Postoperative external beam radiotherapy was considered the standard adjuvant treatment for patients with glioblastoma multiforme until the advent of using the drug temozolomide (TMZ) in addition to radiotherapy. High-dose volume should be focal, minimizing whole brain irradiation. Modern imaging, using several magnetic resonance sequences, has improved the planning target volume definition. The total dose delivered should be in the range of 60 Gy in fraction sizes of 1.8-2.0 Gy. Currently, TMZ concomitant and adjuvant to radiotherapy has become the standard of care for glioblastoma multiforme patients. Radiotherapy dose-intensification and radiosensitizer approaches have not improved the outcome. In spite of the lack of high quality evidence, stereotactic radiotherapy can be considered for a selected group of patients. For elderly patients, data suggest that the same survival benefit can be achieved with similar morbidity using a shorter course of radiotherapy (hypofractionation). Elderly patients with tumors that exhibit methylation of the O-6-methylguanine-DNA methyltransferase promoter can benefit from TMZ alone.
Virtually all glioblastomas treated in the first-line setting will recur in a short period of time, and the search for alternative effective treatments has so far been unsuccessful. Various obstacles remain unresolved, and no effective salvage therapy for recurrent glioblastoma can be envisaged in the short term. One of the main impediments to progress is the low incidence of the disease itself in comparison with other pathologies, which will be made even lower by the recent WHO classification of gliomas, which includes molecular alterations. This new classification helps refine patient prognosis but does not clarify the most appropriate treatment. Other impediments are related to clinical trials: glioblastoma patients are often excluded from trials due to their advanced age and limiting neurological symptoms; there is also the question of how best to measure treatment efficacy, which conditions the design of trials and can affect the acceptance of results by oncologists and medicine agencies. Other obstacles are related to the drugs themselves: most treatments cannot cross the blood-brain-barrier or the brain-to-tumor barrier to reach therapeutic drug levels in the tumor without producing toxicity; the drugs under study may have adverse metabolic interactions with those required for symptom control; identifying the target of the drug can be a complex issue. Additionally, the optimal method of treatment – local vs systemic therapy, the choice of chemotherapy, irradiation, targeted therapy, immunotherapy, or a combination thereof – is not yet clear in glioblastoma in comparison with other cancers. Finally, in addition to curing or stabilizing the disease, glioblastoma therapy should aim at maintaining the neurological status of the patients to enable them to return to their previous lifestyle. Here we review currently available treatments, obstacles in the search for new treatments, and novel lines of research that show promise for the future.
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