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Objectives: To investigate the cost-effectiveness of preimplantation genetic testing for selection and transfer of BRCA negative embryo in BRCA mutation carriers compared to natural conception. Methods: The cost-effectiveness of two strategies, conception through IVF/PGT-M and BRCA negative embryo transfer versus natural conception with a 50% chance of BRCA positive newborn for BRCA mutation carriers, was compared using a Markovian process decision analysis model. Costs of the two strategies were compared using quality-adjusted life years (QALYs'). All costs were discounted by 3%. Incremental cost-effectiveness ratio (ICER) compared to the willingness to pay threshold was used for cost-effectiveness analysis. A probabilistic sensitivity analysis (Monte Carlo simulation) was conducted with all variables, using 100 trials, each included 10,000 couples, to evaluate model uncertainties. Results: IVF/ PGT-M is cost-effective with an ICER of 150,219 new Israeli Shekels, per QALY gained (equivalent to 44,480 USD), at a 3% discount rate. Discount rate and uptake of risk reduction salpingo- oophorectomy (RRSO) are the most influential parameters that affect the ICER. Increasing uptake of RRSO would make the ICER highly cost-effective. Conclusions: IVF/ PGT-M and BRCA negative embryo transfer compared to natural conception among BRCA positive parents is costeffective and may be offered for selected couples with high BRCA mutation-related morbidity or mortality. Our results could impact decisions regarding conception among BRCA positive couples and health care providers. [ABSTRACT FROM AUTHOR]

Objectives: Diagnosis of cervical dysplasia and subsequent conization of the uterine cervix might affect women's sexual health. The study objective was to assess the effect of cervical conization on women's sexual function and psychological wellbeing using structured questionnaires. Methods: Patients undergoing conization of the cervix completed questionnaires before and 6-12 months after conization. Assessment of sexual distress and function was done using the female sexual distress scale-revised (FSDS-r) and the female sexual function inventory (FSFI), respectively. Risk for anxiety and depression was assessed using the Hospital Anxiety and Depression Scale (HADS). Results: From October 2018 to March 2021, 55 patients undergoing cervical conization were recruited. No significant differences were found in FSDS-r scores before and after conization. An equal number of patients indicated having sexual distress (29 patients, 53%, before and after conization, p=1.0). No significant changes were noticed on any FSDS domains or the total FSDS score before and after conization (26.8 vs 26.0, p=0.461). The percent of patients that indicated an overall sexual dysfunction, increased from 49 percent before conization, to 59 percent after conization (p=0.388). A high percentage of patients indicated signs of anxiety on the HADS questionnaire, both before and after conization (49% and 47%, respectively). The median anxiety and depression scores did not change after conization (p=1.0). Conclusions: A high percentage of patients undergoing conization suffer from sexual distress, sexual dysfunction, and general anxiety, both before and after conization. The conization procedure itself did not seem to affect questionnaire scores. Gynecologists should be aware of the psychological and sexual effects of the diagnosis and treatment of cervical pre-cancerous lesions; patients should be counseled accordingly. [ABSTRACT FROM AUTHOR]

Objectives: The objective of the present study was to compare the incidence of endometrial carcinoma following hysterectomy in patients with presurgical diagnoses of atypical endometrial hyperplasia (non-polypoid) versus atypical endometrial hyperplasia confined to an endometrial polyp. Methods: Medical records of women who underwent staging surgery, including hysterectomy, bilateral salpingo-oophorectomy, and sentinel lymph node dissection, for atypical endometrial hyperplasia or atypical endometrial polyp between 2016 and 2020 were reviewed. Results: Seventy-nine women who underwent surgery were included. Of those, 46 women were diagnosed with an atypical endometrial polyp that was resected via hysteroscopy (endometrial polyp group), and 33 women had non-polypoid atypical endometrial hyperplasia following endometrial tissue sampling (non-polypoid group). The mean age at diagnosis was 60.2 ± 9.9 years in the endometrial polyp group compared to 61.7 ± 12 years in the non-polypoid group (p=0.5). Most women (81.8%) in the non-polypoid group presented with post-menopausal bleeding, whereas 41.3% of the women in the endometrial polyp group were asymptomatic (p=0.001). Pathology results from the hysterectomy specimens revealed concurrent endometrial carcinoma in 23.9% of women in the endometrial polyp group compared to 51.5% of women in the non-polypoid group (p=0.001). Ninety-one percent of cancers were grade 1 in the endometrial polyp group compared to 53% of cancers in the non-polypoid group. Grade 2 was found in 9% of cancers in the endometrial polyp group compared to 35% of women in the non-polypoid group (p=0.04). Most women were diagnosed at stage IA, 91% in the endometrial polyp group compared to 82% in the non-polypoid group (p=0.6). In both groups, none of the sentinel lymph nodes harvested during surgery were involved by cancer. Conclusions: Concurrent cancer is less frequent with atypical endometrial polyp as compared to atypical endometrial hyperplasia. Still, the high incidence of endometrial carcinoma in both groups supports the current advice to perform a hysterectomy and bilateral salpingo- oophorectomy for peri and post-menopausal women. Our data do not support performing sentinel lymph node dissection for atypical endometrial hyperplasia. [ABSTRACT FROM AUTHOR]

Objectives: Epithelial ovarian cancer is often diagnosed at an advanced stage due to intraperitoneal spread. Modern treatment strategies have only modestly improved the survival rates of this disease. Chimeric antigen receptor (CAR) T cells enable T cells to directly bind tumor-associated antigens in an MHC-independent manner inducing tumor rejection. A major barrier is the lack of true tumor-specific antigens followed by risk of "on-target off-tumor" toxicity. Innovative approaches are therefore needed to increase the specificity of CAR-modified T cells exclusively against tumors. The aim of this study was to assess the efficacy and safety of intraperitoneal versus intravenous CAR T cell therapy. Our working hypothesis was that intraperitoneal CAR T cell therapy will demonstrate higher cytotoxic activity towards a tumor tissue while sparing non-tumor tissues. Methods: We have constructed CARs targeting HER2 (ErbB2) that are overexpressed in ovarian cancers. CARs were expressed in human lymphocytes, and their functionality toward human ovarian cancer cell lines was evaluated in-vitro and in a murine model. Results: We have found that the anti-ErbB2 CARs secreted IFN-g (600-1800pg/ml) after stimulation with OVCAR8, SKOV3, or NAR cells compared to untransduced lymphocytes CAR T cells (50pg/ml). Treatment with an intraperitoneal injection of anti-ErbB2 CAR T cells leads to remission of the tumor and increased survival compared to the intravenous route. Intraperitoneal treatment of anti-ErbB2 CARs was less toxic to non-tumor tissues compared to the intravenous treatment. Conclusions: Our results demonstrate that the intra-peritoneal approach of CAR T cells offers a safe strategy with a clinical potential for the treatment of ovarian cancer. [ABSTRACT FROM AUTHOR]

Although non-inferior overall survival and reduced surgical morbidity with neoadjuvant therapy (NAC) compared to primary debulking surgery, upfront debulking surgery remains the treatment of choice for newly diagnosed advanced stage ovarian cancer (OC) in the US. This can be partially attributed to the association of aggressive surgical treatment with long term survival (LTS) demonstrated in high grade serous OC (HGSOC). On the contrary, NAC has been shown to lower the odds for LTS. We aimed to identify clinico-pathologic factors associated with LTS in advanced epithelial OC (EOC) treated with NAC. This is a retrospective case-control study. Women with FIGO stage III-IV high grade epithelial cancer of the ovary, fallopian tube or peritoneum diagnosed and treated with NAC prior to 2013 were extracted from consecutive patient records of the Tel-Aviv Sourasky Medical Center. Women surviving longer than 7 years from diagnosis (defined as long-term survivors, LTS) were compared to women surviving 6-24 months from diagnosis (defined as short-term survivors, STS). Patients with low grade or low malignant potential tumors were excluded. We identified 190 women with stage III/IV epithelial OC. Seventy-eight patients (41%) survived longer than 5 years from diagnosis and 47 (24%) survived longer than 7 years from diagnosis, significantly higher proportions compared to previous reports. Thirty-nine patients (20%) survived 6-24 months, similar to previous reports. Clinicopathologic and treatment characteristics of both groups are displayed in Table 1. CA125 pre-treatment or after 4 courses of chemotherapy and the number of adjuvant and total chemotherapy courses administered were similar between the groups. LTS were significantly younger than STS at diagnosis, with a mean age of 60.05 years vs 65.95 years, respectively (p=0.008). The majority of LTS received 3 courses of NAC or less compared to STS (59.6% vs 33.4%), implying a smaller disease burden or better response to NAC. LTS had a significantly longer disease-free interval (80.49 months vs 3.65 months, p<0.0001) and significantly less recurrences (68.1% vs 94.9%, p=0.002) compared to STS. Logistic regression model including age at diagnosis, germline BRCA mutation status, stage and histologic type showed that increased age lowers the odds for long term survivorship (OR-0.929 per 1 year of age, p=0.008). Endometroid carcinoma, compared to serous histology, lowers the odds for LTS as well (OR-0.295, p=0.046). Surprisingly, germline BRCA1 mutation carriers are 5.5 times more likely to survive more than 7 years compared to non-carriers (OR-5.508, p=0.034). Germline BRCA2 mutations do not change the odds for LTS compared to non-carriers p=0.99. Patients diagnosed at stage III have a significantly higher chance of long-term survivorship compared to stage IV, as previously reported for primary-debulked HGSOC patients (OR-7.89, p=0.016). [Display omitted] Our analysis, to the best of our knowledge, is the first to demonstrate that NAC does not compromise the odds of long-term survivorship in women with advanced EOC, further strengthening NAC as an equivalent alternative to primary debulking surgery. In addition, we identified basic clinicpathologic and treatment-related factors associated with long term survival of epithelial OC patients treated with NAC. Further investigation is needed to determine which factors should be integrated into treatment-related decisions. [ABSTRACT FROM AUTHOR]