LGG-14. PEDIATRIC DIFFUSE GLIOMA WHO-GRADE II: PROGNOSTIC IMPACT OF MOLECULAR GENETIC VARIANTS

We investigated the frequency of histological and molecularly defined variants of pediatric diffuse gliomas WHO grade II (DG2) and their prognostic impact within the German and Swiss SIOP-LGG-2004 cohort.

Hundred DG2 were confirmed by central histological review among 1645 pediatric low-grade gliomas, registered between April 1st, 2004 and March 31st, 2012 (6.1%; median age at diagnosis 9.44 years (0.8-17.8); sex ratio (m:f) 1.2:1; neurofibromatosis NF1 4%). Localization: cerebral hemispheres 42, supratentorial midline 27, focal pontine-medullary 11, cerebellar 10, spinal cord 10 cases.

In 64/100 cases, material for molecular genetic investigations was available. We identified 10 IDH-, 4 Histone3-K27M-, 12 BRAF-V600E-mutated DG2, 5 with KIAA1549-BRAF-fusion, and 33 DG2 wild-type for IDH/H3/BRAF. Further rare aberrations were revealed by additional Nanostring RNA analysis and methylation profiling.

Treatment included 1-3 surgical resections without (n=68) or with subsequent non-surgical therapy (16 primary vincristine/carboplatin chemotherapy, 16 primary irradiation, 16/32 multiple salvage treatments). Within a median observation time of 7.1 years (0.04-23.1), progression to high-grade glioma was documented by follow-up surgery in 9 cases, and 13 patients with tumors of the thalamus (6), caudal brain-stem (4) or elsewhere (3) died (4/4 Histone-, 1/10 IDH-, 1/12 BRAF-V600E-mutated, 0/5 BRAF-fusion positive, 3/33 IDH/H3/BRAF wild-type tumors, and 4/36 without material). 5year-OS was 89.6% (±3.1%).

Pediatric DG2 represents a genetically and clinically heterogeneous group. Histone3-K27M-mutation heralded progression and death, while other genetic features lacked prognostic impact. Larger homogeneously treated patient cohorts should be evaluated to validate the impact of molecular characteristics in the setting of multimodal treatment.