Unresectable hepatoblastoma and pre-transplant factors associated with event-free survival
Joao Seda Neto1, Flavia Feier1, Renata Pugliese1, Rodrigo Vincenzi1, Marcel Benavides1, Karina Roda1, Paulo Chapchap1, Eduardo Fonseca1.
1Liver Transplantation, Hospital Sirio-Libanês, Sao Paulo, Brazil
Introduction: The mainstays of irresectable hepatoblastoma (HB) treatment are surgical resection and cisplatin based (CB) chemotherapy (CHT). However, adequate patient selection is a key to achieve acceptable disease-free survival rates in patients with unresectable HB undergoing liver transplantation (LT).
Methods: This single-center retrospective analysis of 28 children with HB submitted to LDLT from 1996 to 2019 aimed at determining the pre-transplant factors associated with worse post-transplant event-free survival. The clinical variables collected were gender, age, PELD score (Pediatric End-Stage Liver Disease scoring system), type of neoadjuvant CHT (CB versus other regimens), pre- and post- CHT AFP levels, %AFP reduction post CHT (AFP pre-CHT – AFP post- CHT /AFP pre- CHT), PRETEXT stage, time between diagnosis and LDLT, presence of metastases at diagnosis, follow-up time.
Results: A total of 21 (75%) patients were classified as PRETEXT IV, 4 (14.3%) patients as PRETEXT III and 3 (10.7%) patients were rescue LT. All of them received pre-LT CHT: 13 (46.4%) received CB CHT, 10 (35.8%) received alternative regimens, and for 5 (17.8%) patients the CHT was not informed. Eighteen patients were event-free, and were included in the Event-No group. Ten patients experienced an event (recurrence or death- Event-Yes group). Comparing the two groups, the statistically different pre-LDLT variables were: time from diagnosis to the LDLT >12 months (p=0.09), post- CHT AFP levels (p=0.07), and AFP post- CHT reduction > 70% (p=0.05). The only statistically different post-LDLT variable among groups was the presence of vascular invasion in the explant analysis (p=0.002). Post-LDLT overall 5-y survival probability was 66% and 5-y event-free survival probability was 63.9% . In those patients who achieved an AFP reduction post- CHT ≥ 70%, 5-y event-free survival was of 81.3% vs. 40% in those who did not (p=0.02). Patients in which the time from HB diagnosis to LDLT was > 12 months had a 5-y event-free survival rate of 40% vs 77% for those who performed the LDLT in <12 months from the diagnosis (p=0.01). In the liver explant analysis, the presence of vascular invasion also impacted in the 5-y event-free survival: no vascular invasion (82.4%) vs microvascular invasion (50%) vs macrovascular invasion (20%) (p=0.04).
Conclusion: LDLT for HB is the preferred treatment option for unresectable HB, with no distant metastasis and adequate response to CHT. AFP reduction ≥ 70%, and time from diagnosis to transplant < 12months were the pre-transplant variables associated with improved event-free survival.