Toward sequencing every core needle biopsy by addressing one "gap" at a time.

Background: Core needle biopsies (CNB) are essential for clinical diagnostics, therapy guidance, and enrollment in certain clinical trials. However, they also represent one of the clinical practice “gaps” that limit the integration of predictive biomarker testing into everyday patient care (Sadik, 2023). Limited starting material, pre-analytic variables and tissue losses during lab processing point to the need to identify a new method to be able to extract more information from these size-limited specimens. Corramedical, Inc., has developed a simple tool capable of utilizing dislodged tumor cells (DTCs) created during the CNB that would otherwise be discarded as medical waste, potentially addressing this unresolved clinical practice “gap”. Methods: The Crow’s Nest Biopsy Catchment system (CrN) is a simple tool designed to recover all the components generated during a CNB procedure. While it is largely known that a sliver of tissue is captured in the sampling chamber during the procedure, it is generally unknown that valuable DTCs in small clumps and single cells are also sampled. These DTCs are routinely discarded with the biopsy needle. The CrN is the first medical device designed to separate and capture both these DTCs and the larger tissue core for downstream needs. The process was tested on two specimens, one to document the recovery of the diagnostic tumor cells, and the other to assess the DNA from these DTCs. In the latter, after extraction, the DNA was sequenced using technology (whole genome amplification via primary templated-directed amplification (PTA)) that is incompatible with formalin-fixed paraffin embedded (FFPE) material, to demonstrate what becomes possible when using high quality starting material. Results: Tumor cells are recovered from the CrN independent of the tissue core, confirmed by cytologic examination. These cells exhibited typical features of malignancy and morphologically corresponded to tumor cells in the parent tissue. The DTC specimen yielded DNA above the 800-1, 200 base pairs (bp) threshold required for PTA. In direct contrast, FFPE DNA is typically less than 400 bp in size. Processing the specimen took less than 5 minutes. The parent tissue core was not needed to generate these molecular results. Conclusions: A novel apparatus that maximizes CNB specimens has been developed that yields: 1) representative tumor cells for molecular studies; 2) diagnostic tumor cells that are of higher quality than the parent tissue that is FFPE; 3) eliminates pre-analytic and formalin fixation technical obstacles associated with traditional FFPE; 4) conserves harvested tissue for ancillary studies. These features represent a significant quality improvement for specimen workflows and sample quality that directly addresses one of the current clinical practice “gaps” that exists in the widespread implementation of Precision Medicine.