Operationalization of Next-Generation Sequencing and Decision Support for Precision Oncology

Abstract

Genomic testing has become a part of routine oncology care and plays critical roles in diagnosis, prognostic assessment, and treatment selection. Thus, in parallel, the variety of genomic testing providers and sequencing platforms has grown exponentially. Selection of the best-fit panel for each case can be daunting, with many factors to consider. Among them is whether alteration interpretation and therapy/clinical trial matching are included and/or sufficient. In this article, we review some common commercially available sequencing platforms for the genes and types of alterations tested, samples needed, and reporting content provided. We review publicly available resources for a do-it-yourself approach to alteration interpretation when it is not provided or when supplemental research is needed, along with resources to identify genomically matched treatment options that are approved and/or investigational. However, with both commercially provided interpretation and publicly available resources, there are still caveats and limitations that can stem from insufficient or ambiguous nomenclature as well as from the presentation of information. Use cases in which clinical decision making was affected are discussed. After treatment options are identified, it is important to assess the level of evidence for use within the patient's tumor type and molecular profile. However, numerous level-of-evidence scales have been published in recent years, so we provide a publicly available tool to facilitate interoperability. The level of evidence, along with other factors, such as allelic frequency and copy number, can be used to prioritize treatment options when multiple are identified.

FIG 1.

Level of Evidence (LoE) mapper. The LoE mapper provides an interface for a user to provide a description of the evidence found for use of a therapy within the context of a specified disease harboring a specific biomarker. On the basis of the evidence criteria selected, the LoE scale associated with seven standards is displayed along with a tier which we have defined within this article.