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. 2019 Aug 8:3:PO.19.00075.
doi: 10.1200/PO.19.00075. eCollection 2019.

Genomic Analysis of Metastatic Solid Tumors in Veterans: Findings From the VHA National Precision Oncology Program

Pradeep J Poonnen  1   2 , Jill E Duffy  1 , Bradley Hintze  1   3 , Maulik Shukla  4 , Thomas S Brettin  4 , Neal R Conrad  4 , Hyunseung Yoo  4 , Christopher Guertin  1 , Jane A Looney  1 , Vishal Vashistha  1   2 , Michael J Kelley  1   2   3 , Neil L Spector  1   2   3
Affiliations

Genomic Analysis of Metastatic Solid Tumors in Veterans: Findings From the VHA National Precision Oncology Program

Pradeep J Poonnen et al. JCO Precis Oncol. .

Abstract

Purpose: The Veterans Health Administration (VHA) is the largest cancer care provider in the United States, with the added challenge of serving more than twice the percentage of patients with cancer in rural areas than the national average. The VHA established the National Precision Oncology Program in 2016 to implement and standardize the practice of precision oncology across the diverse VHA system.

Methods: Tumor or peripheral blood specimens from veterans with advanced solid tumors who were eligible for treatment were submitted for next-generation sequencing (NGS) at two commercial laboratories. Annotated results were generated by the laboratories and independently using IBM Watson for Genomics. Levels-of-evidence treatment recommendations were based on OncoKB criteria.

Results: From July 2016 to June 2018, 3,698 samples from 72 VHA facilities were submitted for NGS testing, of which 3,182 samples (86%) were successfully sequenced. Most samples came from men with lung, prostate, and colorectal cancers. Thirty-four percent of samples were from patients who lived in a rural area. TP53, ATM, and KRAS were among the most commonly mutated genes. Approximately 70% of samples had at least one actionable mutation, with clinical trials identified as the recommended option in more than 50%. Mutations in genes associated with a neuroendocrine prostate cancer phenotype were expressed at increased frequency among veterans than in the general population. The most frequent therapies prescribed in response to NGS testing were immune checkpoint inhibitors, EGFR kinase inhibitors, and PARP inhibitors.

Conclusion: Clinical implementation of precision oncology is feasible across the VHA health care system, including rural sites. Veterans have unique occupational exposures that might inform the nature of the mutational signatures identified here. Importantly, these results underscore the importance of increasing clinical trial availability to veterans.

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Conflict of interest statement

The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/po/author-center. Pradeep J. PoonnenOther Relationship: IBMChristopher GuertinEmployment: Walmart Stock and Other Ownership Interests: WalmartVishal VashisthaOther Relationship: IBMMichael J. KelleyConsulting or Advisory Role: AstraZeneca, Eisai, IBM Japan Research Funding: Bavarian Nordic, Novartis, AstraZeneca, Bristol-Myers Squibb Other Relationship: IBMNeil L. SpectorStock and Other Ownership Interests: Eydis Bio, Bessor Pharma Research Funding: Immunolight Patents, Royalties, Other Intellectual Property: I am on a patent related to my work with the company Immunolight, and I am listed on a patent through Eydis Bio No other potential conflicts of interest were reported.

Figures

FIG 1.
FIG 1.
Overview of the Veterans Health Administration (VHA) National Precision Oncology Program (NPOP) cohort. (A) Number of tumor samples sent for next-generation sequencing testing, reported per month since program inception in 2016. (B) Age distribution of patients included in VHA NPOP cohort. (C) Most common cancer diagnoses of those patients who underwent NGS testing of tumor samples. H&N, head and neck.
FIG 2.
FIG 2.
Frequency of the 20 most common gene variants displayed across tumor types. Color signifies increased frequency from light to dark. H&N, head and neck.
FIG 3.
FIG 3.
Clinical actionability of mutations discovered by next-generation sequencing testing. (A) Actionable alterations were annotated using Watson for Genomics (WfG) according to OncoKB levels of evidence: Food and Drug Administration (FDA)-recognized predictive biomarkers (level 1), standard-of-care biomarkers predictive of response to FDA-approved therapies (level 2), and biomarkers predictive of response to therapeutic agents currently under investigation (level 3), with levels 2 and 3 further categorized by whether evidence existed for the particular tumor type in question (2A, 3A) or a different tumor type (2B, 3B). The distribution of the highest level of evidence across all patient samples is displayed. (B) Distribution of highest level of evidence of actionable mutations by tumor type. H&N, head and neck.
FIG 4.
FIG 4.
Clinical annotation and recommendations of non–small-cell lung cancer specimens on the basis of next-generation sequencing results. (A) Distribution of actionable mutations (ie, eligible for on- or off-label use of a Food and Drug Administration–approved targeted therapy or immune checkpoint inhibitor on the basis of NGS test results) demonstrated by NGS. (B) Targeted and immunotherapy drugs prescribed after NGS testing. Data are reported as the name of gene or drug (no.). (*) DNA repair genes (eg, BRCA1, BRCA2, ATM, ATR). (†) Mismatch repair (MMR) genes (eg, MLH1, MSH2, MSH6, PMS2). MSI-H, microsatellite instability–high; TMB, tumor mutational burden.
FIG 5.
FIG 5.
Clinical annotation and recommendations of prostate cancer specimens on the basis of next-generation sequencing (NGS) results. (A) Distribution of actionable mutations (ie, eligible for on- or off-label use of an Food and Drug Administration–approved targeted therapy or immune checkpoint inhibitor on the basis of NGS test results) demonstrated by NGS. (B) Targeted therapy and immunotherapy drugs prescribed after NGS testing. Data are reported as the name of the gene or drug (no.). (*) DNA repair genes (eg, BRCA1, BRCA2, ATM, ATR). (†) Mismatch repair (MMR) genes (eg, MLH1, MSH2, MSH6, PMS2). TMB, tumor mutational burden.
FIG 6.
FIG 6.
Clinical annotation and recommendations of colorectal cancer specimens on the basis of next-generation sequencing (NGS) results. (A) Distribution of actionable mutations (ie, eligible for on- or off-label use of Food and Drug Administration–approved targeted therapy or immune checkpoint inhibitor on the basis of NGS test results) demonstrated by NGS. (B) Targeted therapy and immunotherapy drugs prescribed after NGS testing. Data are reported as the name of the gene or drug (no.). (*) Mismatch repair (MMR) genes (eg, MLH1, MSH2, MSH6, PMS2). MSI-H, microsatellite instability–high.
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