{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T16:44:44Z","timestamp":1793378684589,"version":"4.5.0"},"reference-count":23,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2023,8,1]],"date-time":"2023-08-01T00:00:00Z","timestamp":1690848000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Hepatoblastoma (HB) is the most common liver malignancy in children. There is no standard of care for management of relapsed\/refractory HB (rrHB) and reports in the literature are limited. Objective: To describe presenting features, biology, treatment strategies, and outcomes for pediatric patients with relapsed\/refractory hepatoblastoma. Methods: An IRB-approved retrospective institutional review of patients with rrHB who presented for consultation and\/or care from 2000\u20132019. Clinical, radiographic, and histologic data were collected from all patients. Results: Thirty subjects were identified with a median age of 19.5 months (range 3\u2013169 months) at initial diagnosis and 32.5 months (range 12\u2013194 months) at time of first relapse. 63% of subjects were male, 70% Caucasian, and 13% were born premature. Three subjects had a known cancer predisposition syndrome. Eight patients had refractory disease while 22 patients had relapsed disease. Average time from initial diagnosis to relapse or progression was 12.5 months. Average alpha-fetoprotein (AFP) at initial diagnosis was 601,203 ng\/mL (range 121\u20132,287,251 ng\/mL). Average AFP at relapse was 12,261 ng\/mL (range 2.8\u2013201,000 ng\/mL). For patients with tumor sequencing (n = 17), the most common mutations were in CTNNB1 (13) and NRF2 (4). First relapse sites were lungs (n = 12), liver (n = 11) and both (n = 6). More than one relapse\/progression occurred in 47% of subjects; 6 had \u22653 relapses. Pathology in patients with multiply relapsed disease was less differentiated including descriptions of small cell undifferentiated (n = 3), pleomorphic (n = 1), transitional liver cell tumor (n = 2) and HB with carcinoma features (n = 1). All subjects underwent surgical resection of site of relapsed disease with 7 subjects requiring liver transplantation. Overall survival was 50%. Survival was associated with use of cisplatin at relapse (78.6% with vs. 25% without, p = 0.012). The most common late effect was ototoxicity with at least mild sensorineural hearing loss found in 80% of subjects; 54% required hearing aids. Conclusions: Retreatment with cisplatin at the time of relapse may provide an advantage for some patients with hepatoblastoma. Multiply relapsed disease was not uncommon and not associated with a worse prognosis. Careful attention should be paid to cumulative therapy-induced toxicity while concurrently aiming to improve cure.<\/jats:p>","DOI":"10.3390\/cancers15153921","type":"journal-article","created":{"date-parts":[[2023,8,2]],"date-time":"2023-08-02T10:57:33Z","timestamp":1690973853000},"page":"3921","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Retreatment with Cisplatin May Provide a Survival Advantage for Children with Relapsed\/Refractory Hepatoblastoma: An Institutional Experience"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8683-9488","authenticated-orcid":false,"given":"Katherine M.","family":"Somers","sequence":"first","affiliation":[{"name":"Division of Pediatric Hematology\/Oncology, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH 45229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2897-4201","authenticated-orcid":false,"given":"Rachel Bernstein","family":"Tabbouche","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology\/Oncology, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH 45229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9802-5948","authenticated-orcid":false,"given":"Alexander","family":"Bondoc","sequence":"additional","affiliation":[{"name":"Department of Pediatric and Thoracic Surgery, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH 45229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1729-5071","authenticated-orcid":false,"given":"Alexander J.","family":"Towbin","sequence":"additional","affiliation":[{"name":"Department of Radiology, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH 45229, USA"},{"name":"Department of Radiology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6214-9167","authenticated-orcid":false,"given":"Sarangarajan","family":"Ranganathan","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH 45229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greg","family":"Tiao","sequence":"additional","affiliation":[{"name":"Department of Pediatric and Thoracic Surgery, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH 45229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James I.","family":"Geller","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology\/Oncology, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH 45229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1007\/s00247-005-0064-3","article-title":"Hepatoblastoma: An oncological review","volume":"36","author":"Roebuck","year":"2006","journal-title":"Pediatr. 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