{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T09:50:25Z","timestamp":1788861025621,"version":"build-2803163510"},"reference-count":29,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,2,6]],"date-time":"2024-02-06T00:00:00Z","timestamp":1707177600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deutsche Kinderkrebsstiftung","award":["A20I9\/07\u2014DKS 2019.04"],"award-info":[{"award-number":["A20I9\/07\u2014DKS 2019.04"]}]},{"name":"Deutsche Kinderkrebsstiftung","award":["668596"],"award-info":[{"award-number":["668596"]}]},{"name":"European Union\u2019s Horizon 2020 Research and Innovation Programme","award":["A20I9\/07\u2014DKS 2019.04"],"award-info":[{"award-number":["A20I9\/07\u2014DKS 2019.04"]}]},{"name":"European Union\u2019s Horizon 2020 Research and Innovation Programme","award":["668596"],"award-info":[{"award-number":["668596"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Survival rates for HB patients have improved; however, outcomes for patients who relapse remain poor. A retrospective review of information gathered for the HB99 study and the German Liver Tumor Registry identified 25 relapse patients (6.9%, 25\/362). The median time from initial diagnosis to first relapse was 13 months (range: 5\u201366 months). Two patients relapsed &gt;36 months after initial diagnosis. A total of 68% (17\/25) of relapses were metastatic, 24% local, and 8% combined. 67% of local relapses were alive at the last follow-up, in contrast to 53% of metastatic and 0% of combined relapses. At the last follow-up, 73% (8\/11) of patients with lung relapses were still alive (0\/4 with peritoneal, 1\/2 with CNS involvement). A total of 20% of the patients had AFP-negative relapses, 64% of the relapse patients achieved a second complete remission, 69% were still in complete second remission at the last follow-up (median FU of 66 months), and 83% (5\/6) of irinotecan-na\u00efve patients who received relapse treatment including irinotecan were in second complete remission at the last follow-up. The 3-year overall survival\/event-free survival from relapse was 63%\/48% respectively. There is a good chance that HB patients will achieve a second remission despite a first relapse. However, patients who suffer further relapses tend to have a poorer prognosis.<\/jats:p>","DOI":"10.3390\/cancers16040696","type":"journal-article","created":{"date-parts":[[2024,2,6]],"date-time":"2024-02-06T12:38:24Z","timestamp":1707223104000},"page":"696","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Hepatoblastoma Relapse\u2014Findings from the German HB99 Trial and the German Liver Tumor Registry"],"prefix":"10.3390","volume":"16","author":[{"given":"Rebecca","family":"Maxwell","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Dr. von Hauner Children\u2019s Hospital, University Hospital, LMU Munich, Lindwurmstra\u00dfe 4, 80337 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beate","family":"H\u00e4berle","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, Dr. von Hauner Children\u2019s Hospital, University Hospital, LMU Munich, 80337 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8581-2803","authenticated-orcid":false,"given":"Roland","family":"Kappler","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, Dr. von Hauner Children\u2019s Hospital, University Hospital, LMU Munich, 80337 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dietrich","family":"von Schweinitz","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, Dr. von Hauner Children\u2019s Hospital, University Hospital, LMU Munich, 80337 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Rassner","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Dr. von Hauner Children\u2019s Hospital, University Hospital, LMU Munich, Lindwurmstra\u00dfe 4, 80337 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"von Frowein","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Dr. von Hauner Children\u2019s Hospital, University Hospital, LMU Munich, Lindwurmstra\u00dfe 4, 80337 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Schmid","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Dr. von Hauner Children\u2019s Hospital, University Hospital, LMU Munich, Lindwurmstra\u00dfe 4, 80337 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1097\/MOT.0000000000000618","article-title":"Contemporary management of hepatoblastoma","volume":"24","author":"Hafberg","year":"2019","journal-title":"Curr. Opin. Organ. Transplant."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/S1089-3261(05)70163-X","article-title":"Hepatic Tumors in Children","volume":"5","author":"Stocker","year":"2001","journal-title":"Clin. Liver Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1097\/MOP.0000000000000046","article-title":"Hepatoblastoma state of the art: Pathology, genetics, risk stratification, and chemotherapy","volume":"26","author":"Czauderna","year":"2014","journal-title":"Curr. Opin. Pediatr."},{"key":"ref_4","unstructured":"Erdmann, F., Kaatsch, P., Grabow, D., and Spix, C. (2020). German Childhood Cancer Registry\u2014Annual Report 2019 (1980\u20132018), Institute of Medical Biostatistics, Epidemio logy and Informatics (IMBEI) at the University Medical Center of the Johannes Gutenberg University Mainz."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1055\/a-1014-3250","article-title":"High Dose Chemotherapy with Autologous Stem Cell Transplantation in Hepatoblastoma does not Improve Outcome. Results of the GPOH Study HB99","volume":"231","author":"Maxwell","year":"2019","journal-title":"Klin. Padiatr."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1016\/j.ejca.2012.10.003","article-title":"Relapses in hepatoblastoma patients: Clinical characteristics and outcome\u2014Experience of the International Childhood Liver Tumour Strategy Group (SIOPEL)","volume":"49","author":"Semeraro","year":"2013","journal-title":"Eur. J. Cancer"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1016\/j.pedneo.2021.03.018","article-title":"A retrospective study of clinical features and outcome in patients with refractory or recurrent hepatoblastoma: A single institution experience","volume":"62","author":"Hou","year":"2021","journal-title":"Pediatr. Neonatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1097\/MPH.0000000000000474","article-title":"Outcomes of Patients with Relapse Hepatoblastoma Enrolled on Children\u2019s Oncology Group (COG) Phase I and II Studies","volume":"38","author":"Meyers","year":"2016","journal-title":"J. Pediatr. Hematol. Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Somers, K.M., Tabbouche, R.B., Bondoc, A., Towbin, A.J., Ranganathan, S., Tiao, G., and Geller, J. (2023). Retreatment with Cisplatin May Provide a Survival Advantage for Children with Relapsed\/Refractory Hepatoblastoma: An Institutional Experience. Cancers, 15.","DOI":"10.3390\/cancers15153921"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1007\/s00247-005-0029-6","article-title":"Radiological staging in children with hepatoblastoma","volume":"36","author":"Roebuck","year":"2006","journal-title":"Pediatr. Radiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1662","DOI":"10.1056\/NEJMoa0810613","article-title":"Cisplatin versus cisplatin plus doxorubicin for standard-risk hepatoblastoma","volume":"361","author":"Perilongo","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2584","DOI":"10.1200\/JCO.2009.22.4857","article-title":"Successful treatment of childhood high-risk hepatoblastoma with dose-Intensive multiagent chemotherapy and surgery: Final results of the SIOPEL-3HR Study","volume":"28","author":"Zsiros","year":"2010","journal-title":"J. Clin. Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1016\/S1470-2045(13)70272-9","article-title":"International Childhood Liver Tumors Strategy Group (SIOPEL) et al. Dose-dense cisplatin-based chemotherapy and surgery for children with high-risk hepatoblastoma (SIOPEL-4): A prospective, single-arm, feasibility study","volume":"14","author":"Zsiros","year":"2013","journal-title":"Lancet Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1080\/01621459.1958.10501452","article-title":"Nonparametric estimation from incomplete oberservations","volume":"53","author":"Kaplan","year":"1958","journal-title":"J. Am. Stat. Assoc."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1016\/j.jpedsurg.2019.01.036","article-title":"Multifocal hepatoblastoma: What is the risk of recurrent disease in the remnant liver?","volume":"54","author":"Fahy","year":"2019","journal-title":"J. Pediatr. Surg."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1002\/pbc.25240","article-title":"Impact of postoperative complications on overall survival of patients with hepatoblastoma","volume":"62","author":"Becker","year":"2015","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1002\/(SICI)1097-0215(20000115)85:2<151::AID-IJC1>3.0.CO;2-6","article-title":"Hepatocyte growth-factor-scatter factor can stimulate post-operative tumor- cell proliferation in childhood hepatoblastoma","volume":"85","author":"Faundez","year":"2000","journal-title":"Int. J. Cancer"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.1007\/s00247-014-3000-6","article-title":"Relapse surveillance in AFP-positive hepatoblastoma: Re-evaluating the role of imaging","volume":"44","author":"Rojas","year":"2014","journal-title":"Pediatr. Radiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e76","DOI":"10.1097\/MPH.0000000000001971","article-title":"AFP-L3 as a Prognostic Predictor of Recurrence in Hepatoblastoma: A Pilot Study","volume":"43","author":"Kawahara","year":"2021","journal-title":"J. Pediatr. Hematol. Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"221","DOI":"10.2165\/11597740-000000000-00000","article-title":"Current and future mangement strategies for relapsed or progressive hepatoblastoma","volume":"14","author":"Venkatramani","year":"2012","journal-title":"Pediatr. Drugs"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1002\/pbc.23069","article-title":"Prognostic implications of serum alpha-fetoprotein response during treatment of hepatoblastoma","volume":"57","author":"Koh","year":"2011","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1007\/s10147-018-1285-4","article-title":"Rapid decrease of serum alpha-fetoprotein and tumor volume predicts outcome in children with hepatoblastoma treated with neoadjuvant chemotherapy","volume":"23","author":"Nguyen","year":"2018","journal-title":"Int. J. Clin. Oncol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3456","DOI":"10.1016\/j.ejca.2012.06.023","article-title":"Efficacy of irinotecan single drug treatment in children with refractory or recurrent hepatoblastoma\u2014A phase II trial of the childhood liver tumour strategy group (SIOPEL)","volume":"48","author":"Zsiros","year":"2012","journal-title":"Eur. J. Cancer"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1002\/pbc.24218","article-title":"Relapsed hepatoblastoma","volume":"59","author":"Feusner","year":"2012","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"18","DOI":"10.3109\/08880018.2014.909913","article-title":"Vincristine and irinotecan in children with relapsed hepatoblastoma: A single-Institution experience","volume":"32","author":"Zhang","year":"2015","journal-title":"Paediatr. Hematol. Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1002\/pbc.10376","article-title":"Liver Transplantation for Hepatoblastoma: Results from the International Society of Paediatric Oncology (SIOP) Study SIOPEL-1 and Review of World Experience","volume":"42","author":"Otte","year":"2004","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1002\/hep.32223","article-title":"European Liver Transplant Registry: Donor and transplant surgery aspects of 16,641 liver transplantations in children","volume":"75","author":"Baumann","year":"2022","journal-title":"Hepatology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1002\/gcc.22390","article-title":"Small cell undifferentiated (SCUD) hepatoblastomas: All malignant rhabdoid tumors?","volume":"55","author":"Vokuhl","year":"2016","journal-title":"Genes Chromosomes Cancer"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1038\/modpathol.2013.80","article-title":"Towards an international pediatric liver tumor concensus classification: Proceedings of the Los Angeles COG liver tumors symposium","volume":"27","author":"Alaggio","year":"2014","journal-title":"Mod. Pathol."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/16\/4\/696\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T13:56:03Z","timestamp":1760104563000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/16\/4\/696"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,6]]},"references-count":29,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2024,2]]}},"alternative-id":["cancers16040696"],"URL":"https:\/\/doi.org\/10.3390\/cancers16040696","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,6]]}}}