title: A pilot study using next-generation sequencing in advanced cancers: feasibility and challenges.
abstract: OBJECTIVE
  New anticancer agents that target a single cell surface receptor, up-regulated or amplified gene product, or mutated gene, have met with some success in treating advanced cancers. However, patients' tumors still eventually progress on these therapies. If it were possible to identify a larger number of targetable vulnerabilities in an individual's tumor, multiple targets could be exploited with the use of specific therapeutic agents, thus possibly giving the patient viable therapeutic alternatives.
  
  
  METHODS
  In this exploratory study, we used next-generation sequencing technologies (NGS) including whole genome sequencing (WGS), and where feasible, whole transcriptome sequencing (WTS) to identify genomic events and associated expression changes in advanced cancer patients.
  
  
  RESULTS
  WGS on paired tumor and normal samples from nine advanced cancer patients and WTS on six of these patients' tumors was completed. One patient's treatment was based on targets and pathways identified by NGS and the patient had a short-lived PET/CT response with a significant reduction in his tumor-related pain. To design treatment plans based on information garnered from NGS, several challenges were encountered: NGS reporting delays, communication of results to out-of-state participants and their treating oncologists, and chain of custody handling for fresh biopsy samples for Clinical Laboratory Improvement Amendments (CLIA) target validation.
  
  
  CONCLUSIONS
  While the initial effort was a slower process than anticipated due to a variety of issues, we demonstrate the feasibility of using NGS in advanced cancer patients so that treatments for patients with progressing tumors may be improved.
authors.affiliation: Virginia G. Piper Cancer Center Clinical Trials at Scottsdale Healthcare (VGPCC), Scottsdale, Arizona, United States of America ; The Translational Genomics Research Institute, Phoenix, Arizona, United States of America.
authors.forename: Glen J
authors.initials: GJ
authors.lastname: Weiss
authors.forename: Winnie S
authors.initials: WS
authors.lastname: Liang
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Demeure
authors.forename: Jeff A
authors.initials: JA
authors.lastname: Kiefer
authors.forename: Galen
authors.initials: G
authors.lastname: Hostetter
authors.forename: Tyler
authors.initials: T
authors.lastname: Izatt
authors.forename: Shripad
authors.initials: S
authors.lastname: Sinari
authors.forename: Alexis
authors.initials: A
authors.lastname: Christoforides
authors.forename: Jessica
authors.initials: J
authors.lastname: Aldrich
authors.forename: Ahmet
authors.initials: A
authors.lastname: Kurdoglu
authors.forename: Lori
authors.initials: L
authors.lastname: Phillips
authors.forename: Hollie
authors.initials: H
authors.lastname: Benson
authors.forename: Rebecca
authors.initials: R
authors.lastname: Reiman
authors.forename: Angela
authors.initials: A
authors.lastname: Baker
authors.forename: Vickie
authors.initials: V
authors.lastname: Marsh
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Von Hoff
authors.forename: John D
authors.initials: JD
authors.lastname: Carpten
authors.forename: David W
authors.initials: DW
authors.lastname: Craig
mesh_terms: D000328:Adult; D000368:Aged; D056915:DNA Copy Number Variations; D005260:Female; D019788:Fluorodeoxyglucose F18; D020869:Gene Expression Profiling; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009369:Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology* / Q000628:therapy; D010865:Pilot Projects; D049268:Positron-Emission Tomography; D014057:Tomography, X-Ray Computed; D059467:Transcriptome; D055815:Young Adult
chemical_list: D019788:Fluorodeoxyglucose F18