Treatment of brain metastases: review of phase III randomized controlled trials

The optimal management of brain metastases remains controversial. Both whole brain radiotherapy (WBRT) and local treatment [surgery (S) or radiosurgery (RS)] are the cornerstones of treatment. The role of systemic therapy is also being explored. Randomized controlled trials (RCT) have tried to assess the individual and combined effects of different therapeutic strategies. (1) RCT in oligometastatic patients: WBRT alone vs. local treatment+WBRT. Combined treatment may improve both overall survival and local control in patients with a single metastasis, but it also leads to a local control benefit in patients with two to four lesions. Exclusive local treatment vs. WBRT plus local treatment. The addition of WBRT to local treatment may result in improved local control, improved freedom from new brain metastases and improved overall brain control. S+WBRT vs. RS+WBRT. There is no evidence of superiority of a combined treatment over the other one. (2) RCT addressing the point of improving WBRT outcome: differences in WBRT fractionation do not significantly alter outcome of treatments. Only a few systemic drugs may cause some significant advantages. (3) RCT that assessed neurocognitive impairment and quality of life: the baseline cognitive performance of most patients is significantly impaired. Intracranial tumor control is an essential factor in stabilizing neurocognitive function. The data on neurocognitive toxicity related to WBRT are still contradictory. Impairment of both neurocognitive function and quality of life of patients with brain metastases needs to be further addressed in RCT.