Nadav Michaan

Medical cannabis and its effect on oncological outcomes in patients with ovarian cancer treated with PARP inhibitors

Poly (ADP-ribose) polymerase inhibitors (PARPi) play a pivotal role in ovarian cancer management. With medical cannabis emerging as a novel component of supportive care, this study investigated the impact of medical cannabis use on oncological outcomes in patients with ovarian cancer undergoing PARPi therapy. The study included patients from a single institution database treated for ovarian cancer between January 2014 and January 2020 who received PARPi maintenance therapy in a first-line or recurrent disease setting after a confirmed response to platinum-based treatment. The study categorized patients as cannabis users and cannabis-naïve. Univariate and multivariate Cox regression analysis and the Kaplan-Meier method were used to assess the effects of medical cannabis use on the duration of PARPi therapy, progression-free survival, and overall survival. Among the eligible patients (n=93), most were cannabis-naïve (69%, n=64) while the rest used medical cannabis (31%, n=29). Medical cannabis use rates were comparable for patients receiving PARPi therapy post-primary treatment or for recurrence (42%, n=9, vs 27%, n=20; p=0.1). Both groups exhibited similar median duration for PARPi therapy (12.1 vs 9.5 months; p=0.89) and progression-free survival (20 vs 21 months; p=0.83). Kaplan-Meier analysis detected no differences in progression-free survival associated with cannabis use. Although cannabis users had an extended overall survival compared with the cannabis-naïve group (129.3 vs 99 months; p=0.03), cannabis use was insignificant for overall survival on multivariate analysis (p=0.10). Multivariate analysis showed stage IV at diagnosis (p=0.02) to be the sole factor associated with progression-free survival (p=0.02). Medical cannabis usage in patients receiving PARPi treatment showed no association with duration of PARPi therapy, progression-free survival, or overall survival.

Effect of BMI change on recurrence risk in patients with endometrial cancer

Our study aimed to explore the effect of body mass index (BMI) change on cancer recurrence risk during the routine surveillance of endometrial cancer patients. Data on patients with endometrial adenocarcinoma that had a staging procedure and continued follow-up was retrospectively collected. We compared patients' BMI at time of surgery and during the last clinic follow-up. Univariate and multivariate analyses were performed to examine the effect of predictors on BMI change and the risk of recurrence. A total of 211 patients were included in the final analysis. The majority of patients had stage I disease (n=176, 89%) and endometrioid histology (n=178, 86%). Median follow-up time was 53.4 (standard deviation (SD) 40) months. The mean BMI was 30.4 kg/m2 (interquartile range (IQR) 25-34) at surgery compared with 30.9 kg/m2 (IQR 26-36) at last follow-up (p<0.001). The BMI increase was most pronounced in patients with endometroid histology that recurred, 31.6 (IQR 24-35) kg/m Patients with endometroid endometrial cancer that had an increase in BMI during follow-up were at an increased risk for cancer recurrence compared with patients that did not change or had a decrease in BMI.

Use of Virtual Reality for Pain Relief During Cervical Conization Under Local Anesthesia: A Randomized Controlled Trial

Objectives Cervical conization (loop electrosurgical excision procedure) under local anesthesia is often associated with anxiety and procedural pain. Virtual reality (VR) glasses may enhance patient experience and reduce discomfort during medical interventions. The authors aimed to prospectively and randomly evaluate whether VR use during loop electrosurgical excision procedure may impact reported pain and anxiety. Methods In this randomized controlled study, women undergoing conization under local anesthesia were assigned to either a control group (no VR) or a study group using VR glasses during the procedure. Demographics, baseline anxiety levels, anticipated pain, intraprocedural pain, heart rate, patient satisfaction, and surgeon-reported procedural difficulty were compared between groups. Anticipated and actual pain was assessed using a 0–10 visual analog scale. Results A total of 67 women were randomized. Groups were comparable in age, body mass index, pathology, and anticipated pain (median 5.0 vs. 6.0, p = .667). No significant difference was found between groups in pain experienced during the procedure (median 3.0 vs. 2.0, p = .318), discomfort, anxiety, or heart rate. Experienced pain was significantly lower than anticipated in both groups ( p &lt; .001). Patient satisfaction was high in both groups, 90% of patients who used VR would recommend it to others. Adverse effects related to VR were rare. Conclusions While the use of VR glasses did not reduce perceived pain compared to standard care, it was safe and associated with high patient satisfaction. Most women overestimated the pain they would experience during conization. Integrating VR technology may improve overall patient experience during cervical conization, even if it does not alter pain perception.

Cost Effectiveness of Whole Population BRCA Genetic Screening for Cancer Prevention in Israel

Abstract With the growing technical ease and reduction in genetic screening costs, whole population BRCA screening may be a feasible option. Our objective was to investigate the cost effectiveness of whole population screening for BRCA mutations in Israel, for varying degrees of BRCA carrier state. Lifetime costs of whole female population screening for BRCA mutation carrier state versus nonscreening were compared using a Markovian process decision analysis model. Model parameters including ovarian and breast cancer risks were obtained from previously published data. Screening and other treatment-related costs were received from the Israeli Ministry of Health pricing list according to specified codes. Quality-adjusted life years were used for cost-effectiveness analysis. Sensitivity analysis was conducted to evaluate model uncertainties, specifically varying degrees of BRCA prevalence. Results show that whole population BRCA screening in Israel is cost effective across a wide range of BRCA prevalence rates with an incremental cost-effectiveness ratio of 81,493 new Israeli Shekels for a BRCA prevalence of 2.5%, increasing to 250,000 new Israeli Shekels for a 0.75% prevalence rate, per quality-adjusted life year gained. Discount rate and population BRCA prevalence and rate of risk reduction salpingo-oophorectomy are the most influential parameters in the model. Whole population screening for BRCA mutations should be offered as part of general health screening strategies by national medical insurance providers, even for non-Ashkenazi Jews. Our algorithm can be applied for other countries, adjusting local costs of screening and treatment. Prevention Relevance: Whole population BRCA mutation screening in Israel is cost effective across a wide prevalence rate and should be offered as part of general health screening strategies by national medical insurance providers for cancer prevention.

Preimplantation genetic testing for BRCA gene mutation carriers: a cost effectiveness analysis

Abstract Background Gynecologic oncologists should be aware of the option of conception through IVF/PGT-M for families with high BRCA related morbidity or mortality. Our objective was 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 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 at 3%. Incremental cost effectiveness ratio (ICER) compared to willingness to pay threshold was used for cost-effectiveness analysis. 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. Conclusions IVF/ PGT-M and BRCA negative embryo transfer compared to natural conception among BRCA positive parents is cost effective 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.

Prognostic significance of delayed complete metabolic response on PET/CT after primary chemoradiation treatment of cervical cancer

To investigate the prognostic significance of near-complete metabolic response on initial follow-up PET/CT after primary chemoradiation treatment of cervical cancer. Survival data were retrospectively compared between patients who had complete metabolic response on first follow-up PET/CT, 3 months after chemoradiation (group 1) with those who had near-complete metabolic response on first PET/CT and later showed complete metabolic response at subsequent PET/CT, 6 months or more after treatment (group 2). Of the 108 patients included in the final analysis, 74 (68.5%) showed complete metabolic response on initial PET/CT, 3 months after treatment, and 34 patients (31.5%) showed complete metabolic response on subsequent PET/CT, 6 months after treatment. Tumor characteristics were comparable between groups. Group 1 had higher percent of stage 1 (12% vs 0%) and lower percent of stage 4 disease (3% vs 14%) than those of group 2. Group 2 patients had significantly fewer cases of recurrences and deaths than group 1 patients (6% vs 26%, p=0.018; 0% vs 20%, p=0.003, respectively), with comparable 3-year survival rates (group 1, 90% vs group 2, 100%, p=0.31). Twelve patients had progressive disease on first follow-up PET/CT; these patients had significantly worse overall survival compared with all other patients (log-rank test, p<0.001). Younger age and delayed complete metabolic response were associated with lower chance of recurrence and death on univariate analysis. On multivariate analysis, delayed complete metabolic response remained significantly associated with no recurrence HR=0.14 (95% CI 0.25 to 0.84), p=0.031. Survival outcome of patients with cervical cancer who show residual 18F-fluorodeoxyglucose uptake on initial PET/CT after treatment, but reach complete metabolic response on follow-up PET/CT, is not inferior compared with survival of patients who show complete metabolic response on initial PET/CT 3 months after treatment. Watchful waiting with follow-up PET/CT seems a safe option for these patients.

Cytoreductive surgery in advanced epithelial ovarian cancer: a real-world analysis guided by clinical variables, homologous recombination, and BRCA status

Guidelines endorse both interval and primary debulking cytoreductive surgeries in the treatment of epithelial ovarian cancer, emphasizing that the treatment strategy should be tailored to the patient's clinical condition and tumor burden. Despite these recommendations, experts have yet to agree on a definitive surgical approach. A retrospective longitudinal analysis of 929 women diagnosed with advanced-stage (International Federation of Gynecology and Obstetrics stage III-IV) epithelial ovarian cancer between January 2002 and January 2025 was conducted. The effects of interval debulking surgery versus primary debulking surgery on median overall survival and progression-free survival were evaluated. Additionally, we aimed to identify patients who may benefit from a particular surgical approach based on clinical variables, mutation in either of the BRCA1 or BRCA2 genes, and homologous recombination profile. A total of 929 patients were diagnosed with stage III to IV disease (87.2%) and underwent either primary debulking (n = 389, 41.9%) or interval debulking surgery following neoadjuvant chemotherapy (n = 540, 58.1%). Patients treated with primary debulking had a longer median overall survival than those treated with interval debulking surgery (68.40 months, 95% CI 62.92 to 76.45 vs 52.01 months, 95% CI 47.15 to 57.86, HR 1.2, p = .0004). However, when adjusted for age at diagnosis, stage, histology, BRCA status, and tumor resectability, multivariate analysis demonstrated no significant difference in survival between the two surgical groups (HR 1.15, 95% CI 0.96 to 1.39, p = .12). Younger women ( .05). Propensity score analysis demonstrated comparable median overall survival with the two surgical timings (64.39 months, 95% CI 58.38 to 71.23 vs 57.69 months, 95% CI 50.66 to 64.79, HR 1.33, p = .27). Our findings support the use of neoadjuvant chemotherapy followed by interval debulking surgery without compromising survival outcomes, regardless of age and stage, particularly among harder-to-treat patients. We identified a specific subset of patients who may benefit from primary debulking surgery as the optimal intervention. These findings advocate for a personalized treatment approach and the potential for tailored surgical strategies guided by patient clinical variables, homologous recombination, and genetic factors.