Proteomic signature for detection of high-grade ovarian cancer in germline BRCA mutation carriers.

No current screening methods for high-grade ovarian cancer (HGOC) guarantee effective early detection for high-risk women such as germline BRCA mutation carriers. Therefore, the standard-of-care remains risk-reducing salpingo-oophorectomy (RRSO) around age 40. Proximal liquid biopsy is a promising source of biomarkers, but sensitivity has not yet qualified for clinical implementation. We aimed to develop a proteomic assay based on proximal liquid biopsy, as a decision support tool for monitoring high-risk population. Ninety Israeli BRCA1 or BRCA2 mutation carriers were included in the training set (17 HGOC patients and 73 asymptomatic women), (BEDOCA trial; ClinicalTrials.gov Identifier: NCT03150121). The proteome of the microvesicle fraction of the samples was profiled by mass spectrometry and a classifier was developed using logistic regression. An independent cohort of 98 BRCA mutation carriers was used for validation. Safety information was collected for all women who opted for uterine lavage in a clinic setting. We present a 7-protein diagnostic signature, with AUC >0.97 and a negative predictive value (NPV) of 100% for detecting HGOC. The AUC of the biomarker in the independent validation set was >0.94 and the NPV >99%. The sampling procedure was clinically acceptable, with favorable pain scores and safety. We conclude that the acquisition of Müllerian tract proximal liquid biopsies in women at high-risk for HGOC and the application of the BRCA-specific diagnostic assay demonstrates high sensitivity, specificity, technical feasibility and safety. Similar classifier for an average-risk population is warranted.

Changes in Adenoma Detection Rate From Full-Spectrum Endoscopy to Standard Forward-Viewing Endoscopy.

GOALS: The aim was to investigate the adenoma detection rate (ADR) of endoscopists who have used full-spectrum endoscopy (Fuse) for 3 years and revert back to traditional forward-viewing endoscopes (R-TFV) at an ambulatory surgical center. BACKGROUND: Traditional forward viewing (TFV) endoscopes have 1 camera and provide an angle of view of 140 to 170 degrees, whereas Fuse provides a 330 degrees view through the addition of 2 side cameras. It has previously been reported that Fuse increased the ADR by 5.4% when compared with previous rates using TFV. Fuse is no longer commercially available. The ADR of endoscopists who revert back to TFV is unknown. STUDY: We conducted a retrospective analysis of data examining the ADR from average risk screening colonoscopies at a 5-room ambulatory surgical center where endoscopists transitioned from TFV to Fuse in April 2014 and then reverted back to TFV in 2016. The primary outcome was ADR. Secondary outcomes were ADR for advanced and right-sided adenomas. RESULTS: A total of 6110 procedures were reviewed. The ADR was 23.70% for TFV, 29.02% for Fuse and 28.88% for R-TFV. The ADR for advanced adenomas was 3.8% for TFV, 6.0% for Fuse and 7.3% for R-TFV. The ADR for right-sided adenomas was 13.0% for TFV, 16.7% for Fuse and 16.0% for R-TFV. The results for all 3 categories showed a statistical difference between TFV and Fuse as well as between TFV and R-TFV. There were no statistical differences between the ADR of Fuse compared with R-TFV. CONCLUSIONS: During R-TFV, endoscopists are able to maintain their increased ability to detect adenomas. This would suggest that there was a change in behavior in endoscopists using Fuse that was durable.