PAX-FOXO1 fusion status drives unfavorable outcome for children with rhabdomyosarcoma: A children's oncology group report
Background Rhabdomyosarcoma (RMS) is divided into two major histological subtypes: alveolar (ARMS) and embryonal (ERMS), with most ARMS expressing one of two oncogenic genes fusing PAX3 or PAX7 with FOXO1 (P3F and P7F, respectively). The Children's Oncology Group (COG) carried out a multi‐insti...
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| Veröffentlicht in: | Pediatric blood & cancer 2013-09, Vol.60 (9), p.1411-1417 |
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| creator | Skapek, Stephen X. Anderson, James Barr, Frederic G. Bridge, Julia A. Gastier-Foster, Julie M. Parham, David M. Rudzinski, Erin R. Triche, Timothy Hawkins, Douglas S. |
| description | Background
Rhabdomyosarcoma (RMS) is divided into two major histological subtypes: alveolar (ARMS) and embryonal (ERMS), with most ARMS expressing one of two oncogenic genes fusing PAX3 or PAX7 with FOXO1 (P3F and P7F, respectively). The Children's Oncology Group (COG) carried out a multi‐institutional clinical trial to evaluate the prognostic value of PAX‐FOXO1 fusion status.
Methods
Study participants were treated on COG protocol D9803 for intermediate risk ARMS or ERMS using multi‐agent chemotherapy, radiotherapy, and surgery. Central diagnostic pathology review and molecular testing for fusion genes were carried out on prospectively collected specimens. Event‐free (EFS) and overall survival (OS) at 5 years were correlated with histological subtype and PAX‐FOXO1 status.
Results
Of 616 eligible D9803 enrollees, 434 cases had adequate clinical, molecular, and pathology data for definitive classification as ERMS, ARMS P3F+ or P7F+, or ARMSn (without detectable fusion). EFS was worse for those with ARMS P3F+ (54%) and P7F+ (65%) than those with ERMS (77%; P |
| doi_str_mv | 10.1002/pbc.24532 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4646073</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3018524001</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4472-a078e68aa8ced593d92f2ba829c06e50def277ccbe9145ea28b039d6eb639583</originalsourceid><addsrcrecordid>eNpdkUFr3DAQhU1pSdIkh_6BIuihvTiRJUu2eghsl2Zb2GRzCEluQpbHu0pty5XsTf3vq82mpi0INDDfe7zhRdG7BJ8lGJPzrtBnJGWUvIqOEpaymOEkez3NWBxGb71_DCjHLD-IDgllhGdUHEXjzewhvlw9rBJUDd7YFvle9YNHpTNb8GhoK7W1ThU1IDv02jaAKuuQ3pi6dNCiJ9NvkNuoorTNaL1yAVGf0WwiPnpkW21rux7R2tmhQw466_qT6E2lag-nL_9xdHv59Xb-LV6uFt_ns2Ws0zQjscJZDjxXKtdQMkFLQSpSqJwIjTkwXEJFskzrAkSSMlAkLzAVJYeCU8Fyehxd7G27oWig1ND2TtWyc6ZRbpRWGfnvpjUbubZbmfKU44wGg08vBs7-HMD3sjFeQ12rFuzgZZJiHB5nO_TDf-ijHVwbrpMJFYKLjOFdovd_J5qi_CklAOd74MnUME77BMtd2zK0LZ_bljdf5s9DUMR7hfE9_JoUyv2QwTFj8v56Ie-vrhdXyzsil_Q3CDWt4w</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1399697508</pqid></control><display><type>article</type><title>PAX-FOXO1 fusion status drives unfavorable outcome for children with rhabdomyosarcoma: A children's oncology group report</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><creator>Skapek, Stephen X. ; Anderson, James ; Barr, Frederic G. ; Bridge, Julia A. ; Gastier-Foster, Julie M. ; Parham, David M. ; Rudzinski, Erin R. ; Triche, Timothy ; Hawkins, Douglas S.</creator><creatorcontrib>Skapek, Stephen X. ; Anderson, James ; Barr, Frederic G. ; Bridge, Julia A. ; Gastier-Foster, Julie M. ; Parham, David M. ; Rudzinski, Erin R. ; Triche, Timothy ; Hawkins, Douglas S.</creatorcontrib><description>Background
Rhabdomyosarcoma (RMS) is divided into two major histological subtypes: alveolar (ARMS) and embryonal (ERMS), with most ARMS expressing one of two oncogenic genes fusing PAX3 or PAX7 with FOXO1 (P3F and P7F, respectively). The Children's Oncology Group (COG) carried out a multi‐institutional clinical trial to evaluate the prognostic value of PAX‐FOXO1 fusion status.
Methods
Study participants were treated on COG protocol D9803 for intermediate risk ARMS or ERMS using multi‐agent chemotherapy, radiotherapy, and surgery. Central diagnostic pathology review and molecular testing for fusion genes were carried out on prospectively collected specimens. Event‐free (EFS) and overall survival (OS) at 5 years were correlated with histological subtype and PAX‐FOXO1 status.
Results
Of 616 eligible D9803 enrollees, 434 cases had adequate clinical, molecular, and pathology data for definitive classification as ERMS, ARMS P3F+ or P7F+, or ARMSn (without detectable fusion). EFS was worse for those with ARMS P3F+ (54%) and P7F+ (65%) than those with ERMS (77%; P < 0.001). EFS for ARMSn and ERMS were not statistically different (90% vs. 77%, P = 0.15). ARMS P3F+ had poorer OS (64%) than ARMS P7F+ (87%), ARMSn (89%), and ERMS (82%; P = 0.006).
Conclusions
ARMSn has an outcome similar to ERMS and superior EFS compared to ARMS with either P3F or P7F, when given therapy designed for children with intermediate risk RMS. This prospective analysis supports incorporation of PAX‐FOXO1 fusion status into risk stratification and treatment allocation. Pediatr Blood Cancer 2013;60:1411–1417. © 2013 Wiley Periodicals, Inc.</description><identifier>ISSN: 1545-5009</identifier><identifier>EISSN: 1545-5017</identifier><identifier>DOI: 10.1002/pbc.24532</identifier><identifier>PMID: 23526739</identifier><language>eng</language><publisher>United States: Blackwell Publishing Ltd</publisher><subject>Adolescent ; Adult ; Antineoplastic Combined Chemotherapy Protocols - administration & dosage ; Child ; Child, Preschool ; Disease-Free Survival ; Female ; Hematology ; Humans ; Infant ; Male ; Neoplasm Staging ; Oncogene Proteins, Fusion - genetics ; Oncology ; Paired Box Transcription Factors - genetics ; PAX-FOXO1 ; PAX7 Transcription Factor - genetics ; Pediatrics ; Prospective Studies ; Retrospective Studies ; rhabdomyosarcoma ; Rhabdomyosarcoma - drug therapy ; Rhabdomyosarcoma - genetics ; Rhabdomyosarcoma - mortality ; Risk Factors ; survival ; Survival Rate</subject><ispartof>Pediatric blood & cancer, 2013-09, Vol.60 (9), p.1411-1417</ispartof><rights>Copyright © 2013 Wiley Periodicals, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4472-a078e68aa8ced593d92f2ba829c06e50def277ccbe9145ea28b039d6eb639583</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fpbc.24532$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fpbc.24532$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,776,780,881,1411,27903,27904,45553,45554</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23526739$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Skapek, Stephen X.</creatorcontrib><creatorcontrib>Anderson, James</creatorcontrib><creatorcontrib>Barr, Frederic G.</creatorcontrib><creatorcontrib>Bridge, Julia A.</creatorcontrib><creatorcontrib>Gastier-Foster, Julie M.</creatorcontrib><creatorcontrib>Parham, David M.</creatorcontrib><creatorcontrib>Rudzinski, Erin R.</creatorcontrib><creatorcontrib>Triche, Timothy</creatorcontrib><creatorcontrib>Hawkins, Douglas S.</creatorcontrib><title>PAX-FOXO1 fusion status drives unfavorable outcome for children with rhabdomyosarcoma: A children's oncology group report</title><title>Pediatric blood & cancer</title><addtitle>Pediatr Blood Cancer</addtitle><description>Background
Rhabdomyosarcoma (RMS) is divided into two major histological subtypes: alveolar (ARMS) and embryonal (ERMS), with most ARMS expressing one of two oncogenic genes fusing PAX3 or PAX7 with FOXO1 (P3F and P7F, respectively). The Children's Oncology Group (COG) carried out a multi‐institutional clinical trial to evaluate the prognostic value of PAX‐FOXO1 fusion status.
Methods
Study participants were treated on COG protocol D9803 for intermediate risk ARMS or ERMS using multi‐agent chemotherapy, radiotherapy, and surgery. Central diagnostic pathology review and molecular testing for fusion genes were carried out on prospectively collected specimens. Event‐free (EFS) and overall survival (OS) at 5 years were correlated with histological subtype and PAX‐FOXO1 status.
Results
Of 616 eligible D9803 enrollees, 434 cases had adequate clinical, molecular, and pathology data for definitive classification as ERMS, ARMS P3F+ or P7F+, or ARMSn (without detectable fusion). EFS was worse for those with ARMS P3F+ (54%) and P7F+ (65%) than those with ERMS (77%; P < 0.001). EFS for ARMSn and ERMS were not statistically different (90% vs. 77%, P = 0.15). ARMS P3F+ had poorer OS (64%) than ARMS P7F+ (87%), ARMSn (89%), and ERMS (82%; P = 0.006).
Conclusions
ARMSn has an outcome similar to ERMS and superior EFS compared to ARMS with either P3F or P7F, when given therapy designed for children with intermediate risk RMS. This prospective analysis supports incorporation of PAX‐FOXO1 fusion status into risk stratification and treatment allocation. Pediatr Blood Cancer 2013;60:1411–1417. © 2013 Wiley Periodicals, Inc.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Antineoplastic Combined Chemotherapy Protocols - administration & dosage</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Disease-Free Survival</subject><subject>Female</subject><subject>Hematology</subject><subject>Humans</subject><subject>Infant</subject><subject>Male</subject><subject>Neoplasm Staging</subject><subject>Oncogene Proteins, Fusion - genetics</subject><subject>Oncology</subject><subject>Paired Box Transcription Factors - genetics</subject><subject>PAX-FOXO1</subject><subject>PAX7 Transcription Factor - genetics</subject><subject>Pediatrics</subject><subject>Prospective Studies</subject><subject>Retrospective Studies</subject><subject>rhabdomyosarcoma</subject><subject>Rhabdomyosarcoma - drug therapy</subject><subject>Rhabdomyosarcoma - genetics</subject><subject>Rhabdomyosarcoma - mortality</subject><subject>Risk Factors</subject><subject>survival</subject><subject>Survival Rate</subject><issn>1545-5009</issn><issn>1545-5017</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkUFr3DAQhU1pSdIkh_6BIuihvTiRJUu2eghsl2Zb2GRzCEluQpbHu0pty5XsTf3vq82mpi0INDDfe7zhRdG7BJ8lGJPzrtBnJGWUvIqOEpaymOEkez3NWBxGb71_DCjHLD-IDgllhGdUHEXjzewhvlw9rBJUDd7YFvle9YNHpTNb8GhoK7W1ThU1IDv02jaAKuuQ3pi6dNCiJ9NvkNuoorTNaL1yAVGf0WwiPnpkW21rux7R2tmhQw466_qT6E2lag-nL_9xdHv59Xb-LV6uFt_ns2Ws0zQjscJZDjxXKtdQMkFLQSpSqJwIjTkwXEJFskzrAkSSMlAkLzAVJYeCU8Fyehxd7G27oWig1ND2TtWyc6ZRbpRWGfnvpjUbubZbmfKU44wGg08vBs7-HMD3sjFeQ12rFuzgZZJiHB5nO_TDf-ijHVwbrpMJFYKLjOFdovd_J5qi_CklAOd74MnUME77BMtd2zK0LZ_bljdf5s9DUMR7hfE9_JoUyv2QwTFj8v56Ie-vrhdXyzsil_Q3CDWt4w</recordid><startdate>201309</startdate><enddate>201309</enddate><creator>Skapek, Stephen X.</creator><creator>Anderson, James</creator><creator>Barr, Frederic G.</creator><creator>Bridge, Julia A.</creator><creator>Gastier-Foster, Julie M.</creator><creator>Parham, David M.</creator><creator>Rudzinski, Erin R.</creator><creator>Triche, Timothy</creator><creator>Hawkins, Douglas S.</creator><general>Blackwell Publishing Ltd</general><general>Wiley Subscription Services, Inc</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7T5</scope><scope>7TK</scope><scope>7TO</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>201309</creationdate><title>PAX-FOXO1 fusion status drives unfavorable outcome for children with rhabdomyosarcoma: A children's oncology group report</title><author>Skapek, Stephen X. ; Anderson, James ; Barr, Frederic G. ; Bridge, Julia A. ; Gastier-Foster, Julie M. ; Parham, David M. ; Rudzinski, Erin R. ; Triche, Timothy ; Hawkins, Douglas S.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4472-a078e68aa8ced593d92f2ba829c06e50def277ccbe9145ea28b039d6eb639583</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Antineoplastic Combined Chemotherapy Protocols - administration & dosage</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>Disease-Free Survival</topic><topic>Female</topic><topic>Hematology</topic><topic>Humans</topic><topic>Infant</topic><topic>Male</topic><topic>Neoplasm Staging</topic><topic>Oncogene Proteins, Fusion - genetics</topic><topic>Oncology</topic><topic>Paired Box Transcription Factors - genetics</topic><topic>PAX-FOXO1</topic><topic>PAX7 Transcription Factor - genetics</topic><topic>Pediatrics</topic><topic>Prospective Studies</topic><topic>Retrospective Studies</topic><topic>rhabdomyosarcoma</topic><topic>Rhabdomyosarcoma - drug therapy</topic><topic>Rhabdomyosarcoma - genetics</topic><topic>Rhabdomyosarcoma - mortality</topic><topic>Risk Factors</topic><topic>survival</topic><topic>Survival Rate</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Skapek, Stephen X.</creatorcontrib><creatorcontrib>Anderson, James</creatorcontrib><creatorcontrib>Barr, Frederic G.</creatorcontrib><creatorcontrib>Bridge, Julia A.</creatorcontrib><creatorcontrib>Gastier-Foster, Julie M.</creatorcontrib><creatorcontrib>Parham, David M.</creatorcontrib><creatorcontrib>Rudzinski, Erin R.</creatorcontrib><creatorcontrib>Triche, Timothy</creatorcontrib><creatorcontrib>Hawkins, Douglas S.</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Pediatric blood & cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Skapek, Stephen X.</au><au>Anderson, James</au><au>Barr, Frederic G.</au><au>Bridge, Julia A.</au><au>Gastier-Foster, Julie M.</au><au>Parham, David M.</au><au>Rudzinski, Erin R.</au><au>Triche, Timothy</au><au>Hawkins, Douglas S.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>PAX-FOXO1 fusion status drives unfavorable outcome for children with rhabdomyosarcoma: A children's oncology group report</atitle><jtitle>Pediatric blood & cancer</jtitle><addtitle>Pediatr Blood Cancer</addtitle><date>2013-09</date><risdate>2013</risdate><volume>60</volume><issue>9</issue><spage>1411</spage><epage>1417</epage><pages>1411-1417</pages><issn>1545-5009</issn><eissn>1545-5017</eissn><abstract>Background
Rhabdomyosarcoma (RMS) is divided into two major histological subtypes: alveolar (ARMS) and embryonal (ERMS), with most ARMS expressing one of two oncogenic genes fusing PAX3 or PAX7 with FOXO1 (P3F and P7F, respectively). The Children's Oncology Group (COG) carried out a multi‐institutional clinical trial to evaluate the prognostic value of PAX‐FOXO1 fusion status.
Methods
Study participants were treated on COG protocol D9803 for intermediate risk ARMS or ERMS using multi‐agent chemotherapy, radiotherapy, and surgery. Central diagnostic pathology review and molecular testing for fusion genes were carried out on prospectively collected specimens. Event‐free (EFS) and overall survival (OS) at 5 years were correlated with histological subtype and PAX‐FOXO1 status.
Results
Of 616 eligible D9803 enrollees, 434 cases had adequate clinical, molecular, and pathology data for definitive classification as ERMS, ARMS P3F+ or P7F+, or ARMSn (without detectable fusion). EFS was worse for those with ARMS P3F+ (54%) and P7F+ (65%) than those with ERMS (77%; P < 0.001). EFS for ARMSn and ERMS were not statistically different (90% vs. 77%, P = 0.15). ARMS P3F+ had poorer OS (64%) than ARMS P7F+ (87%), ARMSn (89%), and ERMS (82%; P = 0.006).
Conclusions
ARMSn has an outcome similar to ERMS and superior EFS compared to ARMS with either P3F or P7F, when given therapy designed for children with intermediate risk RMS. This prospective analysis supports incorporation of PAX‐FOXO1 fusion status into risk stratification and treatment allocation. Pediatr Blood Cancer 2013;60:1411–1417. © 2013 Wiley Periodicals, Inc.</abstract><cop>United States</cop><pub>Blackwell Publishing Ltd</pub><pmid>23526739</pmid><doi>10.1002/pbc.24532</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Pediatric blood & cancer, 2013-09, Vol.60 (9), p.1411-1417 |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Adolescent Adult Antineoplastic Combined Chemotherapy Protocols - administration & dosage Child Child, Preschool Disease-Free Survival Female Hematology Humans Infant Male Neoplasm Staging Oncogene Proteins, Fusion - genetics Oncology Paired Box Transcription Factors - genetics PAX-FOXO1 PAX7 Transcription Factor - genetics Pediatrics Prospective Studies Retrospective Studies rhabdomyosarcoma Rhabdomyosarcoma - drug therapy Rhabdomyosarcoma - genetics Rhabdomyosarcoma - mortality Risk Factors survival Survival Rate |
| title | PAX-FOXO1 fusion status drives unfavorable outcome for children with rhabdomyosarcoma: A children's oncology group report |
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