Amy Armstrong

Diagnosis and Management of Endometrial Hyperplasia

Endometrial hyperplasia (EH), with or without atypia, is a common gynecologic diagnosis and a known precursor of endometrial carcinoma, the most common gynecologic malignancy. During the reproductive years, the risk of EH is increased by conditions associated with intermittent or absent ovulation, in particular, polycystic ovary syndrome. After menopause when ovulation has ceased, EH is more common in women with conditions that increase levels of circulating estrogen such as obesity or estrogen replacement therapy. Women with EH are at increased risk for both concurrent and subsequent endometrial cancer. The risk of coexisting cancer in women with a diagnosis of EH at endometrial sampling is due to limitations in both endometrial sampling and the diagnostic reproducibility among pathologists. These diagnostic uncertainties add to the complexity of managing EH. This review offers a rational approach to prevention, diagnosis, and treatment of EH, including hormone therapy and conservative surgical methods.

Evaluation of the cost of CA-125 measurement, physical exam, and imaging in the diagnosis of recurrent ovarian cancer

OBJECTIVE Ovarian cancer accounts for 50% of deaths from gynecologic malignancies. We sought to determine the cost of common methods of surveillance of women with ovarian cancer in first clinical remission. The current standard for post treatment surveillance is the National Comprehensive Cancer Network (NCCN) guidelines. METHODS We retrospectively determined how recurrence was initially detected at our institution and a cost model was created and applied to the United States population to calculate surveillance costs using the Surveillance Epidemiology & End Results (SEER) database. RESULTS 57% (n=60) of first recurrences were identified by increasing CA 125 level. Routine office visit identified 27% (n=29) of recurrences, and 15% (n=16) were diagnosed initially with CT scan. In 5% (5/105), CT abnormality was the only finding. 95% (100/105) of patients had either elevated CA 125 or office visit findings at time of recurrence. Of the 22,000 women diagnosed with ovarian cancer yearly, 60% (n=13,266) will have advanced disease and are likely to recur. The surveillance cost for this population for 2 years using our model is

Robotic surgery in gynecologic oncology.

32,500,000 using NCCN guidelines and

Using a novel computational drug-repositioning approach (DrugPredict) to rapidly identify potent drug candidates for cancer treatment

58,000,000 if one CT scan is obtained. CONCLUSIONS Our data suggests that following NCCN guidelines will detect 95% of recurrences. An additional

Phase II study of single-agent cabozantinib in patients with recurrent clear cell ovarian, primary peritoneal or fallopian tube cancer (NRG-GY001)

26 million will be needed to identify the 5% of women with recurrence seen on CT only. Post treatment surveillance of ovarian cancer patients contributes significantly to health care costs. Use of CT scan to follow these patients largely increases cost with only a small increase in recurrence detection.

Patterns of First Recurrence in African American Patients with High Grade Epithelial Ovarian Carcinoma.

Robotic surgery for the management of gynecologic cancers allows for minimally invasive surgical removal of cancer-bearing organs and tissues using sophisticated surgeon-manipulated, robotic surgical instrumentation. Early on, gynecologic oncologists recognized that minimally invasive surgery was associated with less surgical morbidity and that it shortened postoperative recovery. Now, robotic surgery represents an effective alternative to conventional laparotomy. Since its widespread adoption, minimally invasive surgery has become an option not only for the morbidly obese but for women with gynecologic malignancy where conventional laparotomy has been associated with significant morbidity. As such, this paper considers indications for robotic surgery, reflects on outcomes from initial robotic surgical outcomes data, reviews cost efficacy and implications in surgical training, and discusses new roles for robotic surgery in gynecologic cancer management.

The Role of Adjuvant Radiation in High Risk Early-Stage Endometrial Cancer

Computation-based drug-repurposing/repositioning approaches can greatly speed up the traditional drug discovery process. To date, systematic and comprehensive computation-based approaches to identify and validate drug-repositioning candidates for epithelial ovarian cancer (EOC) have not been undertaken. Here, we present a novel drug discovery strategy that combines a computational drug-repositioning system (DrugPredict) with biological testing in cell lines in order to rapidly identify novel drug candidates for EOC. DrugPredict exploited unique repositioning opportunities rendered by a vast amount of disease genomics, phenomics, drug treatment, and genetic pathway and uniquely revealed that non-steroidal anti-inflammatories (NSAIDs) rank just as high as currently used ovarian cancer drugs. As epidemiological studies have reported decreased incidence of ovarian cancer associated with regular intake of NSAIDs, we assessed whether NSAIDs could have chemoadjuvant applications in EOC and found that (i) NSAID Indomethacin induces robust cell death in primary patient-derived platinum-sensitive and platinum- resistant ovarian cancer cells and ovarian cancer stem cells and (ii) downregulation of β-catenin is partially driving effects of Indomethacin in cisplatin-resistant cells. In summary, we demonstrate that DrugPredict represents an innovative computational drug- discovery strategy to uncover drugs that are routinely used for other indications that could be effective in treating various cancers, thus introducing a potentially rapid and cost-effective translational opportunity. As NSAIDs are already in routine use in gynecological treatment regimens and have acceptable safety profile, our results will provide with a rationale for testing NSAIDs as potential chemoadjuvants in EOC patient trials.

Management of a Type I Hypersensitivity Reaction to IV Etoposide in a Woman with a Yolk Sac Tumor: A Case Report

OBJECTIVE To evaluate the efficacy and tolerability of cabozantinib in recurrent clear cell ovarian, primary peritoneal or fallopian tube cancer. METHODS Patients with recurrent ovarian, fallopian or primary peritoneal tumors with at least 50% clear cell histomorphology, measurable disease, one or two prior regimens and ECOG performance status 0-2 received cabozantinib 60 mg orally once daily continuously, in 4-week cycles until disease progression or unacceptable toxicity. Primary endpoints were progression-free survival (PFS) at six months and complete or partial tumor response (as assessed by RECIST 1.1). Secondary endpoints included toxicity, PFS, and overall survival (OS). RESULTS Over 19 months, 13 patients were accrued. Fifty-four percent of patients were ≥60 years of age. Performance statuses of 0 and 1 comprised 8 and 5 patients. No objective tumor responses were seen. Three (23% [95% CI: 5%, 54%]) of 13 patients had PFS ≥6 months, including one patient who received cabozantinib for 23 cycles and was still on treatment as of the data cut-off date. Median PFS and OS were 3.6 and 8.1 months, respectively. There was one patient with a grade 5 event: a thromboembolic event considered possibly related to study therapy; patients cause of death was determined to be due to disease and protocol treatment. Four other patients had thromboembolic events (two grade 3 and one each grade 1 and grade 2). Other grade 3 or higher events reported in two or more patients were nausea, vomiting, fatigue, dyspnea, and dehydration. CONCLUSIONS Cabozantinib demonstrated minimal activity in the second- and third-line treatments of clear cell ovarian, fallopian tube or primary peritoneal carcinoma.

Standardization of Laparoscopic Operative Reporting: Improving Gynaecological Surgeon Communication

Background/Aims: The aim of this study is to compare the distribution of anatomic sites of first recurrence in African American (AA) patients with ovarian carcinoma compared to Caucasians. Methods: Patients diagnosed with high-grade epithelial ovarian, fallopian tube or peritoneal carcinoma from 2007 to 2013 were identified. Patterns of recurrence were compared for AA and Caucasian patients. Progression-free survival (PFS) and overall survival (OS) were compared. Results: A total of 238 patients were included - 210 Caucasians and 28 AAs. At a follow-up time of 28 months, AAs were more likely to have multiple anatomic sites of recurrence rather than a single site when compared to Caucasians (63.6 vs. 35.5%, p = 0.01). Time to first recurrence was shorter for AA patients (12 vs. 18 months, p < 0.01). PFS and OS did not differ. AA patients with multiple sites of first recurrence had a significantly shorter OS than Caucasian patients with multiple sites of first recurrence (24 vs. 30 months, p = 0.022). Conclusion: Patterns of first recurrence differ between AAs and Caucasians. AAs have shorter times to first recurrence and are more likely to have multiple anatomic sites involved. AA patients with multiple sites of recurrence have a shorter OS than Caucasian patients with multiple sites.

Abstract A64: β-catenin as a TIC therapeutic target in epithelial ovarian cancer.

Endometrial cancer is the most commonly diagnosed malignancy of the female genital tract in the United States. The role of adjuvant radiation for the treatment of patients with early stage disease is still heavily debated, as no overall survival benefit has been demonstrated in large prospective trials. There is, however, evidence to suggest a decrease in recurrence risk with administration of adjuvant radiotherapy, especially in patients with high-risk features. In this review, we describe the relevant literature to date, define how we determine which patients are considered high or intermediate risk, and describe the findings related to the addition of chemotherapy to adjuvant brachytherapy.