Cargando…

From somatic variants towards precision oncology: Evidence-driven reporting of treatment options in molecular tumor boards

BACKGROUND: A comprehensive understanding of cancer has been furthered with technological improvements and decreasing costs of next-generation sequencing (NGS). However, the complexity of interpreting genomic data is hindering the implementation of high-throughput technologies in the clinical contex...

Descripción completa

Detalles Bibliográficos
Autores principales: Perera-Bel, Júlia, Hutter, Barbara, Heining, Christoph, Bleckmann, Annalen, Fröhlich, Martina, Fröhling, Stefan, Glimm, Hanno, Brors, Benedikt, Beißbarth, Tim
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5856211/
https://www.ncbi.nlm.nih.gov/pubmed/29544535
http://dx.doi.org/10.1186/s13073-018-0529-2
_version_ 1783307267530031104
author Perera-Bel, Júlia
Hutter, Barbara
Heining, Christoph
Bleckmann, Annalen
Fröhlich, Martina
Fröhling, Stefan
Glimm, Hanno
Brors, Benedikt
Beißbarth, Tim
author_facet Perera-Bel, Júlia
Hutter, Barbara
Heining, Christoph
Bleckmann, Annalen
Fröhlich, Martina
Fröhling, Stefan
Glimm, Hanno
Brors, Benedikt
Beißbarth, Tim
author_sort Perera-Bel, Júlia
collection PubMed
description BACKGROUND: A comprehensive understanding of cancer has been furthered with technological improvements and decreasing costs of next-generation sequencing (NGS). However, the complexity of interpreting genomic data is hindering the implementation of high-throughput technologies in the clinical context: increasing evidence on gene–drug interactions complicates the task of assigning clinical significance to genomic variants. METHODS: Here we present a method that automatically matches patient-specific genomic alterations to treatment options. The method relies entirely on public knowledge of somatic variants with predictive evidence on drug response. The output report is aimed at supporting clinicians in the task of finding the clinical meaning of genomic variants. We applied the method to 1) The Cancer Genome Atlas (TCGA) and Genomics Evidence Neoplasia Information Exchange (GENIE) cohorts and 2) 11 patients from the NCT MASTER trial whose treatment discussions included information on their genomic profiles. RESULTS: Our reporting strategy showed a substantial number of patients with actionable variants in the analyses of TCGA and GENIE samples. Notably, it was able to reproduce experts’ treatment suggestions in a retrospective study of 11 patients from the NCT MASTER trial. Our results establish a proof of concept for comprehensive, evidence-based reports as a supporting tool for discussing treatment options in tumor boards. CONCLUSIONS: We believe that a standardized method to report actionable somatic variants will smooth the incorporation of NGS in the clinical context. We anticipate that tools like the one we present here will become essential in summarizing for clinicians the growing evidence in the field of precision medicine. The R code of the presented method is provided in Additional file 6 and available at https://github.com/jperera-bel/MTB-Report. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13073-018-0529-2) contains supplementary material, which is available to authorized users.
format Online
Article
Text
id pubmed-5856211
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-58562112018-03-22 From somatic variants towards precision oncology: Evidence-driven reporting of treatment options in molecular tumor boards Perera-Bel, Júlia Hutter, Barbara Heining, Christoph Bleckmann, Annalen Fröhlich, Martina Fröhling, Stefan Glimm, Hanno Brors, Benedikt Beißbarth, Tim Genome Med Research BACKGROUND: A comprehensive understanding of cancer has been furthered with technological improvements and decreasing costs of next-generation sequencing (NGS). However, the complexity of interpreting genomic data is hindering the implementation of high-throughput technologies in the clinical context: increasing evidence on gene–drug interactions complicates the task of assigning clinical significance to genomic variants. METHODS: Here we present a method that automatically matches patient-specific genomic alterations to treatment options. The method relies entirely on public knowledge of somatic variants with predictive evidence on drug response. The output report is aimed at supporting clinicians in the task of finding the clinical meaning of genomic variants. We applied the method to 1) The Cancer Genome Atlas (TCGA) and Genomics Evidence Neoplasia Information Exchange (GENIE) cohorts and 2) 11 patients from the NCT MASTER trial whose treatment discussions included information on their genomic profiles. RESULTS: Our reporting strategy showed a substantial number of patients with actionable variants in the analyses of TCGA and GENIE samples. Notably, it was able to reproduce experts’ treatment suggestions in a retrospective study of 11 patients from the NCT MASTER trial. Our results establish a proof of concept for comprehensive, evidence-based reports as a supporting tool for discussing treatment options in tumor boards. CONCLUSIONS: We believe that a standardized method to report actionable somatic variants will smooth the incorporation of NGS in the clinical context. We anticipate that tools like the one we present here will become essential in summarizing for clinicians the growing evidence in the field of precision medicine. The R code of the presented method is provided in Additional file 6 and available at https://github.com/jperera-bel/MTB-Report. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13073-018-0529-2) contains supplementary material, which is available to authorized users. BioMed Central 2018-03-15 /pmc/articles/PMC5856211/ /pubmed/29544535 http://dx.doi.org/10.1186/s13073-018-0529-2 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Perera-Bel, Júlia
Hutter, Barbara
Heining, Christoph
Bleckmann, Annalen
Fröhlich, Martina
Fröhling, Stefan
Glimm, Hanno
Brors, Benedikt
Beißbarth, Tim
From somatic variants towards precision oncology: Evidence-driven reporting of treatment options in molecular tumor boards
title From somatic variants towards precision oncology: Evidence-driven reporting of treatment options in molecular tumor boards
title_full From somatic variants towards precision oncology: Evidence-driven reporting of treatment options in molecular tumor boards
title_fullStr From somatic variants towards precision oncology: Evidence-driven reporting of treatment options in molecular tumor boards
title_full_unstemmed From somatic variants towards precision oncology: Evidence-driven reporting of treatment options in molecular tumor boards
title_short From somatic variants towards precision oncology: Evidence-driven reporting of treatment options in molecular tumor boards
title_sort from somatic variants towards precision oncology: evidence-driven reporting of treatment options in molecular tumor boards
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5856211/
https://www.ncbi.nlm.nih.gov/pubmed/29544535
http://dx.doi.org/10.1186/s13073-018-0529-2
work_keys_str_mv AT pererabeljulia fromsomaticvariantstowardsprecisiononcologyevidencedrivenreportingoftreatmentoptionsinmoleculartumorboards
AT hutterbarbara fromsomaticvariantstowardsprecisiononcologyevidencedrivenreportingoftreatmentoptionsinmoleculartumorboards
AT heiningchristoph fromsomaticvariantstowardsprecisiononcologyevidencedrivenreportingoftreatmentoptionsinmoleculartumorboards
AT bleckmannannalen fromsomaticvariantstowardsprecisiononcologyevidencedrivenreportingoftreatmentoptionsinmoleculartumorboards
AT frohlichmartina fromsomaticvariantstowardsprecisiononcologyevidencedrivenreportingoftreatmentoptionsinmoleculartumorboards
AT frohlingstefan fromsomaticvariantstowardsprecisiononcologyevidencedrivenreportingoftreatmentoptionsinmoleculartumorboards
AT glimmhanno fromsomaticvariantstowardsprecisiononcologyevidencedrivenreportingoftreatmentoptionsinmoleculartumorboards
AT brorsbenedikt fromsomaticvariantstowardsprecisiononcologyevidencedrivenreportingoftreatmentoptionsinmoleculartumorboards
AT beißbarthtim fromsomaticvariantstowardsprecisiononcologyevidencedrivenreportingoftreatmentoptionsinmoleculartumorboards