Cisplatin versus cisplatin plus doxorubicin for standard-risk hepatoblastoma.

Contains fulltext : 79859.pdf (publisher's version ) (Open Access)BACKGROUND: Preoperative cisplatin alone may be as effective as cisplatin plus doxorubicin in standard-risk hepatoblastoma (a tumor involving three or fewer sectors of the liver that is associated with an alpha-fetoprotein level of >100 ng per milliliter). METHODS: Children with standard-risk hepatoblastoma who were younger than 16 years of age were eligible for inclusion in the study. After they received one cycle of cisplatin (80 mg per square meter of body-surface area per 24 hours), we randomly assigned patients to receive cisplatin (every 14 days) or cisplatin plus doxorubicin administered in three preoperative cycles and two postoperative cycles. The primary outcome was the rate of complete resection, and the trial was powered to test the noninferiority of cisplatin alone (<10% difference in the rate of complete resection). RESULTS: Between June 1998 and December 2006, 126 patients were randomly assigned to receive cisplatin and 129 were randomly assigned to receive cisplatin plus doxorubicin. The rate of complete resection was 95% in the cisplatin-alone group and 93% in the cisplatin-doxorubicin group in the intention-to-treat analysis (difference, 1.4%; 95% confidence interval [CI], -4.1 to 7.0); these rates were 99% and 95%, respectively, in the per-protocol analysis. Three-year event-free survival and overall survival were, respectively, 83% (95% CI, 77 to 90) and 95% (95% CI, 91 to 99) in the cisplatin group, and 85% (95% CI, 79 to 92) and 93% (95% CI, 88 to 98) in the cisplatin-doxorubicin group (median follow-up, 46 months). Acute grade 3 or 4 adverse events were more frequent with combination therapy (74.4% vs. 20.6%). CONCLUSIONS: As compared with cisplatin plus doxorubicin, cisplatin monotherapy achieved similar rates of complete resection and survival among children with standard-risk hepatoblastoma. Doxorubicin can be safely omitted from the treatment of standard-risk hepatoblastoma. (ClinicalTrials.gov number, NCT00003912.

Successful treatment of childhood high-risk hepatoblastoma with dose-intensive multiagent chemotherapy and surgery: final results of the SIOPEL-3HR study

The primary objective was to determine the efficacy of a newly designed preoperative chemotherapy regimen in an attempt to improve the cure rate of children with high-risk hepatoblastoma

Dose-dense cisplatin-based chemotherapy and surgery for children with high-risk hepatoblastoma (SIOPEL-4): a prospective, single-arm, feasibility study

none19noneJózsef Zsiros;Laurence Brugieres;Penelope Brock;Derek Roebuck;Rudolf Maibach;Arthur Zimmermann;Margaret Childs;Daniele Pariente;Veronique Laithier;Jean-Bernard Otte;Sophie Branchereau;Daniel Aronson;Arun Rangaswami;Milind Ronghe;Michela Casanova;Michael Sullivan;Bruce Morland;Piotr Czauderna;Giorgio PerilongoJózsef, Zsiros; Laurence, Brugieres; Penelope, Brock; Derek, Roebuck; Rudolf, Maibach; Arthur, Zimmermann; Margaret, Childs; Daniele, Pariente; Veronique, Laithier; Jean Bernard, Otte; Sophie, Branchereau; Daniel, Aronson; Arun, Rangaswami; Milind, Ronghe; Michela, Casanova; Michael, Sullivan; Bruce, Morland; Piotr, Czauderna; Perilongo, Giorgi

Integrated genomic analysis identifies driver genes and cisplatinresistant progenitor phenotype in pediatric liver cancer

International audiencePediatric liver cancers (PLCs) comprise diverse diseases affecting infants, children and adolescents. Despite overall good prognosis, PLCs display heterogeneous response to chemotherapy. Integrated genomic analysis of 126 pediatric liver tumors showed a continuum of driver mechanisms associated with patient age, including new targetable oncogenes. In 10% of hepatoblastoma patients, all before 3 years old, we identified a mosaic premalignant clonal expansion of cells altered at the 11p15.5 locus. Analysis of spatial and longitudinal heterogeneity revealed an important plasticity between 'Hepatocytic', 'Liver Progenitor' and 'Mesenchymal' molecular subgroups of hepatoblastoma. We showed that during chemotherapy, 'Liver Progenitor' cells accumulated massive loads of cisplatin-induced mutations with a specific mutational signature, leading to the development of heavily mutated relapses and metastases. Drug screening in PLC cell lines identified promising targets for cisplatin-resistant progenitor cells, validated in mouse xenograft experiments. These data provide new insights into cisplatin resistance mechanisms in PLC and suggest alternative therapies

Identification of three clinical neurofibromatosis 1 subtypes: Latent class analysis of a series of 1351 patients

International audienc