Results of treatment of patients with high and very high risk hepatoblastoma

Background. Hepatoblastoma (HB) is the most common malignant liver tumor in children aged 0–14 years. The introduction of intensive therapy based on alternating courses of cisplatin and carboplatin/doxorubicin, as well as dose-compression regimens of cisplatin administration, has significantly improved the prognosis in high-risk patients. The aim of the study – to assess the effectiveness of therapy in high-risk (HR) and very high-risk (VHR) patients with HB treated according to the International Group for Optimization of Therapy in Pediatric Liver Tumors (SIOPEL) protocols based on 2 major medical centers in the Russian Federation. Materials and methods . The study included patients with a verified diagnosis of HR and VHR HB, who received therapy at Dmitry Rogachev National Medical Research Center of the Pediatric Hematology, Oncology and Immunology and B.V. Petrovsky Russian Scientific Center of Surgery for the period 02.2012 to 07.2022 (125 months). The criteria of the SIOPEL group were used to stratify into risk groups. Until 2017, all patients were stratified into the HR group and received treatment according to the SIOPEL-4 protocol; since 2017, differentiated therapy has been carried out for patients in the HR group (SIOPEL-3 HR protocol) and VHR (SIOPEL-4 protocol). Since 2017, patients over 8 years of age have been stratified into VHR group. Survival was estimated using the Kaplan–Meier method. This study assessed overall survival (OS), event-free survival (EFS), and cumulative probability of death. Survival analysis was carried out as of 01.08.2023. Results . 49 patients with HR and VHR group HB aged 0 to 13 years were registered. The analysis included 47/49 (95.9 %) patients who received therapy according to the SIOPEL protocols. The median age at diagnosis was 24.9 months (range – 4.7–154.9). The male: female ratio was 1.47:1. Distribution by PRETEXT stage: PRETEXT II – 13 (27.6 %), PRETEXT III – 18 (38.3 %), PRETEXT IV – 16 (34.1 %) patients. The median α-fetoprotein level in patients with known exact values (n = 45) at the time of diagnosis was 182 431 (0.85–1 998 000) ng/ml. 24/47 (51 %) patients had initial lung metastases. The extent of delayed surgery: resection – 32 (68.1 %) patients, transplantation – 12 (25.5 %), without delayed surgery – 3 (6.4 %). Radicality of delayed surgery: R0 – 41/47 (87.2 %) patients, R1 – 3/47 (6.4 %), in 3/47 (6.4 %) patients the surgery wasn’t performed. Median follow-up 39.2 (2.5–129.2) months. Of the 47 patients included in the study, 37 (78.7 %) are alive, 10 (21.3 %) died (2/10 – surgical complications, 1/10 – infectious complications, 7/10 – progression of HB). Relapses/progressions were observed in 14/47 (29.8 %) patients, 7 (50 %) of whom died from disease progression. 3-year OS and EFS of the whole cohort (n = 47) were 80.1 ± 6.0 % and 64.9 ± 7.1 %. In the group of patients after liver transplantation (n = 12), 3-year OS and EFS were 73.3 ± 13.2 % and 64.2 ± 14.4%. The 3-year cumulative probability of death from the tumor was 16.7 ± 5.8 %. The 3-year cumulative probability of death from other causes was 7.2 ± 4.0 %. 3-year OS and EFS in the group of patients with distant metastases were 76.5 ± 9.4 % and 57.1 ± 10.3 %, in the group of patients without metastases 77.6 ± 8.8 % and 73.0 ± 9.4 %, respectively (p = 0,919 for OS; р = 0,440 for EFS). Conclusions . The data obtained in the study are consistent with the original studies of the SIOPEL group. The feasibility and effectiveness of incorporating liver transplantation into the treatment of patients with HB in the HR and VHR groups was confirmed.