Malignant glioma remains an intractable problem for the neurosurgeons, neurologists, medical oncologists, and radiation oncologists that care for patients with these tumors. Glioblastoma multiforme, the most common of these malignant tumors, is also the most deadly. Despite four decades of advances in microneurosurgery, developments in the technology and technique of radiation administration, advances in imaging, and introduction of novel chemotherapeutic agents, the median life expectancy for patients with glioblastoma remains unchanged at twelve months; only 5% of patients or fewer will be alive at five years after diagnosis. The biology of malignant glioma is unique. Although systemic metastases occur, they are relatively rare. The vast majority of glioblastomas recur within two centimeters of their original tumor margin. The tumors are extremely aggressive in a locally invasive fashion and frequently have been referred to as a “whole brain” or “whole CNS” disease. In terms of long-term disease control, surgical attempts at total resection have almost uniformly failed. In fact, patients who undergo lobectomy for tumors occurring in non-eloquent regions of the brain, such as the temporal or frontal poles, might be considered a population that could potentially be treated with a resection with an associated margin of normal tissue. These patients are still subject, however, to recurrences, usually occurring in the margin adjacent to the resection border, consistent with the highly invasive nature of these tumors. Some studies do suggest that surgical removal consistent with gross total resection by postoperative imaging may provide an increase in the median survival of patients with this disease, but no Class I evidence for this presumption exists at this time. The association of tumor with eloquent brain may render attempts at such a gross total resection untenable due to the resulting loss of neurologic function that would occur with such a resection. Chemotherapy and radiation therapy, likewise, have met with only little success in the treatment of glioblastoma. Although the blood-brain barrier is not entirely intact in these tumors, the blood-tumor barrier still prevents many chemotherapy agents from reaching the tumor in sufficient concentration. Additionally, the invasive nature of glioma cells results in malignant cells at the periphery of the tumor being associated with a normal blood-brain barrier, providing further protection from chemotherapeutic agents. Attempts to circumvent this problem range from the use of agents that do cross the blood-brain barrier in sufficient concentrations (e.g., temozolamide), to mechanical disruption of the blood-brain barrier followed by administration of intra-arterial chemotherapy to the use of intracavitary agents such as chemotherapy wafers or convection-enhanced delivery. While exciting, these approaches have yet to produce a major breakthrough in the treatment of these patients. External beam radiation remains the sole agent that demonstrably increases the survival of patients with glioblastoma, and it still provides only modest benefit. Malignant glioma cells are remarkably resistant to ionizing radiation, and the association of a significant portion of these cells with necrotic and hypoxic tissues increases their resistance. Indeed, radiation has been proven to be of most benefit in younger patients, and some studies suggest that elderly patients obtain no benefit in terms of survival or performance from this treatment. Attempts at providing radiation boosts through brachytherapy or more recently stereotactic radiosurgery have not yet provided uniform increases in survival, as confirmed in a recent RTOG study. Despite the lack of success to date in improving patient outcome and survival, there is ample reason to predict improved treatments for these patients in the future. Ongoing studies of the biology of these tumors have produced a remarkable increase in our understanding of their development and progression, as well as potential targets for treatment.
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May 17, 2003
H Akaza 
Open Access