Pretreatment prognostic factors and treatment results in children with hepatoblastoma

Abstract

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 methylation status of RASSF1A promoter predicts responsiveness to chemotherapy and eventual cure in hepatoblastoma patients

“…1 Currently, 20-30% of patients who do not respond to preoperative chemotherapy, or who present with or develop metastatic disease, continue to face a poor outcome. 2,3 To improve the mortality rate, treatment strategies for hepatoblastoma refractory to the standard cisplatin and THP adriamycin regimen or with metastasis should be innovated. 33 To achieve a higher complete resection rate, more effective preoperative chemotherapy for refractory hepatoblastoma is mandatory, and such therapy offers a realistic hope for cure.…”

“…We also examined the dose-response relationships between the percentages of The 5 0 position of the sense unmethylated or sense methylated primer sequences is numbered relative to the transcription start site of the gene concern.-2 The number indicates the location relative to the transcription start site of CASP8 transcript variant B (NM_033355.2).- 3 Designed for bottom strand.…”

“…1 Remarkable progress in clinical outcome has been achieved in the past 20 years due to advances in chemotherapy and surgical procedures; however, the mortality rate remains 20-30% and treatment results in patients in advanced stages who are refractory to standard preoperative chemotherapy regimens are unsatisfactory. 2,3 To improve the mortality of these patients, innovative treatment and potent prognostic markers for better therapy planning are needed. The present clinical factors predicting outcome include the level of alpha-feto protein, histology, disease stage and growth pattern of the tumor.…”

“…The present clinical factors predicting outcome include the level of alpha-feto protein, histology, disease stage and growth pattern of the tumor. [2][3][4] Chromosomal gains of 2q, 8q and 20 and high expression of telomerase or PLK1 were shown to be moleculargenetic markers predicting poor outcome [5][6][7][8] ; however, none have been proven to be independent prognostic factors by multivariate analysis.…”

Loss of imprinting of IGF2 correlates with hypermethylation of the H19 differentially methylated region in hepatoblastoma

“…Remarkable progress in clinical outcome has been achieved in the past 20 years because of advances in chemotherapy and surgical procedures; however, the mortality rate remains 20 -30% and treatment results in patients in advanced stages who are refractory to standard preoperative chemotherapy regimens are unsatisfactory (Perilongo et al, 2000;Fuchs et al, 2002). To improve the mortality of these patients, innovative treatment based on a specific molecular target is needed.…”