SIOP CNS GCT II

Germinoma

• To maintain current high event-free survival (EFS) rates using a risk adapted approach
• In localised germinoma: to omit whole brain and spinal irradiation by using combined treatment with standard chemotherapy and ventricular irradiation (+/- boosts)
• In bifocal tumours (pineal + suprasellar): to treat as non-metastatic disease and to omit whole brain and spinal irradiation by using combined treatment with standard chemotherapy and ventricular irra-diation (+/- boosts)
• In metastatic disease: to maintain current excellent EFS in metastatic germinoma with craniospinal irradiation

NON-GERMINOMA (± TERATOMA)

To improve EFS:

• by dose escalation of chemotherapy in patients identified as high risk at diagnosis ( age < 6 years and/or AFP serum / CSF > 1000 ng/ml)
• by standardising the surgical approach for residual disease after treatment

Teratoma

• To register patients and collect data regarding diagnostics, treatment and outcome in order to develop future treatment strategies

Germinoma

Chemotherapy:

Non-metastatic fully staged germinoma (± teratoma)
Two courses (1 and 3) of Etoposide and Carboplatin, alternating with two courses (2 and 4) of Etoposide and Ifosfamide
Note: Bifocal germinoma (pineal+suprasellar) are treated as non-metastatic germinoma, if staging shows no additional dissemination

Metastatic or incompletely staged germinomas (± teratoma)
Do not receive chemotherapy in this protocol

Radiotherapy:

Non-metastatic pure germinoma in PR/SD
After Chemotherapy: 24 Gy (15 fractions) to whole ventricles with a 16 Gy (10 fraction) boost to tumour bed (total tumour dose 40 Gy)

Non-metastatic germinoma in CR
After Chemotherapy: 24 Gy (15 fractions) to whole ventricles

Metastatic or incompletely staged pure germinoma
24 Gy (15 fractions) to craniospinal axis with a 16 Gy (10 fraction) boost to tumour bed and any intracranial metastases and spinal deposits (total tumour dose 40 Gy)

Non-metastatic germinoma plus teratoma (incompletely resected)
After Chemotherapy: 24 Gy (15 fractions) to whole ventricles; 30.4 Gy (19 fraction) boost to tumour bed (total tumour dose 54.4 Gy)

Metastatic germinoma plus teratoma (incompletely resected)
24 Gy (15 fractions) to craniospinal axis ; 30.4 Gy (19 fraction) boost to tumour bed and 16 Gy (10 frac-tion) boost to metastases (total tumour dose 54.4 Gy)

NON- GERMINOME (± TERATOM)

Chemotherapie:

Standard-Risiko nicht-germinomatöse maligne Keimzelltumoren
Vier Kurse Etoposid, Cisplatin und Ifosfamid (Standardbehandlung)

Hoch-Risiko nicht-germinomatöse maligne Keimzelltumoren
Zwei Kurse Standarddosen Etoposid, Cisplatin und Ifosfamid, gefolgt von zwei dosisintensivierten Kursen Etoposid, Cisplatin und Ifosfamid mit Stammzellsupport
Resektion von Resttumor nach drei Kursen Chemotherapie (wenn indiziert) gefolgt vom vierten Kurs Chemotherapie. Wenn vitale Tumorzellen im Resektat gefunden wurden, wird der Patient der Hoch-Risikogruppe zugeführt.

Radiotherapie

Standard-Risiko und Hoch-Risiko nicht-germinomatöse maligne Keimzelltumoren:

Patienten mit lokalisierter Erkrankung bei Diagnose
Nach Chemotherapie: 54 Gy fokale Bestrahlung (30 Fraktionen)

Patienten mit metastatischer Erkrankung bei Diagnose
Nach Chemotherapie: 30 Gy (20 Fraktionen) kraniospinal mit 24 Gy (15 Fraktionen) Boost des Tumorgebietes sowie jeder intrakranialen Metastase Gesamttumordosis 54Gy) und 20.8 Gy (13 Fraktionen) Boost der spinalen Metastasen (Gesamtdosis 50.8 Gy)

• Main residence in one of the participating countries
• Primary diagnosis of an intracranial germ cell tumour
• Written consent for trial participation, treatment according to the protocol and consent for data transfer

• Tumour entity other than primary intracranial germ cell tumour or CNS GCT as second malignancy
• Primary diagnosis pre-dating the opening of SIOP CNS GCT II in the participating country of registration
• Medical, psychiatric or social conditions incompatible with trial treatment or treatment according to protocol is not intended
• Participation within a different trial for treatment of germ cell tumours and/or concurrent treatment within any other clinical trial. The only exceptions to this are trials with different endpoints, involving aspects of supportive treatment which can run parallel to SIOP CNS GCT II without influencing the outcome of this trial e.g. trials on antiemetics, antimycotics, antibiotics, strategies for psychosocial support etc.
• Pregnancy and lactation
• Any treatment not given according to protocol prior to registration