**7. Standard adjuvant therapy**

After maximally-safe surgical resection, the standard of care for GBM is a 6 week course of External Beam Focused Radiation Therapy with concurrent chemotherapy followed by 6 months of adjuvant chemotherapy.

With the support of Level IA evidence, fractionated focal radiotherapy (60 Gy, 30-33 fractions of 1.8-2 Gy) is the established radiation regimen after resection or biopsy of malignant gliomas [37]. The fundamental nature of the ionizing radiation utilized has, needless to say, not changed; however, leaps and bounds have been made in efforts to focus the beam, tailor it to the highly-serrated and convoluted contours of tumor, and limit the dose to nearby critical structures/tissue by the use of intensity-attenuated and image-guided technologies, all with positive effect.

The single first-line chemotherapeutic agent for GBM is temozolomide, an oral alkylating agent that exerts its anti-tumorigenic effect by methylating/alkylating DNA at the N-7/O-6 positions of guanine residues, thereby causing irreparable damage to (tumor) DNA and instigating the process of tumor cell death. The benefits of the addition of concurrent with adjuvant chemo‐ therapy to the foundation of radiation therapy were demonstrated by a seminal landmark study by Stupp *et al* that showed a 14.6 to 12.1 month median overall survival benefit and showed a sustained survival advantage of 9.8% vs 1.9% at 5 year analysis (Figure 7) [35].

High-dose corticosteroids have a role to play in reduction of tumor-associated edema and associated symptoms but are not indicated for long periods of time [37]. There is an established role for anti-seizure therapy in patients who present with seizures, but the role for seizure prophylaxis after surgery is only indicated in symptomatic patients. It ought to be kept in mind that many anti-epileptics, particularly of the first generation (e.g. phenytoin, carbamazepine), may decrease the serum concentration of certain chemotherapy agents by dint of inducing increased hepatic metabolism [37].

As evinced by the yet-sobering statistics on overall GBM survival/patient outcome, there are many-a-challenge and obstacle that remain in treatment, especially regarding the development of resistance to both radiation therapy and, more so, to temozolomide chemotherapy.
