title: Institutional implementation of clinical tumor profiling on an unselected cancer population.
abstract: BACKGROUND.Comprehensive genomic profiling of a patient's cancer can be used to diagnose, monitor, and recommend treatment. Clinical implementation of tumor profiling in an enterprise-wide, unselected cancer patient population has yet to be reported.METHODS.We deployed a hybrid-capture and massively parallel sequencing assay (OncoPanel) for all adult and pediatric patients at our combined cancer centers. Results were categorized by pathologists based on actionability. We report the results for the first 3,727 patients tested.RESULTS.Our cohort consists of cancer patients unrestricted by disease site or stage. Across all consented patients, half had sufficient and available (>20% tumor) material for profiling; once specimens were received in the laboratory for pathology review, 73% were scored as adequate for genomic testing. When sufficient DNA was obtained, OncoPanel yielded a result in 96% of cases. 73% of patients harbored an actionable or informative alteration; only 19% of these represented a current standard of care for therapeutic stratification. The findings recapitulate those of previous studies of common cancers but also identify alterations, including inAXLandEGFR, associated with response to targeted therapies. In rare cancers, potentially actionable alterations suggest the utility of a "cancer-agnostic" approach in genomic profiling. Retrospective analyses uncovered contextual genomic features that may inform therapeutic response and examples where diagnoses revised by genomic profiling markedly changed clinical management.CONCLUSIONS.Broad sequencing-based testing deployed across an unselected cancer cohort is feasible. Genomic results may alter management in diverse scenarios; however, additional barriers must be overcome to enable precision cancer medicine on a large scale.FUNDING.This work was supported by DFCI, BWH, and the National Cancer Institute (5R33CA155554 and 5K23CA157631).
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Lynette M
authors.initials: LM
authors.lastname: Sholl
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute (DFCI), Boston, Massachusetts, USA; Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.|Early Drug Discovery Center.
authors.forename: Khanh
authors.initials: K
authors.lastname: Do
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Priyanka
authors.initials: P
authors.lastname: Shivdasani
authors.affiliation: Department of Biostatistics and Computational Biology, and.
authors.forename: Ethan
authors.initials: E
authors.lastname: Cerami
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Adrian M
authors.initials: AM
authors.lastname: Dubuc
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Frank C
authors.initials: FC
authors.lastname: Kuo
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Elizabeth P
authors.initials: EP
authors.lastname: Garcia
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Yonghui
authors.initials: Y
authors.lastname: Jia
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Phani
authors.initials: P
authors.lastname: Davineni
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA.|Center for Cancer Genome Discovery, DFCI, Boston, Massachusetts, USA.
authors.forename: Ryan P
authors.initials: RP
authors.lastname: Abo
authors.affiliation: Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada; Department of Medical Biophysics, University of Toronto, Ontario, Canada.
authors.forename: Trevor J
authors.initials: TJ
authors.lastname: Pugh
authors.affiliation: Department of Biostatistics and Computational Biology, and.
authors.forename: Paul
authors.initials: P
authors.lastname: van Hummelen
authors.affiliation: Center for Cancer Genome Discovery, DFCI, Boston, Massachusetts, USA.
authors.forename: Aaron R
authors.initials: AR
authors.lastname: Thorner
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA.|Center for Cancer Genome Discovery, DFCI, Boston, Massachusetts, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Ducar
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute (DFCI), Boston, Massachusetts, USA; Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.|Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.
authors.forename: Alice H
authors.initials: AH
authors.lastname: Berger
authors.affiliation: Department of Radiology, DFCI and Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Mizuki
authors.initials: M
authors.lastname: Nishino
authors.affiliation: Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts, USA.
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Janeway
authors.affiliation: Department of Pathology, Boston Children's Hospital, Boston, Massachusetts, USA.
authors.forename: Alanna
authors.initials: A
authors.lastname: Church
authors.affiliation: Department of Pathology, Boston Children's Hospital, Boston, Massachusetts, USA.
authors.forename: Marian
authors.initials: M
authors.lastname: Harris
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Lauren L
authors.initials: LL
authors.lastname: Ritterhouse
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute (DFCI), Boston, Massachusetts, USA; Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Campbell
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA.|Department of Medical Oncology, Dana-Farber Cancer Institute (DFCI), Boston, Massachusetts, USA; Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Vanesa
authors.initials: V
authors.lastname: Rojas-Rudilla
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Azra H
authors.initials: AH
authors.lastname: Ligon
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Shakti
authors.initials: S
authors.lastname: Ramkissoon
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute (DFCI), Boston, Massachusetts, USA; Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.|Early Drug Discovery Center.
authors.forename: James M
authors.initials: JM
authors.lastname: Cleary
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute (DFCI), Boston, Massachusetts, USA; Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Ursula
authors.initials: U
authors.lastname: Matulonis
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute (DFCI), Boston, Massachusetts, USA; Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Geoffrey R
authors.initials: GR
authors.lastname: Oxnard
authors.affiliation: Mirati Therapeutics, San Diego, California.
authors.forename: Richard
authors.initials: R
authors.lastname: Chao
authors.affiliation: Mirati Therapeutics, San Diego, California.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Tassell
authors.affiliation: Mirati Therapeutics, San Diego, California.
authors.forename: James
authors.initials: J
authors.lastname: Christensen
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute (DFCI), Boston, Massachusetts, USA; Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.|Center for Cancer Genome Discovery, DFCI, Boston, Massachusetts, USA.|Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.|Lank Center for Genitourinary Oncology and.
authors.forename: William C
authors.initials: WC
authors.lastname: Hahn
authors.affiliation: Lank Center for Genitourinary Oncology and.
authors.forename: Philip W
authors.initials: PW
authors.lastname: Kantoff
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute (DFCI), Boston, Massachusetts, USA; Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Kwiatkowski
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute (DFCI), Boston, Massachusetts, USA; Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Johnson
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA.|Department of Medical Oncology, Dana-Farber Cancer Institute (DFCI), Boston, Massachusetts, USA; Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.|Center for Cancer Genome Discovery, DFCI, Boston, Massachusetts, USA.|Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Meyerson
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute (DFCI), Boston, Massachusetts, USA; Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.|Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.|Center for Cancer Precision Medicine, DFCI, Boston, Massachusetts, USA.
authors.forename: Levi A
authors.initials: LA
authors.lastname: Garraway
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute (DFCI), Boston, Massachusetts, USA; Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.|Early Drug Discovery Center.
authors.forename: Geoffrey I
authors.initials: GI
authors.lastname: Shapiro
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute (DFCI), Boston, Massachusetts, USA; Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Barrett J
authors.initials: BJ
authors.lastname: Rollins
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Neal I
authors.initials: NI
authors.lastname: Lindeman
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA.|Center for Cancer Genome Discovery, DFCI, Boston, Massachusetts, USA.
authors.forename: Laura E
authors.initials: LE
authors.lastname: MacConaill
mesh_terms: D004252:DNA Mutational Analysis; D023281:Genomics; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000235:genetics*; D057285:Precision Medicine; D012189:Retrospective Studies