P10.28.A PATTERN OF FAILURE IN PEDIATRIC HIGH GRADE GLIOMAS TREATED WITH FOCAL RADIOTHERAPY

Abstract BACKGROUND Radiotherapy (RT) is the backbone of treatment of pediatric high grade gliomas (pHGGs), tipically characterized by very high rates of treatment failures. The aim of the present study was to describe the recurrence patterns (POF) after focal RT. MATERIAL AND METHODS We retrospectively compared RT plans with MRI imaging at relapse of an institutional series of pHGG-patients (pts) to describe the pattern of treatment failure. Local Failures(LFs) were mapped to the planning target volume (PTV) and classified as in-field (completely within the PTV), marginal (partially within the PTV), or out-of-field (completely outside the PTV). RESULTS 34 relapsed HGG pts, 17 females and 17 males, with a median age of 11 years (3-21), accrued from 2012 to 2022 were retrospectively evaluated. Primary sites consisted of diffuse cerebral lesions compatible with gliomatosis cerebri (GC) in 5 (13.8%), while among focal disease presenting cases, 15 were supratentorial, 2 cerebellar and 12 located in the brainstem. 24/34 (70.5%) patients received surgery after first imaging, with 1 gross total resection, 13 partial resection and 10 biopsies. Histological analysis identifed diffuse pediatric HGG H3 wild type, IDH 1/2 wild type in 1 case, diffuse hemispheric glioma, H3 G34-mutant in four cases, diffuse midline glioma, H3 K27-altered in four case, IDH1-mutant grade 3 astrocytoma in 1 case, BRAFV600E mutated anaplastic pleomorphic xantoastrocytoma in one case, while for 10 patient the diagnosis could only be HGG. Almost all (33/34, 97%) underwent to focal tumour bed irradiation, except one patient that received whole brain irradiation according to pGBM-WBRT/DOX2020 clinical trial (Eudract 2020-005131-74). All patients also underwent concomitant and adjuvant chemotherapy based mainly on temozolomide (TMZ) in 19 cases, nimotuzumab plus vinorelbine in 4 cases, and with a combination of TMZ and doxorubicine according to GBM TMZ/DOX 2015 Eudract: 2015-002307-28p) and GBM-WBRT/DOX2. Radiotherapy was performed with VMAT technique for a mean dose of 59,4Gy (range 54-59.4). At a median time of 7 months (range 3-39) 24 LFs were in field, 4 out-of-field, 3 marginal and 3 mixed (both in and out-of-field). All out-of-field LFs were diagnosed in supratentorial pts. CONCLUSION In supratentorial pediatric HGG POF may justify a different approach in terms of RT volumes (e.g. whole brain RT) in order to achieve a better outcome and possibly facilitating a higher penetrability of active drugs through the brain-blood barrier.