{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T13:07:00Z","timestamp":1773493620306,"version":"3.50.1"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,10,10]],"date-time":"2022-10-10T00:00:00Z","timestamp":1665360000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100001543","name":"Children's Cancer Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001543","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pediatr."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Between 5 and 15% of children with neuroblastoma (NB) present with or develop spinal canal invasion (SCI). The majority of these children have symptoms of epidural compression of spinal cord and\/or spinal nerves. Treatment of NB-SCI is considered an emergency but its modalities are not yet well-established. Independently of treatment, NB-SCI may result in significant long-term disabilities. We report on the first prospective study of NB-SCI focused on presenting characteristics of both symptomatic and asymptomatic patients and correlation between SCI-related symptoms and imaging features.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and methods<\/jats:title><jats:p>This SIOPEN prospective NB-SCI study opened in June 2014. Patient data including SCI symptoms evaluated by standardized measures and spinal cord imaging studies were collected for each patient. For the purpose of this study data entry was locked on July 2021.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of the 208 NB-SCI patients registered, 196 were evaluable for this analysis of whom 67% were symptomatic and 33% asymptomatic. Median age was 11 months. The thorax was the commonest primary tumor site. The median intervals between initial symptoms and diagnosis and between first medical visit and diagnosis were 14 and 3 days, respectively. The was no statistical difference in frequency of presenting characteristics between symptomatic and asymptomatic patients. Presenting features of NB-SCI patients differed from other NBs for older median age, prevalence of thoracic vs. abdominal primary site, prevalence of localized vs. metastatic disease and lower incidence of MYCN gene amplification. The most common SCI features were motor deficit in the younger and pain in the older patients that correlated on imaging with both transverse and longitudinal extent but not with the level of intraspinal tumor. Spinal cord T2-hyperintensity was more frequently detected in symptomatic patients (not significant).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This prospective study confirms that children with NB-SCI differ from NBs without SCI. Compared to previous studies, it provides more detailed information regarding presenting symptoms, time intervals between SCI symptoms, medical visit and diagnosis, and correlations between symptoms and imaging features.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fped.2022.1023498","type":"journal-article","created":{"date-parts":[[2022,10,10]],"date-time":"2022-10-10T05:58:06Z","timestamp":1665381486000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Presenting features of neuroblastoma with spinal canal invasion. A prospective study of the International Society of Pediatric Oncology Europe - Neuroblastoma (SIOPEN)"],"prefix":"10.3389","volume":"10","author":[{"given":"Stefania","family":"Sorrentino","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shifra","family":"Ash","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Riccardo","family":"Haupt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dominique","family":"Plantaz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabelle","family":"Schiff","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara","family":"Hero","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thorsten","family":"Simon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Denis","family":"Kachanov","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatyana","family":"Shamanskaya","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katheljine","family":"Kraal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annemieke","family":"Littooij","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexsandra","family":"Wieczoreck","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Walentyna","family":"Balwierz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Genevi\u00e8ve","family":"Laureys","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catherine","family":"Trager","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fiammetta","family":"Sertorio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanni","family":"Erminio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martina","family":"Fragola","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maja","family":"Beck Popovic","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruno","family":"De Bernardi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toby","family":"Trahair","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,10,10]]},"reference":[{"key":"B1","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1002\/9781444300222.ch47","article-title":"Peripheral neuroblastic tumors","volume-title":"Clinical Endocrine Oncology","author":"De Bernardi","year":"2008"},{"key":"B2","doi-asserted-by":"publisher","first-page":"2106","DOI":"10.1016\/S0140-6736(07)60983-0","article-title":"Neuroblastoma","volume":"369","author":"Maris","year":"2007","journal-title":"Lancet."},{"key":"B3","first-page":"1644","article-title":"Tumors of the spine and spinal cord","volume-title":"Pediatric Neuroradiology: Head, Neck and Spine","author":"Tortori-Donati","year":"2005"},{"key":"B4","doi-asserted-by":"publisher","first-page":"3095","DOI":"10.1002\/1097-0142(19800615)45:12<3095::AID-CNCR2820451236>3.0.CO;2-Y","article-title":"Neuroblastoma: a review of 21 cases presenting with spinal cord compression","volume":"45","author":"Punt","year":"1980","journal-title":"Cancer."},{"key":"B5","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1007\/978-3-030-18396-7_9","article-title":"Spinal canal involvement in peripheral neuroblastic tumors","volume-title":"Neuroblastoma Clinical and Surgical Management","author":"Ash","year":"2020"},{"key":"B6","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1016\/j.jpeds.2017.05.051","article-title":"Spinal canal involvement in neuroblastoma","volume":"188","author":"Trahair","year":"2017","journal-title":"J Pediatr."},{"key":"B7","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1056\/NEJM195106142442406","volume":"244","year":"1951","journal-title":"N Engl J Med"},{"key":"B8","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1002\/(SICI)1097-0142(19960715)78:2<311::AID-CNCR19>3.0.CO;2-Z","article-title":"The treatment of neuroblastoma with intraspinal extension with chemotherapy followed by surgical removal of residual disease. A prospective study of 42 patients - results of the NBL 90 Study of the French Society of Paediatric Oncology","volume":"78","author":"Plantaz","year":"1996","journal-title":"Cancer."},{"key":"B9","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1200\/JCO.2001.19.1.183","article-title":"Neuroblastoma with symptomatic spinal cord compression at diagnosis: treatment and results with 76 cases","volume":"19","author":"De Bernardi","year":"2001","journal-title":"J Clin Oncol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"1047","DOI":"10.1200\/JCO.2001.19.4.1047","article-title":"Treatment and outcome of 83 children with intraspinal neuroblastoma: the Pediatric Oncology Group experience","volume":"19","author":"Katzenstein","year":"2001","journal-title":"J Clin Oncol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1111\/j.1469-8749.2012.04219.x","article-title":"Short- and long-term outcome of patients with symptoms of spinal cord compression by neuroblastoma","volume":"54","author":"Simon","year":"2012","journal-title":"Develop Med Child Neurol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1369","DOI":"10.1002\/pbc.25028","article-title":"Neuroblastoma with symptomatic epidural compression in the infant: the AIEOP experience","volume":"61","author":"De Bernardi","year":"2014","journal-title":"Pediatr Blood Cancer."},{"key":"B13","doi-asserted-by":"publisher","first-page":"907","DOI":"10.3892\/ol.2014.2795","article-title":"Intraspinal neuroblastoma: treatment options and neurological outcome of spinal cord compression","volume":"9","author":"Fawzy","year":"2015","journal-title":"Oncol Lett."},{"key":"B14","doi-asserted-by":"publisher","first-page":"e26451","DOI":"10.1002\/pbc.26451","article-title":"Treatment and outcome of neuroblastoma with intraspinal extension: a systematic review","volume":"64","author":"Kraal","year":"2017","journal-title":"Pediatr Blood Cancer."},{"key":"B15","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1002\/(SICI)1096-911X(199905)32:5<353::AID-MPO8>3.0.CO;2-2","article-title":"Long-term outcome of patients with intraspinal neuroblastoma","volume":"32","author":"Hoover","year":"1999","journal-title":"Med Pediatr Oncol"},{"key":"B16","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1002\/pbc.23037","article-title":"Late sequelae of symptomatic epidural compression in children with localized neuroblastoma","volume":"57","author":"Angelini","year":"2011","journal-title":"Pediatr Blood Cancer."},{"key":"B17","doi-asserted-by":"publisher","first-page":"990","DOI":"10.1002\/pbc.25925","article-title":"Neuroblastoma with intraspinal extension: health problems in long-term survivors","volume":"63","author":"Kraal","year":"2016","journal-title":"Pediatr Blood Cancer."},{"key":"B18","doi-asserted-by":"publisher","first-page":"e27670","DOI":"10.1002\/pbc.27670","article-title":"Multidisciplinary surgical strategy for dumbbell neuroblastoma: a single-center experience of 32 cases","volume":"66","author":"Pio","year":"2016","journal-title":"Pediatr Blood Cancer."},{"key":"B19","doi-asserted-by":"publisher","first-page":"2330","DOI":"10.1200\/JCO.1995.13.9.2330","article-title":"Surgical treatment of spinal cord compression from epidural metastasis","volume":"13","author":"Sundaresan","year":"1995","journal-title":"J Clin Oncol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1016\/S0022-3476(84)80996-8","article-title":"Chemotherapy as an alternative to laminectomy and radiation in the management of epidural tumor","volume":"104","author":"Hayes","year":"1984","journal-title":"J Pediatr."},{"key":"B21","unstructured":"Neuroblastoma producing spinal cord compression. Rapid relief with low dose of radiation468790\n            NguyenNP\n            SallahS\n            LudinA\n            SalehpourMR\n            KarlssonU\n            FilesB\n          11205201Anticancer Res.202000"},{"key":"B22","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1016\/j.canlet.2005.01.053","article-title":"Epidural compression in neuroblastoma. Diagnostic and therapeutic aspects","volume":"228","author":"De Bernardi","year":"2005","journal-title":"Cancer Lett."},{"key":"B23","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1002\/(SICI)1097-0142(19990715)86:2<364::AID-CNCR21>3.0.CO;2-7","article-title":"The international neuroblastoma pathology classification (the Shimada system)","volume":"86","author":"Shimada","year":"1999","journal-title":"Cancer."},{"key":"B24","doi-asserted-by":"publisher","first-page":"1466","DOI":"10.1200\/JCO.1993.11.8.1466","article-title":"Revisions of the international criteria for neuroblastoma diagnosis, staging, and response to treatment","volume":"11","author":"Brodeur","year":"1993","journal-title":"J Clin Oncol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1200\/JCO.2008.16.6785","article-title":"The International Neuroblastoma Risk Group (INRG) classification system: an INRG Task Force report","volume":"27","author":"Cohn","year":"2009","journal-title":"J Clin Oncol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"S50","DOI":"10.1080\/10790268.2003.11754575","article-title":"International standards for neurological classification of spinal cord injury","volume":"26","author":"Kirshblum","year":"2003","journal-title":"J Spinal Cord Med."},{"key":"B27","year":"2009","journal-title":"Common Terminology Criteria for Adverse Events v4.0, NCI, NIH, DHHS. NIH publication # 09\u20137473"},{"key":"B28","first-page":"293","article-title":"The FLACC: a behavioral scale for scoring postoperative pain in young children","volume":"23","author":"Merkel","year":"1997","journal-title":"Pediatr Nurs."},{"key":"B29","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1016\/j.rcl.2013.11.002","article-title":"Imaging approach to the cord T2 hyperintensity (myelopathy)","volume":"52","author":"Grayev","year":"2014","journal-title":"Radiol Clin North Am."},{"key":"B30","doi-asserted-by":"publisher","first-page":"6459","DOI":"10.1200\/JCO.2005.05.571","article-title":"Evidence of an age cut-off greater than 365 days for neuroblastoma risk group stratification in the Children's Oncology Group","volume":"23","author":"London","year":"2005","journal-title":"J Clin Oncol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"2331","DOI":"10.1200\/JCO.2009.24.8351","article-title":"Improved survival of children with neuroblastoma between 1979-2005: a report of the Italian Neuroblastoma Registry","volume":"28","author":"Haupt","year":"2010","journal-title":"J Clin Oncol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"1710","DOI":"10.1200\/JCO.2006.08.8799","article-title":"Retrospective study of childhood ganglioneuroma","volume":"26","author":"De Bernardi","year":"2008","journal-title":"J Clin Oncol."}],"container-title":["Frontiers in Pediatrics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2022.1023498\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,10]],"date-time":"2022-10-10T05:58:14Z","timestamp":1665381494000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2022.1023498\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,10]]},"references-count":32,"alternative-id":["10.3389\/fped.2022.1023498"],"URL":"https:\/\/doi.org\/10.3389\/fped.2022.1023498","relation":{},"ISSN":["2296-2360"],"issn-type":[{"value":"2296-2360","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,10]]},"article-number":"1023498"}}