P2D384: Surgical Management of Relapsed and Refractory Hepatoblastoma in Children

Background: Hepatoblastoma (HB) is the most common primary liver cancer in children. With improvements in risk stratification, chemotherapy, and surgical management, 5-year disease-free survival now exceeds 70%. Relapse occurs in approximately 20% of cases with only 38% overall survival. Currently, there is no standard approach and minimal evidence-based guidance on the management of relapsed HB. Here, we report a single center experience of surgical management of patients with relapsed hepatoblastoma.

Methods: An IRB-approved retrospective review was conducted of pediatric patients who were evaluated at our institution for clinical consultation and/or management of HB from January 1, 2010, to July 1, 2019. A total of 97 patients diagnosed with hepatoblastoma were in the cohort.

Results: 30 patients were treated for relapsed disease with median time from diagnosis to relapse of three months (IQR 1.25 – 9). The mean survival for all patients was 4.3 years with 76 patients alive at time of censoring (78.4%). There was no significant difference in patient sex, ethnicity, or PRETEXT staging between those with relapsed or non-relapsed disease (Table 1). Patients with relapse were more likely to have metastasis at diagnosis (relapsed 56.7% vs non-relapsed 16.4%, p< 0.0001). Most patients (85%) received neoadjuvant chemotherapy. There was no difference among groups with reference to AFP response after chemotherapy or margin status on pathology. Tumor viability greater than 70% in the resection specimen was associated with a higher rate of relapse (relapsed 25.8% vs. non-relapsed 16.1%, p=0.05). There was no difference in relapse between patients who underwent liver resection or transplant primarily (relapsed 30% vs. non-relapsed 36.5%, p=0.24). Management of relapsed disease included a combination of chemotherapy and surgery with 43% achieving disease remission. Patients with relapsed disease had significantly shorter survival compared to non-relapsed patients (2.9 vs. 4.7 years, p=0.0001). Among all patients with relapse, 19 (63%) had pulmonary metastasis and among those, patients who underwent pulmonary metastectomy had improved survival (2.5 years vs 2.1, p=0.0005). In our relapsed cohort, 7 patients (23.3%) underwent salvage transplantation with no statistically significant difference in survival during the study period (Fig. 1).

Conclusion: This represents one of the largest single-center reports on relapsed hepatoblastoma. We found that primary liver transplant, which is offered for unresectable and advanced PRETEXT HB, has similar relapse rates to resection. Importantly, among patients who relapse with pulmonary metastasis, those that undergo resection have significantly improved survival compared to chemotherapy alone. These findings demonstrate that surgery remains an option in relapsed hepatoblastoma. In addition, salvage transplant is an oncologic option for patients with unresectable, relapsed disease as our center found no difference in overall survival. Further multi-center, retrospective, and prospective study is needed to guide treatment of hepatoblastoma in the pediatric population.