乳腺癌脑转移患者不同全脑放疗技术中血清载脂蛋白与认知功能衰退的关系分析

Relationship between serum apolipoprotein and cognitive decline after different whole-brain radiotherapy techniques for breast cancer with brain metastases

目的:探讨乳腺癌脑转移全脑放疗(whole-brain radiotherapy,WBRT)不同放疗技术中血清载脂蛋白E(ApoE)、ApoJ和ApoA1与认知功能衰退的相关性。方法:选取2021年01月至2023年01月就诊于该院放射治疗科的乳腺癌脑转移瘤患者42例。随机分为调强放疗(intensity modulated radiotherapy,IMRT)和容积调强放疗(volume modulated radiotherapy,VMAT)。采用酶联免疫吸附法检测血清ApoE、ApoJ和ApoA1水平及简易智能精神状态检查量表(mini-mental state examination,MMSE)评估患者的认知功能。采用不同统计学方法分析治疗前、治疗后、治疗后1月、治疗后3月两组患者的临床特征及血清标志物等的差异。结果:治疗后3月,与IMRT组相比,VMAT组患者的MMSE评分较高(P<0.05),同时,VMAT组患者的血清ApoE、ApoJ和ApoA1水平均显著降低(P均<0.05)。IMRT组和VMAT组出现认知功能障碍分别19例(90.50%)和13例(40.60%),差异有统计学意义(P=0.030);ApoE、ApoJ和ApoA1水平在认知功能障碍的患者中均显著低于认知功能正常的患者(P均<0.05)。ROC分析显示,ApoE、ApoJ和ApoA1的曲线下面积(area under curve,AUC)分别为0.830、0.795和0.836,差异有统计学意义(P<0.05)。Cox多因素回归分析显示,ApoA1和ApoJ水平的升高是无认知衰退生存率(cognitive-dysfunction-free survival,CDFS)的保护因素(HR=0.02和0.04);而转移瘤个数是导致认知功能衰退的风险因子(HR=7.43)。生存分析显示,相较于ApoJ≤132.6 pg/mL和ApoA1≤150.9 pg/mL,ApoJ>132.6 pg/mL和ApoA1>150.9 pg/mL的患者的认知功能衰退均显著升高(P均<0.05)。结论:相较于IMRT,VMAT技术在WBRT治疗后保护患者认知功能方面具有一定的优势;患者认知功能衰退可能与血清ApoJ和ApoA1水平降低、转移瘤个数有关。

Objective:To investigate the correlation between serum apolipoprotein E(ApoE),ApoJ,ApoA1 and cognitive decline in different radiotherapy techniques on whole-brain radiotherapy(WBRT)for breast cancer with brain metastases.Methods:42 patients with brain metastases from breast cancer were enrolled from the department of radiotherapy,the our hospital from January 2021 to January 2023,which were divided into intensity modulated radiotherapy(IMRT)group and volume modulated radiotherapy(VMAT)group.Serum ApoE,ApoJ,ApoA1 were examined by enzyme-linked immunosorbent assay(ELISA),and cognitive function in patients were evaluated by mini-mental state examination(MMSE).Differential statistical methods were used to analyze the difference of clinical characteristics and serum markers between two groups in pre-and-post treatment,1 month-post-treatment,3 month-post-treatment.Results:At 3 months after treatment,compared with IMRT group,MMSE was higher in VMAT group(P<0.05),meanwhile,serum ApoE,ApoJ,ApoA1 were significantly decreased in VMAT group(all P<0.05).There were 19 cases(90.50%)in VMAT group and 13 cases(40.60%)in IMRT group of cognitive dysfunctions,respectively,with statistical significance(P=0.030).The level of ApoE,ApoJ and ApoA1 in patients with cognitive impairment were obviously lower than those in patients with normal cognitive function(all P<0.05).ROC analysis showed that the area under curve(AUC)of ApoE,ApoJ and ApoA1 were 0.830,0.795 and 0.836,respectively,with difference in statistics(all P<0.05).Cox multivariate regression analysis showed that the increase of ApoA1 and ApoJ was a protective factor for cognitive-dysfunction-free survival(CDFS)(HR=0.02 and 0.04),the number of metastases was a risk for cognitive decline(HR=7.43).Survival analysis showed that the patients with ApoJ>132.6 pg/mL and ApoA1>150.9 pg/mL had remarkably higher in cognitive decline than those in patients with ApoJ≤132.6 pg/mL and ApoA1≤150.9 pg/mL,respectively(all P<0.05).Conclusion:Compared with IMRT,VMAT technology has certain advantage in protection patients with cognitive function after WBRT.The decline of cognitive function maybe related to the decrease of serum ApoJ,ApoA1 and the number of metastatic tumors.