Cisplatin, Doxorubicin, and Delayed Surgery for Childhood Hepatoblastoma: A Successful Approach—Results of the First Prospective Study of the International Society of Pediatric Oncology

Pritchard, Jon; Brown, Julia; Shafford, E.; Perilongo, Giorgio; Brock, Pénélope; Dicks‐Mireaux, C.; Keeling, Jean W.; Phillips, Angela; Vos, A.; Plaschkes, J.

doi:10.1200/jco.2000.18.22.3819

Cited by 252 publications

(236 citation statements)

References 26 publications

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“…The cases who underwent partial hepatectomy were given preoperative chemotherapy (cisplatin and doxorubicin) according to the protocols of the Société Internationale d'Oncologie Pediatrique. 18 Guardians of the patients gave written informed consent to biomedical studies after verbal counseling. Thirteen patients were male, 8 female; ages ranged from 2 to 132 months.…”

Section: Patients and Tissue Samplesmentioning

confidence: 99%

Sporadic childhood hepatoblastomas show activation of β-catenin, mismatch repair defects and p53 mutations

et al. 2008

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Hepatoblastoma, a rare embryonic tumor that may arise sporadically or in the context of hereditary syndromes (familial adenomatous polyposis and Beckwith-Wiedemann's) is the most frequent liver cancer of childhood. Deregulation of the APC/b-catenin pathway occurs in a consistent fraction of hepatoblastomas, with mutations in the APC and b-catenin genes implicated in familial adenomatous polyposis-associated and sporadic hepatoblastomas, respectively. Alterations in other cancer-related molecular pathways have not been reported. We investigated a series of 21 sporadic paraffin-embedded hepatoblastoma cases for mutations in the p53 (exons 5-8) and b-catenin (exon 3) genes, loss of heterozygosity at APC, microsatellite instability and immunohistochemical expression of b-catenin and of the two main mismatch repair proteins, MLH1 and MSH2. No loss of heterozygosity at APC was detected. We found mutations in b-catenin and p53 in 4/21 (19%) and 5/21 (24%) cases respectively, b-catenin protein accumulation in 14/21 cases (67%), microsatellite instability in 17/21 cases (81%), of which eight resulted positive for high-level of microsatellite instability (in four cases associated with loss of MLH1/MSH2 immunostaining). No correlations between involved molecular pathway(s) and hepatoblastoma histotype(s) emerged. This study confirms that b-catenin deregulation is involved in sporadic hepatoblastoma and also suggests that mismatch repair defects and p53 mutations contribute to this rare liver cancer. Sporadic hepatoblastoma appears to be molecularly and phenotypically heterogeneous and may reflect different pathways of liver carcinogenesis.

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Section: Patients and Tissue Samplesmentioning

confidence: 99%

Sporadic childhood hepatoblastomas show activation of β-catenin, mismatch repair defects and p53 mutations

et al. 2008

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“…The treatment protocol consisted of preoperative chemotherapy followed by delayed surgery and postoperative chemotherapy according to two risk groups (standard-versus high-risk). The two risk groups were based on the International Childhood Liver Tumor Strategy Group risk criteria (23). Standard risk patients received two or three courses of neoadjuvant ifosfamide, cisplatin and doxorubicin (IPA) chemotherapy prior to surgery (1 g/m 2 ifosfamide every 72 h, days 1-3; 20 mg/m 2 cisplatin every 1 h, days 4-8; and 60 mg/m 2 doxorubicin every 48 h, days 9-10).…”

Section: Methodsmentioning

confidence: 99%

Truncated neurokinin-1 receptor is an ubiquitous antitumor target in hepatoblastoma, and its expression is independent of tumor biology and stage

et al. 2015

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Abstract. The substance P (SP; also known as TAC1)/neurokinin-1 receptor (NK1R; also known as TACR1) complex is a critical part in the development of cancer. Therefore, NK1R antagonists, such as the clinical drug aprepitant, are currently under investigation as future anticancer agents. In a previous study, NK1R (TACR1) was identified as a potent anticancer target in hepatoblastoma (HB). However, little is known regarding the exact distribution of this target among HB subsets and whether it correlates with clinical features and prognosis. In the present study, mRNA was isolated from 47 children with HB, and reverse transcription-quantitative polymerase chain reaction was performed on the samples to analyze the expression of full-length-TACR1 (fl-TACR1) and truncated-TACR1 (tr-TACR1). These data were correlated with data obtained from 9 tumor-free controls, as well as with the presence of metastasis, PRETEXT, vascular invasion, histology, age of diagnosis, multifocality, CTNNB1 mutation, gender and overall survival. Additionally, the present study investigated a recently described 16-gene signature characteri zing HB known to correlate with prognosis. Compared with tumor-free liver tissue, tumorous tissue expressed TACR1 significantly higher for the truncated version (P=0.0301), and by trend also for the full-length version. Accordingly, the expression of fl-TACR1 correlated with the expression of the truncated version (P=0.0074). Furthermore, a low expression of fl-TACR1 correlated with characteristics of the 16-gene signature known to predict prognosis (P=0.0222). However, there was no correlation between tr-TACR1 and the tumor characteristics investigated, including outcome, although a clear trend was observed for some tumor characteristics. The current results reinforced the previously described findings that in HB, tr-TACR1 is overexpressed compared with tumor-free liver tissue. Furthermore, to the best of our knowledge, the present study demonstrated for the first time that tr-TACR1 is expressed ubiquitously among the different subsets of HB. Therefore, NK1R may serve as a potent anticancer target in a large variety of patients with HB, independent of tumor biology and clinical stage.

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“…Doxorubicin has also been noted as an active agent and continues to be used throughout Europe [47]. Toxicity in previous North American trials has limited its use [46]; however, there are ongoing discussions regarding the reintroduction of doxorubicin in North American clinical trials.…”

Section: Treatmentmentioning

confidence: 99%

Liver Tumors in Children

2008

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After completing this course, the reader should be able to:1. Describe the current epidemiologic trends in hepatoblastoma.2. Identify the genetic syndromes that are seen in a subset of liver tumors.3. Assess the need for complete tumor resection in the treatment of liver tumors in children as well as the increasingly important option of liver transplantation for those patients with unresectable tumors.4. Discuss the impact of the hepatitis vaccine in reducing the incidence of hepatocellular carcinoma.5. Explain the prognostic impact of different histologic subtypes of hepatoblastoma.6. Promote the need for future clinical trials in testing new agents for hepatocellular carcinoma in children.7. Employ the different staging systems used in liver tumors, including the traditional North American postsurgical staging system and the European presurgical staging system using imaging.This article is available for continuing medical education credit at CME.TheOncologist.com. CME CME ABSTRACT

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Cisplatin, Doxorubicin, and Delayed Surgery for Childhood Hepatoblastoma: A Successful Approach—Results of the First Prospective Study of the International Society of Pediatric Oncology

Cited by 252 publications

References 26 publications

Sporadic childhood hepatoblastomas show activation of β-catenin, mismatch repair defects and p53 mutations

Sporadic childhood hepatoblastomas show activation of β-catenin, mismatch repair defects and p53 mutations

Truncated neurokinin-1 receptor is an ubiquitous antitumor target in hepatoblastoma, and its expression is independent of tumor biology and stage

Liver Tumors in Children

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