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JCI Insight. 2016 Nov 17;1(19):e87062.

Institutional implementation of clinical tumor profiling on an unselected cancer population.

Author information

1
Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
2
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.
3
Department of Biostatistics and Computational Biology, and.
4
Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA.; Center for Cancer Genome Discovery, DFCI, Boston, Massachusetts, USA.
5
Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada; Department of Medical Biophysics, University of Toronto, Ontario, Canada.
6
Center for Cancer Genome Discovery, DFCI, Boston, Massachusetts, USA.
7
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.
8
Department of Radiology, DFCI and Brigham and Women's Hospital, Boston, Massachusetts, USA.
9
Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts, USA.
10
Department of Pathology, Boston Children's Hospital, Boston, Massachusetts, USA.
11
Department of Medical Oncology, Dana-Farber Cancer Institute (DFCI), Boston, Massachusetts, USA; Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
12
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.
13
Mirati Therapeutics, San Diego, California.
14
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.
15
Lank Center for Genitourinary Oncology and.
16
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.
17
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.

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 in AXL and EGFR, 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).

PMID:
27882345
PMCID:
PMC5111542
DOI:
10.1172/jci.insight.87062
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

M. Nishino is a consultant for Bristol-Myers Squibb. G.R. Oxnard is a consultant for AstraZeneca, Ariad, and Boehringer-Ingelheim and has honoraria from AstraZeneca and Chugai. L.M. Sholl is a consultant for Genentech. M. Meyerson has research funding from Bayer and a patent on the use of EGFR mutation analysis for lung cancer diagnosis and is a founder of Foundation Medicine. L.A. Garraway is a founder, consultant, and equity holder in Foundation Medicine.

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