Characteristics of African American women at high-risk for ovarian cancer in the southeast: Results from a Gynecologic Cancer Risk Assessment Clinic.

OBJECTIVES: Describe patient characteristics in African American (AA) women seen for gynecologic cancer related genetic counseling at a large southeastern comprehensive cancer center. METHODS: We reviewed an IRB approved, prospective observational cohort of patients from a Gynecologic Cancer Risk Assessment Clinic. Data evaluated included personal cancer history, family history, frequency of genetic testing, frequency/type of genetic mutations, and frequency of surgical intervention. Standard statistical statistics were utilized. RESULTS: 1227 patients were evaluated from 2003 to 2015, of which 95 (7.7%) were AA. Sixteen patients had a personal history of ovarian cancer. 21 women (22%) underwent genetic counseling only; subsequent genetic testing was not recommended based on absence of risk factors. Of the seventy-four AA patients in whom genetic testing was recommended, sixty-six (69.5%) completed testing. Of women tested, 37 (56%) had abnormal results. Eight and 14 patients had pathogenic variants in BRCA1 and BRCA2, respectively. Two were found to have pathogenic PALB2 variants; one had a pathogenic ATM variant and one constitutional MLH1 epimutation case was identified. Eleven had BRCA variants of uncertain significance. Of the patients with abnormal testing, six of 22 women with pathogenic BRCA variants underwent risk-reducing salpingo-oophorectomy (RRSO). CONCLUSIONS: Our study demonstrates that in a region where AAs represent 27% of the population, the proportion of AA patients referred to a Gynecologic Cancer Risk Assessment Clinic remains low. Pathogenic variant and variant of uncertain significance rates were high in patients tested, likely representing a selection bias of high-risk patients. Endeavors should continue to identify minorities at risk for ovarian cancer and institute measures to provide thorough genetic counseling and testing.

PARP inhibitor maintenance therapy for patients with platinum-sensitive recurrent ovarian cancer: a cost-effectiveness analysis.

PURPOSE: To determine the cost-effectiveness of olaparib, a PARP inhibitor, as maintenance therapy for platinum-sensitive (PS) recurrent ovarian cancer. METHODS: Two separate decision analysis models compared the cost of observation versus olaparib maintenance therapy in patients with PS recurrent ovarian cancer, one for patients with a germline BRCA1/2 mutation and one for patients with wild-type BRCA1/2. Patients received six cycles of paclitaxel and carboplatin. Drug costs were estimated using 2014-2015 wholesale acquisition costs. The cost of olaparib was estimated at $13,440 per month. Rate of germline BRCA1/2 mutation was estimated at 20%. Progression-free survival was determined from published data. Incremental cost-effectiveness ratios (ICERs) per progression-free life-year saved (PF-LYS) were calculated. A sensitivity analysis estimated the cost at which olaparib would be cost-effective. RESULTS: We estimated that there were 5549 patients diagnosed with PS recurrent ovarian cancer in the United States annually. The cost of observation in 1110 patients with a BRCA1/2 mutation was $5.5 million (M) versus $169.2M for maintenance therapy with olaparib. The ICER for olaparib maintenance therapy in patients with a BRCA mutation was $258,864 per PF-LYS. If the cost of olaparib was decreased to $2500 per month, the ICER was $49,584. For the 4439 patients with wild-type BRCA, the cost of maintenance therapy was $444.2M; the ICER was $600,552 per PF-LYS. CONCLUSIONS: For patients with a germline BRCA1/2 mutation, maintenance therapy with olaparib is not cost-effective with an ICER of $258,864 per PF-LYS. To achieve an ICER of less than $50,000, the cost of olaparib should be $2500 or less per month. For wild-type BRCA1/2 patients, maintenance therapy with olaparib is not cost-effective.

Niclosamide Analogs for Treatment of Ovarian Cancer.

OBJECTIVE: Niclosamide has shown activity against ovarian cancer in vitro; however, it has low bioavailability in vivo. Therefore, we investigated the cytotoxicity of niclosamide analogs in combination with carboplatin against ovarian cancer patient ascites cells and tissue slices. MATERIALS/METHODS: Tumorspheres were isolated from ascites collected from patients undergoing ovarian cancer surgery and plated at 10,000 cells per 50 µL into low attachment plates. Tumor slices were also processed at the time of surgery. These were treated concurrently with niclosamide or analogs (0.1-5 µM) and carboplatin (5-150 µM). At 48 hours, cell viability was assessed with ATPlite assay. Western blotting was used to determine expression of Wnt/ß-catenin proteins in ascites cells. RESULTS: Cytotoxicity of niclosamide and its analogs in combination with carboplatin was demonstrated in 24 patient ascites samples. Increased cytotoxicity was seen with 2 analogs in 23 patient ascites samples when compared with niclosamide. Similar cytotoxicity was produced in an ex vivo tumor slice model. Western blot analysis showed decreased expression of Wnt/ß-catenin proteins with niclosamide and analog treatment in a dose-dependent fashion. CONCLUSIONS: The niclosamide-like analogs produced cytotoxicity both alone and in combination with carboplatin against tumorspheres from patient ascites and slices from solid tumor samples. Tumor slices showed similar cytotoxicity to matched ascites samples. Western blots showed down-regulation of Wnt pathway-associated proteins in patient samples treated with niclosamide analogs. These results suggest that more soluble niclosamide analogs may be useful for the treatment of ovarian cancer in combination with chemotherapy.

Utilization of an Alternative Docetaxel-based Intraperitoneal Chemotherapy Regimen in Patients With Ovarian, Fallopian Tube or Primary Peritoneal Carcinoma: A Continued Need for Ovarian Cancer Patients.

OBJECTIVE: The objective of this study was to report the tolerability and toxicity of a regimen consisting of intravenous (IV) docetaxel and intraperitoneal (IP) cisplatin and paclitaxel with granulocyte colony-stimulating factor support. MATERIALS AND METHODS: We conducted a retrospective cohort study of patients with surgical stage II-IV epithelial ovarian, fallopian tube or primary peritoneal carcinoma treated with an outpatient IP chemotherapy regimen consisting of docetaxel 75 mg/m IV and cisplatin 75 mg/m IP day 1 followed by paclitaxel 60 mg/m IP day 8 every 21 days. Grade 3 and 4 toxicity, dose delays and reductions, port complications, and tolerability are reported. Outcomes, including response rate, progression-free survival (PFS), overall survival (OS) are also reported. RESULTS: A total of 60 patients received this IP regimen. Most common toxicities included neutropenia (47%), gastrointestinal (28%), and anemia (25%). Most patients (85%) experienced no IP port complications. Dose delay or reduction was required in 30% of patients. Two-thirds completed all prescribed cycles, with 80% of total planned cycles completed. Complete response was achieved for 88%, and 43% are currently without evidence of disease. Median PFS for all patients was 25.5 months (95% confidence interval [CI], 20.4-30.5 mo) while OS for all patients was 56.8 months (95% CI, 47.7-65.9 mo). For the 44 patients with stage III disease, median PFS was 22.1 months (95% CI, 16.3-28.0 mo), while median OS was 56.8 months (95% CI, 47.3-66.3 mo). CONCLUSIONS: This docetaxel-based IP chemotherapy regimen demonstrates an improved tolerability profile compared with GOG172. Additional evaluations on alternative IP regimens remain warranted. Short follow-up time limits survival assessment, but results are encouraging.

Ovarian cancer stem cells: Can targeted therapy lead to improved progression-free survival?

Despite significant effort and research funds, epithelial ovarian cancer remains a very deadly disease. There are no effective screening methods that discover early stage disease; the majority of patients are diagnosed with advanced disease. Treatment modalities consist primarily of radical debulking surgery followed by taxane and platinum-based chemotherapy. Newer therapies including limited targeted agents and intraperitoneal delivery of chemotherapeutic drugs have improved disease-free intervals, but failed to yield long-lasting cures in most patients. Chemotherapeutic resistance, particularly in the recurrent setting, plagues the disease. Targeting the pathways and mechanisms behind the development of chemoresistance in ovarian cancer could lead to significant improvement in patient outcomes. In many malignancies, including blood and other solid tumors, there is a subgroup of tumor cells, separate from the bulk population, called cancer stem cells (CSCs). These CSCs are thought to be the cause of metastasis, recurrence and resistance. However, to date, ovarian CSCs have been difficult to identify, isolate, and target. It is felt by many investigators that finding a putative ovarian CSC and a chemotherapeutic agent to target it could be the key to a cure for this deadly disease. This review will focus on recent advances in this arena and discuss some of the controversies surrounding the concept.

Outcomes of gynecologic oncology patients undergoing robotic-assisted laparoscopic procedures in a university setting.

This study evaluated intraoperative complications and postoperative outcomes of gynecologic oncology patients undergoing robotic-assisted (RA) laparoscopic procedures in a university setting. A retrospective chart review evaluated all gynecologic oncology patients at the University of Alabama at Birmingham who underwent attempted RA procedures between August 2006 and October 2011. Patient demographics, medical/surgical history, intraoperative complications, postoperative outcomes, conversion rates, readmission rates, and length of stay were examined. Total complication rates were assessed over time for each surgeon. 681 patients underwent planned RA procedures by seven gynecologic oncologists. The mean body mass index was 33.5 kg/m(2) (range 16.6-71.0 kg/m(2)). 61.4 % were diagnosed with malignancy. The most common procedure was RA hysterectomy with unilateral/bilateral salpingo-oophorectomy (37.2 %). Robotic staging was performed in 291 patients (45.1 %). Mean estimated blood loss was 75 ml (range 5-700 ml). 36 patients (5.3 %) were converted to laparotomy. The most common reason for conversion was adhesions (30.1 %), followed by uterine size (22.2 %). In 107 cases, a surgical modification was required for specimen removal including mini-laparotomy (24), extension of accessory port (36), morcellation (9), and difficult vaginal delivery (38). 3.7 % had intraoperative complications; 6 patients had a cystotomy and 5 had a vascular injury. Postoperatively, 20 patients had a febrile episode, 9 had wound complications, and 3 had a vaginal cuff dehiscence. 27 (4.2 %) patients were readmitted within 30 days. Complication rates and conversion rates were similar per surgeon. Total complication rates for evaluable surgeons were similar between the first 10 cases and subsequent 50 cases. Although patients undergoing RA procedures in a university setting are high risk, the conversion rate to laparotomy is low and intraoperative and postoperative complications are acceptable. Total complication rates for each surgeon were not impacted by the number of cases performed.