摘要
目的:放射配体治疗(radioligand therapy,RLT)是一种结合靶向治疗和辐射细胞杀伤能力的新兴疗法.本文探讨了177Lu-成纤维细胞活化蛋白(fibroblast activation protein,FAP)-2286 RLT在晚期肺癌患者中的疗效和安全性,通过临床试验和患者结果分析,全面评估该疗法的治疗潜力,旨在改善晚期肺癌患者的预后.方法:本研究纳入了2022年9月—2024年4月在西南医科大学附属医院接受177Lu-FAP-2286 RLT治疗的晚期肺癌患者.所有患者在治疗前进行了68Ga-FAP-2286正电子发射体层成像(positron emission tomography,PET)/计算机体层成像(computed tomography,CT),并显示病灶内FAP高表达.每个治疗周期的177Lu-FAP-2286剂量约为200 mCi(7.4 GBq),通过静脉输注于4 h内完成,治疗间隔为8～12周,总治疗次数为4～6周期.安全性和有效性评估包括实验室检查、不良事件记录、与实体瘤临床疗效评价标准(response evaluation criteria in solid tumor,RECIST)1.1和基于PET/CT的实体瘤PET疗效评价标准(PET response criteria in solid tumor,PERCIST)1.0标准评估.数据分析使用SPSS 26.0进行,正态性检验后采用配对样本t检验比较治疗前后的差异.结果:纳入的10例患者中(8例男性和2例女性,年龄范围为53～73岁),治疗周期分布为1例接受6个周期,3例接受4个周期,1例接受3个周期,4例接受2个周期,1例仅接受1个周期.中位随访时间为13个月.治疗显示,177Lu-FAP-2286具有良好的耐受性,主要不良反应为疲劳和腹胀,无严重血液系统毒性和肝肾功能损伤.疗效评估显示,PR率为30.0%,SD率为50.0%,进展性疾病(progressive disease,PD)率为20.0%.总体缓解率为30.0%,疾病控制率为80.0%.根据改良的PERCIST 1.0标准,PR率为30.0%,SD率为50.0%,PD率为20.0%.结论:177Lu-FAP-2286 RLT在晚期肺癌患者中显示出良好的安全性和显著的疗效,具有较高的疾病控制率和总体缓解率.虽然本研究的样本量较小,但结果支持了177Lu-FAP-2286 RLT作为一种有效治疗晚期肺癌的新策略.未来需要更大规模和长期随访的研究来进一步验证其疗效和安全性.
Abstract
Objective:Radioligand therapy(RLT)is an emerging modality that combines targeted therapy with radiation-induced cytotoxicity.This study investigates the efficacy and safety of 177Lu-fibroblast activation protein(FAP)-2286 RLT in patients with advanced lung cancer.A comprehensive assessment was conducted through clinical trials and patient outcome analyses to evaluate the therapeutic potential of this treatment,aiming to improve the prognosis of patients with advanced lung cancer.Methods:The study included patients with advanced lung cancer treated with 177Lu-FAP-2286 RLT in the Affiliated Hospital of Southwest Medical University from September 2022 to April 2024.Baseline scans using 68Ga-FAP-2286 positron emission tomography(PET)/computed tomography(CT)confirmed high expression of FAP within the lesions.Each treatment cycle administered approximately 200 mCi(7.4 GBq)of 177Lu-FAP-2286 via intravenous infusion over 4 h,with intervals of 8-12 weeks between cycles,for a total of 4-6 cycles.The evaluation of safety and efficacy included laboratory tests,adverse event documentation,and assessments according to response evaluation criteria in solid tumor(RECIST)1.1 and adopted PET response criteria in solid tumor(PERCIST)1.0 criteria.Data analysis was performed using SPSS version 26.0,with paired sample t-tests applied to compare pre-and post-treatment differences following normality tests.Results:Among the 10 patients included in the study(8 males and 2 females,aged 53-73),treatment cycles varied:one patient received six cycles,three patients received four cycles,one patient received three cycles,four patients received two cycles,and one patient received only one cycle.The median follow-up period was 13 months.Treatment with 177Lu-FAP-2286 was well-tolerated,with the primary adverse effects being fatigue and abdominal distension.No severe hematological toxicity or significant impairment of liver and kidney function was observed.Efficacy evaluation revealed a partial response(PR)rate of 30.0%,a stable disease(SD)rate of 50.0%,and a progressive disease(PD)rate of 20.0%.The overall response rate was 30.0%,and the disease control rate was 80.0%.According to the adopted PERCIST 1.0 criteria,the PR rate was 30.0%,the SD rate was 50.0%,and the PD rate was 20.0%.Conclusion:177Lu-FAP-2286 RLT demonstrated good safety and significant efficacy in patients with advanced lung cancer,with high disease control and overall response rates.Although the sample size in this study was small,the results support 177Lu-FAP-2286 RLT as a promising new strategy for treating advanced lung cancer.Further research involving larger sample sizes and longer follow-up periods is required to validate its efficacy and safety.
基金项目
国家自然科学基金(U20A20384)
泸州市人民政府西南医科大学科技战略合作项目(2021LZXNYD-P03)
四川省卫生健康委员会医学科技项目(21ZD005)
甘肃省科技重大专项(23ZDFA014)
同位素及药物国家工程研究中心同位素及药物创新基金(TWSCX-2023-CXJJ-3-1)
万方数据