Liver transplantation combined with chemotherapy provided long-term DFS in pediatric patients with advanced hepatoblastoma and hepatocellular carcinoma, according to the results of a retrospective analysis.
Favorable outcomes with transplantation persisted even among patients with hepatocellular carcinoma (HCC) larger than Milan and University of California, San Francisco (UCSF) criteria for transplant eligibility, results also showed.
“Hepatoblastoma (HBL) and HCC are the most common primary liver cancers in infancy and childhood,” C. Andrew Bonham, MD, associate professor of surgery in the division of abdominal transplantation at Stanford University School of Medicine, and colleagues wrote. “HBL alone accounts for 91% of all liver tumors diagnosed in children younger than 5 years, and most HBLs arise in children by 3 years of age. … HCC is rare and represents less than 1% of all tumors in the pediatric population but is the second most common primary liver tumor after HBL.”
Updated long-term data are needed due to the rarity of these tumors and their likelihood to be diagnosed at advanced stages, according to researchers. Further, it was unclear whether the Milan and UCSF criteria to determine transplant eligibility — which has been studied in the adult population — applies to a pediatric population.
Bonham and colleagues sought to determine the efficacy of liver transplantation in pediatric patients with HBL or HCC. They performed a single-institution retrospective medical record review of pediatric patients treated between January 1997 and September 2014 at Stanford University.
A total of 40 patients aged younger than 18 years underwent liver transplantation for the treatment of HBL (n = 30) or HCC (n = 10). Patients undergoing transplantation for HBL had a significantly younger mean age than patients with HCC (4 years vs. 12 years; P < .01). Boys comprised 67% of patients with HBL and 50% of patients with HCC.
Eight patients who underwent treatment for HCC included those with tumors greater in size than proposed by the Milan (a single tumor measuring ≤ 5 cm or ≤ 3 nodules measuring ≤ 3 cm) and UCSF (a single tumor measuring ≤ 6.5 cm or ≤ 3 nodules measuring ≤ 4.5 cm and a total diameter of ≤ 8 cm) criteria.
DFS, OS and graft survival served as primary endpoints.
Ninety-three percent of patients with HBL achieved 1-year DFS, 82% achieved 5-year DFS and 82% achieved 10-year DFS. Ninety percent of patients with HCC achieved 1-year DFS, 78% achieved 5-year DFS and 78% achieved 10-year DFS.
Among patients with HBL, risk factors associated with recurrence after transplantation included having pretreatment extent of disease stage IV lesions (P ≤ .01), longer waiting list time (mean wait list time, 31 days vs. 15 days; P≤ .01) and being older at transplantation (mean age, 78 months vs. 36 months; P = .01). Although recurrence occurred in two patients with HBL and pretreated metastases, the researchers did not deem pretreated metastases an independent risk factor for recurrence.
Among patients with HCC, older age at transplantation (18 years vs. 11 years; P = .04) and the presence of metastatic disease (n = 1 vs. 0; P = .05) served as recurrence risk factors.
However, patients with HCC and tumors larger than those proposed by the Milan and UCSF criteria achieved favorable 5-year DFS (82%) and OS (78%) following transplantation.
The researchers acknowledged the small study cohort and the potential for selection bias inherent in retrospective analyses as study limitations.
“Liver transplant combined with chemotherapy provides the best curative chance in children with advanced, unresectable HBL,” Bonham and colleagues wrote. “HCC in children behaves differently than in adults because transplant for lesions well outside the Milan and UCSF criteria results in excellent long-term survival. More investigation is needed to further establish the role of transplant in children with HCC.”
Further data are needed to fully understand the role of transplantation in pediatric patients with HBL and HCC, Elaine Y. Cheng, MD, a general surgeon at UCLA’s David Geffen School of Medicine, and Ronald W. Busuttil, MD, PhD, William P. Longmire Jr. chair in surgery and founding chief of the division of liver and pancreas transplantation at UCLA’s David Geffen School of Medicine, wrote in an accompanying editorial.
“The data published by the Pediatric Liver Unresectable Tumor Observatory [PLUTO] registry supports liver transplantation as a primary treatment option for children with HBL and HCC and those with HCC in the setting of chronic underlying liver disease,” Cheng and Busuttil wrote. “However, the true incidence of tumor recurrence after liver transplantation remains poorly defined in the available literature, as are the risk factors associated with inferior survival outcomes. Additional results from prospective, multicenter studies such as the PLUTO registry will be integral for the development of optimal management protocols and to increase cure rates for pediatric malignant neoplasms of the liver.” – by Cameron Kelsall
Disclosure: The researchers, Cheng and Busuttil report no relevant financial disclosures.