The most common type of brain cancer is GLIOBLASTOMA MULTIFORME, or GBM. According to the World Health Organization (WHO) classification, it is a Grade IV primary brain tumor originating from particular brain cells called astrocytes. It is characterized by unclear boundaries, extensive infiltration, endothelial proliferation, and necrosis. It is highly malignant and aggressive.

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Grade III astrocytoma, or ANAPLASTIC ASTROCYTOMA (AA) has the same cell origin and also belongs to the category of malignant glioma, although with slightly more favorable prognosis. Malignant gliomas comprise 54% of all gliomas and 16% of all primary brain tumors. They have incidence of 3.19/100,000 people in the US. 16,000 newly diagnosed patients are being reported annually in the US. These tumors are known to affect mostly adults (the median age at diagnosis is 64).

 

Conventional treatment of GBM includes maximal surgical resection, followed by radiation and chemotherapy. The prognosis is poor and has changed very little in the past few decades. Because of the aggressive and diffuse nature of the tumor, recurrence is seen in 90% of patients. The median survival duration is ~ 1 year following initial presentation and ranges from 19 to 52 weeks following recurrence. These data underscore the need for innovative treatment approaches.

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Multimodal treatment regimens have been shown to be the most effective strategy to prolong survival, delay recurrence, and improve quality of life in patients with GBM. Despite the benefits of these therapies, recurrence is frequent, with a predominantly local failure pattern. Surgical outcomes have been augmented by technological advances such as intraoperative frameless MRI-guided navigation, use of DTI (Diffuse Tensor Imaging), intraoperative MRI, brain mapping, as well as intraoperative fluorescent visualization using photo imaging agents (5-Aminolevulonic Acid, 5-ALA, GLEOLAN), to name just a few.

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Because recurrence is often within 2 cm of the initial tumor margin, various treatment strategies have been attempted to prevent or delay disease progression, including repeated operation, conformal radiation, brachytherapy (Iodine-125 seeds) and local chemotherapy (GLIADEL).

 

Despite of the above intraoperative advances however, surgery is rarely the answer to this devastating disease.

Chemotherapy plays a major role in the non-surgical treatment of malignant gliomas. Temodar (temozolomide) is a DNA-ankylating agent inhibiting the DNA replication of tumor cells. It’s oral form is easy to administer and requires long-term intake under the close monitoring by neuro-oncologist. Avastin (Bevacizumab) is a second line agent with the characteristics of an engineered monoclonal antibody inhibiting the vascular proliferation in cancer cells including brain cancer.

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Immunotherapies carry the promise of becoming mainstream therapies for GBM. There are multiple ongoing clinical trials in the US and Europe studying the efficacy of a wide spectrum of novel therapeutic avenues such as: immune checkpoint inhibitors (nivolumab), vaccines, hypofractionated stereotactic radiation, MRI-guided laser ablation, CSF-1R inhibitors, TGF-beta inhibitors independently, or in combination as “cocktail” treatments.