Faculty Bibliography

Dostarlimab in combination with carboplatin-paclitaxel was approved for primary advanced or recurrent endometrial cancer (pA/rEC). The first interim analysis (IA1) of RUBY Part 1 (NCT03981796) showed no significant exposure-response (ER) relationship for progression-free survival or for the five most common dostarlimab-related adverse events (AEs), except rash. Herein, we report the ER relationship between dostarlimab exposure and overall survival (OS) and between dostarlimab exposure and dostarlimab-related AEs. Population pharmacokinetic model was based on IA1, and the predicted exposure metrics from Cycle 1 were used to perform ER analysis at the second interim analysis (IA2). AE analysis was completed for three periods: Cycles 1-6 (chemotherapy phase), Cycle 7 and beyond (monotherapy phase), and all cycles. Included in the OS analysis were 232 patients treated with dostarlimab + carboplatin-paclitaxel. Cox regression of OS showed no significant ER relationship based on dostarlimab Cycle 1 exposure, except for rash and arthralgia. The increase in predicted probabilities for rash and arthralgia for patients with high versus low exposure was limited, ranging from 5.6% to 10.4% for rash and 4.3% to 17.7% for arthralgia (deemed not clinically relevant). These data support the risk/benefit profile at the selected dose of dostarlimab + carboplatin-paclitaxel as standard of care in patients with pA/rEC.

BACKGROUND:The Essentials in Minimally Invasive Gynecologic Surgery (EMIGS) is a new assessment employed by the American Board of Obstetrics and Gynecology to evaluate physicians' surgical skills for certification. The program assesses the minimal laparoscopic skills needed to qualify for the certifying exam. We aimed to use checklist assessments to predict performance on the Running Stitch task of EMIGS OBJECTIVES: We strove to develop and evaluate a novel metric to predict competency in the EMIGS Running Stitch task. Secondarily to assess resident PGY year, prior laparoscopic suturing experience, and prior laparoscopic simulation experience correlation with passage. STUDY DESIGN/METHODS:A novel task specific checklist was developed by expert teaching surgeons to assess the Running Stitch task of EMIG. The checklist was tested for inter-rater reliability. Settings Residency programs at four participating academic centers PARTICIPANTS: 71 participants completed 97 videotaped trials Interventions participants completed a pre-study survey prior to each video-taped laparoscopic skills session (one to four sessions over four months of study). The video and the completed EMIGS task Penrose were evaluated both by the study team with checklists and later by EMIGs MEASUREMENT: The two scores were correlated using linear regression and Bland-Altman plots for agreement. RESULTS:53% of trials received a passing score by AAGL. AAGL and study team checklist scores were moderately correlated (0.73) however study team metrics consistently overrated performance. Laparoscopic case numbers and PGY level correlated with passing score. CONCLUSIONS:Scoring using our novel metric correlated with passing scores but overrated performance. This tool may aid educators in assessment during resident preparation for the EMIGS skills exam, but metrics for grading of this examination remain poorly understood.

Lichen sclerosus (LS) is a chronic inflammatory condition of the vulva. Although LS is thought to arise from autoimmune mechanisms, it is unclear whether disease drivers differ by menopausal status-an important distinction given its potential progression to differentiated vulvar intraepithelial neoplasia (dVIN) and vulvar squamous cell carcinoma (VSCC). We performed a retrospective review of 182 biopsy-proven LS cases (2020-2025), stratified by menopause status. In addition, we examined 27 VSCC cases for PD-L1 staining to assess immune modulation and potential therapeutic relevance. Premenopausal patients were diagnosed at a much younger age (37.8 vs. 67.5 yr, P<0.001) and experienced longer delays to diagnosis (3.9 vs. 1.5 yr, P<0.001). Their biopsies were less often reported with definitive LS terminology (40% vs. 75%, P<0.001), suggesting under-recognition in younger women. Comorbidities were more common in this group, especially autoimmune disease (46.7% vs. 10.9%, P<0.001), whereas postmenopausal patients more frequently had atrophic vaginitis (15.9%, P=0.02). Progression to dVIN or VSCC occurred more often in postmenopause (13.1% vs. 8.9%), though this was not statistically significant. PD-L1 expression was frequent in VSCC and precursor lesions (HSIL: 80%; dVIN: 81%) and less common in LS (50%), though these differences were not statistically significant. Expression patterns varied by lesion type, suggesting potential differences in the local immune microenvironment. Taken together, these findings support differences in clinical presentation and immune features of LS by menopausal status, warranting further investigation in larger cohorts.

OBJECTIVE:To estimate the cumulative probability of achieving at least one live birth (LB) after up to six sequential single euploid embryo transfers (euploid SET) and characterize per-transfer outcomes to inform evidence-based counseling for patients undergoing in vitro fertilization (IVF) with preimplantation genetic testing for aneuploidy (PGT-A). DESIGN/METHODS:Retrospective cohort study. SETTING/METHODS:University-affiliated fertility center. SUBJECTS/METHODS:Patients who underwent IVF with PGT-A followed by euploid SET between January 2014 and December 2024. EXPOSURE/METHODS:Up to six sequential euploid SETs until a live birth was achieved, or the patient discontinued additional transfers. MAIN OUTCOME MEASURES/METHODS:Estimated cumulative probability of achieving ≥1 LB and per-transfer rates of live birth, spontaneous abortion, biochemical pregnancy, and non-pregnant. RESULTS:Among 5811 patients undergoing 7763 euploid SETs attempts, the estimated cumulative probability of a LB increased from 63.1% after one SET to 92.0% after three, 98.3% after five, and 98.8% after six SETs. Per-transfer live birth rate declined from 63.1% at the first euploid SET to 54.0% at the second, then remained stable across subsequent attempts. Rates of spontaneous abortion, biochemical pregnancy, and non-pregnant followed a similar trend. Fewer than 5% of patients met criteria for recurrent implantation failure after three euploid SETs, and fewer than 2% remained without live birth after five SETs. CONCLUSION/CONCLUSIONS:Continued sequential transfer of euploid embryos is supported as the primary management strategy after early transfer failure. For patients able to generate an adequate euploid embryo inventory aligned with their individual risk tolerance, persistence with treatment is associated with a high likelihood of achieving a live birth.

PURPOSE/OBJECTIVE:Young adults with cancer (YAs) are rarely provided the necessary resources to make informed decisions about fertility preservation (FP) prior to beginning treatment. Digital decision aids are a promising strategy to ensure YAs receive timely, guideline-concordant information. We developed an alpha version Fertilit-e, a digital FP navigator, and conducted usability testing to obtain feedback from YAs. METHODS:We designed an alpha version of Fertilit-e that drew from existing evidence-based FP resources. Feedback was obtained from two waves of participants using a think-aloud framework, and modifications were made to the decision aid. RESULTS:Across waves, participants (n = 12) understood the purpose of Fertilit-e and thought modules were comprehensive and easy to understand. The usability of Fertilit-e was rated as excellent across waves and devices (iPad and computer). Participants suggested reducing the use of and better defining medical terminology and adding text to videos to enhance comprehensibility. CONCLUSIONS:YAs reported that Fertilit-e provided important information regarding FP in an understandable manner. Participants made suggestions for how to improve comprehensibility and usability that will guide future iterations of Fertilit-e. For example, tailoring algorithms and reorganization may direct users to the most relevant information. IMPLICATIONS FOR CANCER SURVIVORS/CONCLUSIONS:Digital decision aids may be a feasible and useful strategy for helping YAs navigate decisions regarding whether to pursue FP at the time of diagnosis. Additional research is needed to refine and evaluate such tools before integration into routine care.

Local community populations ("survivors") exposed to the World Trade Center (WTC) disaster experienced complex exposures to mixtures of dust and combustion products with potential carcinogenic effects. Survivors with certifiable WTC-related conditions are eligible for inclusion in the federally funded WTC Health Program. We provide an updated description of cancers in the WTC Environmental Health Center (EHC), a program for WTC survivors, through 31 December 2024. Using data from the WTC EHC Pan Cancer Database, we summarized demographics, exposure history, and tumor characteristics among enrollees with pathologically confirmed primary cancers meeting WTC Health Program certification criteria. Among 17,449 members, 7274 had a certifiable cancer diagnosis; excluding non-melanoma skin cancers, 6588 patients with 7643 eligible cancers were analyzed. Women comprised 50.3% of the cohort and 47.5% of diagnoses. Solid tumors accounted for 87% of certifications, with breast (22%) and prostate (19%) cancers most frequent, followed by lung (8%), thyroid (6%), colorectal (6%), and melanoma (4.5%). Lymphoproliferative and hematopoietic malignancies represented 13% of cases. Fourteen percent developed multiple primary cancers, and median latency clustered around 14-16 years. Compared with our previous report in 2020, the enrolled number of cancers increased 2.5-fold. These findings support the need for sustained surveillance and additional epidemiologic studies to improve cancer prevention and survivorship in this uniquely exposed population.

PURPOSE/OBJECTIVE:This study aimed to examine associations of bisphenol and phthalate exposure with arterial stiffness among women of reproductive age. METHODS:Participants include 637 adult women enrolled in the New York University Children's Health and Environment Study (NYU CHES), a prospective pregnancy cohort. The concentrations of eight bisphenols and 22 phthalate metabolites were quantified in up to three spot urine samples. Primary outcomes included brachial artery distensibility (BrachD) and carotid-femoral pulse wave velocity (cfPWV) as measures of peripheral and central arterial stiffness, respectively, along with blood pressure assessed at repeated study visits up to seven years from exposure measures. Associations between averaged, log2-transformed, creatinine-standardized chemical concentrations and subclinical vascular outcomes of interest were examined using linear mixed-effects models. RESULTS:In covariate-adjusted models, a doubling of bisphenol A was positively associated with BrachD (0.09%/mmHg, 95% confidence interval [CI] = 0.02, 0.16), a doubling of bisphenol S was negatively associated with mean arterial pressure (MAP) (-0.52 mmHg, 95% CI = -0.98, -0.05), a doubling of di(2-ethylhexyl) phthalate (DEHP) metabolites was negatively associated with diastolic blood pressure (DBP) (-0.81 mmHg, 95% CI = -1.38, -0.23) and MAP (-0.83 mmHg, 95% CI = -1.45, -0.21), and a doubling of antiandrogenic phthalate metabolites was associated with 0.62 mmHg lower DBP (95% CI = -1.22, -0.03) and 0.66 mmHg lower MAP (95% CI = -1.30, -0.02). CONCLUSION/CONCLUSIONS:These findings suggest that routine exposure to bisphenols and DEHP may be associated with vasorelaxation, potentially related to these chemicals' estrogenic and/or antiandrogenic effects.

OBJECTIVE:The objectives of this study were to determine 1) the prevalence of perceived mistreatment, 2) the source of mistreatment, and 3) the location where mistreatment occurred among obstetrics and gynecology residents. METHODS:We conducted a national survey of obstetrics and gynecology residents using an adapted validated questionnaire. RESULTS:Over half of participating obstetrics and gynecology residents reported mistreatment. The most common type of mistreatment reported was verbal or emotional abuse (57%). Patients/patients' families, attendings, nurses, and other residents were all common sources of mistreatment. The most frequent location was labor and delivery. Female, gender-diverse, Black, and lesbian, gay, bisexual, queer+ (LGBQ+) residents experienced mistreatment at higher rates. CONCLUSION/CONCLUSIONS:Obstetrics and gynecology residents report a high prevalence of mistreatment. Interventions to reduce mistreatment, especially on labor and delivery, will prove important to promote the respectful work environment necessary for optimal learning and patient care.

BACKGROUND:Emerging data suggests that glyphosate, a non-selective herbicide, can influence reproductive health. We investigated associations of prenatal exposure to glyphosate and aminomethylphosphonic acid (AMPA), with preterm birth and its subtypes. METHODS:We used data from the NYU Children's Health and Environmental Study, a prospective birth cohort in New York City (2016-2019). Participants (n=1450) provided urine samples at 4 to <18 weeks and 18 to 25 weeks gestation. Exposure was adjusted for creatinine and natural log transformed. Preterm birth was defined as a birth occurring before 37 weeks of gestation. We also explored preterm birth subtypes, spontaneous preterm births and medically indicated preterm births as secondary outcomes. To examine associations between glyphosate and AMPA at both timepoints with preterm birth, we used generalized estimating equations with a logit link function. RESULTS:Overall, 7% (n=103) of births were preterm. Glyphosate concentrations at 18-25 weeks was associated with preterm birth (OR: 1.35, 95% CI: 1.04, 1.76) and spontaneous preterm birth (OR: 2.01, 95% CI: 1.40, 2.90). AMPA was not associated with preterm birth in any model. CONCLUSIONS:These results support evidence that glyphosate may act upon pathways leading to preterm birth and spontaneous preterm birth. Our study highlights pregnancy as a vulnerable period to glyphosate exposure.

OBJECTIVE:We assessed the underlying etiology of MMR deficiency (dMMR), genetic (germline/somatic) versus epigenetic hMLH1, and associations between response rate, and survival outcomes in patients with advanced and recurrent dMMR endometrial adenocarcinoma treated with immune checkpoint inhibitors. METHODS:The Endometrial Cancer Molecularly Targeted Therapy Consortium (ECMT2) database was used to identify patients with mismatch repair deficient (dMMR) tumors treated with pembrolizumab or dostarlimab from 2016 to 2023. Cases were categorized into two groups- germline Lynch Syndrome mutation (gLS) and somatic Lynch Syndrome mutation (sLS), or MLH1 promoter hypermethylation (hMLH1). Clinical and pathologic data included patient demographics, tumor characteristics, recurrence date, survival, and treatment. RESULTS:A total of 133 patients were included: gLS/sLS (n = 34, 25.6%) or hMLH1 (n = 99, 74.4%). Demographic and tumor characteristics, including stage at diagnosis and histology were similar between groups. The response rate was 57.1% for the entire cohort [55.9% gLS/sLS, 57.6% hMLH1; (p = 0.90)]. The survival outcomes were not significantly different in the gLS/sLS and hMLH1 groups [2-year progression-free survival: 68.0% and 59.0% (p = 0.77); 2-year overall survival: 70.9% and 62.2% (p = 0.55)], respectively. CONCLUSION/CONCLUSIONS:Our findings suggest that response to immune checkpoint inhibitors and survival outcomes are not associated with different mechanisms of dMMR.