Personalized Clinical Decision Making Through Implementation of a Molecular Tumor Board: A German Single-Center Experience

Abstract

Purpose Dramatic advances in our understanding of the molecular pathophysiology of cancer, along with a rapidly expanding portfolio of molecular targeted drugs, have led to a paradigm shift toward personalized, biomarker-driven cancer treatment. Here, we report the 2-year experience of the Comprehensive Cancer Center Freiburg Molecular Tumor Board (MTB), one of the first interdisciplinary molecular tumor conferences established in Europe. The role of the MTB is to recommend personalized therapy for patients with cancer beyond standard-of-care treatment. Methods This retrospective case series includes 198 patients discussed from March 2015 through February 2017. The MTB guided individual molecular diagnostics, assessed evidence of actionability of molecular alterations, and provided therapy recommendations, including approved and off-label treatments as well as available matched clinical trials. Results The majority of patients had metastatic solid tumors (73.7%), mostly progressive (77.3%) after a mean of 2.0 lines of standard treatment. Diagnostic recommendations resulted in 867 molecular diagnostic tests for 172 patients (five per case), including exome analysis in 36 cases (18.2%). With a median turnaround time of 28 days, treatment recommendations were given to 104 patients (52.5%). These included single-agent targeted therapies (42.3%), checkpoint inhibitors (37.5%), and combination therapies (18.3%). Treatment recommendations were implemented in 33 of 104 patients (31.7%), of whom 19 (57.6%) showed stable disease or partial response, including 14 patients (7.1% of the entire population) receiving off-label treatments. Conclusion Personalized extended molecular-guided patient care is effective for a small but clinically meaningful proportion of patients in challenging clinical situations. Limited access to targeted drugs, lack of trials, and submission at late disease stage prevents broader applicability, whereas genome-wide analyses are not a strict requirement for predictive molecular testing.

Variant classification in precision oncology

“…We analyzed the three most prominent classifications that have been developed over the last years: ( i ) A joint consensus recommendation (JCR) for the interpretation and reporting of sequence variants in cancer by the Association for Molecular Pathology (AMP), American College of Medical Genetics and Genomics (ACMG), American Society of Clinical Oncology (ASCO) and College of American Pathologists (CAP); ( ii ) A framework for ranking molecular targets for cancer precision medicine by the European Society for Medical Oncology (ESMO); ( iii ) A classification developed for the MTBs within the German Cancer Consortium (DKTK) applied at the National Center for Tumor Diseases (NCT) in Heidelberg and implemented by other institutions nationwide …”

“…During the last few years, the use of diagnostic genetic analyses of tumor samples has markedly expanded, facilitating the growth of precision oncology through the identification of a continuously increasing number of therapeutic targets and molecularly defined stratification of patients . Panel‐based next‐generation sequencing (NGS) for the detection of tumor‐specific somatic mutations is already widely available in routine clinical use and a number of bioinformatics tools have been developed for their assessment, including data quality, which is paramount for all subsequent steps (for summaries of these tools see Refs.…”

Genomic expertise in action: molecular tumour boards and decision‐making in precision oncology

“…Oncology practitioners themselves have called attention to the development of MTBs as a noteworthy characteristic of the emerging field of precision oncology (Erdmann , Hoefflin et al . , Horak et al . , Knepper et al .…”

“…Oncology practitioners themselves have called attention to the development of MTBs as a noteworthy characteristic of the emerging field of precision oncology (Erdmann 2015, Hoefflin et al 2018, Horak et al 2017, Knepper et al 2017, McGraw et al 2017, Schwaederle et al 2014, Stoekl e et al 2017, Tafe et al 2015. The purpose of these practitioners' contributions is to document and promote the role and practices of these novel institutions, whose multidisciplinary line-up is justified by relation to the introduction of innovative diagnostic and therapeutic approaches such as targeted therapies, immunotherapies, molecular biomarkers and next-generation sequencing techniques (NGS).…”

Requirements Analysis and Specification for a Molecular Tumor Board Platform Based on cBioPortal

“…Several German medical centers have already started to implement MTBs in their clinical environment, all working with various types of omics data from, e.g., NGS and other technologies [3,4]. To handle the many results from a large amount of omics data there is a high need for a standardized toolset that supports clinicians in analyzing and interpreting these data and creating high-quality presentations of complex multi-dimensional data effectively.…”