Authors: Jordan A Holmes Anna K Paulsson Brandi R Page Lance D Miller Wennuan Liu Jianfeng Xu William H Hinson Glenn J Lesser Adrian W Laxton Stephen B Tatter Waldemar Debinski Michael D Chan
Publish Date: 2015/07/18
Volume: 124, Issue: 3, Pages: 447-453
Abstract
We present a retrospective investigation of the role of genomics in the prediction of central versus marginal disease progression patterns for glioblastoma GBM Between August 2000 and May 2010 41 patients with GBM and gene expression and methylation data available were treated with radiotherapy with or without concurrent temozolomide Location of disease progression was categorized as within the high dose 60 Gy or low dose 46 Gy volume Samples were grouped into previously described TCGA genomic groupings Mesenchymal m classical c proneural pn and neural n and were also classified by MGMTMethylation status and GCimp methylation phenotype Genomic groupings and methylation status were investigated as a possible predictor of disease progression in the high dose region progression in the low dose region and time to progression Based on TCGA category there was no difference in OS p = 026 60 Gy progression PN 71 N 60 M 89 C 83 p = 019 46 Gy progression PN 57 N 40 M 61 C 50 p = 08 or time to progression PN 9 months N15 months M 9 months C 7 months p = 058 MGMT methylation predicted for improved OS median 25 vs 13 months p = 001 improved DFS median 13 vs 8 months p = 0007 and decreased 60 Gy p = 0003 and 46 Gy p = 0006 progression There was a cohort of MGMT methylated patients with late marginal disease progression 4/22 patients 18 TCGA groups demonstrated no difference in survival or progression patterns MGMT methylation predicted for a statistically significant decrease in infield and marginal disease progression There was a cohort of MGMT methylated patients with late marginal progression Validations of these findings would have implications that could affect radiation field size
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