Pediatric liver transplantation for hepatocellular cancer and rare liver malignancies: US multicenter and single‐center experience (1981‐2015)

Abstract

A tenth of all pediatric liver transplantations (LTs) are performed for unresectable liver malignancies, especially the more common hepatoblastoma (HBL). Less understood are outcomes after LT for the rare hepatocellular carcinoma, nonhepatoblastoma embryonal tumors (EMBs), and slow growing metastatic neuroendocrine tumors of childhood. Pediatric LT is increasingly performed for rare unresectable liver malignancies other than HBL. We performed a retrospective review of outcomes after LT for malignancy in the multicenter US Scientific Registry of Transplant Recipients (SRTR; n = 677; 1987‐2015). We then reviewed the Children's Hospital of Pittsburgh (CHP; n = 74; 1981‐2014) experience focusing on LT for unresectable hepatocellular cancer (HCC), EMBs, and metastatic liver tumors (METS). HBL was included to provide reference statistics. In the SRTR database, LT for HCC and HBL increased over time (P < 0.001). Compared with other malignancies, the 149 HCC cases received fewer segmental grafts (P < 0.001) and also experienced 10‐year patient survival similar to 15,710 adult HCC LT recipients (51.6% versus 49.6%; P = 0.848, not significant [NS], log‐rank test). For 22 of 149 cases with incidental HCC, 10‐year patient survival was higher than 127 primary HCC cases (85% [95% confidence interval (CI), 70.6%‐100%] versus 48.3% [95% CI, 38%‐61%]; P = 0.168, NS) and similar to 3392 biliary atresia cases (89.9%; 95% CI, 88.7%‐91%). Actuarial 10‐year patient survival for 17 EMBs, 10 METS, and 6 leiomyosarcoma patients exceeded 60%. These survival outcomes were similar to those seen for HBL. At CHP, posttransplant recurrence‐free and overall survival among 25 HCC, 17 (68%) of whom had preexisting liver disease, was 16/25 or 64%, and 9/25 or 36%, respectively. All 10 patients with incidental HCC and tumor‐node‐metastasis stage I and II HCC survived recurrence‐free. Only vascular invasion predicted poor survival in multivariate analysis (P < 0.0001). A total of 4 of 5 EMB patients (80%) and all patients with METS (neuroendocrine‐2, pseudopapillary pancreatic‐1) also survived recurrence‐free. Among children, LT can be curative for unresectable HCC confined to the liver and without vascular invasion, incidental HCC, embryonal tumors, and metastatic neuroendocrine tumors. Liver Transplantation 23 1577–1588 2017 AASLD.

Surgical management of children and adolescents with upfront completely resected hepatocellular carcinoma

“…Another single‐institution experience with LT in 10 children with HCC, in which 70% exceeded MC, demonstrated a 5‐year OS of 83.3% . Several additional studies have continued to demonstrate good transplant outcomes in children with HCC who exceed MC, highlighting the need for distinct pediatric criteria . In our study, 71% (5/7) of patients that were transplanted exceeded the original MC (Table ), and all seven remain alive and cancer free.…”

“…24,35,36 However, the MC have been criticized as being too strict; several studies have demonstrated good outcomes with more liberal criteria. [37][38][39][40] 13,17,32 In our study, 71% (5/7) of patients that were transplanted exceeded the original MC (Table 2), and all seven remain alive and cancer free.…”

“…LT in adult patients with HCC in whom surgical resection is not feasible has been shown to improve survival . In children with HCC, LT has been associated with improved disease‐free survival (range = 63–89%) compared to conventional treatment with chemotherapy and resection, particularly in children with advanced‐stage tumors or chronic underlying liver disease . The Pediatric Liver Unresectable Tumor Observatory registry was initiated to collect prospective data on pediatric patients (age < 18 years) undergoing LT for treatment of unresectable primary malignant liver tumors .…”

“…24,31 In children with HCC, LT has been associated with improved disease-free survival (range = 63-89%) compared to conventional treatment with chemotherapy and resection, particularly in children with advancedstage tumors or chronic underlying liver disease. [10][11][12][13][14][15]32 The Pediatric Liver Unresectable Tumor Observatory registry was initiated to collect prospective data on pediatric patients (age < 18 years) undergoing LT for treatment of unresectable primary malignant liver tumors. 33 An interim report from 2015 included 53 patients with HCC who received an LT (29 with underlying genetic predisposition and 24 in the setting of a normal background liver).…”

Improved contemporary outcomes of liver transplantation for pediatric hepatoblastoma and hepatocellular carcinoma

“…These findings have led to recent interest in LT even for some resectable cases of HCC . In an analysis of pooled SRTR data from 1987‐2015, Vinayak et al noted 1‐ and 5‐year OS of 85% and 51.7%, respectively. Our contemporary data show that outcomes of LT have dramatically improved over time to 1‐ and 5‐year OS of 94.7% and 80.8% and are now equivalent with HB.…”