In an international study, pre-resection neoadjuvant chemotherapy (doxorubicin and cisplatin) was given to all children with PRETEXT stage 2, 3, or 4 hepatoblastoma with or without metastases. The chemotherapy was well tolerated. PRETEXT stage 1 hepatoblastoma was resected and treated with the same chemotherapy. Following chemotherapy, and excluding those who received liver transplant (less than 5% of patients), complete resection was obtained in 87% of children. This strategy resulted in an OS of 75% at 5 years after diagnosis for all children entered in the study. Identical overall results were seen in a follow-up international study. The Childhood Liver Tumour Strategy Group (SIOPEL) compared cisplatin with cisplatin and doxorubicin in patients with preoperative standard-risk hepatoblastoma. Standard-risk was defined as tumor confined to the liver and not involving more than three sectors. The rates of resection were similar for the cisplatin (95%) and cisplatin/doxorubicin (93%) groups, as were OS (95% and 93%), respectively.[Level of evidence:1iiA] Another SIOPEL study of high-risk hepatoblastoma treated patients with cisplatin alternating with carboplatin/doxorubicin in a dose intensive fashion. In 74 patients with PRETEXT stage 4 tumors, 22 of whom also had metastases, 31 became resectable and 26 underwent transplant. The 3-year OS of this group was 69% � 11%. The 3-year OS of all patients with metastases was 62% � 12%.
In contrast, an American Intergroup protocol for treatment of children with hepatoblastoma, encouraged resection at the time of diagnosis for all tumors amenable to resection without undue risk. The protocol (COG-P9645) did not treat children with stage I tumors of purely fetal histology with preoperative or postoperative chemotherapy unless they developed progressive disease. Further study will be needed to determine whether presurgical chemotherapy is preferable to resection followed by chemotherapy for children with PRETEXT stage 2, 3, and 4 hepatoblastoma.
Chemotherapy and metastatic disease
In rare cases, chemotherapy has eradicated pulmonary metastases and eliminated multinodular tumor foci in the liver. Intensive platinum- and doxorubicin-based multidrug chemotherapy can induce complete regressions in approximately 50% of patients, with subsequent 3-year event-free survival of 56%. Chemotherapy has been much more successful in the treatment of hepatoblastoma than in hepatocellular carcinoma.[4,5,11,12,31,32,33]
Limited Role for Radiation Therapy
The utility of radiation therapy is questioned because the liver cannot tolerate high doses of radiation.[32,34]
Radiation therapy, even in combination with chemotherapy, has not cured children with nonresectable tumors. There may be a role for radiation therapy in the management of incompletely resected hepatoblastoma,[32,34] although a study of 154 patients with hepatoblastoma did not confirm this finding. This study showed that second resection of positive margins and/or radiation therapy may not be necessary in patients with incompletely resected hepatoblastoma whose residual tumor is microscopic.