Therapeutic efficacy and prognosis of childhood hepatoblastoma: retrospective analysis of 23 cases in a single center

Objective To explore the clinical and pathological features, therapeutic efficacy, survival, related risk factors of prognosis and clinical diagnosis and treatments of children with hepatoblastoma (HB). Methods A total of 23 cases of newly diagnosed HB children in Department of Pediatric Hematology and Oncology, West China Second University Hospital, Sichuan University, from January 2010 to September 2017, were enrolled in this study and selected as research subjects. The clinical data regarding age at diagnosis, gender, clinical manifestations, histopathological types, staging of pre-treatment extent of disease (PRETEXT) and divided group by Children′s Oncology Group (COG) of United States after operation, and clinical protocols, therapeutic effect, prognosis and chemotherapy-related adverse reactions and so on were retrospectively analyzed. Kaplan-Meier method was used for survival analysis of childhood HB, such as rates of 2-year overall survival (OS) and 2-year event-free survival (EFS), and log-rank test was employed for comparisons of OS and EFS curves between HB children with different clinical features. The incidences of adverse reactions between children treated with different chemotherapy regimens were compared by Fisher exact probability method. This study was in line with the requirements of World Medical Association Declaration of Helsinki revised in 2013. Results ①The median age of 23 cases of children with HB at diagnosis was 25.9 months (2.3-155.0 months). There were 12 boys and 11 girls. Clinically, abdominal mass was the most frequent presenting manifestations, identified in 56.5% (13/23) of HB children. Rates of complete remission (CR) and partial remission (PR) were 65.2% (15/23) and 8.7% (2/23), respectively at the end of chemotherapy, and 5 cases (21.7%) died. ②With median follow-up time of 21.5 months (7.5-81.4 months), the rates of 2-year EFS and 2-year OS among the 23 cases of HB children were 60.1% and 75.0%, respectively. Univariate analysis revealed that the 2-year EFS rate was 38.9% in children with vascular involvement of HB, which was significantly lower than 81.8% in children without vascular involvement of HB, and the difference was statistically significant (χ2=4.293, P=0.038). The 2-year EFS rate of children with stage Ⅳ in PRETEXT stage was 33.3%, which was also significantly lower than 70.6% in children with stage Ⅰ-Ⅲ in PRETEXT stage, and the difference was statistically significant (χ2=5.258, P=0.022). The rates of 2-year EFS and OS in children with lung metastasis were 20.0% and 30.0%, respectively, which were statistically lower than those of 71.4% and 85.7%, respectively in children without lung metastasis, and both the differences were statistically significant (χ2=5.491, P=0.015; χ2=7.773, P=0.005). The rates of 2-year EFS and OS in children with failure of serum alpha-fetoprotein (AFP) normalization after 3 courses of postoperative chemotherapy were 27.2% and 37.7%, respectively, which were statistically lower than those of 91.7% and 100.0%, respectively in children with normalization in AFP after ≤ 3 courses of postoperative chemotherapy, and both the differences were statistically significant (χ2=9.837, P=0.015; χ2=8.682, P=0.003). ③Severe hematological toxicity was the most common chemotherapy associated adverse reaction, particularly in children who received the treatment of doxorubicin-based combination chemotherapy. Among the 22 cases of HB children who who received chemotherapy, the incidences of hematologic toxicity in grade 3 or higher and mild transaminase elevation in 14 children receiving doxorubicin-based combination chemotherapy were 100.0% (14/14) and 64.3% (9/14), respectively, which were significantly higher than those of 37.8% (3/8) and 0 (0/8) in children who did not receive doxorubicin in the chemotherapy regimen, and both the differences were statistically significant (P=0.002, P=0.006). Conclusions The children with HB collected in this study share similar clinical and pathological features as reported previously. Lung metastasis and failure of serum AFP normalization after 3 courses of postoperative chemotherapy are risk factors intimately associated with adverse clinical outcomes of HB children. Key words: Hepatoblastoma; Drug toxicity; Chemotherapy, adjuvant; Disease-free survival; Multidisciplinary treatment; Prognosis; Alpha-fetoproteins; Child