TEST:

AmoyDx® HRD Focus Panel

Age at diagnosis was not affected by both BRCA and wGI status. HRD Insight assay could accurately and robustly determine the HRD status of ovarian tissue samples, including those with low quality.

However, thanks to the SNP analysis, a consistent number of partial or complete single-copy deletions or duplications in several chromosomes. The AmoyDX HRD focus assay performed well on pancreatic samples, despite being originally designed for ovarian cancer and used on samples stored for over a year. Larger studies are needed to further assess the role of HRD assays in pNETs research.

The initiative underscores the importance of personalized medicine for Vietnam. The key lessons learned emphasizes the need for local expertise, quality control, patient education, collaboration, and contextual adaptation to ensure the success and sustainability of such advanced diagnostic facilities.

Compared with the 3 kits, our assay showed a concordance rate of 94.6%, positive percent agreement and negative percent agreement of 96.4% and 92.9% respectively. Conclusions HRD status could be accurately and reliably determined by our HRD Insight assay to help physicians select approved PARPi for OC patients.

However, the efficacy and survival of Olaparib in some patients is dismal, in which the effective molecular biomarkers remain to be explored. Total 60 patients (January 2016 to March 2021) received Olaparib (300 mg, BID) with or without Bevacizumab (7.5-15 mg/kg, once every 21 days) (PSR OCs, N=19; Non-PSR OCs, N = 41), and undergo HRD test by AmoyDx® HRD Focus Panel (HRD-positive, GSS score ≥ 50 or BRCA1/2 mutated). In the study, we confirmed that HRD-positive patients can benefit from Olaparib therapy, and have a good prognosis. ICOSLGhigh and ICOSLGhigh & DLX2high, as potential biomarkers of survival and Olaparib efficacy, may help to better identify patients who will benefit most from Olaparib treatment and require further validation in clinical studies.

There is new hope for BRCA -negative ovarian cancer patients receiving targeted therapy. Up to 50% of patients could benefit from PARP inhibitor treatment, depending on their HRD status. However, there are important factors to consider when choosing the right test method.

In our preliminary validation cohor t, we observed a 90% concordance rate between assays, consistent with the results of other series (81.6% to 87.8%). When applying the AmoyDX HRD focus panel in HGSOC, we detected HRD positivity in 48.22% of tumors, similar with the incidences reported in PAOLA1 (48%), PRIMA (50.9%), and VELIA (50.1%) trials. While the global prevalence of BRCA1/2 alterations in ovarian cancer ranges from 20% to 25%, we found that 32% of positive cases in our series exhibited gene variants consistent with previous reports of BRCA variant frequencies in Mexican patients.

Resistance mechanism of PARPi is complex. BRCA restoration mutation is a frequent cause of PARPi resistance. PARPi resistance could be driven without DNA mutation.

A trend for a clinical benefit of second-line therapy with re-exposure to platinum-based agents as compared to irinotecan-based regimens was observed (HR= 0.79, 95%CI 0.34-1.8, P= 0.56)... Platinum-based chemotherapy associates with more favorable outcomes in HRRm BTC patients. Further investigation is needed to delineate HRD in the context of personalizing systemic therapies of BTC.

False-positive rates were 31.6% (6/19) for AmoyDx GI status and 31.9% (7/22) for OncoScanâ„¢, while false-negative rates were 0% (0/28, AmoyDx) and 11.1% (2/18, OncoScanâ„¢) compared with the Myriad MyChoice GI status. While substantial concordance between Myriad MyChoice and alternative assays was demonstrated, prospective validation of the analytical performance and clinical relevance of these assays is warranted.

Our data shows that the implementation of in-house HRD testing in diagnostic laboratories is technically feasible and can be reliably performed with commercial assays. Also, the turnaround time is compatible with clinical needs, making it an ideal alternative to offer to a broader number of patients while maintaining high-quality standards at more accessible price tiers.

"We developed the Seraseq HRD reference materials to meet the needs of laboratories looking to analyze HRD in cancer patient samples. The HRD status of each material was evaluated using several assays using different measurement approaches. Although the materials showed similar trends and concordance among formats, there was variability in GIS across the methods tested."