The role of treatments in IDH mutant molecular astrocytomas

Abstract

Background: Low grade glioma (LGG) is a heterogeneous disease. Recently, the 2016 WHO classification of brain tumors has underlined the role of genetic and molecular features. Molecular astrocytomas have been defined as grade II tumors with IDH mutation and without 1p19q codeletion. Methods: We evaluated 213 consecutive patients with LGG who received surgery or biopsy and had adequate tissue to assess molecular characterization. IDH mutations were assessed by immunohistochemistry (IHC) and next generation sequencing (NGS) in IHC negative cases, MGMT methylation status was assessed by polymerase chain reaction (PCR) and 1p19q deletion was assessed by fluorescence in situ hybridation (FISH). Results: 198 patients (93.0%) showed IDH-mutation. Ninety patients (49.2%) were 1p19q non codeleted (molecular astrocytomas). The median follow up was 98.3 months. Median age was 36 (range: 18-69), 11 patients (12.2%) underwent biopsy, 48 (53.3%) patients subtotal resection and 31 (34.4%) patients total resection. According to RTOG criteria, 68 patients (75.6%) were considered high risk (> 40 years and/or incomplete resection), and 22 patients (24.4%) were considered low risk (< 40 years and/or complete resection). 59 patients (65.5%) did not receive any post-surgical treatment, but only follow-up, 31 patients (34.4%) received post-surgical treatments: 20 (22.2%) received radiotherapy (RT), 7 (7.8%) received chemotherapy (CT), 4 (4.4%) received CT+RT. Median progression-free survival (PFS) was 44.3 months. Significant differences in PFS were observed between treated and untreated patients (64.8 vs 35.7 months p = 0.004) and treated with RT versus follow-up (60.0 vs 35.7 months p = 0.004). Multivariate analysis confirmed the treatment after surgery as an independent prognostic factor (HR 0.456, p = 0.005). Median overall survival (OS) was 164.0 months. At time of analysis no significant differences in OS were available. Conclusions: Post-surgical treatment after resection of IDH mutant molecular astrocytomas is an independent prognostic factor. A longer follow-up is needed for worthy results in terms of OS.