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Nat Genet. 2017 Mar;49(3):332-340. doi: 10.1038/ng.3756. Epub 2017 Jan 16.

Precision oncology for acute myeloid leukemia using a knowledge bank approach.

Author information

1
Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK.
2
European Bioinformatics Institute EMBL-EBI, Hinxton, UK.
3
Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
4
Department of Internal Medicine III, Ulm University, Ulm, Germany.
5
Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
6
Division of Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori, University of Milan, Milan, Italy.
7
Department of Pathology (UOC), University of Otago, Christchurch, New Zealand.
8
Department of Haematology, University of Cambridge, Cambridge, UK.

Abstract

Underpinning the vision of precision medicine is the concept that causative mutations in a patient's cancer drive its biology and, by extension, its clinical features and treatment response. However, considerable between-patient heterogeneity in driver mutations complicates evidence-based personalization of cancer care. Here, by reanalyzing data from 1,540 patients with acute myeloid leukemia (AML), we explore how large knowledge banks of matched genomic-clinical data can support clinical decision-making. Inclusive, multistage statistical models accurately predicted likelihoods of remission, relapse and mortality, which were validated using data from independent patients in The Cancer Genome Atlas. Comparison of long-term survival probabilities under different treatments enables therapeutic decision support, which is available in exploratory form online. Personally tailored management decisions could reduce the number of hematopoietic cell transplants in patients with AML by 20-25% while maintaining overall survival rates. Power calculations show that databases require information from thousands of patients for accurate decision support. Knowledge banks facilitate personally tailored therapeutic decisions but require sustainable updating, inclusive cohorts and large sample sizes.

PMID:
28092685
PMCID:
PMC5764082
DOI:
10.1038/ng.3756
[Indexed for MEDLINE]
Free PMC Article

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