Treatment of patients with hepatoblastoma according to interim recommendations

Author:  Maria Yiallouros, Reviewer:  Prof. Dr. med. Irene Schmid, English Translation:  Dr. med. Gesche Riabowol (nee Tallen), Last modification: 2024/07/06 https://kinderkrebsinfo.de/doi/e260093

Depending on their individual disease condition and the associated risk of recurrence, hepatoblastoma patients are assigned to one of four treatment regimens or risk groups, respectively.

The risk groups are as follows:

• very low risk hepatoblastoma
• low risk hepatoblastoma
• intermediate risk hepatoblastoma
• high risk hepatoblastoma

Risk groups are classified according to the so-called CHIC system of the CHIC group (Childhood Hepatic Tumour International Consortium), a consortium for liver tumours to which all major study groups worldwide (including the GPOH) belong. This complex stratification system takes into account the extent of the tumour in the liver (PRETEXT stage I-IV), the presence of distant metastases, additional anatomical risk factors (V+, P+, E+, F+, R+ or N) and, depending on the stage, the alpha-1 fetoprotein (AFP) serum level as well as the age of the patient at the time of diagnosis (see Hepatoblastoma – Brief information, chapter "Treatment planning"). The less extensive the tumour, the more favourable the chances of recovery and the less intensive the treatment. A low AFP serum level (up to 100 ng/ml) is considered prognostically unfavourable, as is a patient age of 8 years and older, and, in case of PRETEXT stage IV, the age of 3 years and older.

In patients with "very low risk" hepatoblastoma, attention is also paid to the histological type of the tumour: patients with hepatoblastoma with well-matured (differentiated) fetal tumour cells („well-differentiated fetal"; WDF) have a better prognosis than those with hepatoblastomas of other histological types, which is taken into account for treatment planning (see next chapter).

The following table provides an overview of the most important criteria for the classification of the disease:

Note on the abbreviations used: P: thrombosis in portal vein or tumour surrounding portal vein; V: thrombosis in hepatic veins or inferior vena cava or walling of the same caused by the tumour; E: expansion outside the liver; F: multifocal tumour extension; R: tumour rupture; N: involvement of lymph nodes; AFP: alpha-1-fetoprotein (tumour marker)

Treatment procedures in the different therapy groups

The international interim recommendations provide for the following treatment options within the four therapy groups for patients with hepatoblastoma, which we briefly present to you here. Your treatment team will inform you about the therapy group that is suitable for your child as well as corresponding therapy options and procedures.

Therapy goup A: very low risk hepatoblastoma

This therapy group is assigned to children and adolescents whose tumour is already fully operable at diagnosis due to its small size and the absence of other risk factors and who, therefore, have only a very low risk of recurrence.

The first step of treatment consists of surgery to remove the tumour. Subsequently, based on the histological analysis of the tumour tissue, a decision is made as to whether surgery alone is sufficient or whether chemotherapy is still necessary: If hepatoblastoma consisting of well-differentiated fetal tumor cells is present (WDF type), the treatment is over with the operation. In patients with another type of hepatoblastoma (no WDF histology), chemotherapy consisting of two cycles of cisplatin, 5-fluorouracil and vincristine is carried out after surgical tumour removal. To prevent hearing loss, sodium thiosulfate (STS) is recommended after each cisplatin administration.

Therapy group B: low risk hepatoblastoma

This therapy group treats children and adolescents whose tumour is inoperable at the time of diagnosis due to its size or extent, but for whom there are no other risk factors.

Patients in this group will initially all receive preoperative chemotherapy consisting of four cycles of cisplatin. To prevent hearing loss, the administration of sodium thiosulfate (STS) is recommended after each cisplatin administration. If possible, surgical tumour removal is then performed, followed by postoperative chemotherapy consisting of two cycles of cisplatin. In total, no more than six cycles of cisplatin should be given. If the operation is not performed after the fourth, but (at the latest) after the cycle, another cisplatin cycle should definitely be administered after the operation.

Therapy group C: intermediate risk hepatoblastoma

All children and adolescents with locally advanced hepatoblastoma are assigned to this therapy group. These include PRETEXT I-III hepatoblastomas with additional risk factors as well as some PRETEXT IV hepatoblastomas.

Treatment consists of pre- and postoperative chemotherapy (see supplementary note below) and surgery/transplantation/. To plan the surgical procedure and/or transplant, a referral to a transplant centre is made at an early stage. The time of surgery is determined individually, but takes place during chemotherapy, at the latest before the start of the last two chemotherapy cycles.

According to the current interim recommendations, patients will receive chemotherapy consisting of five cycles of combined cisplatin (on day 1) and carboplatin/doxorubicin (on days 15–16). The administration of sodium thiosulfate (STS) is recommended after each cisplatin cycle in order to prevent chemotherapy-induced hearing loss.

Therapy group D: high risk hepatoblastoma

The presence of distant metastases (usually lung metastases) at the time of diagnosis generally requires treatment in the high-risk group – regardless of the local extent of the tumour in the liver (PRETEXT stage). Apart from this, depending on the PRETEXT stage, other factors (such as anatomical risk factors, age of the patient, AFP value) are decisive for the need for treatment in the high-risk group, even if there are no distant metastases.

All patients in this therapy group will initially receive standard induction therapy consisting of three cycles of combined chemotherapy (with cisplatin and doxorubicin). For patients who do not have metastases, the administration of sodium thiosulfate (STS) is always recommended six hours after cisplatin. The liver tumour is then completely removed surgically. If the (lung) metastases regress as a result of induction therapy (remission), a consolidation of three blocks of combined carboplatin/doxorubicin chemotherapy takes place after the operation. If, on the other hand, metastases are still present after induction therapy, there is no standard recommendation. The procedure should be determined in a national or international tumour board.

Surgical liver surgery may include a liver transplant. As a rule, therefore, a referral to a transplant centre is made at an early stage for the planning of the operation and/or transplant. If a liver transplant is necessary, the lungs must first be rehabilitated before this procedure, either through chemotherapy or surgery.