Secreting germ cell tumors of the central nervous system (CNS). First results of the cooperative German/Italian pilot study (CNS sGCT).

BACKGROUND

Secreting germ cell tumors are an invariably fatal subgroup within the malignant pediatric brain tumors. Thus in 1993, an international working group was initiated to establish a cooperative study for diagnostic and treatment of intracranial secreting germ cell tumors of the CNS. To pilot this protocol, since 1994 German and Italian patients are treated in accordance with the established guidelines.

METHODS

Regarding to the achieved consensus within the international protocol committee a characteristical diagnostic imaging (CT/MRI scan) of head and spine and a significant increase of tumor markers beta-HCG (> 50 IU/l) and/or AFP (> 25 ng/ml) are defined as sufficient diagnostic criteria. Additionally staging procedures include an initial CSF cytology. Treatment consists of 4 courses PEI: platinum (20 mg/m2 day 1-5), VP16 (100 mg/ m2 day 1-3), and ifosfamide (1.5 g/m2 day 1-5). Surgery of the residual tumor is administered after chemotherapy, if resection is possible, followed by craniospinal irradiation (30 Gy with tumor boost 24 Gy).

RESULTS

Until September 96, 19 patients (16 boys and 3 girls) aged 8 to 19 years are registered and have finished their treatment. Seven children are diagnosed by elevated tumor markers. Six of 7 children with stereotactic fine needle biopsy and histology of germinoma have a significant marker increase as a specific characteristic for secreting non-germinomatous germ cell tumors. In 6 patients, the tumor is primarily resected, 2 children are biopsied. In 2 children spinal metastases are diagnosed initially. Tumor marker response is evaluated in 16 children. Thirteen of 16 patients show a clear marker normalization after 2 courses of PEI. One boy with a slight increase of the tumor marker after the 4th course developed an early spinal relapse and died. One girl showed a spinal recurrence during focal radiotherapy. She is still under relapse treatment. A significant decrease of tumor volume after chemotherapy is documented in 10/13 children, who have a definite signal tumor at start of therapy. In 3 children tumor volume does not change despite of marker normalization. Histology of these tumors is teratoma. One of these children died postoperatively because of tumor bleeding. 17/19 patients are alive, 16 of them are in complete remission with a median follow-up of 11 months.

CONCLUSION

These results show a further significant increase of event-free survival (EFS 81%). The piloted chemotherapy is proven to be effective and the protocol is now open as an international SIOP CNS GCT study that is started in October 1996.