Comparison of three commercial decision support platforms for matching of next-generation sequencing results with therapies in patients with cancer

ESMO Open

article

Samantha O. Perakis¹  Sabrina Weber¹  Qing Zhou¹  Ricarda Graf¹  Sabine Hojas²  Jakob M. Riedl³  Armin Gerger³  Nadia Dandachi³  Marija Balic³  Gerald Hoefler⁴  Ed Schuuring⁵  Harry J.M. Groen⁶  Jochen B. Geigl¹  Ellen Heitzer¹  Michael R. Speicher¹ 

[1] Institute of Human Genetics, Diagnostic and Research Center for Molecular BioMedicine, Medical University of Graz;Department of Internal Medicine;Department of Internal Medicine, Division of Oncology, Medical University of Graz;Institute of Pathology, Diagnostic and Research Center for Molecular BioMedicine, Medical University of Graz;Department of Pathology, University of Groningen, University Medical Centre Groningen;Department of Pulmonary Diseases, University of Groningen, University Medical Centre Groningen;Christian Doppler Laboratory for Liquid Biopsies for Early Detection of Cancer;BioTechMed-Graz

关键词: circulating tumour DNA;    next-generation sequencing;    molecular profiling;    clinical decision support;    variant interpretation;   

DOI  :  10.1136/esmoopen-2020-000872

学科分类：社会科学、人文和艺术（综合）

来源: BMJ Publishing Group

【 摘 要 】

Objective Precision oncology depends on translating molecular data into therapy recommendations. However, with the growing complexity of next-generation sequencing-based tests, clinical interpretation of somatic genomic mutations has evolved into a formidable task. Here, we compared the performance of three commercial clinical decision support tools, that is, NAVIFY Mutation Profiler (NAVIFY; Roche), QIAGEN Clinical Insight (QCI) Interpret (QIAGEN) and CureMatch Bionov (CureMatch).Methods In order to obtain the current status of the respective tumour genome, we analysed cell-free DNA from patients with metastatic breast, colorectal or non-small cell lung cancer. We evaluated somatic copy number alterations and in parallel applied a 77-gene panel (AVENIO ctDNA Expanded Panel). We then assessed the concordance of tier classification approaches between NAVIFY and QCI and compared the strategies to determine actionability among all three platforms. Finally, we quantified the alignment of treatment suggestions across all decision tools.Results Each platform varied in its mode of variant classification and strategy for identifying druggable targets and clinical trials, which resulted in major discrepancies. Even the frequency of concordant actionable events for tier I-A or tier I-B classifications was only 4.3%, 9.5% and 28.4% when comparing NAVIFY with QCI, NAVIFY with CureMatch and CureMatch with QCI, respectively, and the obtained treatment recommendations differed drastically.Conclusions Treatment decisions based on molecular markers appear at present to be arbitrary and dependent on the chosen strategy. As a consequence, tumours with identical molecular profiles would be differently treated, which challenges the promising concepts of genome-informed medicine.

【 授权许可】

CC BY|CC BY-NC-ND