased OS. CONCLUSION: Uterine factors such as grade 3 disease, cervical stromal invasion and deep MMI seem to be independently associated with decreased OS in LVSI-positive women with stage IIIC endometrioid EC. The high distant recurrence rate in this subgroup of patients warrants further studies in order to identify the most effective treatment strategy for those patients.

Carcinosarcoma of the ovary compared to ovarian high-grade serous carcinoma: impact of optimal cytoreduction and standard adjuvant treatment.

OBJECTIVE: The purpose of this retrospective study was to compare the prognoses of women with ovarian carcinosarcoma (OCS) who had optimal cytoreductive surgery followed by platinum plus taxane combination chemotherapy to those of women with ovarian high-grade serous carcinoma (HGSC) treated in the same manner. METHODS: A multicenter, retrospective department database review was performed to identify patients with OCS at eight gynecologic oncology centers in Turkey. A total of 54 women with OCS who had undergone optimal cytoreductive surgery followed by platinum plus taxane combination chemotherapy between 1999 and 2017 were included in this case-control study. Each case was matched to two women with ovarian HGSC who had undergone optimal cytoreductive surgery followed by platinum plus taxane combination chemotherapy. The Kaplan-Meier method was used to generate survival data. Factors predictive of outcome were analysed using Cox proportional hazards models. RESULTS: Median disease-free survival (DFS) was 29 months [95% confidence interval (CI) 0-59, standard error (SE) 15.35] versus 27 months (95% CI 22.6-31.3, SE 2.22; p = 0.765) and median overall survival (OS) was 62 versus 82 months (p = 0.53) for cases and controls, respectively. For the entire cohort, the presence of ascites [hazard ratio (HR) 2.32; 95% CI 1.02-5.25, p = 0.04] and platinum resistance [HR 5.05; 95% CI 2.32-11, p < 0.001] were found to be independent risk factors for decreased OS. CONCLUSION: DFS and OS rates of patients with OCS and HGSC seem to be similar whenever optimal cytoreduction is achieved and followed by platinum plus taxane combination chemotherapy.

Impact of lymph node ratio on survival in stage III ovarian high-grade serous cancer: a Turkish Gynecologic Oncology Group study.

OBJECTIVE: The purpose of this study was to investigate the prognostic value of lymph node ratio (LNR) in patients with stage III ovarian high-grade serous carcinoma (HGSC). METHODS: A multicenter, retrospective department database review was performed to identify patients with ovarian HGSC at 6 gynecologic oncology centers in Turkey. A total of 229 node-positive women with stage III ovarian HGSC who had undergone maximal or optimal cytoreductive surgery plus systematic lymphadenectomy followed by paclitaxel plus carboplatin combination chemotherapy were included. LNR, defined as the percentage of positive lymph nodes (LNs) to total nodes recovered, was stratified into 3 groups: LNR1 (<10%), LNR2 (10%≤LNR<50%), and LNR3 (≥50%). Kaplan-Meier method was used to generate survival data. Factors predictive of outcome were analyzed using Cox proportional hazards models. RESULTS: Thirty-one women (13.6%) were classified as stage IIIA1, 15 (6.6%) as stage IIIB, and 183 (79.9%) as stage IIIC. The median age at diagnosis was 56 (range, 18-87), and the median duration of follow-up was 36 months (range, 1-120 months). For the entire cohort, the 5-year overall survival (OS) was 52.8%. An increased LNR was associated with a decrease in 5-year OS from 65.1% for LNR1, 42.5% for LNR2, and 25.6% for LNR3, respectively (p<0.001). In multivariate analysis, women with LNR≥0.50 were 2.7 times more likely to die of their tumors (hazard ratio [HR]=2.7; 95% confidence interval [CI]=1.42-5.18; p<0.001). CONCLUSION: LNR seems to be an independent prognostic factor for decreased OS in stage III ovarian HGSC patients.

Predictors of failure of the commonly used single-dose methotrexate protocol for treating tubal ectopic pregnancies.

OBJECTIVES: This study identified patients who would benefit from an earlier additional medical intervention and/or continuing close surveillance even if commonly used parameters indicated sufficient medical treatment to determine markers of treatment failure. MATERIALS AND METHODS: A retrospective analysis of patients with a preliminary diagnosis of ectopic pregnancy treated with the single-dose methotrexate protocol. Group 1: cases cured with a single dose of methotrexate; Group 2: cases who required more than one dose of methotrexate or surgery following the first dose. Demographics, clinical/sonographic findings, observation period, and ß-human chorionic gonadotropin (hCG) levels were compared among the two groups. Thresholds were defined and a regression analysis was performed to define independent predictors of failure. RESULTS: Data from 120 patients were analyzed: Group 1 (n = 92); Group 2 (n = 28). ß-hCG levels measured at all time points, and day (0-4) and day (4-7) changes, presence of adnexial masses, and infertility were significantly different among the two groups. Only the day (0-4) and day (4-7) changes in ß-hCG levels were independent predictors of failure. CONCLUSION: Day (0-4) thresholds or newly defined day (4-7) thresholds were not more sensitive than the conventional day (4-7) criteria. Day (0-4) ß-hCG levels increased by more than 9.7% in half the patients who required additional methotrexate doses or surgery despite fulfillment of the conventional day (4-7) criteria. In contrast, no cases of treatment failure were observed if the day (0-4) decrease was >26.6%.

Preoperatively Assessable Clinical and Pathological Risk Factors for Parametrial Involvement in Surgically Treated FIGO Stage IB-IIA Cervical Cancer.

OBJECTIVE: Determining the risk factors associated with parametrial involvement (PMI) is of paramount importance to decrease the multimodality treatment in early-stage cervical cancer. We investigated the preoperatively assessable clinical and pathological risk factors associated with PMI in surgically treated stage IB1-IIA2 cervical cancer. METHODS: A retrospective cohort study of women underwent Querleu-Morrow type C hysterectomy for cervical cancer stage IB1-IIA2 from 2001 to 2015. All patients underwent clinical staging examination under anesthesia by the same gynecological oncologists during the study period. Evaluated variables were age, menopausal status, body mass index, smoking status, FIGO (International Federation of Obstetrics and Gynecology) stage, clinically measured maximal tumor diameter, clinical presentation (exophytic or endophytic tumor), histological type, tumor grade, lymphovascular space invasion, clinical and pathological vaginal invasion, and uterine body involvement. Endophytic clinical presentation was defined for ulcerative tumors and barrel-shaped morphology. Two-dimensional transvaginal ultrasonography was used to measure tumor dimensions. RESULTS: Of 127 eligible women, 37 (29.1%) had PMI. On univariate analysis, endophytic clinical presentation (P = 0.01), larger tumor size (P < 0.001), lymphovascular space invasion (P < 0.001), pathological vaginal invasion (P = 0.001), and uterine body involvement (P < 0.001) were significantly different among the groups with and without PMI. In multivariate analysis endophytic clinical presentation (odds ratio, 11.34; 95% confidence interval, 1.34-95.85; P = 0.02) and larger tumor size (odds ratio, 32.31; 95% confidence interval, 2.46-423.83; P = 0.008) were the independent risk factors for PMI. Threshold of 31 mm in tumor size predicted PMI with 71% sensitivity and 75% specificity. We identified 18 patients with tumor size of more than 30 mm and endophytic presentation; 14 (77.7%) of these had PMI. CONCLUSIONS: Endophytic clinical presentation and larger clinical tumor size (>3 cm) are independent risk factors for PMI in stage IB-IIA cervical cancer. Approximately 78% of the patients with a tumor size of more than 3 cm and endophytic presentation will require adjuvant chemoradiation for PMI following radical surgery. Considering clinical tumor presentation along with tumor size can enhance the physician's prediction of PMI in early-stage cervical cancer.