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Support systems to guide clinical decision-making in precision oncology: The Cancer Core Europe Molecular Tumor Board Portal

Nature Medicine volume 26, pages 992–994 (2020)Cite this article

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To the Editor — The optimal management of patients with cancer is increasingly dependent on individualized treatments guided by tumor sequencing data. As comprehensive genomic tests become routine in many disease settings and academic centers promote ‘-omics-guided’ recruitment into clinical trials, accurate and scalable data interpretation represents a major challenge. The meticulous task of matching tumor alterations with approved or experimental therapies relies heavily on the expertise of each center. Unsurprisingly, we see similar sequencing results leading to different clinical recommendations1. While the number of drug biomarkers with target specificities is constantly growing, these disparities are likely to escalate, which may ultimately impair patients’ outcomes and research progress. Access to commercial test results does not simplify decision-making, as such tests often deliver generic reports that lack the necessary information for prioritizing emerging therapies. In addition, data interpretation must also contend with incidental germline findings, which further complicates the process. Medical teams face the extra burden of manually searching for the latest scientific evidence associated with detected gene alterations, which is a complex, time-consuming and error-prone task. Here we argue for the need to streamline expert-driven genomic-data interpretation and reporting workflows and to employ user-friendly decision support tools that foster interactive treatment planning.

A precision oncology decision support tool must give access to the latest clinical actionability evidence and computational analytical tools. Data interpretation can benefit from a variety of publicly available genomics resources, but as variant information exchange standards have not yet been adopted by the community3, the MTBP implements an extensive data format harmonization to ensure their accurate aggregation. We interpret the patient’s germline and tumor variants in terms of both functional relevance and predictive relevance, two distinct and complementary analyses required for the full range of decision-making of a molecular tumor board. First, the variants’ functionality informs the need for genetic-counseling referral when deleterious (pathogenic) germline events in actionable disease-causing genes are detected4,5,6. Importantly, this analysis also provides the necessary information for matching of the patient to clinical trials with ‘categorical’ inclusion criteria — those that rely on estimating the functional effect of variants observed in drug targets, such as ‘activating’ mutations in a given oncogene or ‘loss-of-function’ alterations of a tumor suppressor. The MTBP classifies a variant as functionally relevant by integrating up-to-date evidence from multiple expert-curated knowledge bases, bona fide biological assumptions and bioinformatics predictions. Second, the predictive interpretation matches functionally relevant variants to biomarkers of disease diagnosis, prognosis and drug response reported at present7,8,9. In addition to on-label prescribing, this informs off-label and experimental drug opportunities to be considered according to current knowledge. Decision support tools are especially useful for target-drug prioritization in complex molecular scenarios, such as tumors with co-occurring alterations known to interact and modify the efficacy of a given drug. The portal ranks the variants’ predictive relevance according to the Clinical Actionability of Molecular Targets scale of the European Society for Medical Oncology10, which factors in the scientific evidence that supports the biomarker effect and gene–drug–disease interactions. As a resource to investigators outside of our network, we recently launched an open-access version of the MTBP genomics-interpretation pipeline (https://mtbp.org), which provides a general framework for classifying the functional and predictive relevance of a given list of variants.

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Fig. 1: The Molecular Tumor Board Portal.

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Author information

Author notes

  1. These authors contributed equally: David Tamborero, Rodrigo Dienstmann.

Authors and Affiliations

  1. Department of Oncology and Pathology, Science for Life Laboratory, Karolinska Institutet, Stockholm, Sweden

    David Tamborero, Maan Haj Rachid, Jorrit Boekel, Päivi Östling & Janne Lehtiö

  2. Medical Oncology–Oncology Data Science (ODysSey) Group, Vall d’Hebron Institute of Oncology, Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain

    Rodrigo Dienstmann

  3. Research Coordination Area, Vall d’Hebron Institute of Oncology, Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain

    Xenia Villalobos, Elena Chavarria, Alejandro Piris-Giménez & Ignacio Sánchez Valdivia

  4. Cancer Research UK Cambridge Centre, Cambridge, UK

    Richard Baird, Kenneth Seamon & Carlos Caldas

  5. Medical Oncology Department, Vall d’Hebron Institute of Oncology, Hospital Universitari Vall d’Hebron, Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain

    Irene Braña, Elena Garralda, Analía Azaro, Judith Balmaña, Omar Saavedra & Jordi Rodon

  6. Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden

    Luigi De Petris & Jeffrey Yachnin

  7. Theme Cancer, Karolinska University Hospital, Stockholm, Sweden

    Luigi De Petris, Jeffrey Yachnin, Jonas Bergh & Rolf Lewensohn

  8. Département d’Innovation Thérapeutique et d’Essais Précoces, Gustave Roussy, Université Paris-Saclay, Villejuif, France

    Christophe Massard

  9. Department of Medical Oncology and Clinical Pharmacology, The Netherlands Cancer Institute, Amsterdam, the Netherlands

    Frans L. Opdam

  10. NCT Trial Center, German Cancer Research Center and Heidelberg University Hospital, Heidelberg, Germany

    Richard Schlenk

  11. Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

    Claudio Vernieri

  12. IFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Milan, Italy

    Claudio Vernieri

  13. Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden

    Michele Masucci, Anders Wennborg & Ingemar Ernberg

  14. Gustave Roussy Cancer Campus Grand Paris, Villejuif, France Cancer Core Europe, Villejuif, France

    Fabien Calvo

  15. Division of Translational Medical Oncology, National Center for Tumor Diseases Heidelberg and German Cancer Research Center, Heidelberg, Germany

    Peter Horak, Simon Kreutzfeldt, Petra Oberrauch, Julia Wolfart & Stefan Fröhling

  16. German Cancer Consortium, Heidelberg, Germany

    Peter Horak, Simon Kreutzfeldt, Petra Oberrauch & Stefan Fröhling

  17. Scientific Directorate, Princess Máxima Center, Utrecht, the Netherlands

    Alexander Eggermont

  18. Scientific Directorate, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

    Valentina Fornerone, Paola Gabaldi, Giovanni Scoazec & Giovanni Apolone

  19. Division of Molecular Oncology & Immunology, The Netherlands Cancer Institute, Amsterdam, the Netherlands

    Emile E. Voest

  20. Oncode Institute, The Netherlands Cancer Institute, Amsterdam, the Netherlands

    Emile E. Voest

  21. Vall d’Hebron Institute of Oncology, Vall d’Hebron Barcelona Hospital Campus, UVic-UCC, Barcelona, Spain

    Josep Tabernero

  22. Investigational Cancer Therapeutics Department, University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Jordi Rodon

  23. Cancer Molecular Diagnostics Laboratory, Department of Oncology, University of Cambridge, Cambridge, UK

    Shubha Anand & Jose-Ezequiel Martin

  24. Biometrics Department EDC Design, Netherlands Cancer Institute, Amsterdam, Netherlands

    Danny Baars

  25. Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden

    Svetlana Bajalica-Lagercrantz, Jonas Bergh, Johan Hartman, Claes Karlsson, Rolf Lewensohn, Andreas Lundqvist & Christina von Gertten

  26. Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden

    Svetlana Bajalica-Lagercrantz

  27. Department of Pathology, The Netherlands Cancer Institute, Amsterdam, the Netherlands

    Mariska Bierkens & Gerrit Meijer

  28. Department of Imaging and Physiology, Karolinska University Hospital, Stockholm, Sweden

    Lennart Blomqvist

  29. Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden

    Lennart Blomqvist

  30. Department of Oncology, Cambridge University Hospitals NHS Foundation Trust, Cambridge Biomedical Campus, Cambridge, UK

    Gary J. Doherty

  31. Institut Gustave Roussy, Villejuif, France

    Arnauld Forest

  32. Department of Oncology, University of Cambridge, CRUK Cambridge Institute, Cambridge, UK

    Ionut Gabriel Funingana

  33. Department of Hematology, Karolinska University Hospital, Stockholm, Sweden

    Claes Karlsson

  34. National Institute for Health Research Cambridge Biomedical Research Centre, University of Cambridge, Cambridge, UK

    Mary Kasanicki

  35. Department of Medical Epidemiology and Biostatistics, Science for Life Laboratory, Karolinska Institutet, Stockholm, Sweden

    Johan Lindberg

  36. Business Development Area, Vall d’Hebron Institute of Oncology, Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain

    Carlos Lopez

  37. DITEP–Drug Development Department, Institut Gustave Roussy, Villejuif, France

    Patricia Martin-Romano, Maud Ngo Camus & Claudio Nicotra

  38. Clinical Research Support Unit, Vall d’Hebron Institute of Oncology, Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain

    Susana Muñoz

  39. Molecular Oncology Group, Vall d’Hebron Institute of Oncology, Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain

    Paolo Nuciforo

  40. Department of Histopathology, National Institute for Health Research Cambridge Biomedical Research Centre, University of Cambridge, Cambridge, UK

    Elena Provenzano

  41. Tumor Genetic Lab, Institut Gustave Roussy, INSERM UMR 981, Villejuif, France

    Etienne Rouleau

  42. Cancer Core Europe, Institut Gustave Roussy, Villejuif, France

    John Rowell

  43. Department of Medical Genetics, National Institute for Health Research Cambridge Biomedical Research Centre, University of Cambridge, Cambridge, UK

    Marc Tischkowitz

  44. Family Cancer Clinic, The Netherlands Cancer Institute, Amsterdam, the Netherlands

    Lizet van der Kolk

  45. The Netherlands Cancer Institute, Amsterdam, the Netherlands

    Ruud van der Noll

  46. Division of Molecular Carcinogenesis, The Netherlands Cancer Institute and Oncode Institute, Amsterdam, the Netherlands

    Daniel Vis & Lodewyk Wessels

  47. Cancer Genomics Group, Vall d’Hebron Institute of Oncology, Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain

    Ana Vivancos

  48. Department of Microbiology, Tumor and Cell Biology, Science for Life Laboratory, Karolinska Institutet, Stockholm, Sweden

    Valtteri Wirta

Authors
  1. David Tamborero
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  2. Rodrigo Dienstmann
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  3. Maan Haj Rachid
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  4. Jorrit Boekel
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  5. Richard Baird
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  6. Irene Braña
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  7. Luigi De Petris
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  8. Jeffrey Yachnin
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  9. Christophe Massard
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  10. Frans L. Opdam
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  11. Richard Schlenk
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  12. Claudio Vernieri
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  13. Elena Garralda
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  14. Michele Masucci
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  15. Xenia Villalobos
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  22. Carlos Caldas
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Consortia

Cancer Core Europe consortium

  • Shubha Anand
  • , Analía Azaro
  • , Danny Baars
  • , Svetlana Bajalica-Lagercrantz
  • , Judith Balmaña
  • , Jonas Bergh
  • , Mariska Bierkens
  • , Lennart Blomqvist
  • , Gary J. Doherty
  • , Arnauld Forest
  • , Valentina Fornerone
  • , Ionut Gabriel Funingana
  • , Paola Gabaldi
  • , Johan Hartman
  • , Peter Horak
  • , Claes Karlsson
  • , Mary Kasanicki
  • , Simon Kreutzfeldt
  • , Rolf Lewensohn
  • , Johan Lindberg
  • , Carlos Lopez
  • , Andreas Lundqvist
  • , Patricia Martin-Romano
  • , Jose-Ezequiel Martin
  • , Gerrit Meijer
  • , Susana Muñoz
  • , Maud Ngo Camus
  • , Claudio Nicotra
  • , Paolo Nuciforo
  • , Petra Oberrauch
  • , Päivi Östling
  • , Alejandro Piris-Giménez
  • , Elena Provenzano
  • , Etienne Rouleau
  • , John Rowell
  • , Omar Saavedra
  • , Ignacio Sánchez Valdivia
  • , Giovanni Scoazec
  • , Kenneth Seamon
  • , Marc Tischkowitz
  • , Lizet van der Kolk
  • , Ruud van der Noll
  • , Daniel Vis
  • , Ana Vivancos
  • , Christina von Gertten
  • , Anders Wennborg
  • , Lodewyk Wessels
  • , Valtteri Wirta
  •  & Julia Wolfart

Corresponding authors

Correspondence to David Tamborero or Janne Lehtiö.

Ethics declarations

Competing interests

D. T. reports consultant and/or advisory fees from Roche. R. D. reports receiving honoraria for speaker activities from Roche, Ipsen, Amgen, Sanofi, Servier Laboratories and Merck Sharp & Dohme; an advisory role at Roche and Boehringer Ingelheim; and research grants from Merck and Pierre Fabre. R. B. reports consultant or advisory roles (with funding to the institution) at AstraZeneca, Daiichi-Sankyo, Lilly, Molecular Partners, Novartis, Roche and Shionogi; is a principal or sub-investigator of clinical trials for Astex, AstraZeneca, Boehringer-Ingelheim, Boston Therapeutics, Genentech/Roche, Johnson & Johnson, Lilly, Molecular Partners, PharmaMar, Roche, Sanofi-Aventis, Shionogi and Taiho; and reports research grants from AstraZeneca, Boehringer-Ingelheim and Genentech. I. B. reports a consultant or advisory role at Orion Pharma and speaker activities for Bristol Myers Squibb; reports travel grants from AstraZeneca and Merck Serono; and is a principal investigator of clinical trials for AstraZeneca, Bristol Myers Squibb, Celgene, Gliknik, GlaxoSmithKline, Janssen, Kura, Merck, Sharp & Dohme, Novartis, Orion Pharma, Pfizer, Shattuck, Northern Biologics, Rakutan Aspirian and Nanobiotics. C. M. reports consultant and/or advisory fees from Amgen, Astellas, Astra Zeneca, Bayer, BeiGene, Bristol Myers Squibb, Celgene, Debiopharm, Genentech, Ipsen, Janssen, Lilly, MedImmune, Merck, Sharp & Dohme, Novartis, Pfizer, Roche, Sanofi, Orion; and is a principal or sub-investigator of clinical trials for Abbvie, Aduro, Agios, Amgen, Argen-x, Astex, AstraZeneca, Aveopharmaceuticals, Bayer, Beigene, Blueprint, Bristol Myers Squibb, Boeringer Ingelheim, Celgene, Chugai, Clovis, Daiichi Sankyo, Debiopharm, Eisai, Eos, Exelixis, Forma, Gamamabs, Genentech, Gortec, GlaxoSmithKline, H3 biomedicine, Incyte, Innate Pharma, Janssen, Kura Oncology, Kyowa, Lilly, Loxo, Lysarc, Lytix Biopharma, Medimmune, Menarini, Merus, Merck, Sharp & Dohme, Nanobiotix, Nektar Therapeutics, Novartis, Octimet, Oncoethix, Oncopeptides, Orion, Pfizer, Pharmamar, Pierre Fabre, Roche, Sanofi, Servier, Sierra Oncology, Taiho, Takeda, Tesaro and Xencor. R. S. reports research funding from Pfizer, AstraZeneca, PharmaMar, Roche and Daiichi Sankyo; speaker honoraria from Pfizer, Daiichi Sankyo and Novartis; and participation in advisory boards at Pfizer, Daiichi Sankyo and Novartis. E. G. reports consultant honoraria from Roche/Genentech, F. Hoffmann La Roche, Ellipses Pharma, Neomed Therapeutics, Boehringer Ingelheim–Janssen Global Services, AstraZeneca, SeaGen, TFS–Alkermes; reports research for Novartis/Roche; is a principal or sub-investigator of clinical trials for Principia Biopharma, Lilly, Novartis Farmacéutica, Genentech, Loxo Oncology, F. Hoffmann La Roche, Symphogen, Merck, Sharp & Dohme de España, Incyte Biosciences International, Pharma Mar, Kura Oncology, Macrogenics, Glycotope, Pierre Fabre Medicament, Cellestia Biotech, Menarini Ricerche Spa, Blueprint Medicines, Beigene Usa, Sierra Oncology and Genmab; reports travel grants from Bristol-Mayers Squibb, Merck Sharp & Dohme, Menarini, Glycotope; and is on the speakers bureau for Bristol-Mayers Squibb, Merck Sharp & Dohme, Roche and ThermoFisher. S. F. reports a consulting or advisory role, having received honoraria, research funding, and/or travel/accommodation expenses funding from Bayer, Roche, Amgen, Eli Lilly, PharmaMar, AstraZeneca, and Pfizer. A. E. has received personal fees from Actelion, Agenus, Amgen, Bayer, Bristol Myers Squibb, Catalym, CellDex, Gilead, GlaxoSmithKline, HalioDX, Incyte, IO Biotech, ISA Pharmaceuticals, MedImmune, Merck Sharp & Dohme, Nektar, Novartis, Pfizer, Polynoma, Regeneron, Sanofi and SkylineDx; and has equity in RiverDx, SkylineDx and Theranovir. E. E. V. is legally responsible for all contracts with pharmaceutical companies, as medical director of the Netherlands Cancer Institute. C. C. is a member of the External Science Panel of AstraZeneca and of Illumina’s Scientific Advisory Board, and his laboratory has received research grants (administered by the University of Cambridge) from Genentech, Roche, AstraZeneca and Servier. J. T. provides a scientific consultancy role for Array Biopharma, AstraZeneca, Bayer, BeiGene, Boehringer Ingelheim, Chugai, Genentech, Genmab, Halozyme, Imugene, Inflection Biosciences, Ipsen, Kura Oncology, Lilly, Merck Sharp & Dohme, Menarini, Merck Serono, Merrimack, Merus, Molecular Partners, Novartis, Peptomyc, Pfizer, Pharmacyclics, ProteoDesign, Rafael Pharmaceuticals, F. Hoffmann La Roche, Sanofi, SeaGen, Seattle Genetics, Servier, Symphogen, Taiho, VCN Biosciences, Biocartis, Foundation Medicine, HalioDX SAS and Roche Diagnostics. J. R. reports research funding from Bayer & Novartis; clinical research for Spectrum Pharmaceuticals, Tocagen, Symphogen, BioAlta, Pfizer, GenMab, CytomX, KELUN-BIOTECH, Takeda-Millennium, GlaxoSmithKline and Ipsen; is on the scientific advisory board of Novartis, Eli Lilly, Orion Pharmaceuticals, Servier Pharmaceuticals, Peptomyc, Merck Sharp & Dohme, Kelun Pharmaceuticals/Klus Pharma, Spectrum Pharmaceuticals, Pfizer, Roche Pharmaceuticals and Ellipses Pharma; and reports research funding for Bayer & Novartis. J. L. reports research funding from AstraZeneca, Novartis and GE healthcare; and is a co-founder and shareholder of FenoMark Diagnostics.

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Tamborero, D., Dienstmann, R., Rachid, M.H. et al. Support systems to guide clinical decision-making in precision oncology: The Cancer Core Europe Molecular Tumor Board Portal. Nat Med 26, 992–994 (2020). https://doi.org/10.1038/s41591-020-0969-2

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