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Objective To compare oncological outcomes in women with lower uterine segment involvement (LUSI) in endometrial carcinoma (EC) stage ≥ II - staged by a minimally invasive surgery (MIS) versus laparotomy. Study design A retrospective multi-center cohort study. Univariate analysis, Kaplan-Meier survival and Cox proportional hazard analysis were performed to compare between women staged by MIS and those staged by laparotomy. Results Over a median follow-up period of 3 years (interquartile range, 1.5–6 years) 212 women were included, 68 (32.1%) were surgically staged by MIS. Stages of disease did not vary between MIS and laparotomy and were 32.1%, 51.9%, and 16.0%, in stages II, III and IV – respectively. Adjuvant radiation and chemotherapy rate did not differ between groups. Overall recurrence rate was comparable (p = 0.084). Locoregional recurrence rate was higher in the MIS group odds ratio 2.17, 95% confidence interval 1.19–4.20). Overall and progression free survival were similar in both groups (log rank test p = 0.08 and p = 0.912 respectively). In Cox regression model adjusting for age, comorbidities, tumor grade, stage and adjuvant therapy, route of surgery (MIS vs. laparotomy) was not associated with overall survival (p = 0.169). Conclusions In women with advanced EC and LUSI, although MIS is associated with locoregional recurrences, survival is comparable to laparotomy.

ObjectiveEndometrial cancer prognosis is related to stage, histology, myometrial invasion, and lymphovascular space invasion. Several studies have examined the association between pretreatment thrombocytosis and patient outcomes with contrasting results regarding prognosis. Our aim was to evaluate the association of pretreatment platelet count with outcomes in endometrial cancer patients.MethodsThis is an Israeli Gynecologic Oncology Group multicenter retrospective cohort study of consecutive patients with endometrial cancer, who underwent surgery between January 2002 and December 2014. Patients were grouped as low risk (endometrioid G1-G2 and villoglandular) and high risk (endometrioid G3, uterine serous papillary carcinoma, clear cell carcinoma, and carcinosarcoma). Those with stage I disease were compared with stages II–IV. Disease stages were reviewed and updated to reflect International Federation of Gynecology and Obstetrics (FIGO) 2009 staging. All patients underwent pelvic washings for cytology and total abdominal or laparoscopic hysterectomy with bilateral salpingo-oophorectomy. Pelvic lymph node assessment was performed in patients with tumors of moderate–high risk histology or deep myometrial invasion. Para-aortic sampling was performed at the surgeon’s discretion. Patients were categorized by pretreatment platelet count into two groups: ≤400×109/L and >400×109/L (defined as thrombocytosis). Clinical and pathological features were compared using Student t-test, χ2 or Fisher’s exact test. Survival measures were plotted with the Kaplan-Meier method and compared using the log-rank test. A Cox proportional hazards model was used for multivariable comparison of associations.ResultsOf the 1482 patients included, most had stage I disease (961; 74.8%) and most had endometrioid histology (927; 64.1%). A total of 1392 patients (94%) had pretreatment platelet counts ≤400×109/L and 90 (6%) had pretreatment thrombocytosis. Patients with thrombocytosis had a significantly higher rate of high-grade malignancy, advanced stage, lymphovascular space invasion, low uterine segment involvement, and lymph node metastases. They also had shorter 5 year disease-free survival (65% vs 80%, p=0.003), disease-specific survival (63% vs 83%, pConclusionsPretreatment thrombocytosis is an independent prognostic factor for decreased disease-specific survival and overall survival among patients with endometrial cancer, and can serve as a predictor of poor outcome.

No current screening methods for high-grade ovarian cancer (HGOC) guarantee effective early detection for high-risk women such as germline BRCA mutation carriers. Therefore, the standard-of-care remains risk-reducing salpingo-oophorectomy (RRSO) around age 40. Proximal liquid biopsy is a promising source of biomarkers, but sensitivity has not yet qualified for clinical implementation. We aimed to develop a proteomic assay based on proximal liquid biopsy, as a decision support tool for monitoring high-risk population. Ninety Israeli BRCA1 or BRCA2 mutation carriers were included in the training set (17 HGOC patients and 73 asymptomatic women), (BEDOCA trial; ClinicalTrials.gov Identifier: NCT03150121). The proteome of the microvesicle fraction of the samples was profiled by mass spectrometry and a classifier was developed using logistic regression. An independent cohort of 98 BRCA mutation carriers was used for validation. Safety information was collected for all women who opted for uterine lavage in a clinic setting. We present a 7-protein diagnostic signature, with AUC0.97 and a negative predictive value (NPV) of 100% for detecting HGOC. The AUC of the biomarker in the independent validation set was0.94 and the NPV99%. The sampling procedure was clinically acceptable, with favorable pain scores and safety. We conclude that the acquisition of Müllerian tract proximal liquid biopsies in women at high-risk for HGOC and the application of the BRCA-specific diagnostic assay demonstrates high sensitivity, specificity, technical feasibility and safety. Similar classifier for an average-risk population is warranted.

Objective To compare outcomes of symptomatic and asymptomatic women with endometrial cancer and a preoperative diagnosis of an endometrial polyp. Design An Israel Gynecologic Oncology Group multi-center retrospective cohort study. Methods Of 635 patients with endometrial cancer and a preoperative diagnosis of an endometrial polyp who underwent surgery between 2002 and 2014 in one of 11 centers in Israel were divided into two groups according to the presence of bleeding symptoms. Outcome measures included recurrence-free survival, disease-specific survival and overall survival. Survival data were plotted according to the method of Kaplan and Meier and compared using the log-rank test. Results There were 513 symptomatic and 122 asymptomatic women with endometrial cancer and a preoperative diagnosis of an endometrial polyp. The median follow-up was 52 months (range 12-120 months). There were no differences between patients who experienced bleeding and those who did not in 5-year recurrence-free survival (85.2 % vs. 85.7 %; p=0.83, respectively), disease-specific survival (88.2 % vs. 89.2 %; p=0.71, respectively), or overall survival (80.2% vs. 78.4 %; p=0.97, respectively). Conclusion The diagnosis of endometrial cancer in patients with asymptomatic endometrial polyps is not associated with improved outcomes as compared with patients with bleeding. In the absence of factors indicating a high risk of endometrial cancer, clinical and sonographic follow-up is the advised management strategy for these patients.

Background This retrospective study compared perioperative measures, costs, quality of life and survival after open vs. robotic surgery, among obese women diagnosed with low-grade endometrial cancer. Methods Obese women (body mass index (BMI) ≥ 30) who underwent open or robotic surgery for endometrial cancer, in one of two tertiary medical centers in the center of Israel, 2013–2016, postoperative grade 1–2, were included. Costs per patient, including 30-days post-surgery were calculated. Quality of life was evaluated by Physical and Mental Components of the SF-36 and a recovery from surgery questionnaire. Overall survival outcomes were obtained from patients’ files. Surgical outcomes, including operating and anesthesia times, length of hospital stay, and intraoperative and postoperative complications according to the Clavien-Dindo classification scale were reviewed. Results In all, 138 women with BMI ≥30 underwent open (n = 61) or robotic surgery (n = 77) during the study period. The groups had similar BMI, comorbidities, demographics and tumor characteristics. Robotic surgery was associated with shorter hospital stays (mean 1.7 vs. 4.8 days; P > 2, 5.2% vs. 19.7%; P = .0008), but longer operating theater time (3.8 vs. 2.8 h; P P P P P = 0.330). Conclusions Obese women with low-grade endometrial cancer had better quality of life after robotic vs. open surgery. They also had shorter hospital stays and fewer postoperative complications. Centers with high volumes of robotic surgery can achieve similar costs when comparing both methods. These results were achieved without jeopardizing survival. Our results further emphasize the need for the Israeli healthcare system to include specific reimbursement for robotic procedures in the population we studied.

INTRODUCTION Advanced age is considered an adverse factor in endometrial cancers but may be a surrogate for other conditions that impact outcomes. The study objective was to assess the association of age with endometrial cancer features, treatment and prognosis. MATERIAL AND METHODS In this multicenter cohort study, consecutive women with endometrial cancer treated at 10 Israeli institutions between 2000 and 2014 were accrued in an assimilated database. Postmenopausal women were stratified into age groups with a cut-off of 80. Clinical, pathological and treatment data were compared using t test or Mann-Whitney test for continuous variables, and Chi-square Test or Fisher's Exact test for categorical variables. Main outcome measures included disease recurrence and disease-specific and overall survival; these were plotted using the Kaplan-Meier method and compared using the log-rank test. The association between age and recurrence and survival, adjusted for other clinical and pathological factors, was assessed using multivariable Cox regression modeling. RESULTS A total of 1764 postmenopausal women with endometrial cancer were identified. Adverse pathological features were more prevalent in older women, including high-risk histologies (35% vs 27%, P = .025), deep myoinvasion (44% vs 29%, P = .001) and lymphovascular involvement (22% vs 15%, P = .024). Surgical staging was performed less frequently among older women (33% vs 56%; P

Objective: To evaluate perioperative outcomes and complications in elderly patients with endometrial cancer undergoing surgical staging with robotic assisted laparoscopy (RAL) versus laparotomy. De...

Objectives Primary, to explore correlation between the extent of pelvic lymphadenectomy in the surgical staging of endometrial cancer and the number of nodes with metastasis. Secondary, evaluate survival measures in relation to the number of excised nodes. Methods A retrospective multi-center study of prospectively collected information of 2014 women with endometrial cancer, 1032 of whom underwent lymph node staging. Spearman's rank correlation was used to assess the correlation between the number of pelvic nodes excised and the number of metastatic nodes. Women's data were dichotomized by the median number of excised pelvic nodes. Kaplan-Meier and log rank tests were used to examine the effect of the number of pelvic nodes excised on survival. Results There was no significant correlation between the number of pelvic nodes harvested and the number of metastatic lymph nodes (r = 0.301; p = 0.28). The median number of excised pelvic nodes was 9 (range 1–77). There was no difference between women with up to 9 and women with more than 9 lymph nodes excised in the 5-year recurrence-free survival (82.4% vs. 83.9%; p = 0.90), disease-specific survival (83.6% vs. 86.7%; p = 0.37), or overall survival (75.8% vs. 82.8%; p = 0.11). Conclusions The extent of pelvic lymphadenectomy in the surgical staging of endometrial cancer is not associated with a higher yield of metastatic nodes or with longer survival. Current focus should be on sentinel node procedures that offer women the benefit of accurate staging without the complications associated with extensive lymphadenectomy.

Endometrial cancer is the most common gynecologic malignancy in developed countries. The overall risk of recurrence is associated with traditional risk factors.Machine learning was used to predict recurrence among women who were diagnosed and treated for endometrial cancer between 2002 and 2012 at elven university-affiliated centers. The median follow-up time was 5 years. The following data were retrieved from the medical records and fed into the algorithm: age, chronic metabolic diseases, family and personal cancer history, hormone replacement therapy use, endometrial thickness, uterine polyp presence, complete blood count results, albumin, Ca-125 level, surgical staging, histology, depth of myometrial invasion, LVSI, grade, pelvic washing cytology, and adjuvant treatment. We used XGBoost algorithm, which fits the training data using decision trees, and can also rate the factors according to their influence on the prediction.1935 women were identified of whom 325 had recurrent disease. On the randomly picked samples, the specificity was 55% and the sensitivity was 98%. Our model showed an operating characteristic curve with AUC of 0.84.A machine learning algorithm presented promising ability to predict recurrence of endometrial cancer. The algorithm provides an opportunity to identify at-risk patients who may benefit from adjuvant therapy, tighter surveillance, and early intervention.

Successful embryo implantation is associated with intensive endometrium matrix remodeling, in which fibrillar collagens and matrix metalloproteinases play a key role. Here we report that topical treatment with a single dose of human collagenase-1 improves the rate of embryo implantation in murine models regardless of genetic background. Collagenase-1 treatment reduces endometrial collagen-fiber tension affecting their aligned configuration while preserving the overall integrity of the uterine tissue. The collagenase treatment causes enhanced local vascular permeability and creates an inflammatory-like environment, all of which are necessary for successful embryo implantation. We show that this specific treatment rescued heat stress and embryo transfer induced embryo failure in mice. Our findings highlight the clinical feasibility to improve endometrial receptivity for embryo implantation. This treatment approach may be used to improve livestock breeding and for assisted human reproduction medical treatments.TeaserMild specific collagen remodeling improves endometrial receptivity for natural and embryo- transfer-derived embryo implantation.

Objective To compare survival measures of women with early-stage endometrial cancer who underwent either hysteroscopy or a non-hysteroscopic procedure as a diagnostic procedure. Study design An Israel Gynecologic Oncology Group multicenter study of 1324 patients with stage I endometrial cancer who underwent surgery between 2002 and 2014. Patients were divided into two groups: hysteroscopy and non-hysteroscopy (curettage or office endometrial biopsy). Clinical, pathological, and survival measures were compared between the groups. Results There were 355 patients in the hysteroscopy group and 969 patients in the non-hysteroscopy group. The median follow-up was 52 months (range 12–120 months). There were no differences between the groups in the 5-year recurrence-free survival (90.2% vs. 88.2%; p = 0.53), disease-specific survival (93.4% vs. 91.7%; p = 0.5), and overall survival (86.2% vs. 80.6%; p = 0.22). Conclusion Our findings affirm that hysteroscopy does not compromise the survival of patients with early-stage endometrial cancer.

OBJECTIVES To evaluate the prognostic significance of neutrophil-to-lymphocyte ratio (NLR) upon diagnosis, and its impact on surgical outcome, among patients with advanced stage ovarian carcinoma treated with neoadjuvant chemotherapy (NACT). METHODS A retrospective cohort study included all women with stage IIIC and IV ovarian carcinoma receiving NACT in Rabin Medical Center, Petah-Tikva, Israel; January 1, 2005, to June 30, 2017. Demographics and treatment outcome were compared between patients with NLR at diagnosis ≥6.0 and those with NLR

Objective To assess whether statin use by endometrial cancer patients was associated with a survival advantage. Methods A retrospective chart review study, by the Israeli Gynecologic Oncology Group, of consecutive endometrial cancer patients who underwent surgery in one of 11 medical centers between 2002 and 2014. Clinical and pathological reports, and measures of survival were compared between statin users and nonusers. Kaplan-Meier and Cox proportional hazard models were used to assess the effect of using statins on survival measures. Results Over a mean follow-up period of 6.2 years (range, 1-12 years) for 2017 endometrial cancer patients with complete data, 663 (32.8%) used statins prior to diagnosis and 1354 (67.1%) did not. No statistically significant differences between the groups were observed for most demographic and clinical characteristics. There was no difference between statin users and nonusers in 5-year recurrence-free survival (82% vs 83%; P=0.508), disease-specific survival (86% vs 84%; P=0.549), or overall survival (77% vs 75%; P=0.901). Conclusions In this large cohort of patients with endometrial cancer, no significant associations were found between use of statins and endometrial cancer survival.

High-grade ovarian cancer (HGOC) is the leading cause of mortality from gynecological malignancies, because of diagnosis at a metastatic stage. Current screening options fail to improve mortality because of the absence of early-stage-specific biomarkers. We postulated that a liquid biopsy, such as utero-tubal lavage (UtL), may identify localized lesions better than systemic approaches of serum/plasma analysis. Further, while mutation-based assays are challenged by the rarity of tumor DNA within nonmutated DNA, analyzing the proteomic profile, is expected to enable earlier detection, as it reveals perturbations in both the tumor as well as in its microenvironment. To attain deep proteomic coverage and overcome the high dynamic range of this body fluid, we applied our method for microvesicle proteomics to the UtL samples. Liquid biopsies from HGOC patients (n = 49) and controls (n = 127) were divided into a discovery and validation sets. Data-dependent analysis of the samples on the Q-Exactive mass spectrometer provided depth of 8578 UtL proteins in total, and on average ∼3000 proteins per sample. We used support vector machine algorithms for sample classification, and crossed three feature-selection algorithms, to construct and validate a 9-protein classifier with 70% sensitivity and 76.2% specificity. The signature correctly identified all Stage I lesions. These results demonstrate the potential power of microvesicle-based proteomic biomarkers for early cancer diagnosis.

Little is known on the impact of neoadjuvant chemotherapy (NACT) treatment modifications on surgical outcome and progression-free survival (PFS) in patients with ovarian carcinoma. We aimed to report the changes we made during NACT and to evaluate its impact on patient outcome.A retrospective cohort study of all women with advanced stage ovarian carcinoma treated with NACT followed by interval cytoreduction in one university-affiliated medical center (January 2005 to June 2017). We excluded those who were treated with NACT without any surgical intervention. NACT modifications included delay in treatment, change in chemotherapy, and dose reduction. Demographics, tumor characteristics, surgical outcome, and PFS were compared between patients exposed to NACT treatment modifications and those who received standard treatment.Seventy-nine patients met inclusion criteria of whom, 59 patients received standard, nonmodified treatment and 20 patients modified NACT. There were no intergroup differences with respect to age at diagnosis (59.5±11.6 vs. 64.70±8.09, P=0.09) and stage of disease (P=0.13). Radiologic complete response rates (25.0% vs. 32.2%, P=0.545) and optimal cytoreduction rates (75.0% vs. 86.4%, P=0.23) were similar in both treatment groups. Mean PFS (in months) was comparable between patients receiving standard treatment and those who required NACT modifications (18.5 vs. 12.2, P=0.125).NACT treatment modifications did not affect surgical outcome and PFS. We conclude that when clinically indicated, dose alteration and scheduling can be implemented without apparent detriment to outcome.

Study Objective To compare oncological outcomes of women with stage II -IIIc endometrial cancer (EC) who underwent minimally invasive surgery (MIS) versus laparotomy. Design A retrospective cohort study. Setting Academic multi-center. Patients or Participants Consecutive women with EC treated at 11 Israeli institutions between 2002 and 2017 were recorded in an assimilated database with a median follow-up of 52 months (range 12-120 months). Women with stage II -IIIc were stratified into groups by intentional route of surgery; MIS vs. laparotomy. Clinical, pathological and outcome data were compared. Interventions MIS and laparotomy. Measurements and Main Results Three hundred and four women met criteria: 200 underwent laparotomy and 104 MIS. Women in the MIS group were younger, had lower rate of diabetes and lower CA-125 level. Women who underwent laparotomy had higher grade EC and more advanced stage disease; Odds Ratio (OR) and 95% Confidence Interval (CI) 0.34 (0.21-0.56) and 0.56 (0.34-0.92), respectively. Brachytherapy rate was comparable between groups (p=0.715). In a multivariable analysis, including age, comorbidities, disease stage, tumor grade and lymph-vascular space invasion, MIS was not associated with an increased risk for recurrence, progression or decreased overall survival. However, patients operated by MIS had higher risk to recur locally (vaginal cuff or pelvic) (26.9% vs. 16.5%, p=0.032, OR, 1.86, 95% CI 1.05-3.30). MIS was the only independent factor associated with local recurrence, adjusted OR, 2.09, 95% CI 1.12-3.90. Conclusion In women with stage II-IIIc EC, MIS was associated with an increased risk for local recurrence compared to laparotomy.

Women with cervical cancer who undergo radical hysterectomy are often treated postoperatively with chemoradiation. Patient selection that minimizes adjuvant treatment is valuable. We compared two methods for predicting postoperative adjuvant treatment of women with tumor size ≥2 cm and4 cm.This multicenter retrospective study included 272 women with tumor size ≥2 cm and4 cm. A receiver operating characteristic curve (ROC) analysis was used to determine the optimal tumor cutoff size to predict adjuvant treatment. A second analysis compared the rate of adjuvant treatment between women with and without lymph vascular space involvement (LVSI).According to the ROC, the optimal cutoff value of tumor size for predicting adjuvant treatment was 2.95 cm (sensitivity 0.70, specificity 0.67). Tumors were ≥3.0 cm in 166 (61.0%) women. The rate of adjuvant treatment was higher in women with larger tumor diameter (73.8% vs. 47.9%, p 0.0001). Of the 241 women with a LVSI record, LVSI was present in 81 (34%) women. Among women with LVSI, rates were higher of positive lymph nodes (41.0% vs 14.5%, p 0.0001) and postoperative adjuvant treatment (83.3% vs. 53.7%, p 0.001). Among women with tumor size ≥3.0 cm and LVSI, the rate of adjuvant treatment was 90.0%. In the multivariate analysis, both tumor size ≥3.0 cm and the presence of LVSI were independently associated with adjuvant treatment (OR 3.9, 95% CI 2.1-7.1; p 0.0001 and OR 4.9, 95% CI 2.4-10.0; p 0.0001, respectively).In women with cervical cancer who underwent radical hysterectomy, tumors ≥3 cm were associated with a70% rate of adjuvant treatment, and LVSI was associated with a80% rate. These data should be weighed in multidisciplinary consultation with radiation oncologists when deciding treatment strategy.

Objectives: We aimed to investigate whether surgery for adnexal detorsion within 6 h from admission to the hospital was associated with less adnexal ischemia. Design: This is a retrospective cohort study. Participants/Materials, Setting, and Methods: This retrospective study was conducted at two university-affiliated medical centers and assessed women aged 18–45 years with adnexal torsion who were hospitalized within 12 h from the pain onset and underwent surgery for detorsion within 24 h. The study group was divided into 2 groups: early, surgical intervention within less than 6 h and late, surgical intervention between 6 and 24 h. The primary outcome was the rate of macroscopic appearance of ischemic adnexa. Results: Two hundred and twenty women fulfilled the inclusion criteria. In 101 women, the adnexa with the torsion appeared macroscopically ischemic. There was no difference in ischemic adnexa between the early and late intervention groups (48% vs. 40%; p = 0.269). No significant association was found between the physical examination or ultrasonographic findings and the rate of ischemic adnexa within each group. Limitations: The main limitations of our study are its retrospective nature. Much of the clinical and ultrasonographic data are subjective and operator-dependent. The decision to operate may vary from one surgeon to another. Conclusion: Immediate surgical intervention in patients with adnexal torsion is not associated with a lower rate of adnexal ischemia. These findings suggest that in acute adnexal torsion, there is a wider time window for a thorough evaluation before surgery.

We aimed to assess the association of pre-operatively evaluated ultrasonographic endometrial thickness with outcomes of patients with endometrial cancer.An Israel Gynecologic Oncology Group multicenter retrospective cohort study of consecutive patients with endometrial cancer who underwent surgery between 2002 and 2014 in one of eleven academic centers. Patients were categorized by endometrial thickness into two groups: ≤20 mm and20 mm. Clinical and pathological features were compared using Student T-test for continuous variables and Chi-square or Fisher's exact test for categorical variables. Survival measures were plotted with the Kaplan-Meier method and compared using the log-rank test. A Cox proportional hazards model was used for multivariable comparison of associations.1113 patients in whom endometrial thickness data was recorded were the subject of this study and included 2 groups: ≤20 mm (n = 930),20 mm (n = 183). The median follow-up was 52 months (range 12-120 months). Patients with endometrial thickness20 mm had significantly lower recurrence-free survival (log rank, p .0001), disease-specific survival (log rank, p = .01), and overall survival (log rank, p .0001). On multivariate Cox proportional hazards analysis, endometrial thickness20 mm remained independently associated with an increased hazard of recurrence and death (HR = 1.77, 95% CI 1.07-2.96, p = .03 for recurrence; and HR = 1.68; 95% CI 1.07-2.65; p = .03 for overall survival).In patients with endometrial cancer, endometrial thickness20 mm as measured preoperatively by ultrasound, is independently associated with decreased recurrence-free and overall survival. This finding suggests that thick endometrium may be considered as one of the risk factors for poor prognosis.

The treatment of elderly patients with advanced stage ovarian carcinoma is challenging due to a high morbidity.To evaluate the clinical course and outcome of elderly patients with advanced stage ovarian carcinoma receiving neoadjuvant chemotherapy (NACT).A retrospective study of all patients with stage IIIC and IV ovarian carcinoma receiving NACT in one medical center (between 2005 and 2017). The study group criteria age was above 70 years. The control group criteria was younger than 70 years old at diagnosis. Demographics and treatment outcomes were compared between groups. Primary outcomes were progression-free survival (PFS) and overall survival (OS).Overall, 105 patients met the inclusion criteria, 71 patients (67.6%) were younger than 70 years and 34 patients (32.4%) older. Rates of interval cytoreduction were significantly higher in younger patients (76.1% vs. 50.0%, P = 0.01). Of those who underwent interval cytoreduction, no difference was found in rates of optimal debulking between groups (83.35% vs. 100%, P = 0.10). Using a Kaplan-Meier survival analysis, no significant differences were observed between groups in PFS or OS, P0.05. Among the elderly group alone, patients who underwent interval cytoreduction had significantly longer PFS than those without surgical intervention (0.4 ± 1.7 vs. 19.3 ± 19.4 months, P = 0.001).Elderly patients with ovarian carcinoma who received NACT undergo less interval cytoreduction than younger patients, with no difference in PFS and OS. However, among the elderly, interval cytoreduction is associated with significantly higher PFS.

Objectives Data on the outcome of stage IIA1 cervical cancer is limited, as these tumors comprise a small percentage of early tumors. NCCN guidelines suggest consideration of surgical management for small tumors with vaginal involvement. Our objective was to evaluate the risk of adjuvant radiotherapy in stage IIA1 cervical cancer and its associated features, in order to improve selection of patients for surgical management. Methods A retrospective cohort study comparing surgically treated cervical cancer patients with stage IB1 and stage IIA1 disease. Women treated between 2000 and 2015 in ten Israeli medical centers were included. Patient and disease features were compared between stages. The relative risk (Fisher's exact test) of receiving post-operative radiation was calculated and compared for each risk factor. A general linear model (GLM) was used for multivariable analysis. Results 199 patients were included, of whom 21 had stage IIA1 disease. Most features were comparable for stage IB1 and stage IIA1 disease, although patients with vaginal involvement were more likely to have close surgical margins (23.8% vs 8.5%, p = 0.03). Patients with stage IIA1 disease were more likely to receive radiation after surgery (76% vs. 46%, RR = 1.65 (1.24–2.2), p = 0.011). Vaginal involvement as well as depth of stromal invasion, LVSI and lymph node metastases were independent predictors of radiation on multivariable general linear modeling. Conclusions Cervical cancer patients with vaginal involvement are highly more likely to require postoperative radiation. We recommend careful evaluation of these patients before surgical management is offered.

Study Objective To compare oncological outcomes of women with high-grade endometrial carcinoma (HGEC) who underwent surgery by minimally invasive surgery (MIS) versus laparotomy. Design A retrospective cohort study. Setting Academic multi-center. Patients or Participants Consecutive women with HGEC cancer treated at 11 Israeli institutions between 2002 and 2017 were accrued in an assimilated database with a median follow-up of 52 months (range 12-120 months). Women with HGEC were stratified into two groups by route of surgery; MIS vs. laparotomy by an intention to treat. Clinical, pathological and outcome data were compared. Interventions MIS and laparotomy. Measurements and Main Results Six hundred and seventy-eight women met the inclusion criteria: 160 underwent MIS and 518 laparotomy. The two groups were comparable in demographic and clinical characteristics. Local recurrence was more common in the MIS group, Odds Ratio (OR) 95% Confidence Interval (CI) 2.80 (1.80-4.36). Disease progression rates were comparable (p=0.537). In a multivariable analysis, including age, comorbidities, disease stage, CA-125 and lymph-vascular space invasion, MIS was not associated with an increased risk for either overall recurrence rate, disease progression, or overall survival. Independent risk factors for local recurrence were diabetes, stage III-IV, LVSI and MIS, adjusted OR 95% CI 3.30 (1.69-6.48). Conclusion In women with HGEC, MIS is associated with higher rates of local recurrence as compared to laparotomy.

Objectives Bevacizumab is used in combination with chemotherapy in advanced stage ovarian carcinoma. Clinical trials have shown improved progression-free survival in these patients. Nevertheless, its impact on overall survival (OS) remains unclear. Hence, we aimed to evaluate the impact of bevacizumab on OS in real-world patients, treated outside of clinical trials. Methods A retrospective cohort study of all patients with advanced stage epithelial ovarian carcinoma (Stage III and IV) treated in one university affiliated medical center (2000–6/2017). Demographics and treatment outcome were compared between patients receiving bevacizumab in addition to standard chemotherapy to those treated with chemotherapy alone before the incorporation of bevacizumab into clinical practice. P value Results Overall, 188 patients met inclusion criteria. Of them, 59 (31.4%) received bevacizumab and 129 (68.6%) received chemotherapy only. Median age and levels of CA-125 at diagnosis did not differ between patients receiving bevacizumab and those who did not (61 vs. 62 years, p=0.75 and 638 vs 561 U/mL, p=0.78, respectively). Rates of stage IV disease were similar between groups (16.9% vs 12.4%, p=0.4). Rates of optimal cytoreduction ( Conclusions In our center, the addition of bevacizumab to standard chemotherapy in patients with advanced stage ovarian carcinoma had no impact on OS.

Objectives We aimed to evaluate the impact of first-to-second progression free survival (PFS1/PFS2) ratio on overall survival (OS) in patients with ovarian cancer. Methods A retrospective cohort study of all patients with ovarian carcinoma treated in one university-affiliated medical center (2000–7/2017). We included patients who had at-least a second recurrence. We included patients who were initially platinum sensitive, therefore patients with first progression-free survival (PFS) less than 12 months were excluded. Study groups included patients with PFS1/PFS2 P value Results Overall, 65 patients met inclusion criteria. In this cohort, the mean of first PFS was 64.6±54.3 months, and the mean for the second PFS was 20.8±32.4. Overall, 13 (20%) had PFS1/PFS2 Conclusions In patients with ovarian cancer, longer first PFS seems to be associated with longer second PFS. However, first-to-second PFS ratio does not predict OS.

Objectives To compare survival measures of women with early-stage endometrial cancer who underwent either hysteroscopy or a non-hysteroscopic procedure as a diagnostic procedure. Methods An Israel Gynecologic Oncology Group multicenter study of 1324 patients with stage I endometrial cancer who underwent surgery between 2002 and 2014. Patients were divided into two groups: hysteroscopy and non-hysteroscopy (curettage or office endometrial biopsy). Clinical, pathological, and survival measures were compared between the groups. Results There were 355 patients in the hysteroscopy group and 969 patients in the non-hysteroscopy group. The median follow-up was 52 months (range 12–120 months). There were no differences between the groups in the 5-year recurrence-free survival (90.2% vs. 88.2%; p=0.53), disease-specific survival (93.4% vs. 91.7%; p=0.5), and overall survival (86.2% vs. 80.6%; p=0.22). Conclusions Our findings affirm that hysteroscopy does not compromise the survival of patients with early-stage endometrial cancer.

Objectives Biopsy proven newly diagnosed Low-grade Squamous Intraepithelial lesions(LGSIL), are considered reversible lesions and as such are usually treated conservatively with follow-up or ablation. In this study we aimed to evaluate the outcome of women with LGSIL who underwent surgical conization, and assess risk factors for higher risk disease. Methods We performed a retrospective study of all patients who underwent surgical conization for LGSIL disease, in one university affiliated medical center (2012–2017). Study group was defined as patients who had their histological classification upgraded, and control group as patients who were either downgraded or diagnosis remained. Demographics, histological outcome and indications were compared between groups. Results Overall, 111 patients met inclusion criteria of whom 44(39%) were histologically upgraded, 1 patient was found to have Adenocarcinoma of the cervix. Upgraded women were younger (34y vs 44y, p Conclusions Contrary to common practice, in this study, younger women with a biopsy diagnosis of LSIL, should be evaluated for high risk disease especially if they report PCB.

Objective To assess the rate of postoperative adjuvant treatment in patients who underwent radical hysterectomy for early cervical cancer and to suggest criteria for the triage of patients who have a high probability of multimodality treatment. Methods This was a multicenter retrospective study of 514 patients with FIGO stages IA2-IIA cervical cancer who underwent radical hysterectomy between 1999 and 2010. The patients were divided into 2 groups according to whether or not postoperative radiation was administered. The 2 groups were compared with regard to clinical and histopathologic variables divided into major and minor criteria (intermediate risk factors) based on lymph nodes status, parametrial involvement, tumor size, deep stromal invasion, and lymph-vascular space invasion. Results We identified 294 (57.2%) patients who received adjuvant postoperative radiotherapy (RT) or chemoradiation. Fifty-three percent of these patients who were treated by adjuvant radiation had only intermediate risk factors. Combining the various combinations of 2 out of 3 of the following criteria, we found that 89% of patients with tumors ≥2 cm and lymph-vascular space invasion received RT, 76% of patients with tumors ≥2 cm and depth of invasion >10 mm received RT, and 87% of patients with tumors depth of invasion >10 mm and lymph-vascular space invasion received RT. Conclusions This study suggests that in patients with early cervical cancer, clinicopathologic evaluation of tumor size and lymph-vascular space invasion should be undertaken before performing radical hysterectomy. This approach can serve to tailor treatment, reducing the rate of employing both radical hysterectomy and chemoradiation.

Highlights • Extra-peritoneal metastasis is uncommon in epithelial ovarian carcinoma. • Metastasis of epithelial ovarian carcinoma to axillary lymph node is rare. • Lymphatic drainage system can explain the rout of this distant metastasis. • Tissue diagnosis is the mainstay in identifying the origin of axillary metastasis.

The vast majority of high-grade ovarian cancer (HGOC) patients are diagnosed at a metastatic stage, resulting in exceptionally low cure rates. Current screening options fail to improve mortality due to the absence of early-stage-specific biomarkers and the poor systemic representation of early-stage tumors. We postulated that a gynecologic liquid biopsy, such as utero-tubal lavage (UtL), may identify localized lesions better than systemic approaches of serum/plasma analysis. Furthermore, while mutation-based assays are challenged by the rarity of tumor DNA within nonmutated DNA, analyzing the proteomic profile may potentially enable earlier detection, as it reveals perturbations in both the tumor compartment as well as in its microenvironment. To attain deep proteomic coverage and overcome the high dynamic range of this body fluid, we isolated microvesicles and performed mass spectrometric proteomic analysis of the UtL samples. Liquid biopsies from HGOC patients (n=85), controls (n=183), and healthy BRCA mutation carriers (n=37), were divided into discovery and validation sets. Data-dependent analysis of the samples on the Q-Exactive mass spectrometer provided depth of 8,578 UtL proteins in total, and on average ~3,000 proteins per sample. We used support vector machine algorithms for sample classification, and crossed three feature-selection algorithms, to construct and validate a 9-protein classifier with 63% sensitivity and 73% specificity. The signature correctly identified all Stage I lesions and highlighted increased risk in healthy BRCA carriers. These results demonstrate the potential power of microvesicle-based proteomic biomarkers for early cancer diagnosis but require integration with other biomarker types for improved prediction. Citation Format: Georgina D. Barnabas, Keren Bahar-Shany, Stav Sapoznik, Jacob Korach, Tamar Perri, Eitan Friedman, David Stockheim, Ariella Jakobson-Setton, Ram Eitan, Limor Helpman, Yfat Kadan, Sarit Aviel-Ronen, Michal Harel, Tamar Geiger, Keren Levanon. Proteomic biomarker for detection of ovarian cancer using gynecologic liquid biopsy [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr B06.

Ascites is a common finding in patients with ovarian cancer. Paracentesis is a relatively simple, safe, and effective procedure for draining fluid from the peritoneum, but valid quality-of-life tools are needed to determine its subjective value for alleviating symptoms and improving patient quality of life. The objective of this study was to prospectively evaluate the performance of a novel Ascites Symptom Mini-Scale (ASmS) and compare it with a previously available questionnaire.Patients with ovarian cancer-related ascites presenting for paracentesis were asked to complete the newly devised ASmS before the procedure and 1 and 24 hours after. Patients also completed a pain assessment scale and a previously validated ascites questionnaire at the same time points.The cohort included 28 patients of median age 68 years (range, 51-86 years), 13 (46.4%) with primary ovarian cancer and 15 with recurrent disease. A median of 3300 mL of ascites was drained. The median score on the ASmS decreased significantly from 21.5 before paracentesis to 11.0 at 1 hour after paracentesis (P0.001) and remained low at 24 hours. No demographic factor predicted greater benefit from the procedure. Patients with both mild and severe symptoms reported significant relief.The ASmS is a robust quality-of-life tool for the specific assessment of symptoms of ovarian cancer-related malignant ascites. It can be used in the clinical trial setting assessing interventions aimed at treating ascites and in the clinic to identify those patients with mild symptoms, who may benefit from paracentesis.

Objective Many patients undergo hysterectomy for the treatment of cervical dysplasia. Factors that correlate with residual high-grade squamous intraepithelial lesions (HGSIL) at hysterectomy are not clear. We set out to determine preoperative features that may predict residual disease for patients treated for cervical dysplasia. Materials and methods A retrospective database was reviewed for women who underwent simple hysterectomy for HGSIL between 1990 and 2013. Clinical data included age, history of dysplasia, initial treatment, follow-up colposcopy, indications for surgery, time elapsed between initial treatments, and pathology findings after hysterectomy. Significant residual disease was defined as HGSIL or cervical carcinoma. Statistical analyses were performed with the SPSS, independent Student t test, and Pearson χ test. Significance was set at p Results Eighty-three women met the study criteria. The indication for hysterectomy was residual histological finding at conization pathology in 30 women and patients' request in 53 women. Residual disease was found in 42 hysterectomy specimens: in 16 of 30 with residual histological finding and in 26 of the 53 patients' request. Reason for the hysterectomy was not statistically significant for residual disease (p = .708). Median age of patients with residual disease was 46.5 years versus 44.1 years for those without residua (p = .02). Postmenopausal patients had a higher rate of residual disease, 12 (32.4%) of the 28 premenopausal patients and 25 (67.6%) of the 54 postmenopausal patients (p = .04). Conization margin status was not associated with residual disease (p = .878). Conclusions Older women and those in menopause are at significantly higher risk of residual disease at hysterectomy.