How I treat recurrent paediatric high-grade glioma (pHGG): A Europe-wide survey study

BACKGROUND: As there is no standard of care treatment for recurrent/progressing paediatric high-grade gliomas (pHGG), we aimed to gain an overview of different treatment strategies. METHODS: In a web-based questionnaire, members of the SIOPE-BTG and the GPOH were surveyed on therapeutic options in four case scenarios (children/adolescents with recurrent/progressing HGG). RESULTS: Most respondents (139 clinicians from 22 European countries) preferred further oncological treatment in three out of four cases and chose palliative care in one case with marked symptoms. Depending on the case, 8-92% would initiate a re-resection (preferably hemispheric pHGG), combined with molecular diagnostics. Throughout all case scenarios, 55-77% recommended (re-)irradiation, preferably local radiotherapy >20 Gy, and most respondents would participate in clinical trials and use targeted therapy (79-99%), depending on molecular genetic findings ( BRAF alterations: BRAF/MEK inhibitor, 64-88%; EGFR overexpression: anti-EGFR treatment, 46%; CDKN2A deletion: CDK inhibitor, 18%; S MARCB1 deletion: EZH2 inhibitor, 12%). 31-72% would administer chemotherapy (CCNU, 17%; PCV, 8%; temozolomide, 19%; oral etoposide/trofosfamide, 8%), and 20-69% advocated immunotherapy (checkpoint inhibitors, 30%; tumour vaccines, 16%). Depending on the individual case, respondents would also include bevacizumab (6-18%), HDAC inhibitors (4-15%), tumour-treating fields (1-26%), and intraventricular chemotherapy (4-24%). CONCLUSIONS: In each case, experts would combine conventional multimodal treatment concepts, including reirradiation, with targeted therapy based on molecular genetic findings. International cooperative trials combining a (chemo-)therapy backbone with targeted therapy approaches for defined subgroups may help to gain valid clinical data and improve treatment in paediatric patients with recurrent/progressing HGG.