Abstract 4929: Leveraging multi-omics tumor boards for precision medicine in the OHSU SMMART Treatments Program
Authors: Keck Jamie M. , Parmar Swapnil , Kong Ben , Mitri Zahi , Corless Christopher , Kolodzie Annette , Creason Allison , Goecks Jeremy , Leyshock Patrick , Siex Kiara , Johnson Brett E. , Patterson Janice , Heiser Laura , Olson Anastasiya , Viehdorfer Matt , Mayfield Georgia , Laverdure Jennifer , Gray Joe W. , Mills Gordon B. , Bergan Raymond C. 
Published: August 2019

Abstract
Comprehensive characterization of an individual’s cancer using multi-omic analyses and an expanding list of targeted therapies is providing an opportunity to uncover therapeutic vulnerabilities and rationally target multiple driving alterations in the tumor. To leverage this opportunity, a multi-disciplinary team is required to unravel the complexity of tumor behavior and genomic variant information, integrate data from multi-omic assays, and exploit potential synergies from combination therapy while avoiding toxicity, all of which occurs within the context of the patient’s clinical history and comorbidities. We report the preliminary experience of OHSU Knight Cancer Institute’s SMMART (Serial Measurements of Molecular and Architectural Responses to Therapy) Treatments Program Multi-omics Tumor Board (MTB). The role of the SMMART MTB, to date, has been to develop and optimize procedures in a feasibility protocol for future application in the clinical setting where we will provide personalized combinatorial treatment suggestions. Here we report our preliminary experience over the last 15 months with multi-disciplinary tumor boards for metastatic breast cancer. A deep analysis of data, in many cases from serial biopsies, enabled identification of personalized, multi-targeted therapy. Clinical and laboratory data are explored individually and collectively by oncologists, oncology pharmacists, molecular pathologists, cancer biologists, and computational biologists. Data from CLIA-certified analytics include, but are not limited to, a 124 gene targeted panel, whole exome sequencing, MSI, gene-fusion, RNAseq, and clinical IHC assays that provide status information about receptors (ER/PR/AR/HER2), proliferation rate, and tumor immunogenicity along with reflexive assays for expression of relevant proteins such as p16, RB, and PTEN. A customized LabKey® system allows for visual display of a patient’s clinical timeline with information about diagnoses, treatments, biopsies events, radiographic changes, and blood biomarkers; thereby providing MTB participants with a holistic view of the patient’s case summary. Our experience with several example breast cancer case scenarios identified therapeutic vulnerabilities that would not have been considered by a standard clinical tumor board with genomic data alone. Recent cases have included observations such as HER2 status switching, a rare pathogenic germline mutation, high PD-L1 expression, and gained expression of the androgen receptor. These cases further emphasize the value and importance of MTB discussions to oncologists for interpreting and analyzing complex multi-omic data and uncovering therapeutic options for patients. This experience will be utilized in the future for employing SMMART MTBs in a clinical setting as a platform to triage patients into different multi-targeted combinatorial treatment options.
Citation Format: Jamie M. Keck, Swapnil Parmar, Ben Kong, Zahi Mitri, Christopher Corless, Annette Kolodzie, Allison Creason, Jeremy Goecks, Patrick Leyshock, Kiara Siex, Brett E. Johnson, Janice Patterson, Laura Heiser, Anastasiya Olson, Matt Viehdorfer, Georgia Mayfield, Jennifer Laverdure, Joe W. Gray, Gordon B. Mills, Raymond C. Bergan. Leveraging multi-omics tumor boards for precision medicine in the OHSU SMMART Treatments Program [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4929.