Universal Germline Testing of Unselected Cancer Patients Detects Pathogenic Variants Missed by Standard Guidelines without Increasing Healthcare Costs.

PURPOSE: To accurately ascertain the frequency of pathogenic germline variants (PGVs) in a pan-cancer patient population with universal genetic testing and to assess the economic impact of receiving genetic testing on healthcare costs. METHODS: In this prospective study, germline genetic testing using a 105-gene panel was administered to an unselected pan-cancer patient population irrespective of eligibility by current guidelines. Financial records of subjects were analyzed to assess the effect of PGV detection on cost of care one year from the date of testing. RESULTS: A total of 284 patients participated in this study, of which 44 patients (15%) tested positive for a PGV in 14 different cancer types. Of the patients with PGVs, 23 patients (52%) were ineligible for testing by current guidelines. Identification of a PGV did not increase cost of care. CONCLUSION: Implementation of universal genetic testing for cancer patients in the clinic, beyond that specified by current guidelines, is necessary to accurately assess and treat hereditary cancer syndromes and does not increase healthcare costs.

An elevated neutrophil-to-lymphocyte ratio associates with weight loss and cachexia in cancer.

Systemic inflammation is present during and serves as a diagnostic tool for cancer-associated cachexia and is detrimental to serum 25-hydroxyvitamin D (25(OH)D) concentrations in non-cancer conditions. The neutrophil-to-lymphocyte ratio (NLR) is a desirable measure of systemic inflammation because it is easily calculated from a routine complete blood cell count with differentials. We sought to determine if an elevation in the NLR associates with greater weight loss, cachexia, and lower serum 25-hydroxyvitamin D (25(OH)D) concentrations in patients with advanced cancer. Advanced colon, lung, and prostate cancer patients (stages III/IV; n = 50) were retrospectively studied and separated into one of two groups: 1) Above (n = 25) or 2) Below (n = 25) the median NLR of 3.15 determined at diagnosis. Around the time of diagnosis, serum 25(OH)D and body weight were assessed, while body weight was assessed again at a later date. Weight loss and cachexia were significantly (both p < 0.05) greater and there was a trend (p < 0.10) for lower serum 25(OH)D concentrations in the Above group. We conclude that an elevation in the NLR associates with greater weight loss and cachexia, and potentially, a lower serum 25(OH)D concentration in patients with advanced colon, lung, or prostate cancer.

Therapeutic Monitoring of Circulating DNA Mutations in Metastatic Cancer with Personalized Digital PCR.

As a high-performance solution for longitudinal monitoring of patients being treated for metastatic cancer, a single-color digital PCR (dPCR) assay that detects and quantifies specific cancer mutations present in circulating tumor DNA (ctDNA) was developed. This customizable assay has a high sensitivity of detection. One can detect a mutation allelic fraction of 0.1%, equivalent to three mutation-bearing DNA molecules among 3000 genome equivalents. The objective of this study was to validate the use of personalized dPCR mutation assays to monitor patients with metastatic cancer. The dPCR results were compared with serum biomarkers indicating disease progression or response. Patients had metastatic colorectal, biliary, breast, lung, and melanoma cancers. Mutations occurred in essential cancer drivers such as BRAF, KRAS, and PIK3CA. Patients were monitored over multiple cycles of treatment for up to a year. All patients had detectable ctDNA mutations. The results correlated with serum markers of metastatic cancer burden, including carcinoembryonic antigen, CA-19-9, and CA-15-3, and qualitatively corresponding to imaging studies. Corresponding trends were observed among these patients receiving active treatment with chemotherapy or targeted agents. For example, in one patient under active treatment, increasing quantities of ctDNA molecules were detected over time, indicating recurrence of tumor. This study demonstrates that personalized dPCR enables longitudinal monitoring of patients with metastatic cancer and may be a useful indicator for treatment response.