Metastatic Brain Tumors: Viewpoint: Whole Brain Radiation Therapy

Abstract

Whole brain radiation therapy (WBRT) is the standard of care for most patients with greater than four brain metastases. WBRT in these patients has been shown to improve neurologic symptoms, decrease progression of intracranial disease, and lengthen survival. In patients with one to four brain metastases, the utility of focal therapies such as neurosurgery or stereotactic radiosurgery (SRS), as well as concern over the possible neurotoxicities of WBRT, has lead to questions regarding its use in this population. However, studies looking at combined regimens of focal treatment plus WBRT vs. WBRT alone have not been able to produce conclusive evidence of either increased neurotoxicity or improved survival with the use of WBRT due to issues of lack of power, significant crossover between the randomized groups, and inconsistent endpoints. Similarly, investigations into the neurocognitive functioning of patients being treated for brain metastases have not effectively taken into account confounding factors including baseline neurologic status, radiation dose and fractionation, the effects of other palliative and anti-cancer medications, and the definition of truly clinically relevant endpoints. Two findings that have been consistently shown in these trials are that progression of disease within the brain leads to a significant decline in neurocognitive functioning, and that WBRT significantly decreases recurrence of disease within the brain. Fortunately, studies looking at various fractionation schemes have shown that there is enough flexibility in the delivery of WBRT to accommodate the patient’s overall goals of therapy while somewhat mediating the risk of unwanted effects. Finally, it is important to understand that, the shortcomings of the current body of literature notwithstanding, the process of reconciling the benefits of WBRT with the risks must include a clear perspective regarding the fact that while the concerns surrounding this therapy remain unproven, the detrimental clinical consequences of omitting WBRT are clear.