Faculty Bibliography

OBJECTIVE:Mismatch repair deficiency (dMMR), high microsatellite instability (MSI-H), and high tumor mutation burden (TMB-H) are predictive and prognostic biomarkers in endometrial cancer. We aimed to characterize the racial/ethnic distribution of molecular markers and the clinical characteristics among endometrial cancer patients with TMB-H and MSI-H/dMMR. METHODS:The Endometrial Cancer Molecularly Targeted Therapy Consortium is a centrally verified clinical and molecular repository. Patients with endometrial cancer who underwent tumor profiling were included. TMB-H was defined as ≥10-12 mutations per megabase. MSI-H was determined by next-generation sequencing or polymerase chain reaction, and dMMR by loss of MLH1, MSH2, MSH6, or PMS2 on immunohistochemistry. Tumor biomarker positivity was defined as TMB-H and/or MSI-H/dMMR. Overall survival was assessed using Kaplan-Meier and Cox proportional hazard models. RESULTS:Among 742 patients, 22 % (n = 164) were biomarker positive: 12 % (n = 87) had both TMB-H and MSI-H/dMMR, 8 % (n = 63) had MSI-H/dMMR alone, and 2 % (n = 14) had 14 TMB-H alone. Only 9 % of non-Hispanic Black patients had biomarker positive tumors compared to 26 % of patients from other racial/ethnic groups. Pathogenic POLE mutations were rare (<1 %, n = 5). Patients with TMB-H had a higher proportion of high-risk histologies (43 %) than those with MSI-H/dMMR (24 %). Biomarker positive tumors were associated with a lower risk of death compared to biomarker negative tumors (aHR 0.63, 95 % CI: 0.46, 0.88). CONCLUSION/CONCLUSIONS:Less than 10 % of non-Hispanic Black patients with endometrial cancer had TMB-H and/or MSI-H/dMMR, and biomarker positivity was associated with improved survival. Prospective studies are necessary to elucidate how these molecular differences impact treatment and outcomes.

OBJECTIVE:To obtain perspectives about existing compensation structures in gynecologic oncology, including common challenges and successful strategies within diverse systems. METHODS:Electronic mail was used to recruit OB/GYN department chairs and directors of cancer centers who were gynecologic oncologists and responsible for administering compensation structures at their institution. Using a semi-structured guide, three interviewers conducted 30-min qualitative interviews, which were recorded and transcribed. Two coders used the constant comparative method to summarize key themes. RESULTS:Response rate was 65 %, resulting in 17 interviewees. Participants were a third women and in their current position for a median of 7 years. The most prominent theme was the tension of balancing reimbursement for revenue-generating clinical activities with non-clinical work in research and education. Chair discretionary funds were useful to offset unfunded responsibilities. Broad clinical productivity measures were used: from more traditional work Relative Value Units (wRVUs) to measures that captured downstream impact, such as number of new patients or surgeries. Even in institutions with centralized funds flow systems, disparities were frequently noted for the monetary value assigned per wRVU. Academic scorecards were described as a method to ascribe value for academic work, often for bonus incentives. Another common stressor unique to gynecologic oncology was low reimbursement for chemotherapy-related services compared to surgery. Provision of regular productivity reports was common, but full transparency was controversial. CONCLUSIONS:Our inquiry demonstrates that our academic leaders are unable to use compensation to fully support areas they deem important.

INTRODUCTION/BACKGROUND:Ischemic acute kidney injury (AKI) frequently occurs in the intensive care unit. However, early diagnosis is challenging, and specific treatment strategies are still lacking. Here, our study identified endogenous hepcidin was induced with increasing severity of ischemia/reperfusion (I/R) injury mostly in collecting duct (CD) principal and intercalated cells. METHODS:We employed RNA sequencing, immunoprecipitation, mass spectrometry, and gene knockdown and knockin technologies to define the role of hepcidin during I/R-induced kidney injury. RESULTS:Mechanically, RNA seq revealed hepcidin protected M-1 cells (murine cortical CD cell line) against ferroptosis following hypoxia/reoxygenation (H/R). Furthermore, immunoprecipitation-mass spectrometry identified hepcidin interacting with lactoferrin, consequently preserving the expression of lactoferrin following H/R which mediated the protective effect of hepcidin. Correspondingly, lactoferrin knockdown reduced the anti-ferroptotic effect of hepcidin in M-1 cells exposed to H/R revealing a novel function of hepcidin independent of the iron transporter ferroportin. In vivo, utilizing CD-specific hepcidin-knockin (HepcidinKspKI) and CD-specific hepcidin-knockdown mice (Adeno Associated Virus-Hep), we found that endogenous hepcidin protected against CD ferroptosis by preserving lactoferrin which consequently mitigated ischemic kidney injury and dysfunction, remarkedly improving the survival rate. Finally, recombinant hepcidin administration exhibited a comparable protective effect, albeit with less efficacy in reducing the mortality rate compared to conditional knockin of CD hepcidin. CONCLUSION/CONCLUSIONS:Collectively, our study identified an endogenous protective mechanism of injured CD cells via a hepcidin/lactoferrin/ferroptosis axis which may suggest a novel pharmacologic therapeutic for ischemic AKI.

The objective of this prospective, longitudinal cohort study was to evaluate the pilot effects of a 24-month exercise and nutrition intervention, called the Lifestyle Intervention for Fibroid Elimination Program (LIFE), at NYU Langone Health's Center for Fibroid Care. Specifically, we evaluate the impact on quality of life (QOL), symptom severity (SS), and clinical lab markers in 22 fibroid patients. Patients who underwent a procedure within 3 months of the start of the LIFE Program and completed up to 12 months of the program were included in this study. Participants were excluded if currently pregnant, postmenopausal, or had dietary restrictions or physical constraints that prevented them from participating fully in the intervention. This intervention required participants to follow a prescribed nutrition and exercise regimen for up to 12 months and attend at least 2 office visits with a physician. Participants also completed two quality of life questionnaires and regular ultrasound imaging. The demographic breakdown of our study cohort was 63.6% Black and 18.2% Hispanic/LatinX. A clinically meaningful improvement in QOL and symptom severity was found within the first year of the LIFE program. The QOL sub-scale scores that showed the greatest improvement were concern and energy/mood. Vitamin D lab values also showed a clinically meaningful improvement. The LIFE Program was associated with a reduction in symptom burden and an improvement in quality of life up to 12 months after a procedural fibroid intervention, yielding insight into how a lifestyle intervention may be an effective adjunct in improving patient quality of life.

INTRODUCTION/BACKGROUND:Hospital-to-skilled nursing facility (SNF) transitions have been characterised as fragmented and having poor quality. The drivers, or the factors and actions, that directly lead to these poor experiences are not well described. It is essential to understand the drivers of these experiences so that specific improvement targets can be identified. This study aimed to generate a theory of contributing factors that determine patient and caregiver experiences during the transition from the hospital to SNF. METHODS:We conducted a grounded theory study on the Medicine Service at an academic medical centre (AMC) and a short-term rehabilitation SNF. We conducted individual in-depth interviews with patients, caregivers and clinicians, as well as ethnographic observations of hospital and SNF care activities. We analysed data using dimensional analysis to create an explanatory matrix that identified prominent dimensions and considered the context, conditions and processes that result in patient and caregiver consequences and experiences. RESULTS:We completed 41 interviews (15 patients, 5 caregivers and 15 AMC and 6 SNF clinicians) and 40 h of ethnographic observations. 'They were talking to each other, but not to me' was the dimension with the greatest explanatory power regarding patient and caregiver experience. Patients and caregivers consistently felt disconnected from their care teams and lacked sufficient information leading to uncertainty about their SNF admission and plans for recovery. Key conditions driving these outcomes were patient and care team processes, including interdisciplinary team-based care, clinical training and practice norms, pressure to maintain hospital throughput, patient behaviours, the availability and provision of information, and patient's physical and emotional vulnerability. The relationships between conditions and processes were complex, dynamic and, at times, interrelated. CONCLUSION/CONCLUSIONS:This study has conceptualised the root causes of poor-quality experiences within the hospital-to-SNF care transition. Our theory generation identifies targets for clinical practice improvement, tailored intervention development and medical education innovations. PATIENT OR PUBLIC CONTRIBUTION/UNASSIGNED:We partnered with the Hospital Medicine Reengineering Network (HOMERuN) Patient and Family Advisory Council during all stages of this study.

OBJECTIVES/UNASSIGNED:The primary study objective was to determine the proportion of oncology physicians treating gynecologic oncology patients screening for sexual health concerns among patients with gynecologic malignancies. The secondary objective was to describe these physicians' perspectives on their role in evaluating sexual health concerns and barriers to managing sexual health in a gynecologic oncology office, by training level and gender. METHODS/UNASSIGNED:This was a cross-sectional, quantitative, 23-item survey based on a previously validated questionnaire. It was administered across the United States to physicians (attendings and fellows) treating gynecologic oncology patients using the Society of Gynecologic Oncology database. RESULTS/UNASSIGNED:There was a 10.2 % response rate with 166/1621 physicians completing the survey. Thirty-four (23.1 %) were fellow trainees and 113 (77.0 %) were attendings. Most participants were gynecologic oncologists (155/166, 93.4 %), with radiation oncologists (1/166, 0.6 %), and other physicians (10/166, 6.0 %) also responding. The majority (137/166, 82.0 %) identified as female providers and (29/166, 17.4 %) identified as male. Just over half (99/166, 59.6 %) of providers routinely asked about sexual health concerns of their patients. Attendings more often discussed sexual health with patients when compared to fellows when controlling for academic setting and gender (OR 2.8, 95 % CI 1.6-4.1, p < 0.01). Most providers (117/166, 70.5 %) felt they needed to improve their knowledge on sexual function. CONCLUSIONS/UNASSIGNED:surveyed, almost all feel sexual health should be discussed with their patients. Only about 59% routinely ask about sex health concerns. Future studies should focus on effective ways to incorporate sexual health screenings into gynecologic oncology clinics.

PURPOSE/OBJECTIVE:To evaluate outcomes from the Trainers in Oncofertility Reproductive Communication and Health (TORCH) program, which trains Allied Health Professionals (AHPs) to become leaders in counseling AYA cancer patients on reproductive health. METHODS:ECHO-TORCH was developed for alumni of the Enriching Communication Skills for Health Professionals in Oncofertility (ECHO) program. It included web-based modules on evidence-based content, adult learning principles, and a simulation exercise for skill practice. Evaluation involved pre/post-tests, skills assessments during simulation via standardized learners (SLs) and faculty observers, and online focus groups. RESULTS:ECHO-TORCH learners (n = 10) showed improved knowledge, from 76% on pre-test to 86% on post-test (p < 0.01). Both SLs (86%) and faculty observers (90%) showed high likelihood of inviting learners back for future presentations. In online focus groups, participants described the modules as clear, relevant, and highly satisfying. Learners appreciated the opportunity for practice and structured review of the ECHO content. CONCLUSIONS:The ECHO-TORCH program improved AHPs' knowledge and skills in teaching reproductive health content to AYA cancer patients. The train-the-trainer model empowers AHPs to disseminate knowledge within their institutions, ultimately improving care quality and empowering AYA patients to make informed decisions about reproductive health. IMPLICATIONS FOR CANCER SURVIVORS/CONCLUSIONS:Continued development of professionals in reproductive healthcare will significantly enhance cancer survivors' quality of life by supporting informed decision-making regarding their reproductive health.

OBJECTIVE:In part 1 of the phase 3 RUBY trial (NCT03981796) in patients with primary advanced or recurrent endometrial cancer, dostarlimab plus carboplatin-paclitaxel significantly improved progression-free and overall survival vs placebo plus carboplatin-paclitaxel. Post hoc analyses examined the impact of adding dostarlimab to chemotherapy, compared with placebo plus chemotherapy, on quality-adjusted time without symptoms of disease progression or toxicity of treatment in this patient population. METHODS:Patients were randomized 1:1 to receive dostarlimab/placebo plus chemotherapy every 3 weeks for 6 cycles, followed by dostarlimab/placebo monotherapy every 6 weeks for up to 3 years. Data from the first interim analysis (September 28, 2022) were used, and quality of life (QoL) was assessed with the EuroQoL 5-Dimensions 5-Level questionnaire. Quality-adjusted time without symptoms of disease progression or toxicity of treatment was calculated as the sum product of the restricted mean survival times spent in 3 mutually exclusive states: toxicity, time without symptoms of disease progression or treatment toxicity, and relapse, and utilized each state's corresponding QoL. RESULTS:In the dostarlimab and placebo arms, 241 and 246 patients were analyzed for safety, respectively. In the overall population, the mean (95% CI) duration of quality-adjusted time without symptoms of disease progression or toxicity of treatment was significantly longer in the dostarlimab arm (24.75 months [22.88 to 26.65 months]) than in the placebo arm (20.34 months [18.95 to 21.76 months]; the mean difference [95% CI] of 4.41 months [2.01 to 6.77 months], p < .001). Benefits in quality-adjusted time without symptoms of disease progression or toxicity of treatment after dostarlimab treatment were observed regardless of mismatch repair/microsatellite instability status or toxicity criteria used and were predominantly driven by the time without symptoms of disease. CONCLUSIONS:Dostarlimab plus carboplatin-paclitaxel treatment is associated with meaningful improvement in survival, avoidance of substantial toxicity, and maintenance of patient-reported QoL in patients with primary advanced or recurrent endometrial cancer.

BACKGROUND/OBJECTIVES/OBJECTIVE:The Family-centered Adolescent Sperm banking values clarification Tool (FAST) was developed to facilitate sperm banking communication and decision-making pre-cancer treatment. The FAST was tested in a pilot parallel randomized controlled trial (Fertility Preservation Discussions And Decisions: "FP-DAD"-NCT04268004), aiming to (i) assess feasibility/acceptability of FP-DAD; and (ii) examine efficacy regarding banking attempts (yes/no) and decision quality. Differences in decision quality by banking attempt were explored. DESIGN/METHODS/METHODS:Males (12-25 years, new cancer diagnosis) and caregivers were randomized to standard of care (fertility consult) or FP-DAD (fertility consult + FAST + interventionist-led discussion). One month later, FP-DAD participants completed acceptability surveys. Both arms completed the Brief Subjective Decision Quality measure. Descriptive statistics, chi-square, and independent samples t-tests/mixed-models examined relationships between variables. RESULTS:Acceptability ratings of FP-DAD were high (88%-100%). Recruitment and participation challenges limited the final sample size (21 adolescents and 32 caregivers). Banking attempts (67% in standard of care vs. 82% in FP-DAD) did not differ by arm. While decision quality was not significantly different between groups, effect sizes were medium-large for four of six items for adolescents (d = 0.6 to -0.90) and two of six for caregivers (d = 0.36 to -0.78). Decision quality was significantly higher across several domains among those who banked. CONCLUSIONS:FP-DAD had high acceptability, though feasibility challenges (e.g., time contraints) limited full family participation. Findings showed limited efficacy, but effect sizes suggest this may be due to sample size. Relationships between banking attempts and decision quality emphasize banking benefits. Findings will inform adaptations to the FAST for clinical implementation.