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Hepatocellular Carcinoma in Children and Adolescents: Results From the Pediatric Oncology Group and the Children’s Cancer Group Intergroup Study

From the Department of Pediatrics and Surgery, Northwestern University and Children’s Memorial Hospital, Chicago, IL; Department of Preventive Medicine, Keck School of Medicine, University of Southern California Los Angeles; Department of Pediatrics Children’s Hospital, Los Angeles; Group Operations Center, Children’s Oncology Group, Arcadia; Department of Hematology/Oncology, Children’s Hospital; Department of Hematology/Oncology, Children’s Hospital, Oakland, CA; AstraZeneca Pharmaceuticals LP, Wilmington, DE; Department of Pediatric Surgery, Children’s National Medical Center, Washington DC; Baylor College of Medicine, Houston, TX; Department of Pathology, Children’s Hospital, Denver, CO; Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL; Department of Pediatrics, University of Tennessee, Memphis, TN.

Address reprint requests to: Howard M. Katzenstein, MD, Children’s Oncology Group, P.O. Box 60012, Arcadia, CA 91066; email: hmk476{at}northwestern.edu

PURPOSE: To determine surgical resectability, event-free survival (EFS), and toxicity in children with hepatocellular carcinoma (HCC) randomized to treatment with either cisplatin (CDDP), vincristine, and fluorouracil (regimen A) or CDDP and continuous-infusion doxorubicin (regimen B).

PATIENTS AND METHODS: Forty-six patients were enrolled onto Pediatric Intergroup Hepatoma Protocol INT-0098 (Pediatric Oncology Group (POG) 8945/Children’s Cancer Group (CCG) 8881). After initial surgery or biopsy, children with stage I (n = 8), stage III (n = 25), and stage IV (n = 13) HCC were randomly assigned to receive regimen A (n = 20) or regimen B (n = 26).

RESULTS: For the entire cohort, the 5-year EFS estimate was 19% (SD = 6%). Patients with stage I, III, and IV had 5-year EFS estimates of 88% (SD = 12%), 8% (SD = 5%), and 0%, respectively. Five-year EFS estimates were 20% (SD = 9%) and 19% (SD = 8%) for patients on regimens A and B, respectively (P = .78), with a relative risk of 1.2 (95% confidence interval, 0.60 to 2.3) for regimen B when compared with regimen A. Outcome was similar for either regimen within disease stages. Events occurred before postinduction surgery I in 18 (47%) of 38 patients with stage III or IV disease, and tumor resection was possible in two (10%) of the remaining 20 children with advanced-stage disease after chemotherapy.

CONCLUSION: Children with initially resectable HCC have a good prognosis and may benefit from the use of adjuvant chemotherapy. Outcome was uniformly poor for children with advanced-stage disease treated with either regimen. New therapeutic strategies are needed for the treatment of advanced-stage pediatric HCC.

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