Objective. To analyze the impact of the early COVID-19 pandemic on the diagnosis and initiation of treatment for patients with gynecologic cancer.Methods. Patients diagnosed with gynecologic cancer in the National Cancer Database during 2017-2020 were included. For the first aim, incidence rate ratios were calculated to compare gynecologic cancer diagnosis in the first year of the COVID-19 pandemic to the three years prior, and factors associated with a reduction in diagnosis were identified. For the second aim, patients who experienced an 8-week delay in cancer treatment were compared to those who did not. Multivariate logistic regression was used to identify factors associated with treatment delay. Propensity score analysis was utilized to compare the rate of cancer treatment delay in patients who were diagnosed with COVID-19 to those who were not.Results. The incidence rate ratio of being diagnosed with gynecologic cancer in 2020 versus 2017-2019 was 0.90 (95%CI 0.90-0.91). Factors associated with increased risk of missed or delayed diagnosis in 2020 included cervical cancer, earlier cancer stage, younger age, lower levels of medical comorbidity, and lack of health insurance. In 2020, factors associated with treatment delay included COVID-19 diagnosis (aOR 1.50, 95%CI 1.35-1.67), in addition to race and ethnicity, insurance type, comorbidity, cancer stage, and primary site. The risk of treatment delay remained significantly elevated in patients diagnosed with COVID-19 after propensity-score matching.Conclusions. Gynecologic cancer diagnosis and timely provision of care were negatively impacted during the first year of the COVID-19 pandemic, with certain subgroups at elevated risk.(c) 2023 Elsevier Inc. All rights reserved.

Epithelioid trophoblastic tumor (ETT) is a rare variant of gestational trophoblastic neoplasia (GTN) that develops from chorionic-type intermediate trophoblast, is more resistant to chemotherapy than choriocarcinoma, and presents with metastatic disease in 25–35% of cases.We report a case of a 32-year-old who presented one week postpartum with severe abdominal pain and was found to have profound anemia and an elevated hCG level. CT scans and MRI revealed bleeding from hepatic masses, multiple hemorrhagic pulmonary nodules, a 7 cm uterine mass, and brain metastases. She underwent emergent hepatic embolization, was started on induction chemotherapy with weekly low-dose etoposide and cisplatin followed by a transition to etoposide, high-dose methotrexate, actinomycin D, etoposide, and cisplatin (HD EMA-EP), received stereotactic brain radiotherapy, and subsequently underwent minimally-invasive hysterectomy. She remains disease free over one year after the completion of treatment.An aggressive multimodal treatment approach employing etoposide/cisplatin-based chemotherapy as well as surgical procedures to control hemorrhage or excise resistant disease, and radiotherapy for brain metastases can result in successful treatment of stage IV ETT.

Objectives: To estimate the incidence of and factors associated with acute kidney injury (AKI) in women undergoing elective open gynecologic oncology surgery using an Enhanced Recovery After Surgery (ERAS) protocol. Methods: A retrospective cohort study was performed. All women who underwent open gynecologic surgery for suspected or confirmed malignancy using an ERAS protocol between March 2018 to December 2019 were identified. Incidence and degree of AKI were classified by the Kidney Disease Improving Global Outcomes (KDIGO) staging system. Descriptive statistics and univariate analysis for associated factors were performed using Fisher's exact test. Results: A total of 114 patients met inclusion criteria. The majority underwent abdominal hysterectomy (102/114, 89%) with anesthesia time ≥240 minutes in 73% of patients. Median age and body mass index (BMI) were 54 years and 28.1 kg/m2, respectively. A total of 9 patients (9/114, 7.9%) developed KDIGO class 1 (7/114, 6.1%) or class 2 (2/114, 1.8%) AKI. All but one case of AKI (8/9, 88.8%) resolved by day of discharge. Factors associated with AKI included: obesity (OR 13.8, p=0.003), ASA 3+ (OR 11.8, p=0.01), complication other than AKI (OR 9.3, p=0.02), cardiovascular disease (OR 8.3, p=0.03) diabetes mellitus (OR 4.7, p=0.04), and baseline creatinine of ≥1.0 (OR 9.3, p=0.04). Procedural blood loss, age >65, ECOG performance status, receipt of neoadjuvant chemotherapy, intraoperative time, intraoperative albumin infusion, and postoperative transfusion were not significantly associated with AKI. Conclusions: AKI is uncommon in women undergoing open gynecology oncology surgery using an ERAS protocol. Nearly all cases resolved prior to discharge and were associated with patient-specific factors. While care should be taken during protocol implementation to monitor for and to prevent AKI, fluid restriction principles used in ERAS protocols are safe in this study population. To estimate the incidence of and factors associated with acute kidney injury (AKI) in women undergoing elective open gynecologic oncology surgery using an Enhanced Recovery After Surgery (ERAS) protocol. A retrospective cohort study was performed. All women who underwent open gynecologic surgery for suspected or confirmed malignancy using an ERAS protocol between March 2018 to December 2019 were identified. Incidence and degree of AKI were classified by the Kidney Disease Improving Global Outcomes (KDIGO) staging system. Descriptive statistics and univariate analysis for associated factors were performed using Fisher's exact test. A total of 114 patients met inclusion criteria. The majority underwent abdominal hysterectomy (102/114, 89%) with anesthesia time ≥240 minutes in 73% of patients. Median age and body mass index (BMI) were 54 years and 28.1 kg/m2, respectively. A total of 9 patients (9/114, 7.9%) developed KDIGO class 1 (7/114, 6.1%) or class 2 (2/114, 1.8%) AKI. All but one case of AKI (8/9, 88.8%) resolved by day of discharge. Factors associated with AKI included: obesity (OR 13.8, p=0.003), ASA 3+ (OR 11.8, p=0.01), complication other than AKI (OR 9.3, p=0.02), cardiovascular disease (OR 8.3, p=0.03) diabetes mellitus (OR 4.7, p=0.04), and baseline creatinine of ≥1.0 (OR 9.3, p=0.04). Procedural blood loss, age >65, ECOG performance status, receipt of neoadjuvant chemotherapy, intraoperative time, intraoperative albumin infusion, and postoperative transfusion were not significantly associated with AKI. AKI is uncommon in women undergoing open gynecology oncology surgery using an ERAS protocol. Nearly all cases resolved prior to discharge and were associated with patient-specific factors. While care should be taken during protocol implementation to monitor for and to prevent AKI, fluid restriction principles used in ERAS protocols are safe in this study population.

Abstract Approximately one-third of epithelial ovarian tumors exhibit higher levels of c-Met, a receptor tyrosine kinase, activated by Hepatocyte Growth Factor (HGF). c-Met plays an important role in the growth and metastasis of tumor cells. Increased c-Met expression is associated with decreased survival and resistance to chemotherapy in various tumors. More recently, our team identified c-Met overexpression as a mechanism of resistance to neoadjuvant chemotherapy (NACT) in ovarian cancer (OC). The c-Met pathway has been explored as a therapeutic target in various solid tumors, and antibodies targeting c-Met have been proposed as novel anticancer agents. This project aims to investigate the effectiveness of a c-Met monoclonal antibody-drug conjugate (c-Met ADC) in OC models. Here we show that the anti-c-Met antibody alone effectively diminishes c-Met signaling (phosphorylation of c-Met and downstream Akt) but does not inhibit OC cell proliferation. In contrast, the c-Met ADC significantly decreases viability and induces apoptosis in c-Met-expressing OC cells. To validate c-Met expression as a predictor of resistance to NACT in OC, we analyzed c-Met expression in matched pre- and post-treatment samples collected from OC patients undergoing treatment with NACT and in a tissue microarray containing 20 ovarian tumors post-NACT. Detectable c-Met was recorded in ~50% of post-NACT specimens. We evaluated the in vitro antitumor activity of c-Met-ADC on the primary cells isolated from patients, before and after NACT, to assess tumor cell sensitivity to c-Met ADC. The results from these studies support the development of c-Met-ADC as a novel treatment for OC. Citation Format: Anusha Chaparala, Wendy M. Swetzig, Anna E. Strohl, Jian-Jun Wei, Daniela Matei, Shohreh Shahabi. Developing a novel treatment for advanced ovarian cancer by targeting the c-Met pathway [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research; 2019 Sep 13-16, 2019; Atlanta, GA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(13_Suppl):Abstract nr A36.

Placental site trophoblastic tumor (PSTT) is a rare variant of gestational trophoblastic neoplasia (GTN) that is characterized by slow growth resulting in mostly uterine-confined disease, low human chorionic gonadotropin (hCG) levels, and resistance to chemotherapy. Our objective was to update our center's experience with PSTT with respect to presentation, prognostic factors, treatment, and outcomes from 2003 to 2019. Thirteen women with PSTT were identified. Mean age was 32 years. The most frequent presenting symptom was abnormal uterine bleeding (69%). A uterine mass was noted in 62%. The diagnosis was usually established by endometrial biopsy or curettage (62%). Nonmolar pregnancy was the preceding gestation in 85%. Median time from last pregnancy to diagnosis was 13 months (range 0–240 months). Serum hCG levels at diagnosis ranged from 1 to 2606 mIU/mL (median 98 mIU/mL). Three women (23%) presented with metastatic disease. All 13 women underwent surgery: 12 had a hysterectomy, 1 had a fertility-sparing hysteroscopic resection, and 2 underwent pulmonary metastatectomy. Nine women (69%) also received chemotherapy for persistently elevated hCG levels after hysterectomy (2), high-risk factors (4), or metastatic disease (3). Overall survival was 100% with a median survival of 65 months (range 30–167 months). Survival for PSTT increased from 57% to 100%, including from 33% to 100% for metastatic disease, at our center from 1982 to 2003 to 2003–2017. Surgery is the most important component in the treatment of women with PSTT. Multidrug platinum/etoposide- chemotherapy should be used in women with metastatic disease and considered in women with nonmetastatic disease with high-risk features.

Perivascular epithelioid cell tumors (PEComa) represent a rare family of tumors characterized by distinct histology and immunohistochemistry characteristics. Approximately one-quarter of reported cases are gynecologic in origin and associated pregnancies are rare. We report a case of PEComa in pregnancy with initial undiagnosed presentation at 18 weeks of gestation and subsequent presentation and diagnosis at 30 weeks of gestation. Abdominal pain led to the use of magnetic resonance imaging, which raised concerns about placentation abnormality and abdominal pregnancy. Exploratory laparotomy was notable for a 10 cm by 15 cm posterior uterine defect through which the placenta and amniotic sac containing the fetus were extruded. Placenta-like tissue was noted to be invading through the anterior wall of the uterus, which led to concern regarding placenta percreta. A total abdominal hysterectomy and bilateral salpingectomy were then performed, given the complete loss of normal uterine architecture. Pathology returned with findings of placenta accreta and PEComa. Indolent uterine rupture in the setting of PEComa led to an ongoing viable abdominal pregnancy. Uterine PEComa can masquerade as a placenta and lead to obstetrical complications.

OBJECTIVE:To compare the rate of delayed 30-day lower genitourinary tract injury in women who underwent cystoscopy at the time of hysterectomy for benign indications to those who did not.METHODS:This was a retrospective cohort study of patients who underwent hysterectomy without a concomitant procedure for prolapse or incontinence for benign pathology with a general obstetrician-gynecologist (ob-gyn) recorded in the National Surgical Quality Improvement Program targeted hysterectomy file between 2015 and 2017. The primary outcome was a delayed lower genitourinary tract injury in the 30 days after hysterectomy. Secondary outcomes included urinary tract infection and operative time. The exposure of interest was cystoscopy at the time of hysterectomy. Stratified analysis was performed by route of surgery. Bivariable tests were used to examine associations.RESULTS:We identified 39,529 women who underwent hysterectomy for benign indications with a general ob-gyn. Surgical approach was open (26%), laparoscopic or robotic assisted laparoscopic (46%), and vaginal or vaginally assisted (28%). Overall, 25% of women underwent cystoscopy at the time of hysterectomy; cystoscopy was more commonly performed in laparoscopic or robotic (32%) and vaginal hysterectomy (25%) as compared with open hysterectomy (11%) (P<.001). There was no difference in delayed lower genitourinary tract injury between patients who underwent cystoscopy at time of hysterectomy compared with those who did not undergo cystoscopy (0.27% vs 0.24%, P=.64). Patients who underwent cystoscopy were more likely to be diagnosed with a urinary tract infection (2.6% vs 2.0%, RR 1.27 95% CI 1.09-1.47). Median operative time was increased by 17 minutes in cases where cystoscopy was performed (132 vs 115 minutes, P<.001).CONCLUSION:Cystoscopy at the time of hysterectomy for benign indications does not result in a lower rate of 30-day delayed lower genitourinary tract injury compared with no cystoscopy.

OBJECTIVE To estimate the associations among race, route of hysterectomy, and postoperative complications among women undergoing hysterectomy for benign indications. METHODS A cohort study was performed. All patients undergoing hysterectomy for benign indications, recorded in the National Surgical Quality Improvement Program and its targeted hysterectomy file in 2015, were identified. The primary exposure was patient race. The primary outcome was route of hysterectomy and the secondary outcome was postoperative complication. Associations were examined using both bivariable tests and logistic regression. RESULTS Of 15,136 women who underwent hysterectomy for benign indications, 75% were white and 25% were black. Black women were more likely to undergo an open hysterectomy than white women (50.1% vs 22.9%; odds ratio [OR] 3.36, 95% CI 3.11-3.64). Black women had larger uteri (median 262 g vs 123 g; 60.7% vs 25.6% with uterus greater than 250 g), more prior pelvic surgery (58.5% vs 53.2%), and higher body mass indices (32.7 vs 30.4). After adjusting for these and other clinical factors, black women remained more likely to undergo an open hysterectomy (adjusted OR 2.02, 95% CI 1.85-2.20). Black women experienced more major complications than white women (4.1% vs 2.3%; P<.001) and more minor complications (11.4% vs 6.7%; OR 1.78, P<.001). Again these disparities persisted with adjustment (major adjusted OR 1.56, 95% CI 1.25-1.95; minor adjusted OR 1.27, 95% CI 1.11-1.47). CONCLUSIONS Black women undergo a higher proportion of open hysterectomy and experience more major and minor postoperative complications. These differences persisted even after adjusting for confounding medical, surgical, and gynecologic factors.

Objective: In the United States, where centralization of the initial management of gestational trophoblasic neoplasia (GTN) does not exist, outcomes may be suboptimal. We used the National Cancer Database (NCDB) to describe the real-world overall survival of American women with GTN.

Objective: To investigate associations between race, route of hysterectomy, and complications from hysterectomy while controlling for patient-level factors.

In 2018, women diagnosed with gestational trophoblastic neoplasia (GTN) who receive appropriate treatment can expect cure rates approaching 100% [1]. Historically, however, this has not always been the case. Before the introduction of chemotherapy into their management over 50 years ago, outcomes for GTN were poor. The mortality rate for invasive mole approached 15%, most often because of hemorrhage, sepsis, embolic phenomena, or complications from surgery. Choriocarcinoma carried a particularly grave diagnosis, with mortality rates of nearly 100% when metastases were present and approximately 60% when hysterectomy was done for apparent non-metastatic disease [2].

There is no reliable way to distinguish symptomatic uterine fibroids from sarcoma without a surgical specimen. Many women with a uterine sarcoma are initially managed without hysterectomy under a presumed fibroid diagnosis, without understanding sarcoma risks. Currently many alternatives to hysterectomy, including medical and procedural interventions, for treatment of fibroids are promoted. The sarcoma incidence among women with presumed fibroids is 0.29% (1/340) to 0.05% (1/2000). Nonmetastatic leiomyosarcoma has a 63% 5-year survival rate whereas metastatic leiomyosarcoma has a 14% 5-year survival rate. In uterine sarcoma, we often cannot identify who has sarcoma before making a potentially cure-denying decision by delaying surgery. Therefore, women electing an alternative to hysterectomy for fibroids should undergo an informed consent process that specifically includes discussion of uterine sarcoma incidence and mortality. Alternatives to hysterectomy for presumed fibroids remain preferable treatment options for many women with symptomatic fibroids, so long as underlying sarcoma risks are adequately discussed. The challenge for obstetrician- gynecologists then is how to provide better informed consent and maintain the primacy of patient autonomy over our concern to "First, do no harm." Major threats to patient's autonomy are faced in the sarcoma risk discussion. How we should present sarcoma risk information to avoid being dismissive of sarcoma or frightening women toward hysterectomy is unstudied. Research is needed to determine how to provide sarcoma risk information with less bias during informed consent.

Objective: To determine overall survival (OS) and factors associated with OS after pelvic exenteration for cervical cancer.Methods: Women with cervical cancer who underwent exenteration (n = 517) were identified from the 1998 to 2011 National Cancer Database. Kaplan-Meier and multivariate Cox proportional-hazards survival analyses were performed to test for associations of potential explanatory variables with OS. Analyzed confounders included age, insurance status, income, distance from home to treatment center, stage, exenteration type, surgical margin status, and treatment with adjuvant radiation and/or chemotherapy.Results: Among the entire cohort with clinical follow-up (n = 313), median OS was 24 months. Stage (P= 2.5 x 10(-12)), lymph node status (P= 1.3 x 10(-7)), insurance status (P = 1.5 x 10(-5)), and histologic type (P = 0.04) were significantly associated with OS by the log-rank test. Unadjusted median OS was 24.2 and 61.8 months for women with squamous and adenocarcinoma histologies, respectively. By multivariate Cox regression, age, insurance status, stage, margin status, and adjuvant radiation were associated with OS. Histology was not independently associated with OS on multivariate regression. Among women with node-negative disease, median OS was 73.2 months.Conclusions: Exenteration may be curative for more than half of women with node-negative cervical cancer. Stage, insurance status, lymph node status, and surgical margin are independently associated with differential OS after exenteration.

Uterine smooth muscle tumors (USMTs) consist of a group of histologically heterogeneous and clinically diverse diseases ranging from malignant leiomyosarcoma (LMS) to benign leiomyoma (ULM). The genetic alterations in LMS are complex, with some genetic alterations present in both LMS and other atypical histologic variants of USMT. In this study, we reviewed 119 USMTs with a diagnosis of LMS, smooth muscle tumor of uncertain malignant potential, atypical leiomyomas/leiomyoma with bizarre nuclei, and cellular leiomyoma, as well as 46 ULMs and 60 myometrial controls. We selected 17 biomarkers highly relevant to LMS in 4 tumorigenic pathways including steroid hormone receptors (estrogen receptor [ER] and progesterone receptor [PR]), cell cycle/tumor suppressor genes, AKT pathway markers, and associated oncogenes. ER and PR expression was significantly lower in LMS than smooth muscle tumor of uncertain malignant potential, atypical leiomyomas/leiomyoma with bizarre nuclei, cellular leiomyoma, and ULM (P < .01). Sixty-five percent of LMSs showed complete loss of ER, and 75% of LMSs showed complete loss of PR. All cell cycle genes were differentially expressed in different types of tumor, but significant overlap was noted. More than 75% of LMSs had Ki-67 index greater than 33%, and only 5% in all other types of USMT. Expression of the selected oncogenes varied widely among different types of USMT. PR positivity and p53 had a borderline association with progression-free survival (P = .055 for PR and P = .0847 for p53). Furthermore, high PR expression was significantly associated with a longer overall survival (P = .0163, hazard ratio 0.198). Cell proliferative indices (Ki-67) and sex steroid hormone receptors were the most valuable markers in differentiating LMS from other USMT variants.

Objective: To determine overall survival (OS) and factors associated with OS of women with gynecologic leiomyosarcoma (LMS).

To determine the cost-effectiveness of transversus abdominis plane block with liposomal bupivacaine (TAP) compared to oral opioids alone for acute postoperative pain after laparoscopic hysterectomy for early endometrial cancer.

Objective The aim of this study was to compare overall survival (OS) of women with advanced ovarian cancer treated with primary debulking surgery (PDS) or neoadjuvant chemotherapy (NAC) using a large national cohort. Methods The 1998–2011 National Cancer Database was queried to identify women with stage III or IV ovarian cancer treated with multiagent chemotherapy and stage-appropriate surgery. Overall survival was estimated and compared using Kaplan-Meier analysis between women who received PDS followed by multiagent chemotherapy or NAC followed by interval surgery. Multivariable Cox proportional hazards regression model tested for associations of potential explanatory variables with OS. Analyzed confounders included age, composite comorbidity scores, stage, grade, histology, insurance status, income quartile, and race. Results Overall, 44,907 women (85.9%) underwent PDS, and 7348 women (14.1%) received NAC. Women who received NAC were older (64 vs 61 years, P < 0.001), had higher comorbidity scores (P < 0.001), and more often had stage IV disease (44.1% vs 26.1%, P < 0.001). Median OS was 41.1 (40.5–41.7) months among women who underwent PDS compared with 30.3 (29.3–31.1) months among women who received NAC (log-rank, P < 0.001). Among women with stage III disease, PDS was associated with increased OS compared with NAC (median OS, 44.9 [44.2–45.7] vs 31.4 [30.2–33.0] months; hazard ratio [95% confidence interval], 0.70 [0.66–0.76]; P < 0.001). Among women with stage IV disease, there was no OS difference between PDS and NAC cohorts (median OS, 31.2 [30.4–32.3] vs 28.4 [27.2–30.2] months; hazard ratio [95% confidence interval], 0.93 [0.85–1.02]; P = 0.12). Conclusions Primary debulking surgery was associated with increased OS among women with stage III but not stage IV ovarian cancer in a nationally representative cohort with low NAC use. If this finding reflects treatment assignment bias, it suggests that providers often well select candidates for PDS rather than NAC, although median OS times remain low.

e13047 Background: Women with deleterious BRCA1/2mutations have a significantly increased lifetime risk to develop ovarian cancer. Prophylactic surgery can significantly reduce ovarian cancer risk. The Northwestern Ovarian Cancer Early Detection and Prevention Program (NOCEDPP) was established to monitor this high-risk population prior to risk-reducing surgery. For such patients, providers in the NOCEDPP recommend screening with CA-125 and transvaginal ultrasound (TVUS) biannually. The aim of this study was to examine screening rates of women who have not had surgery but attend the NOCEDPP. Methods: We reviewed electronic health records of 1,662 women who attended the NOCEDPP clinic between October 2005 – October 2015. Demographic and clinical characteristics and utilization of screening were analyzed retrospectively using descriptive statistics and Kruskal-Wallis H-tests to examine differences in screening rates by age, race, ethnicity and insurance type. Results: Of the 1,662 women initially identified, 385 had a known BRCA mutation, 303 had an appointment with at least 6 months between first and last procedure – the sample included in the final analysis. Compared with women ages 35-45 (median = 1.91) and 45+ (median = 1.18), women ages 20-35 attended the most screenings per year (median = 2.12) p = 0.001, a rate consistent with biannual recommendations. There were no significant differences in screening rate by race, ethnicity, or insurance coverage. Conclusions: Despite changes in national guidelines, providers in our high-risk clinic continue to recommend CA-125 and TVUS biannually. Our preliminary data indicates patients’ attendance is uninfluenced by race, ethnicity, or insurance coverage. Further exploration of the impact of age is warranted. Implication of findings indicate a high-risk clinic may positively impact screening behaviors above and beyond factors typically associated with non-adherence.

Objective: To examine the current experience with cancer in pregnancy at a high-volume academic institution.

Objective: Bioinformatics analyses may suggest incorrect inferences regarding disease biology or biomarkers if clinical confounders that determine key outcomes are unrecognized. To reconcile previously reported gene expression biomarkers in ovarian cancer, we determined biomarker genes robust to differences in modeling versus excluding survival-determining clinical confounders.