title: Evaluation and comparison of two commercially available targeted next-generation sequencing platforms to assist oncology decision making.
abstract: BACKGROUND
  It is widely acknowledged that there is value in examining cancers for genomic aberrations via next-generation sequencing (NGS). How commercially available NGS platforms compare with each other, and the clinical utility of the reported actionable results, are not well known. During the course of the current study, the Foundation One (F1) test generated data on a combination of somatic mutations, insertion and deletion polymorphisms, chromosomal abnormalities, and deoxyribonucleic acid (DNA) copy number changes at ~250× coverage, while the Paradigm Cancer Diagnostic (PCDx) test generated the same type of data at >5,000× coverage, plus provided messenger RNA (mRNA) expression levels. We sought to compare and evaluate paired formalin-fixed paraffin-embedded tumor tissue using these two platforms.
  
  
  METHODS
  Samples from patients with advanced solid tumors were submitted to both the F1 and PCDx vendors for NGS analysis. Turnaround time (TAT) was calculated. Biomarkers were considered clinically actionable if they had a published association with treatment response in humans and were assigned to the following categories: commercially available drug (CA), clinical trial drug (CT), or neither option (hereafter referred to as "None").
  
  
  RESULTS
  The demographics of the 21 unique patient tumor samples included ten men and eleven women, with a median age of 56 years. Due to insufficient archival tissue from the same collection period, in one case, we used samples from different collections. PCDx reported first results faster than F1 in 20 cases. When received at both vendors on the same day, PCDx reported first results for 14 of 15 cases, with a median TAT of 9 days earlier than F1 (P<0.0001). Categorization of CA compared to CT and none significantly favored PCDx (P=0.012).
  
  
  CONCLUSIONS
  In the current analysis, commercially available NGS platforms provided clinically relevant actionable targets (CA or CT) in 47%-67% of diverse cancer types. In the samples analyzed, PCDx significantly outperformed F1 in TAT, and had statistically significant higher clinically relevant actionable targets categorized as CA.
authors.affiliation: Cancer Treatment Centers of America, Western Regional Medical Center, Goodyear, AZ, USA.
authors.forename: Glen J
authors.initials: GJ
authors.lastname: Weiss
authors.affiliation: Cancer Treatment Centers of America, Western Regional Medical Center, Goodyear, AZ, USA.
authors.forename: Brandi R
authors.initials: BR
authors.lastname: Hoff
authors.affiliation: Cancer Treatment Centers of America, Western Regional Medical Center, Goodyear, AZ, USA.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Whitehead
authors.affiliation: Cancer Treatment Centers of America, Western Regional Medical Center, Goodyear, AZ, USA.
authors.forename: Ashish
authors.initials: A
authors.lastname: Sangal
authors.affiliation: Cancer Treatment Centers of America, Western Regional Medical Center, Goodyear, AZ, USA.
authors.forename: Susan A
authors.initials: SA
authors.lastname: Gingrich
authors.affiliation: Paradigm Diagnostics, Phoenix, AZ, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Penny
authors.affiliation: Paradigm Diagnostics, Phoenix, AZ, USA.
authors.forename: David W
authors.initials: DW
authors.lastname: Mallery
authors.affiliation: Paradigm Diagnostics, Phoenix, AZ, USA.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Morris
authors.affiliation: Paradigm Diagnostics, Phoenix, AZ, USA.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Thompson
authors.affiliation: Paradigm Diagnostics, Phoenix, AZ, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Loesch
authors.affiliation: Cancer Treatment Centers of America, Western Regional Medical Center, Goodyear, AZ, USA.
authors.forename: Vivek
authors.initials: V
authors.lastname: Khemka
keywords: assay; cancer; next-generation sequencing; platform; treatment decision making