Factors influencing clinical trial enrollment among ovarian cancer patients.

OBJECTIVE: To characterize patients who did not enroll on a clinical trial and identify barriers that may limit enrollment among patients with advanced epithelial ovarian cancer (EOC) presenting for first-line chemotherapy. METHODS: We conducted a retrospective review of patients diagnosed with stage II-IV EOC from 10/2009-4/2013, a time period during which multiple trials were available to all EOC patients, including optimally debulked, suboptimally debulked, or undergoing neoadjuvant chemotherapy. Enrollment status, demographics, tumor characteristics, and treatment details were recorded. SAS version 9.3 was used for all analyses. RESULTS: 144 patients met study criteria; 67% were enrolled on a trial. Enrolled patients were significantly younger (median 61 vs 68years, p=0.002). Stage (p=0.30), race (p=0.75), and performance status (p=0.38) were similar between enrolled and non-enrolled patients. Distance did not impact enrollment, as nearly half of patients in both groups lived >50miles from the treatment center (39.0% vs 47.8%, p=0.36). Mode of chemotherapy administration significantly differed based on participation (all p<0.05). Despite similar residual disease status (p=1.00) and number of chemotherapy regimens received (p=0.59), patients treated on trial had a higher 3-year survival rate (70.7% vs 51.7%, p=0.031). The difference in median progression-free survival approached significance (20.2 vs 9.2months, p=0.091). CONCLUSION: In an institution where the culture is to offer clinical trials to all eligible patients, 33% of front-line EOC patients did not participate. Increasing age was associated with non-participation. Modifiable barriers must be overcome so that trial enrollment can better reflect true EOC demographics.

Initiation of a formalized precision medicine program in gynecologic oncology.

OBJECTIVE: In an effort to better incorporate precision medicine into clinical practice, we initiated a pilot project to screen, discuss, and genetically characterize patients with metastatic or recurrent gynecologic malignancies for whom no curative standard of care exists. METHODS: In 7/2014, we initiated a multi-disciplinary Precision Medicine Board (PMB) whose purpose was to apply molecular profiling to select and prioritize early phase clinical trial enrollment for high-risk gynecologic malignancies. Additional objectives were to record outcomes and enable scientific discussions of mutations which may foster local translational research. FoundationOne was the preferred genomic platform; results were reviewed by a team comprised of disease site specialists, phase I trialists, and basic and translational scientists affiliated with the Gynecologic Cancer Program. A detailed database for each patient was created and is followed prospectively for treatment use and resultant outcomes. RESULTS: To date, we have presented 62 cases with interpretable FoundationOne testing on 60 tumor samples (31 ovarian, 18 uterine, 9 cervical, and 4 other female genital tract). Significant genomic alterations were commonly found in all tumor types (median: 3); TP53 (45%) and PIK3CA (27%) were the most frequently noted mutations; however, molecular profiling resulted in identification of few actionable mutations (6%). To date, we have matched 4 patients on therapies based on actionable mutations. CONCLUSIONS: The predominant function of our PMB is establishment of a forum to enhance research while providing clinical care for refractory malignancies. We have matched patients with specific mutations to ongoing trials and are developing investigator-initiated studies based on trends within genomic profiling results. Longer-term follow up will be required to determine the success of this strategy.

Cost-utility comparison of neoadjuvant chemotherapy versus primary debulking surgery for treatment of advanced-stage ovarian cancer in patients 65 years old or older.

OBJECTIVE: Treatment for advanced-stage epithelial ovarian cancer (AEOC) includes primary debulking surgery (PDS) or neoadjuvant chemotherapy (NACT). A randomized controlled trial comparing these treatments resulted in comparable overall survival (OS). Studies report more complications and lower chemotherapy completion rates in patients 65 years old or older receiving PDS. We sought to evaluate the cost implications of NACT relative to PDS in AEOC patients 65 years old or older. STUDY DESIGN: A 5 year Markov model was created. Arm 1 modeled PDS followed by 6 cycles of carboplatin and paclitaxel (CT). Arm 2 modeled 3 cycles of CT, followed by interval debulking surgery and then 3 additional cycles of CT. Parameters included OS, surgical complications, probability of treatment initiation, treatment cost, and quality of life (QOL). OS was assumed to be equal based on the findings of the international randomized control trial. Differences in surgical complexity were accounted for in base surgical cost plus add-on procedure costs weighted by occurrence rates. Hospital cost was a weighted average of diagnosis-related group costs weighted by composite estimates of complication rates. Sensitivity analyses were performed. RESULTS: Assuming equal survival, NACT produces a cost savings of $5616. If PDS improved median OS by 1.5 months or longer, PDS would be cost effective (CE) at a $100,000/quality-adjusted life-year threshold. If PDS improved OS by 3.2 months or longer, it would be CE at a $50,000 threshold. The model was robust to variation in costs and complication rates. Moderate decreases in the QOL with NACT would result in PDS being CE. CONCLUSION: A model based on the RCT comparing NACT and PDS showed NACT is a cost-saving treatment compared with PDS for AEOC in patients 65 years old or older. Small increases in OS with PDS or moderate declines in QOL with NACT would result in PDS being CE at the $100,000/quality-adjusted life-year threshold. Our results support further evaluation of the effects of PDS on OS, QOL and complications in AEOC patients 65 years old or older.

Induced abortions and the risk of all cancers combined and site-specific cancers in Shanghai.

Although some previous case-control studies found an increased risk of breast cancer in women who had an induced abortion, the evidence from prospective studies suggests that induced abortions do not cause breast cancer. We have assessed risks of 12 types of cancer in women who have had induced abortions in a prospective study in China. Female textile workers (n = 267,400) completed a baseline questionnaire (1989-1991) that ascertained information on the major risk factors for breast cancer, contraceptive use, and induced abortions and were actively followed until July 2000. Cox Proportional Hazards analysis was used to calculate incidence rate ratios for specific types of cancer in women who ever had an induced abortion and by number of induced abortions. Women who had had an abortion were not at increased risk of cancer. There was a significant reduction in risk of uterine corpus cancer in women who had ever had an induced abortion, and a significant decreasing trend in risk with increasing number of induced abortions. No convincing associations with other cancers were observed. Women who have induced abortions after a live birth are not at increased risk of cancer and induced abortions may reduce risk of cancer of the corpus uteri.