title: A Distributed Network for Intensive Longitudinal Monitoring in Metastatic Triple-Negative Breast Cancer.
abstract: Accelerating cancer research is expected to require new types of clinical trials. This report describes the Intensive Trial of OMics in Cancer (ITOMIC) and a participant with triple-negative breast cancer metastatic to bone, who had markedly elevated circulating tumor cells (CTCs) that were monitored 48 times over 9 months. A total of 32 researchers from 14 institutions were engaged in the patient's evaluation; 20 researchers had no prior involvement in patient care and 18 were recruited specifically for this patient. Whole-exome sequencing of 3 bone marrow samples demonstrated a novel ROS1 variant that was estimated to be present in most or all tumor cells. After an initial response to cisplatin, a hypothesis of crizotinib sensitivity was disproven. Leukapheresis followed by partial CTC enrichment allowed for the development of a differential high-throughput drug screen and demonstrated sensitivity to investigational BH3-mimetic inhibitors of BCL-2 that could not be tested in the patient because requests to the pharmaceutical sponsors were denied. The number and size of CTC clusters correlated with clinical status and eventually death. Focusing the expertise of a distributed network of investigators on an intensively monitored patient with cancer can generate high-resolution views of the natural history of cancer and suggest new opportunities for therapy. Optimization requires access to investigational drugs.
authors.affiliation: Center for Cancer Innovation, University of Washington, Seattle, Washington|Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington|Department of Medicine/Hematology, University of Washington, Seattle, Washington|Seattle Cancer Care Alliance, Seattle, Washington
authors.forename: C Anthony
authors.initials: CA
authors.lastname: Blau
authors.affiliation: Center for Cancer Innovation, University of Washington, Seattle, Washington|RareCyte Inc., Seattle, Washington
authors.forename: Arturo B
authors.initials: AB
authors.lastname: Ramirez
authors.affiliation: Center for Cancer Innovation, University of Washington, Seattle, Washington|Department of Medicine/Hematology, University of Washington, Seattle, Washington|Northwest Medical Specialities, Puyallup and Tacoma, Washington
authors.forename: Sibel
authors.initials: S
authors.lastname: Blau
authors.affiliation: Center for Cancer Innovation, University of Washington, Seattle, Washington|Department of Laboratory Medicine, University of Washington, Seattle, Washington
authors.forename: Colin C
authors.initials: CC
authors.lastname: Pritchard
authors.affiliation: Center for Cancer Innovation, University of Washington, Seattle, Washington|Department of Laboratory Medicine, University of Washington, Seattle, Washington|Department of Pathology, University of Washington, Seattle, Washington
authors.forename: Michael O
authors.initials: MO
authors.lastname: Dorschner
authors.affiliation: Center for Cancer Innovation, University of Washington, Seattle, Washington|Department of Pathology, University of Washington, Seattle, Washington
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Schmechel
authors.affiliation: Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington|Quellos High Throughput Screening Core, Institute for Stem Cell & Regenerative Medicine, University of Washington, Seattle, Washington
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Martins
authors.affiliation: Center for Cancer Innovation, University of Washington, Seattle, Washington|Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington|Department of Medicine/Hematology, University of Washington, Seattle, Washington
authors.forename: Elisabeth M
authors.initials: EM
authors.lastname: Mahen
authors.affiliation: Center for Cancer Innovation, University of Washington, Seattle, Washington|Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington|Department of Medicine/Hematology, University of Washington, Seattle, Washington
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Burton
authors.affiliation: Center for Cancer Innovation, University of Washington, Seattle, Washington|Trialomics LLC, Seattle, Washington
authors.forename: Vitalina M
authors.initials: VM
authors.lastname: Komashko
authors.affiliation: Center for Cancer Innovation, University of Washington, Seattle, Washington|University of California at Santa Cruz, Santa Cruz, California
authors.forename: Amie J
authors.initials: AJ
authors.lastname: Radenbaugh
authors.affiliation: Seattle Cancer Care Alliance, Seattle, Washington|Department of Laboratory Medicine, University of Washington, Seattle, Washington
authors.forename: Katy
authors.initials: K
authors.lastname: Dougherty
authors.affiliation: Seattle Cancer Care Alliance, Seattle, Washington|Department of Laboratory Medicine, University of Washington, Seattle, Washington
authors.forename: Anju
authors.initials: A
authors.lastname: Thomas
authors.affiliation: Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington|Department of Medicine/Hematology, University of Washington, Seattle, Washington
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Miller
authors.affiliation: Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington|Quellos High Throughput Screening Core, Institute for Stem Cell & Regenerative Medicine, University of Washington, Seattle, Washington
authors.forename: James
authors.initials: J
authors.lastname: Annis
authors.affiliation: Department of Laboratory Medicine, University of Washington, Seattle, Washington
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Fromm
authors.affiliation: Center for Cancer Innovation, University of Washington, Seattle, Washington|Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington
authors.forename: Chaozhong
authors.initials: C
authors.lastname: Song
authors.affiliation: Department of Medicine/Hematology, University of Washington, Seattle, Washington
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Chang
authors.affiliation: Covance/LabCorp Inc., Seattle, Washington
authors.forename: Kellie
authors.initials: K
authors.lastname: Howard
authors.affiliation: Covance/LabCorp Inc., Seattle, Washington
authors.forename: Sharon
authors.initials: S
authors.lastname: Austin
authors.affiliation: Department of Pathology, University of Washington, Seattle, Washington
authors.forename: Rodney A
authors.initials: RA
authors.lastname: Schmidt
authors.affiliation: Department of Medicine/Hematology, University of Washington, Seattle, Washington|Seattle Cancer Care Alliance, Seattle, Washington|Fred Hutchinson Cancer Research Center, Seattle, Washington
authors.forename: Michael L
authors.initials: ML
authors.lastname: Linenberger
authors.affiliation: Center for Cancer Innovation, University of Washington, Seattle, Washington|Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington|Department of Medicine/Hematology, University of Washington, Seattle, Washington|Seattle Cancer Care Alliance, Seattle, Washington|Fred Hutchinson Cancer Research Center, Seattle, Washington
authors.forename: Pamela S
authors.initials: PS
authors.lastname: Becker
authors.affiliation: Center for Cancer Innovation, University of Washington, Seattle, Washington|Department of Medicine/Hematology, University of Washington, Seattle, Washington|Northwest Medical Specialities, Puyallup and Tacoma, Washington
authors.forename: Francis M
authors.initials: FM
authors.lastname: Senecal
authors.affiliation: Center for Cancer Innovation, University of Washington, Seattle, Washington|Trialomics LLC, Seattle, Washington
authors.forename: Brigham H
authors.initials: BH
authors.lastname: Mecham
authors.affiliation: School of Computer Science and Engineering, University of Washington, Seattle, Washington
authors.forename: Su-In
authors.initials: SI
authors.lastname: Lee
authors.affiliation: Covance/LabCorp Inc., Seattle, Washington
authors.forename: Anup
authors.initials: A
authors.lastname: Madan
authors.affiliation: Center for Cancer Innovation, University of Washington, Seattle, Washington|Data4Cure Inc., La Jolla, California
authors.forename: Roy
authors.initials: R
authors.lastname: Ronen
authors.affiliation: Center for Cancer Innovation, University of Washington, Seattle, Washington|Data4Cure Inc., La Jolla, California
authors.forename: Janusz
authors.initials: J
authors.lastname: Dutkowski
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington
authors.forename: Shelly
authors.initials: S
authors.lastname: Heimfeld
authors.affiliation: Seattle Cancer Care Alliance, Seattle, Washington|Department of Laboratory Medicine, University of Washington, Seattle, Washington|Department of Pathology, University of Washington, Seattle, Washington
authors.forename: Brent L
authors.initials: BL
authors.lastname: Wood
authors.affiliation: Center for Cancer Innovation, University of Washington, Seattle, Washington|RareCyte Inc., Seattle, Washington
authors.forename: Jackie L
authors.initials: JL
authors.lastname: Stilwell
authors.affiliation: Center for Cancer Innovation, University of Washington, Seattle, Washington|RareCyte Inc., Seattle, Washington
authors.forename: Eric P
authors.initials: EP
authors.lastname: Kaldjian
authors.affiliation: Center for Cancer Innovation, University of Washington, Seattle, Washington|University of California at Santa Cruz, Santa Cruz, California
authors.forename: David
authors.initials: D
authors.lastname: Haussler
authors.affiliation: Center for Cancer Innovation, University of Washington, Seattle, Washington|University of California at Santa Cruz, Santa Cruz, California
authors.forename: Jingchun
authors.initials: J
authors.lastname: Zhu
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000556:secondary; D019058:Community Networks; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D005104:Expert Testimony; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007937:Leukapheresis; D008137:Longitudinal Studies; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009360:Neoplastic Cells, Circulating; D012108:Research Personnel; D064726:Triple Negative Breast Neoplasms / Q000175:diagnosis* / Q000473:pathology / Q000628:therapy