Hepatocellular Carcinoma in Children: Does Modified Platinum- and Doxorubicin-Based Chemotherapy Increase Tumor Resectability and Change Outcome? Lessons Learned From the SIOPEL 2 and 3 Studies

J Clin Oncol. 2016 Apr 1;34(10):1050-6. doi: 10.1200/JCO.2014.60.2250. Epub 2016 Jan 25.

Abstract

Introduction: The aim of this article is to present an experience of two prospective studies from the International Childhood Liver Tumor Strategy Group (SIOPEL 2 [S2] and SIOPEL [S3]) trials and to evaluate whether modified platinum- and doxorubicin-based chemotherapy is capable of increasing tumor resectability and changing patient outcomes.

Methods: Between 1995 and 2006, 20 patients with hepatocellular carcinoma (HCC) were included in the S2 trial and 70 were included in the S3 trial. Eighty-five patients remained evaluable.

Results: Response to preoperative chemotherapy was observed in 29 of 72 patients (40%) who did not have primary surgery, whereas 13 patients underwent upfront surgery. Thirty-three patients had a delayed resection. Thirty-nine tumors never became resectable. Complete tumor resection was achieved in 34 patients (40%), including seven of those treated with liver transplantation (LTX). After a median follow-up period of 75 months, 63 patients (74%) had an event (a progression during treatment, a relapse after treatment, or death from any cause). Sixty patients died. Twenty-three of 46 patients (50%) who underwent tumor resection died. Eighteen of 27 patients (63%) with complete tumor resection (without LTX) and 20 of 34 patients (59%) with LTX survived. Only one of seven patients (14%) with microscopically involved margins survived. Overall survival at 5 years was 22%.

Conclusion: Survival in pediatric HCC is more likely when complete tumor resection can be achieved. Intensification of platinum agents in the S2 and S3 trials has not resulted in improved survival. New treatment approaches in pediatric HCC should be postulated.

Publication types

  • Comparative Study

MeSH terms

  • Adolescent
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / mortality
  • Carcinoma, Hepatocellular / surgery*
  • Chemotherapy, Adjuvant
  • Child
  • Child, Preschool
  • Cisplatin / administration & dosage
  • Clinical Trials as Topic
  • Databases, Factual
  • Doxorubicin / administration & dosage
  • Drug Administration Schedule
  • Female
  • Hepatectomy* / methods
  • Humans
  • Kaplan-Meier Estimate
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / mortality
  • Liver Neoplasms / surgery*
  • Liver Transplantation
  • Male
  • Multicenter Studies as Topic
  • Neoadjuvant Therapy / methods*
  • Prospective Studies
  • Treatment Outcome
  • alpha-Fetoproteins / metabolism

Substances

  • Biomarkers, Tumor
  • alpha-Fetoproteins
  • Doxorubicin
  • Cisplatin