Combination of Radiotherapy and Targeted Agents in Brain Metastasis: An Update

The combination of radiation therapy and targeted agents (molecular inhibitors or immunotherapy) represents an opportunity to improve the outcomes of patients with brain metastases. The combination of whole-brain radiation therapy (WBRT) with targeted agents takes advantage of radiosensitization, while the combination with stereotactic radiosurgery (SRS) may allow one to substitute an effective systemic agent for adjuvant WBRT, the historical standard of care. This strategy may in turn allow the promotion of secondary prevention paradigms with possibly less cognitive toxicity. At present, the combination of targeted therapy with SRS rather than with WBRT is the more viable option although both avenues will likely have a role in the future management of brain metastases. Patients should be encouraged to enter clinical trials since the off-study use of these combinations will delay the advancement of the field. Caution is advised in the combination of radiation and targeted agents as unexpected toxicities can occur. Clinicians should avail themselves of clinical trials in order to offer patients these promising options and to move the field forward. In the absence of a clinical trial, we recommend the combination of SRS with targeted agents and deferred WBRT. Small, asymptomatic brain metastases may be best managed with single-modality targeted agents with deferred radiation therapy, preferably on a clinical trial. Advances in targeted therapies combined with radiation therapy will most likely improve local control and hopefully the quality of life and survival of patients with brain metastasis.