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Plain language summary Maintenance therapy is a treatment option intended to keep ovarian cancer from coming back or getting worse for as long as possible after responding to chemotherapy. PARP inhibitors are a new type of maintenance therapy for ovarian cancer. This study aimed to understand the patients' and physicians' preferences for the benefits and risks associated with different PARP inhibitors used as maintenance therapy for ovarian cancer. Participants were asked to compare various treatment options based on their different safety profiles, effectiveness and form of medication (e.g., three capsules by mouth once a day versus two tablets by mouth twice a day), and then choose the treatment they most preferred. Through this exercise, the treatment features that mattered most to patients and physicians were identified. The most important treatment feature for patients was decreasing the chance of experiencing a serious side effect that requires medical intervention or hospitalization. In contrast, physicians valued lengthening the time that a cancer remains stable and does not worsen. To accept a 37% higher chance of experiencing a side effect that requires medical intervention or hospitalization, patients expect their cancer to remain stable and not worsen for an additional 28 months. This was a large difference from the 6 months that the physicians would consider as acceptable. The least important treatment features for patients are the amount of pills required per dose, the form of the given medication (e.g., tablet vs capsule) and the schedule of taking the treatment. On the other hand, physicians were least concerned about lowering the risk of experiencing low blood counts that, requiring medical intervention.

ObjectivePlasma energy ablation vaporizes tissues similar to carbon dioxide laser ablation, but is not hindered by the unique hazards and regulation of laser technology. We aimed to evaluate the complication rate and effectiveness of plasma versus laser ablation in the treatment of vulvovaginal high-grade squamous intra-epithelial lesions (HSIL).MethodsWe performed a retrospective cohort study of women treated with plasma or carbon dioxide laser ablation for histologically proven HSIL of the vulva or vagina from January 2014 to October 2019 at a single institution. Demographic factors, surgical characteristics, and complications were compared by ablation type using Fisher’s exact tests. Recurrence-free survival was evaluated by ablation type using Kaplan–Meier curves, weighted log-rank tests, and Cox proportional hazards ratio estimates.ResultsForty-two women were included; 50% underwent plasma and 50% underwent carbon dioxide laser ablation. Demographic factors were similar between the groups. 50% (n=21) were immunosuppressed, 45.2% (n=19) had prior vulvovaginal HSIL treatment, and 35.7% (n=15) were current smokers. Most women (n=25, 59.5%) were treated for vulvar HSIL, 38.1% (n=16) for vaginal HSIL. Complication rates did not differ by treatment: 9.5% (n=2) for laser ablation versus 4.8% (n=1) for plasma ablation (p=1.0). Over a median follow-up time of 29.3 months (IQR 11.0–45.0 months), recurrence rates were similar: 28.6% in the laser ablation group versus 33.3% in the plasma ablation group (weighted log rank p=0.43; 24-month HR 0.54, 95% CI 0.15 to 2.01).ConclusionPlasma energy ablation of vulvovaginal HSIL has similar complication rates and recurrence risk to carbon dioxide laser ablation. This technique could be considered as an alternative treatment modality for vulvovaginal HSIL and warrants further investigation.

Background Human epidermal growth factor receptor 2 (HER2) has emerged as an important prognostic and therapeutic target in advanced stage and recurrent uterine serous carcinoma (USC). The significance of tumoral HER2 expression in early-stage disease has not been established. Methods This multi-center cohort study included women with stage I USC treated from 2000 to 2019. Demographic, treatment, recurrence, and survival data were collected. Immunohistochemistry (IHC) was performed for HER2 and scored 0–3+. Equivocal IHC results (2+) were further tested with fluorescence in-situ hybridization (FISH). HER2 positivity was defined as 3+ IHC or FISH positive. Results One hundred sixty-nine patients with stage I USC were tested for HER2; 26% were HER2-positive. There were no significant differences in age, race, stage, adjuvant therapy, or follow-up duration between the HER2-positive and negative cohorts. Presence of lymph-vascular space invasion was correlated with HER2-positive tumors (p = .003). After a median follow-up of 50 months, there were 43 (25.4%) recurrences. There were significantly more recurrences in the HER2-positive cohort (50.0% vs 16.8%, p Conclusions Given its significant association with worse recurrence and survival outcomes, HER2 positivity appears to be a prognostic biomarker in women with stage I uterine serous carcinoma. These data provide support for clinical trials with anti-HER2-directed therapy in early-stage disease.

To evaluate the effects of an enhanced recovery after minimally invasive surgery (MIS-ERAS) protocol on opioid requirements and post-operative pain in patients undergoing minimally invasive hysterectomy on a gynecologic oncology service.For this retrospective study, opioid use (oral morphine equivalents (OME)) and post-operative pain scores were compared between patients undergoing minimally invasive hysterectomy pre and post MIS-ERAS protocol implementation. Patients with chronic opioid use or chronic pain were excluded. Opioid use and pain scores were compared between groups using Wilcoxon Rank Sum, Student's t-test, and multiple linear regression. Compliance and factors associated with opioid use and pain scores were assessed.The MIS-ERAS cohort (n = 127) was compared to the historical cohort (n = 99) with no differences in patient demographic, clinical or surgical characteristics observed between groups. Median intra-operative and inpatient post-operative opioid use were lower among the MIS-ERAS cohort (12.0 vs 32.0 OME, p .0001 and 20.0 vs 35.0 OME, p = .02, respectively). Pain scores among MIS-ERAS patients were also lower (mean 3.6 vs 4.1, p = .03). After controlling for age, BMI, operative time, length of stay, cancer diagnosis, and surgical approach, the MIS-ERAS cohort used 10.43 fewer OME intra-operatively (p .001), 10.97 fewer OME post-operatively (p = .019) and reported pain scores 0.56 points lower than historical controls (p = .013). Compliance was ≥81% for multimodal analgesia elements and ≥75% overall.Enhanced recovery after minimally invasive surgery protocol implementation is an effective means to reduce opioid use, both in the intra-operative and post-operative phases of care, among gynecologic oncology patients undergoing minimally invasive hysterectomy.

HPV vaccination is an important form of cancer prevention. Gynecologic oncologists have an opportunity to improve adult vaccination rates. We aimed to describe current HPV vaccination practices and barriers to vaccination reported by gynecologic oncologists.An online survey was developed, pilot tested and sent to U.S. members of the Society of Gynecologic Oncology.Of the 226 respondents, most were female (73%),45 years old (64%) and practiced in urban (60%) and academic settings (69%). Ninety percent had recommended the HPV vaccine in the past year. Nearly half (47%) had facilitated vaccination by: administering the HPV vaccine in clinic (40%), stocking the vaccine (35%), or prescribing the vaccine (30%). Recommending the vaccine was associated with higher outpatient volume, practicing in the South vs. Northeast, and having higher levels of vaccine knowledge.Of the 90% who recommended the vaccine, 60% did not prescribe or know if they could prescribe the vaccine in their state. Prioritization of cancer treatment was the most commonly reported barrier to HPV vaccination (88%). Approximately half of providers reported other systems-level hinderances such as high cost of stocking the vaccine, clinic flow disruption, or uncertainty surrounding insurance coverage. Almost all recommenders offered the vaccine at HPV-related dysplasia (92%) or cancer (80%) visits, while only 24-50% offered it at non-HPV-related visits.These survey results identify patient, provider, and systems-level barriers that could be targeted to help increase adult HPV vaccination in gynecologic oncology clinics.

A 30-year-old woman was referred with a diagnosis of placental site trophoblastic tumor. Her history was notable for two first trimester miscarriages due to a uterine septum. When hysteroscopic resection of the septum was performed, a lesion was discovered along the left septal wall. Her serum human

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OBJECTIVE: To estimate whether gastrointestinal-type chemotherapy was associated with improved survival compared to standard gynecologic regimens for women with ovarian mucinous carcinoma. METHODS: We conducted a retrospective cohort study of patients with ovarian mucinous carcinoma who received postoperative adjuvant chemotherapy at two academic centers. Demographic and clinical information was abstracted from the medical records. Gastrointestinal-type chemotherapy contained 5-fluorouracil, capecitabine, irinotecan, or oxaliplatin. Gynecologic regimens included standard carboplatin or cisplatin. Bevacizumab treatment was allowed in both groups. Summary statistics were used to compare baseline characteristics; Kaplan-Meier product-limit estimator was used to compare survival outcomes. RESULTS: Fifty-two patients received either gastrointestinal-type chemotherapy (n=26; 50%) or a standard gynecologic regimen (n=26; 50%). Three-quarters of tumors were early-stage (I or II), 68% grade 1 or 2 and 88% of patients had no gross residual disease after surgery. Patients receiving gastrointestinal-type chemotherapy were more likely to receive bevacizumab (50% vs. 4%; P < .001), but there were no other differences in clinical or demographic characteristics. Unadjusted overall survival analyses showed that gastrointestinal-type chemotherapy was associated with better overall survival (HR 0.2, 95% CI 0.1–0.8), as were early stage tumors and having no gross residual disease. CONCLUSION: Gastrointestinal-type chemotherapy with or without bevacizumab was associated with improved survival and should be considered in patients with ovarian mucinous carcinoma requiring adjuvant therapy.

To examine the association between ovarian conservation and oncologic outcome in surgically-treated young women with early-stage, low-grade endometrial cancer.This multicenter retrospective study examined women aged50 with stage I grade 1-2 endometrioid endometrial cancer who underwent primary surgery with hysterectomy from 2000 to 2014 (US cohort n = 1196, and Japan cohort n = 495). Recurrence patterns, survival, and the presence of a metachronous secondary malignancy were assessed based on ovarian conservation versus oophorectomy.During the study period, the ovarian conservation rate significantly increased in the US cohort from 5.4% to 16.4% (P = 0.020) whereas the rate was unchanged in the Japan cohort (6.3-8.7%, P = 0.787). In the US cohort, ovarian conservation was not associated with disease-free survival (hazard ratio [HR] 0.829, 95% confidence interval [CI] 0.188-3.663, P = 0.805), overall survival (HR not estimated, P = 0.981), or metachronous secondary malignancy (HR 1.787, 95% CI 0.603-5.295, P = 0.295). In the Japan cohort, ovarian conservation was associated with decreased disease-free survival (HR 5.214, 95% CI 1.557-17.464, P = 0.007) and an increased risk of a metachronous secondary malignancy, particularly ovarian cancer (HR 7.119, 95% CI 1.349-37.554, P = 0.021), but was not associated with overall survival (HR not estimated, P = 0.987). Ovarian recurrence or metachronous secondary ovarian cancer occurred after a median time of 5.9 years, and all cases were salvaged.Our study suggests that adoption of ovarian conservation in young women with early-stage low-grade endometrial cancer varies by population. Ovarian conservation for young women with early-stage, low-grade endometrial cancer may be potentially associated with increased risks of ovarian recurrence or metachronous secondary ovarian cancer in certain populations; nevertheless, ovarian conservation did not negatively impact overall survival.

Highlights • NRH-L is a rare disease that may lead to non-cirrhotic portal hypertension. • NRH-L may present as a paraneoplastic disorder, complicating oncologic treatment. • This is the first case of NRH-L as a potential paraneoplastic disorder due to PSTT.

Objectives: The Human Papillomavirus (HPV) vaccine is FDA approved up to age 45 and emerging evidence suggests it may prevent recurrent infections. This has important implications for patients commonly seen by gynecologic oncologists. Our objective was to describe factors that influence HPV vaccine recommendation amongst gynecologic oncologists and identify barriers and missed opportunities for vaccination. Methods: A pilot-tested online survey was electronically sent to all members of the Society of Gynecologic Oncology in the U.S. Questions evaluated the following domains: demographics, practice patterns, barriers and knowledge regarding the HPV vaccine. We defined HPV vaccine champions as providers who both recommended and either administered, stocked or prescribed the vaccine in the outpatient setting, and surveyed their practice patterns to identify possible missed opportunities for vaccination. Descriptive statistics were used to calculate the rate of HPV vaccine recommendation, explore barriers to vaccination and identify practice patterns. Univariate logistic regression was used to identify factors associated with vaccine recommendation. Results: A total of 183 gynecologic oncology providers completed the survey, representing 10% of invitations sent. Most were ≤ 45 years old (65%, n=99), practicing in urban (57%, n=105) and academic settings (67%, n=122). Eighty-one percent (n=147) had completed training, and of these, 68% (n=101) had been in practice for > 5 years. Ten percent (n=18/174) of respondents had not recommended the HPV vaccine in the past 12 months. Vaccine recommendation was associated with better HPV vaccine knowledge (Odds Ratio (OR) 1.7, 95% Confidence Interval (CI) 1.0-2.9), being a non-trainee (OR 3.8, CI 1.3-11.2) and practicing in the South (OR 10.8, CI 1.3-90.7). Among all providers, the most commonly reported barriers to vaccinating were that the patient's cancer diagnosis took precedence (88%, n=146/165), the cost to the clinic (48%, n=79/165), uncertainty about insurance coverage (43%, n=71/165) and that the vaccine history was not asked (48%, n=79/165). Forty eight percent (n=87) met criteria as HPV vaccine champions. Of those, 96% (n=78/81) at least sometimes offer the HPV vaccine at a visit for vulvar or cervical dysplasia. Eighty-three percent (n=67/81) offer it to patients with an HPV-related cancer diagnosis. In contrast, only 35% (n=29/82) were likely to offer it in a consultation for BRCA management and 28% (n=23/82) were likely to offer it at a surgical consultation for fibroids (Figure). Download : Download high-res image (89KB) Download : Download full-size image Conclusions: Gynecologic oncologists have a unique opportunity to educate and increase vaccination rates in eligible women. There are significant barriers to HPV vaccine administration in the gynecologic oncology office, and we identify examples of missed opportunities to vaccinate in non-HPV related clinical scenarios.

Objectives: PD-L1 is an important axis of immunotolerance in normal pregnancy and this may be perpetuated as a mechanism of immune evasion in the pathobiologic development of gestational trophoblastic neoplasia (GTN). There are early efficacy signals for anti-PD-1 immunotherapy in chemoresistant GTN, however response rates are variable. The characteristics of predictive biomarkers used for triaging anti-PD-1 immunotherapy are not well-known in GTN. The aim of this study was to quantify trophoblast PD-L1 expression in GTN using the FDA approved PD-L1 22C3 immunohistochemical (IHC) companion assay and to profile GTN-infiltrating immune cells. Methods: Choriocarcinoma (CC), epithelioid trophoblastic tumor (ETT) and placental site trophoblastic tumor (PSTT) cases with available tissue blocks in the Johns Hopkins GTN library were used for this investigation. IHC staining for PD-L1 and each immune marker (CD68, CD8, CD4, FOXP3) was performed on paired, fresh cut 4 micrometer tissue sections. Tumor proportion scores (TPS, percentage of viable tumor cells with any PD-L1 membrane staining) were assigned by 2 independent gynecologic pathologists. Discrepancies in scoring were adjudicated by a third gynecologic pathologist. Digital image analyses using QuPath v0.2.3 to average CD68, CD8, CD4 and FOXP3 immune cell density in three 40x hotspots per case was performed. Hotspots were targeted to the tumor-immune cell interface. Descriptive statistics and the Wilcoxon Rank Sum Test were performed for analysis. Results: A large proportion of PSTT (n=6/8,75%) and CC (n=22/32, 69%) and approximately half of ETT (n=9/19, 47%) cases have highpositive PD-L1 expression defined as the clinically relevant TPS cutoff of >50%. These exceed the rates of high PD-L1 positivity observed in all other solid tumor sites, which ranges from 2-31%. PSTT and CC have significantly higher trophoblast PD-L1 expression than ETT; the median TPS for PSTT and CC is 90% and 85%, compared to 35% for ETT (p=0.02). CD68 monocytes were more abundant in CC and PSTT compared to ETT. However, CD8 cytotoxic T (p 5% (Table). Conclusions: PD-L1 expression in GTN is heterogeneous, yet disproportionately high compared to other primary tumor sites. Of the 3 GTN subtypes, ETT has the lowest and broadest range of PD-L1 expression; this is associated with lower CD68 monocyte infiltration and correlates with degree of lymphocytic infiltration. How these expression patterns predict response to anti-PD-L1/PD-1 agents in GTN will be need to be explored. In a tumor type with such lineage inherent PD-L1 expression, characterization of tumor cell PD-L1 expression in conjunction with the tumor immune-microenvironment may provide a unique opportunity to study mechanisms of immune escape.Funding was provided by the Bruce Patsner Research Grant for Innovative Research and Technology through the Foundation for Women's Cancer.

Objectives: Olaparib is approved as a first line (1L) maintenance (mtx) option, as monotherapy for BRCA mutated (BRCAm) ovarian cancer (OC) and in combination with bevacizumab (Bev) for homologous recombination deficient (HRD) OC. Niraparib monotherapy is approved as 1L mtx irrespective of BRCA/HRD status. Despite its broad approval, niraparib demonstrated relatively shorter progression free survival (PFS) gains outside of an HRD test positive population in the PRIMA trial. Given the recent PARPi data in frontline mtx and the cost of HRD testing beyond standard of care gBRCA testing, there is debate over using an HRD biomarker guided (BMG) or non-biomarker guided (NBMG) approach to prescribing 1L mtx. The objective of this model is to compare the PFS and costs per month of PFS between: (1) BMG 1L mtx approach which restricts the prescribing of 1L mtx PARPi and PARPi combination based on Myriad myChoice results vs (2) NBMG PARPi mtx for all approach. Methods: This model is a parametric Markov model for a cohort of 100 newly diagnosed stage 3/4 OC patients (pts) prescribed 1L mtx according to HRD BMG and NBMG approaches. The model focuses on maintenance after first line treatment and evaluates costs and PFS after first line chemotherapy. To focus on the impact of testing, drugs are treated as classes. Treatment costs include 1L mtx PARP inhibitor (PARPi), Bev, and PARPi + Bev, subsequent therapy, management of adverse events, and administration costs over 60 months. PFS is estimated by applying an exponential curve to adjusted trial data. The BMG pt group undergoes HRD tumor testing and has a test positive (HRD+) rate of 47% (20% BRCAm, 27% non-BRCAm). Germline BRCAm testing cost is not included as it is assumed to be the standard of care and equally conducted in both groups. An estimated 65% are eligible for a PARPi (received and responded to 1L platinum chemotherapy). Calculations for the BMG PARPi eligible group assume all HRD+ pts receive PARPi + Bev and 30% of HRD test negative pts receive Bev (70% receive routine surveillance). The model assumes all pts in the NBMG group receive a PARPi. Results: In the BMG group 31 pts receive PARPi + Bev mtx and in the NBMG arm 65 pts receive PARPi mtx. The 31 BMG PARPi + Bev pts averaged 36.6 months of 1L PFS compared to 26.3 months in the 65 NBMG PARPi pts. The overall 1L PFS for the total cohorts were similar but slightly favored the BMG approach (1715.4 vs 1711.7 months). Over a 60 month horizon, the BMG approach was $1,002 less per month of 1L PFS gained ($15,475 vs. $16,477). HRD biomarker testing represented 1.5% of the total costs for the cohort. Download : Download high-res image (95KB) Download : Download full-size image Conclusions: Despite initial testing costs, this model projects that use of an HRD BMG approach with PARPi + bev may minimize long-term costs and afford at least similar, if not greater, 1L PFS compared to an approach which omits HRD tumor testing and prescribes PARPi to all-comers.

BackgroundAdjuvant therapy in early-stage endometrial cancer has not shown a clear overall survival benefit, and hence, patient selection remains crucial.ObjectiveTo determine whether women with high-intermediate risk, early-stage endometrial cancer with lymphovascular space invasion particularly benefit from adjuvant treatment in improving oncologic outcomes.MethodsA multi-center retrospective study was conducted in women with stage IA, IB, and II endometrial cancer with lymphovascular space invasion who met criteria for high-intermediate risk by Gynecologic Oncology Group (GOG) 99. Patients were stratified by the type of adjuvant treatment received. Clinical and pathologic features were abstracted. Progression-free and overall survival were evaluated using multivariable analysis.Results405 patients were included with the median age of 67 years (range 27–92, IQR 59–73). 75.0% of the patients had full staging with lymphadenectomy, and 8.6% had sentinel lymph node biopsy (total 83.6%). After surgery, 24.9% of the patients underwent observation and 75.1% received adjuvant therapy, which included external beam radiation therapy (15.1%), vaginal brachytherapy (45.4%), and combined brachytherapy + chemotherapy (19.1%). Overall, adjuvant treatment resulted in improved oncologic outcomes for both 5-year progression-free survival (77.2% vs 69.6%, HR 0.55, p=0.01) and overall survival (81.5% vs 60.2%, HR 0.42, pConclusionAdjuvant therapy improves both progression-free survival and overall survival in women with early-stage endometrial cancer meeting high-intermediate risk criteria with lymphovascular space invasion. External beam radiation or adding chemotherapy did not confer additional survival advantage compared with vaginal brachytherapy alone.

An 84-year-old woman presented to an outside institution with a 1-month history of generalized malaise, anorexia, abdominal distension, shortness of breath, and unintentional 20-pound weight loss. She had a past medical history of JAK2-positive polycythemia rubra vera, stage 4 chronic kidney disease

Highlights • Radical trachelectomy is a fertility sparing option for select stage I cervical patients. • Indications for adjuvant treatment following trachelectomy are based on standard recommendations following hysterectomy. • Case report outlining specifics of imaged-guided brachytherapy as part of the adjuvant treatment after trachelectomy.

Objectives: The American Society of Clinical Oncology (ASCO) recommends early palliative care assessment (PCA) for patients with advanced or recurrent malignancy. We report initial findings of a protocol designed to meet this standard. Methods: We used key stakeholders from a multi-disciplinary team of gynecologic oncologists and palliative care providers to inform an initiative to increase compliance with the ASCO recommendation. As a result, in April of 2020, a quality improvement protocol was initiated whereby a palliative care consult was ordered for all patients with a gynecologic cancer diagnosis admitted to the gynecologic oncology service. Admissions for 23-hour observation and those who did not receive outpatient care from the gynecology oncology team were excluded. Admissions meeting the inclusion criteria 3 months prior to protocol initiation (PPI) were compared to admissions in months 4-6 after protocol initiation (API) to allow for a 3 month wash out period. A retrospective chart review was completed to identify clinicodemographic characteristics for each admission. The primary outcome was completion of inpatient PCA calculated per admission. Secondary outcomes were palliative care and hospice interventions, and advanced care documentation (code status, power of attorney or living will). T-test, Fisher's exact test, relative risk (RR) and exact binomial confidence intervals (CIs) were used. Results: There were 152 admissions, 82 PPI and 70 API. The mean age was 61 years (±13), the majority were White (49%) or Black (39%), had a primary diagnosis of ovarian/primary peritoneal (37%) or uterine cancer (32%) and had advanced/recurrent disease (93%). The majority were medical admissions (n=91, 62%) with 10 (7%) for radiation and 44 (30%) for postoperative care. The demographics of admissions PPI and API are summarized in Table 1. PCA was significantly higher API versus PPI (63% vs. 38%, RR 1.95, 95% CI 1.26-3.02). Additionally, API admissions were more likely to receive follow-up outpatient PCA referrals (20% vs 5%, p=0.005). Death (inpatient or outpatient) was more commonly observed in Black patients compared to White (61% vs 39%, p=0.049). Of the 24 patients who died during the study period, 7 died inpatient. Notably all patients who died inpatient were Black (0% White vs 0% other vs 100% Black p=0.03). Documentation of goals of care discussions, code status, or power of attorney did not change after protocol implementation (RR 1.14, CI 0.90-1.41). Conclusions: This universal palliative care consultation protocol improved the frequency of PCA on an inpatient gynecologic oncology service and increased outpatient PCA referrals, but did not achieve complete compliance. Early observations have also identified a potential disparity in frequency and location of death that warrants further exploration. The next phase of this QI initiative will explore and address barriers to achieving universal PCA.

ObjectiveThe aim of this study was to report the utility and false-negative rates of sentinel lymph node (SLN) mapping during surgical staging of women with high-grade, apparent uterine-confined endometrial cancer.MethodsThis was a single-institution study performed at a high-volume academic center. From December 2012 to December 2015, women with high-grade endometrial cancer (grade 3 endometrioid, serous, clear cell, and carcinosarcoma) underwent SLN mapping via cervical injection followed by robot-assisted total laparoscopic hysterectomy and completion lymphadenectomy. Ultrastaging of SLNs was performed in patients with tumors with any degree of myoinvasion. Patient demographics, SLN test characteristics, treatment, and recurrence outcomes were prospectively evaluated for analysis.ResultsFifty-two patients with high-grade histologic findings underwent SLN mapping followed by completion lymphadenectomy. The median patient age was 64 years, and median body mass index was 31.8 kg/m2. Most patients had either serous (46%) or grade 3 endometrioid histology (27%) on preoperative biopsy. Nine patients had nodal metastases, 7 of whom had metastases identified in SLNs. No low-volume nodal metastases were identified on ultrastaging. Two patients had false-negative SLN mapping (22%). After a median follow-up of 15.6 months, 14 recurrences (27%) were diagnosed; all were distant or multisite relapses. Sentinel lymph node mapping did not impact the choice of adjuvant therapy or recurrence risk in node-positive patients.ConclusionsSentinel lymph node detection of metastases in patients with high-grade endometrial cancer is high, but false-negative results were encountered. More research is needed to determine whether SLN mapping can safely replace systemic lymphadenectomy in women with high-risk histologic findings.

To describe the US national trends and factors associated with cytoreductive surgical radicality in women with advanced ovarian cancer (OC).An analysis of the National Inpatient Sample database was performed. All admissions from 1993 to 2011 for advanced OC cytoreductive surgery (CRS) were identified and categorized as simple pelvic (SP), extensive pelvic (EP), and extensive upper abdominal (EUA) surgery. Annual trends in CRS were analyzed. Associations between patient- and hospital-specific factors, with CRS radicality as well as perioperative complications were explored between 2007 and 2011.In total, 28,677 un-weighted admissions were analyzed. The rate of EP and EUA resections increased over time (8% to 18.1% and 1.3% to 5.4%, P0.01, respectively). On multivariate analysis, patients were more likely to undergo EUA resections in the Northeast (OR 1.44) or West Coast (OR 1.47) at urban (OR 2.3), or large hospitals (OR 1.4), or if they had private insurance (OR 1.45). EUA surgeries were performed more frequently at high-volume ovarian cancer centers (OR 2.65); additionally, fewer complications were observed after EUA at high compared with low and medium volume hospitals (10.2%, 21.2%, and 21.7%, respectively; P=0.01). Specifically, patients treated at high volume hospitals experienced lower rates of hemorrhage, vascular/nerve injury, prolonged hospitalization, and non-routine discharge than at lower (P0.05).The US rate of radical cytoreductive surgery for advanced ovarian cancer is increasing. At high-volume hospitals, patients receive more radical surgery with fewer complications, supporting further study of a centralized ovarian cancer care model.

Objectives Thirty-day readmission is used as a quality measure for patient care and Medicare-based hospital reimbursement. The primary study objective was to describe the 30-day readmission rate to an academic gynecologic oncology service. Secondary objectives were to identify risk factors and costs related to readmission. Methods This was a retrospective, concurrent cohort study of all surgical admissions to an academic, high volume gynecologic oncology service during a two-year period (2013–2014). Data were collected on patient demographics, medical comorbidities, psychosocial risk factors, and results from a hospital discharge screening survey. Mixed logistic regression was used to identify factors associated with 30-day readmission and costs of readmission were assessed. Results During the two-year study period, 1605 women underwent an index surgical admission. Among this population, a total of 177 readmissions (11.0%) in 135 unique patients occurred. In a surgical subpopulation with >1 night stay, a readmission rate of 20.9% was observed. The mean interval to readmission was 11.8days (SD 10.7) and mean length of readmission stay was 5.1days (SD 5.0). Factors associated with readmission included radical surgery for ovarian cancer (OR 2.87) or cervical cancer (OR 4.33), creation of an ostomy (OR 11.44), a Charlson score of ≥5 (OR 2.15), a language barrier (OR 3.36), a median household income in the lowest quartile (OR 6.49), and a positive discharge screen (OR 2.85). The mean cost per readmission was $25,416 (SD $26,736), with the highest costs associated with gastrointestinal complications at $32,432 (SD $32,148). The total readmission-related costs during the study period were $4,523,959. Conclusions Readmissions to a high volume gynecologic oncology service were costly and related to radical surgery for ovarian and cervical cancer as well as to medical, socioeconomic and psychosocial patient variables. These data may inform interventional studies aimed at decreasing unplanned readmissions in gynecologic oncology surgical populations.

Cancer affects approximately one in 1000 pregnancies. Three to six percent of antepartum adnexal masses typically detected during routine obstetrical ultrasounds are malignant. Germ cell ovarian malignancies are most common, followed by stromal and epithelial cancers (Cordeiro & Gemignani, 2017). About one third of women have extra-ovarian spread at diagnosis (Blake et al., 2015). As more women delay childbearing, the incidence of ovarian cancer in pregnancy may increase. This warrants greater understanding of the optimal treatment of this complex condition. Additionally, the utilization of cell-free DNA (cfDNA) screening for fetal aneuploidy has dramatically increased among women over 34. Careful interpretation of test results is of utmost importance, as false positive abnormal fetal aneuploidy screening results can signify occult malignancy. Here, we present a case of high grade serous ovarian cancer detected by cfDNA fetal aneuploidy screening six weeks prior to the clinical diagnosis of stage IVA disease.

Objectives Lymphovascular space invasion (LVSI) is an independent risk factor for recurrence and poor survival in early-stage endometrioid endometrial cancer (EEC), but optimal adjuvant treatment is unknown. We aimed to compare the survival of women with early-stage EEC with LVSI treated postoperatively with observation (OBS), radiation (RAD, external beam and/or vaginal brachytherapy), or chemotherapy (CHEMO)+/−RAD. Methods This was a multi-institutional, retrospective cohort study of women with stage I or II EEC with LVSI who underwent hysterectomy+/−lymphadenectomy from 2005 to 2015 and received OBS, RAD, or CHEMO+/−RAD postoperatively. Progression-free survival and overall survival were evaluated using Kaplan-Meier estimates and Cox proportional hazards models. Results In total, 478 women were included; median age was 64 years, median follow-up was 50.3 months. After surgery, 143 (30%) underwent OBS, 232 (48.5%) received RAD, and 103(21.5%) received CHEMO+/−RAD (95% of whom received RAD). Demographics were similar among groups, but those undergoing OBS had lower stage and grade. A total of 101 (21%) women recurred. Progression-free survival (PFS) was improved in both CHEMO+/−RAD (HR = 0.18, 95% CI: 0.09–0.39) and RAD (HR = 0.31, 95% CI: 0.18–0.54) groups compared to OBS, though neither adjuvant therapy was superior to the other. However, in grade 3 tumors, the CHEMO+/−RAD group had superior PFS compared to both RAD (HR 0.25; 95% CI: 0.12–0.52) and OBS cohorts (HR = 0.10, 95% CI: 0.03–0.32). Overall survival did not differ by treatment. Conclusions In early-stage EEC with LVSI, adjuvant therapy improved PFS compared to observation alone. In those with grade 3 EEC, adjuvant chemotherapy with or without radiation improved PFS compared to observation or radiation alone.

Objective Our objectives were 1) to compare the efficacy of progestin therapy combined with metformin (Prog-Met) to Prog alone as primary fertility sparing treatment in women with atypical hyperplasia/endometrial intraepithelial neoplasia (AH/EIN) or early-stage endometrioid carcinoma (EC), and 2) to analyze the proportion of women achieving live birth following treatment. Methods A retrospective cohort study of all reproductive-aged women with AH/IN or EC treated with Prog ± Met from 1999–2018 was conducted. Complete response (CR) was assessed and Kaplan-Meier analysis used to calculate time to CR. Comparison of potential response predictors was performed with multivariable Cox regression models. Results Ninety-two women met criteria; 59% (n = 54) were treated for AH/EIN and 41% (n = 38) for EC. Their median age, body mass index, and follow up time was 35 years, 37.7 kg/m2, and 28.4 months, respectively. Fifty-eight women (63%) received Prog and 34 (37%) received Prog-Met. Overall, 79% (n = 73) of subjects responded to treatment with a CR of 69% (n = 63). There was no difference in CR (p = 0.90) or time to CR (p = 0.31) between the treatment cohorts. Overall, 22% experienced a disease recurrence. On multivariable analysis, EC histology was the only covariate associated with a decreased Prog response (HR 0.48; p = 0.007). Only 17% of the cohort achieved a live-birth pregnancy, the majority of which required assisted reproductive technologies (81%) and occurred in the Prog treatment group. Conclusions Our study does not support the use of Prog-Met therapy for treatment of AH/EIN or EC. Additionally, fewer than 20% of women achieved a live-birth pregnancy during the study period, with most requiring ART.

ObjectiveTo determine whether the rate of sentinel lymph node (SLN) dissections that do not yield a lymph node on pathological analysis ('empty packet dissection') changes with increasing surgeon experience in the setting of patients undergoing minimally invasive hysterectomy and SLN mapping using indocyanine green dye for endometrial cancer.MethodsAll patients undergoing SLN mapping using indocyanine green dye at the time of minimally invasive hysterectomy for endometrial cancer or complex atypical hyperplasia were identified between January 2013 and September 2017 at our institution. All surgeons had prior experience performing SLN mapping for endometrial cancer using other methods. The rate of empty packet dissections and SLN counts were evaluated using a logistic regression model analysis.ResultsIn total, 236 patients undergoing SLN mapping for either endometrial cancer (85%) or complex atypical hyperplasia (15%) were identified from a prospectively maintained database. When examining all six surgeons together, the percentage of empty packet dissections decreased with increasing number of procedures performed. Each additional procedure was associated with a 3.6% reduction in the odds of an empty packet SLN dissection. After adjusting for individual surgeons, each additional procedure was associated with a 4.9% reduction in the odds of an empty packet. The expected odds of an empty packet after 10 additional procedures decreased by 40.1% (95% CI 12.4% to 58.6%). The addition of two covariates (age and body mass index) did not contribute significantly to the model (likelihood ratio test: X2=2.75, p=0.25). The rate of empty packets appeared to stabilize after approximately 30 procedures. The number of SLNs removed did not change with increasing surgeon experience.ConclusionThe rate of empty packet SLN dissections using indocyanine green dye decreases with increasing number of procedures. This stabilizes after 30 procedures, suggesting completion of a learning curve.

Objective Our study objective was to determine feasibility and mapping rates using indocyanine green (ICG) for sentinel lymph node (SLN) mapping in early-stage cervical cancer. Methods We performed a retrospective review of all women who underwent SLN mapping with ICG during primary surgical management of early-stage cervical cancer by robotic-assisted radical hysterectomy (RA-RH) or fertility-sparing surgery. Patients were treated at two high-volume centers from 10/2012 to 02/2016. Completion pelvic lymphadenectomy was performed after SLN biopsy; additionally, removal of clinically enlarged/suspicious nodes was part of the SLN treatment algorithm. Results Thirty women with a median age of 42.5 and BMI of 26.5 were included. Most (90%) had stage IB disease, and 67% had squamous histology. RA-RH was performed in 86.7% of cases. One patient underwent fertility-sparing surgery. Median cervical tumor size was 2.0cm. At least one SLN was detected in all cases (100%), with bilateral mapping achieved in 87%. SLN detection was not impacted by tumor size and was most commonly identified in the hypogastric (40.3%), obturator (26.0%), and external iliac (20.8%) regions. Five cases of lymphatic metastasis were identified (16.7%): three in clinically enlarged SLNs, one in a clinically enlarged non-SLN, and one case with cytokeratin positive cells in an SLN. All metastatic disease would have been detected even if full lymphadenectomy had been omitted from our treatment algorithm, Conclusions SLN mapping with ICG is feasible and results in high detection rates in women with early-stage cervical cancer. Prospective studies are needed to determine if SLN mapping can replace lymphadenectomy in this setting.

ObjectivesThe objective of this study is to explore how cytoreductive surgical outcomes such as residual disease (RD) and use of the term “optimal cytoreduction” (OCR) have changed over time in the ovarian cancer literature.MethodsWe identified all English-language publications referring to ovarian cancer cytoreduction for a 12-year period. Publications were evaluated for how the diameter of RD was categorized and whether OCR was defined. In addition, the use of RD and OCR terminology trends over time and associations between terminology and the region of corresponding author, study type, and journal impact factor were explored.ResultsOf the 772 publications meeting inclusion criteria, the RD stratification points used to demarcate patient groups were as follows: 0 mm (45%), 5 mm (3.6%), 10 mm (65%), and 20 mm (24%). The use of 0-mm RD (odds ratio [OR], 1.1; 95% confidence interval, 1.05–1.15) and 10-mm RD (OR, 1.1; 95% confidence interval, 1.09–1.20) to delineate patient outcomes increased over time. The use of OCR terminology did not change over time but was more commonly used in clinical studies as well as those from North America. Many studies (70%) defined OCR as less than or equal to 10-mm RD, whereas 30% defined OCR differently or not at all.ConclusionsOptimal cytoreduction terminology remains ambiguous and inconsistently used in the ovarian cancer surgical literature. On the basis of this literature review, we propose a novel classification system to categorize RD without reference to OCR while accurately and succinctly identifying meaningful clinical subgroups and minimizing bias.

To evaluate the association between lymphopenia and survival in women with cervical cancer treated with primary chemoradiation.A single institution, retrospective analysis of patients with stage IB2-IVA cervical cancer who received upfront chemoradiation from 1998 to 2013 was performed. Complete blood counts from pre-treatment to 36 months post-treatment were analyzed. Lymphopenia and known prognostic factors were evaluated for an association with progression-free (PFS) and overall survival (OS).Seventy-one patients met study criteria for whom 47 (66%) had a documented total lymphocyte count (TLC) two months after initiating chemoradiation. FIGO stage distribution was 6% Stage I, 46% Stage II, 45% Stage III and 3% Stage IV. Pre-treatment TLC was abnormal (1000 cells/mm3) in 15% of patients. The mean reduction in TLC was 70% two months after initiating chemoradiation. Severe post-treatment lymphopenia (TLC500 cells/mm3) was observed in 53% of patients; they experienced inferior median OS (21.2 vs. 45.0 months, P=0.03) and similar 25th percentile PFS (6.3 vs. 7.7 months, P=0.06) compared to patients without severe lymphopenia. Multivariate analysis demonstrated pre-treatment TLC ≥1000 cells/mm3 and post-treatment TLC500 cells/mm3 had a 77% (HR: 0.23; 95% CI 0.05-1.03; P=0.053) and 58% decrease in hazards of death (HR: 0.42; 95%CI 0.12-1.46; P=0.17) respectively.More than half of cervical cancer patients treated with chemoradiation experienced severe and prolonged lymphopenia. Although statistical significance was not reached, the findings suggest that pre- and post-treatment lymphopenia may be associated with decreased survival. Further research is warranted, given that lymphopenia could be a reversible prognostic factor.

6084 Background: Uterine serous carcinoma (USC) is a rare and aggressive malignancy, accounting for 40% of all endometrial cancer deaths. Human Epidermal Growth Factor Receptor 2 (HER2) has emerged as an important prognostic and therapeutic target in USC. Given recent randomized trial results, HER2-directed therapy is now recommended in advanced-stage or recurrent, HER2-positive disease. The significance of tumoral HER2 expression in early-stage disease has not yet been established. Methods: In this IRB-approved, retrospective, multi-institutional cohort, women diagnosed with stage I USC from 2000-2018 were identified. Patient demographic, treatment, and survival data were collected. Immunohistochemistry (IHC) was performed for HER2 and scored 0-3+. Equivocal IHC results (2+) were further tested with in-situ hybridization (ISH) per the 2007 ASCO-CAP HER2 breast cancer guidelines. HER2 overexpression (“positive”) was defined as 3+ IHC or ISH positive. Kaplan-Meier analyses and Cox-proportional hazards were used to compare survival between the cohorts. Results: In total, 173 patients with stage I USC were tested for HER2; 25% were HER2-positive, 77.4% had stage IA and 22.6% had stage IB disease. Adequate clinical follow up was available for 168 patients. There were no significant differences in age, race/ethnicity, body mass index, surgical management, sub-stage, tumor size, adjuvant therapy, or follow-up duration between the HER2-positive and negative cohorts. On univarite analysis, presence of lymph-vascular space invasion was correlated with HER2-positive tumors (p=0.003). After a median follow-up of 50 months, there were 41 (24.4%) recurrences. Significantly more recurrences were observed in the HER2-positive cohort (47.6% vs. 16.7%, p

Inactivating somatic mutations of ARID1A, a chromatin remodeling gene, are common in endometrioid endometrial carcinoma (EEC) but rare in complex atypical hyperplasia (CAH). Our objectives were to determine the clinical significance of ARID1A loss during tumor progression from CAH to EEC and to assess its role as a predictive cancer biomarker.In cohort A, ARID1A immunoreactivity was evaluated in endometrial sampling (biopsy/curettage) specimens showing CAH to determine whether ARID1A expression correlates with the presence of EEC at subsequent hysterectomy. In cohort B, ARID1A immunoreactivity was evaluated in the hysterectomy specimens with concurrent CAH and EEC to assess for the concordance of ARID1A expression in both components.In cohort A, loss of ARID1A immunoreactivity was identified in the endometrial sampling specimen of 31% of patients undergoing hysterectomy for a preoperative diagnosis of CAH. EEC was identified in the hysterectomy specimen of 94% of patients with loss of ARID1A in the endometrial sampling specimen while only 15% of patients with retained ARID1A expression (P 0.0001). No association was observed between ARID1A expression and demographic characteristics. In cohort B, 14 (31%) of 45 patients with concurrent CAH/EEC in their hysterectomy specimens had complete loss of ARID1A expression in the EEC components. Among these 14 patients, 50% also had loss of ARID1A immunoreactivity in the CAH component.ARID1A immunostaining may correlate with malignant transformation and the presence of concurrent EEC in patients with CAH identified at pre-hysterectomy endometrial sampling. Further investigation to determine the potential utility of ARID1A expression as a tissue biomarker is warranted.

Objectives Enhanced Recovery After Surgery (ERAS) programs are mechanisms for achieving value-based improvements in surgery. This report provides a detailed analysis of the impact of an ERAS program on patient outcomes as well as quality and safety measures during implementation on a gynecologic oncology service at a major academic medical center. Methods A retrospective review of gynecologic oncology patients undergoing elective laparotomy during the implementation phase of an ERAS program (January 2016 through December 2016) was performed. Patient demographics, surgical variables, postoperative outcomes, and adherence to core safety measures, including antimicrobial and venous thromboembolism (VTE) prophylaxis, were compared to a historical patient cohort (January 2015 through December 2015). Statistical analyses were performed using t -tests, Wilcoxon rank sum tests, and Chi squared tests. Results The inaugural 109 ERAS program participants were compared to a historical patient cohort ( n =158). There was no difference in BMI, race, malignancy, or complexity of procedure between cohorts. ERAS patients required less narcotics (70.7 vs 127.4, p =0.007, oral morphine equivalents) and PCA use (32.1% vs. 50.6%, p =0.002). Despite this substantial reduction in narcotics, ERAS patients did not report more pain and in fact reported significantly less pain by postoperative day 3. There were no differences in length of stay (5days), complication rates (13.8% vs. 20.3%, p =0.17) or 30-day readmission rates (9.5 vs 11.9%, p =0.54) between ERAS and historical patients, respectively. Compliance with antimicrobial prophylaxis was 97.2%. However, 33.9% of ERAS patients received substandard preoperative VTE prophylaxis. Conclusions ERAS program implementation resulted in reductions in narcotic requirements and PCA use without changes in length of stay or readmission rates. Compliance should be diligently audited during the implementation phase of ERAS programs, with special attention to adherence to pre-existing core safety measures.

OBJECTIVES: Minimally invasive surgery (MIS) is a quality measure for endometrial cancer (EC) established by the Society of Gynecologic Oncology and the American College of Surgeons. Our study objective was to assess the proportion of EC cases performed by MIS at National Comprehensive Cancer Network (NCCN) centers and evaluate perioperative outcomes. METHODS: A retrospective cohort study of women who underwent surgical treatment for EC from 2013–2014 was conducted at four NCCN centers. Multivariable mixed logistic regression models analyzed factors associated with failure to perform MIS and perioperative complications. RESULTS: In total 1,621 patients were evaluated; 86.5% underwent MIS (robotic-assisted 72.5%, laparoscopic 20.9%, vaginal 6.6%). On multivariable analysis, factors associated with failure to undergo MIS were uterine size >12cm (Odds Ratio [OR]: 0.17, 95% CI 0.03–0.9), stage III (OR: 0.16, 95% CI 0.05–0.49) and IV disease (OR: 0.07, 95% CI 0.02–0.22). For stage I/II disease, complications occurred in 5.1% of MIS and 21.7% of laparotomy cases (p80% in EC care is feasible when performed at high volume centers.

SummaryWhile recombinant human erythropoietin (rhEpo) has been widely used to treat anemia in cancer patients, concerns about its adverse effects on patient survival have emerged. A lack of correlation between expression of the canonical EpoR and rhEpo’s effects on cancer cells prompted us to consider the existence of an alternative Epo receptor. Here, we identified EphB4 as an Epo receptor that triggers downstream signaling via STAT3 and promotes rhEpo-induced tumor growth and progression. In human ovarian and breast cancer samples, expression of EphB4 rather than the canonical EpoR correlated with decreased disease-specific survival in rhEpo-treated patients. These results identify EphB4 as a critical mediator of erythropoietin-induced tumor progression and further provide clinically significant dimension to the biology of erythropoietin.

Patterns of invasion and stromal response are understudied in vulvar squamous cell carcinoma. The aim of this study was to explore whether histologic features such as an infiltrative pattern of invasion and fibromyxoid stromal response (FMX-SR) are meaningful prognostic factors. We reviewed 143 vulvar squamous cell carcinoma resections and correlated patterns of invasion and stromal response with patient age, ethnicity, depth of invasion, tumor size, perineural invasion (S100/AE1/3 stain), lymph node involvement (LNI), extranodal extension, margin status, pathologic stage, and recurrence. Univariate analyses of continuous variables were performed using t tests, whereas Pearson χ tests were used for categorical variables. Logistic regression analyses examined the relationship between histopathologic characteristics and clinical outcomes. There was a statistically significant association between infiltrative tumors and an FMX-SR in comparison with noninfiltrative tumors (P

Background: We compared survival outcomes and risk of venous thromboembolism (VTE) among patients with advanced and early-stage ovarian clear cell carcinoma (OCCC) and serous ovarian carcinoma (SOC), as well as potential links with interleukin-6 (IL-6) levels. Methods: A multicenter case-control study was conducted in 370 patients with OCCC and 938 with SOC. In a subset of 200 cases, pretreatment plasma IL-6 levels were examined. Findings: Patients with advanced OCCC had the highest 2-year cumulative VTE rates (advanced OCCC 43.1%, advanced SOC 16.2%, early-stage OCCC 11.9% and early-stage SOC 6.4%, P < 0.0001) and the highest median levels of IL-6 (advanced OCCC 17.8 pg/mL, advanced SOC 9.0 pg/mL, early-stage OCCC 4.2 pg/mL and early-stage SOC 5.0 pg/mL, P = 0.006). Advanced OCCC (hazard ratio [HR] 3.38, P < 0.0001), thrombocytosis (HR 1.42, P = 0.032) and elevated IL-6 (HR 8.90, P = 0.046) were independent predictors of VTE. In multivariate analysis, patients with advanced OCCC had significantly poorer 5-year progression-free and overall survival rates than those with advanced SOC (P < 0.01), and thrombocytosis was an independent predictor of decreased survival outcomes (P < 0.01). Elevated IL-6 levels led to poorer 2-year progression-free survival rates in patients with OCCC (50% versus 87.5%, HR 4.89, P = 0.016) than in those with SOC (24.9% versus 40.8%, HR 1.40, P = 0.07). Interpretation: Advanced OCCC is associated with an increased incidence of VTE and decreased survival outcomes, which has major implications for clinical management of OCCC.

Objective As our understanding of sentinel lymph node (SLN) mapping for endometrial cancer (EC) evolves, tailoring the technique to individual patients at high risk for failed mapping may result in a higher rate of successful bilateral mapping (SBM). The study objective is to identify patient, tumor, and surgeon factors associated with successful SBM in patients with EC and complex atypical hyperplasia (CAH). Methods From September 2012 to November 2014, women with EC or CAH underwent SLN mapping via cervical injection followed by robot-assisted total laparoscopic hysterectomy (RA-TLH) at a tertiary care academic center. Completion lymphadenectomy and ultrastaging were performed according to an institutional protocol. Patient demographics, tumor and surgeon/intraoperative variables were prospectively collected and analyzed. Univariate and multivariate analyses were performed evaluating factors known or hypothesized to impact the rate of successful lymphatic mapping. Results RA-TLH and SLN mapping was performed in 111 women; 93 had EC and 18 had CAH. Eighty women had low grade and 31 had high grade disease. Overall, at least one SLN was identified in 85.6% of patients with SBM in 62.2% of patients. Dye choice (indocyanine green versus isosulfan blue), odds ratio (OR: 4.5), body mass index (OR: 0.95), and clinically enlarged lymph nodes (OR: 0.24) were associated with SBM rate on multivariate analyses. The use of indocyanine green dye was particularly beneficial in patients with a body mass index greater than 30. Conclusion Injection dye, BMI, and clinically enlarged lymph nodes are important considerations when performing sentinel lymph node mapping for EC.

Objective The study objective was to examine the safety and cost savings of selective cardiac surveillance (CS) during treatment with pegylated liposomal doxorubicin (PLD). Methods A retrospective, dual institution study of women receiving PLD for the treatment of a gynecologic malignancy was performed. The study period was 2002–2014. At both institutions, a selective strategy for CS was implemented in which only high-risk women with a cardiac history or with symptoms suggestive of cardiac toxicity during PLD treatment underwent a cardiac evaluation. Patient demographics, clinical and treatment history were evaluated. Cost analyses were performed utilizing professional/technical fee rates for echocardiogram and multi-gated acquisition scan for each state. Results PLD was administered in 184 women. The mean patient age was 62.7years, and 79% were treated for recurrent ovarian or peritoneal carcinoma. The median cumulative administered dose of PLD was 300mg/m 2 ; 24 received >550mg/m 2 . The median follow-up time was 20months. Of the 184 patients, the majority ( n =157, 85.3%) did not undergo either an initial cardiac evaluation or surveillance during or post-PLD treatment. Fifty-three patients considered high risk for anthracycline-induced cardiotoxicity underwent CS. Only three patients (1.6%) in the entire cohort developed CHF that was possibly related to PLD treatment; all had significant pre-existing cardiac risk factors. Selective instead of routine use of CS in the study population resulted in a cost savings of $182,552.28. Conclusion Utilizing cardiac surveillance in select women undergoing PLD treatment for gynecologic malignancies resulted in significant health care cost savings without adversely impacting clinical outcomes.

Increased adrenergic signaling facilitates tumor progression, but the underlying mechanisms remain poorly understood. We examined factors responsible for stress-mediated effects on monocyte/macrophage recruitment into the tumor microenvironment, and the resultant effects on tumor growth. In vitro, MCP1 was significantly increased after catecholamine exposure, which was mediated by cAMP and PKA. Tumor samples from mice subjected to daily restraint stress had elevated MCP1 gene and protein levels, increased CD14+ cells, and increased infiltration of CD68+ cells. hMCP1 siRNA-DOPC nanoparticles significantly abrogated daily restraint stress-induced tumor growth and inhibited infiltration of CD68+ and F4/80+ cells. In ovarian cancer patients, elevated peripheral blood monocytes and tumoral macrophages were associated with worse overall survival. Collectively, we demonstrate that increased adrenergic signaling is associated with macrophage infiltration and mediated by tumor cell-derived MCP1 production.

OBJECTIVE: To examine the cumulative incidence of subsequent ovarian cancer among young women with stage I endometrioid endometrial cancer who had ovarian conservation at surgical treatment. METHODS: This retrospective study examined the Surveillance, Epidemiology, and End Results Program to identify women aged younger than 50 years who underwent hysterectomy with ovarian conservation for stage I endometrioid endometrial cancer between 1983 and 2013. Time-dependent risk of ovarian cancer diagnosed during the follow-up after endometrial cancer diagnosis was examined. RESULTS: Among 1,322 women in the study cohort, 16 women developed subsequent ovarian cancer with 5- and 10-year cumulative incidences of 1.0% and 1.3%, respectively. Median time to develop subsequent ovarian cancer was 2.4 years, and the majority of subsequent ovarian cancer was diagnosed within the first 3 years from the diagnosis of endometrial cancer (68.8%). The majority of subsequent ovarian cancer was endometrioid type (81.3%) and stage I disease (75.0%). With a median follow-up time of 11.6 years, there were no ovarian cancer deaths. Younger age at endometrial cancer diagnosis was significantly associated with increased risk of subsequent ovarian cancer (10-year cumulative incidences: age younger than 40 compared with 40–49 years, 2.6% compared with 0.4%, hazard ratio 5.00, 95% confidence interval [CI] 1.60–15.7, P=.002). CONCLUSION: Young women with stage I endometrioid endometrial cancer have an approximately 1% risk of developing subsequent ovarian cancer after ovarian conservation at the time of hysterectomy that was associated with favorable tumor factors resulting in good ovarian cancer-specific survival. Our results endorse the importance of genetic testing and close follow-up when counseling about this procedure, especially for those who are younger than 40 years.

Objectives Women with advanced-stage, low-grade serous ovarian carcinoma (LGSC) have low chemotherapy response rates and poor overall survival. Most LGSC tumors overexpress hormone receptors, which represent a potential treatment target. Our study objective was to determine the outcomes of patients with advanced-stage LGSC treated with primary cytoreductive surgery (CRS) and hormone therapy (HT). Methods A retrospective study was performed at two academic cancer centers. Patients with Stage II–IV LGSC underwent either primary or interval CRS followed by adjuvant HT between 2004 and 2016. Gynecologic pathologists reviewed all cases. Two-year progression-free (PFS) and overall survival (OS) were calculated. Results Twenty-seven patients were studied; primary CRS followed by HT were administered in 26, while 1 patient had neoadjuvant chemotherapy followed by CRS and HT. The median patient age was 47.5, and patients had Stage II (n=2), Stage IIIA (n=6), Stage IIIC (n=18), and Stage IV (n=1) disease. Optimal cytoreduction to no gross residual was achieved in 85.2%. Ninety six percent of tumors expressed estrogen receptors, while only 32% expressed progesterone receptors. Letrozole was administered post operatively in 55.5% cases, anastrozole in 37.1% and tamoxifen in 7.4%. After a median follow up of 41months, only 6 patients (22.2%) have developed a tumor recurrence and two patients have died of disease. Median PFS and OS have not yet been reached, but 2-year PFS and OS were 82.8% and 96.3%, respectively, and 3-year PFS and OS were 79.0% and 92.6%, respectively. Conclusions Our series describes the initial experience with cytoreductive surgery and hormonal monotherapy for women with Stage II–IV primary ovarian LGSC. While surgery remains the mainstay of treatment, chemotherapy may not be necessary in patients with advanced-stage disease who receive adjuvant hormonal therapy. A cooperative group, Phase III trial is planned to define the optimal therapy for women with this ovarian carcinoma subtype.

Besides their function in limiting blood loss and promoting wound healing, experimental evidence has highlighted platelets as active players in all steps of tumorigenesis including tumor growth, tumor cell extravasation, and metastasis. Additionally, thrombocytosis in cancer patients is associated with adverse patient survival. Due to the secretion of large amounts of microparticles and exosomes, platelets are well positioned to coordinate both local and distant tumor-host crosstalk. Here, we present a review of recent discoveries in the field of platelet biology and the role of platelets in cancer progression as well as challenges in targeting platelets for cancer treatment.

Leiomyosarcoma, a rare tumor subtype, accounts for 1% of all uterine malignancies, but contributes to a significant proportion of uterine cancer deaths. Surgery is considered the mainstay of treatment for all soft tissue sarcomas, including uterine variants. However, uterine leiomyosarcoma is challenging to diagnose preoperatively and can mimic the appearance of benign uterine leiomyomas. Recently, concerns have grown in this regard, as surgeons have utilized uterine morcellation and myomectomy procedures unknowingly in the setting of occult uterine sarcoma. Because of aggressive tumor biology and relative chemotherapy and radiotherapy resistance, efficacious therapies to achieve prolonged survival or cure in those with both early and advanced-stage uterine leiomyosarcoma have been elusive. The strongest determinant of survival remains stage at diagnosis, though prediction models may provide a more accurate prognosis. Given the aggressive nature of this sarcoma subtype, novel early detection strategies and targeted therapies are the focus of several recently published and ongoing studies. While gemcitabine/docetaxel and doxorubicin remain the most active regimens in the treatment of advanced or recurrent disease, currently available cytotoxic regimens remain inadequate, with 5-year disease-specific survival of

This investigation describes the clinical significance of phosphorylated focal adhesion kinase (FAK) at the major activating tyrosine site (Y397) in epithelial ovarian cancer (EOC) cells and tumor-associated endothelial cells. FAK gene amplification as a mechanism for FAK overexpression and the effects of FAK tyrosine kinase inhibitor VS-6062 on tumor growth, metastasis, and angiogenesis were examined. FAK and phospho-FAKY397 were quantified in tumor (FAK-T; pFAK-T) and tumor-associated endothelial (FAK-endo; pFAK-endo) cell compartments of EOCs using immunostaining and qRT-PCR. Associations between expression levels and clinical variables were evaluated. Data from The Cancer Genome Atlas were used to correlate FAK gene copy number and expression levels in EOC specimens. The in vitro and in vivo effects of VS-6062 were assayed in preclinical models. FAK-T and pFAK-T overexpression was significantly associated with advanced stage disease and increased microvessel density (MVD). High MVD was observed in tumors with elevated endothelial cell FAK (59%) and pFAK (44%). Survival was adversely affected by FAK-T overexpression (3.03 vs 2.06 y, P = 0.004), pFAK-T (2.83 vs 1.78 y, P < 0.001), and pFAK-endo (2.33 vs 2.17 y, P = 0.005). FAK gene copy number was increased in 34% of tumors and correlated with expression levels (P < 0.001). VS-6062 significantly blocked EOC and endothelial cell migration as well as endothelial cell tube formation in vitro. VS-6062 reduced mean tumor weight by 56% (P = 0.005), tumor MVD by 40% (P = 0.0001), and extraovarian metastasis (P < 0.01) in orthotopic EOC mouse models. FAK may be a unique therapeutic target in EOC given the dual anti-angiogenic and anti-metastatic potential of FAK inhibitors.