Real-world evidence regarding the value of integrating genomic profiling (GP) in managing cancer of unknown primary (CUP) is limited. We assessed this clinical utility using a prospective trial of 158 patients with CUP (October 2016-September 2019) who underwent GP using next-generation sequencing designed to identify genomic alterations (GAs). Only 61 (38.6%) patients had sufficient tissue for successful profiling. GAs were seen in 55 (90.2%) patients of which GAs with US Food and Drug Administration–approved genomically matched therapy were seen in 25 (40.9%) patients. A change in therapy was recommended and implemented (primary endpoint of the study) in 16 (10.1%) and 4 (2.5%) patients of the entire study cohort, respectively. The most common reason for inability to implement the profiling-guided therapy was worsening of performance status (56.3%). Integrating GP in management of CUP is feasible but challenging because of paucity of tissue and aggressive natural history of the disease and requires innovative precision strategies.

The standard of care in oncology has been genomic profiling of tumor tissue biopsies for the treatment and management of disease, which can prove to be quite challenging in terms of cost, invasiveness of procedure, and potential risk for the patient. As the number of available drugs in oncology continues to increase, so too does the demand for technologies and testing applications that can identify genomic alterations targetable by these new therapies. Liquid biopsies that use a blood draw from the diseased patient may offset the many disadvantages of the invasive procedure. However, as with any new technology or finding in the clinical field, the clinical utility of an analytical test such as that of the liquid biopsy has to be established. Here, we review the clinical testing space for liquid biopsy offerings and elucidate the technical and regulatory considerations to develop such an assay, using our recently validated PlasmaMonitor ^TM test.

In contrast to most solid tumors, cancers of the central nervous system (CNS) pose a unique challenge for effective detection and tracking via plasma because of the blood-brain barrier. Informed diagnosis of primary and metastatic CNS tumors can be facilitated using a liquid biopsy assay that evaluates tumor-derived DNA from the cerebrospinal fluid (CSF), potentially increasing the efficacy of diagnosis and reducing the uncertainty and morbidities associated with the current standard of care that involves neurosurgical procedures. The Belay Summit assay involves tumor-derived DNA-based genomic profiling of CSF to inform diagnosis of CNS tumors. The analytical sensitivity of Summit for single-nucleotide/multinucleotide variants and insertions/deletions is 96% at a 95% limit of detection of 0.30% variant allele fraction. Analytical sensitivity for chromosomal arm-level aneuploidy is 91% at abs(log2r) of 0.09 limit of detection. Clinical sensitivity across a cohort of 124 specimens, including primary and metastatic CNS tumors, was demonstrated to be 90% with a specificity of 95%, supporting the potential for positive clinical utility. These results demonstrate that the Belay Summit assay can accurately and reproducibly be used to inform the diagnosis of primary and metastatic CNS tumors using CSF.