Institutional implementation of clinical tumor profiling on an unselected cancer population
Lynette M. Sholl, … , Neal I. Lindeman, Laura E. MacConaill
Lynette M. Sholl, … , Neal I. Lindeman, Laura E. MacConaill
Published November 17, 2016
Citation Information: JCI Insight. 2016;1(19):e87062. https://doi.org/10.1172/jci.insight.87062.
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Clinical Medicine Genetics Oncology

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 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).

Authors

Lynette M. Sholl, Khanh Do, Priyanka Shivdasani, Ethan Cerami, Adrian M. Dubuc, Frank C. Kuo, Elizabeth P. Garcia, Yonghui Jia, Phani Davineni, Ryan P. Abo, Trevor J. Pugh, Paul van Hummelen, Aaron R. Thorner, Matthew Ducar, Alice H. Berger, Mizuki Nishino, Katherine A. Janeway, Alanna Church, Marian Harris, Lauren L. Ritterhouse, Joshua D. Campbell, Vanesa Rojas-Rudilla, Azra H. Ligon, Shakti Ramkissoon, James M. Cleary, Ursula Matulonis, Geoffrey R. Oxnard, Richard Chao, Vanessa Tassell, James Christensen, William C. Hahn, Philip W. Kantoff, David J. Kwiatkowski, Bruce E. Johnson, Matthew Meyerson, Levi A. Garraway, Geoffrey I. Shapiro, Barrett J. Rollins, Neal I. Lindeman, Laura E. MacConaill

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Figure 1

An overview of the Profile program, including specimen availability, adequacy, and sequencing success.

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An overview of the Profile program, including specimen availability, ade...
(A) For consented patients, a cancer specimen is genomically profiled in a CLIA laboratory. Results are tiered by a team that interprets pathology, incorporating information from each patient’s electronic health record and provided to the patient’s treating physician(s). Genomic, pathologic, and clinical data are deposited in a central knowledge base that can link to full clinical annotation. The knowledge base can be queried to facilitate development and enrollment of basket trials and inform tumor board discussions. (B) Once patient consent and a test requisition are received in the laboratory, pathology records are reviewed for available cancer specimens. Unavailable materials are defined as those not physically located within the participating institutions and not actively requested by the treating physician for OncoPanel testing. Cases are most commonly insufficient because material is too small, tumor content is less than 20%, or generates <50 ng of DNA. Sequencing failure is defined as mean target coverage of less than 50 reads. Tumors lacking single nucleotide variation (SNV), copy number variation (CNV), or structural variants (SV) were rare, but 22 were cases with low tumor content. Reported P value calculated by Fisher’s exact test.