SwissMTB: establishing comprehensive molecular cancer diagnostics in Swiss clinics

Abstract

BackgroundMolecular precision oncology is an emerging practice to improve cancer therapy by decreasing the risk of choosing treatments that lack efficacy or cause adverse events. However, the challenges of integrating molecular profiling into routine clinical care are manifold. From a computational perspective these include the importance of a short analysis turnaround time, the interpretation of complex drug-gene and gene-gene interactions, and the necessity of standardized high-quality workflows. In addition, difficulties faced when integrating molecular diagnostics into clinical practice are ethical concerns, legal requirements, and limited availability of treatment options beyond standard of care as well as the overall lack of awareness of their existence.MethodsTo the best of our knowledge, we are the first group in Switzerland that established a workflow for personalized diagnostics based on comprehensive high-throughput sequencing of tumors at the clinic. Our workflow, named SwissMTB (Swiss Molecular Tumor Board), links genetic tumor alterations and gene expression to therapeutic options and clinical trial opportunities. The resulting treatment recommendations are summarized in a clinical report and discussed in a molecular tumor board at the clinic to support therapy decisions.ResultsHere we present results from an observational pilot study including 22 late-stage cancer patients. In this study we were able to identify actionable variants and corresponding therapies for 19 patients. Half of the patients were analyzed retrospectively. In two patients we identified resistance-associated variants explaining lack of therapy response. For five out of eleven patients analyzed before treatment the SwissMTB diagnostic influenced treatment decision.ConclusionsSwissMTB enables the analysis and clinical interpretation of large numbers of potentially actionable molecular targets. Thus, our workflow paves the way towards a more frequent use of comprehensive molecular diagnostics in Swiss hospitals.Electronic supplementary materialThe online version of this article (10.1186/s12911-018-0680-0) contains supplementary material, which is available to authorized users.

Personalizedin-silicodrug response prediction based on the genetic landscape of muscle-invasive bladder cancer

“…15,16 In contrast to single marker driven diagnostics and decisions, molecular responses. 20 In BLCA, genomic biomarker driven FGFR-inhibitors have only recently been approved. 13 Despite known targetable mutations, further genomic marker driven therapy has yet to be approved in BLCA.…”

“…Similarly as described in Singer et al 20 , we queried DGIdb 7,49,50 to identify the drug-gene interactions reported in a collection of 30 databases, of which several are expert-curated (e.g.…”

Improving prediction performance of colon cancer prognosis based on the integration of clinical and multi-omics data

“…Exarchos and colleagues combined clinical, imaging tissue and gene expression data from circulating blood cells to model the progression of oral cancer [22]. Recently, a workflow named SwissMTB was reported that could link molecular profiling to treatment decisions [23]. Combining clinical data with single-scale omics data has shown a considerable effect on cancer prognosis, but it remains unclear whether the integration of clinical data and multiscale omics data can help improve cancer prognosis performance.…”

From Somatic Variants Toward Precision Oncology: An Investigation of Reporting Practice for Next-Generation Sequencing-Based Circulating Tumor DNA Analysis

“…To address this situation, a multidisciplinary molecular tumor board (MTB) has been proposed that brings together clinicians, pathologists, geneticists, molecular biologists, and bioinformaticians to assess appropriate tumor profiling and to discuss acceptable therapeutic options for patients. However, owing to the low penetration rate, the low level of patient coverage, and the long lead time for gathering experts, MTB is not currently a viable option . Therefore, guaranteeing the accuracy, comprehensiveness, and standardization of clinical reports is of great importance to help integrate the genomic information into appropriate clinical care decisions.…”

“…Because of the unique biological characteristics of ctDNA and the particular clinical significance of ctDNA analysis (such as readily available for observation of tumor dynamics and assessment of resistance to treatment), some additional information, including description of detailed clinical information and previous medication, may be needed for the reporting of variants detected in ctDNA. Currently, ctDNA report experiences are scarcely shared in the literature and standardized clinical reports for NGS‐based ctDNA analysis have not yet been published . Moreover, little is known about whether accurate and sufficient information about detected variants, relevant medications, and methodological details is being reported to clinicians.…”