title: Precision oncology for acute myeloid leukemia using a knowledge bank approach.
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.
authors.affiliation: Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK.|European Bioinformatics Institute EMBL-EBI, Hinxton, UK.
authors.forename: Moritz
authors.initials: M
authors.lastname: Gerstung
authors.affiliation: Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK.|Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
authors.forename: Elli
authors.initials: E
authors.lastname: Papaemmanuil
authors.affiliation: Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK.
authors.forename: Inigo
authors.initials: I
authors.lastname: Martincorena
authors.affiliation: Department of Internal Medicine III, Ulm University, Ulm, Germany.
authors.forename: Lars
authors.initials: L
authors.lastname: Bullinger
authors.affiliation: Department of Internal Medicine III, Ulm University, Ulm, Germany.
authors.forename: Verena I
authors.initials: VI
authors.lastname: Gaidzik
authors.affiliation: Department of Internal Medicine III, Ulm University, Ulm, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Paschka
authors.affiliation: Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Heuser
authors.affiliation: Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
authors.forename: Felicitas
authors.initials: F
authors.lastname: Thol
authors.affiliation: Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK.|Division of Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori, University of Milan, Milan, Italy.
authors.forename: Niccolo
authors.initials: N
authors.lastname: Bolli
authors.affiliation: Department of Pathology (UOC), University of Otago, Christchurch, New Zealand.
authors.forename: Peter
authors.initials: P
authors.lastname: Ganly
authors.affiliation: Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
authors.forename: Arnold
authors.initials: A
authors.lastname: Ganser
authors.affiliation: Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK.
authors.forename: Ultan
authors.identifier: http://orcid.org/0000-0001-9032-4700
authors.initials: U
authors.lastname: McDermott
authors.affiliation: Department of Internal Medicine III, Ulm University, Ulm, Germany.
authors.forename: Konstanze
authors.initials: K
authors.lastname: Döhner
authors.affiliation: Department of Internal Medicine III, Ulm University, Ulm, Germany.
authors.forename: Richard F
authors.initials: RF
authors.lastname: Schlenk
authors.affiliation: Department of Internal Medicine III, Ulm University, Ulm, Germany.
authors.forename: Hartmut
authors.initials: H
authors.lastname: Döhner
authors.affiliation: Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK.|Department of Haematology, University of Cambridge, Cambridge, UK.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Campbell
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002986:Clinical Trials as Topic; D003657:Decision Making; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D057285:Precision Medicine / Q000379:methods; D016032:Randomized Controlled Trials as Topic; D015996:Survival Rate; D055815:Young Adult