Collaborative, Multidisciplinary Evaluation of Cancer Variants Through Virtual Molecular Tumor Boards Informs Local Clinical Practices

Abstract

Purpose: The cancer research community is constantly evolving to better understand tumor biology, disease etiology, risk stratification, and pathways to novel treatments. Yet the clinical cancer genomics field has been hindered by redundant efforts to meaningfully collect and interpret disparate data types from multiple high-throughput modalities and integrate into clinical care processes. Bespoke data models, knowledgebases, and one-off customized resources for data analysis often lack adequate governance and quality control needed for these resources to be clinical grade. Many informatics efforts focused on genomic interpretation resources for neoplasms are underway to support data collection, deposition, curation, harmonization, integration, and analytics to support case review and treatment planning.

Methods: In this review, we evaluate and summarize the landscape of available tools, resources, and evidence used in the evaluation of somatic and germline tumor variants within the context of molecular tumor boards.

Results: Molecular tumor boards (MTBs) are collaborative efforts of multidisciplinary cancer experts equipped with genomic interpretation resources to aid in the delivery of accurate and timely clinical interpretations of complex genomic results for each patient, within an institution or hospital network. Virtual MTBs (VMTBs) provide an online forum for collaborative governance, provenance, and information sharing between experts outside a given hospital network with the potential to enhance MTB discussions. Knowledge sharing in VMTBs and communication with guideline-developing organizations can lead to progress evidenced by data harmonization across resources, crowd-sourced and expert-curated genomic assertions, and a more informed and explainable usage of artificial intelligence.

Conclusion: Advances in cancer genomics interpretation aid in better patient and disease classification, more streamlined identification of relevant literature, and a more thorough review of available treatments and predicted patient outcomes.

FIG 1.

Incorporation of molecular tumor board (MTB) and virtual molecular tumor board (VMTB) workflows into clinical reporting practices. After a patient consults with a clinician and provides a tumor specimen, the clinical next-generation sequencing (NGS) testing is ordered. The clinical laboratory performs the NGS assay and sequencing and reports genomic variants of clinical relevance. The MTB leverages local expertise and available resources to interpret the clinical significance of genomic data. Because MTBs operate locally, there is often opportunity for adding insight directly from the physician and patient that can help guide and/or prepare clinical recommendations. When local expertise is insufficient to make appropriate clinical recommendations, variants are prioritized and patient data are de-identified before VMTB submission. VMTB members from multiple institutions use their cumulative genomic resources and expertise to evaluate an NGS case and to discuss consensus recommendations for the patient.