{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T11:40:13Z","timestamp":1793878813803,"version":"4.7.0"},"reference-count":25,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2019,11,17]],"date-time":"2019-11-17T00:00:00Z","timestamp":1573948800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006244","name":"Stichting Kinderen Kankervrij","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006244","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2020,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The clinical course of neuroblastoma stage 4S or MS is characterized by a high rate of spontaneous tumor regression and favorable outcome. However, the clinical course and rate of the regression are poorly understood.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A retrospective cohort study was performed, including all patients with stage 4S neuroblastoma without MYCN amplification, from two Dutch centers between 1972 and 2012. We investigated the clinical characteristics, the biochemical activity reflected in urinary catecholamine excretion, and radiological imaging to describe the kinetics of tumor regression, therapy response and outcome.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The cohort of 31 patients reached a 10\u2010year overall survival of 84% \u00b1 7% (median follow\u2010up 16 years; range, 3.3\u201039). During the regressive phase, liver size normalized in 91% of the patients and catecholamine excretion in 83%, both after a median of two months (liver size: range, 0\u2010131; catecholamines: range, 0\u2010158). The primary tumors completely regressed in 69% after 13 months (range, 6\u201073), and the liver architecture normalized in 52% after 15 months (range, 5\u2010131). Antitumor treatment was given in 52% of the patients. Interestingly, regression rates were similar for treated and untreated patients. Four of seven patients\u00a0&lt;\u00a04\u00a0weeks old died of rapid liver expansion and organ compression. Three patients progressed to stage 4, 3 to 13 months after diagnosis; all had persistently elevated catecholamines.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Patients\u00a0&lt;\u00a04\u00a0weeks old with neuroblastoma stage 4S are at risk of fatal outcome caused by progression of liver metastases. In other patients, tumor regression is characterized by a rapid biochemical normalization that precedes radiological regression.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pbc.28061","type":"journal-article","created":{"date-parts":[[2019,11,18]],"date-time":"2019-11-18T04:31:17Z","timestamp":1574051477000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Neuroblastoma stage 4S: Tumor regression rate and risk factors of progressive disease"],"prefix":"10.1002","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4585-5411","authenticated-orcid":false,"given":"Michelle L.","family":"Tas","sequence":"first","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1234-4890","authenticated-orcid":false,"given":"Michelle","family":"Nagtegaal","sequence":"additional","affiliation":[{"name":"Department of Social Pediatrics Emma Children's Hospital\/Amsterdam University Medical Centers  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9630-0814","authenticated-orcid":false,"given":"Kathelijne C.J.M.","family":"Kraal","sequence":"additional","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2356-5197","authenticated-orcid":false,"given":"Godelieve A.M.","family":"Tytgat","sequence":"additional","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology  Utrecht The Netherlands"},{"name":"Department of Social Pediatrics Emma Children's Hospital\/Amsterdam University Medical Centers  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nico G.G.M.","family":"Abeling","sequence":"additional","affiliation":[{"name":"Laboratory for Genetic Metabolic Diseases Amsterdam University Medical Centers  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0890-7585","authenticated-orcid":false,"given":"Jan","family":"Koster","sequence":"additional","affiliation":[{"name":"Department of Oncogenomics Amsterdam University Medical Centers\/University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7695-030X","authenticated-orcid":false,"given":"Saskia M.F.","family":"Pluijm","sequence":"additional","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1353-9166","authenticated-orcid":false,"given":"C. Michel","family":"Zwaan","sequence":"additional","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology  Utrecht The Netherlands"},{"name":"Department of Pediatric Oncology Erasmus Medical Center, Sophia Children's Hospital  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6270-9483","authenticated-orcid":false,"given":"Bart","family":"de Keizer","sequence":"additional","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology  Utrecht The Netherlands"},{"name":"Department of Radiology and Nuclear Medicine University Medical Center Utrecht  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2007-0431","authenticated-orcid":false,"given":"Jan J.","family":"Molenaar","sequence":"additional","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0503-5838","authenticated-orcid":false,"given":"Max M.","family":"van Noesel","sequence":"additional","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,11,17]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1993.11.8.1466"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.16.6876"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(197102)27:2<374::AID-CNCR2820270221>3.0.CO;2-G"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-8049(98)00395-5"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19800301)45:5<833::AID-CNCR2820450502>3.0.CO;2-U"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2000.18.3.477"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6601154"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-911X(199612)27:6<521::AID-MPO3>3.0.CO;2-N"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(12)70012-8"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.175141.114"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.2214\/ajr.171.6.9843315"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/0009-8981(84)90181-5"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-911X(199904)32:4<294::AID-MPO11>3.0.CO;2-2"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.16.0630"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.23077"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.20067"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(71)91606-0"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19860715)58:2<372::AID-CNCR2820580229>3.0.CO;2-2"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19920915)70:6<1625::AID-CNCR2820700631>3.0.CO;2-6"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1998.16.6.2007"},{"issue":"1","key":"e_1_2_9_22_1","article-title":"Diagnostic and prognostic markers in infants with disseminated neuroblastoma: a retrospective analysis from the Italian Cooperative Group for Neuroblastoma","volume":"15","author":"Di Cataldo A","year":"2009","journal-title":"Med Sci Monit"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.18.00419"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.06.104"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6603820"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aat6768"}],"container-title":["Pediatric Blood &amp; 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