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Brain Tumor Pathol. 2013 Apr;30(2):67-72. doi: 10.1007/s10014-012-0109-x. Epub 2012 Jul 3.

IDH1 mutation as a potential novel biomarker for distinguishing pseudoprogression from true progression in patients with glioblastoma treated with temozolomide and radiotherapy.

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  • 1Department of Neurosurgery, Graduate School of Medicine, Hokkaido University, North 15 West 7, Kita-ku, Sapporo, 060-8638, Japan.


The purpose of this study was to distinguish pseudoprogression (PP) from early true progression in patients with glioblastoma (GBM) based on the presence of a mutation in isocitrate dehydrogenase 1 (IDH1). We retrospectively surveyed 32 patients with GBM or GBM with oligodendroglioma component (GBMO) who underwent biopsy or maximal tumor resection followed by concurrent radiotherapy and temozolomide (TMZ). We then selected patients with early radiological progression in magnetic resonance imaging within 6 months after concurrent radiotherapy and TMZ treatment. DNA was extracted from their tumor blocks. The IDH1 mutation was analyzed in the genomic region by direct sequencing as a biomarker for PP. Twenty-eight patients were diagnosed with GBM and four with GBMO. Eleven patients were discovered to have early radiological progression. PP was detected in two patients (6.3%) diagnosed with GBMO and one patient with GBM. Both of the GBMO patients with PP had the IDH1 mutation, the one GBM patient with PP and the other eight patients with early true progression with wild type. The sensitivity and specificity of the IDH1 mutation for detecting PP were 66.7 and 100%, respectively. This study suggests the IDH1 mutation may become a novel molecular biomarker for PP. Analyzing the IDH1 mutation, in the case of recognizing early radiological progression, may enable distinction of PP from early true progression, and we could determine the need for second-look surgery.

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