Melanocortin Receptor-4 Gene Polymorphisms in Glioblastoma Patients Treated with Concomitant Radio-Chemotherapy

Abstract

Melanocortins are peptides with well-recognized antiinflammatory and neuroprotective activity. No data are currently available on melanocortin receptor-4 (MC4R) gene polymorphisms and tumors, including glioblastomas (GBMs), or their relationship with radiotherapy or chemotherapy. The aim of this study was to evaluate the possible predictive/prognostic role of the MC4R SNPs on GBM patients. Fifty-five patients with a proven diagnosis of GBM, treated with radiotherapy and temozolomide, were consecutively enrolled. MC4R gene SNPs (rs17782313, rs489693, rs8087522, rs17700633) were analyzed by a validated TaqMan® SNP genotyping assays. Univariate and multivariate analyses were performed. A P < 0.0125 (Bonferroni's correction) was considered significant ( Clinicaltrial.gov identifier NCT02458508). The median progression-free survival (PFS) and median overall survival (OS) of these patients were 9.54 (95% CI 5.4-14.3) months and 24.9 (95% CI 17.8-34.6) months, respectively. The MC4R rs489693 AA genotype was significantly associated with a shorter PFS and OS. Indeed, with regard to PFS, patients harboring the rs489693 AA genotype had a median PFS of 2.99 months whereas patients with AC/CC genotypes had a median PFS of 10.82 months (P = 0.009). Interestingly, the rs489693 AA patients also had a lower median OS as compared with the median OS of the AC/CC genotypes (10.75 vs. 29.5 months, respectively, P = 0.0001). This study suggests that the MC4R rs489693 AA genotype is significantly associated with a shorter PFS and OS in patients treated with radiotherapy and temozolomide. These findings represent a relevant effort to identify novel clinical markers for RT-CT therapy in GBM to be validated in future pharmacogenetic clinical trials.

Glioblastoma and Internal Carotid Artery Calcium Score: A Possible Novel Prognostic Partnership?

“…Following the diagnosis of a grade 4 glioma, the postoperative therapeutic approach is primarily determined based on the patients’ overall conditions and their age [ 8 , 16 ]. Furthermore, despite the results of various translational studies, there are no biomarkers that can enable stratification of patients based on radiosensitivity and factors correlated with better or worse response to radiotherapy [ 18 , 19 ].…”

Old and New Systemic Immune-Inflammation Indexes Are Associated with Overall Survival of Glioblastoma Patients Treated with Radio-Chemotherapy

“…To overcome the limits reached in GBM therapy, one of the main issues to be addressed in neuro-oncology is the lack of biomarkers necessary for planning translational studies. While previous attempts to identify novel radio- and chemo-sensitive biomarkers in GBM have occurred, they were focused on tumor samples and experienced a series of limitations, such as the difficulty of obtaining tumor tissue from all GBM patients [ 5 , 6 , 7 , 8 , 9 ].…”

Different Timing to Use Bevacizumab in Patients with Recurrent Glioblastoma: Early Versus Delayed Administration

“…Glioblastoma (GBM) is the most common and baleful malignant brain tumor in adults (1,2). Despite recent advances in several fields of neuro-oncology and the identification of new targets, the disease recurs within a year of standard upfront therapy, with increased aggressiveness and a dismal prognosis (3)(4)(5)(6)(7)(8). After the diagnosis of relapsed glioblastoma, multimodality salvage treatments are not incisive enough to improve overall survival (OS) beyond a few months, and their best use and timing are not yet well established (4,(9)(10)(11).…”