Analytical validation of a novel comprehensive genomic profiling informed circulating tumor DNA monitoring assay for solid tumors.

Emerging technologies focused on the detection and quantification of circulating tumor DNA (ctDNA) in blood show extensive potential for managing patient treatment decisions, informing risk of recurrence, and predicting response to therapy. Currently available tissue-informed approaches are often limited by the need for additional sequencing of normal tissue or peripheral mononuclear cells to identify non-tumor-derived alterations while tissue-naïve approaches are often limited in sensitivity. Here we present the analytical validation for a novel ctDNA monitoring assay, FoundationOne®Tracker. The assay utilizes somatic alterations from comprehensive genomic profiling (CGP) of tumor tissue. A novel algorithm identifies monitorable alterations with a high probability of being somatic and computationally filters non-tumor-derived alterations such as germline or clonal hematopoiesis variants without the need for sequencing of additional samples. Monitorable alterations identified from tissue CGP are then quantified in blood using a multiplex polymerase chain reaction assay based on the validated SignateraTM assay. The analytical specificity of the plasma workflow is shown to be 99.6% at the sample level. Analytical sensitivity is shown to be >97.3% at ≥5 mean tumor molecules per mL of plasma (MTM/mL) when tested with the most conservative configuration using only two monitorable alterations. The assay also demonstrates high analytical accuracy when compared to liquid biopsy-based CGP as well as high qualitative (measured 100% PPA) and quantitative precision (<11.2% coefficient of variation).

DIGITAL NIST: An examination of the obstacles and opportunities in the digital transformation of NIST's reference materials.

Early in 2022, NIST embarked on a pilot project to produce digital calibration reports and digital certificates of analysis for reference materials. The goal is to produce examples of digital reports and certificates to assess the scope and challenges of digital transformation in those particular measurement services. This paper focuses on the Reference Material Certificate effort of the pilot project. Our aims for this part of the pilot project are: to generate a digital Reference Material Certificate from certification data; descriptive information about the material, and other data and metadata as needed; to generate a human-readable report from the digital Reference Material Certificate; and to hold a workshop to gather stakeholder feedback. The challenges for NIST include the diverse and complex information presently contained in NIST certificates, converting values to non-SI units to match the needs of stakeholders, and format updates to NIST Reference Material Certificates necessary to allow for machine generation. Other practical challenges include the wide variety of Reference Materials offered by NIST, as well as the needs of internal and external stakeholders. This presentation will report on the progress of the NIST effort and discuss some of the challenges and solutions to producing Digital Reference Material Certificates.