Molecular grouping and outcomes of young children with newly diagnosed ependymoma treated on the multi-institutional SJYC07 trial
This report documents the clinical characteristics, molecular grouping, and outcome of young children with ependymoma treated prospectively on a clinical trial. Fifty-four children (aged ≤3 y) with newly diagnosed ependymoma were treated on the St Jude Young Children 07 (SJYC07) trial with maximal s...
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Veröffentlicht in: | Neuro-oncology (Charlottesville, Va.) Va.), 2019-10, Vol.21 (10), p.1319-1330 |
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creator | Upadhyaya, Santhosh A Robinson, Giles W Onar-Thomas, Arzu Orr, Brent A Billups, Catherine A Bowers, Daniel C Bendel, Anne E Hassall, Tim Crawford, John R Partap, Sonia Fisher, Paul G Tatevossian, Ruth G Seah, Tiffany Qaddoumi, Ibrahim A Vinitsky, Anna Armstrong, Gregory T Sabin, Noah D Tinkle, Christopher L Klimo, Paul Indelicato, Danny J Boop, Frederick A Merchant, Thomas E Ellison, David W Gajjar, Amar |
description | This report documents the clinical characteristics, molecular grouping, and outcome of young children with ependymoma treated prospectively on a clinical trial.
Fifty-four children (aged ≤3 y) with newly diagnosed ependymoma were treated on the St Jude Young Children 07 (SJYC07) trial with maximal safe surgical resection, 4 cycles of systemic chemotherapy, consolidation therapy using focal conformal radiation therapy (RT) (5-mm clinical target volume), and 6 months of oral maintenance chemotherapy. Molecular groups were determined by tumor DNA methylation using Infinium Methylation EPIC BeadChip and profiled on the German Cancer Research Center/Molecular Neuropathology 2.0 classifier.
One of the 54 study patients had metastases (cerebrospinal fluid positive) at diagnosis. Gross or near-total resection was achieved in 48 (89%) patients prior to RT. At a median follow-up of 4.4 years (range, 0.2-10.3 y), 4-year progression-free survival (PFS) was 75.1% ± 7.2%, and overall survival was 92.6% ± 4.4%. The molecular groups showed no significant difference in PFS (4-year estimates: posterior fossa ependymoma group A [PF-EPN-A; 42/54], 71.2% ± 8.3%; supratentorial ependymoma positive for v-rel avian reticuloendotheliosis viral oncogene homolog A [ST-EPN-RELA; 8/54], 83.3% ± 17.0%; and supratentorial ependymoma positive for Yes-associated protein [4/54], 100%, P = 0.22). Subtotal resection prior to RT was associated with an inferior PFS compared with gross or near-total resection (4-year PFS: 41.7% ± 22.5% vs 79.0% ± 7.1%, P = 0.024), as was PF-EPN-A group with 1q gain (P = 0.05). Histopathologic grading was not associated with outcomes (classic vs anaplastic; P = 0.89).
In this prospectively treated cohort of young children with ependymoma, ST-EPN-RELA tumors had a more favorable outcome than reported from retrospective data. Histologic grade did not impact outcome. PF-EPN-A with 1q gain and subtotal resection were associated with inferior outcomes. |
doi_str_mv | 10.1093/neuonc/noz069 |
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fullrecord | <record><control><sourceid>pubmed_cross</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6784269</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>30976811</sourcerecordid><originalsourceid>FETCH-LOGICAL-c387t-723256efab65bd92c762f78a3ccf69a0f1a2adb015a55f92bd4a73b12eaa10cd3</originalsourceid><addsrcrecordid>eNpVkU1LxDAQhoMofh-9Sv5ANR8maS-CLH6ieFAPnso0SXcjabKkqct6859bXRU9zfDOO-_APAgdUHJEScWPgx1i0MchvhFZraFtKhgvRCnl-lfPilJQtYV2-v6FEEaFpJtoi5NKyZLSbfR-F73Vg4eEpykOcxemGILBccg6drbHscXLOIyqnjlvkg144fIMB7vwS2wcTEPsrcF2boNZdrEDnJOFPEox4DyzuBt8doULfXZ5yC4G8Pjh5nlC1Oh04PfQRgu-t_vfdRc9XZw_Tq6K2_vL68nZbaF5qXKhGGdC2hYaKRpTMa0ka1UJXOtWVkBaCgxMQ6gAIdqKNeYEFG8oswCUaMN30ekqdz40nTXahpzA1_PkOkjLOoKr_0-Cm9XT-FpLVZ4wWY0BxSpAp9j3yba_u5TUnyzqFYt6xWL0H_49-Ov-eT7_ANYDjSY</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Molecular grouping and outcomes of young children with newly diagnosed ependymoma treated on the multi-institutional SJYC07 trial</title><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Oxford University Press Journals All Titles (1996-Current)</source><source>PubMed Central</source><creator>Upadhyaya, Santhosh A ; Robinson, Giles W ; Onar-Thomas, Arzu ; Orr, Brent A ; Billups, Catherine A ; Bowers, Daniel C ; Bendel, Anne E ; Hassall, Tim ; Crawford, John R ; Partap, Sonia ; Fisher, Paul G ; Tatevossian, Ruth G ; Seah, Tiffany ; Qaddoumi, Ibrahim A ; Vinitsky, Anna ; Armstrong, Gregory T ; Sabin, Noah D ; Tinkle, Christopher L ; Klimo, Paul ; Indelicato, Danny J ; Boop, Frederick A ; Merchant, Thomas E ; Ellison, David W ; Gajjar, Amar</creator><creatorcontrib>Upadhyaya, Santhosh A ; Robinson, Giles W ; Onar-Thomas, Arzu ; Orr, Brent A ; Billups, Catherine A ; Bowers, Daniel C ; Bendel, Anne E ; Hassall, Tim ; Crawford, John R ; Partap, Sonia ; Fisher, Paul G ; Tatevossian, Ruth G ; Seah, Tiffany ; Qaddoumi, Ibrahim A ; Vinitsky, Anna ; Armstrong, Gregory T ; Sabin, Noah D ; Tinkle, Christopher L ; Klimo, Paul ; Indelicato, Danny J ; Boop, Frederick A ; Merchant, Thomas E ; Ellison, David W ; Gajjar, Amar</creatorcontrib><description>This report documents the clinical characteristics, molecular grouping, and outcome of young children with ependymoma treated prospectively on a clinical trial.
Fifty-four children (aged ≤3 y) with newly diagnosed ependymoma were treated on the St Jude Young Children 07 (SJYC07) trial with maximal safe surgical resection, 4 cycles of systemic chemotherapy, consolidation therapy using focal conformal radiation therapy (RT) (5-mm clinical target volume), and 6 months of oral maintenance chemotherapy. Molecular groups were determined by tumor DNA methylation using Infinium Methylation EPIC BeadChip and profiled on the German Cancer Research Center/Molecular Neuropathology 2.0 classifier.
One of the 54 study patients had metastases (cerebrospinal fluid positive) at diagnosis. Gross or near-total resection was achieved in 48 (89%) patients prior to RT. At a median follow-up of 4.4 years (range, 0.2-10.3 y), 4-year progression-free survival (PFS) was 75.1% ± 7.2%, and overall survival was 92.6% ± 4.4%. The molecular groups showed no significant difference in PFS (4-year estimates: posterior fossa ependymoma group A [PF-EPN-A; 42/54], 71.2% ± 8.3%; supratentorial ependymoma positive for v-rel avian reticuloendotheliosis viral oncogene homolog A [ST-EPN-RELA; 8/54], 83.3% ± 17.0%; and supratentorial ependymoma positive for Yes-associated protein [4/54], 100%, P = 0.22). Subtotal resection prior to RT was associated with an inferior PFS compared with gross or near-total resection (4-year PFS: 41.7% ± 22.5% vs 79.0% ± 7.1%, P = 0.024), as was PF-EPN-A group with 1q gain (P = 0.05). Histopathologic grading was not associated with outcomes (classic vs anaplastic; P = 0.89).
In this prospectively treated cohort of young children with ependymoma, ST-EPN-RELA tumors had a more favorable outcome than reported from retrospective data. Histologic grade did not impact outcome. PF-EPN-A with 1q gain and subtotal resection were associated with inferior outcomes.</description><identifier>ISSN: 1522-8517</identifier><identifier>EISSN: 1523-5866</identifier><identifier>DOI: 10.1093/neuonc/noz069</identifier><identifier>PMID: 30976811</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><subject>Pediatric Neuro-Oncology</subject><ispartof>Neuro-oncology (Charlottesville, Va.), 2019-10, Vol.21 (10), p.1319-1330</ispartof><rights>The Author(s) 2019. 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.</rights><rights>The Author(s) 2019. 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 2019</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c387t-723256efab65bd92c762f78a3ccf69a0f1a2adb015a55f92bd4a73b12eaa10cd3</citedby><cites>FETCH-LOGICAL-c387t-723256efab65bd92c762f78a3ccf69a0f1a2adb015a55f92bd4a73b12eaa10cd3</cites><orcidid>0000-0001-6101-149X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6784269/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6784269/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27922,27923,53789,53791</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30976811$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Upadhyaya, Santhosh A</creatorcontrib><creatorcontrib>Robinson, Giles W</creatorcontrib><creatorcontrib>Onar-Thomas, Arzu</creatorcontrib><creatorcontrib>Orr, Brent A</creatorcontrib><creatorcontrib>Billups, Catherine A</creatorcontrib><creatorcontrib>Bowers, Daniel C</creatorcontrib><creatorcontrib>Bendel, Anne E</creatorcontrib><creatorcontrib>Hassall, Tim</creatorcontrib><creatorcontrib>Crawford, John R</creatorcontrib><creatorcontrib>Partap, Sonia</creatorcontrib><creatorcontrib>Fisher, Paul G</creatorcontrib><creatorcontrib>Tatevossian, Ruth G</creatorcontrib><creatorcontrib>Seah, Tiffany</creatorcontrib><creatorcontrib>Qaddoumi, Ibrahim A</creatorcontrib><creatorcontrib>Vinitsky, Anna</creatorcontrib><creatorcontrib>Armstrong, Gregory T</creatorcontrib><creatorcontrib>Sabin, Noah D</creatorcontrib><creatorcontrib>Tinkle, Christopher L</creatorcontrib><creatorcontrib>Klimo, Paul</creatorcontrib><creatorcontrib>Indelicato, Danny J</creatorcontrib><creatorcontrib>Boop, Frederick A</creatorcontrib><creatorcontrib>Merchant, Thomas E</creatorcontrib><creatorcontrib>Ellison, David W</creatorcontrib><creatorcontrib>Gajjar, Amar</creatorcontrib><title>Molecular grouping and outcomes of young children with newly diagnosed ependymoma treated on the multi-institutional SJYC07 trial</title><title>Neuro-oncology (Charlottesville, Va.)</title><addtitle>Neuro Oncol</addtitle><description>This report documents the clinical characteristics, molecular grouping, and outcome of young children with ependymoma treated prospectively on a clinical trial.
Fifty-four children (aged ≤3 y) with newly diagnosed ependymoma were treated on the St Jude Young Children 07 (SJYC07) trial with maximal safe surgical resection, 4 cycles of systemic chemotherapy, consolidation therapy using focal conformal radiation therapy (RT) (5-mm clinical target volume), and 6 months of oral maintenance chemotherapy. Molecular groups were determined by tumor DNA methylation using Infinium Methylation EPIC BeadChip and profiled on the German Cancer Research Center/Molecular Neuropathology 2.0 classifier.
One of the 54 study patients had metastases (cerebrospinal fluid positive) at diagnosis. Gross or near-total resection was achieved in 48 (89%) patients prior to RT. At a median follow-up of 4.4 years (range, 0.2-10.3 y), 4-year progression-free survival (PFS) was 75.1% ± 7.2%, and overall survival was 92.6% ± 4.4%. The molecular groups showed no significant difference in PFS (4-year estimates: posterior fossa ependymoma group A [PF-EPN-A; 42/54], 71.2% ± 8.3%; supratentorial ependymoma positive for v-rel avian reticuloendotheliosis viral oncogene homolog A [ST-EPN-RELA; 8/54], 83.3% ± 17.0%; and supratentorial ependymoma positive for Yes-associated protein [4/54], 100%, P = 0.22). Subtotal resection prior to RT was associated with an inferior PFS compared with gross or near-total resection (4-year PFS: 41.7% ± 22.5% vs 79.0% ± 7.1%, P = 0.024), as was PF-EPN-A group with 1q gain (P = 0.05). Histopathologic grading was not associated with outcomes (classic vs anaplastic; P = 0.89).
In this prospectively treated cohort of young children with ependymoma, ST-EPN-RELA tumors had a more favorable outcome than reported from retrospective data. Histologic grade did not impact outcome. PF-EPN-A with 1q gain and subtotal resection were associated with inferior outcomes.</description><subject>Pediatric Neuro-Oncology</subject><issn>1522-8517</issn><issn>1523-5866</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNpVkU1LxDAQhoMofh-9Sv5ANR8maS-CLH6ieFAPnso0SXcjabKkqct6859bXRU9zfDOO-_APAgdUHJEScWPgx1i0MchvhFZraFtKhgvRCnl-lfPilJQtYV2-v6FEEaFpJtoi5NKyZLSbfR-F73Vg4eEpykOcxemGILBccg6drbHscXLOIyqnjlvkg144fIMB7vwS2wcTEPsrcF2boNZdrEDnJOFPEox4DyzuBt8doULfXZ5yC4G8Pjh5nlC1Oh04PfQRgu-t_vfdRc9XZw_Tq6K2_vL68nZbaF5qXKhGGdC2hYaKRpTMa0ka1UJXOtWVkBaCgxMQ6gAIdqKNeYEFG8oswCUaMN30ekqdz40nTXahpzA1_PkOkjLOoKr_0-Cm9XT-FpLVZ4wWY0BxSpAp9j3yba_u5TUnyzqFYt6xWL0H_49-Ov-eT7_ANYDjSY</recordid><startdate>20191009</startdate><enddate>20191009</enddate><creator>Upadhyaya, Santhosh A</creator><creator>Robinson, Giles W</creator><creator>Onar-Thomas, Arzu</creator><creator>Orr, Brent A</creator><creator>Billups, Catherine A</creator><creator>Bowers, Daniel C</creator><creator>Bendel, Anne E</creator><creator>Hassall, Tim</creator><creator>Crawford, John R</creator><creator>Partap, Sonia</creator><creator>Fisher, Paul G</creator><creator>Tatevossian, Ruth G</creator><creator>Seah, Tiffany</creator><creator>Qaddoumi, Ibrahim A</creator><creator>Vinitsky, Anna</creator><creator>Armstrong, Gregory T</creator><creator>Sabin, Noah D</creator><creator>Tinkle, Christopher L</creator><creator>Klimo, Paul</creator><creator>Indelicato, Danny J</creator><creator>Boop, Frederick A</creator><creator>Merchant, Thomas E</creator><creator>Ellison, David W</creator><creator>Gajjar, Amar</creator><general>Oxford University Press</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-6101-149X</orcidid></search><sort><creationdate>20191009</creationdate><title>Molecular grouping and outcomes of young children with newly diagnosed ependymoma treated on the multi-institutional SJYC07 trial</title><author>Upadhyaya, Santhosh A ; Robinson, Giles W ; Onar-Thomas, Arzu ; Orr, Brent A ; Billups, Catherine A ; Bowers, Daniel C ; Bendel, Anne E ; Hassall, Tim ; Crawford, John R ; Partap, Sonia ; Fisher, Paul G ; Tatevossian, Ruth G ; Seah, Tiffany ; Qaddoumi, Ibrahim A ; Vinitsky, Anna ; Armstrong, Gregory T ; Sabin, Noah D ; Tinkle, Christopher L ; Klimo, Paul ; Indelicato, Danny J ; Boop, Frederick A ; Merchant, Thomas E ; Ellison, David W ; Gajjar, Amar</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c387t-723256efab65bd92c762f78a3ccf69a0f1a2adb015a55f92bd4a73b12eaa10cd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Pediatric Neuro-Oncology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Upadhyaya, Santhosh A</creatorcontrib><creatorcontrib>Robinson, Giles W</creatorcontrib><creatorcontrib>Onar-Thomas, Arzu</creatorcontrib><creatorcontrib>Orr, Brent A</creatorcontrib><creatorcontrib>Billups, Catherine A</creatorcontrib><creatorcontrib>Bowers, Daniel C</creatorcontrib><creatorcontrib>Bendel, Anne E</creatorcontrib><creatorcontrib>Hassall, Tim</creatorcontrib><creatorcontrib>Crawford, John R</creatorcontrib><creatorcontrib>Partap, Sonia</creatorcontrib><creatorcontrib>Fisher, Paul G</creatorcontrib><creatorcontrib>Tatevossian, Ruth G</creatorcontrib><creatorcontrib>Seah, Tiffany</creatorcontrib><creatorcontrib>Qaddoumi, Ibrahim A</creatorcontrib><creatorcontrib>Vinitsky, Anna</creatorcontrib><creatorcontrib>Armstrong, Gregory T</creatorcontrib><creatorcontrib>Sabin, Noah D</creatorcontrib><creatorcontrib>Tinkle, Christopher L</creatorcontrib><creatorcontrib>Klimo, Paul</creatorcontrib><creatorcontrib>Indelicato, Danny J</creatorcontrib><creatorcontrib>Boop, Frederick A</creatorcontrib><creatorcontrib>Merchant, Thomas E</creatorcontrib><creatorcontrib>Ellison, David W</creatorcontrib><creatorcontrib>Gajjar, Amar</creatorcontrib><collection>PubMed</collection><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>Upadhyaya, Santhosh A</au><au>Robinson, Giles W</au><au>Onar-Thomas, Arzu</au><au>Orr, Brent A</au><au>Billups, Catherine A</au><au>Bowers, Daniel C</au><au>Bendel, Anne E</au><au>Hassall, Tim</au><au>Crawford, John R</au><au>Partap, Sonia</au><au>Fisher, Paul G</au><au>Tatevossian, Ruth G</au><au>Seah, Tiffany</au><au>Qaddoumi, Ibrahim A</au><au>Vinitsky, Anna</au><au>Armstrong, Gregory T</au><au>Sabin, Noah D</au><au>Tinkle, Christopher L</au><au>Klimo, Paul</au><au>Indelicato, Danny J</au><au>Boop, Frederick A</au><au>Merchant, Thomas E</au><au>Ellison, David W</au><au>Gajjar, Amar</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Molecular grouping and outcomes of young children with newly diagnosed ependymoma treated on the multi-institutional SJYC07 trial</atitle><jtitle>Neuro-oncology (Charlottesville, Va.)</jtitle><addtitle>Neuro Oncol</addtitle><date>2019-10-09</date><risdate>2019</risdate><volume>21</volume><issue>10</issue><spage>1319</spage><epage>1330</epage><pages>1319-1330</pages><issn>1522-8517</issn><eissn>1523-5866</eissn><abstract>This report documents the clinical characteristics, molecular grouping, and outcome of young children with ependymoma treated prospectively on a clinical trial.
Fifty-four children (aged ≤3 y) with newly diagnosed ependymoma were treated on the St Jude Young Children 07 (SJYC07) trial with maximal safe surgical resection, 4 cycles of systemic chemotherapy, consolidation therapy using focal conformal radiation therapy (RT) (5-mm clinical target volume), and 6 months of oral maintenance chemotherapy. Molecular groups were determined by tumor DNA methylation using Infinium Methylation EPIC BeadChip and profiled on the German Cancer Research Center/Molecular Neuropathology 2.0 classifier.
One of the 54 study patients had metastases (cerebrospinal fluid positive) at diagnosis. Gross or near-total resection was achieved in 48 (89%) patients prior to RT. At a median follow-up of 4.4 years (range, 0.2-10.3 y), 4-year progression-free survival (PFS) was 75.1% ± 7.2%, and overall survival was 92.6% ± 4.4%. The molecular groups showed no significant difference in PFS (4-year estimates: posterior fossa ependymoma group A [PF-EPN-A; 42/54], 71.2% ± 8.3%; supratentorial ependymoma positive for v-rel avian reticuloendotheliosis viral oncogene homolog A [ST-EPN-RELA; 8/54], 83.3% ± 17.0%; and supratentorial ependymoma positive for Yes-associated protein [4/54], 100%, P = 0.22). Subtotal resection prior to RT was associated with an inferior PFS compared with gross or near-total resection (4-year PFS: 41.7% ± 22.5% vs 79.0% ± 7.1%, P = 0.024), as was PF-EPN-A group with 1q gain (P = 0.05). Histopathologic grading was not associated with outcomes (classic vs anaplastic; P = 0.89).
In this prospectively treated cohort of young children with ependymoma, ST-EPN-RELA tumors had a more favorable outcome than reported from retrospective data. Histologic grade did not impact outcome. PF-EPN-A with 1q gain and subtotal resection were associated with inferior outcomes.</abstract><cop>England</cop><pub>Oxford University Press</pub><pmid>30976811</pmid><doi>10.1093/neuonc/noz069</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0001-6101-149X</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Pediatric Neuro-Oncology |
title | Molecular grouping and outcomes of young children with newly diagnosed ependymoma treated on the multi-institutional SJYC07 trial |
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