Abstract
PURPOSE: Prognosis of pediatric high-grade gliomas (pedHGG) is dismal, and there is no standard of care treatment in case of recurrence/progression. We aimed to gain an overview of different treatment strategies in the setting of recurrent/progressing pedHGG. METHODS: In a web-based questionnaire, members of the SIOPE-BTG and the GPOH were surveyed on different therapeutic options in four real-world case scenarios (children/adolescents with recurrent/progressing HGG). RESULTS: One hundred and thirty-nine clinicians with experience in pediatric neuro-oncology from 22 European countries participated in the survey. Most respondents preferred further active (multimodal) oncological treatment in three out of four cases and chose palliative care with pure symptom control measures only in one case (gliomatosis cerebri and marked symptoms). Depending on the case, 8-92% of experts would initiate a re-resection (maximal safe resection in case of localized hemispheric pedHGG), combined with molecular diagnostics, and 55-77% recommended (re-)irradiation, preferably local radiotherapy >20 Gy (or craniospinal irradiation in one case with disseminated spinal HGG, 65%). Throughout all case scenarios, most respondents would participate in clinical trials and use targeted therapy (79-99%), depending on molecular genetic findings (BRAF alterations: BRAF/MEK inhibitors, 64-88%; EGFR overexpression: anti-EGFR treatment, 46%; SMARCB1 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%; tumor vaccines, 16%). Depending on the individual case, respondents would also include bevacizumab (6-18%), HDAC inhibitors (4-15%), tumor-treating fields (1-26%), and intraventricular chemotherapy (4-24%). CONCLUSIONS: In each case, experts would combine conventional multimodal treatment concepts, including re-irradiation, with targeted therapy based on molecular genetic findings. International cooperative trials combining a standard (chemo-)therapy backbone with targeted therapy approaches for defined subgroups may help to gain valid clinical data and improve treatment in pediatric patients with recurrent/progressive HGG.