Whole brain radiotherapy (WBRT) is a standard treatment approach for patients with cancer who develop brain metastases. Unfortunately, this approach can negatively impact brain function, including loss of memory, poor learning, and deterioration of executive function. In a phase III study published last month in the Journal of Clinical Oncology, researchers compared WBRT plus memantine with hippocampal avoidance (HA) to standard WBRT and memantine in 518 patients with brain metastases to see if limiting radiation of the hippocampus could improve cognitive outcomes.
At a median follow-up of 7.9 months, risk of cognitive failure was significantly lower in patients who received WBRT with HA compared to those who received standard WBRT (HR 0.74, P = .02). Differences in cognitive functioning between the two groups took approximately 4 months to develop. At 4 months post-WBRT, patients receiving WBRT with HA had significantly less deterioration in executive functioning compared to those receiving WBRT (23.3% vs 40.4%; P = .01). Likewise, at 6 months WBRT with HA was associated with less deterioration in learning than WBRT (16.4% vs 33.3%; P = .02). Patients receiving WBRT with HA also had less fatigue and fewer cognitive symptoms than those receiving standard WBRT. There were no differences in overall survival, intracranial progression-free survival, or toxicity between the two treatment groups.
The investigators concluded avoiding the hippocampus during WBRT reduces the risk of cognitive decline following radiotherapy for brain metastases. In an editorial accompanying this study, Joseph Weiner, MD (Rutgers Cancer Institute, New Jersey, United States), called this study “practice-changing,” and indicated that moving forward all radiotherapy for brain metastases should adopt a hippocampal sparing approach.
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