Using personalized medicine in gliomas: a genomic approach to diagnosis and overcoming treatment resistance in a case with pleomorphic xanthoastrocytoma
Identifieur interne : 000287 ( Main/Exploration ); précédent : 000286; suivant : 000288Using personalized medicine in gliomas: a genomic approach to diagnosis and overcoming treatment resistance in a case with pleomorphic xanthoastrocytoma
Auteurs : Yolanda Pi A ; Michael J. Fusco ; Robert J. Macaulay ; Christine M. Walko ; Edwin Peguero ; Brittany R. Evernden ; Keiran S. Smalley ; Peter ForsythSource :
- Journal of Neurology [ 0340-5354 ] ; 2019.
Abstract
A patient who was initially considered to have a glioblastoma (GBM) had molecular analysis, showing that it was a pleomorphic xanthoastrocytoma (PXA). Up to 78% of PXA tumors have
A 20-year-old man found to have a large brain mass with midline shift underwent resection. He was diagnosed with “GBM” and treated with radiation and temozolomide with subsequent disease recurrence. Review of histology showed malignant PXA with
This is the first report of a PXA patient receiving therapy with BRAF MEKi and an autophagy inhibitor with prolonged stable disease. This patient highlights the importance of a molecular interrogation in gliomas to provide an integrated diagnosis and effective treatment. This may be useful in up to 3% of glioma patients with
Url:
DOI: 10.1007/s00415-019-09575-8
PubMed: 31748891
PubMed Central: 7035305
Affiliations:
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Using personalized medicine in gliomas: a genomic approach to diagnosis and overcoming treatment resistance in a case with pleomorphic xanthoastrocytoma</title><author><name sortKey="Pi A, Yolanda" sort="Pi A, Yolanda" uniqKey="Pi A Y" first="Yolanda" last="Pi A">Yolanda Pi A</name><affiliation><nlm:aff id="Aff1"></nlm:aff></affiliation></author><author><name sortKey="Fusco, Michael J" sort="Fusco, Michael J" uniqKey="Fusco M" first="Michael J." last="Fusco">Michael J. Fusco</name><affiliation><nlm:aff id="Aff1"></nlm:aff></affiliation></author><author><name sortKey="Macaulay, Robert J" sort="Macaulay, Robert J" uniqKey="Macaulay R" first="Robert J." last="Macaulay">Robert J. Macaulay</name><affiliation><nlm:aff id="Aff1"></nlm:aff></affiliation></author><author><name sortKey="Walko, Christine M" sort="Walko, Christine M" uniqKey="Walko C" first="Christine M." last="Walko">Christine M. Walko</name><affiliation><nlm:aff id="Aff1"></nlm:aff></affiliation></author><author><name sortKey="Peguero, Edwin" sort="Peguero, Edwin" uniqKey="Peguero E" first="Edwin" last="Peguero">Edwin Peguero</name><affiliation><nlm:aff id="Aff1"></nlm:aff></affiliation></author><author><name sortKey="Evernden, Brittany R" sort="Evernden, Brittany R" uniqKey="Evernden B" first="Brittany R." last="Evernden">Brittany R. Evernden</name><affiliation><nlm:aff id="Aff1"></nlm:aff></affiliation></author><author><name sortKey="Smalley, Keiran S" sort="Smalley, Keiran S" uniqKey="Smalley K" first="Keiran S." last="Smalley">Keiran S. Smalley</name><affiliation><nlm:aff id="Aff1"></nlm:aff></affiliation></author><author><name sortKey="Forsyth, Peter" sort="Forsyth, Peter" uniqKey="Forsyth P" first="Peter" last="Forsyth">Peter Forsyth</name><affiliation><nlm:aff id="Aff1"></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">31748891</idno><idno type="pmc">7035305</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7035305</idno><idno type="RBID">PMC:7035305</idno><idno type="doi">10.1007/s00415-019-09575-8</idno><date when="2019">2019</date><idno type="wicri:Area/Pmc/Corpus">000123</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000123</idno><idno type="wicri:Area/Pmc/Curation">000123</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000123</idno><idno type="wicri:Area/Pmc/Checkpoint">000251</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000251</idno><idno type="wicri:Area/Ncbi/Merge">000C29</idno><idno type="wicri:Area/Ncbi/Curation">000C29</idno><idno type="wicri:Area/Ncbi/Checkpoint">000C29</idno><idno type="wicri:doubleKey">0340-5354:2019:Pi A Y:using:personalized:medicine</idno><idno type="wicri:Area/Main/Merge">000287</idno><idno type="wicri:Area/Main/Curation">000287</idno><idno type="wicri:Area/Main/Exploration">000287</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Using personalized medicine in gliomas: a genomic approach to diagnosis and overcoming treatment resistance in a case with pleomorphic xanthoastrocytoma</title><author><name sortKey="Pi A, Yolanda" sort="Pi A, Yolanda" uniqKey="Pi A Y" first="Yolanda" last="Pi A">Yolanda Pi A</name><affiliation><nlm:aff id="Aff1"></nlm:aff></affiliation></author><author><name sortKey="Fusco, Michael J" sort="Fusco, Michael J" uniqKey="Fusco M" first="Michael J." last="Fusco">Michael J. Fusco</name><affiliation><nlm:aff id="Aff1"></nlm:aff></affiliation></author><author><name sortKey="Macaulay, Robert J" sort="Macaulay, Robert J" uniqKey="Macaulay R" first="Robert J." last="Macaulay">Robert J. Macaulay</name><affiliation><nlm:aff id="Aff1"></nlm:aff></affiliation></author><author><name sortKey="Walko, Christine M" sort="Walko, Christine M" uniqKey="Walko C" first="Christine M." last="Walko">Christine M. Walko</name><affiliation><nlm:aff id="Aff1"></nlm:aff></affiliation></author><author><name sortKey="Peguero, Edwin" sort="Peguero, Edwin" uniqKey="Peguero E" first="Edwin" last="Peguero">Edwin Peguero</name><affiliation><nlm:aff id="Aff1"></nlm:aff></affiliation></author><author><name sortKey="Evernden, Brittany R" sort="Evernden, Brittany R" uniqKey="Evernden B" first="Brittany R." last="Evernden">Brittany R. Evernden</name><affiliation><nlm:aff id="Aff1"></nlm:aff></affiliation></author><author><name sortKey="Smalley, Keiran S" sort="Smalley, Keiran S" uniqKey="Smalley K" first="Keiran S." last="Smalley">Keiran S. Smalley</name><affiliation><nlm:aff id="Aff1"></nlm:aff></affiliation></author><author><name sortKey="Forsyth, Peter" sort="Forsyth, Peter" uniqKey="Forsyth P" first="Peter" last="Forsyth">Peter Forsyth</name><affiliation><nlm:aff id="Aff1"></nlm:aff></affiliation></author></analytic><series><title level="j">Journal of Neurology</title><idno type="ISSN">0340-5354</idno><idno type="eISSN">1432-1459</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Introduction</title><p id="Par1">A patient who was initially considered to have a glioblastoma (GBM) had molecular analysis, showing that it was a pleomorphic xanthoastrocytoma (PXA). Up to 78% of PXA tumors have <italic>BRAF</italic> V600E mutations. Primary brain tumors with <italic>BRAF</italic> mutations can have a good response to <italic>BRAF</italic> MEK inhibitors (BRAF MEKi), and there may be a synergistic response when combined with autophagy inhibitors.</p></sec><sec><title>Presentation of the case</title><p id="Par2">A 20-year-old man found to have a large brain mass with midline shift underwent resection. He was diagnosed with “GBM” and treated with radiation and temozolomide with subsequent disease recurrence. Review of histology showed malignant PXA with <italic>BRAF</italic> V600E mutation. Treatment with Dabrafenib and Trametinib was started, and tumor size increased in size after 14 months of treatment. Given studies showing that resistance to <italic>BRAF</italic> inhibition can be overcome by autophagy inhibition, chloroquine was added. Patient has been on “triple” therapy for 15 months and has radiographically Stable Disease. At MCC, 3% of patients with gliomas have <italic>BRAF</italic> mutations who could potentially benefit from this combination therapy.</p></sec><sec><title>Conclusion</title><p id="Par3">This is the first report of a PXA patient receiving therapy with BRAF MEKi and an autophagy inhibitor with prolonged stable disease. This patient highlights the importance of a molecular interrogation in gliomas to provide an integrated diagnosis and effective treatment. This may be useful in up to 3% of glioma patients with <italic>BRAF</italic> mutations. 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sortKey="Evernden, Brittany R" sort="Evernden, Brittany R" uniqKey="Evernden B" first="Brittany R." last="Evernden">Brittany R. Evernden</name><name sortKey="Forsyth, Peter" sort="Forsyth, Peter" uniqKey="Forsyth P" first="Peter" last="Forsyth">Peter Forsyth</name><name sortKey="Fusco, Michael J" sort="Fusco, Michael J" uniqKey="Fusco M" first="Michael J." last="Fusco">Michael J. Fusco</name><name sortKey="Macaulay, Robert J" sort="Macaulay, Robert J" uniqKey="Macaulay R" first="Robert J." last="Macaulay">Robert J. Macaulay</name><name sortKey="Peguero, Edwin" sort="Peguero, Edwin" uniqKey="Peguero E" first="Edwin" last="Peguero">Edwin Peguero</name><name sortKey="Pi A, Yolanda" sort="Pi A, Yolanda" uniqKey="Pi A Y" first="Yolanda" last="Pi A">Yolanda Pi A</name><name sortKey="Smalley, Keiran S" sort="Smalley, Keiran S" uniqKey="Smalley K" first="Keiran S." last="Smalley">Keiran S. Smalley</name><name sortKey="Walko, Christine M" sort="Walko, Christine M" uniqKey="Walko C" first="Christine M." last="Walko">Christine M. 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