{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T15:22:55Z","timestamp":1790695375714,"version":"4.1.0"},"reference-count":34,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2018,7,17]],"date-time":"2018-07-17T00:00:00Z","timestamp":1531785600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"European Commission 5th Framework Grant"},{"name":"St Anna Kinderkrebsforschung"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2018,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Risk stratification is crucial to treatment decision\u2010making in neuroblastoma. This study aimed to explore factors present at diagnosis affecting outcome in patients aged\u00a0\u226518 months with metastatic neuroblastoma and to develop a simple risk score for prognostication.<\/jats:p><\/jats:sec><jats:sec><jats:title>Procedure<\/jats:title><jats:p>Data were derived from the European high\u2010risk neuroblastoma 1 (HR\u2010NBL1)\/International Society for Paediatric Oncology European Neuroblastoma (SIOPEN) trial with analysis restricted to patients aged \u226518 months with metastatic disease and treated prior to the introduction of immunotherapy. Primary endpoint was 5\u2010year event\u2010free survival (EFS). Prognostic factors assessed were sex, age, tumour MYCN amplification (MNA) status, serum lactate dehydrogenase (LDH)\/ferritin, primary tumour and metastatic sites. Factors significant in univariate analysis were incorporated into a multi\u2010variable model and an additive scoring system developed based on estimated log\u2010cumulative hazard ratios.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The cohort included 1053 patients with median follow\u2010up 5.5\u00a0years and EFS 27\u00a0\u00b1\u00a01%. In univariate analyses, age; serum LDH and ferritin; involvement of bone marrow, bone, liver or lung; and &gt;1 metastatic system\/compartment were associated with worse EFS. Tumour MNA was not associated with worse EFS. A multi\u2010variable model and risk score incorporating age (&gt;5 years, 2 points), serum LDH (&gt;1250\u00a0U\/L, 1 point) and number of metastatic systems (&gt;1, 2 points) were developed. EFS was significantly correlated with risk score: EFS 52\u00a0\u00b1\u00a09% for score\u00a0=\u00a00\u00a0versus 6\u00a0\u00b1\u00a03% for score\u00a0=\u00a05 (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.0001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>A simple score can identify an \u201cultra\u2010high risk\u201d (UHR) cohort (score\u00a0=\u00a05) comprising 8% of patients with 5\u2010year EFS\u00a0&lt;10%. These patients appear not to benefit from induction therapy and could potentially be directed earlier to alternative experimental therapies in future trials.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pbc.27363","type":"journal-article","created":{"date-parts":[[2018,7,17]],"date-time":"2018-07-17T10:31:30Z","timestamp":1531823490000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":67,"title":["Risk stratification of high\u2010risk metastatic neuroblastoma: A report from the HR\u2010NBL\u20101\/SIOPEN study"],"prefix":"10.1002","volume":"65","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4859-1108","authenticated-orcid":false,"given":"Daniel A.","family":"Morgenstern","sequence":"first","affiliation":[{"name":"Paediatric Haematology\/Oncology Hospital for Sick Children and University of Toronto  Toronto Canada"},{"name":"Paediatric Haematology\/Oncology Great Ormond Street Hospital and UCL Institute of Child Health  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrike","family":"P\u00f6tschger","sequence":"additional","affiliation":[{"name":"Studies and Statistics on Integrated Research and Projects St Anna Kinderkrebsforschung  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas","family":"Moreno","sequence":"additional","affiliation":[{"name":"Paediatric Haematology\/Oncology Hospital Nino Jes\u00fas  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vassilios","family":"Papadakis","sequence":"additional","affiliation":[{"name":"Paediatric Haematology\/Oncology Agia Sofia Children's Hospital  Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cormac","family":"Owens","sequence":"additional","affiliation":[{"name":"Paediatric Haematology\/Oncology Our Lady's Children's Hospital  Crumlin Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0461-1867","authenticated-orcid":false,"given":"Shifra","family":"Ash","sequence":"additional","affiliation":[{"name":"Paediatric Haematology\/Oncology Schneider Children's Medical Center of Israel  Petah Tikva Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Pasqualini","sequence":"additional","affiliation":[{"name":"Department of Paediatric and Adolescent Oncology Institut Gustav Roussy  Viellejuif France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7203-4176","authenticated-orcid":false,"given":"Roberto","family":"Luksch","sequence":"additional","affiliation":[{"name":"Dipartimento di Ematologia e Onco\u2010ematologia Pediatrica Fondazione IRCCS Istituto Nazionale dei Tumori  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Garaventa","sequence":"additional","affiliation":[{"name":"Paediatric Oncology Istituto Giannia Gaslini  Genova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adela","family":"Canete","sequence":"additional","affiliation":[{"name":"Pediatric Oncology Unit Hospital Universitario y Politecnico La Fe  Valencia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Elliot","sequence":"additional","affiliation":[{"name":"Paediatric Oncology Leeds Teaching Hospital NHS Trust  Leeds UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandra","family":"Wieczorek","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology and Hematology Institute of Pediatrics Jagiellonian University Medical College  Krakow Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Genevi\u00e8ve","family":"Laureys","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology\/Oncology and Stem Cell Transplantation University Hospital Ghent  Ghent Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Per","family":"Kogner","sequence":"additional","affiliation":[{"name":"Department of Women's and Children's Health, Karolinska Institutet Astrid Lindgren Children's Hospital Karolinska University Hospital  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josef","family":"Malis","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology and Oncology University Hospital Motol  Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen","family":"Ruud","sequence":"additional","affiliation":[{"name":"Department of Paediatric Medicine Rikshospitalet Oslo University Hospital  Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maja","family":"Beck\u2010Popovic","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Pediatric Surgery Pediatric Haematology Oncology Unit University Hospital Lausanne  Lausanne Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gudrun","family":"Schleiermacher","sequence":"additional","affiliation":[{"name":"Department of Paediatrics Institut Curie  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique","family":"Valteau\u2010Couanet","sequence":"additional","affiliation":[{"name":"Department of Paediatric and Adolescent Oncology Institut Gustav Roussy  Viellejuif France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth","family":"Ladenstein","sequence":"additional","affiliation":[{"name":"Paediatric Haematology\/Oncology St Anna Kinderspital and St Anna Kinderkrebforschung  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,7,17]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.16.6785"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(07)60983-0"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2013.53.6342"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2016.06.005"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.21684"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2012.375"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00259-014-2909-1"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.112.112334"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00259-017-3829-7"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2013.53.3604"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(08)70069-X"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.27.3524"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(17)30070-0"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6605014"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6605029"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6605621"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/9781118032985"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/0197-2456(96)00075-X"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.2864"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1177\/0962280209105020"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.1742"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0006-341X.2005.030814.x"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(13)70309-7"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000421-199208000-00004"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1097\/00043426-199208000-00005"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.4143\/crt.2015.481"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00432-015-2054-7"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00259-016-3516-0"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2014.09.019"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature14980"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3438"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-016-0896-7"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.29461"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molonc.2014.01.010"}],"container-title":["Pediatric Blood &amp; Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fpbc.27363","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pbc.27363","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,17]],"date-time":"2023-09-17T08:17:37Z","timestamp":1694938657000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/pbc.27363"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,7,17]]},"references-count":34,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2018,11]]}},"alternative-id":["10.1002\/pbc.27363"],"URL":"https:\/\/doi.org\/10.1002\/pbc.27363","archive":["Portico"],"relation":{},"ISSN":["1545-5009","1545-5017"],"issn-type":[{"value":"1545-5009","type":"print"},{"value":"1545-5017","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,7,17]]},"assertion":[{"value":"2018-02-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-06-23","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-07-17","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e27363"}}