GCT-12. SIOP CNS GCT II: High Risk (HR) CNS Non-germinomatous Germ Cell Tumours (NGGCT) treated with Dose intensified PEI – final results

Based on results of SIOP CNS GCT 96, patients enrolled in SIOP CNS GCT II with AFP higher or 1000 ng/ml (serum and/or CSF) and/or age less than 6 years with NGGCTs at diagnosis received two standard cycles of PEI and two higher dose PEI courses followed by radiotherapy according to dissemination (54 Gy local RT or 30 Gy CSI/24 Gy tumour boost). Between 2/2012 and 7/2018, 112 patients with CNS NGGCT were registered, of whom 23 were identified as HR patients; 18/23 had an AFP higher or 1000 ng/ml and were older than 6 years. Five children were < 6 years and showed YST elements in histology. of whom 3 received chemotherapy alone due to age. Primary site was pineal in 15/23, suprasellar in 5/23, bifocal in 3/23 patients; 3/23 patients were metastatic at diagnosis and 9/23 patients relapsed. Three years EFS was 0.60±0.10 with a median observation time of 3.96 years. Two recurrences were local, 4 distant (metastatic) and 3 combined, local and distant. HR CNS NGGCTs appeared to benefit from dose intensified PEI, compared with those treated in SIOP CNS GCT 96 with standard dose PEI. These results support the further exploration of this chemotherapy regimen in future clinical trials in such patient groups, including the consideration of delivering three dose intensified courses after one standard chemotherapy course, as is the practice in some groups treating very high risk extracranial GCTs.