Precision oncology for acute myeloid leukemia using a knowledge bank approach

Moritz Gerstung, Elli Papaemmanuil, Inigo Martincorena, Lars Bullinger, Verena I. Gaidzik, Peter Paschka, Michael Heuser, Felicitas Thol, Niccolo Bolli, Peter Ganly, Arnold Ganser, Ultan McDermott, Konstanze Döhner, Richard F. Schlenk, Hartmut Döhner, Peter J. Campbell

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)332-340
Number of pages9
JournalNature Genetics
Volume49
Issue number3
DOIs
Publication statusPublished - Mar 1 2017

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Acute Myeloid Leukemia
Neoplasms
Precision Medicine
Mutation
Atlases
Statistical Models
Therapeutics
Sample Size
Survival Rate
Genome
Databases
Transplants
Recurrence
Survival
Mortality

ASJC Scopus subject areas

  • Genetics

Cite this

Gerstung, M., Papaemmanuil, E., Martincorena, I., Bullinger, L., Gaidzik, V. I., Paschka, P., ... Campbell, P. J. (2017). Precision oncology for acute myeloid leukemia using a knowledge bank approach. Nature Genetics, 49(3), 332-340. https://doi.org/10.1038/ng.3756

Precision oncology for acute myeloid leukemia using a knowledge bank approach. / Gerstung, Moritz; Papaemmanuil, Elli; Martincorena, Inigo; Bullinger, Lars; Gaidzik, Verena I.; Paschka, Peter; Heuser, Michael; Thol, Felicitas; Bolli, Niccolo; Ganly, Peter; Ganser, Arnold; McDermott, Ultan; Döhner, Konstanze; Schlenk, Richard F.; Döhner, Hartmut; Campbell, Peter J.

In: Nature Genetics, Vol. 49, No. 3, 01.03.2017, p. 332-340.

Research output: Contribution to journalArticle

Gerstung, M, Papaemmanuil, E, Martincorena, I, Bullinger, L, Gaidzik, VI, Paschka, P, Heuser, M, Thol, F, Bolli, N, Ganly, P, Ganser, A, McDermott, U, Döhner, K, Schlenk, RF, Döhner, H & Campbell, PJ 2017, 'Precision oncology for acute myeloid leukemia using a knowledge bank approach', Nature Genetics, vol. 49, no. 3, pp. 332-340. https://doi.org/10.1038/ng.3756
Gerstung M, Papaemmanuil E, Martincorena I, Bullinger L, Gaidzik VI, Paschka P et al. Precision oncology for acute myeloid leukemia using a knowledge bank approach. Nature Genetics. 2017 Mar 1;49(3):332-340. https://doi.org/10.1038/ng.3756
Gerstung, Moritz ; Papaemmanuil, Elli ; Martincorena, Inigo ; Bullinger, Lars ; Gaidzik, Verena I. ; Paschka, Peter ; Heuser, Michael ; Thol, Felicitas ; Bolli, Niccolo ; Ganly, Peter ; Ganser, Arnold ; McDermott, Ultan ; Döhner, Konstanze ; Schlenk, Richard F. ; Döhner, Hartmut ; Campbell, Peter J. / Precision oncology for acute myeloid leukemia using a knowledge bank approach. In: Nature Genetics. 2017 ; Vol. 49, No. 3. pp. 332-340.
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