Current Standards of Care in Glioblastoma Therapy

Abstract

Glioblastoma (GBM) is the most common primary malignant brain tumor in adults. Regardless of ideal multidisciplinary treatment, including maximal surgical resection, followed by radiotherapy plus concomitant and maintenance temozolomide (TMZ), almost all patients experience tumor progression with nearly universal mortality and a median survival of less than 15 months. The addition of bevacizumab to standard treatment with TMZ revealed no increase in overall survival (OS) but improved progression-free survival (PFS). In newly diagnosed GBM, methylation of the O6-methylguanine-DNA methyltransferase (MGMT) promoter has been shown to predict response to alkylating agents, as well asgnosis. Therefore, MGMT promoter status may have a crucial role in the choice of single modality treatment in fragile elderly population. No standard of care is established in recurrent or progressive GBM. Treatment alternatives may include supportive care, surgery, re-irradiation, systemic therapies, and combined modality therapy. Despite numerous clinical trials, the identification of effective therapies is complex because of the lack of appropriate control arms, selection bias, small sample sizes, and disease heterogeneity. Tumor-treating fields plus TMZ represent a major advance in the field of GBM therapy, and should be Standards of Care in Glioblastoma Therapy 198 considered for patients with newly diagnosed GBM with no contraindications. As a disease with such a poor prognosis, treatment of GBM should go beyond improving survival and aim at preserving and even improving the quality of life of both the patient and the caregiver.

Paths for Improving Bevacizumab Available in 2018: The ADZT Regimen for Better Glioblastoma Treatment

“…When a glioblastoma progresses while on bevacizumab, survival is under half a year [22][23][24]. Performance status and quality of life usually improve with bevacizumab but often overall survival does not.…”

Influence of Therapeutic Proton Beam on Glioblastoma Multiforme Proliferation Index — A Preliminary Study

“…Furthermore, these cells may penetrate neighboring tissues [2]. Current treatments include surgery, systemic temozolomide (TMZ) chemotherapy, and radiotherapy [3]. For radiotherapy, there are a number of new prospects such as proton therapy which offers better dose delivery and distribution compared to photons, which can be exploited to reduce the probability of collateral normal tissue damage and post-treatment complication [4].…”

Fibulin‐7 is overexpressed in glioblastomas and modulates glioblastoma neovascularization through interaction with angiopoietin‐1

“…The pathology of GBM is characterized by the three morphological findings: proliferation of atypical astrocytic neoplastic cells, tumor cell necrosis and aberrant microvasculature composed of hypertrophied and glomeruloid blood vessels . Current therapeutic strategies for patients with inoperable or recurrent GBM are to target neoplastic cells through a combination of cytotoxic and antiangiogenic drugs …”

“…4,6 Current therapeutic strategies for patients with inoperable or recurrent GBM are to target neoplastic cells through a combination of cytotoxic and antiangiogenic drugs. 7,8 The tumor vessels in GBM lack the hierarchical arrangement of arterioles, capillaries, and venules, and are formed by disorganized endothelial cells and pericytes. 5 Although vascular endothelial growth factor (VEGF) is an essential factor to the neovascularization in this tumor, 6 other regulatory factors are also involved in angiogenesis.…”