EU-RHAB

Rhabdoid tumors are rather rare, highly aggressive malignancies that usually take a dismal clinical course and occure mostly in infants and small children. Despite a multitude of case series and single reports, little reliable data exist in regard to incidence, molecular basis, a potential rhabdoid stem cell and, most important, promising consistent national or international therapeutic approaches.

Genetics

Unifying features of rhabdoid tumors derived from the kidney, CNS and soft tissue are genetic mutations of the tumor suppressor gene candidate SMARCB1on gene 22.
Over 80% of tumors (independend of the anatomic location) lack the expression of the protein SMARCB1.To detect this change of the gene, it is necessary to perform immunohistochemical tests of the tumour tissue and genetical tests of tumour and blood cells of the patient. In rare cases a germline mutation can be detected. For theses cases genetic tests of the parents and familiy are adviced.

Frequency

In Germany every year ca. 30-40 patients fall ill with a rhabdoid-tumour. Comparable numbers are found in other european countries. Therefore there was the decision made on a consensus conference of representatives of the SIOP Brain Tumor Committee as of the italien and german CWS-and Neuroblastoma Study Groups in Genua 2007 to etablish a registry for rhabdoid-Tumours.

Aim of the European Rhabdoid-Registry is the complete registration of clinical, moleculargenetic and therapy associated data of all patients with rhabdoid tumours of the brain (AT/RT), the kidneys (RTK) and the soft tissue (MRT) in Europe.
In detail the following objectives were definded:

Primary objectives

• Creation of a comprehensive database for patients with rhabdoid tumors of any anatomical site diagnosed in European countries.
• Development of a structured plan for central review of histology (including SMARCB1 immunhistochemistry) and molecular genetics. To improve (neuro-) pathological, clinical and molecular genetic characterization of rhabdoid tumors.
• To render support to existing tumor banks and to perform biological studies, to identify future therapeutic targets.
• To cooperate with: Groups specialized in pediatric Soft Tissue Sarcoma (e.g. CWS, EPSSG) and Nephroblastoma, in studying similarities between extra- (RTK and MRT) and intra-CNS (AT/RT) rhabdoid tumors and in defining common treatment elements used in AT/RT and extra-CNS rhabdoid tumours. To communicate with groups in the USA and Australia to define points of reciprocal interest and potential for cooperation.

This project is not a drug study in the sense of the AMG. However there is an detailed therapy recommandation in the appendix. It was harmonised with all european partners. To learn as much as possible over the biology, epidemiology and promising treatment courses, the registry collects data about all of these items. Thereof result

Secondary objectives

• To determine event free and overall survival of patients.
• To evaluate the time to progression in patients with rhabdoid tumors treated on consensus therapeutic regimen.
• To assess the importance of surgical technique, particularly the effect of complete surgical
• resection.
• To assess the importance of involved field radiotherapy.

The collected data will be background for later Phase 1/2 trials.

Diagnosis

A rhabdoid-tumour can be diagnosed on tumours of the central nervous system (AT/RT), the kidneys (RTK) and the soft tissue (MRT). The target high-risk population comprises newborns and infants up to the age of three years, however rhabdoid tumors may be encountered in school children and as a rarity also in adults. At diagnosisi of AT/RT the average age lies between 20 and 25 month. At diagnosis of rhabdoid-tumours of the soft-tissue 60% of the patients are under 10 years old.

Therapy

Untill recently all patients with a rhabdoid-tumour were registered following the anatomical origin of the tumour in databanks belonging to the trial for kidney-tumours (e.g. SIOP 2001), soft-tissue tumours (e.g. CWS) and CNS-tumours (e.g. HIT). Within theses trials the group with the rhabdoid-tumours stood out with a specially high resistance to therapy.The GPOH (German association for pediatric oncology and haematology) therefore decided to collect the data and treat all patients with a rhabdoid-tumour with a consensus therapy.

This tratment persists either out of 9 alternate therapy-courses (3x DOX, ICE, VCA) or 6 alternate courses (2x DOX, ICE, VCA), followed by a high-dose chemotherapy (Carboplatin / Thiotepa).

A high significance in the treatment has the radiotherapy. This should be performed as early as possible. The age limit for radiation is 18 month. Radiation of younger children must be dicussed with the registry.

Patients of any age with histologically proven rhabdoid tumors, verified by central pathology review.
Informed consent by legal guardians to contribute data to the registry

Bitte E-Mailkontakt über diese Adresse: eurhab@uk-augsburg.de