A population-based study of low-grade gliomas and mutated isocitrate dehydrogenase 1 (IDH1)

Abstract

Low-grade gliomas (LGG) have a slow growth rate, but transformations into malignant gliomas with a rapid deterioration occur in many patients. The aim of this study was to evaluate clinical prognostic factors in a population-based cohort of patients with LGG. In addition we investigated the expression and prognostic value of the isocitrate dehydrogenase 1 (IDH1) R132H mutation. Seventy-four patients diagnosed between 2005 and 2009 in the Region of Southern Denmark were identified using the Danish Cancer Register and The Danish Pathology Databank. Survival analysis using Cox regression was performed in 52 patients with tumor samples useable for immunohistochemical evaluation of IDH1 status. Patients with a contrast enhancing tumor, neurological deficits, headache, an astrocytic tumor and PS 2-4 had an increased risk of recurrence. In univariate analysis age > 50 years (HR 2.14, 95 % CI 1.08-4.24), having neurological deficit (HR 2.28, 95 % CI 1.15-4.52), receiving post-surgical treatment (HR 2.52, 95 % CI 1.19-5.32), being in performance status 2-4 (HR 1.44, 95 % CI 1.15-1.81), and having an astrocytic tumor (HR 3.79, 95 % CI 1.64-8.73) were associated with poor survival. Mutated IDH1 (mIDH1) was identified in 46 % of the patients and was significantly correlated to a good survival in both univariate (HR 0.24, 95 % CI 0.11-0.53) and in multivariate analysis (HR 0.40, 95 % CI 0.17-0.91). The other clinical variables were not significant when adjusted for the effect of mIDH1 status. We find that young age, the absence of neurologic deficit, PS 0-1 and oligodendroglial histology were associated with better survival. IDH1 status showed independent prognostic information when adjusting for classical prognostic factors, and should be validated in a larger patient population.

Trends in tumors in the central nervous system in elderly in Denmark, 2008–2012

“…This is in accordance with a study performed in our group [15], which showed that all patients do benefit from the Stupp regimen. The benefit is largest in patient younger than 60 years as compared to patients aged 60-70 years and 70+.…”

“…In this material, we did not have access to information regarding the proportion of cancers with a histological verification of the diagnosis, and it is difficult to interpret the results for the different histological subgroups of CNS tumors. However, based on a material of histologically verified malignant gliomas, we showed a similar trend in these patients [15]. To our knowledge studies regarding elderly patients and treatment have only been published regarding patients with malignant gliomas.…”

“…In the region of southern Denmark, which represents 20% of the Danish inhabitants, the number of patients with (Table I) [15]. …”

Development and validation of a prognostic model for recurrent glioblastoma patients treated with bevacizumab and irinotecan

“…Response assessment is susceptible to considerable inter-observer variability and this may explain most of the difference in our observed response rates and why we were not able to predict 19 (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29) 18 11 (5- Figure 1. Survival of risk groups.…”

Analysis of Olig2 and YKL-40 expression: a clinicopathological/immunohistochemical study for the distinction between subventricular zone II and III glioblastomas

“…Median survival of GB patients treated with aggressive multimodal thera py, including total resection, combined radiation and chemotherapy, and adjuvant chemotherapy is about 12 months [9,18,24,25]. Glioblastoma is actually con sidered a heterogeneous and dynamic disease [13,17,21].…”