Trial reportJournal of clinical oncology : official journal of the American Society of Clinical Oncology2015
Vismodegib Exerts Targeted Efficacy Against Recurrent Sonic Hedgehog-Subgroup Medulloblastoma: Results From Phase II Pediatric Brain Tumor Consortium Studies PBTC-025B and PBTC-032.
Abstract readClinical Trial, Phase II
In one paragraph
Trial report in Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 254 papers, 4 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
254citing papers in PubMed, 4 pooled it
–field-weighted citation impact
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
254 citing papers in PubMed, 4 syntheses or guidelines pooled it.
- Diagnostic and predictive molecular biomarkers in brain tumors across the lifespan: an age-stratified consensus statement.Journal of neuro-oncology · 2025Pooled it
- European Association of Neuro-Oncology guideline on molecular testing of meningiomas for targeted therapy selection.Neuro-oncology · 2025Guideline
- SEOM clinical guideline for management of adult medulloblastoma (2020).Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2021Guideline
- Phase I and phase II sonidegib and vismodegib clinical trials for the treatment of paediatric and adult MB patients: a systemic review and meta-analysis.Acta neuropathologica communications · 2019Pooled it
- Molecularly matched targeted therapies plus radiotherapy in glioblastoma: the phase 1/2a NNature medicine · 2025Trial
- MEVITEM-a phase I/II trial of vismodegib + temozolomide vs temozolomide in patients with recurrent/refractory medulloblastoma with Sonic Hedgehog pathway activation.Neuro-oncology · 2021Trial
- Bridging pediatric and adult neuro-oncology: Insights into adolescents and young adults (AYA) central nervous system tumors.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Review
- Age-Dependent Toxicity Patterns in Medulloblastoma: A Comparative Analysis of Treatment-Related Adverse Events Between Pediatric and Adult Populations.Journal of clinical medicine · 2026Article
- From developmental origins to relapse: molecular and therapeutic insights in medulloblastoma.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2026Review
- Context-dependent synthetic lethality - an emerging precision therapeutic approach.Nature reviews. Cancer · 2026Review
- Identification of Markers on the Basis of Transcriptomic Analysis for Molecular Assignment of Medulloblastoma.International journal of molecular sciences · 2026Article
- A 10-year-long ongoing complete response to vismodegib as first-line treatment in adult metastatic medulloblastoma.Acta oncologica (Stockholm, Sweden) · 2026Article
- Brain-Targeted Delivery of Phenformin Using Phospholipid and Non-Phospholipid Vesicles for SHH Medulloblastoma.Nanomaterials (Basel, Switzerland) · 2026Article
- Targeted therapies in adolescent and young adult patients with central nervous system tumors.Neuro-oncology advances · 2026Review
- From blunt tools to bullseyes: The impact of targeted therapy in pediatric neuro-oncology.Neuro-oncology advances · 2026Review
- The future of targeted therapies for pediatric central nervous system tumors.Neuro-oncology advances · 2026Review
- Real-world management and long-term outcomes in adolescent, young adult, and adult medulloblastoma: Experience from a monocentric series with multimodal and targeted approaches.Neuro-oncology practice · 2026Article
- Treatment strategies for relapsed medulloblastoma in the pediatric population: illustrative case.Journal of neurosurgery. Case lessons · 2026Article
- Medulloblastoma: Current Standard of Care and Future Treatment Opportunities.Paediatric drugs · 2026Review
- Precision medicine directed therapy enabling long-term survival in medulloblastoma: a case report.Frontiers in oncology · 2026Article
194 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
23 authors.
Giles W RobinsonGiles W. Robinson, Brent A. Orr, Gang Wu, Tong Lin, Ibrahim Qaddoumi, Sue C. Kaste, Michael Rusch, Sariah J. Allen, Arzu Onar-Thomas, Clinton F. Stewart, James M. Boyett, Richard J. Gilbertson, David W. Ellison, and Amar Gajjar, St Jude Children's Research Hospital, Memphis, TN; Sridharan Gururangan and Annick Desjardins, Duke University Medical Center, Durham, NC; Roger J. Packer, Children's National Medical Center, Washington, DC; Stewart Goldman, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL; Michael D. Prados, University of California San Francisco, San Francisco, CA; Murali Chintagumpala, Texas Children's Cancer Center, Houston, TX; Naoko Takebe, National Cancer Institute, Bethesda, MD; Maryam Fouladi, Cincinnati Children's Hospital, Cincinnati, OH; and Tom Curran, Children's Hospital of Philadelphia, Philadelphia, PA. giles.robinson@stjude.org.
Brent A OrrGiles W. Robinson, Brent A. Orr, Gang Wu, Tong Lin, Ibrahim Qaddoumi, Sue C. Kaste, Michael Rusch, Sariah J. Allen, Arzu Onar-Thomas, Clinton F. Stewart, James M. Boyett, Richard J. Gilbertson, David W. Ellison, and Amar Gajjar, St Jude Children's Research Hospital, Memphis, TN; Sridharan Gururangan and Annick Desjardins, Duke University Medical Center, Durham, NC; Roger J. Packer, Children's National Medical Center, Washington, DC; Stewart Goldman, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL; Michael D. Prados, University of California San Francisco, San Francisco, CA; Murali Chintagumpala, Texas Children's Cancer Center, Houston, TX; Naoko Takebe, National Cancer Institute, Bethesda, MD; Maryam Fouladi, Cincinnati Children's Hospital, Cincinnati, OH; and Tom Curran, Children's Hospital of Philadelphia, Philadelphia, PA.
Gang WuGiles W. Robinson, Brent A. Orr, Gang Wu, Tong Lin, Ibrahim Qaddoumi, Sue C. Kaste, Michael Rusch, Sariah J. Allen, Arzu Onar-Thomas, Clinton F. Stewart, James M. Boyett, Richard J. Gilbertson, David W. Ellison, and Amar Gajjar, St Jude Children's Research Hospital, Memphis, TN; Sridharan Gururangan and Annick Desjardins, Duke University Medical Center, Durham, NC; Roger J. Packer, Children's National Medical Center, Washington, DC; Stewart Goldman, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL; Michael D. Prados, University of California San Francisco, San Francisco, CA; Murali Chintagumpala, Texas Children's Cancer Center, Houston, TX; Naoko Takebe, National Cancer Institute, Bethesda, MD; Maryam Fouladi, Cincinnati Children's Hospital, Cincinnati, OH; and Tom Curran, Children's Hospital of Philadelphia, Philadelphia, PA.
Sridharan GururanganGiles W. Robinson, Brent A. Orr, Gang Wu, Tong Lin, Ibrahim Qaddoumi, Sue C. Kaste, Michael Rusch, Sariah J. Allen, Arzu Onar-Thomas, Clinton F. Stewart, James M. Boyett, Richard J. Gilbertson, David W. Ellison, and Amar Gajjar, St Jude Children's Research Hospital, Memphis, TN; Sridharan Gururangan and Annick Desjardins, Duke University Medical Center, Durham, NC; Roger J. Packer, Children's National Medical Center, Washington, DC; Stewart Goldman, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL; Michael D. Prados, University of California San Francisco, San Francisco, CA; Murali Chintagumpala, Texas Children's Cancer Center, Houston, TX; Naoko Takebe, National Cancer Institute, Bethesda, MD; Maryam Fouladi, Cincinnati Children's Hospital, Cincinnati, OH; and Tom Curran, Children's Hospital of Philadelphia, Philadelphia, PA.
Tong LinGiles W. Robinson, Brent A. Orr, Gang Wu, Tong Lin, Ibrahim Qaddoumi, Sue C. Kaste, Michael Rusch, Sariah J. Allen, Arzu Onar-Thomas, Clinton F. Stewart, James M. Boyett, Richard J. Gilbertson, David W. Ellison, and Amar Gajjar, St Jude Children's Research Hospital, Memphis, TN; Sridharan Gururangan and Annick Desjardins, Duke University Medical Center, Durham, NC; Roger J. Packer, Children's National Medical Center, Washington, DC; Stewart Goldman, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL; Michael D. Prados, University of California San Francisco, San Francisco, CA; Murali Chintagumpala, Texas Children's Cancer Center, Houston, TX; Naoko Takebe, National Cancer Institute, Bethesda, MD; Maryam Fouladi, Cincinnati Children's Hospital, Cincinnati, OH; and Tom Curran, Children's Hospital of Philadelphia, Philadelphia, PA.
Ibrahim QaddoumiGiles W. Robinson, Brent A. Orr, Gang Wu, Tong Lin, Ibrahim Qaddoumi, Sue C. Kaste, Michael Rusch, Sariah J. Allen, Arzu Onar-Thomas, Clinton F. Stewart, James M. Boyett, Richard J. Gilbertson, David W. Ellison, and Amar Gajjar, St Jude Children's Research Hospital, Memphis, TN; Sridharan Gururangan and Annick Desjardins, Duke University Medical Center, Durham, NC; Roger J. Packer, Children's National Medical Center, Washington, DC; Stewart Goldman, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL; Michael D. Prados, University of California San Francisco, San Francisco, CA; Murali Chintagumpala, Texas Children's Cancer Center, Houston, TX; Naoko Takebe, National Cancer Institute, Bethesda, MD; Maryam Fouladi, Cincinnati Children's Hospital, Cincinnati, OH; and Tom Curran, Children's Hospital of Philadelphia, Philadelphia, PA.
Roger J PackerGiles W. Robinson, Brent A. Orr, Gang Wu, Tong Lin, Ibrahim Qaddoumi, Sue C. Kaste, Michael Rusch, Sariah J. Allen, Arzu Onar-Thomas, Clinton F. Stewart, James M. Boyett, Richard J. Gilbertson, David W. Ellison, and Amar Gajjar, St Jude Children's Research Hospital, Memphis, TN; Sridharan Gururangan and Annick Desjardins, Duke University Medical Center, Durham, NC; Roger J. Packer, Children's National Medical Center, Washington, DC; Stewart Goldman, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL; Michael D. Prados, University of California San Francisco, San Francisco, CA; Murali Chintagumpala, Texas Children's Cancer Center, Houston, TX; Naoko Takebe, National Cancer Institute, Bethesda, MD; Maryam Fouladi, Cincinnati Children's Hospital, Cincinnati, OH; and Tom Curran, Children's Hospital of Philadelphia, Philadelphia, PA.
Stewart GoldmanGiles W. Robinson, Brent A. Orr, Gang Wu, Tong Lin, Ibrahim Qaddoumi, Sue C. Kaste, Michael Rusch, Sariah J. Allen, Arzu Onar-Thomas, Clinton F. Stewart, James M. Boyett, Richard J. Gilbertson, David W. Ellison, and Amar Gajjar, St Jude Children's Research Hospital, Memphis, TN; Sridharan Gururangan and Annick Desjardins, Duke University Medical Center, Durham, NC; Roger J. Packer, Children's National Medical Center, Washington, DC; Stewart Goldman, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL; Michael D. Prados, University of California San Francisco, San Francisco, CA; Murali Chintagumpala, Texas Children's Cancer Center, Houston, TX; Naoko Takebe, National Cancer Institute, Bethesda, MD; Maryam Fouladi, Cincinnati Children's Hospital, Cincinnati, OH; and Tom Curran, Children's Hospital of Philadelphia, Philadelphia, PA.
Michael D PradosGiles W. Robinson, Brent A. Orr, Gang Wu, Tong Lin, Ibrahim Qaddoumi, Sue C. Kaste, Michael Rusch, Sariah J. Allen, Arzu Onar-Thomas, Clinton F. Stewart, James M. Boyett, Richard J. Gilbertson, David W. Ellison, and Amar Gajjar, St Jude Children's Research Hospital, Memphis, TN; Sridharan Gururangan and Annick Desjardins, Duke University Medical Center, Durham, NC; Roger J. Packer, Children's National Medical Center, Washington, DC; Stewart Goldman, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL; Michael D. Prados, University of California San Francisco, San Francisco, CA; Murali Chintagumpala, Texas Children's Cancer Center, Houston, TX; Naoko Takebe, National Cancer Institute, Bethesda, MD; Maryam Fouladi, Cincinnati Children's Hospital, Cincinnati, OH; and Tom Curran, Children's Hospital of Philadelphia, Philadelphia, PA.
Annick DesjardinsGiles W. Robinson, Brent A. Orr, Gang Wu, Tong Lin, Ibrahim Qaddoumi, Sue C. Kaste, Michael Rusch, Sariah J. Allen, Arzu Onar-Thomas, Clinton F. Stewart, James M. Boyett, Richard J. Gilbertson, David W. Ellison, and Amar Gajjar, St Jude Children's Research Hospital, Memphis, TN; Sridharan Gururangan and Annick Desjardins, Duke University Medical Center, Durham, NC; Roger J. Packer, Children's National Medical Center, Washington, DC; Stewart Goldman, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL; Michael D. Prados, University of California San Francisco, San Francisco, CA; Murali Chintagumpala, Texas Children's Cancer Center, Houston, TX; Naoko Takebe, National Cancer Institute, Bethesda, MD; Maryam Fouladi, Cincinnati Children's Hospital, Cincinnati, OH; and Tom Curran, Children's Hospital of Philadelphia, Philadelphia, PA.
Murali ChintagumpalaGiles W. Robinson, Brent A. Orr, Gang Wu, Tong Lin, Ibrahim Qaddoumi, Sue C. Kaste, Michael Rusch, Sariah J. Allen, Arzu Onar-Thomas, Clinton F. Stewart, James M. Boyett, Richard J. Gilbertson, David W. Ellison, and Amar Gajjar, St Jude Children's Research Hospital, Memphis, TN; Sridharan Gururangan and Annick Desjardins, Duke University Medical Center, Durham, NC; Roger J. Packer, Children's National Medical Center, Washington, DC; Stewart Goldman, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL; Michael D. Prados, University of California San Francisco, San Francisco, CA; Murali Chintagumpala, Texas Children's Cancer Center, Houston, TX; Naoko Takebe, National Cancer Institute, Bethesda, MD; Maryam Fouladi, Cincinnati Children's Hospital, Cincinnati, OH; and Tom Curran, Children's Hospital of Philadelphia, Philadelphia, PA.
Naoko TakebeGiles W. Robinson, Brent A. Orr, Gang Wu, Tong Lin, Ibrahim Qaddoumi, Sue C. Kaste, Michael Rusch, Sariah J. Allen, Arzu Onar-Thomas, Clinton F. Stewart, James M. Boyett, Richard J. Gilbertson, David W. Ellison, and Amar Gajjar, St Jude Children's Research Hospital, Memphis, TN; Sridharan Gururangan and Annick Desjardins, Duke University Medical Center, Durham, NC; Roger J. Packer, Children's National Medical Center, Washington, DC; Stewart Goldman, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL; Michael D. Prados, University of California San Francisco, San Francisco, CA; Murali Chintagumpala, Texas Children's Cancer Center, Houston, TX; Naoko Takebe, National Cancer Institute, Bethesda, MD; Maryam Fouladi, Cincinnati Children's Hospital, Cincinnati, OH; and Tom Curran, Children's Hospital of Philadelphia, Philadelphia, PA.
Sue C KasteGiles W. Robinson, Brent A. Orr, Gang Wu, Tong Lin, Ibrahim Qaddoumi, Sue C. Kaste, Michael Rusch, Sariah J. Allen, Arzu Onar-Thomas, Clinton F. Stewart, James M. Boyett, Richard J. Gilbertson, David W. Ellison, and Amar Gajjar, St Jude Children's Research Hospital, Memphis, TN; Sridharan Gururangan and Annick Desjardins, Duke University Medical Center, Durham, NC; Roger J. Packer, Children's National Medical Center, Washington, DC; Stewart Goldman, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL; Michael D. Prados, University of California San Francisco, San Francisco, CA; Murali Chintagumpala, Texas Children's Cancer Center, Houston, TX; Naoko Takebe, National Cancer Institute, Bethesda, MD; Maryam Fouladi, Cincinnati Children's Hospital, Cincinnati, OH; and Tom Curran, Children's Hospital of Philadelphia, Philadelphia, PA.
Michael RuschGiles W. Robinson, Brent A. Orr, Gang Wu, Tong Lin, Ibrahim Qaddoumi, Sue C. Kaste, Michael Rusch, Sariah J. Allen, Arzu Onar-Thomas, Clinton F. Stewart, James M. Boyett, Richard J. Gilbertson, David W. Ellison, and Amar Gajjar, St Jude Children's Research Hospital, Memphis, TN; Sridharan Gururangan and Annick Desjardins, Duke University Medical Center, Durham, NC; Roger J. Packer, Children's National Medical Center, Washington, DC; Stewart Goldman, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL; Michael D. Prados, University of California San Francisco, San Francisco, CA; Murali Chintagumpala, Texas Children's Cancer Center, Houston, TX; Naoko Takebe, National Cancer Institute, Bethesda, MD; Maryam Fouladi, Cincinnati Children's Hospital, Cincinnati, OH; and Tom Curran, Children's Hospital of Philadelphia, Philadelphia, PA.
Sariah J AllenGiles W. Robinson, Brent A. Orr, Gang Wu, Tong Lin, Ibrahim Qaddoumi, Sue C. Kaste, Michael Rusch, Sariah J. Allen, Arzu Onar-Thomas, Clinton F. Stewart, James M. Boyett, Richard J. Gilbertson, David W. Ellison, and Amar Gajjar, St Jude Children's Research Hospital, Memphis, TN; Sridharan Gururangan and Annick Desjardins, Duke University Medical Center, Durham, NC; Roger J. Packer, Children's National Medical Center, Washington, DC; Stewart Goldman, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL; Michael D. Prados, University of California San Francisco, San Francisco, CA; Murali Chintagumpala, Texas Children's Cancer Center, Houston, TX; Naoko Takebe, National Cancer Institute, Bethesda, MD; Maryam Fouladi, Cincinnati Children's Hospital, Cincinnati, OH; and Tom Curran, Children's Hospital of Philadelphia, Philadelphia, PA.
Arzu Onar-ThomasGiles W. Robinson, Brent A. Orr, Gang Wu, Tong Lin, Ibrahim Qaddoumi, Sue C. Kaste, Michael Rusch, Sariah J. Allen, Arzu Onar-Thomas, Clinton F. Stewart, James M. Boyett, Richard J. Gilbertson, David W. Ellison, and Amar Gajjar, St Jude Children's Research Hospital, Memphis, TN; Sridharan Gururangan and Annick Desjardins, Duke University Medical Center, Durham, NC; Roger J. Packer, Children's National Medical Center, Washington, DC; Stewart Goldman, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL; Michael D. Prados, University of California San Francisco, San Francisco, CA; Murali Chintagumpala, Texas Children's Cancer Center, Houston, TX; Naoko Takebe, National Cancer Institute, Bethesda, MD; Maryam Fouladi, Cincinnati Children's Hospital, Cincinnati, OH; and Tom Curran, Children's Hospital of Philadelphia, Philadelphia, PA.
Clinton F StewartGiles W. Robinson, Brent A. Orr, Gang Wu, Tong Lin, Ibrahim Qaddoumi, Sue C. Kaste, Michael Rusch, Sariah J. Allen, Arzu Onar-Thomas, Clinton F. Stewart, James M. Boyett, Richard J. Gilbertson, David W. Ellison, and Amar Gajjar, St Jude Children's Research Hospital, Memphis, TN; Sridharan Gururangan and Annick Desjardins, Duke University Medical Center, Durham, NC; Roger J. Packer, Children's National Medical Center, Washington, DC; Stewart Goldman, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL; Michael D. Prados, University of California San Francisco, San Francisco, CA; Murali Chintagumpala, Texas Children's Cancer Center, Houston, TX; Naoko Takebe, National Cancer Institute, Bethesda, MD; Maryam Fouladi, Cincinnati Children's Hospital, Cincinnati, OH; and Tom Curran, Children's Hospital of Philadelphia, Philadelphia, PA.
Maryam FouladiGiles W. Robinson, Brent A. Orr, Gang Wu, Tong Lin, Ibrahim Qaddoumi, Sue C. Kaste, Michael Rusch, Sariah J. Allen, Arzu Onar-Thomas, Clinton F. Stewart, James M. Boyett, Richard J. Gilbertson, David W. Ellison, and Amar Gajjar, St Jude Children's Research Hospital, Memphis, TN; Sridharan Gururangan and Annick Desjardins, Duke University Medical Center, Durham, NC; Roger J. Packer, Children's National Medical Center, Washington, DC; Stewart Goldman, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL; Michael D. Prados, University of California San Francisco, San Francisco, CA; Murali Chintagumpala, Texas Children's Cancer Center, Houston, TX; Naoko Takebe, National Cancer Institute, Bethesda, MD; Maryam Fouladi, Cincinnati Children's Hospital, Cincinnati, OH; and Tom Curran, Children's Hospital of Philadelphia, Philadelphia, PA.
James M BoyettGiles W. Robinson, Brent A. Orr, Gang Wu, Tong Lin, Ibrahim Qaddoumi, Sue C. Kaste, Michael Rusch, Sariah J. Allen, Arzu Onar-Thomas, Clinton F. Stewart, James M. Boyett, Richard J. Gilbertson, David W. Ellison, and Amar Gajjar, St Jude Children's Research Hospital, Memphis, TN; Sridharan Gururangan and Annick Desjardins, Duke University Medical Center, Durham, NC; Roger J. Packer, Children's National Medical Center, Washington, DC; Stewart Goldman, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL; Michael D. Prados, University of California San Francisco, San Francisco, CA; Murali Chintagumpala, Texas Children's Cancer Center, Houston, TX; Naoko Takebe, National Cancer Institute, Bethesda, MD; Maryam Fouladi, Cincinnati Children's Hospital, Cincinnati, OH; and Tom Curran, Children's Hospital of Philadelphia, Philadelphia, PA.
Richard J GilbertsonGiles W. Robinson, Brent A. Orr, Gang Wu, Tong Lin, Ibrahim Qaddoumi, Sue C. Kaste, Michael Rusch, Sariah J. Allen, Arzu Onar-Thomas, Clinton F. Stewart, James M. Boyett, Richard J. Gilbertson, David W. Ellison, and Amar Gajjar, St Jude Children's Research Hospital, Memphis, TN; Sridharan Gururangan and Annick Desjardins, Duke University Medical Center, Durham, NC; Roger J. Packer, Children's National Medical Center, Washington, DC; Stewart Goldman, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL; Michael D. Prados, University of California San Francisco, San Francisco, CA; Murali Chintagumpala, Texas Children's Cancer Center, Houston, TX; Naoko Takebe, National Cancer Institute, Bethesda, MD; Maryam Fouladi, Cincinnati Children's Hospital, Cincinnati, OH; and Tom Curran, Children's Hospital of Philadelphia, Philadelphia, PA.
Tom CurranGiles W. Robinson, Brent A. Orr, Gang Wu, Tong Lin, Ibrahim Qaddoumi, Sue C. Kaste, Michael Rusch, Sariah J. Allen, Arzu Onar-Thomas, Clinton F. Stewart, James M. Boyett, Richard J. Gilbertson, David W. Ellison, and Amar Gajjar, St Jude Children's Research Hospital, Memphis, TN; Sridharan Gururangan and Annick Desjardins, Duke University Medical Center, Durham, NC; Roger J. Packer, Children's National Medical Center, Washington, DC; Stewart Goldman, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL; Michael D. Prados, University of California San Francisco, San Francisco, CA; Murali Chintagumpala, Texas Children's Cancer Center, Houston, TX; Naoko Takebe, National Cancer Institute, Bethesda, MD; Maryam Fouladi, Cincinnati Children's Hospital, Cincinnati, OH; and Tom Curran, Children's Hospital of Philadelphia, Philadelphia, PA.
David W EllisonGiles W. Robinson, Brent A. Orr, Gang Wu, Tong Lin, Ibrahim Qaddoumi, Sue C. Kaste, Michael Rusch, Sariah J. Allen, Arzu Onar-Thomas, Clinton F. Stewart, James M. Boyett, Richard J. Gilbertson, David W. Ellison, and Amar Gajjar, St Jude Children's Research Hospital, Memphis, TN; Sridharan Gururangan and Annick Desjardins, Duke University Medical Center, Durham, NC; Roger J. Packer, Children's National Medical Center, Washington, DC; Stewart Goldman, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL; Michael D. Prados, University of California San Francisco, San Francisco, CA; Murali Chintagumpala, Texas Children's Cancer Center, Houston, TX; Naoko Takebe, National Cancer Institute, Bethesda, MD; Maryam Fouladi, Cincinnati Children's Hospital, Cincinnati, OH; and Tom Curran, Children's Hospital of Philadelphia, Philadelphia, PA.
Amar GajjarGiles W. Robinson, Brent A. Orr, Gang Wu, Tong Lin, Ibrahim Qaddoumi, Sue C. Kaste, Michael Rusch, Sariah J. Allen, Arzu Onar-Thomas, Clinton F. Stewart, James M. Boyett, Richard J. Gilbertson, David W. Ellison, and Amar Gajjar, St Jude Children's Research Hospital, Memphis, TN; Sridharan Gururangan and Annick Desjardins, Duke University Medical Center, Durham, NC; Roger J. Packer, Children's National Medical Center, Washington, DC; Stewart Goldman, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL; Michael D. Prados, University of California San Francisco, San Francisco, CA; Murali Chintagumpala, Texas Children's Cancer Center, Houston, TX; Naoko Takebe, National Cancer Institute, Bethesda, MD; Maryam Fouladi, Cincinnati Children's Hospital, Cincinnati, OH; and Tom Curran, Children's Hospital of Philadelphia, Philadelphia, PA.
Funding
Viral Vector Technology (VVTSR)P30CA021765 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI CHARLES ROBERTS · 1985 to 2026
$166.9MPediatric Brain Tumor Consortium (PBTC)UM1CA081457 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI Ira J Dunkel, Arzu Onar-Thomas · 2014 to 2026
$41.4MThe DNA Damage Response and Tumorigenesis in the BrainP01CA096832 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI BAKER, SUZANNE J. · 2003 to 2025
$38.0MThe Pediatric Brain Tumor Consortium (PBTC)U01CA081457 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI BOYETT, JAMES MILFORD · 1999 to 2013
$29.2MAn Investigation of Radial Glia as the Source of Ependymoma Stem CellsR01CA129541 · NCI · UNIVERSITY OF CAMBRIDGE · PI GILBERTSON, RICHARD · 2007 to 2016
$3.0MCancer Research UK 22492NCI NIH HHS P01 CA096832NCI NIH HHS P30 CA021765NCI NIH HHS R01 CA129541NCI NIH HHS U01 CA081457NCI NIH HHS U01 CA81457NCI NIH HHS UM1 CA081457
Abstract
purposeTwo phase II studies assessed the efficacy of vismodegib, a sonic hedgehog (SHH) pathway inhibitor that binds smoothened (SMO), in pediatric and adult recurrent medulloblastoma (MB). PATIENTS AND
methodsAdult patients enrolled onto PBTC-025B and pediatric patients enrolled onto PBTC-032 were treated with vismodegib (150 to 300 mg/d). Protocol-defined response, which had to be sustained for 8 weeks, was confirmed by central neuroimaging review. Molecular tests to identify patterns of response and insensitivity were performed when tissue was available.
resultsA total of 31 patients were enrolled onto PBTC-025B, and 12 were enrolled onto PBTC-032. Three patients in PBTC-025B and one in PBTC-032, all with SHH-subgroup MB (SHH-MB), exhibited protocol-defined responses. Progression-free survival (PFS) was longer in those with SHH-MB than in those with non-SHH-MB, and prolonged disease stabilization occurred in 41% of patient cases of SHH-MB. Among those with SHH-MB, loss of heterozygosity of PTCH1 was associated with prolonged PFS, and diffuse staining of P53 was associated with reduced PFS. Whole-exome sequencing identified mutations in SHH genes downstream from SMO in four of four tissue samples from nonresponders and upstream of SMO in two of four patients with favorable responses.
conclusionVismodegib exhibits activity against adult recurrent SHH-MB but not against recurrent non-SHH-MB. Inadequate accrual of pediatric patients precluded conclusions in this population. Molecular analyses support the hypothesis that SMO inhibitor activity depends on the genomic aberrations within the tumor. Such inhibitors should be advanced in SHH-MB studies; however, molecular and genomic work remains imperative to identify target populations that will truly benefit.
Indexed as
AdultAnilidesBrain NeoplasmsFemaleHedgehog ProteinsHumansMaleMedulloblastomaMiddle AgedPyridinesYoung AdultAnilidesHedgehog ProteinsHhAntag691PyridinesSHH protein, human
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