Abstract

INTRODUCTION

Whole brain radiation therapy (WBRT) is administered both prophylactically and therapeutically in patients with suspected and confirmed brain metastasis. Despite effective intracerebral tumor control and reduction in neurological mortality, WBRT is associated with a substantial risk of cognitive decline. Hippocampus-sparing WBRT (HS-WBRT) allows for the preservation of memory and other cognitive functions. We aimed to evaluate the neurocognitive outcomes of HS-WBRT in comparison with WBRT in patients with brain metastases.

METHODS

We searched MEDLINE (PubMed), Google Scholar, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) for cohort studies and clinical trials reporting on HS-WBRT compared to WBRT for neurocognitive outcomes in brain metastasis patients, from inception to March 2024. Studies that were published in non-English language(s) and/or did not report neurocognitive outcomes of HS-WBRT compared with WBRT were excluded. Summary data of the eligible studies was extracted, which was analyzed for neurocognitive function testing.

RESULTS

Of the total nine studies, seven were included in the quantitative analysis. HS-WBRT led to a statistically significant reduction in cognitive decline as measured by the Hopkins Verbal Learning Test (HVLT) raw scores for total recall (TR) [SMD = 0.34 [0.16,0.53]; I2= 65%; p = 0.0003], and delayed recall (DR) [SMD = 0.26 [0.13,0.39]; I2= 62%; p = 0.0001]. Cognitive impairment, as measured by the Montreal Cognitive Assessment (MoCA), was also lower in the HS-WBRT group compared to the WBRT group [SMD = 0.82 [0.53,1.10]; I2= 88%; p < 0.00001].

CONCLUSION

The findings of our study demonstrate that HS-WBRT confers a therapeutic advantage to WBRT in improving neurocognitive outcomes for patients with brain metastasis as measured by scores on HVLT-TR, HVLT-DR, and MoCA. Additional studies analyzing both treatment modalities’ adverse effects and mean survival time are imperative for informing future clinical recommendations.

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