VA National Precision Oncology Program

Another complexity in annotation for actionability is tumor type ontogeny—the classification system used for cancer types. WfG uses a subset of the National Cancer Institute Thesaurus (ncithesaurus.nci.nih.gov), OncoKB uses the unique OncoTree (oncotree.mskcc.org), and Foundation Medicine (www.foundationmed icine.com), and N-of-One use propriety classification systems. The WfG and OncoKB tumor types have evolved over time, while it is unclear what changes have been made in the FMI and N-of-One tumor type classification systems. Thus, a gene variant observed in a single patient may be annotated differently by these services because of how the tumor type is mapped onto the services’ tumor type ontogeny. NPOP has been assigning WfG diagnoses since 2017, including historic assignment for prior samples back to the pilot project in 2015. In early 2019, NPOP began requiring test requesters to include International Classification of Diseases for Oncology, 3rd Edition (ICD-O-3) diagnoses (histology and site codes) with the sample. ICD-O-3 codes are used in all cancer registry data in North America, including the VA Cancer Registry System. The approximately 50,000 possible diagnoses allow fine precision in diagnoses, which is important for less common and rare cancer types; however, the large number of diagnoses adds complexity. NPOP has created a partial translation table for ICD-O-3 to WfG diagnosis that includes all diagnoses seen to date; this table facilitates continuing provision of WfG diagnosis without manual review as was previously required.

NPOP-Provided Genetic Services

Given these complexities in interpretation of NGS multigene panel results, NPOP provides several services to assist health care providers and other members of the care team. First, the NPOP Interfacility Consult (IFC) is a virtual “phone-a-friend” service that provides asynchronous patient-specific expert recommendations in precision oncology. By far the most requested service is assistance with interpretation of a patient’s DNA sequence results. Other requests include advice on whether to perform NGS testing and what molecular testing to perform. The IFC is integral to the VA Computerized Patient Record System electronic health record. Additional requests have been submitted and answered by e-mail.

The Molecular Oncology Tumor Board is a monthly case-based educational conference supported by the VA Employee Education Service, which provides continuing education credits for attendees. NPOP staff coordinate the conference, and a panel of specialists from around the country provide expert commentary.

In 2016, IBM gifted the services of WfG to VA. WfG’s main functionality is annotation of NGS results. About 5,000 samples were processed from 2017 to 2019; sample processing is expected to resume shortly. The availability of WfG annotations early in NPOP operation was very useful to the implementation of NPOP in general and the NPOP consultation services in particular, resulting in improved thoroughness of opinions provided by NPOP staff.

Informatics

Informatics is an essential component of NPOP that facilitates both clinical care and research (Figure 3). Results of NGS gene panels are returned to the facility that submitted the sample for testing as a PDF document. NPOP receives the same PDF report in real time but also structured data of the results including a variant callformat file and XML file. The secondary sequence data in binary alignment map or FASTQ format is received in batches. NPOP program staff extract data from these files and then load it into SQL tables in the VA Corporate Data Warehouse. In partnership with the VA Pharmacy Benefits Management Service, NPOP has constructed user-friendly dashboards that allow users with no technical skills and who have the appropriate data access permissions to view various portions of the NPOP database. There are dashboards to display a list of NPOP samples by facility, find a patient by name or other identifying information, and display a list of patients who have received any antineoplastic drug, among other functions.