Support of a molecular tumour board by an evidence-based decision management system for precision oncology

Mario Lamping; Manuela Benary; Serge Leyvraz; Clemens Messerschmidt; Eric Blanc; Thomas Kessler; Moritz Schütte; Dido Lenze; Korinna Jöhrens; Susen Burock; Konrad Klinghammer; Sebastian Ochsenreither; Christine Sers; Reinhold Schäfer; Ingeborg Tinhofer; Dieter Beule; Frederick Klauschen; Marie-Laure Yaspo; Ulrich Keilholz; Damian T Rieke

doi:10.1016/j.ejca.2019.12.017

Support of a molecular tumour board by an evidence-based decision management system for precision oncology

Eur J Cancer. 2020 Mar:127:41-51. doi: 10.1016/j.ejca.2019.12.017. Epub 2020 Jan 23.

Authors

Mario Lamping¹, Manuela Benary², Serge Leyvraz³, Clemens Messerschmidt⁴, Eric Blanc⁴, Thomas Kessler⁵, Moritz Schütte⁵, Dido Lenze⁶, Korinna Jöhrens⁶, Susen Burock³, Konrad Klinghammer⁷, Sebastian Ochsenreither⁸, Christine Sers⁶, Reinhold Schäfer⁹, Ingeborg Tinhofer¹⁰, Dieter Beule⁴, Frederick Klauschen⁶, Marie-Laure Yaspo¹¹, Ulrich Keilholz⁹, Damian T Rieke¹²

Affiliations

¹ Charité Comprehensive Cancer Center, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Charitéplatz 1, 10117, Berlin, Germany. Electronic address: mario.lamping@charite.de.
² Department of Pathology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Charitéplatz 1, 10117, Berlin, Germany; IRI Life Sciences, Humboldt-Universität zu Berlin, Philippstraße 13, 10115, Berlin, Germany.
³ Charité Comprehensive Cancer Center, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Charitéplatz 1, 10117, Berlin, Germany.
⁴ Core Unit Bioinformatics, Berlin Institute of Health (BIH), Anna-Louisa-Karsch-Straße 2, 10178, Berlin, Germany.
⁵ Alacris Theranostics GmbH, Max Planck Straße 3, 12489, Berlin, Germany.
⁶ Department of Pathology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Charitéplatz 1, 10117, Berlin, Germany.
⁷ Department of Hematology and Oncology, Campus Benjamin Franklin, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Hindenburgdamm 30, 12203 Berlin, Germany.
⁸ Charité Comprehensive Cancer Center, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Charitéplatz 1, 10117, Berlin, Germany; Department of Hematology and Oncology, Campus Benjamin Franklin, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Hindenburgdamm 30, 12203 Berlin, Germany.
⁹ Charité Comprehensive Cancer Center, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Charitéplatz 1, 10117, Berlin, Germany; German Cancer Consortium (DKTK) and German Cancer Research Centre (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany.
¹⁰ German Cancer Consortium (DKTK) and German Cancer Research Centre (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany; Department of Radiooncology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Charitéplatz 1, 10117, Berlin, Germany.
¹¹ Alacris Theranostics GmbH, Max Planck Straße 3, 12489, Berlin, Germany; Max Planck Institute for Molecular Genetics, Otto Warburg Laboratory Gene Regulation and Systems Biology of Cancer, Ihnestraße 63, 14195, Berlin, Germany.
¹² Charité Comprehensive Cancer Center, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Charitéplatz 1, 10117, Berlin, Germany; Department of Hematology and Oncology, Campus Benjamin Franklin, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Hindenburgdamm 30, 12203 Berlin, Germany; Berlin Institute of Health (BIH), Anna-Louisa-Karsch-Straße 2, 10178, Berlin, Germany. Electronic address: damian.rieke@charite.de.

PMID: 31982633
DOI: 10.1016/j.ejca.2019.12.017

Abstract

Background: Reliable and reproducible interpretation of molecular aberrations constitutes a bottleneck of precision medicine. Evidence-based decision management systems may improve rational therapy recommendations. To cope with an increasing amount of complex molecular data in the clinical care of patients with cancer, we established a workflow for the interpretation of molecular analyses.

Methods: A specialized physician screened results from molecular analyses for potential biomarkers, irrespective of the diagnostic modality. Best available evidence was retrieved and categorized through establishment of an in-house database and interrogation of publicly available databases. Annotated biomarkers were ranked using predefined evidence levels and subsequently discussed at a molecular tumour board (MTB), which generated treatment recommendations. Subsequent translation into patient treatment and clinical outcomes were followed up.

Results: One hundred patients were discussed in the MTB between January 2016 and May 2017. Molecular data were obtained for 70 of 100 patients (50 whole exome/RNA sequencing, 18 panel sequencing, 2 immunohistochemistry (IHC)/microsatellite instability analysis). The MTB generated a median of two treatment recommendations each for 63 patients. Thirty-nine patients were treated: 6 partial responses and 12 stable diseases were achieved as best responses. Genetic counselling for germline events was recommended for seven patients.

Conclusion: The development of an evidence-based workflow allowed for the clinical interpretation of complex molecular data and facilitated the translation of personalized treatment strategies into routine clinical care. The high number of treatment recommendations in patients with comprehensive genomic data and promising responses in patients treated with combination therapy warrant larger clinical studies.

Keywords: Molecular tumour board; Molecular tumour conference; Personalized therapy; Precision oncology; Targeted therapy.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Aged, 80 and over
Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
Biomarkers, Tumor / genetics
Decision Support Techniques*
Female
Follow-Up Studies
High-Throughput Nucleotide Sequencing / methods*
Humans
Male
Middle Aged
Molecular Targeted Therapy*
Neoplasms / drug therapy*
Neoplasms / genetics
Neoplasms / pathology
Pathology, Molecular / statistics & numerical data*
Precision Medicine*
Prognosis
Young Adult

Substances

Biomarkers, Tumor