ABSTRACT
Although anti-VEGF therapy is widely used in high-grade gliomas, no predictor of response or toxicity has been reported yet. We investigated here the association of the functional single nucleotide polymorphism (SNP) rs2010963, located in the 5' untranslated terminal region of the VEGFA gene, with survival, response to bevacizumab (BVZ) and vascular toxicity. The rs2010963 was genotyped by Taqman assay in blood DNA from 954 glioma patients with available survival data, including 225 glioblastoma (GBM) patients treated with BVZ. VEGFA plasma levels were assessed by ELISA in 87 patients before treatment. Thrombo-hemorragic adverse events were recorded during BVZ treatment or not, and in an independent population of 92 GBM patients treated with temozolomide. The CC genotype was associated with the occurrence of thrombo-hemorragic events (CC 25 versus CG 13.5 and GG 5.2 %; P = 0.0044) during BVZ. A similar but weaker and non significant trend was observed in patients not receiving BVZ. A CC genotype was associated with higher levels of plasma VEGFA at baseline (107.6 versus 57.50 pg/mL in heterozygotes (CG) and 52.75 pg/mL in GG patients, P = 0.035 and P = 0.028 respectively). The CC genotype tended to be associated to longer PFS when treated with BVZ (P = 0.05), but not when treated with the temozolomide treatment. Our data suggest that the rs2010963 genotype is associated with longer PFS, higher risk of vascular events in recurrent GBM especially treated with BVZ, and higher plasma VEGFA concentration. It may help to identify patients at risk of vascular adverse events during BVZ treatment.
Subject(s)
Angiogenesis Inhibitors/adverse effects , Antibodies, Monoclonal, Humanized/adverse effects , Brain Neoplasms/drug therapy , Glioblastoma/drug therapy , Polymorphism, Single Nucleotide , Vascular Endothelial Growth Factor A/genetics , Bevacizumab , Brain Neoplasms/blood , Brain Neoplasms/mortality , Disease-Free Survival , Enzyme-Linked Immunosorbent Assay , Genotype , Glioblastoma/blood , Glioblastoma/mortality , Hemorrhage/chemically induced , Hemorrhage/epidemiology , Hemorrhage/genetics , Humans , Kaplan-Meier Estimate , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/genetics , Thrombosis/chemically induced , Thrombosis/epidemiology , Thrombosis/genetics , Vascular Endothelial Growth Factor A/bloodABSTRACT
Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder, which confers an increased risk of a wide range of cancers, and malignant tumors are the most common cause of death in individuals with NF1. Although in children with NF1, the most common neoplasms are optic nerve gliomas and brain tumors, an elevated risk of myeloid leukemia and an increased relative risk of acute lymphoblastic leukemia and non-Hodgkin lymphoma were reported. In adults with NF1, the relative risk of brain tumor is 100 times higher than in the general population. Cases of malignant lymphoma occurring in NF1 adult patients have been reported. However, the association between NF1 and lymphoproliferative diseases is still debated. We report a case of CNS primitive lymphoma in an adult patient who resulted positive for NF1 at genetic testing. At present, only one case of CNS lymphoma in an adult patient displaying clinical criteria for NF1 diagnosis has been reported.
