title: Clinical application of amplicon-based next-generation sequencing to therapeutic decision making in lung cancer.
abstract: BACKGROUND
  The clinical implementation of genomic profiling for lung cancer with high-throughput, multiplex tests is warranted to allow prioritization of appropriate therapies for individual patients. We have now applied such testing to detect actionable mutations that may inform treatment recommendations in lung cancer.
  
  
  METHODS
  We prospectively applied amplicon sequencing panels that cover both mutational hotspots in 22 genes related to lung and colon tumorigenesis as well as 72 major variants of ALK, RET, ROS1, and NTRK1 fusion transcripts. We then determined the proportion of patients who received genotype-directed therapy and their overall survival (OS).
  
  
  RESULTS
  Tumor specimens from 110 patients with lung cancer recruited between July 2013 and March 2015 were analyzed. The most common genetic alterations were TP53 mutations in 42 patients, followed by EGFR mutations in 25, STK11 mutations in 12, and KRAS mutations in 10. Potentially actionable mutations were identified in 44 patients including 50% of those with adenocarcinoma and 14% of those with squamous cell carcinoma. The OS of patients with advanced or recurrent cancer who had an actionable mutation and received targeted therapy (median OS not achieved) was significantly longer than that of those with no mutation (18.1 months, P = 0.041) or of those with a mutation not so treated (6.1 months, P = 0.0027).
  
  
  CONCLUSIONS
  Multiplex genomic testing was performed on formalin-fixed, paraffin-embedded tumor specimens with a success rate of ≥95%. Such testing can assist physicians in matching patients with approved or experimental targeted treatments.
  
  
  BACKGROUND
  The University Medical Hospital Information Network (UMIN) Clinical Trials Registry under the identifier UMIN000014782.
authors.affiliation: Department of Medical Oncology.
authors.forename: M
authors.initials: M
authors.lastname: Takeda
authors.affiliation: Department of Genome Biology.
authors.forename: K
authors.initials: K
authors.lastname: Sakai
authors.affiliation: Department of Genome Biology.
authors.forename: M
authors.initials: M
authors.lastname: Terashima
authors.affiliation: Department of Medical Oncology.
authors.forename: H
authors.initials: H
authors.lastname: Kaneda
authors.affiliation: Department of Medical Oncology.
authors.forename: H
authors.initials: H
authors.lastname: Hayashi
authors.affiliation: Department of Medical Oncology.
authors.forename: K
authors.initials: K
authors.lastname: Tanaka
authors.affiliation: Department of Medical Oncology.
authors.forename: K
authors.initials: K
authors.lastname: Okamoto
authors.affiliation: Department of Medical Oncology.
authors.forename: T
authors.initials: T
authors.lastname: Takahama
authors.affiliation: Department of Medical Oncology.
authors.forename: T
authors.initials: T
authors.lastname: Yoshida
authors.affiliation: Department of Medical Oncology.
authors.forename: T
authors.initials: T
authors.lastname: Iwasa
authors.affiliation: Department of Medical Oncology.
authors.forename: T
authors.initials: T
authors.lastname: Shimizu
authors.affiliation: Department of Medical Oncology.
authors.forename: Y
authors.initials: Y
authors.lastname: Nonagase
authors.affiliation: Department of Medical Oncology.
authors.forename: K
authors.initials: K
authors.lastname: Kudo
authors.affiliation: Department of Genome Biology.
authors.forename: S
authors.initials: S
authors.lastname: Tomida
authors.affiliation: Division of Thoracic Surgery, Department of Surgery.
authors.forename: T
authors.initials: T
authors.lastname: Mitsudomi
authors.affiliation: Department of Neurology Department of Medical Genetics.
authors.forename: K
authors.initials: K
authors.lastname: Saigo
authors.affiliation: Department of Pathology, Kinki University Faculty of Medicine, Osaka-Sayama, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Ito
authors.affiliation: Department of Medical Oncology.
authors.forename: K
authors.initials: K
authors.lastname: Nakagawa
authors.affiliation: Department of Genome Biology knishio@med.kindai.ac.jp.
authors.forename: K
authors.initials: K
authors.lastname: Nishio
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000066491:Clinical Decision-Making / Q000379:methods*; D005260:Female; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012042:Registries; D017423:Sequence Analysis, RNA / Q000379:methods*
keywords: driver mutation; lung cancer; next-generation sequencing; targeted therapy; transbronchial biopsy