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


METHODS
High risk was defined as follows: tumor in all liver sections (ie, Pretreatment Extension IV [PRETEXT-IV]), or vascular invasion (portal vein [P+], three hepatic veins [V+]), or intra-abdominal extrahepatic extension (E+), or metastatic disease, or alpha-fetoprotein less than 100 ng/mL at diagnosis. Patients were treated with alternating cycles of cisplatin and carboplatin plus doxorubicin (preoperatively, n = 7; postoperatively, n = 3) and delayed tumor resection.


RESULTS
Of the 151 patients (150 evaluable for response) 118 (78.7%) achieved a partial response to chemotherapy. Complete resection of the liver tumor could be achieved in 115 patients (76.2%) either by partial hepatectomy (55.6%) or by liver transplantation (20.6%). In 106 children (70.2%), complete resection of all tumor lesions (including metastases) was achieved. Among the patients with initial lung metastases, 52.2% achieved complete remission of the lung lesions with chemotherapy alone. In half of the patients with initial PRETEXT-IV tumor as the only high-risk feature, the tumor could be completely resected with partial hepatectomy. Event-free (EFS) and overall survival (OS) estimates at 3 years were 65% (95% CI, 57% to 73%) and 69% (95% CI, 62% to 77%) for the whole group. EFS and OS for all patients with PRETEXT-IV tumor were 68% and 69%, respectively, and they were 56% and 62%, respectively, for patients with metastasis.


CONCLUSIONS
The applied treatment rendered a great proportion of tumors resectable, and, in comparison with previously published results, led to an improved survival in patients with high-risk hepatoblastoma.
Zsíros
József
J
Department of Pediatric Oncology, Emma Children's Hospital Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands. j.zsiros@amc.uva.nl
Maibach
Rudolf
R
Shafford
Elizabeth
E
Brugieres
Laurence
L
Brock
Penelope
P
Czauderna
Piotr
P
Roebuck
Derek
D
Childs
Margaret
M
Zimmermann
Arthur
A
Laithier
Veronique
V
Otte
Jean-Bernard
JB
de Camargo
Beatriz
B
MacKinlay
Gordon
G
Scopinaro
Marcelo
M
Aronson
Daniel
D
Plaschkes
Jack
J
Perilongo
Giorgio
G
D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D017024:Chemotherapy, Adjuvant; D002648:Child; D002675:Child, Preschool; D002945:Cisplatin / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D018197:Hepatoblastoma / Q000188:drug therapy* / Q000601:surgery*; D006801:Humans; D007223:Infant; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000601:surgery*; D008297:Male; D011300:Preoperative Care; D011446:Prospective Studies; D012307:Risk Factors; D016019:Survival Analysis; D016896:Treatment Outcome
D004317:Doxorubicin; D016190:Carboplatin; D002945:Cisplatin