Abstracts

Rationale: Primary brain tumors frequently present with seizures. In the recent decade, although there is development in the understanding of tumor genetics, genetic features influencing seizures and patient survival is not widely studied. This retrospective study was carried out to report the identified genetic factors like isocitrate dehydrogenase (IDH1) mutation, 1p19q co-deletion and O6-methylgua-nine DNA methyltransferase (MGMT) promoter methylation, in relation to their effect on seizure at presentation and survival.   Methods: After obtaining IRB approval, Henry Ford Health System (HFHS) Tumor Registry was used to identify patients who had a diagnosis of brain tumor at HFHS between January 1, 2006 and December 31, 2014.  Genetic information was obtained from the TCGA (The cancer genome atlas) data and EPIC (electronic medical records). Demographics and clinical data were collected, and a death index check was performed on each patient. Results: A total of 315 brain tumor patients with genetic information was available, of which 211 patients with glioblastoma (GBM) were not included, as GBMs have a very poor survival and a very low rates of IDH and 1p/19q co-deletion that would influence the results. Of the 104 patients included, 53 (51%) were males, 87 (84%) were Caucasian, 10 (10%) were African American with their mean age of 46.7 (range 22 to 81) and median follow-up of 53.2 months (interquartile range 32.7-77.6 months).  Almost half of the patients had oligodendrogliomas (n=51, 49%) followed by anaplastic oligodendrogliomas (n=14, 13%) and anaplastic astrocytomas (n=12, 12%).  Sixty-one (59%) of the patients had seizures as a presenting symptom and 34 (34%) had seizure occurrence after tumor diagnosis (25 of which also had seizures as a presenting symptom).  For the genetic information, 54 (60%) had MGMT, 41 (41%) had IDH mutant and 56 (55%) had 1p/19q co-deletion.  Most commonly, MGMT was noted with Oligodendroglioma (63%), IDH mutant with anaplastic astrocytoma (67%) and 1p/19q co-deletion status with Oligodendroglioma (78%). The associations between seizure at presentation and the genetic information were not significant. During follow-up, 35 (34%) patients died.  Increased survival was associated with seizures at presentation (mortality: 23% vs 48%, p=0.017), 1p/19q co-deletion (mortality: 21% vs 48%, p=0.002) and IDH/1p/19q combined status (mortality: 19% yes/yes, 27% yes/no, 24% no/yes and 55% no/no, p=0.002).  The associations with survival for MGMT (mortality: 32% vs 31%, p=0.912) and IDH status (mortality: 22% vs 39%, p=0.149) were not significant.   Given that seizures at presentation had a significant association with better survival, the association between seizures and survival were assessed within the different subgroups of patients based on their genetic profiles. Among patients with MGMT, those with seizures at presentation had significantly better survival compared to those without seizures (HR=0.33, 95%CI=[0.11, 0.95], p=0.039).  This was also true for patients with IDH WT status (HR=0.30, 95%CI=[0.12, 0.74], p=0.008), patients without 1p/19q co-deletion (HR=0.36, 95%CI=[0.15, 0.87], p=0.023) and patients with IDH WT status and no 1p/19q co-deletion (HR=0.20, 95%CI=[0.06, 0.64], p=0.006).  Conclusions: This study indicates that seizures as a presenting symptom may provide additional information about patient survival beyond IDH and IDH and 1p/19q co-deletion status in Grade II/III brain tumors. Many of these sample sizes are small and these results should be verified with a larger cohort of patients.  However, the results are consistent across the IDH and 1p/19q co-deletion status. Funding: This study was partly supported by Henry Ford Internal Grant Funding.