Comparison of two electroacupuncture regimens on symptoms and brain structures in breast cancer survivors: a randomized, controlled trial

BACKGROUND: Although electroacupuncture (EA) has shown usefulness in managing neuropsychiatric symptoms in cancer survivors, a specific acupoint regimen has not been established.We conducted a randomized, controlled, patient- and assessor-blinded pilot trial to compare two EA regimens on neuropsychiatric symptoms and associated brain structural changes in breast cancer survivors. (Clinicaltrials.gov: NCT05283577). METHODS: Breast cancer survivors who self-reported cognitive impairment, fatigue, insomnia, or psychological distress were randomized (1:1) to receive ten weekly therapeutic EA to target either neuropsychiatric-specific (nEA) or non-neuropsychiatric-specific (sham EA, sEA) acupoints. Outcomes were assessed using patient-reported outcomes (EORTC QLQ-C30, FACT-Cog, MFSI-SF) neurocognitive tests (CANTAB) and neuroimaging (measuring gray matter, white matter, cerebrospinal fluid, diffusion tensor metrics, and volume and mean intensity of the hippocampus) before and after treatment. We computed group-specific treatment effect sizes (Glass's D) adjusted for baseline variability using linear mixed models. A Pearson's correlation analysis was performed between the neurocognitive scores and the imaging metrics. Multiple testing was controlled via the Benjamini-Hochberg method, with statistical significance set at P-adjusted , 0.05. Adverse events (AEs) were graded with CTCAE v5. RESULTS: Thirty-five participants were recruited, of which five dropped out, leaving 30 (86%) completing all treatment sessions. The average (6SD) age was 58.2 612.2 years, with 66% non-Hispanic White, 77% holding a Bachelor's degree or higher, 94% received systemic treatment and/or radiotherapy for cancer, 86% reporting ≥2 neuropsychiatric symptoms. Both groups showed statistically significant pre-post mediumto- large effect sizes in perceived cognitive function, fatigue, and quality of life. nEA group observed significant improvement in cognitive domains of attention (ES=0.708, Padjusted= 0.004) memory (ES=0.488, P-adjusted=0.026) and emotional functioning (ES=0.664, P-adjusted=0.004). Neuroimages showed greater gray matter volume change (P=0.0327) and post-treatment hippocampus mean intensity (P=0.0468) in nEA versus sEA. In the nEA group, correlations were observed between attention and gray matter volume (P=0.0198) and between executive function and hippocampus volume (P=0.0204). All AEs were grade 2 or lower : nEA participants reported pain (n=1) and bleeding (n=1) while sEA participants reported numbness (n=2) bruising (n=1) nausea (n=1) and redness (n=1). CONCLUSIONS: Ten weeks of electroacupuncture targeting neuropsychiatric-related acupoints, compared to sham acupoints, improves neuropsychiatric symptoms in breast cancer survivors, supported by clinically relevant structural brain changes.