Gabriel Levin

Revisiting intraperitoneal chemotherapy for advanced high‐grade serous ovarian cancer

Abstract Objective To compare overall survival (OS) in patients with high‐grade serous ovarian cancer (HGSOC) treated with intraperitoneal (IP) chemotherapy versus intravenous (IV) chemotherapy. Methods A retrospective study of Stage III HGSOC with optimal primary cytoreduction during 2007–2019, followed by adjuvant IP or IV chemotherapy. Results Overall, 54 patients were included, 23 (43%) treated by IP and 31 (57%) by IV chemotherapy. Median progression‐free survival (PFS) in the IP group was 39 months (95% confidence interval [CI] 34–44 months) versus 23 months (95% CI 18–28 months) in the IV group ( P  = 0.294). The IP chemotherapy had superior OS compared with IV chemotherapy, with median OS not reached, versus 76 months (95% CI 37–115 months) for the IV group ( P  = 0.075, hazard ratio 0.45, 95% CI 0.18–1.10). At 72 months, OS was 82% for the IP group versus 53% in the IV group. In a sensitivity analysis for Stage IIIc patients only ( n  = 39), the median OS was 130 months (95% CI 86–174 months) in the IP group, compared with 56 months (95% CI 35–76 months) for the IV group ( P  = 0.152). Toxicity profiles were similar in both groups, with no Grade ≥3 toxicity. Conclusion Stage III HGSOC patients treated with IP chemotherapy had significantly longer OS.

Racial and ethnic enrollment disparities in clinical trials leading to Food and Drug Administration approvals for gynecologic malignancies

Compared to White women, Black women and other minority groups have a higher age-adjusted incidence risk of cervical and endometrial cancer. However, the extent of racial and ethnic disparities in clinical trial enrollment among studies performed mainly in North America and Europe for gynecologic malignancy is unknown. This study analyzed enrollment rates by race/ethnicity in trials that led to Food and Drug Administration approvals for gynecological cancers from 2010 to 2024. This cross-sectional study examined clinical trials registered with ClinicalTrials.gov that resulted in new Food and Drug Administration approvals for gynecologic malignancies between 2010 and 2024. Exclusion criteria were studies not conducted in North America or Europe. Enrollment fractions were obtained by dividing the number of trial participants segregated by the racial/ethnic group by the corresponding U.S. cancer prevalence (uterine, ovarian, and cervical cancer) for 2016 to 2020 for each racial/ethnic group. Odds ratios and 95% confidence intervals were calculated to compare enrollment fractions of minority groups to non-Hispanic Whites. A total of 31 studies met the inclusion criteria, with 21 reporting race/ethnicity data. Three (3/21) studies dichotomized race as non-Hispanic White and non-White and 7 (7/21) reported ethnicity. The median number of participants was 494 [interquartile range 150-674]. Fifteen studies were phase III, and 6 were phase IB/II trials. Treatments included immune checkpoint inhibitors (7 studies), poly (ADP-ribose) polymerase inhibitors (5), vascular endothelial growth factor inhibitors (4), antibody-drug conjugates (4), and an imaging marker (1). Across all studies, 11,258 patients were included, 5563 (49.4%) in ovarian cancer studies, 2963 (26.3%) in endometrial cancer studies, and 2732 (24.3%) in cervical cancer studies. Three studies (n=1734) dichotomized participants into non-Hispanic White and non-White; non-Hispanic White 1291 [74.4%] and non-White 443 [25.6%], and enrollment fractions were 0.51% for non-Hispanic White and 0.43% for no-White, with non-White being underrepresented odds ratio 0.85, 95% confidence interval [0.76-0.95], P=.004. In an Analysis of 18 studies reporting race categories, non-Hispanic Black patients were significantly underrepresented (odds ratio 0.50, 95% confidence interval [0.45-0.54], P<.001), while Asian patients were overrepresented (odds ratio 2.81, 95% confidence interval [2.64-2.99], P<.001). In the 4 studies reporting ethnicity, Hispanic patients were also significantly underrepresented (odds ratio 0.69, 95% confidence interval [0.61-0.78], P<.001). In clinical trials, performed in North America and Europe mainly, leading to Food and Drug Administration approvals for gynecologic malignancies, non-Hispanic Black and Hispanic patients are significantly underrepresented compared to non-Hispanic White participants when enrollment is benchmarked to the U.S. female population with gynecological cancer. These trials do not adequately reflect the U.S. populations diagnosed with these malignancies. Enrollment strategies to increase diversity are urgently needed to ensure clinical trial results are equitable and applicable across all populations. Efforts from the American Society of Clinical Oncology, the Association of Community Cancer Centers, and the Gynecologic Oncologic Group/Society of Gynecologic Oncology Inclusion, Diversity, Equity, and Access initiative provide a comprehensive framework for achieving this goal.

GD2 and GD3 gangliosides as prognostic biomarkers in high grade serous ovarian cancer

Gangliosides GD2 and GD3 have been proposed to be of significance in diagnosis of ovarian masses. We aim to study serum GD2 and GD3 gangliosides as predictors of oncological outcomes among high grade serous (HGS) ovarian cancer (OC). A retrospective study including biobanked serum samples of HGS OC treated between 2005 and 2016. Serum GD2 and GD3 concentrations were quantified using indirect ELISA and analyzed with respect to survival. Sixty patients were included. Patients with GD3>12.8 ng/mL had shorter PFS when compared to patients with lower level; median 31 vs. 67 months, p = 0.005. Patients with GD2> 7.1 ng/mL had shorter median PFS than those with lower level of (23 vs. 52 months, p = 0.024.) Patients with GD3>14.5 ng/mL had shorter OS vs. patients with lower level (median 31 vs. 70 months, p = 0.002). In a Cox regression, following adjustment for age, CA-125, disease stage and age, serum elevated GD3 was independently associated with short PFS (adjusted hazard ratio 2.0, 95 % CI 1.1-3.8, p=.024). In a separate Cox regression, elevated GD2 was independently associated with PFS (adjusted hazard ratio3.0 (1.2-7.7). p=.019. High serum GD3 and GD2 were independently associated with short OS as well. High levels of serum GD2 and GD3 in HGS OC were associated with shorter PFS and OS. GD3 is superior to GD2 as a biomarker for prognosis.

Gynecologic oncology robot‐assisted surgery in octogenarians: Impact of age on hospital stay

AbstractObjectiveTo compare postoperative stay in octogenarians and younger patients undergoing gynecologic oncology robot‐assisted surgery.MethodsA retrospective review of robot‐assisted surgery in Gynecological Oncology division during 2019–2022. We included all consecutive cases. Octogenarians (age ≥80 years) and younger patients were investigated by univariable analysis for characteristics and outcome.ResultsA total of 816 robot‐assisted surgeries were performed, 426 (52.2%) endometrial cancer, 159 (19.5%) ovarian cancer, 27 (3.3%) cervical cancer, 35 (4.3%) endometrial intraepithelial neoplasia, and in 169 (20.7%) the final pathology was benign. There were 60 (7.4%) octogenarians and 756 (92.6%) younger patients. The proportion of patients with an American Society of Anesthesiology score greater than 2 was higher among octogenarians (66.7% vs 32.0%, P &lt; 0.001). The median console time, surgical time, and total operation theater time were similar between groups (P = 0.303, P = 0.643 and P = 0.688, respectively). Conversion rate did not differ between groups (0.4% among younger patients vs 0% in octogenarians, P &gt; 0.99). The median length of stay in the recovery room was similar in both groups (median 170 min, interquartile range [IQR] 125–225 min vs 170 min, IQR 128–240 min in octogenarians, P = 0.731). Length of hospital stay was similar in both age groups; median 1 day (IQR 1–1) among octogenarians versus 1 (0–1) in younger patients (P = 0.136).ConclusionOctogenarians undergoing robotic surgery have no increased risk of length of stay or conversion to laparotomy compared with younger patients.

Association between BMI and oncologic outcomes in epithelial ovarian cancer: a predictors-matched case-control study

Abstract Objective We aimed to study the association between obesity and survival in ovarian cancer (OC) patients, accounting for confounders as disease stage, histology, and comorbidities. Methods Retrospective matched case-control study of consecutive patients, with epithelial OC. Obese (body mass index [BMI] ≥ 35 kg m−2) patients were matched in a 1:4 ratio with patients having lower BMIs (BMI &lt; 35 kg m−2) based on disease stage, cytoreduction state, tumor histology and ASA score. We compared the 3-year and total recurrence-free survival and overall survival through Kaplan–Meier survival curves and Cox proportional hazards. Results Overall, 153 consecutive patients were included, of whom 32 (20.9%) had a BMI ≥ 35. and 121 a BMI &lt; 35. The median follow-up time was 39 months (interquartile range 18–67). Both study groups were similar in multiple prognostic factors, including American Society of Anesthesiologists physical status, completion of cytoreduction, histology and stage of disease (p = 0.981, p = 0.992, p = 0.740 and p = 0.984, respectively). Ninety-five (62.1%) patients underwent robotic surgery and conversion rate from robotic to laparotomy was similar in both groups 2 (6.3%) in obese group vs. 6 (5.0%) in lower BMI patients, p = 0.673. During the follow-up time, the rate of recurrence was similar in both groups; 21 (65.6%) in obese group vs. 68 (57.1%), p = 0.387 and the rate of death events was similar; 16 (50.0%) in obese group vs. 49 (40.5%), p = 0.333). The 3-year OS was higher in the obese group (log rank p = 0.042) but the 3-year RFS was similar in both groups (log rank p = 0.556). Median total OS was similar in both groups 62 months (95% confidence interval 25–98 months) in obese vs. 67 months (95% confidence interval 15–118) in the lower BMI group, log rank p = 0.822. Median RFS was similar in both groups; 61 months (95% confidence interval 47–74) in obese, vs. 54 (95% confidence interval 43–64), log rank p = 0.842. In Cox regression analysis for OS, including obesity, age, laparotomy and neoadjuvant treatment – only neoadjuvant treatment was independently associated with longer OS: odds ratio 1.82 (95% confidence interval 1.09–3.05) and longer RFS: odds ratio 2.16 (95% confidence interval 1.37–3.41). Conclusions In the present study on consecutive cases of ovarian cancer, obesity did not seem to be associated with outcome, except for an apparent improved 3-year survival that faded away thereafter.

Machine learning for prediction of concurrent endometrial carcinoma in patients diagnosed with endometrial intraepithelial neoplasia

To identify predictive clinico-pathologic factors for concurrent endometrial carcinoma (EC) among patients with endometrial intraepithelial neoplasia (EIN) using machine learning. a retrospective analysis of 160 patients with a biopsy proven EIN. We analyzed the performance of multiple machine learning models (n = 48) with different parameters to predict the diagnosis of postoperative EC. The prediction variables included: parity, gestations, sampling method, endometrial thickness, age, body mass index, diabetes, hypertension, serum CA-125, preoperative histology and preoperative hormonal therapy. Python 'sklearn' library was used to train and test the models. The model performance was evaluated by sensitivity, specificity, PPV, NPV and AUC. Five iterations of internal cross-validation were performed, and the mean values were used to compare between the models. Of the 160 women with a preoperative diagnosis of EIN, 37.5% (60) had a post-op diagnosis of EC. In univariable analysis, there were no significant predictors of EIN. For the five best machine learning models, all the models had a high specificity (71%-88%) and a low sensitivity (23%-51%). Logistic regression model had the highest specificity 88%, XG Boost had the highest sensitivity 51%, and the highest positive predictive value 62% and negative predictive value 73%. The highest area under the curve was achieved by the random forest model 0.646. Even using the most elaborate AI algorithms, it is not possible currently to predict concurrent EC in women with a preoperative diagnosis of EIN. As women with EIN have a high risk of concurrent EC, there may be a value of surgical staging including sentinel lymph node evaluation, to more precisely direct adjuvant treatment in the event EC is identified on final pathology.

Time interval from biopsy of endometrial atypical hyperplasia to surgery and risk for concurrent endometrial carcinoma – A retrospective study

Association of body mass index with pathologic agreement of preoperative and postoperative tumor grade in endometrial cancer

Abstract Objective We aim to study association of BMI of EC patients, with the level of agreement between preoperative and postoperative tumor grade. Methods A retrospective study. We included patients with EC diagnosed in an outpatient clinic which had surgical staging as in our division. We categorized patients into BMI categories according to the World Health Organization; (BMI &lt; 18.5 kg/m2), (BMI 18.5–24.9 kg/m2), (BMI 25–29.9 kg/m2), (BMI 30–34.9 kg/m2), (BMI 35–39.9 kg/m2), and (BMI ≥ 40 kg/m2). We further dichotomized the study population for obesity, defined as BMI ≥ 30.0. We analyzed agreement between preoperative and postoperative tumor grade, stratified by patient’s BMI. Results Overall, 623 women met study inclusion criteria, with a median age of 64 [interquartile range (IQR) 57–72]. Among the study cohort, the median BMI was 30.7 [IQR 25.6–38.8], with 330 (53.0%) patients being obese. EC grade 1 was diagnosed preoperatively in 353 (56.7%), grade 3 in 148 (23.8%), and grade 2 in 122 (19.6%). Endometrioid histology was diagnosed in 463 (74.3%), serous in 78 (12.5%), mixed histotype in 51 (8.2%), clear cell in 20 (3.2%) and carcinosarcoma in 11 (1.8%). In 68.7% (n = 428), there was no change in postoperative grade, and in 24.9% (n = 155), there was upgrading of tumor, and in 6.4% (n = 40), there was a tumor downgrade. There were 3 (0.5%) cases in which no tumor was found on final pathology. The rate of no change was higher in preoperative grade 3 (89.9%) vs. grades 1 (63.5%) and grade 2 (58.2%), p &lt; .001). There was no difference in grading agreement when obese patients were compared to non-obese, p = .248. There was no difference in grading agreement when comparing the various BMI categories, with no change proportion ranging between 58.2% in BMI 30.0–34.9 mg/kg2 and 79.7% in BMI 35.0–39.9 mg/kg2, p = .104. ROC analysis of BMI as predictor of no-change yielded an area under the curve of 0.466 (95% confidence interval 0.418–0.515) with a maximal performance at a BMI of 33.8 mg/kg2. The agreement between preoperative and postoperative tumor grade among all patients was kappa = 0.517. The agreement did not differ when compared between obese patients (kappa = 0.456) and non-obese (kappa = 0.575). Conclusion Our study found no significant association between BMI and the agreement between preoperative and postoperative tumor grading in EC.

Minimally invasive approach in endometrial cancer with lower uterine segment involvement in stage ≥ II: A retrospective study

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. 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. 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). In women with advanced EC and LUSI, although MIS is associated with locoregional recurrences, survival is comparable to laparotomy.

Gynecologic perivascular epithelioid cell tumors (PEComas): a review of recent evidence

AbstractGynecologic perivascular epithelioid cell (PEC) tumors, or 'PEComas,' represent a rare and intriguing subset of tumors within the female reproductive tract. This systematic literature review aims to provide an updated understanding of gynecologic PEComas based on available literature and data. Although PEComa is rare, there are varied tumor-site presentations across gynecologic organs, with uterine PEComas being the most prevalent. There is scarce high-quality literature regarding gynecologic PEComa, and studies on malignant PEComa underscore the challenges in diagnosis. Among the diverse mutations, mTOR alterations are the most prominent. Survival analysis reveals a high rate of local recurrence and metastatic disease, which commonly affects the lungs. Treatment strategies are limited, however mTOR inhibitors have pivotal role when indicated and chemotherapy may also be used. with some cases demonstrating promising responses. The paucity of data underscores the need for multicentric studies, an international registry for PEComas, and standardized reporting in case series to enhance clinical and pathological data.

Association between body mass index, obesity, and vulvar cancer recurrence

AbstractObjectiveThe objective of this paper is to study the association between obesity and tumor recurrence in patients with vulvar cancer.MethodsThis is a retrospective study including vulvar cancer patients from 2003 to 2022. Our primary outcome was progression‐free survival (PFS) stratified by status of obesity, defined as body mass index (BMI) &gt;30.0 kg/m2.ResultsOverall, 48 patients were included in the study, with 32 (66.7%) diagnosed at early stages (I–II). The median BMI was 28.0 kg/m2 [interquartile range 24.9–32.3 kg/m2]. There were 13 obese patients (27%), and the median follow‐up time was 55 months [interquartile range 14–102]. Most patients (80%) were HPV‐independent of human papilloma virus. Surgical intervention was the primary treatment modality for 88% (n = 42) of the cohort, and 26 patients (54%) received adjuvant chemoradiation. Disease recurrence was identified in 28 patients (58%). The median PFS was 68 months, and the median overall survival was 109 months. There was no difference in the median PFS between obese patients and non‐obese patients (P = 0.370). In a Cox regression analysis, after adjusting for patient age, margin‐free distance, and stage of disease, BMI was not associated with PFS hazard ratio 1.06 (0.99–1.12).ConclusionObesity is not associated with PFS in patients with vulvar cancer, and BMI might not be considered a risk factor for recurrence.

Silicon dioxide, sodium selenite and citric acid vaginal gel, HPV infection, and cervical preinvasive disease: a narrative review

Cervical cancer continues to be a major public health concern, particularly in low- and middle-income countries. It is mainly caused by persistent infection with human papillomavirus (HPV). Screening has been the most effective strategy to reduce mortality, but over the last 2 decades, vaccination has emerged as an important adjunct, helping to decrease incidence and mortality. Given the natural history of HPV infection, most low-grade lesions will spontaneously resolve over time; therefore, observation is the preferred approach for low-grade squamous intraepithelial lesions. Some authors have suggested that this period without intervention may cause anxiety among patients and physicians. A vaginal gel containing 10.0 mg of silicon dioxide, 24.8 mg citric acid, and 0.25 mg selenium per dose, marketed as DeflaGyn, Deflamin, or Deflamed, has been approved in Europe, the United Arab Emirates, Uzbekistan, and Colombia. A literature search was conducted to identify all published clinical trials on DeflaGyn. As of January 2025, 6 studies have been published: 1 retrospective study, 1 randomized clinical trial (RCT) with 2 post hoc analyses, 1 prospective non-randomized trial, and 1 in vitro study. A methodological risk-of-bias assessment was performed, revealing a number of domains with high or unknown risk of bias in the RCT and its post hoc analyses. This review aims to summarize the available evidence and perform a critical analysis of the research. Current evidence is insufficient to support its use for treating HPV infection or dysplasia.