多伦多病童医院脑干胶质瘤PPT.ppt

Pediatric High Grade Astrocytoma and Histone Mutations Me H3F3A replication-independent histone 3 variant 3.3 two critical positions within the histone tail -K27M, G34R HIST1H3B/C Replication-dependent histone 3 variant 3.1 K27M only Location and frequency of Histone 3 mutations in pediatric HGG H3K27M is a midline disease H3G34R/V is a hemispheric disease Hemispheric Thalamic Pontine (DIPG) 20% H3.3K27M H3.3G34R/V 65% 50% 15% H3.1K27M 50% Spinal cord CONCLUSIONS Pediatric DIPGs are one of the main causes of brain tumor death in children After decades of clinical trials, largely based on protocols for adult brain tumors, no effective treatment has yet been found Ongoing studies are now based on the results of genomic studies that have identified potential target. Still radiation is the mainstay of treatment and re-irradiations offer benefit in some children The frame is secured as inferiorly as possible and one of the post is removed * * * * * * Large recurrent regions of gain common to both HGAs and DIPGs most frequently involved chromosomes 1q and 9q, while recurrent regions of gain in 17q and 10p were unique to DIPGs. Both the DIPGs and HGAs show large recurrent regions of loss in 13q. However, HGAs show more frequent loss of 9p and 4q while DIPGs show more frequent loss of 11p, 17p, 14q, 18p and 22q. * while recurrent regions of gain in 17q and 10p were unique to DIPGs. DIPGs show more frequent loss of 11p, 17p, 14q, 18p and 22q. * * * * * * * * Are they true DIPG? October 2011 January 2012 January 2017 Long term survivor Diffuse brainstem GliomasNorth American studies Few studies open Future studies Brainstem Gliomas Recently closed ACNS 0927: phase II study of SAHA (vorinostat) during and after radiation Open ADVL 1217 (A phase I study of MK-1775 concurrent with local radiation therapy for the treatment of newly diagnosed children with diffuse intrinsic pontine gliomas (DIPG)) Soon? Arsenic trioxyde (antivascular effect, radiosensitizer) Brainstem