Navigating relapsed hepatoblastoma: Predictive factors and surgical treatment strategy

Abstract

Objective: Hepatoblastoma (HB) is the most common primary hepatic malignancy in childhood. Relapse occurs in more than 50% of high-risk patients with a high mortality due to ineffective salvage therapies. The purpose of this study is to identify risk factors for relapsed HB and predictors of survival in a single tertiary referral center.

Methods: A retrospective chart review showed 129 surgically treated HB patients from October 2004 to July 2020. Of the cohort, 22 patients presented with relapsed HB. Relapse was defined as re-appearance of malignancy after 4 weeks of normalized AFP and disappearance of all tumors on imaging.

Results: Patients with relapsed HB had a 5-year overall survival (OS) of 45.4% compared to 93.1% in those without relapse (p = 0.001). When comparing PRETEXT IV, microvascular invasion, metastatic disease, and age on multivariate logistic regression, only PRETEXT IV was an independent risk factor for relapsed HB with an OR of 2.39 (95% CI: 1.16-4.96; p = 0.019). Mixed epithelial and mesenchymal HB (12/19, 63.2%) was the most common histology of primary tumors while pure epithelial HB (13/15, 86.6%) was the most common relapsed histology. Combination of surgical and medical therapy for relapsed disease was predictive of survival with an HR of 16.3 (95% CI: 1.783-149.091; p = 0.013) compared to only chemotherapy.

Conclusions: This study demonstrates that PRETEXT IV staging is an independent predictor of relapsed disease. The most common relapsed histology was epithelial, suggesting a potential selection or resistance of this component. Surgical resection is a critical component of multimodal therapy for relapsed HB.

Keywords: hepatoblastoma; patient-derived xenograft; relapse.

FIGURE 1

(A) The overall survival of relapsed patients versus those without relapse is plotted over a 5‐year interval since resection. There was a 93.1% overall survival in the non‐relapsed patients versus 45.4% survival in the relapsed patients (p = 0.001). (B) The overall survival of the relapsed patients that underwent medical management, medical management, and surgical intervention, or none over a 5‐year interval since resection. There was an 80% overall survival in the medical management and surgically intervened patients versus 0.0% in the medically managed cohort (p = 0.001) at 5‐year interval. The patients with no management, due to progression of disease, all died of disease. To note, one patient in the medically managed cohort was alive but was lost to follow‐up after the 1.1 year mark.