Negative impact of hippocampal radiotherapy dose on memory function in patients with brain metastases

Background: Brain metastases (BMs) are often treated with stereotactic radiosurgery (SRS). Even with the high dose fall-off at tumor borders, some dose is delivered outside the BMs to ensure adequate tumor coverage. This may include radiation to the neurogenic niches (ie, subventricular zones [SVZ] and hippocampi), which possibly play a role in neurocognitive functioning (NCF). In this study, we assessed the impact of radiotherapy dose on the SVZ and hippocampi compared with changes in NCF 3 months post-SRS, focusing on memory and information processing speed (IPS) in adult patients with BMs. Methods: Neurocognitive assessments were performed before and 3 months post-SRS, and reliable change indices were calculated to assess NCF changes. The SVZ and hippocampal regions were delineated on pre-SRS T1-weighted MRI images and median radiotherapy dose per region was calculated. Results: Multivariable linear regression analyses in 36 patients corrected for age, previous brain radiotherapy, number of BMs, and previous systemic therapy indicated a significant association between higher hippocampal radiotherapy dose and decline in memory, specifically in Hopkins Verbal Learning Test-Revised immediate recall, delayed recall, and Rey Osterieth Complex Figure Test delayed copy (all P < .05). Conversely, no significant association was found between dose to the SVZ and memory, nor between dose to either region and IPS. Conclusions: These results suggest potential benefits of minimizing radiation exposure to the hippocampi, even with SRS, to help preserve memory in patients with BMs. Further prospective evaluation is warranted to validate these findings and inform clinical decision-making regarding radiotherapy protocols for preserving NCF in this patient population.