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

被引：355

作者：

Sholl, Lynette M. ^{[1
]}

Do, Khanh ^{[2
,3
,4
]}

Shivdasani, Priyanka ^{[1
]}

Cerami, Ethan ^{[5
]}

Dubuc, Adrian M. ^{[1
]}

Kuo, Frank C. ^{[1
]}

Garcia, Elizabeth P. ^{[1
]}

Jia, Yonghui ^{[1
]}

Davineni, Phani ^{[1
]}

Abo, Ryan P. ^{[1
,6
]}

Pugh, Trevor J. ^{[7
,8
]}

van Hummelen, Paul ^{[5
]}

Thorner, Aaron R. ^{[6
]}

Ducar, Matthew ^{[1
,6
]}

Berger, Alice H. ^{[2
,3
,9
]}

Nishino, Mizuki ^{[10
,11
]}

Janeway, Katherine A. ^{[12
]}

Church, Alanna ^{[13
]}

Harris, Marian ^{[13
]}

Ritterhouse, Lauren L. ^{[1
]}

Campbell, Joshua D. ^{[2
,3
]}

Rojas-Rudilla, Vanesa ^{[1
,2
,3
]}

Ligon, Azra H. ^{[1
]}

Ramkissoon, Shakti ^{[1
]}

Cleary, James M. ^{[2
,3
,4
]}

Matulonis, Ursula ^{[2
,3
]}

Oxnard, Geoffrey R. ^{[2
,3
]}

Chao, Richard ^{[14
]}

Tassell, Vanessa ^{[14
]}

Christensen, James ^{[14
]}

Hahn, William C. ^{[2
,3
,15
]}

Kantoff, Philip W. ^{[15
]}

Kwiatkowski, David J. ^{[2
,3
]}

Johnson, Bruce E. ^{[2
,3
]}

Meyerson, Matthew ^{[1
,2
,3
,6
,9
]}

Garraway, Levi A. ^{[2
,3
,16
]}

Shapiro, Geoffrey I. ^{[2
,3
,4
]}

Rollins, Barrett J. ^{[2
,3
]}

Lindeman, Neal I. ^{[1
]}

MacConaill, Laura E. ^{[1
,6
]}

机构：

[1] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA

[2] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA

[3] Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA

[4] DFCI, Early Drug Discovery Ctr, Boston, MA USA

[5] DFCI, Dept Biostat & Computat Biol, Boston, MA USA

[6] DFCI, Ctr Canc Genome Discovery, Boston, MA USA

[7] Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON, Canada

[8] Univ Toronto, Dept Med Biophys, Toronto, ON M5S 1A1, Canada

[9] Broad Inst Harvard & MIT, Cambridge, MA USA

[10] DFCI, Dept Radiol, Boston, MA USA

[11] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA

[12] Dana Farber Boston Childrens Canc & Blood Disorde, Boston, MA USA

[13] Boston Childrens Hosp, Dept Pathol, Boston, MA USA

[14] Mirati Therapeut, San Diego, CA USA

[15] DFCI, Lank Ctr Genitourinary Oncol, Boston, MA USA

[16] DFCI, Ctr Canc Precis Med, Boston, MA USA

来源：

JCI INSIGHT | 2016年 / 1卷 / 19期

关键词：

ACTIONABLE GENOMIC ALTERATIONS; FIND POTENTIAL TARGETS; PERSONALIZED MEDICINE; KINASE INHIBITORS; TYROSINE KINASE; LUNG-CANCER; MUTATIONS; THERAPY; EFFICACY; IMPACT;

D O I：

10.1172/jci.insight.87062

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

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.

引用

页数：19

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