Analysis of Differentially Expressed MicroRNAs and Circulating Tumor Cells as Predictive Biomarkers of Platinum Chemoresistance in Primary Ovarian Carcinomas: A Prospective Study.

LESSON LEARNED: Circulating tumor cells, microRNA markers, or other biomarkers merit examination as part of correlative scientific analyses in prospective clinical trials. BACKGROUND: Platinum chemotherapy resistance occurs in approximately 25% of patients with ovarian carcinoma; however, no biomarkers of ovarian carcinoma chemoresistance have been validated. We performed a prospective trial designed to identify tumor-based predictive biomarkers of platinum resistance. METHODS: Tumor specimens were collected from 29 women with newly diagnosed histopathologically proven primary ovarian carcinoma. Of these, 23 women had specimens accessible for assessment and outcome data available regarding chemosensitive versus chemoresistance status via review of the medical record. Tumor slices were stained with antibodies against two microRNAs (miRNAs 29b and 199a) differentially expressed in chemoresistant ovarian cancer cell lines. Additionally, blood samples obtained at the time of diagnosis were analyzed for the presence of circulating tumor cells (CTCs). RESULTS: The average age of the patients was 64 years, and 82.6% had high-grade epithelial carcinomas. The baseline median CA-125 was 464 (range 32-2,782). No statistically significant differences were observed in miR29b or 199a expression in platinum-resistant/refractory versus platinum-sensitive tumors. Furthermore, the presence of CTCs was not found to be statistically significantly predictive of eventual platinum resistance. CONCLUSION: Our analysis showed no differences in miR29b and 199a expression, and differences in baseline CTCs in women with newly diagnosed ovarian tumors were not statistically significant.

Assessment of Circulating Tumor Cells as a Predictive Biomarker of Histology in Women With Suspected Ovarian Cancer.

BACKGROUND: The clinical assessment of circulating tumor cells (CTCs) as a blood-based biomarker is FDA-approved for use in breast, colorectal, and prostate cancers. The objective of this prospective clinical study was to determine whether pretreatment CTCs are a useful diagnostic biomarker in women with complex pelvic masses. METHODS: Whole blood was collected from 49 women with newly diagnosed pelvic masses. The presence of CTCs was compared between women with and without ovarian cancer histopathologic diagnosis after surgery using a Chi-squared test. RESULTS: CTCs were absent in those with benign disease (0/14), present in 17% (5/29) of patients with a histologic diagnosis of ovarian carcinoma, and present in 80% (4/5) of patients with ovarian metastases from other cancers (P = 0.001). All 5 women with ovarian cancer who had CTCs present presented stage III or IV of the disease (P = 0.13). CONCLUSIONS: CTCs were more prevalent in patients with metastases to the ovary than in primary ovarian carcinomas.

Single Health System Adherence to 2012 Cervical Cancer Screening Guidelines at Extremes of Age and Posthysterectomy.

OBJECTIVE: To estimate the proportion of guideline nonadherent Pap tests in women aged younger than 21 years and older than 65 years and posthysterectomy in a single large health system. Secondary objectives were to describe temporal trends and patient and health care provider characteristics associated with screening in these groups. METHODS: A retrospective cross-sectional chart review was performed at Fairview Health Services and University of Minnesota Physicians. Reasons for testing and patient and health care provider information were collected. Tests were designated as indicated or nonindicated per the 2012 cervical cancer screening guidelines. Point estimates and descriptive statistics were calculated. Patient and health care provider characteristics were compared between indicated and nonindicated groups using χ and Wilcoxon rank-sum tests. RESULTS: A total of 3,920 Pap tests were performed between September 9, 2012, and August 31, 2014. A total of 257 (51%; 95% confidence interval [CI] 46.1-54.9%) of tests in the younger than 21 years group, 536 (40%; 95% CI 37.7-43.1%) in the older than 65 years group, and 605 (29%; 95% CI 27.1-31.0%) in the posthysterectomy group were not indicated. White race in the older than 65 years group was the only patient characteristic associated with receipt of a nonindicated Pap test (P=.007). Health care provider characteristics associated with nonindicated Pap tests varied by screening group. Temporal trends showed a decrease in the proportion of nonindicated tests in the younger than 21 years group but an increase in the posthysterectomy group. CONCLUSION: For women aged younger than 21 years and older than 65 years and posthysterectomy, 35% of Pap tests performed in our health system were not guideline-adherent. There were no patient or health care provider characteristics associated with guideline nonadherent screening across all groups.