Support of a Molecular Tumour Board by an Evidence-Based Decision Management System for Precision Oncology

Affiliations

PMID: 31982633
DOI: 10.1016/j.ejca.2019.12.017

Abstract

Background: Reliable and reproducible interpretation of molecular aberrations constitutes a bottleneck of precision medicine. Evidence-based decision management systems may improve rational therapy recommendations. To cope with an increasing amount of complex molecular data in the clinical care of patients with cancer, we established a workflow for the interpretation of molecular analyses.

Methods: A specialized physician screened results from molecular analyses for potential biomarkers, irrespective of the diagnostic modality. Best available evidence was retrieved and categorized through establishment of an in-house database and interrogation of publicly available databases. Annotated biomarkers were ranked using predefined evidence levels and subsequently discussed at a molecular tumour board (MTB), which generated treatment recommendations. Subsequent translation into patient treatment and clinical outcomes were followed up.

Results: One hundred patients were discussed in the MTB between January 2016 and May 2017. Molecular data were obtained for 70 of 100 patients (50 whole exome/RNA sequencing, 18 panel sequencing, 2 immunohistochemistry (IHC)/microsatellite instability analysis). The MTB generated a median of two treatment recommendations each for 63 patients. Thirty-nine patients were treated: 6 partial responses and 12 stable diseases were achieved as best responses. Genetic counselling for germline events was recommended for seven patients.

Conclusion: The development of an evidence-based workflow allowed for the clinical interpretation of complex molecular data and facilitated the translation of personalized treatment strategies into routine clinical care. The high number of treatment recommendations in patients with comprehensive genomic data and promising responses in patients treated with combination therapy warrant larger clinical studies.

Keywords: Molecular tumour board; Molecular tumour conference; Personalized therapy; Precision oncology; Targeted therapy.

Conflict of interest statement

Conflict of interest statement M.L., M.B., C.M., E.B., K.J., S.B., K.K., S.O., R.S., and F.K. reported no conflicts of interest. S.L. received support and consulting compensation from Bayer. M.L.Y., T.K. and M.S. are employees of Alacris Theranostics. D.L. is currently an employee of AstraZeneca and reported employment, stock ownership and patents/royalties/intellectual property for her spouse at Bayer. C.S. received honoraria from Merck Serono, I.T. took part in an advisory board by Merck Serono. D.B. is a shareholder of MicroDiscovery GmbH. U.K. reported research funding from Merck Sharp & Dohme, Novartis, Bristol-Myers Squibb, Roche, GlaxoSmithKline, AstraZeneca and Merck Serono and served as a consultant or as a member of the advisory board with Merck Sharp & Dohme, Bristol-Myers Squibb, AstraZeneca, Merck Serono and GlaxoSmithKline. D.T.R. received payments as a consultant for Alacris Theranostics and honoraria from Bristol-Myers Squibb.