Advances in treatment therapies for non-small cell lung cancer —including chemotherapy options capable of crossing the blood-brain barrier and widespread availability of precision radiotherapy devices — offer new strategies for the management of brain metastases, dramatically improving overall survival (OS).

“There has been quite a shift in the use of whole-brain irradiation versus stereotactic radiosurgery,” said Nagy Elsayyad, MD, a radiation oncologist and associate professor at the University of Miami’s Sylvester Comprehensive Cancer Center in Florida. “The whole idea of using irradiation or surgery has been that there are very few chemotherapeutic agents, until recently, that cross the blood-brain barrier.”

The growing list of options and the expanding body of research, said Dr Elsayyad, is leading to increasingly individualized therapeutic strategies “aiming more and more toward sparing the brain.”

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But the rapidly changing treatment landscape is causing debate over the efficacy and adverse effects of the various therapeutic strategies along with calls for more studies to determine the most effective management strategies.

One of the most recent additions to the discussion, a multi-institutional analysis published in January, compared outcomes for patients with epidermal growth factor receptor (EGFR) mutation who developed brain metastases.1 Of the 351 patients included in the study, 131 (37%) received a EGFR-tyrosine kinase inhibitor (TKI) followed by stereotactic radiosurgery (SRS) or whole-brain radiotherapy (WBRT) at intracranial progression. Another 120 (34%) received WBRT followed by an EGFR-TKI. A third group of 100 patients (29%) were treated with SRS followed by an EGFR-TKI.

The findings showed vivid differences in OS among the 3 groups, with initial SRS treatment yielding distinctly better results.

The study fueled the controversy over the use of WBRT. The authors noted that WBRT is associated with declines in cognitive functioning and quality of life scores, while “numerous studies have demonstrated that SRS has less acute and late toxicity.”

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An editorial accompanying the study noted that “it seems time to weigh the benefits of deferring or withholding WBRT in the era of targeted therapies.”2