Pretreatment prognostic factors and treatment results in children with hepatoblastoma: a report from the German Cooperative Pediatric Liver Tumor Study HB 94.
BACKGROUND
In the past 20 years, a dramatic improvement in the prognosis of patients with hepatoblastoma (HB) has been achieved by combining surgery with chemotherapy in several national and international trials. A worldwide, unsolved problem remains the treatment of patients with advanced or metastatic HB.


METHODS
The German Cooperative Pediatric Liver Tumor Study HB 94 was a prospective, multicenter, single-arm study. The study ran from January 1994 to December 1998. The protocol assessed the efficiency of chemotherapy consisting of cisplatin, ifosfamide, and doxorubicin (CDDP/IFO/DOXO) and/or etoposide and carboplatin (VP16/CARBO). The prognostic significance of the surgical strategy, pretreatment factors, and tumor characteristics for disease free survival (DFS) were analyzed.


RESULTS
Sixty-nine children with HB were treated in the HB 94 study. The median follow-up of survivors was 58 months (range, 32-93 months). Fifty-three of 69 patients (77%) remained alive, and 16 of 69 patients (23%) died. Long-term DFS was as follows: 26 of 27 patients had Stage I HB, 3 of 3 patients had Stage II HB, 19 of 25 patients had Stage III HB, and 5 of 14 patients had Stage IV. A complete resection of the primary tumor was achieved in 54 of 63 patients (86%). Six children (8%) had no surgical treatment. Twenty-two tumors were resected primarily, and 41 children underwent surgery after initial chemotherapy. Two children underwent liver transplantation. There was no perioperative death. Forty-eight children received primary chemotherapy with CDDP/IFO/DOXO. Forty-one of 48 children achieved partial remission after CDDP/IFO/DOXO. Eighteen children with advanced or recurrent HB underwent VP16/CARBO chemotherapy, with a response achieved by 12 children. The relevant pretreatment prognostic factors were growth pattern of the liver tumor (P = 0.0135), vascular tumor invasion (P = 0.0039), occurrence of distant metastases (P = 0.0001), initial alpha-fetoprotein level (P = 0.0034), and surgical radicality (P < 0.0001).


CONCLUSIONS
The current results underline the necessity of preoperative chemotherapy in all children with HB. Complete tumor resection is one of the main prognostic factors.
Department of Pediatric Surgery, University of Tuebingen, Tuebingen, Germany. joerg.fuchs@med.uni-tuebingen.de
Jörg
J
Fuchs
Jana
J
Rydzynski
Dietrich
D
Von Schweinitz
Udo
U
Bode
Hartmut
H
Hecker
Peter
P
Weinel
Dietrich
D
Bürger
Dieter
D
Harms
Rudolf
R
Erttmann
Karl
K
Oldhafer
Hermann
H
Mildenberger
D002648:Child; D002675:Child, Preschool; D005260:Female; D006498:Hepatectomy; D018197:Hepatoblastoma / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008113:Liver Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008297:Male; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D000509:alpha-Fetoproteins / Q000032:analysis
D000509:alpha-Fetoproteins