Journal of Neuro-Oncology

, Volume 137, Issue 1, pp 155–169 | Cite as

Development of the CNS TAP tool for the selection of precision medicine therapies in neuro-oncology

  • Joseph R. Linzey
  • Bernard L. Marini
  • Amy Pasternak
  • Cory Smith
  • Zac Miklja
  • Lili Zhao
  • Chandan Kumar-Sinha
  • Alyssa Paul
  • Nicholas Harris
  • Patricia L. Robertson
  • Lindsey M. Hoffman
  • Arul Chinnaiyan
  • Rajen Mody
  • Carl KoschmannEmail author
Clinical Study


The number of targeted therapies utilized in precision medicine are rapidly increasing. Neuro-oncology offers a unique challenge due to the varying blood brain barrier (BBB) penetration of each agent. Neuro-oncologists face a difficult task weighing the growing number of potential targeted therapies and their likelihood of BBB penetration. We developed the CNS TAP Working Group and performed an extensive literature review for the evidence-based creation of the CNS TAP tool, which was retrospectively validated by analyzing brain tumor patients who underwent therapy targeted based on genomic results from an academic sequencing study (MiOncoseq, n = 17) or private molecular profiling (Foundation One, n = 7). The CNS TAP tool scores relevant targeted agents by applying multiple variables (i.e., pre-clinical data, clinical data, BBB permeability) to patient specific genomic information and clinical trial availability. In the Michigan cohort, the CNS TAP tool predicted the selected agent 85.7% of the time. The CNS TAP tool predicted the agent independently selected by pediatric neuro-oncologists in the Colorado cohort 50% of the time. Patients with recurrent brain tumors treated with agents predicted by the CNS TAP tool demonstrated a median progression-free survival of 4 months and four patients with recurrent high-grade glioma maintained ongoing partial responses of at least 6 months. The CNS TAP tool is a formalized algorithm to assist clinicians select the optimal targeted therapy for neuro-oncology patients. The CNS TAP tool has relatively high concordance with selected therapies and clinical outcomes in patients receiving targeted therapy in this heterogeneous retrospective cohort were promising.


Precision medicine Neuro-oncology Algorithm Targeted therapy 



The authors thank the patients and their families. Additionally, the authors thank the Michigan Center for Translational Pathology for whole exome and transcriptome tumor sequencing analysis through the PEDS-MIONCOSEQ program.


CK is supported by NIH/NINDS K08-NS099427-01, the University of Michigan Pediatric Brain Cancer Research Initiative. The PEDS-MIONCOSEQ study was supported by Grant 1UM1HG006508 from the National Institutes of Health Clinical Sequencing Exploratory Research Award (PI: Arul Chinnaiyan).

Compliance with ethical standards

Conflict of interest

The authors report no disclosures or conflicts of interests.

Supplementary material

11060_2017_2708_MOESM1_ESM.tif (142 kb)
Supplementary Figure 1: A finalized copy of a report that is currently returned to a clinician summarizing the data from the CNS TAP tool. (Abbreviations: DIPG = diffuse intrinsic pontine glioma, ACVR = activin receptor, HDAC = histone deacetylase). (TIF 142 KB)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2017

Authors and Affiliations

  • Joseph R. Linzey
    • 1
  • Bernard L. Marini
    • 2
  • Amy Pasternak
    • 2
  • Cory Smith
    • 2
  • Zac Miklja
    • 1
  • Lili Zhao
    • 4
  • Chandan Kumar-Sinha
    • 5
  • Alyssa Paul
    • 1
  • Nicholas Harris
    • 1
  • Patricia L. Robertson
    • 3
  • Lindsey M. Hoffman
    • 6
  • Arul Chinnaiyan
    • 7
  • Rajen Mody
    • 1
  • Carl Koschmann
    • 1
    Email author
  1. 1.Division of Pediatric Hematology/Oncology, Department of PediatricsUniversity of Michigan Medical SchoolAnn ArborUSA
  2. 2.Department of Pharmacy ServicesUniversity of Michigan Medical SchoolAnn ArborUSA
  3. 3.Division of Neurology, Department of PediatricsUniversity of Michigan Medical SchoolAnn ArborUSA
  4. 4.Department of Biostatistics, School of Public HeathUniversity of MichiganAnn ArborUSA
  5. 5.Department of Pathology, Michigan Center for Translational PathologyUniversity of Michigan Medical SchoolAnn ArborUSA
  6. 6.University of Colorado Denver School of MedicineDenverUSA
  7. 7.Department of UrologyUniversity of Michigan Medical SchoolAnn ArborUSA

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