Author: Julia Dobke, Prof. Dr. med. I. Schmidt, Last modification: 2024/10/04
https://kinderkrebsinfo.de/doi/e92017
GPOH Liver tumour registry |
Registry for liver tumours in children and adolescents |
Disease |
Primary (malignant and benign) liver tumour |
Type |
Registry |
Rationale / Objectives |
Primary liver tumours in children and adolescents are rare, affecting 0.3–1 % of all paediatric tumour patients. In Central Europe, the incidence is 0.5–2 cases per 1 million children. The most common hepatocellular malignancies are hepatoblastoma (HB) in infants and young children and hepatocellular carcinoma (HCC) in schoolchildren and adolescents. Malignant, non-epithelial tumours of the sarcoma group as well as germ cell tumours, rhabdoid tumours and others are much rarer.
The liver tumor registry aims at a comprehensive registration of all children, adolescents and young adults suffering from a benign or malignant liver tumour in Germany. Special emphasis is placed on the collection of comprehensive epidemiological data, therapy documentation, the recording and verification of the function of the reference centres and the biobanking of tumour and patient material in a GPOH tumour bank.
Objectives
- Epidemiology: gain more knowledge on the following epidemiological aspects regarding primary liver tumours in childhood and adolescence (in addition to the data recorded within IMBEI, see initial IMBEI report): incidence, age distribution, family history and potential genetic predisposition, associated diseases and infections, tumour symptoms, tumor stage at diagnosis, histology and course of disease (survey questionnaire, follow-up / late effects questionnaire, histology questionnaire)
- Care research: Recording and checking the function of the reference centres (clinical reference centre - study management and pathology reference centre in the Institute of Pathology of the University Hospital Bonn). Simultaneous recording of the quality of therapy in the paediatric oncology centres of the GPOH with regard to therapy strategy, chemotherapy given, surgeries performed, side effects, complications and long-term effects as well as the therapy results (see also event sheet, aftercare/late effects surgery sheet, chemotherapy sheet)
- Preservation of material: Ensuring the most comprehensive biobanking of tumour and patient material in the KPOH Reference Laboratory of the Neuropathology Institute of the University of Bonn for molecular biological and cell biological research (Ernestus et al., 2006)
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Therapy / Study arms |
The Paediatric Hepatic International Tumour Trial, PHITT) was closed by 31/12/2023. Study results may be expected in about three years. All patients should be further reported to the liver tumour registry. Until the opening of trial PHITT II, therapy recommendations are as described below. Hepatoblastoma is classified according to the CHIC classification, hepatocellular carcinomas according to resectability.
Hepatoblastoma (HB)
Therapy group A (very low risk): 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. The first step of treatment consists of surgery to remove the tumour. If hepatoblastoma consisting of well-differentiated fetal tumour cells is present (WDF type), treatment consists of surgery only. In all other patients, surgery is followed by chemotherapy consisting of two cycles of cisplatin, 5-fluorouracil and vincristine each. To prevent hearing loss, sodium thiosulfate (STS) is recommended after each cisplatin administration.
Therapy group B (low risk):: 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. The patients will initially 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. Then, surgical tumour removal is performed, followed by two more cycles of cisplatin. In total, no more than six cycles of cisplatin should be given.
Therapy group C (intermediate risk):: All patients with locally advanced hepatoblastoma are assigned to this therapy group. 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. Liver tumour removal is carried out by means of a conventional surgery or a liver transplant following cisplatin in cycle 4.
Therapy group D (high risk): ALL patients with distant metastases (usually lung metastases) or with extensive liver tumours and the presence of risk factors (such as anatomical risk factors, age of the patient, AFP value) will be assigned to this therapy group. All patients 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 and a liver transplant may also be indicated. If the (lung) metastases regress as a result of induction therapy (remission), a consolidation of three cycles of combined carboplatin/doxorubicin chemotherapy takes place after surgery. If, on the other hand, metastases are still present after induction therapy, there is no standard recommendation. Favourable treatment options should be assessed in a national or international tumour board.
Hepatocellular Carcinoma (HCC)
Therapy group E (tumour is limited to the liver and can be removed without any problems):: If the HCC has developed as a result of a disease of the liver, no chemotherapy is given after resection of the HCC. In all other patients, treatment with four cycles of PLADO (cisplatin and doxorubicin) is carried out after complete resection. The administration of sodium thiosulfate (STS) is always recommended six hours after cisplatin.
Therapy group F (all patients with metastases or inoperable liver tumour):: Patients will receive at least four cycles of PLADO (cisplatin and doxorubicin) + sorafenib. If resection is still not possible (in HCC, any tumour must be surgically removed), a switch to four cycles of GemOx (gemcitabine and oxaliplatin) + sorafenib followed by immunotherapy is the recommended treatment.
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Inclusion Criteria |
- All patients with a primary (malignant or benign) liver tumour who are aged 0–20 years and have been diagnosed and treated within a GPOH centre should be included in the registry.
- The patient’s or legal guardian’s written consent regarding transfer, storage and evaluation of personal data must be available.
- Note: for a patient treated within another GPOH trial or registry, e.g. in case of liver sarcoma (CWS), germ cell tumour (MAKEI), rhabdoid tumour (EU-RHAB), recording should occur into the respective registry; no data will be recorded within this registry.
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Exclusion Criteria |
- Lack of consent regarding storage, evaluation and disclosure/transfer of personal data
- Treatment within another GPOH trial
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Recruitment |
35 to 40 children and adolescents with a primary liver tumour per year |
Status |
Start: 01/01/2011 |
Principal Investigator |
Prof. Dr. med. I. Schmidt |
E-Mail |
Irene.Schmid@med.uni-muenchen.de
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Contact |
Principal Investigator
Prof. Dr. med.
Irene Schmid
Klinikum der Universität München, LMU München
Kinderklinik und Kinderpoliklinik im Dr. von Haunerschen Kinderspital
Lindwurmstraße 4
80337
München
Telefon +49 (89) 4400 54498
Fax +49 (89) 4400 57514
Irene.Schmid@med.uni-muenchen.de
Subinvestigator
PD Dr. med.
Beate Häberle
Klinikum der Universität München, LMU München
Kinderchirurgische Klinik im Dr. von Haunerschen Kinderspital
Lindwurmstraße 4
80337
München
Telefon +49 0(89) 4400 52811
beate.haeberle@med.uni-muenchen.de
Tissue bank / molecular biology
Prof. Dr. med.
Torsten Pietsch
Universitätsklinikum Bonn
Institut für Neuropathologie, Geb. 81
Venusberg-Campus 1
53127
Bonn
Telefon +49 (228) 287 16602
Fax +49 (228) 287 14331
neuropath@uni-bonn.de
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Participants |
GPOH clinics |
Weitere Informationen |
The study group participates in the international CHIC project aiming at analysing pooled patient data from all cooperative hepatoblastoma studies of the last 20 years (n = 1605). Currently, HCC patients are included in the registry as well.
Since there are no available standard recommendations for patients with recurrent disease or progression under therapy, an international registry has been established for data collection. Under the supervision of the Vienna group, over 300 patients have been registered up to now.
Since the end of the international cooperative therapy trial for HB and HCC (PHITT - Paediatric Hepatic Malignancy International Therapeutic Trial) by the study groups SIOPEL, COG and JPLT on 31/12/2023, discussions have been pursued, on the one hand within the SIOPEL group regarding an interim trial for high-risk hepatoblastoma (SIOPEL Explorer), on the other hand on a worldwide scale regarding a PHITT II trial. |
Link(s) |
Literature on liver tumours
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Sponsoring |
German Childhood Cancer Foundation (Deutsche Kinderkrebsstiftung) |