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 α‐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. Cancer 2002;95:172–82. © 2002 American Cancer Society. DOI 10.1002/cncr.10632
The median follow-up of the survivors was 72 months (range 24 - 132 months). 98/141 (78 %) patients were alive and 31/141 (22 %) died. 12/141 (8.5 %) children had no surgical treatment. A complete resection of the primary tumour was achieved in 107/129 (83 %) cases. Forty-eight children were primary resected and eighty-one children were operated on after initial chemotherapy. In 36 cases, an atypical tumour resection, in 90 cases an anatomical liver resection, was performed. Three children were transplanted. There was no perioperative death. 14/48 (30 %) children with primary tumour resection had microscopical or macroscopical residual tumour in the liver. Despite the larger number of advanced HB in the primary chemotherapy group, an incomplete tumour resection was performed in only 15/78 (19 %) cases after liver resection (p < 0.044). 14/36 (38 %) cases with atypical tumour resection and only 16/90 (18 %) cases with anatomical liver resection had residual tumours in the liver (p < 0.019). These results underline the necessity for preoperative chemotherapy in all HB, which was accepted in the following study HB 99. Atypical tumour resection should be avoided because of the higher rate of incomplete tumour resections and local relapse compared to the group with anatomical tumour resection.
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