Assay Validation of Cell-Free DNA Shallow Whole-Genome Sequencing to Determine Tumor Fraction in Advanced Cancers.

Blood-based liquid biopsy is increasingly used in clinical care of patients with cancer, and fraction of tumor-derived DNA in circulation (tumor fraction; TFx) has demonstrated clinical validity across multiple cancer types. To determine TFx, shallow whole-genome sequencing of cell-free DNA (cfDNA) can be performed from a single blood sample, using an established computational pipeline (ichorCNA), without prior knowledge of tumor mutations, in a highly cost-effective manner. We describe assay validation of this approach to facilitate broad clinical application, including evaluation of assay sensitivity, precision, repeatability, reproducibility, pre-analytic factors, and DNA quality/quantity. Sensitivity to detect TFx of 3% (lower limit of detection) was 97.2% to 100% at 1× and 0.1× mean sequencing depth, respectively. Precision was demonstrated on distinct sequencing instruments (HiSeqX and NovaSeq) with no observable differences. The assay achieved prespecified 95% agreement of TFx across replicates of the same specimen (repeatability) and duplicate samples in different batches (reproducibility). Comparison of samples collected in EDTA and Streck tubes from single venipuncture in 23 patients demonstrated that EDTA or Streck tubes were comparable if processed within 8 hours. On the basis of a range of DNA inputs (1 to 50 ng), 20 ng cfDNA is the preferred input, with 5 ng minimum acceptable. Overall, this shallow whole-genome sequencing of cfDNA and ichorCNA approach offers sensitive, precise, and reproducible quantitation of TFx, facilitating assay application in clinical cancer care.

Physicians, prescribe education to address population health equity.

Structural barriers embedded within American society contribute to health inequities and social determinants of health (SDOH) in ways that systematically influence one's ability to succeed and to maintain a healthy overall quality of life in the United States. This article leverages educational attainment as an upstream SDOH factor that can be used to address downstream implications of population health equity. As providers learn to prescribe more innovative treatments that directly influence SDOH, an exploration is made to develop an intervention that integrates education, public health, and medicine as systems in a coordinated process to increase educational attainment for vulnerable populations. This article develops and analyzes the use of health equity management (HEM) model as a conceptual framework to identify precursors for educational attainment and provide an equitable solution for mending the educational attainment gap. It provides theoretical framing, conceptualizes stakeholder engagement, and creates a conceptual framework for identifying and addressing population health issues with education prescriptions. Operationalizing an educational prescription intervention will utilize provider-based screening methods to decrease the gaps in educational attainment by fostering partnerships between education, public health, and medicine. HEM identifies ideal partnership relationships to increase educational attainment and address long-standing quality of life issues, with a primary focus on coordinated activities among systems. Incorporating provider expertise into upstream educational decision-making legitimizes educational attainment as a critical component of population health equity. For many Americans, this is a necessary call to action to demand real structural change to ensure prosperity for all. An educational prescription intervention is a step towards increasing population health equity.