A Cost-Effective and Non-Invasive pfeRNA-Based Test Differentiates Benign and Suspicious Pulmonary Nodules from Malignant Ones.

The ability to differentiate between benign, suspicious, and malignant pulmonary nodules is imperative for definitive intervention in patients with early stage lung cancers. Here, we report that plasma protein functional effector sncRNAs (pfeRNAs) serve as non-invasive biomarkers for determining both the existence and the nature of pulmonary nodules in a three-stage study that included the healthy group, patients with benign pulmonary nodules, patients with suspicious nodules, and patients with malignant nodules. Following the standards required for a clinical laboratory improvement amendments (CLIA)-compliant laboratory-developed test (LDT), we identified a pfeRNA classifier containing 8 pfeRNAs in 108 biospecimens from 60 patients by sncRNA deep sequencing, deduced prediction rules using a separate training cohort of 198 plasma specimens, and then applied the prediction rules to another 230 plasma specimens in an independent validation cohort. The pfeRNA classifier could (1) differentiate patients with or without pulmonary nodules with an average sensitivity and specificity of 96.2% and 97.35% and (2) differentiate malignant versus benign pulmonary nodules with an average sensitivity and specificity of 77.1% and 74.25%. Our biomarkers are cost-effective, non-invasive, sensitive, and specific, and the qPCR-based method provides the possibility for automatic testing of robotic applications.

JAK3 Variant, Immune Signatures, DNA Methylation, and Social Determinants Linked to Survival Racial Disparities in Head and Neck Cancer Patients.

To inform novel personalized medicine approaches for race and socioeconomic disparities in head and neck cancer, we examined germline and somatic mutations, immune signatures, and epigenetic alterations linked to neighborhood determinants of health in Black and non-Latino White (NLW) patients with head and neck cancer. Cox proportional hazards revealed that Black patients with squamous cell carcinoma of head and neck (HNSCC) with PAX5 (P = 0.06) and PAX1 (P = 0.017) promoter methylation had worse survival than NLW patients, after controlling for education, zipcode, and tumor-node-metastasis stage (n = 118). We also found that promoter methylation of PAX1 and PAX5 (n = 78), was correlated with neighborhood characteristics at the zip-code level (P < 0.05). Analyses also showed differences in the frequency of TP53 mutations (n = 32) and tumor-infiltrating lymphocyte (TIL) counts (n = 24), and the presence of a specific C → A germline mutation in JAK3, chr19:17954215 (protein P132T), in Black patients with HNSCC (n = 73; P < 0.05), when compared with NLW (n = 37) patients. TIL counts are associated (P = 0.035) with long-term (>5 years), when compared with short-term survival (<2 years). We show bio-social determinants of health associated with survival in Black patients with HNSCC, which together with racial differences shown in germline mutations, somatic mutations, and TIL counts, suggests that contextual factors may significantly inform precision oncology services for diverse populations.

Cost-Savings Analysis of AR-V7 Testing in Patients With Metastatic Castration-Resistant Prostate Cancer Eligible for Treatment With Abiraterone or Enzalutamide.

INTRODUCTION: Identification of cancer biomarkers that inform clinical decisions and reduce the use of ineffective therapies is a major goal of precision oncology. An abnormal splice variant of the androgen receptor, AR-V7, was recently found to confer resistance to novel hormonal therapies (abiraterone and enzalutamide) in men with metastatic castration-resistant prostate cancer (mCRPC), but did not negatively affect responses to taxane chemotherapies, suggesting that early use of chemotherapy may be a more effective option for AR-V7(+) patients. METHODS: We calculated the cost savings of performing AR-V7 testing in mCRPC patients prior to starting abiraterone/enzalutamide (and avoiding these drugs in AR-V7(+) men) versus treating all mCRPC patients empirically with abiraterone/enzalutamide (without use of the biomarker). RESULTS: We determined that AR-V7 testing would result in substantial cost savings as long as the true prevalence of AR-V7 was >5%. In our prior studies, we estimated that approximately 30% of mCRPC patients may have detectable AR-V7 in circulating tumor cells (CTCs). In this population, upfront testing of AR-V7 status (at a price of $1,000 per test) would result in a net cost savings of $150 Million in the United States per year. CONCLUSIONS: AR-V7 testing in mCRPC patients would be cost-beneficial when considering the current price of treatment, and may reduce the ineffective use of abiraterone/enzalutamide, leading to a significant net cost savings to the healthcare system. Clinical-grade AR-V7 testing is currently available at our institution. Prostate 76:1484-1490, 2016. © 2016 Wiley Periodicals, Inc.