Treatment Adaptation to Surgical Timing in Pediatric Hepatoblastoma: A 19-Year Single-Center Experience With Resection and Liver Transplantation.
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BACKGROUND: The management of hepatoblastoma (HB) relies on chemotherapy combined with surgery, either liver resection (LR) or liver transplantation (LT), with reported overall survival (OS) of 80%, cardiac toxicity of 6%, nephrotoxicity of 21%, ototoxicity of 32%-46%. In clinical practice, deviations from protocol-defined chemotherapy are often required to achieve resectability or bridge to transplantation. We aimed to evaluate the impact of treatment adaptation to surgical timing on OS and toxicity in a selected group of patients referred to a transplantation center. METHODS: We retrospectively analyzed patients with HB treated according to SIOPEL protocols at our center between 2004 and 2022. We collected clinical data, focusing on deviations from protocol-specified therapy, timing of medical and surgical treatment, OS, treatment-related toxicities (left ventricular ejection fraction, LVEF< 50%, estimated glomerular filtration rate, eGFR< 90 mL/mL/m2, increased hearing threshold of 20-40 dB at 4 kHz). RESULTS: Forty-two patients, median age at diagnosis 1.9 years (IQR 0.7-3.5), 16/42 (38.1%) with metastatic disease, 24/42 (57.1%) with vascular involvement were recorded. Additional chemotherapy beyond protocol indications, due to persistent pulmonary metastases, delayed organ availability, or disease progression was administered to 17/20 (85%) who underwent first-line LT and 10/22 (45%) who underwent LR (p = 0.007). Death occurred in 3/20 (15%) versus 7/22 (31.8%) (p = 0.2) respectively. After median follow-up of 4.5 years (IQR 1.2-6.2) OS is 32/42 (71.4%); cardiotoxicity developed in 1/42 (2.4%), nephrotoxicity in 8/42 (19%), ototoxicity in 9/42 (21.4%). CONCLUSIONS: A large proportion of patients with HB require adaptation of protocol-specified therapy, especially LT candidates. This favors successful management and is not associated with increased toxicity compared to previous reports.