Precision oncology for acute myeloid leukemia using a knowledge bank approach. - PubMed - NCBI
Nat Genet. 2017 Jan 16. doi: 10.1038/ng.3756. [Epub ahead of print]
Precision oncology for acute myeloid leukemia using a knowledge bank approach.
Gerstung M1,2,
Papaemmanuil E1,3,
Martincorena I1,
Bullinger L4,
Gaidzik VI4,
Paschka P4,
Heuser M5,
Thol F5,
Bolli N1,6,
Ganly P7,
Ganser A5,
McDermott U1,
Döhner K4,
Schlenk RF4,
Döhner H4,
Campbell PJ1,8.
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.
- [PubMed - as supplied by publisher]
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