Abstract SY08-02: Reshaping cancer care delivery through multi-disciplinary molecular tumor boards

Rapidly growing access to next-generation DNA sequencing technology has put the promise of precision oncology in reach, which is to individualize cancer care by matching molecular abnormalities found in a patient9s tumor with specific treatments. As a result, clinicians strive to integrate molecular information into routine oncologic decision-making at accelerating pace. While some findings are associated with well-established treatment recommendations, such as KRAS mutations in colorectal cancer indicating lack of benefit of EGFR inhibitors, clinicians are frequently confronted with complex molecular findings that are difficult to interpret from a diagnostic and therapeutic perspective. In particular, tumors harboring multiple potentially targetable mutations or variants of unknown significance, pose challenges. Beyond this, perplexing complexities of cellular signaling networks dynamically responding to targeted therapies, intra-tumoral heterogeneity, as well as access to drugs as part of clinical trials or off-label use add to the difficulties in bringing precision oncology to patients. With the goal of assisting oncologists at the University of California San Francisco (UCSF) in addressing some of these challenges, we assembled the UCSF Molecular Tumor Board (MTB) in July of 2014. The Board constituents represent a wide spectrum of areas of expertise and include disease-area focused oncologists, pediatric oncologists, molecular pathologists, genetic counselors, pharmacists, clinical trialists, and molecular biologists. All patients undergoing molecular testing at UCSF are listed for possible MTB discussion by default unless the treating oncologist decides otherwise. The main source of molecular results is the UCSF500 test, a next-generation DNA sequencing targeted capture assay that is used to analyze paired tumor and normal DNA. On average, 22 cases are being discussed per month during initially weekly, now bi-weekly meetings. Approximately 20% of the cases are pediatric malignancies. As a result of differential utilization of the UCSF500 within the UCSF Comprehensive Cancer Center, CNS malignancies, colorectal, and neuroendocrine carcinomas as well as melanomas are the predominant tumor types discussed. In agreement with results published by other groups, pathogenic or likely pathogenic germline mutations are present in 15% of the cases, highlighting the importance of integration of genetic counselors in the process. Based on an in-depth analysis of 350 patients seen between April 2015 and November 2017, therapeutically actionable mutations were present in 67% of the cases. Molecularly targeted therapies were recommended in 73% of patients in this subset and recommendations to avoid particular therapies were made in 8%. In 21% of the cases with a recommendation for targeted therapies, clinical action was taken (e.g. drug prescription, clinical trial enrollment). In 62% of the cases with a recommendation, no action had been taken at time of data analysis, with the following reasons cited: patient performance status declined rapidly, patient continued standard therapy, patients declined MTB recommended therapy, or a plan is in place to take action in case of disease progression. Thus, only 16% of cases received treatment as recommended by the MTB. However, there was a trend that cases that were discussed at MTB had higher rates of clinical action taken compared to cases that were not discussed by the MTB. Overall, our experience with the UCSF Molecular Tumor Board is encouraging. Additional efforts need to be undertaken to further increase translation of molecular tumor board recommendations into clinical action. Citation Format: W. Michael Korn. Reshaping cancer care delivery through multi-disciplinary molecular tumor boards [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr SY08-02.