Advertisement

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 Koschmann
Clinical Study

Abstract

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.

Keywords

Precision medicine Neuro-oncology Algorithm Targeted therapy 

Notes

Acknowledgements

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.

Funding

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)

References

  1. 1.
    Gupta S, Smith TR, Broekman ML (2017) Ethical considerations of neuro-oncology trial design in the era of precision medicine. J Neurooncol.  https://doi.org/10.1007/s11060-017-2502-0 PubMedCentralGoogle Scholar
  2. 2.
    Sawyers C (2004) Targeted cancer therapy. Nature 432:294–297.  https://doi.org/10.1038/nature03095 CrossRefPubMedGoogle Scholar
  3. 3.
    Brastianos PK, Shankar GM, Gill CM, Taylor-Weiner A, Nayyar N, Panka DJ, Sullivan RJ, Frederick DT, Abedalthagafi M, Jones PS, Dunn IF, Nahed BV, Romero JM, Louis DN, Getz G, Cahill DP, Santagata S, Curry WT, Barker FG (2016) Dramatic response of BRAF V600E mutant papillary craniopharyngioma to targeted therapy. J Natl Cancer Inst 108  https://doi.org/10.1093/jnci/djv310
  4. 4.
    Norden AD, Drappatz J, Wen PY (2007) Targeted drug therapy for meningiomas. Neurosurg Focus 23:E12.  https://doi.org/10.3171/FOC-07/10/E12 CrossRefPubMedGoogle Scholar
  5. 5.
    Wang P, Xiao P, Ye Y, Liu P, Han L, Dong L, She C, Yu J (2017) Rapid response of brain metastasis to crizotinib in a patient with KLC1-ALK fusion and MET gene amplification positive non-small cell lung cancer: a case report. Cancer Biol Med 14:183–186.  https://doi.org/10.20892/j.issn.2095-3941.2017.0017 CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Prados MD, Chang SM, Butowski N, DeBoer R, Parvataneni R, Carliner H, Kabuubi P, Ayers-Ringler J, Rabbitt J, Page M, Fedoroff A, Sneed PK, Berger MS, McDermott MW, Parsa AT, Vandenberg S, James CD, Lamborn KR, Stokoe D, Haas-Kogan DA (2009) Phase II study of erlotinib plus temozolomide during and after radiation therapy in patients with newly diagnosed glioblastoma multiforme or gliosarcoma. J Clin Oncol 27:579–584.  https://doi.org/10.1200/JCO.2008.18.9639 CrossRefPubMedGoogle Scholar
  7. 7.
    Lasorella A, Sanson M, Iavarone A (2017) FGFR-TACC gene fusions in human glioma. Neuro Oncol 19:475–483.  https://doi.org/10.1093/neuonc/now240 PubMedGoogle Scholar
  8. 8.
    Prados MD, Byron SA, Tran NL, Phillips JJ, Molinaro AM, Ligon KL, Wen PY, Kuhn JG, Mellinghoff IK, de Groot JF, Colman H, Cloughesy TF, Chang SM, Ryken TC, Tembe WD, Kiefer JA, Berens ME, Craig DW, Carpten JD, Trent JM (2015) Toward precision medicine in glioblastoma: the promise and the challenges. Neuro Oncol 17:1051–1063.  https://doi.org/10.1093/neuonc/nov031 CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Marini BL, Benitez LL, Zureick AH, Salloum R, Gauthier AC, Brown J, Wu YM, Robinson DR, Kumar C, Lonigro R, Vats P, Cao X, Kasaian K, Anderson B, Mullan B, Chandler B, Linzey JR, Camelo-Piragua SI, Venneti S, Mc Keever PE, McFadden KA, Lieberman AP, Brown N, Shao L, Leonard MAS, Junck L, McKean E, Maher CO, Garton HJL, Muraszko KM, Hervey-Jumper S, Mulcahy-Levy JM, Green A, Hoffman LM, Dorris K, Vitanza NA, Wang J, Schwartz J, Lulla R, Smiley NP, Bornhorst M, Haas-Kogan DA, Robertson PL, Chinnaiyan AM, Mody R, Koschmann C (2017) Blood-brain barrier-adapted precision medicine therapy for pediatric brain tumors. Transl Res.  https://doi.org/10.1016/j.trsl.2017.08.001 Google Scholar
  10. 10.
    Parsons DW, Roy A, Yang Y, Wang T, Scollon S, Bergstrom K, Kerstein RA, Gutierrez S, Petersen AK, Bavle A, Lin FY, López-Terrada DH, Monzon FA, Hicks MJ, Eldin KW, Quintanilla NM, Adesina AM, Mohila CA, Whitehead W, Jea A, Vasudevan SA, Nuchtern JG, Ramamurthy U, McGuire AL, Hilsenbeck SG, Reid JG, Muzny DM, Wheeler DA, Berg SL, Chintagumpala MM, Eng CM, Gibbs RA, Plon SE (2016) Diagnostic yield of clinical tumor and germline whole-exome sequencing for children with solid tumors. JAMA Oncol.  https://doi.org/10.1001/jamaoncol.2015.5699 PubMedPubMedCentralGoogle Scholar
  11. 11.
    Li MM, Datto M, Duncavage EJ, Kulkarni S, Lindeman NI, Roy S, Tsimberidou AM, Vnencak-Jones CL, Wolff DJ, Younes A, Nikiforova MN (2017) Standards and guidelines for the interpretation and reporting of sequence variants in cancer: a joint consensus recommendation of the association for molecular pathology, American Society of Clinical Oncology, and College of American Pathologists. J Mol Diagn 19:4–23.  https://doi.org/10.1016/j.jmoldx.2016.10.002 CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Pardridge WM (2006) Molecular Trojan horses for blood-brain barrier drug delivery. Discov Med 6:139–143PubMedGoogle Scholar
  13. 13.
    de Gooijer MC, Zhang P, Thota N, Mayayo-Peralta I, Buil LC, Beijnen JH, van Tellingen O (2015) P-glycoprotein and breast cancer resistance protein restrict the brain penetration of the CDK4/6 inhibitor palbociclib. Invest New Drugs 33:1012–1019.  https://doi.org/10.1007/s10637-015-0266-y CrossRefPubMedGoogle Scholar
  14. 14.
    Minocha M, Khurana V, Qin B, Pal D, Mitra AK (2012) Co-administration strategy to enhance brain accumulation of vandetanib by modulating P-glycoprotein (P-gp/Abcb1) and breast cancer resistance protein (Bcrp1/Abcg2) mediated efflux with m-TOR inhibitors. Int J Pharm 434:306–314.  https://doi.org/10.1016/j.ijpharm.2012.05.028 CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Minocha M, Khurana V, Qin B, Pal D, Mitra AK (2012) Enhanced brain accumulation of pazopanib by modulating P-gp and Bcrp1 mediated efflux with canertinib or erlotinib. Int J Pharm 436:127–134.  https://doi.org/10.1016/j.ijpharm.2012.05.038 CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Campbell LK, Scaduto M, Sharp W, Dufton L, Van Slyke D, Whitlock JA, Compas B (2007) A meta-analysis of the neurocognitive sequelae of treatment for childhood acute lymphocytic leukemia. Pediatr Blood Cancer 49:65–73.  https://doi.org/10.1002/pbc.20860 CrossRefPubMedGoogle Scholar
  17. 17.
    Sasongko L, Link JM, Muzi M, Mankoff DA, Yang X, Collier AC, Shoner SC, Unadkat JD (2005) Imaging P-glycoprotein transport activity at the human blood-brain barrier with positron emission tomography. Clin Pharmacol Ther 77:503–514.  https://doi.org/10.1016/j.clpt.2005.01.022 CrossRefPubMedGoogle Scholar
  18. 18.
    Chen Y, Agarwal S, Shaik NM, Chen C, Yang Z, Elmquist WF (2009) P-glycoprotein and breast cancer resistance protein influence brain distribution of dasatinib. J Pharmacol Exp Ther 330:956–963.  https://doi.org/10.1124/jpet.109.154781 CrossRefPubMedGoogle Scholar
  19. 19.
    Mody RJ, Wu YM, Lonigro RJ, Cao X, Roychowdhury S, Vats P, Frank KM, Prensner JR, Asangani I, Palanisamy N, Dillman JR, Rabah RM, Kunju LP, Everett J, Raymond VM, Ning Y, Su F, Wang R, Stoffel EM, Innis JW, Roberts JS, Robertson PL, Yanik G, Chamdin A, Connelly JA, Choi S, Harris AC, Kitko C, Rao RJ, Levine JE, Castle VP, Hutchinson RJ, Talpaz M, Robinson DR, Chinnaiyan AM (2015) Integrative clinical sequencing in the management of refractory or relapsed cancer in youth. Jama 314:913–925.  https://doi.org/10.1001/jama.2015.10080 CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Robinson DR, Wu YM, Vats P, Su F, Lonigro RJ, Cao X, Kalyana-Sundaram S, Wang R, Ning Y, Hodges L, Gursky A, Siddiqui J, Tomlins SA, Roychowdhury S, Pienta KJ, Kim SY, Roberts JS, Rae JM, Van Poznak CH, Hayes DF, Chugh R, Kunju LP, Talpaz M, Schott AF, Chinnaiyan AM (2013) Activating ESR1 mutations in hormone-resistant metastatic breast cancer. Nat Genet 45:1446–1451.  https://doi.org/10.1038/ng.2823 CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Wu YM, Su F, Kalyana-Sundaram S, Khazanov N, Ateeq B, Cao X, Lonigro RJ, Vats P, Wang R, Lin SF, Cheng AJ, Kunju LP, Siddiqui J, Tomlins SA, Wyngaard P, Sadis S, Roychowdhury S, Hussain MH, Feng FY, Zalupski MM, Talpaz M, Pienta KJ, Rhodes DR, Robinson DR, Chinnaiyan AM (2013) Identification of targetable FGFR gene fusions in diverse cancers. Cancer Disc 3:636–647.  https://doi.org/10.1158/2159-8290.CD-13-0050 CrossRefGoogle Scholar
  22. 22.
    Robinson DR, Wu YM, Lonigro RJ, Vats P, Cobain E, Everett J, Cao X, Rabban E, Kumar-Sinha C, Raymond V, Schuetze S, Alva A, Siddiqui J, Chugh R, Worden F, Zalupski MM, Innis J, Mody RJ, Tomlins SA, Lucas D, Baker LH, Ramnath N, Schott AF, Hayes DF, Vijai J, Offit K, Stoffel EM, Roberts JS, Smith DC, Kunju LP, Talpaz M, Cieślik M, Chinnaiyan AM (2017) Integrative clinical genomics of metastatic cancer. Nature 548:297–303.  https://doi.org/10.1038/nature23306 CrossRefPubMedGoogle Scholar
  23. 23.
    Duarte TT, Spencer CT (2016) Personalized proteomics: the future of precision medicine. Proteomes 4  https://doi.org/10.3390/proteomes4040029
  24. 24.
    Ruggiero A, Cefalo G, Garre ML, Massimino M, Colosimo C, Attina G, Lazzareschi I, Maurizi P, Ridola V, Mazzarella G, Caldarelli M, Di Rocco C, Madon E, Abate ME, Clerico A, Sandri A, Riccardi R (2006) Phase II trial of temozolomide in children with recurrent high-grade glioma. J Neurooncol 77:89–94.  https://doi.org/10.1007/s11060-005-9011-2 CrossRefPubMedGoogle Scholar
  25. 25.
    Wetmore C, Daryani VM, Billups CA, Boyett JM, Leary S, Tanos R, Goldsmith KC, Stewart CF, Blaney SM, Gajjar A (2016) Phase II evaluation of sunitinib in the treatment of recurrent or refractory high-grade glioma or ependymoma in children: a children’s Oncology Group Study ACNS1021. Cancer Med 5:1416–1424.  https://doi.org/10.1002/cam4.713 CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Janeway KA, Place AE, Kieran MW, Harris MH (2013) Future of clinical genomics in pediatric oncology. J Clin Oncol 31:1893–1903.  https://doi.org/10.1200/JCO.2012.46.8470 CrossRefPubMedGoogle Scholar
  27. 27.
    Gajjar A, Pfister SM, Taylor MD, Gilbertson RJ (2014) Molecular insights into pediatric brain tumors have the potential to transform therapy. Clin Cancer Res 20:5630–5640.  https://doi.org/10.1158/1078-0432.CCR-14-0833 CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Wei W, Shin YS, Xue M, Matsutani T, Masui K, Yang H, Ikegami S, Gu Y, Herrmann K, Johnson D, Ding X, Hwang K, Kim J, Zhou J, Su Y, Li X, Bonetti B, Chopra R, James CD, Cavenee WK, Cloughesy TF, Mischel PS, Heath JR, Gini B (2016) Single-cell phosphoproteomics resolves adaptive signaling dynamics and informs targeted combination therapy in glioblastoma. Cancer Cell 29:563–573.  https://doi.org/10.1016/j.ccell.2016.03.012 CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Bouffet E, Larouche V, Campbell BB, Merico D, de Borja R, Aronson M, Durno C, Krueger J, Cabric V, Ramaswamy V, Zhukova N, Mason G, Farah R, Afzal S, Yalon M, Rechavi G, Magimairajan V, Walsh MF, Constantini S, Dvir R, Elhasid R, Reddy A, Osborn M, Sullivan M, Hansford J, Dodgshun A, Klauber-Demore N, Peterson L, Patel S, Lindhorst S, Atkinson J, Cohen Z, Laframboise R, Dirks P, Taylor M, Malkin D, Albrecht S, Dudley RW, Jabado N, Hawkins CE, Shlien A, Tabori U (2016) Immune checkpoint inhibition for hypermutant glioblastoma multiforme resulting from germline biallelic mismatch repair deficiency. J Clin Oncol 34:2206–2211.  https://doi.org/10.1200/JCO.2016.66.6552 CrossRefPubMedGoogle Scholar

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
  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

Personalised recommendations