ReviewNeuro-oncology2026
Evaluating "brain permeability": A critical issue for the development of therapeutic agents for primary and metastatic brain tumors.
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In one paragraph
Review in Neuro-oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
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Authors and funding
22 authors.
Stuart A GrossmanDepartment of Oncology, Johns Hopkins University (S.A.G., R.R., C.H., K.C.S., C.R., J.O.B., D.O.K., P.S., T.P.); Food and Drug Administration (FDA), Silver Spring, Maryland, USA (A.B., E.D., E.W., L.S.L.P., T.P.); Department of Pharmaceutics, University of Minnesota, Minneapolis, Minnesota, USA (W.F.E.); Wake Forest School of Medicine, Winston-Salem, North Carolina, USA (R.E.S., G.L.); Department of Neurosurgery, Barrow's Neurologic Institute, Phoenix, Arizona, USA (N.S.); Medical Oncology, City of Hope, Duarte, California, USA (J.P.); Department of Neurology, University of Alabama Birmingham, Birmingham, Alabama, USA (B.N.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota, USA (J.N.S.); Department of Medicine, Cleveland Clinic, Cleveland, Ohio, USA (D.P.); Department of Neurology, University of Virginia, Charlottesville, Virginia, USA (D.S.).ORCID 0000-0002-3726-7679
Amy BaroneDepartment of Oncology, Johns Hopkins University (S.A.G., R.R., C.H., K.C.S., C.R., J.O.B., D.O.K., P.S., T.P.); Food and Drug Administration (FDA), Silver Spring, Maryland, USA (A.B., E.D., E.W., L.S.L.P., T.P.); Department of Pharmaceutics, University of Minnesota, Minneapolis, Minnesota, USA (W.F.E.); Wake Forest School of Medicine, Winston-Salem, North Carolina, USA (R.E.S., G.L.); Department of Neurosurgery, Barrow's Neurologic Institute, Phoenix, Arizona, USA (N.S.); Medical Oncology, City of Hope, Duarte, California, USA (J.P.); Department of Neurology, University of Alabama Birmingham, Birmingham, Alabama, USA (B.N.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota, USA (J.N.S.); Department of Medicine, Cleveland Clinic, Cleveland, Ohio, USA (D.P.); Department of Neurology, University of Virginia, Charlottesville, Virginia, USA (D.S.).ORCID 0000-0002-5205-9544
Roy E StrowdDepartment of Oncology, Johns Hopkins University (S.A.G., R.R., C.H., K.C.S., C.R., J.O.B., D.O.K., P.S., T.P.); Food and Drug Administration (FDA), Silver Spring, Maryland, USA (A.B., E.D., E.W., L.S.L.P., T.P.); Department of Pharmaceutics, University of Minnesota, Minneapolis, Minnesota, USA (W.F.E.); Wake Forest School of Medicine, Winston-Salem, North Carolina, USA (R.E.S., G.L.); Department of Neurosurgery, Barrow's Neurologic Institute, Phoenix, Arizona, USA (N.S.); Medical Oncology, City of Hope, Duarte, California, USA (J.P.); Department of Neurology, University of Alabama Birmingham, Birmingham, Alabama, USA (B.N.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota, USA (J.N.S.); Department of Medicine, Cleveland Clinic, Cleveland, Ohio, USA (D.P.); Department of Neurology, University of Virginia, Charlottesville, Virginia, USA (D.S.).ORCID 0000-0001-6651-5267
Rana RaisDepartment of Oncology, Johns Hopkins University (S.A.G., R.R., C.H., K.C.S., C.R., J.O.B., D.O.K., P.S., T.P.); Food and Drug Administration (FDA), Silver Spring, Maryland, USA (A.B., E.D., E.W., L.S.L.P., T.P.); Department of Pharmaceutics, University of Minnesota, Minneapolis, Minnesota, USA (W.F.E.); Wake Forest School of Medicine, Winston-Salem, North Carolina, USA (R.E.S., G.L.); Department of Neurosurgery, Barrow's Neurologic Institute, Phoenix, Arizona, USA (N.S.); Medical Oncology, City of Hope, Duarte, California, USA (J.P.); Department of Neurology, University of Alabama Birmingham, Birmingham, Alabama, USA (B.N.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota, USA (J.N.S.); Department of Medicine, Cleveland Clinic, Cleveland, Ohio, USA (D.P.); Department of Neurology, University of Virginia, Charlottesville, Virginia, USA (D.S.).ORCID 0000-0003-4059-2453
Elizabeth DukeDepartment of Oncology, Johns Hopkins University (S.A.G., R.R., C.H., K.C.S., C.R., J.O.B., D.O.K., P.S., T.P.); Food and Drug Administration (FDA), Silver Spring, Maryland, USA (A.B., E.D., E.W., L.S.L.P., T.P.); Department of Pharmaceutics, University of Minnesota, Minneapolis, Minnesota, USA (W.F.E.); Wake Forest School of Medicine, Winston-Salem, North Carolina, USA (R.E.S., G.L.); Department of Neurosurgery, Barrow's Neurologic Institute, Phoenix, Arizona, USA (N.S.); Medical Oncology, City of Hope, Duarte, California, USA (J.P.); Department of Neurology, University of Alabama Birmingham, Birmingham, Alabama, USA (B.N.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota, USA (J.N.S.); Department of Medicine, Cleveland Clinic, Cleveland, Ohio, USA (D.P.); Department of Neurology, University of Virginia, Charlottesville, Virginia, USA (D.S.).ORCID 0000-0002-3361-1436
Emily WearneDepartment of Oncology, Johns Hopkins University (S.A.G., R.R., C.H., K.C.S., C.R., J.O.B., D.O.K., P.S., T.P.); Food and Drug Administration (FDA), Silver Spring, Maryland, USA (A.B., E.D., E.W., L.S.L.P., T.P.); Department of Pharmaceutics, University of Minnesota, Minneapolis, Minnesota, USA (W.F.E.); Wake Forest School of Medicine, Winston-Salem, North Carolina, USA (R.E.S., G.L.); Department of Neurosurgery, Barrow's Neurologic Institute, Phoenix, Arizona, USA (N.S.); Medical Oncology, City of Hope, Duarte, California, USA (J.P.); Department of Neurology, University of Alabama Birmingham, Birmingham, Alabama, USA (B.N.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota, USA (J.N.S.); Department of Medicine, Cleveland Clinic, Cleveland, Ohio, USA (D.P.); Department of Neurology, University of Virginia, Charlottesville, Virginia, USA (D.S.).ORCID 0000-0001-8912-2378
Lauren S L PriceDepartment of Oncology, Johns Hopkins University (S.A.G., R.R., C.H., K.C.S., C.R., J.O.B., D.O.K., P.S., T.P.); Food and Drug Administration (FDA), Silver Spring, Maryland, USA (A.B., E.D., E.W., L.S.L.P., T.P.); Department of Pharmaceutics, University of Minnesota, Minneapolis, Minnesota, USA (W.F.E.); Wake Forest School of Medicine, Winston-Salem, North Carolina, USA (R.E.S., G.L.); Department of Neurosurgery, Barrow's Neurologic Institute, Phoenix, Arizona, USA (N.S.); Medical Oncology, City of Hope, Duarte, California, USA (J.P.); Department of Neurology, University of Alabama Birmingham, Birmingham, Alabama, USA (B.N.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota, USA (J.N.S.); Department of Medicine, Cleveland Clinic, Cleveland, Ohio, USA (D.P.); Department of Neurology, University of Virginia, Charlottesville, Virginia, USA (D.S.).ORCID 0000-0001-7810-0499
Craig HendrixDepartment of Oncology, Johns Hopkins University (S.A.G., R.R., C.H., K.C.S., C.R., J.O.B., D.O.K., P.S., T.P.); Food and Drug Administration (FDA), Silver Spring, Maryland, USA (A.B., E.D., E.W., L.S.L.P., T.P.); Department of Pharmaceutics, University of Minnesota, Minneapolis, Minnesota, USA (W.F.E.); Wake Forest School of Medicine, Winston-Salem, North Carolina, USA (R.E.S., G.L.); Department of Neurosurgery, Barrow's Neurologic Institute, Phoenix, Arizona, USA (N.S.); Medical Oncology, City of Hope, Duarte, California, USA (J.P.); Department of Neurology, University of Alabama Birmingham, Birmingham, Alabama, USA (B.N.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota, USA (J.N.S.); Department of Medicine, Cleveland Clinic, Cleveland, Ohio, USA (D.P.); Department of Neurology, University of Virginia, Charlottesville, Virginia, USA (D.S.).ORCID 0000-0002-5696-8665
Karisa C SchreckDepartment of Oncology, Johns Hopkins University (S.A.G., R.R., C.H., K.C.S., C.R., J.O.B., D.O.K., P.S., T.P.); Food and Drug Administration (FDA), Silver Spring, Maryland, USA (A.B., E.D., E.W., L.S.L.P., T.P.); Department of Pharmaceutics, University of Minnesota, Minneapolis, Minnesota, USA (W.F.E.); Wake Forest School of Medicine, Winston-Salem, North Carolina, USA (R.E.S., G.L.); Department of Neurosurgery, Barrow's Neurologic Institute, Phoenix, Arizona, USA (N.S.); Medical Oncology, City of Hope, Duarte, California, USA (J.P.); Department of Neurology, University of Alabama Birmingham, Birmingham, Alabama, USA (B.N.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota, USA (J.N.S.); Department of Medicine, Cleveland Clinic, Cleveland, Ohio, USA (D.P.); Department of Neurology, University of Virginia, Charlottesville, Virginia, USA (D.S.).ORCID 0000-0001-7181-3269
Glenn LesserDepartment of Oncology, Johns Hopkins University (S.A.G., R.R., C.H., K.C.S., C.R., J.O.B., D.O.K., P.S., T.P.); Food and Drug Administration (FDA), Silver Spring, Maryland, USA (A.B., E.D., E.W., L.S.L.P., T.P.); Department of Pharmaceutics, University of Minnesota, Minneapolis, Minnesota, USA (W.F.E.); Wake Forest School of Medicine, Winston-Salem, North Carolina, USA (R.E.S., G.L.); Department of Neurosurgery, Barrow's Neurologic Institute, Phoenix, Arizona, USA (N.S.); Medical Oncology, City of Hope, Duarte, California, USA (J.P.); Department of Neurology, University of Alabama Birmingham, Birmingham, Alabama, USA (B.N.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota, USA (J.N.S.); Department of Medicine, Cleveland Clinic, Cleveland, Ohio, USA (D.P.); Department of Neurology, University of Virginia, Charlottesville, Virginia, USA (D.S.).ORCID 0009-0003-5471-8907
Nader SanaiDepartment of Oncology, Johns Hopkins University (S.A.G., R.R., C.H., K.C.S., C.R., J.O.B., D.O.K., P.S., T.P.); Food and Drug Administration (FDA), Silver Spring, Maryland, USA (A.B., E.D., E.W., L.S.L.P., T.P.); Department of Pharmaceutics, University of Minnesota, Minneapolis, Minnesota, USA (W.F.E.); Wake Forest School of Medicine, Winston-Salem, North Carolina, USA (R.E.S., G.L.); Department of Neurosurgery, Barrow's Neurologic Institute, Phoenix, Arizona, USA (N.S.); Medical Oncology, City of Hope, Duarte, California, USA (J.P.); Department of Neurology, University of Alabama Birmingham, Birmingham, Alabama, USA (B.N.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota, USA (J.N.S.); Department of Medicine, Cleveland Clinic, Cleveland, Ohio, USA (D.P.); Department of Neurology, University of Virginia, Charlottesville, Virginia, USA (D.S.).ORCID 0000-0002-5581-0516
Carlos RomoDepartment of Oncology, Johns Hopkins University (S.A.G., R.R., C.H., K.C.S., C.R., J.O.B., D.O.K., P.S., T.P.); Food and Drug Administration (FDA), Silver Spring, Maryland, USA (A.B., E.D., E.W., L.S.L.P., T.P.); Department of Pharmaceutics, University of Minnesota, Minneapolis, Minnesota, USA (W.F.E.); Wake Forest School of Medicine, Winston-Salem, North Carolina, USA (R.E.S., G.L.); Department of Neurosurgery, Barrow's Neurologic Institute, Phoenix, Arizona, USA (N.S.); Medical Oncology, City of Hope, Duarte, California, USA (J.P.); Department of Neurology, University of Alabama Birmingham, Birmingham, Alabama, USA (B.N.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota, USA (J.N.S.); Department of Medicine, Cleveland Clinic, Cleveland, Ohio, USA (D.P.); Department of Neurology, University of Virginia, Charlottesville, Virginia, USA (D.S.).ORCID 0000-0002-0260-7047
Jana PortnowDepartment of Oncology, Johns Hopkins University (S.A.G., R.R., C.H., K.C.S., C.R., J.O.B., D.O.K., P.S., T.P.); Food and Drug Administration (FDA), Silver Spring, Maryland, USA (A.B., E.D., E.W., L.S.L.P., T.P.); Department of Pharmaceutics, University of Minnesota, Minneapolis, Minnesota, USA (W.F.E.); Wake Forest School of Medicine, Winston-Salem, North Carolina, USA (R.E.S., G.L.); Department of Neurosurgery, Barrow's Neurologic Institute, Phoenix, Arizona, USA (N.S.); Medical Oncology, City of Hope, Duarte, California, USA (J.P.); Department of Neurology, University of Alabama Birmingham, Birmingham, Alabama, USA (B.N.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota, USA (J.N.S.); Department of Medicine, Cleveland Clinic, Cleveland, Ohio, USA (D.P.); Department of Neurology, University of Virginia, Charlottesville, Virginia, USA (D.S.).ORCID 0000-0002-4257-0891
Jaishri O BlakeleyDepartment of Oncology, Johns Hopkins University (S.A.G., R.R., C.H., K.C.S., C.R., J.O.B., D.O.K., P.S., T.P.); Food and Drug Administration (FDA), Silver Spring, Maryland, USA (A.B., E.D., E.W., L.S.L.P., T.P.); Department of Pharmaceutics, University of Minnesota, Minneapolis, Minnesota, USA (W.F.E.); Wake Forest School of Medicine, Winston-Salem, North Carolina, USA (R.E.S., G.L.); Department of Neurosurgery, Barrow's Neurologic Institute, Phoenix, Arizona, USA (N.S.); Medical Oncology, City of Hope, Duarte, California, USA (J.P.); Department of Neurology, University of Alabama Birmingham, Birmingham, Alabama, USA (B.N.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota, USA (J.N.S.); Department of Medicine, Cleveland Clinic, Cleveland, Ohio, USA (D.P.); Department of Neurology, University of Virginia, Charlottesville, Virginia, USA (D.S.).ORCID 0000-0002-1049-0993
David O KamsonDepartment of Oncology, Johns Hopkins University (S.A.G., R.R., C.H., K.C.S., C.R., J.O.B., D.O.K., P.S., T.P.); Food and Drug Administration (FDA), Silver Spring, Maryland, USA (A.B., E.D., E.W., L.S.L.P., T.P.); Department of Pharmaceutics, University of Minnesota, Minneapolis, Minnesota, USA (W.F.E.); Wake Forest School of Medicine, Winston-Salem, North Carolina, USA (R.E.S., G.L.); Department of Neurosurgery, Barrow's Neurologic Institute, Phoenix, Arizona, USA (N.S.); Medical Oncology, City of Hope, Duarte, California, USA (J.P.); Department of Neurology, University of Alabama Birmingham, Birmingham, Alabama, USA (B.N.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota, USA (J.N.S.); Department of Medicine, Cleveland Clinic, Cleveland, Ohio, USA (D.P.); Department of Neurology, University of Virginia, Charlottesville, Virginia, USA (D.S.).ORCID 0000-0002-0473-658X
Burt NaborsDepartment of Oncology, Johns Hopkins University (S.A.G., R.R., C.H., K.C.S., C.R., J.O.B., D.O.K., P.S., T.P.); Food and Drug Administration (FDA), Silver Spring, Maryland, USA (A.B., E.D., E.W., L.S.L.P., T.P.); Department of Pharmaceutics, University of Minnesota, Minneapolis, Minnesota, USA (W.F.E.); Wake Forest School of Medicine, Winston-Salem, North Carolina, USA (R.E.S., G.L.); Department of Neurosurgery, Barrow's Neurologic Institute, Phoenix, Arizona, USA (N.S.); Medical Oncology, City of Hope, Duarte, California, USA (J.P.); Department of Neurology, University of Alabama Birmingham, Birmingham, Alabama, USA (B.N.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota, USA (J.N.S.); Department of Medicine, Cleveland Clinic, Cleveland, Ohio, USA (D.P.); Department of Neurology, University of Virginia, Charlottesville, Virginia, USA (D.S.).ORCID 0000-0001-5926-2230
Peter SearsonDepartment of Oncology, Johns Hopkins University (S.A.G., R.R., C.H., K.C.S., C.R., J.O.B., D.O.K., P.S., T.P.); Food and Drug Administration (FDA), Silver Spring, Maryland, USA (A.B., E.D., E.W., L.S.L.P., T.P.); Department of Pharmaceutics, University of Minnesota, Minneapolis, Minnesota, USA (W.F.E.); Wake Forest School of Medicine, Winston-Salem, North Carolina, USA (R.E.S., G.L.); Department of Neurosurgery, Barrow's Neurologic Institute, Phoenix, Arizona, USA (N.S.); Medical Oncology, City of Hope, Duarte, California, USA (J.P.); Department of Neurology, University of Alabama Birmingham, Birmingham, Alabama, USA (B.N.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota, USA (J.N.S.); Department of Medicine, Cleveland Clinic, Cleveland, Ohio, USA (D.P.); Department of Neurology, University of Virginia, Charlottesville, Virginia, USA (D.S.).ORCID 0000-0002-5417-0828
Jann N SarkariaDepartment of Oncology, Johns Hopkins University (S.A.G., R.R., C.H., K.C.S., C.R., J.O.B., D.O.K., P.S., T.P.); Food and Drug Administration (FDA), Silver Spring, Maryland, USA (A.B., E.D., E.W., L.S.L.P., T.P.); Department of Pharmaceutics, University of Minnesota, Minneapolis, Minnesota, USA (W.F.E.); Wake Forest School of Medicine, Winston-Salem, North Carolina, USA (R.E.S., G.L.); Department of Neurosurgery, Barrow's Neurologic Institute, Phoenix, Arizona, USA (N.S.); Medical Oncology, City of Hope, Duarte, California, USA (J.P.); Department of Neurology, University of Alabama Birmingham, Birmingham, Alabama, USA (B.N.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota, USA (J.N.S.); Department of Medicine, Cleveland Clinic, Cleveland, Ohio, USA (D.P.); Department of Neurology, University of Virginia, Charlottesville, Virginia, USA (D.S.).ORCID 0000-0001-7489-4885
David PeereboomDepartment of Oncology, Johns Hopkins University (S.A.G., R.R., C.H., K.C.S., C.R., J.O.B., D.O.K., P.S., T.P.); Food and Drug Administration (FDA), Silver Spring, Maryland, USA (A.B., E.D., E.W., L.S.L.P., T.P.); Department of Pharmaceutics, University of Minnesota, Minneapolis, Minnesota, USA (W.F.E.); Wake Forest School of Medicine, Winston-Salem, North Carolina, USA (R.E.S., G.L.); Department of Neurosurgery, Barrow's Neurologic Institute, Phoenix, Arizona, USA (N.S.); Medical Oncology, City of Hope, Duarte, California, USA (J.P.); Department of Neurology, University of Alabama Birmingham, Birmingham, Alabama, USA (B.N.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota, USA (J.N.S.); Department of Medicine, Cleveland Clinic, Cleveland, Ohio, USA (D.P.); Department of Neurology, University of Virginia, Charlottesville, Virginia, USA (D.S.).ORCID 0000-0001-7798-5176
David SchiffDepartment of Oncology, Johns Hopkins University (S.A.G., R.R., C.H., K.C.S., C.R., J.O.B., D.O.K., P.S., T.P.); Food and Drug Administration (FDA), Silver Spring, Maryland, USA (A.B., E.D., E.W., L.S.L.P., T.P.); Department of Pharmaceutics, University of Minnesota, Minneapolis, Minnesota, USA (W.F.E.); Wake Forest School of Medicine, Winston-Salem, North Carolina, USA (R.E.S., G.L.); Department of Neurosurgery, Barrow's Neurologic Institute, Phoenix, Arizona, USA (N.S.); Medical Oncology, City of Hope, Duarte, California, USA (J.P.); Department of Neurology, University of Alabama Birmingham, Birmingham, Alabama, USA (B.N.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota, USA (J.N.S.); Department of Medicine, Cleveland Clinic, Cleveland, Ohio, USA (D.P.); Department of Neurology, University of Virginia, Charlottesville, Virginia, USA (D.S.).ORCID 0000-0002-1896-2502
Tatiana ProwellDepartment of Oncology, Johns Hopkins University (S.A.G., R.R., C.H., K.C.S., C.R., J.O.B., D.O.K., P.S., T.P.); Food and Drug Administration (FDA), Silver Spring, Maryland, USA (A.B., E.D., E.W., L.S.L.P., T.P.); Department of Pharmaceutics, University of Minnesota, Minneapolis, Minnesota, USA (W.F.E.); Wake Forest School of Medicine, Winston-Salem, North Carolina, USA (R.E.S., G.L.); Department of Neurosurgery, Barrow's Neurologic Institute, Phoenix, Arizona, USA (N.S.); Medical Oncology, City of Hope, Duarte, California, USA (J.P.); Department of Neurology, University of Alabama Birmingham, Birmingham, Alabama, USA (B.N.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota, USA (J.N.S.); Department of Medicine, Cleveland Clinic, Cleveland, Ohio, USA (D.P.); Department of Neurology, University of Virginia, Charlottesville, Virginia, USA (D.S.).ORCID 0000-0002-8065-3399
William F ElmquistDepartment of Oncology, Johns Hopkins University (S.A.G., R.R., C.H., K.C.S., C.R., J.O.B., D.O.K., P.S., T.P.); Food and Drug Administration (FDA), Silver Spring, Maryland, USA (A.B., E.D., E.W., L.S.L.P., T.P.); Department of Pharmaceutics, University of Minnesota, Minneapolis, Minnesota, USA (W.F.E.); Wake Forest School of Medicine, Winston-Salem, North Carolina, USA (R.E.S., G.L.); Department of Neurosurgery, Barrow's Neurologic Institute, Phoenix, Arizona, USA (N.S.); Medical Oncology, City of Hope, Duarte, California, USA (J.P.); Department of Neurology, University of Alabama Birmingham, Birmingham, Alabama, USA (B.N.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota, USA (J.N.S.); Department of Medicine, Cleveland Clinic, Cleveland, Ohio, USA (D.P.); Department of Neurology, University of Virginia, Charlottesville, Virginia, USA (D.S.).
Funding
NIH HHS UO1 CA13-7443
Abstract
Current assessments of brain permeability rely predominantly on drug delivery to contrast-enhancing tumor regions. However, substantial portions of central nervous system (CNS) tumors reside within non-enhancing brain (NEB), where drug concentrations frequently remain subtherapeutic. This collaborative Adult Brain Tumor Consortium and Food and Drug Administration workshop aimed to identify criteria for defining NEB permeability to accomplish 2 critical objectives: (1) allocate clinical trial resources toward agents achieving therapeutic NEB concentrations and (2) minimize systemic toxicity when CNS benefit is improbable. The workshop systematically evaluated permeability assessment modalities, including drug physicochemical properties, in vitro blood-brain barrier models, and penetration into cerebrospinal fluid and normal rodent brain. Methodological approaches to determine requisite NEB drug concentrations and approaches to measuring NEB pharmacokinetics and pharmacodynamics were examined. This culminated in developing the Non-Enhancing Brain Permeability Index (NEBPI), which assigns therapeutic agents to 3 categories: sufficiently permeable, insufficiently permeable, or impermeable. The NEBPI provides a standardized framework to assist investigators and regulatory agencies to evaluate NEB penetration before human efficacy studies are initiated for agents that require direct tumor contact. Assessing NEB drug penetration is critical to improving outcomes in CNS tumors and reducing the incidence of brain metastases in systemic malignancies.
Indexed as
Antineoplastic AgentsBlood-Brain BarrierBrainBrain NeoplasmsDrug DevelopmentAnimalsHumansPermeabilityAntineoplastic Agentsblood-brain barrierbrain cancerbrain permeabilitychemotherapytargeted therapies
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