Retreatment with Cisplatin May Provide a Survival Advantage for Children with Relapsed/Refractory Hepatoblastoma: An Institutional Experience

SIMPLE SUMMARY: Treatment of hepatoblastoma at time of first diagnosis has evolved to include well described chemotherapy regimens along with surgical resection, resulting in improved outcomes. Unfortunately, in cases of recurrent or refractory disease, there is no standard of care to employ and these patients are largely under described in the literature. The aim of this retrospective study was to describe the characteristics, treatment and outcomes of a cohort of patients with relapsed or refractory hepatoblastoma at our institution. We report 50% overall survival, which is consistent with other published data, and found that cisplatin remains the most effective chemotherapy agent with improved outcomes. ABSTRACT: Background: Hepatoblastoma (HB) is the most common liver malignancy in children. There is no standard of care for management of relapsed/refractory HB (rrHB) and reports in the literature are limited. Objective: To describe presenting features, biology, treatment strategies, and outcomes for pediatric patients with relapsed/refractory hepatoblastoma. Methods: An IRB-approved retrospective institutional review of patients with rrHB who presented for consultation and/or care from 2000–2019. Clinical, radiographic, and histologic data were collected from all patients. Results: Thirty subjects were identified with a median age of 19.5 months (range 3–169 months) at initial diagnosis and 32.5 months (range 12–194 months) at time of first relapse. 63% of subjects were male, 70% Caucasian, and 13% were born premature. Three subjects had a known cancer predisposition syndrome. Eight patients had refractory disease while 22 patients had relapsed disease. Average time from initial diagnosis to relapse or progression was 12.5 months. Average alpha-fetoprotein (AFP) at initial diagnosis was 601,203 ng/mL (range 121–2,287,251 ng/mL). Average AFP at relapse was 12,261 ng/mL (range 2.8–201,000 ng/mL). For patients with tumor sequencing (n = 17), the most common mutations were in CTNNB1 (13) and NRF2 (4). First relapse sites were lungs (n = 12), liver (n = 11) and both (n = 6). More than one relapse/progression occurred in 47% of subjects; 6 had ≥3 relapses. Pathology in patients with multiply relapsed disease was less differentiated including descriptions of small cell undifferentiated (n = 3), pleomorphic (n = 1), transitional liver cell tumor (n = 2) and HB with carcinoma features (n = 1). All subjects underwent surgical resection of site of relapsed disease with 7 subjects requiring liver transplantation. Overall survival was 50%. Survival was associated with use of cisplatin at relapse (78.6% with vs. 25% without, p = 0.012). The most common late effect was ototoxicity with at least mild sensorineural hearing loss found in 80% of subjects; 54% required hearing aids. Conclusions: Retreatment with cisplatin at the time of relapse may provide an advantage for some patients with hepatoblastoma. Multiply relapsed disease was not uncommon and not associated with a worse prognosis. Careful attention should be paid to cumulative therapy-induced toxicity while concurrently aiming to improve cure.