Advanced Hepatoblastoma: A Review of Current Management Strategies

Hepatoblastoma (HB) is an embryonal tumor comprising nearly 1% of all pediatric malignancies and more than 90% of all liver tumors in patients under 5 years of age. The incidence of HB is increasing due to the rising prevalence of very low birth weight infants, a strong risk factor. Many cases are linked to congenital syndromes such as Beckwith-Wiedemann, Familial Adenomatous Polyposis, and trisomy 18. Wnt pathway activation and a concominant rise in intracytoplasmic levels of beta-catenin are the biochemical hallmarks of tumorgenesis. Innovative chemotherapy and medical advances has increased survival rates over the years to upwards of 80%. Staging systems such as PRETEXT and SIOPEL serve to guide therapy. Various chemotherapeutic regimens have been proposed with platinum based therapy as the mainstay of all treatment regimens. High risk tumors including those with PRETEXT 4, extrahepatic disease, or low AFP levels pose a particular challenge to treatment. Despite advances in medical therapy, surgery still remains at the forefront as a definitive cure, especially with advanced disease. Principles of general surgical liver resection based on segmental anatomy are applied with goal of achieving an enbloc R0 resection. POST-TEXT IV disease is best managed with total hepatectomy and liver transplant. The SIOPEL 4 guidelines have outlined basic principles for utilization of liver transplant, which has shown to improve outcomes in patients with unresectable disease following neoadjuvant chemotherapy. Candidates eligible for liver transplant should be referred to a tertiary transplant center no later than 2 cycles following chemotherapy. Relapsed HB poses a challenge for the treating clinician. High dose chemotherapy (HD-CT) is a sensible option; however, there is no consensus on the optimal regimen currently. Despite medical research and development of novel chemotherapeutic regimens, the outcome for children with relapsed disease remains poor.