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

Sholl LM1, Do K2, Shivdasani P1, Cerami E3, Dubuc AM1, Kuo FC1, Garcia EP1, Jia Y1, Davineni P1, Abo RP4, Pugh TJ5, van Hummelen P3, Thorner AR6, Ducar M4, Berger AH7, Nishino M8, Janeway KA9, Church A10, Harris M10, Ritterhouse LL1, Campbell JD11, Rojas-Rudilla V12, Ligon AH1, Ramkissoon S1, Cleary JM2, Matulonis U11, Oxnard GR11, Chao R13, Tassell V13, Christensen J13, Hahn WC14, Kantoff PW15, Kwiatkowski DJ11, Johnson BE11, Meyerson M16, Garraway LA17, Shapiro GI2, Rollins BJ11, Lindeman NI1, MacConaill LE4.

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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).