MBCL-08. MOLECULAR CHARACTERIZATION OF NODULAR DESMOPLASTIC MEDULLOBLASTOMAS IN YOUNG CHILDREN TREATED ON ACNS1221. A REPORT FROM THE CHILDREN ONCOLOGY GROUP

MBCL-08. MOLECULAR CHARACTERIZATION OF NODULAR DESMOPLASTIC MEDULLOBLASTOMAS IN YOUNG CHILDREN TREATED ON ACNS1221. A REPORT FROM THE CHILDREN ONCOLOGY GROUP

Abstract BACKGROUND ACNS1221 was a single-arm multicenter trial of conventional chemotherapy for children < 4y with localized nodular desmoplastic medulloblastoma and medulloblastoma with extensive nodularity(ND/MBEN), based on a modified HIT SKK 2000 regimen excluding intraventricular methotrexa...

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Veröffentlicht in:Neuro-oncology (Charlottesville, Va.) Va.), 2018-06, Vol.20 (suppl_2), p.i118-i119
Hauptverfasser: Lafay-Cousin, Lucie, Robinson, Giles, Rudneva, Vasilisa, Northcott, Paul, Billups, Catherine, Onar-Thomas, Arzu, Hawkins, Cynthia, Eberhart, Charles, Horbinski, Craig, Heier, Linda, Souweidane, Mark, Strother, Douglas, Fouladi, Maryam, Bouffet, Eric, Gajjar, Amar
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container_end_page i119
container_issue suppl_2
container_start_page i118
container_title Neuro-oncology (Charlottesville, Va.)
container_volume 20
creator Lafay-Cousin, Lucie
Robinson, Giles
Rudneva, Vasilisa
Northcott, Paul
Billups, Catherine
Onar-Thomas, Arzu
Hawkins, Cynthia
Eberhart, Charles
Horbinski, Craig
Heier, Linda
Souweidane, Mark
Strother, Douglas
Fouladi, Maryam
Bouffet, Eric
Gajjar, Amar
description Abstract BACKGROUND ACNS1221 was a single-arm multicenter trial of conventional chemotherapy for children < 4y with localized nodular desmoplastic medulloblastoma and medulloblastoma with extensive nodularity(ND/MBEN), based on a modified HIT SKK 2000 regimen excluding intraventricular methotrexate. The trial prematurely closed for an excess of relapses. Here we provide the final analysis of the clinical and molecular characterization of the cohort. METHODS Tumor samples were prospectively collected to describe the molecular profile of ND/MBEN. DNA methylation was performed using Infinium MethylationEPIC BeadChip and profiled on DKFZ molecularneuropathology2.0 classifier. DNA copy-number variants were inferred from DNA methylation arrays using Conumee. Methylation profiles were added to a founder cohort of 87 infant SHH-MB and analyzed by t-distributed stochastic neighbor embedding (t-SNE) to delineate SHH-I and SHH-II subtypes. RESULTS The cohort included 26 patients(19 ND and 7 MBEN) diagnosed at a median age of 19.7 months. All tumors clustered within the SHH group and separated into 2 subtypes: SHH-I(42%) and SHH-II(58%). SHH-I patients were significantly older than SHH-II patients (p=0.009). Most MBEN were SHH-II(86%) but no significant association was found between histology and subgrouping(p=0.18). Chromosome 2 gain was exclusively described in SHH-I. Eight relapses occurred in SHH-I and 4 in SHH-II (median time of 9.8 months). The 2y PFS for SHH-I and SHH-II was respectively 27.3%(+/-13.4%) and 73.3%(+/-13.4%) (p=0.034). Age
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MOLECULAR CHARACTERIZATION OF NODULAR DESMOPLASTIC MEDULLOBLASTOMAS IN YOUNG CHILDREN TREATED ON ACNS1221. A REPORT FROM THE CHILDREN ONCOLOGY GROUP</title><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Oxford University Press Journals All Titles (1996-Current)</source><source>PubMed Central</source><creator>Lafay-Cousin, Lucie ; Robinson, Giles ; Rudneva, Vasilisa ; Northcott, Paul ; Billups, Catherine ; Onar-Thomas, Arzu ; Hawkins, Cynthia ; Eberhart, Charles ; Horbinski, Craig ; Heier, Linda ; Souweidane, Mark ; Strother, Douglas ; Fouladi, Maryam ; Bouffet, Eric ; Gajjar, Amar</creator><creatorcontrib>Lafay-Cousin, Lucie ; Robinson, Giles ; Rudneva, Vasilisa ; Northcott, Paul ; Billups, Catherine ; Onar-Thomas, Arzu ; Hawkins, Cynthia ; Eberhart, Charles ; Horbinski, Craig ; Heier, Linda ; Souweidane, Mark ; Strother, Douglas ; Fouladi, Maryam ; Bouffet, Eric ; Gajjar, Amar</creatorcontrib><description>Abstract BACKGROUND ACNS1221 was a single-arm multicenter trial of conventional chemotherapy for children &lt; 4y with localized nodular desmoplastic medulloblastoma and medulloblastoma with extensive nodularity(ND/MBEN), based on a modified HIT SKK 2000 regimen excluding intraventricular methotrexate. The trial prematurely closed for an excess of relapses. Here we provide the final analysis of the clinical and molecular characterization of the cohort. METHODS Tumor samples were prospectively collected to describe the molecular profile of ND/MBEN. DNA methylation was performed using Infinium MethylationEPIC BeadChip and profiled on DKFZ molecularneuropathology2.0 classifier. DNA copy-number variants were inferred from DNA methylation arrays using Conumee. Methylation profiles were added to a founder cohort of 87 infant SHH-MB and analyzed by t-distributed stochastic neighbor embedding (t-SNE) to delineate SHH-I and SHH-II subtypes. RESULTS The cohort included 26 patients(19 ND and 7 MBEN) diagnosed at a median age of 19.7 months. All tumors clustered within the SHH group and separated into 2 subtypes: SHH-I(42%) and SHH-II(58%). SHH-I patients were significantly older than SHH-II patients (p=0.009). Most MBEN were SHH-II(86%) but no significant association was found between histology and subgrouping(p=0.18). Chromosome 2 gain was exclusively described in SHH-I. Eight relapses occurred in SHH-I and 4 in SHH-II (median time of 9.8 months). The 2y PFS for SHH-I and SHH-II was respectively 27.3%(+/-13.4%) and 73.3%(+/-13.4%) (p=0.034). Age &lt;12 mos, MBEN histology and female sex were associated with better PFS. CONCLUSIONS With the ACNS1221 cohort, we prospectively validated the existence of 2 SHH subgroups in young children and the worse outcome of SHH-I subgroup.</description><identifier>ISSN: 1522-8517</identifier><identifier>EISSN: 1523-5866</identifier><identifier>DOI: 10.1093/neuonc/noy059.406</identifier><language>eng</language><publisher>US: Oxford University Press</publisher><subject>Abstracts</subject><ispartof>Neuro-oncology (Charlottesville, Va.), 2018-06, Vol.20 (suppl_2), p.i118-i119</ispartof><rights>The Author(s) 2018. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com 2018</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c2256-4941477913cbb9cfdfe86603e2b2a5aace69f8c392a298934af1114ee65951613</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6012819/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6012819/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,1578,27903,27904,53769,53771</link.rule.ids></links><search><creatorcontrib>Lafay-Cousin, Lucie</creatorcontrib><creatorcontrib>Robinson, Giles</creatorcontrib><creatorcontrib>Rudneva, Vasilisa</creatorcontrib><creatorcontrib>Northcott, Paul</creatorcontrib><creatorcontrib>Billups, Catherine</creatorcontrib><creatorcontrib>Onar-Thomas, Arzu</creatorcontrib><creatorcontrib>Hawkins, Cynthia</creatorcontrib><creatorcontrib>Eberhart, Charles</creatorcontrib><creatorcontrib>Horbinski, Craig</creatorcontrib><creatorcontrib>Heier, Linda</creatorcontrib><creatorcontrib>Souweidane, Mark</creatorcontrib><creatorcontrib>Strother, Douglas</creatorcontrib><creatorcontrib>Fouladi, Maryam</creatorcontrib><creatorcontrib>Bouffet, Eric</creatorcontrib><creatorcontrib>Gajjar, Amar</creatorcontrib><title>MBCL-08. MOLECULAR CHARACTERIZATION OF NODULAR DESMOPLASTIC MEDULLOBLASTOMAS IN YOUNG CHILDREN TREATED ON ACNS1221. A REPORT FROM THE CHILDREN ONCOLOGY GROUP</title><title>Neuro-oncology (Charlottesville, Va.)</title><description>Abstract BACKGROUND ACNS1221 was a single-arm multicenter trial of conventional chemotherapy for children &lt; 4y with localized nodular desmoplastic medulloblastoma and medulloblastoma with extensive nodularity(ND/MBEN), based on a modified HIT SKK 2000 regimen excluding intraventricular methotrexate. The trial prematurely closed for an excess of relapses. Here we provide the final analysis of the clinical and molecular characterization of the cohort. METHODS Tumor samples were prospectively collected to describe the molecular profile of ND/MBEN. DNA methylation was performed using Infinium MethylationEPIC BeadChip and profiled on DKFZ molecularneuropathology2.0 classifier. DNA copy-number variants were inferred from DNA methylation arrays using Conumee. Methylation profiles were added to a founder cohort of 87 infant SHH-MB and analyzed by t-distributed stochastic neighbor embedding (t-SNE) to delineate SHH-I and SHH-II subtypes. RESULTS The cohort included 26 patients(19 ND and 7 MBEN) diagnosed at a median age of 19.7 months. All tumors clustered within the SHH group and separated into 2 subtypes: SHH-I(42%) and SHH-II(58%). SHH-I patients were significantly older than SHH-II patients (p=0.009). Most MBEN were SHH-II(86%) but no significant association was found between histology and subgrouping(p=0.18). Chromosome 2 gain was exclusively described in SHH-I. Eight relapses occurred in SHH-I and 4 in SHH-II (median time of 9.8 months). The 2y PFS for SHH-I and SHH-II was respectively 27.3%(+/-13.4%) and 73.3%(+/-13.4%) (p=0.034). Age &lt;12 mos, MBEN histology and female sex were associated with better PFS. CONCLUSIONS With the ACNS1221 cohort, we prospectively validated the existence of 2 SHH subgroups in young children and the worse outcome of SHH-I subgroup.</description><subject>Abstracts</subject><issn>1522-8517</issn><issn>1523-5866</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><recordid>eNqNkc1O4zAUhaMRSPw-wOz8AKT4OrEbb5CM67aRkrhy0wWzsdzgzHQESZXQkXiYeVcCQSB2rO7fOZ90dYLgJ-AJYB5dN_7QNtV10z5jyicxZj-CU6AkCmnC2NFbT8KEwvQkOOv7vxgToAxOg__5rcxCnExQrjMlN5kwSC6FEbJUJv0lylQXSM9RoWdvt5la53qViXWZSpSrYZnp29dR52KN0gLd6U2xGBBpNjOqQKVRolQzNFCELNZACEyQQEattCnR3OgclUv1qdeF1Jle3KGF0ZvVRXBcu4feX77X82AzV6VchoMklSILK0IoC2MeQzydcoiq7ZZX9X3th69x5MmWOOpc5RmvkyrixBGe8Ch2NQDE3jPKKTCIzoObkbs_bB_9feWbp8492H23e3Tds23dzn69NLs_9nf7zzIMJAE-AGAEVF3b952vP7yA7WtAdgzIjgHZIaDBczV62sP-G_IXwW2Kgw</recordid><startdate>20180622</startdate><enddate>20180622</enddate><creator>Lafay-Cousin, Lucie</creator><creator>Robinson, Giles</creator><creator>Rudneva, Vasilisa</creator><creator>Northcott, Paul</creator><creator>Billups, Catherine</creator><creator>Onar-Thomas, Arzu</creator><creator>Hawkins, Cynthia</creator><creator>Eberhart, Charles</creator><creator>Horbinski, Craig</creator><creator>Heier, Linda</creator><creator>Souweidane, Mark</creator><creator>Strother, Douglas</creator><creator>Fouladi, Maryam</creator><creator>Bouffet, Eric</creator><creator>Gajjar, Amar</creator><general>Oxford University Press</general><scope>AAYXX</scope><scope>CITATION</scope><scope>5PM</scope></search><sort><creationdate>20180622</creationdate><title>MBCL-08. MOLECULAR CHARACTERIZATION OF NODULAR DESMOPLASTIC MEDULLOBLASTOMAS IN YOUNG CHILDREN TREATED ON ACNS1221. A REPORT FROM THE CHILDREN ONCOLOGY GROUP</title><author>Lafay-Cousin, Lucie ; Robinson, Giles ; Rudneva, Vasilisa ; Northcott, Paul ; Billups, Catherine ; Onar-Thomas, Arzu ; Hawkins, Cynthia ; Eberhart, Charles ; Horbinski, Craig ; Heier, Linda ; Souweidane, Mark ; Strother, Douglas ; Fouladi, Maryam ; Bouffet, Eric ; Gajjar, Amar</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c2256-4941477913cbb9cfdfe86603e2b2a5aace69f8c392a298934af1114ee65951613</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Abstracts</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lafay-Cousin, Lucie</creatorcontrib><creatorcontrib>Robinson, Giles</creatorcontrib><creatorcontrib>Rudneva, Vasilisa</creatorcontrib><creatorcontrib>Northcott, Paul</creatorcontrib><creatorcontrib>Billups, Catherine</creatorcontrib><creatorcontrib>Onar-Thomas, Arzu</creatorcontrib><creatorcontrib>Hawkins, Cynthia</creatorcontrib><creatorcontrib>Eberhart, Charles</creatorcontrib><creatorcontrib>Horbinski, Craig</creatorcontrib><creatorcontrib>Heier, Linda</creatorcontrib><creatorcontrib>Souweidane, Mark</creatorcontrib><creatorcontrib>Strother, Douglas</creatorcontrib><creatorcontrib>Fouladi, Maryam</creatorcontrib><creatorcontrib>Bouffet, Eric</creatorcontrib><creatorcontrib>Gajjar, Amar</creatorcontrib><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Neuro-oncology (Charlottesville, Va.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lafay-Cousin, Lucie</au><au>Robinson, Giles</au><au>Rudneva, Vasilisa</au><au>Northcott, Paul</au><au>Billups, Catherine</au><au>Onar-Thomas, Arzu</au><au>Hawkins, Cynthia</au><au>Eberhart, Charles</au><au>Horbinski, Craig</au><au>Heier, Linda</au><au>Souweidane, Mark</au><au>Strother, Douglas</au><au>Fouladi, Maryam</au><au>Bouffet, Eric</au><au>Gajjar, Amar</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>MBCL-08. MOLECULAR CHARACTERIZATION OF NODULAR DESMOPLASTIC MEDULLOBLASTOMAS IN YOUNG CHILDREN TREATED ON ACNS1221. A REPORT FROM THE CHILDREN ONCOLOGY GROUP</atitle><jtitle>Neuro-oncology (Charlottesville, Va.)</jtitle><date>2018-06-22</date><risdate>2018</risdate><volume>20</volume><issue>suppl_2</issue><spage>i118</spage><epage>i119</epage><pages>i118-i119</pages><issn>1522-8517</issn><eissn>1523-5866</eissn><abstract>Abstract BACKGROUND ACNS1221 was a single-arm multicenter trial of conventional chemotherapy for children &lt; 4y with localized nodular desmoplastic medulloblastoma and medulloblastoma with extensive nodularity(ND/MBEN), based on a modified HIT SKK 2000 regimen excluding intraventricular methotrexate. The trial prematurely closed for an excess of relapses. Here we provide the final analysis of the clinical and molecular characterization of the cohort. METHODS Tumor samples were prospectively collected to describe the molecular profile of ND/MBEN. DNA methylation was performed using Infinium MethylationEPIC BeadChip and profiled on DKFZ molecularneuropathology2.0 classifier. DNA copy-number variants were inferred from DNA methylation arrays using Conumee. Methylation profiles were added to a founder cohort of 87 infant SHH-MB and analyzed by t-distributed stochastic neighbor embedding (t-SNE) to delineate SHH-I and SHH-II subtypes. RESULTS The cohort included 26 patients(19 ND and 7 MBEN) diagnosed at a median age of 19.7 months. All tumors clustered within the SHH group and separated into 2 subtypes: SHH-I(42%) and SHH-II(58%). SHH-I patients were significantly older than SHH-II patients (p=0.009). Most MBEN were SHH-II(86%) but no significant association was found between histology and subgrouping(p=0.18). Chromosome 2 gain was exclusively described in SHH-I. Eight relapses occurred in SHH-I and 4 in SHH-II (median time of 9.8 months). The 2y PFS for SHH-I and SHH-II was respectively 27.3%(+/-13.4%) and 73.3%(+/-13.4%) (p=0.034). Age &lt;12 mos, MBEN histology and female sex were associated with better PFS. CONCLUSIONS With the ACNS1221 cohort, we prospectively validated the existence of 2 SHH subgroups in young children and the worse outcome of SHH-I subgroup.</abstract><cop>US</cop><pub>Oxford University Press</pub><doi>10.1093/neuonc/noy059.406</doi><oa>free_for_read</oa></addata></record>
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title MBCL-08. MOLECULAR CHARACTERIZATION OF NODULAR DESMOPLASTIC MEDULLOBLASTOMAS IN YOUNG CHILDREN TREATED ON ACNS1221. A REPORT FROM THE CHILDREN ONCOLOGY GROUP
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