Diagnosis It is prudent to biopsy lesions that are considered on clinical and imaging grounds to be glioblastoma. The tissue serves not only to provide potential information regarding prognosis and to some extent, to guide treatment but the main reason for obtaining tissue is to exclude the possibility of another neoplastic or nonneoplastic diagnosis such as lymphoma, brain abscess or other infection (see Chap. 31), tumefactive multiple sclerosis (see Chap. 35), infarction, encephalitis, and others.
Most lesions can be accessed with stereotactic techniques but limit the volume and quality of tissue obtained and obviates a direct visualization of the mass by the surgeon. In stereotactic biopsy, but also with open procedures, there is a risk of sampling error, meaning that parts of the tumor may show more malignant changes.
Treatment At operation, usually only part of the tumor can be removed; its multicentricity and diffusely infiltrative character defy the scalpel. Partial resection of the tumor (“debulking”), however, seems to prolong survival as noted below. Neurosurgeons have developed a number of cortical electrophysiologic mapping and imaging techniques to facilitate maximal resection without injuring adjacent brain tissue.
For a brief period, corticosteroids, usually dexamethasone in doses of 4 to 10 mg q6–12h, are helpful if there are symptoms of mass effect, such as headache or drowsiness; local signs and surrounding edema tend to improve as well. Antiepileptic medications are not required unless there have been seizures. Although some neurologists and neurosurgeons still administer them in order to preempt a convulsion, several series have found antiepileptic medications to be unnecessary for this purpose (see for example, Glantz et al). Serious skin reactions (erythema multiforme and Stevens-Johnson syndrome) may occur in patients receiving phenytoin at the same time as cranial radiation (Delattre et al). A maximally feasible resection, the debulking described above, is combined with radiation and chemotherapy. Cranial irradiation to a total dose of 6,000 cGy increases survival by 5 months on average (see in the following text). This is true even in the elderly who have had only a biopsy without resection according to a trial conducted by Keime-Guibert and colleagues. In many centers, a fraction of this is delivered as a “boost” through focused or stereotactic radiation, particularly if the tumor is small enough to encompass in these fields. Brachytherapy (implantation of iodine-125 or iridium-193 beads or needles) and high-dose focused radiation (stereotactic radiosurgery) have so far not significantly altered survival times but continue to be studied. They have gone through periods of popularity but are currently used only sparsely, partly because they cause local radiation necrosis.
It had been considered for several decades that the addition of chemotherapeutic nitrosourea agents such as carmustine (BCNU) or lomustine (CCNU) increases survival slightly. Cisplatin and carboplatin have provided similar small marginal improvements in survival beyond that obtained by debulking and radiation therapy. Several randomized trials, however, have failed to show substantial benefit of chemotherapy but the Glioma Meta-analysis Trialists (GMT) Group had concluded in 2002 that there was a clear but quite small benefit of chemotherapy.
One trial has demonstrated a 3 month benefit for progression-free survival, but not for overall survival, with the early use of bevicizumab with temozolamide and radiation (Gilbert et al); its use is largely restricted to clinical trials. This anti-VEGF therapy improves the imaging appearance (less edema, small area of enhancement) but fails to inhibit tumor spread. In the field of experimental therapeutics, adoptive T cells (chimeric antigen receptor –T-cell therapy, CAR-T), which had success with leukemia and lymphoma, has demonstrated efficacy in very few studied cases of metastatic glioblastoma (Brown et al).