Faculty Bibliography

Endometrial cancer (EC) is now the leading cause of gynecologic cancer death in the United States. Recognizing the urgent need to improve outcomes for patients diagnosed with EC, The National Cancer Institute (NCI) Gynecologic Cancer Steering Committee (GCSC) convened a Clinical Trials Planning Meeting (CTPM) on January 8th and 9th 2024, "Refining the Approach to Endometrial Cancer in the Immunotherapy Era." Multi-disciplinary experts were charged with addressing critical challenges, to optimize treatment of EC in the new immunotherapy landscape. As part of the CTPM working groups were assembled to address several important aspects of clinical trial design. Working Group 1 (WG1) focused on translational science and was tasked with reviewing the scientific literature for data on validated discriminants of response to immunotherapy to inform trial concept development by the therapy-focused groups. The WG established that molecular subtyping of EC is now the standard approach for classifying endometrial tumors. Molecular subtyping for both prognostic and predictive applications should be considered when assessing biomarkers as well as therapeutic targets. Additionally, strategies to improve immune response like incorporation of radiation as well as therapy sequencing considerations should continue to be explored. A major key observation from WG1 was lack of validated discriminants for immunotherapy response beyond mismatch repair status and tumor mutational burden and exploration of additional discriminants of response and resistance will be critical with the increasing use of immunotherapy in EC.

OBJECTIVE:Next-generation sequencing and tumor testing to direct therapy in advanced/recurrent endometrial cancer are frequently used, but the impact of this approach is unclear. We sought to confirm the proportion of patients with at least 1 actionable alteration and whether the use of molecularly targeted therapy was associated with improved survival in metastatic endometrial cancer. METHODS:A multidisciplinary consortium was formed to study tumor testing and treatment with targeted therapies in advanced/recurrent endometrial cancer. Tumor testing and therapeutic decisions were physician's recommendations. The abstracted data included age, stage, grade, histology, race, ethnicity, treatment, genomic alterations, protein expression for Her2, p53, mismatch repair, estrogen and progesterone receptors, and survival. Statistical analyses were performed using SAS v9.4. RESULTS:A total of 967 patients from 12 centers were included. The median age was 64 years (range; 22-93 years). Of the participants, 68.5% were White, 24.0% were Black, 2.0% were Asian, and 92.7% were non-Hispanic. A total of 656 (67.8%) patients had recurrent/persistent disease and received a median of two (range; 0-9) therapies. 902 (93.3%) underwent tumor testing. Overall, 576 (94.0%) patients with next-generation sequencing testing had at least 1 genomic alteration in 11 pre-specified genes. The most frequent alterations were PI3K (35.8%), TP53 (34.7%), and PTEN (26.5%) mutations, respectively. A subset of 233 patients received 292 matched biologic therapies, and the median follow-up was 29.7 months, while the median progression-free survival and overall survival were 6.9 and 20.5 months, respectively. CONCLUSIONS:The consortium facilitated the development of real-world data on the patterns of genomic testing and molecularly targeted therapy used in a racially and geographically diverse patient cohort with advanced/recurrent endometrial cancer. Survival improved for those receiving matched biologic therapies compared to chemotherapy.

OBJECTIVE:Demonstrate a successful laparoscopic removal of endometriosis from within the inguinal canal via a step-by-step video explanation, underscore the importance of pre-operative MRI imaging, and provide education on anatomy and surgical technique. DESIGN/METHODS:Video case presentation of a successful laparoscopic removal of endometriosis from within the inguinal canal. SUBJECTS/METHODS:A single patient with MRI imaging revealing endometriosis invasion into the inguinal canal and local vasculature. The patient included in this video gave consent for publication of the video and posting of the video online including social media, the journal website, scientific literature websites (such as PubMed, ScienceDirect, Scopus, etc.) and other applicable sites. EXPOSURE/METHODS:The patient's abdomen was entered and vasculature was identified to prevent major bleeding. Appropriate exposure was achieved by transecting the round ligament to provide a landmark for the inguinal canal. The endometriosis was identified and dissected off the external iliac vasculature and the abdominal wall using the squeeze technique. The endometriosis was then dissected out of the inguinal canal, off the femoral artery, and then removed from the abdomen. Post-operatively, the patient was started on norethindrone acetate to suppress any residual disease and prevent recurrence. MAIN OUTCOME MEASURE/METHODS:Patient's pain and quality of life post-operatively. RESULTS:The patient noted immediate pain relief in the recovery room. One year post-operatively, the patient continued to endorse pain relief and no signs of hernia. CONCLUSION/CONCLUSIONS:Inguinal canal endometriosis is of rare occurrence. It typically presents as a groin lump or pain that is worse with menstruation. As the endometriosis is in close proximity to the abdominal wall and local vasculature, MRI imaging, as well as general surgery and vascular surgery consultation, are necessary for proper surgical planning. These are difficult operations that require proper understanding of pelvic and inguinal canal anatomy.

The objective of this review is to determine whether planned oocyte cryopreservation is successfully providing women with reproductive autonomy and the opportunity to shape their families. Planned oocyte cryopreservation is an established means to expand the reproductive function of oocytes and is not associated with an increased risk of congenital anomalies or short-term health risks to the offspring. There is sufficient clinical evidence to support the success of planned oocyte cryopreservation; however, this technology does not guarantee live birth, and outcomes greatly depend on both the age at cryopreservation and the total number of cryopreserved oocytes. While reproducibility between centres must be improved, the results from the authors two large, experienced centres are consistent and provide useful data for patient counselling. Planned oocyte cryopreservation provides the highest cumulative live birth rates (>75%) when it is performed below the age of 35 years and 15-20 or more mature oocytes are cryopreserved. Live birth rates from planned oocyte cryopreservation at an ideal age are higher than live birth rates from women who delay childbearing past their reproductive prime and then attempt natural conception followed by IVF if they are unsuccessful.

OBJECTIVE/UNASSIGNED:Sentinel lymph node biopsy (SLNB) for endometrial cancer staging may identify isolated tumor cells (ITCs). Although guidelines do not classify nodes with ITCs as positive, earlier papers reported that a significant proportion of gynecologic oncologists treat ITCs as they would positive nodes. The objective of this study was to examine practice patterns and determine if the presence of ITCs in endometrial cancer affects adjuvant treatment decision-making. METHODS/UNASSIGNED:test, and logistic regression were used with significance set at p < 0.05. RESULTS/UNASSIGNED:Of seven hundred thirty-four patients included, ITCs were identified in 41 patients (5.6 %). Deep myometrial invasion (61.0 % vs 20.5 %, p < 0.001) and lymphovascular invasion (58.4 % vs 17.7 %, p < 0.001) were more common in patients with ITCs than in those with negative lymph nodes. Patients with ITCs were more likely to receive adjuvant treatment (30 of 41, 73.2 % vs 289 of 693, 41.7 %, p < 0.001). When controlling for age, stage, histology, grade, and lymphovascular space invasion, ITCs were not associated with an increased likelihood of adjuvant therapy receipt. CONCLUSIONS/UNASSIGNED:Although patients with ITCs were more likely to receive adjuvant treatment, this was accounted for by other clinical and histological factors. Clinicians were likely to make decisions based on established risk factors, and more data are needed on the role of ITCs in the landscape of molecularly based decision making.

BACKGROUND:The relationship between fetal fraction and birth weight in twin gestations is poorly understood. OBJECTIVE:To investigate the relationship between first trimester cfDNA fetal fraction and birth weight < 10th percentile in twin gestations. STUDY DESIGN/METHODS:This is a planned secondary analysis of the Twin cfDNA Study, a 17-center retrospective cohort of twin pregnancies screened for aneuploidy using cfDNA in the first trimester from 12/2011 - 2/2022, excluding those with positive screen results for chromosomal aneuploidy. CfDNA testing was performed by a single lab using massively parallel sequencing (MPSS). Baseline characteristics and birth weight of pregnancies with normal fetal fraction were compared to those with low (<5%) and high (>95%) fetal fraction using univariable analyses and multivariable regression. RESULTS:A total of 1041 twin pregnancies were included. Chronic hypertension, elevated BMI, and self-identified Black race were associated with fetal fraction <5th percentile. There was no difference in median fetal fraction between those with birth weight <10th percentile in at least one twin (median [IQR] fetal fraction 12.2% [9.8, 14.8] versus those with normal birth weight (10th percentile) in both twins (median [IQR] fetal fraction 12.3% [9.7, 15.2] for normal birth weight, p = 0.49). There was no association between high or low fetal fraction and birth weight <10th percentile for one (p=0.45) or both (p=0.81) twins, and there was no association between high or low fetal fraction and birth weight <5th percentile for one (p=0.44) or both (p=0.74) twins. The results were unchanged after adjustment for potential confounders. CONCLUSION/CONCLUSIONS:In this large cohort, there was no association between the extremes of cfDNA fetal fraction and birthweight < 10th percentile, suggesting that first trimester fetal fraction may not predict impaired fetal growth in twin gestations.

BACKGROUND/UNASSIGNED:Studies have reported higher lung cancer incidence among groups with lower socioeconomic position (SEP). However, it is not known how this difference in lung cancer incidence between SEP groups varies across different geographical settings. Furthermore, most prior studies that assessed the association between SEP and lung cancer incidence were conducted without detailed adjustment for smoking. Therefore, we aimed to assess this relationship across world regions. METHODS/UNASSIGNED:In this international prospective cohort consortium study, we used data from the Lung Cancer Cohort Consortium (LC3), which includes 20 prospective population cohorts from 16 countries in North America, Europe, Asia, and Australia. Participants were enrolled between 1985 and 2010 and followed for cancer outcomes using registry linkages and/or active follow-up. We estimated hazard ratios (HRs) for the association between educational level (our primary measure of SEP, in 4 categories) and incident lung cancer using Cox proportional hazards models separately for participants with and without a smoking history. The models were adjusted for age, sex, cohort (when multiple cohorts were included), smoking duration, cigarettes per day, and time since cessation. FINDINGS/UNASSIGNED: = 0.75, 95% CI = 0.62-0.90). INTERPRETATION/UNASSIGNED:Based on longitudinal data from 2.5 million participants from 16 countries, our findings suggest that higher educational attainment was associated with lower lung cancer risk among participants with a smoking history, but not among participants who never smoked. Limitations of our study include that cohort participants cannot fully represent the general populations of the geographical regions included, and education was the only measure of SEP consistently available across our consortium. FUNDING/UNASSIGNED:This study was supported in part by the National Cancer Institute (NCI), the Lung Cancer Research Foundation (LCRF), and the World Cancer Research Fund (WCRF).

OBJECTIVE:Social determinants of health (SDOH) may impact the incidence of Respiratory Syncytial Virus (RSV) infection and the uptake of vaccinations in pregnancy. The objective of this study is to identify contributors to disparities in RSV vaccination in pregnancy. DESIGN/METHODS:This is a retrospective cohort study of patients delivering at term within three hospitals during February and March 2024, comparing pregnant patients identified as receiving vs not receiving RSV vaccinations. This period and gestational age were chosen to include patients who would have qualified for RSV vaccination administration. Vaccination status was extracted from standardized admission templates where these variables were recorded as discrete fields. Patients without RSV vaccination information were excluded. Sociodemographic factors, COVID vaccination status, and delivery campus were evaluated. Outcomes were analyzed using chi-squared, t-test, and McNemar test. RESULT/RESULTS:2181 patients met inclusion criteria and RSV vaccination information was available for 1548 patients (71%) with a 14% vaccination rate. Compared to those not vaccinated (n=1332), RSV vaccinated patients (n=216) were more likely to be older (30.7 vs 34.8, p<0.001), have private insurance (42% vs 85%, p<0.001), speak English (82% vs 95%, p<0.001), and deliver at our regional perinatal center (26% vs 77%, p<0.001). 50% of RSV vaccinated patients had a history of COVID vaccination compared to 33% of those not vaccinated against RSV (p<0.001). CONCLUSIONS:SDOH were associated with differences in RSV vaccination status. In addition, patients without RSV vaccination were less likely to have had COVID vaccination. These findings highlight the need to address SDOH to increase vaccination rates for vulnerable populations.

PURPOSE/OBJECTIVE:To provide updated fertility preservation (FP) recommendations for people with cancer. METHODS:A multidisciplinary Expert Panel convened and updated the systematic review. RESULTS:One hundred sixty-six studies comprise the evidence base. RECOMMENDATIONS/CONCLUSIONS:People with cancer should be evaluated for and counseled about reproductive risks at diagnosis and during survivorship. Patients interested in or uncertain about FP should be referred to reproductive specialists. FP approaches should be discussed before cancer-directed therapy. Sperm cryopreservation should be offered to males before cancer-directed treatment, with testicular sperm extraction if unable to provide semen samples. Testicular tissue cryopreservation in prepubertal males is experimental and should be offered only in a clinical trial. Males should be advised of potentially higher genetic damage risks in sperm collected soon after cancer-directed therapy initiation and completion. For females, established FP methods should be offered, including embryo, oocyte, and ovarian tissue cryopreservation (OTC), ovarian transposition, and conservative gynecologic surgery. In vitro maturation of oocytes may be offered as an emerging method. Post-treatment FP may be offered to people who did not undergo pretreatment FP or cryopreserve enough oocytes or embryos. Gonadotropin-releasing hormone agonist (GnRHa) should not be used in place of established FP methods but may be offered as an adjunct to females with breast cancer. For patients with oncologic emergencies requiring urgent oncologic therapy, GnRHa may be offered for menstrual suppression. Established FP methods in children who have begun puberty should be offered with patient assent and parent/guardian consent. The only established method for prepubertal females is OTC. Oncology teams should ensure prompt access to a multidisciplinary FP team. Clinicians should advocate for comprehensive FP services coverage and help patients access benefits.Additional information is available at www.asco.org/survivorship-guidelines.

Electronic health records (EHRs) present opportunities to study uterine fibroids uterine fibroids and endometriosis within diverse populations. When using EHR data, it is important to validate outcome classification via diagnosis codes. We performed a validation study of three approaches (1: ICD-10 code alone, 2: ICD-10 code + diagnostic procedure, and 3: ICD-10 code + all diagnostic information) to identify incident uterine fibroids and endometriosis patients among n=750 NYU Langone Health 2016-2023. Chart review was used to determine the true diagnosis status. When using a binary classification system (incident vs. non-incident patient), Approaches 2 and 3 had higher positive predictive values (PPVs) for uterine fibroids (0.86 and 0.87 vs. 0.78) and for endometriosis (0.70 and 0.73 vs. 0.66), but Approach 1 outperformed the other two in negative predictive values (NPVs) for both outcomes. When using a three-level classification system (incident vs. prevalent vs. disease free patients), PPV for prevalent patients was low for all approaches, while PPV/NPV of disease-free patients was generally above 0.8. Using ICD-10 codes alone yielded higher NPVs but resulted in lower PPVs compared with the other approaches. Continued validation of uterine fibroids/endometriosis EHR studies is warranted to increase research into these understudied gynecologic conditions.