Trial reportNeuro-oncology2014
Phase II study of sorafenib in children with recurrent or progressive low-grade astrocytomas.
Open access · bronzeAbstract readClinical Trial, Phase IIMulticenter Study
In one paragraph
Trial report in Neuro-oncology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 129 papers.
0numbers the graph read from it
0cells of the map it votes in
129citing papers in PubMed
13.5field-weighted citation impact, top 1% of its field
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.
Who cites it
129 citing papers in PubMed, 217 citations in OpenAlex.
- The type II RAF inhibitor tovorafenib in relapsed/refractory pediatric low-grade glioma: the phase 2 FIREFLY-1 trial.Nature medicine · 2024Trial
- Selumetinib in paediatric patients with BRAF-aberrant or neurofibromatosis type 1-associated recurrent, refractory, or progressive low-grade glioma: a multicentre, phase 2 trial.The Lancet. Oncology · 2019Trial
- Trial
- Tempered optimism: Advances in the precision medicine era for pediatric low-grade glioma.Neuro-oncology · 2026Review
- Decoding the Raf-Mek-Erk-Rsk pathway in prostate cancer: from molecular mechanisms to clinical opportunities.British journal of cancer · 2026Review
- Current Perspectives on Pediatric Low-Grade Gliomas: Focus on BRAF and MEK Inhibition.Brain tumor research and treatment · 2026Review
- Precision Medicine for Pediatric Glioma and NF1-Associated Tumors: The Role of Small Molecule Inhibitors.Current oncology (Toronto, Ont.) · 2025Review
- Molecular testing and targeting for solid tumors with CNS metastases.Journal of neuro-oncology · 2025Review
- Oncogenic gene fusions in cancer: from biology to therapy.Signal transduction and targeted therapy · 2025Review
- The state of targeted therapeutic pharmacological approaches in pediatric neurosurgery: report from the European Society for Pediatric Neurosurgery (ESPN) Consensus Conference 2024.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2025Review
- A Review of FDA-Approved Multi-Target Angiogenesis Drugs for Brain Tumor Therapy.International journal of molecular sciences · 2025Review
- Targeted Treatment of Pediatric Craniopharyngioma: Lesson Learnt After 20-Year Experience with Intracystic Interferon Alpha.Advances and technical standards in neurosurgery · 2025Article
- Targeted therapy in pediatric central nervous system tumors: a review from the National Pediatric Cancer Foundation.Frontiers in oncology · 2025Review
- Targeting the RAS/MAPK pathway in children with glioma.Journal of neuro-oncology · 2025Review
- Future perspective of targeted treatments in pediatric low-grade glioma (pLGG): the evolution of standard-of-care and challenges of a new era.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2024Review
- Low-grade glioma in children with neurofibromatosis type 1: surveillance, treatment indications, management, and future directions.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2024Review
- Molecular-targeted therapy for childhood low-grade glial and glioneuronal tumors.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2024Review
- Molecular markers for pediatric low-grade glioma.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2024Review
- Molecular Determinants for Photodynamic Therapy Resistance and Improved Photosensitizer Delivery in Glioma.International journal of molecular sciences · 2024Review
- Review
69 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors at 5 institutions in 2 countries.
Matthias A KarajannisNYU Comprehensive Neurofibromatosis Center, Division of Pediatric Hematology/Oncology, Department of Pediatrics and Laura and Isaac Perlmutter Cancer Center at NYU Langone Medical Center, New York, New York (M.A.K., G.L., A.M., J.C.A.); Division of Oncology, Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania (M.J.F., A.J.S.); Department of Radiology, NYU Langone Medical Center, New York, New York (S.S.M., M.C.B.); The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland (K.J.C.); Division of Pediatric Neurosurgery, Department of Neurosurgery, NYU Langone Medical Center, New York, New York (J.H.W., D.H.H.); Division of Biostatistics, Department of Population Health and The Laura and Isaac Perlmutter Cancer Center at NYU Langone Medical Center, New York, New York (J.D.G., T.H.); Department of Neurosurgery, Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania (A.C.R); Division of Hematology/Oncology, Children's Hospital Los Angeles, Los Angeles, California (G.D.); German Cancer Research Center and University Hospital, Heidelberg, Germany (D.T.W.J., A.K., S.M.P.); Division of Neuropathology, Department of Pathology, Johns Hopkins University, Baltimore, Maryland (C.G.E.); Division of Neuropathology, Department of Pathology, Department of Neurosurgery and Laura and Isaac Perlmutter Cancer Center at NYU Langone Medical Center, New York, New York (D.Z.).
Geneviève LegaultNYU Comprehensive Neurofibromatosis Center, Division of Pediatric Hematology/Oncology, Department of Pediatrics and Laura and Isaac Perlmutter Cancer Center at NYU Langone Medical Center, New York, New York (M.A.K., G.L., A.M., J.C.A.); Division of Oncology, Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania (M.J.F., A.J.S.); Department of Radiology, NYU Langone Medical Center, New York, New York (S.S.M., M.C.B.); The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland (K.J.C.); Division of Pediatric Neurosurgery, Department of Neurosurgery, NYU Langone Medical Center, New York, New York (J.H.W., D.H.H.); Division of Biostatistics, Department of Population Health and The Laura and Isaac Perlmutter Cancer Center at NYU Langone Medical Center, New York, New York (J.D.G., T.H.); Department of Neurosurgery, Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania (A.C.R); Division of Hematology/Oncology, Children's Hospital Los Angeles, Los Angeles, California (G.D.); German Cancer Research Center and University Hospital, Heidelberg, Germany (D.T.W.J., A.K., S.M.P.); Division of Neuropathology, Department of Pathology, Johns Hopkins University, Baltimore, Maryland (C.G.E.); Division of Neuropathology, Department of Pathology, Department of Neurosurgery and Laura and Isaac Perlmutter Cancer Center at NYU Langone Medical Center, New York, New York (D.Z.).
Michael J FisherNYU Comprehensive Neurofibromatosis Center, Division of Pediatric Hematology/Oncology, Department of Pediatrics and Laura and Isaac Perlmutter Cancer Center at NYU Langone Medical Center, New York, New York (M.A.K., G.L., A.M., J.C.A.); Division of Oncology, Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania (M.J.F., A.J.S.); Department of Radiology, NYU Langone Medical Center, New York, New York (S.S.M., M.C.B.); The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland (K.J.C.); Division of Pediatric Neurosurgery, Department of Neurosurgery, NYU Langone Medical Center, New York, New York (J.H.W., D.H.H.); Division of Biostatistics, Department of Population Health and The Laura and Isaac Perlmutter Cancer Center at NYU Langone Medical Center, New York, New York (J.D.G., T.H.); Department of Neurosurgery, Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania (A.C.R); Division of Hematology/Oncology, Children's Hospital Los Angeles, Los Angeles, California (G.D.); German Cancer Research Center and University Hospital, Heidelberg, Germany (D.T.W.J., A.K., S.M.P.); Division of Neuropathology, Department of Pathology, Johns Hopkins University, Baltimore, Maryland (C.G.E.); Division of Neuropathology, Department of Pathology, Department of Neurosurgery and Laura and Isaac Perlmutter Cancer Center at NYU Langone Medical Center, New York, New York (D.Z.).
Sarah S MillaNYU Comprehensive Neurofibromatosis Center, Division of Pediatric Hematology/Oncology, Department of Pediatrics and Laura and Isaac Perlmutter Cancer Center at NYU Langone Medical Center, New York, New York (M.A.K., G.L., A.M., J.C.A.); Division of Oncology, Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania (M.J.F., A.J.S.); Department of Radiology, NYU Langone Medical Center, New York, New York (S.S.M., M.C.B.); The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland (K.J.C.); Division of Pediatric Neurosurgery, Department of Neurosurgery, NYU Langone Medical Center, New York, New York (J.H.W., D.H.H.); Division of Biostatistics, Department of Population Health and The Laura and Isaac Perlmutter Cancer Center at NYU Langone Medical Center, New York, New York (J.D.G., T.H.); Department of Neurosurgery, Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania (A.C.R); Division of Hematology/Oncology, Children's Hospital Los Angeles, Los Angeles, California (G.D.); German Cancer Research Center and University Hospital, Heidelberg, Germany (D.T.W.J., A.K., S.M.P.); Division of Neuropathology, Department of Pathology, Johns Hopkins University, Baltimore, Maryland (C.G.E.); Division of Neuropathology, Department of Pathology, Department of Neurosurgery and Laura and Isaac Perlmutter Cancer Center at NYU Langone Medical Center, New York, New York (D.Z.).
Kenneth J CohenNYU Comprehensive Neurofibromatosis Center, Division of Pediatric Hematology/Oncology, Department of Pediatrics and Laura and Isaac Perlmutter Cancer Center at NYU Langone Medical Center, New York, New York (M.A.K., G.L., A.M., J.C.A.); Division of Oncology, Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania (M.J.F., A.J.S.); Department of Radiology, NYU Langone Medical Center, New York, New York (S.S.M., M.C.B.); The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland (K.J.C.); Division of Pediatric Neurosurgery, Department of Neurosurgery, NYU Langone Medical Center, New York, New York (J.H.W., D.H.H.); Division of Biostatistics, Department of Population Health and The Laura and Isaac Perlmutter Cancer Center at NYU Langone Medical Center, New York, New York (J.D.G., T.H.); Department of Neurosurgery, Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania (A.C.R); Division of Hematology/Oncology, Children's Hospital Los Angeles, Los Angeles, California (G.D.); German Cancer Research Center and University Hospital, Heidelberg, Germany (D.T.W.J., A.K., S.M.P.); Division of Neuropathology, Department of Pathology, Johns Hopkins University, Baltimore, Maryland (C.G.E.); Division of Neuropathology, Department of Pathology, Department of Neurosurgery and Laura and Isaac Perlmutter Cancer Center at NYU Langone Medical Center, New York, New York (D.Z.).
Jeffrey H WisoffNYU Comprehensive Neurofibromatosis Center, Division of Pediatric Hematology/Oncology, Department of Pediatrics and Laura and Isaac Perlmutter Cancer Center at NYU Langone Medical Center, New York, New York (M.A.K., G.L., A.M., J.C.A.); Division of Oncology, Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania (M.J.F., A.J.S.); Department of Radiology, NYU Langone Medical Center, New York, New York (S.S.M., M.C.B.); The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland (K.J.C.); Division of Pediatric Neurosurgery, Department of Neurosurgery, NYU Langone Medical Center, New York, New York (J.H.W., D.H.H.); Division of Biostatistics, Department of Population Health and The Laura and Isaac Perlmutter Cancer Center at NYU Langone Medical Center, New York, New York (J.D.G., T.H.); Department of Neurosurgery, Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania (A.C.R); Division of Hematology/Oncology, Children's Hospital Los Angeles, Los Angeles, California (G.D.); German Cancer Research Center and University Hospital, Heidelberg, Germany (D.T.W.J., A.K., S.M.P.); Division of Neuropathology, Department of Pathology, Johns Hopkins University, Baltimore, Maryland (C.G.E.); Division of Neuropathology, Department of Pathology, Department of Neurosurgery and Laura and Isaac Perlmutter Cancer Center at NYU Langone Medical Center, New York, New York (D.Z.).
David H HarterNYU Comprehensive Neurofibromatosis Center, Division of Pediatric Hematology/Oncology, Department of Pediatrics and Laura and Isaac Perlmutter Cancer Center at NYU Langone Medical Center, New York, New York (M.A.K., G.L., A.M., J.C.A.); Division of Oncology, Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania (M.J.F., A.J.S.); Department of Radiology, NYU Langone Medical Center, New York, New York (S.S.M., M.C.B.); The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland (K.J.C.); Division of Pediatric Neurosurgery, Department of Neurosurgery, NYU Langone Medical Center, New York, New York (J.H.W., D.H.H.); Division of Biostatistics, Department of Population Health and The Laura and Isaac Perlmutter Cancer Center at NYU Langone Medical Center, New York, New York (J.D.G., T.H.); Department of Neurosurgery, Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania (A.C.R); Division of Hematology/Oncology, Children's Hospital Los Angeles, Los Angeles, California (G.D.); German Cancer Research Center and University Hospital, Heidelberg, Germany (D.T.W.J., A.K., S.M.P.); Division of Neuropathology, Department of Pathology, Johns Hopkins University, Baltimore, Maryland (C.G.E.); Division of Neuropathology, Department of Pathology, Department of Neurosurgery and Laura and Isaac Perlmutter Cancer Center at NYU Langone Medical Center, New York, New York (D.Z.).
Judith D GoldbergNYU Comprehensive Neurofibromatosis Center, Division of Pediatric Hematology/Oncology, Department of Pediatrics and Laura and Isaac Perlmutter Cancer Center at NYU Langone Medical Center, New York, New York (M.A.K., G.L., A.M., J.C.A.); Division of Oncology, Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania (M.J.F., A.J.S.); Department of Radiology, NYU Langone Medical Center, New York, New York (S.S.M., M.C.B.); The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland (K.J.C.); Division of Pediatric Neurosurgery, Department of Neurosurgery, NYU Langone Medical Center, New York, New York (J.H.W., D.H.H.); Division of Biostatistics, Department of Population Health and The Laura and Isaac Perlmutter Cancer Center at NYU Langone Medical Center, New York, New York (J.D.G., T.H.); Department of Neurosurgery, Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania (A.C.R); Division of Hematology/Oncology, Children's Hospital Los Angeles, Los Angeles, California (G.D.); German Cancer Research Center and University Hospital, Heidelberg, Germany (D.T.W.J., A.K., S.M.P.); Division of Neuropathology, Department of Pathology, Johns Hopkins University, Baltimore, Maryland (C.G.E.); Division of Neuropathology, Department of Pathology, Department of Neurosurgery and Laura and Isaac Perlmutter Cancer Center at NYU Langone Medical Center, New York, New York (D.Z.).
Tsivia HochmanNYU Comprehensive Neurofibromatosis Center, Division of Pediatric Hematology/Oncology, Department of Pediatrics and Laura and Isaac Perlmutter Cancer Center at NYU Langone Medical Center, New York, New York (M.A.K., G.L., A.M., J.C.A.); Division of Oncology, Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania (M.J.F., A.J.S.); Department of Radiology, NYU Langone Medical Center, New York, New York (S.S.M., M.C.B.); The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland (K.J.C.); Division of Pediatric Neurosurgery, Department of Neurosurgery, NYU Langone Medical Center, New York, New York (J.H.W., D.H.H.); Division of Biostatistics, Department of Population Health and The Laura and Isaac Perlmutter Cancer Center at NYU Langone Medical Center, New York, New York (J.D.G., T.H.); Department of Neurosurgery, Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania (A.C.R); Division of Hematology/Oncology, Children's Hospital Los Angeles, Los Angeles, California (G.D.); German Cancer Research Center and University Hospital, Heidelberg, Germany (D.T.W.J., A.K., S.M.P.); Division of Neuropathology, Department of Pathology, Johns Hopkins University, Baltimore, Maryland (C.G.E.); Division of Neuropathology, Department of Pathology, Department of Neurosurgery and Laura and Isaac Perlmutter Cancer Center at NYU Langone Medical Center, New York, New York (D.Z.).
Amanda MerkelsonNYU Comprehensive Neurofibromatosis Center, Division of Pediatric Hematology/Oncology, Department of Pediatrics and Laura and Isaac Perlmutter Cancer Center at NYU Langone Medical Center, New York, New York (M.A.K., G.L., A.M., J.C.A.); Division of Oncology, Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania (M.J.F., A.J.S.); Department of Radiology, NYU Langone Medical Center, New York, New York (S.S.M., M.C.B.); The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland (K.J.C.); Division of Pediatric Neurosurgery, Department of Neurosurgery, NYU Langone Medical Center, New York, New York (J.H.W., D.H.H.); Division of Biostatistics, Department of Population Health and The Laura and Isaac Perlmutter Cancer Center at NYU Langone Medical Center, New York, New York (J.D.G., T.H.); Department of Neurosurgery, Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania (A.C.R); Division of Hematology/Oncology, Children's Hospital Los Angeles, Los Angeles, California (G.D.); German Cancer Research Center and University Hospital, Heidelberg, Germany (D.T.W.J., A.K., S.M.P.); Division of Neuropathology, Department of Pathology, Johns Hopkins University, Baltimore, Maryland (C.G.E.); Division of Neuropathology, Department of Pathology, Department of Neurosurgery and Laura and Isaac Perlmutter Cancer Center at NYU Langone Medical Center, New York, New York (D.Z.).
Michael C BloomNYU Comprehensive Neurofibromatosis Center, Division of Pediatric Hematology/Oncology, Department of Pediatrics and Laura and Isaac Perlmutter Cancer Center at NYU Langone Medical Center, New York, New York (M.A.K., G.L., A.M., J.C.A.); Division of Oncology, Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania (M.J.F., A.J.S.); Department of Radiology, NYU Langone Medical Center, New York, New York (S.S.M., M.C.B.); The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland (K.J.C.); Division of Pediatric Neurosurgery, Department of Neurosurgery, NYU Langone Medical Center, New York, New York (J.H.W., D.H.H.); Division of Biostatistics, Department of Population Health and The Laura and Isaac Perlmutter Cancer Center at NYU Langone Medical Center, New York, New York (J.D.G., T.H.); Department of Neurosurgery, Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania (A.C.R); Division of Hematology/Oncology, Children's Hospital Los Angeles, Los Angeles, California (G.D.); German Cancer Research Center and University Hospital, Heidelberg, Germany (D.T.W.J., A.K., S.M.P.); Division of Neuropathology, Department of Pathology, Johns Hopkins University, Baltimore, Maryland (C.G.E.); Division of Neuropathology, Department of Pathology, Department of Neurosurgery and Laura and Isaac Perlmutter Cancer Center at NYU Langone Medical Center, New York, New York (D.Z.).
Angela J SievertNYU Comprehensive Neurofibromatosis Center, Division of Pediatric Hematology/Oncology, Department of Pediatrics and Laura and Isaac Perlmutter Cancer Center at NYU Langone Medical Center, New York, New York (M.A.K., G.L., A.M., J.C.A.); Division of Oncology, Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania (M.J.F., A.J.S.); Department of Radiology, NYU Langone Medical Center, New York, New York (S.S.M., M.C.B.); The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland (K.J.C.); Division of Pediatric Neurosurgery, Department of Neurosurgery, NYU Langone Medical Center, New York, New York (J.H.W., D.H.H.); Division of Biostatistics, Department of Population Health and The Laura and Isaac Perlmutter Cancer Center at NYU Langone Medical Center, New York, New York (J.D.G., T.H.); Department of Neurosurgery, Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania (A.C.R); Division of Hematology/Oncology, Children's Hospital Los Angeles, Los Angeles, California (G.D.); German Cancer Research Center and University Hospital, Heidelberg, Germany (D.T.W.J., A.K., S.M.P.); Division of Neuropathology, Department of Pathology, Johns Hopkins University, Baltimore, Maryland (C.G.E.); Division of Neuropathology, Department of Pathology, Department of Neurosurgery and Laura and Isaac Perlmutter Cancer Center at NYU Langone Medical Center, New York, New York (D.Z.).
Adam C ResnickNYU Comprehensive Neurofibromatosis Center, Division of Pediatric Hematology/Oncology, Department of Pediatrics and Laura and Isaac Perlmutter Cancer Center at NYU Langone Medical Center, New York, New York (M.A.K., G.L., A.M., J.C.A.); Division of Oncology, Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania (M.J.F., A.J.S.); Department of Radiology, NYU Langone Medical Center, New York, New York (S.S.M., M.C.B.); The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland (K.J.C.); Division of Pediatric Neurosurgery, Department of Neurosurgery, NYU Langone Medical Center, New York, New York (J.H.W., D.H.H.); Division of Biostatistics, Department of Population Health and The Laura and Isaac Perlmutter Cancer Center at NYU Langone Medical Center, New York, New York (J.D.G., T.H.); Department of Neurosurgery, Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania (A.C.R); Division of Hematology/Oncology, Children's Hospital Los Angeles, Los Angeles, California (G.D.); German Cancer Research Center and University Hospital, Heidelberg, Germany (D.T.W.J., A.K., S.M.P.); Division of Neuropathology, Department of Pathology, Johns Hopkins University, Baltimore, Maryland (C.G.E.); Division of Neuropathology, Department of Pathology, Department of Neurosurgery and Laura and Isaac Perlmutter Cancer Center at NYU Langone Medical Center, New York, New York (D.Z.).
Girish DhallNYU Comprehensive Neurofibromatosis Center, Division of Pediatric Hematology/Oncology, Department of Pediatrics and Laura and Isaac Perlmutter Cancer Center at NYU Langone Medical Center, New York, New York (M.A.K., G.L., A.M., J.C.A.); Division of Oncology, Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania (M.J.F., A.J.S.); Department of Radiology, NYU Langone Medical Center, New York, New York (S.S.M., M.C.B.); The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland (K.J.C.); Division of Pediatric Neurosurgery, Department of Neurosurgery, NYU Langone Medical Center, New York, New York (J.H.W., D.H.H.); Division of Biostatistics, Department of Population Health and The Laura and Isaac Perlmutter Cancer Center at NYU Langone Medical Center, New York, New York (J.D.G., T.H.); Department of Neurosurgery, Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania (A.C.R); Division of Hematology/Oncology, Children's Hospital Los Angeles, Los Angeles, California (G.D.); German Cancer Research Center and University Hospital, Heidelberg, Germany (D.T.W.J., A.K., S.M.P.); Division of Neuropathology, Department of Pathology, Johns Hopkins University, Baltimore, Maryland (C.G.E.); Division of Neuropathology, Department of Pathology, Department of Neurosurgery and Laura and Isaac Perlmutter Cancer Center at NYU Langone Medical Center, New York, New York (D.Z.).
David T W JonesNYU Comprehensive Neurofibromatosis Center, Division of Pediatric Hematology/Oncology, Department of Pediatrics and Laura and Isaac Perlmutter Cancer Center at NYU Langone Medical Center, New York, New York (M.A.K., G.L., A.M., J.C.A.); Division of Oncology, Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania (M.J.F., A.J.S.); Department of Radiology, NYU Langone Medical Center, New York, New York (S.S.M., M.C.B.); The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland (K.J.C.); Division of Pediatric Neurosurgery, Department of Neurosurgery, NYU Langone Medical Center, New York, New York (J.H.W., D.H.H.); Division of Biostatistics, Department of Population Health and The Laura and Isaac Perlmutter Cancer Center at NYU Langone Medical Center, New York, New York (J.D.G., T.H.); Department of Neurosurgery, Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania (A.C.R); Division of Hematology/Oncology, Children's Hospital Los Angeles, Los Angeles, California (G.D.); German Cancer Research Center and University Hospital, Heidelberg, Germany (D.T.W.J., A.K., S.M.P.); Division of Neuropathology, Department of Pathology, Johns Hopkins University, Baltimore, Maryland (C.G.E.); Division of Neuropathology, Department of Pathology, Department of Neurosurgery and Laura and Isaac Perlmutter Cancer Center at NYU Langone Medical Center, New York, New York (D.Z.).
Andrey KorshunovNYU Comprehensive Neurofibromatosis Center, Division of Pediatric Hematology/Oncology, Department of Pediatrics and Laura and Isaac Perlmutter Cancer Center at NYU Langone Medical Center, New York, New York (M.A.K., G.L., A.M., J.C.A.); Division of Oncology, Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania (M.J.F., A.J.S.); Department of Radiology, NYU Langone Medical Center, New York, New York (S.S.M., M.C.B.); The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland (K.J.C.); Division of Pediatric Neurosurgery, Department of Neurosurgery, NYU Langone Medical Center, New York, New York (J.H.W., D.H.H.); Division of Biostatistics, Department of Population Health and The Laura and Isaac Perlmutter Cancer Center at NYU Langone Medical Center, New York, New York (J.D.G., T.H.); Department of Neurosurgery, Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania (A.C.R); Division of Hematology/Oncology, Children's Hospital Los Angeles, Los Angeles, California (G.D.); German Cancer Research Center and University Hospital, Heidelberg, Germany (D.T.W.J., A.K., S.M.P.); Division of Neuropathology, Department of Pathology, Johns Hopkins University, Baltimore, Maryland (C.G.E.); Division of Neuropathology, Department of Pathology, Department of Neurosurgery and Laura and Isaac Perlmutter Cancer Center at NYU Langone Medical Center, New York, New York (D.Z.).
Stefan M PfisterNYU Comprehensive Neurofibromatosis Center, Division of Pediatric Hematology/Oncology, Department of Pediatrics and Laura and Isaac Perlmutter Cancer Center at NYU Langone Medical Center, New York, New York (M.A.K., G.L., A.M., J.C.A.); Division of Oncology, Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania (M.J.F., A.J.S.); Department of Radiology, NYU Langone Medical Center, New York, New York (S.S.M., M.C.B.); The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland (K.J.C.); Division of Pediatric Neurosurgery, Department of Neurosurgery, NYU Langone Medical Center, New York, New York (J.H.W., D.H.H.); Division of Biostatistics, Department of Population Health and The Laura and Isaac Perlmutter Cancer Center at NYU Langone Medical Center, New York, New York (J.D.G., T.H.); Department of Neurosurgery, Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania (A.C.R); Division of Hematology/Oncology, Children's Hospital Los Angeles, Los Angeles, California (G.D.); German Cancer Research Center and University Hospital, Heidelberg, Germany (D.T.W.J., A.K., S.M.P.); Division of Neuropathology, Department of Pathology, Johns Hopkins University, Baltimore, Maryland (C.G.E.); Division of Neuropathology, Department of Pathology, Department of Neurosurgery and Laura and Isaac Perlmutter Cancer Center at NYU Langone Medical Center, New York, New York (D.Z.).
Charles G EberhartNYU Comprehensive Neurofibromatosis Center, Division of Pediatric Hematology/Oncology, Department of Pediatrics and Laura and Isaac Perlmutter Cancer Center at NYU Langone Medical Center, New York, New York (M.A.K., G.L., A.M., J.C.A.); Division of Oncology, Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania (M.J.F., A.J.S.); Department of Radiology, NYU Langone Medical Center, New York, New York (S.S.M., M.C.B.); The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland (K.J.C.); Division of Pediatric Neurosurgery, Department of Neurosurgery, NYU Langone Medical Center, New York, New York (J.H.W., D.H.H.); Division of Biostatistics, Department of Population Health and The Laura and Isaac Perlmutter Cancer Center at NYU Langone Medical Center, New York, New York (J.D.G., T.H.); Department of Neurosurgery, Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania (A.C.R); Division of Hematology/Oncology, Children's Hospital Los Angeles, Los Angeles, California (G.D.); German Cancer Research Center and University Hospital, Heidelberg, Germany (D.T.W.J., A.K., S.M.P.); Division of Neuropathology, Department of Pathology, Johns Hopkins University, Baltimore, Maryland (C.G.E.); Division of Neuropathology, Department of Pathology, Department of Neurosurgery and Laura and Isaac Perlmutter Cancer Center at NYU Langone Medical Center, New York, New York (D.Z.).
David ZagzagNYU Comprehensive Neurofibromatosis Center, Division of Pediatric Hematology/Oncology, Department of Pediatrics and Laura and Isaac Perlmutter Cancer Center at NYU Langone Medical Center, New York, New York (M.A.K., G.L., A.M., J.C.A.); Division of Oncology, Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania (M.J.F., A.J.S.); Department of Radiology, NYU Langone Medical Center, New York, New York (S.S.M., M.C.B.); The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland (K.J.C.); Division of Pediatric Neurosurgery, Department of Neurosurgery, NYU Langone Medical Center, New York, New York (J.H.W., D.H.H.); Division of Biostatistics, Department of Population Health and The Laura and Isaac Perlmutter Cancer Center at NYU Langone Medical Center, New York, New York (J.D.G., T.H.); Department of Neurosurgery, Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania (A.C.R); Division of Hematology/Oncology, Children's Hospital Los Angeles, Los Angeles, California (G.D.); German Cancer Research Center and University Hospital, Heidelberg, Germany (D.T.W.J., A.K., S.M.P.); Division of Neuropathology, Department of Pathology, Johns Hopkins University, Baltimore, Maryland (C.G.E.); Division of Neuropathology, Department of Pathology, Department of Neurosurgery and Laura and Isaac Perlmutter Cancer Center at NYU Langone Medical Center, New York, New York (D.Z.).
Jeffrey C AllenNYU Comprehensive Neurofibromatosis Center, Division of Pediatric Hematology/Oncology, Department of Pediatrics and Laura and Isaac Perlmutter Cancer Center at NYU Langone Medical Center, New York, New York (M.A.K., G.L., A.M., J.C.A.); Division of Oncology, Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania (M.J.F., A.J.S.); Department of Radiology, NYU Langone Medical Center, New York, New York (S.S.M., M.C.B.); The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland (K.J.C.); Division of Pediatric Neurosurgery, Department of Neurosurgery, NYU Langone Medical Center, New York, New York (J.H.W., D.H.H.); Division of Biostatistics, Department of Population Health and The Laura and Isaac Perlmutter Cancer Center at NYU Langone Medical Center, New York, New York (J.D.G., T.H.); Department of Neurosurgery, Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania (A.C.R); Division of Hematology/Oncology, Children's Hospital Los Angeles, Los Angeles, California (G.D.); German Cancer Research Center and University Hospital, Heidelberg, Germany (D.T.W.J., A.K., S.M.P.); Division of Neuropathology, Department of Pathology, Johns Hopkins University, Baltimore, Maryland (C.G.E.); Division of Neuropathology, Department of Pathology, Department of Neurosurgery and Laura and Isaac Perlmutter Cancer Center at NYU Langone Medical Center, New York, New York (D.Z.).
Johns Hopkins University · USNYU Langone Health · USChildren's Hospital of Los Angeles · USChildren's Hospital of Philadelphia · USNew York University · US
Funding
Vaccine FacilityP30CA016087 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI ADRIANA HEGUY · 1985 to 2026
$83.1MInstitutional Clinical and Translational Science AwardUL1TR000003 · NCATS · UNIVERSITY OF PENNSYLVANIA · PI FITZGERALD, GARRET A · 2012 to 2015
$38.9MInstitutional Clinical and Translational Science AwardUL1TR000038 · NCATS · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI CRONSTEIN, BRUCE NEIL, HOCHMAN, JUDITH S · 2012 to 2014
$16.8MNCATS NIH HHS UL1 TR000003NCATS NIH HHS UL1TR000003NCATS NIH HHS UL1TR000038NCI NIH HHS 5P30CA016087NCI NIH HHS P30 CA016087
Abstract
backgroundActivation of the RAS-RAF-MEK-ERK signaling pathway is thought to be the key driver of pediatric low-grade astrocytoma (PLGA) growth. Sorafenib is a multikinase inhibitor targeting BRAF, VEGFR, PDGFR, and c-kit. This multicenter phase II study was conducted to determine the response rate to sorafenib in patients with recurrent or progressive PLGA.
methodsKey eligibility criteria included age ≥ 2 years, progressive PLGA evaluable on MRI, and at least one prior chemotherapy treatment. Sorafenib was administered twice daily at 200 mg/m(2)/dose (maximum of 400 mg/dose) in continuous 28-day cycles. MRI, including 3-dimensional volumetric tumor analysis, was performed every 12 weeks. BRAF molecular testing was performed on tumor tissue when available.
resultsEleven patients, including 3 with neurofibromatosis type 1 (NF1), were evaluable for response; 5 tested positive for BRAF duplication. Nine patients (82%) came off trial due to radiological tumor progression after 2 or 3 cycles, including 3 patients with confirmed BRAF duplication. Median time to progression was 2.8 months (95% CI, 2.1-31.0 months). Enrollment was terminated early due to this rapid and unexpectedly high progression rate. Tumor tissue obtained from 4 patients after termination of the study showed viable pilocytic or pilomyxoid astrocytoma.
conclusionsSorafenib produced unexpected and unprecedented acceleration of tumor growth in children with PLGA, irrespective of NF1 or tumor BRAF status. In vitro studies with sorafenib indicate that this effect is likely related to paradoxical ERK activation. Close monitoring for early tumor progression should be included in trials of novel agents that modulate signal transduction.
Indexed as
AdolescentAnimalsAntineoplastic AgentsAstrocytomaBrain NeoplasmsChild, PreschoolFemaleHumansKaplan-Meier EstimateMagnetic Resonance ImagingMaleMAP Kinase Signaling SystemMiceNiacinamideNIH 3T3 CellsPhenylurea CompoundsAntineoplastic AgentsNiacinamidePhenylurea CompoundsProtein Kinase InhibitorsSorafeniblow-grade gliomapediatric low-grade astrocytomaphase II trialsorafenib
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.