SIOPEL guidelines for the treatment of hepatoblastoma

Standard risk patients are eligible for entry to the SIOPEL 6 study however, we recommend the following treatment strategy for patients not entered into a clinical trial

Standard Risk Tumours: These are localised tumours (Pretext 1, 2 or 3) with no additional adverse features (e.g. low AFP, vascular involvement (V3 or P2), extrahepatic spread, tumour rupture, metastatic disease). The recommendation is to follow the cisplatin monotherapy arm of the SIOPEL 3 study (Perilongo et al 2009 NEJM 361:1662). The standard treatment is 4 cycles of preoperative chemotherapy followed by surgical resection and 2 post operative cycles of therapy.

High risk tumours: These tumours are defined as any tumour not meeting the standard risk or very high risk criteria. The recommendation is to receive the dose intensive “superPLADO” arm of the SIOPEL 3 study (Zsiros et al 2010 J Clin Oncol 28:2584). Patients in this group are likely to have challenging surgical disease and we would recommend consultation at the time of diagnosis with a specialist liver surgery/transplant service.

Very high risk tumours: These tumours are defined by the presence of metastatic disease (usually lung) or very low AFP (<100 ng/ml). Pulmonary lesions documented on the chest X-ray and/or lung CT  scan will be considered to be unequivocal metastatic tumour deposits if there is one nodule larger than 10 mm or several nodules with at least one larger than 5 mm. In the other cases, the metastases will be considered as doubtful and a surgical biopsy of one of the nodules should be discussed if the general condition of the child permits it. Patients should be treated with the approach utilised in the SIOPEL4 protocol with dose-intensive weekly cisplatin/doxorubicin induction therapy. This is an experimental regimen with limited pilot data shortly to be published. Particular attention should be paid to the potential toxicity and supportive care needs of patients on this regimen. All patients with low AFP should have an initial biopsy. The loss of INI1 expression is suggestive of rhabdoid tumour (sometimes confused with small cell undifferentiated hepatoblastoma) and we would recommend such patients are treated with a rhabdoid-style chemotherapy approach. Note some low risk localised tumours with small volume disease may also have a low AFP.