GENE-30. INCREASED TUMOR MUTATIONAL LOAD AFTER RADIOTHERAPY AND TEMOZOLOMIDE IN PROGRESSING GLIOBLASTOMA A PROSPECTIVE STUDY. (5th November 2018)

• Record Type: Journal Article
• Authors: Nørøxe, Dorte Schou; Yde, Christina Westmose; Østrup, Olga; Nielsen, Finn Cilius; Skjøth-Rasmussen, Jane; Brennum, Jannick; Hamerlik, Petra; Poulsen, Hans; Lassen, Ulrik
• Is Part Of: Neuro-oncology. Volume 20(2018)Supplement 6
• Page Start: vi109
• Page End: vi110
• Publication Date: 2018-11-05
• Subjects: Brain Neoplasms -- Periodicals; Brain -- Tumors -- Periodicals; Brain -- Cancer -- Periodicals; Nervous system -- Cancer -- Periodicals; 616.99481
• DOI: 10.1093/neuonc/noy148.456
• Languages: English
• ISSNs: 1522-8517

Abstract

Abstract: BACKGROUND: Tumor mutational load (TML) is the number of nonsynonymous mutations in a tumor sample. TML has proved predictive of response to immune therapy (IT) in other TML-high tumors. Research in TML in glioblastoma (GBM) is limited and has to our knowledge not been done prospectively in paired samples before and after treatment. MATERIALS AND METHODS: Over a 2-year period from February 2016 to March 2018, 27 patients with newly diagnosed GBM were included. All patients had one biopsy at diagnosis and another when having secondary surgery due to progression. Three patients had three surgeries. We noted clinical and pathological data. Blood samples were extracted and whole exome sequencing has been performed. We are now investigating TML including clonal and subclonal mutations, mutations in mismatch repair genes and the aberrant cell fraction. TML will be reported as per Megabase exome and will be adjusted for coverage in each sample. RESULTS: All the included patients had primary GBM with isocitrate dehydrogenase ( IDH ) wild type. O -6-methylguanine-DNA methyltransferase (MGMT) was methylated in 6 patients (22%) and the majority of patients have been treated with chemo/radiation with Temozolomide. Since the patients were included from our daily clinical oncological department, the clinical characteristics resembled the average GBM patient according to age, performance status, treatment, progression-free survival and overall survival. CONCLUSION: Analyses are forthgoing and will be ready at the time of the SNO-meeting. An agreement of how to report TML is strongly needed and TML should be included in future trials in GBM.