PD-1抑制剂治疗耐药复发妊娠滋养细胞肿瘤的初步探讨  

Preliminary study of PD-1 inhibitor in the treatment of drug-resistant recurrent gestational trophoblastic neoplasia

作　　者：程红燕 杨隽钧[1] 赵峻[1] 任彤[1] 冯凤芝[1] 万希润 向阳[1] Cheng Hongyan;Yang Junjun;Zhao Jun;Ren Tong;Feng Fengzhi;Wan Xirun;Xiang Yang(Department of Obstetrics and Gynecology,Peking Union Medical College Hospital,Peking Union Medical College,Chinese Academy of Medical Sciences,Beijing 100730,China)

机构地区：[1]中国医学科学院北京协和医学院北京协和医院妇产科,100730

出　　处：《中华妇产科杂志》2020年第6期390-394,共5页Chinese Journal of Obstetrics and Gynecology

基　　金：国家自然科学基金(81971475,81672586,81972451);中国医学科学院医学与健康科技创新工程(2017-I2M-1-002)。

摘　　要：目的探讨程序性细胞死亡受体1(PD-1)抑制剂在耐药复发妊娠滋养细胞肿瘤(GTN)中的治疗作用。方法收集2018年8月—2019年6月在中国医学科学院北京协和医学院北京协和医院接受PD-1抑制剂——派姆单抗(pembrolizumab)治疗的8例耐药复发GTN患者的临床病理资料,回顾性分析其临床病理特点、既往治疗、PD-1抑制剂治疗及预后。结果(1)临床病理特点:8例GTN患者的平均发病年龄为32.9岁(31~39岁);病理类型:绒毛膜癌7例,上皮样滋养细胞肿瘤1例;国际妇产科联盟(FIGO)分期:Ⅲ期5例,Ⅳ期3例;FIGO预后评分:7~12分(高危)4例,≥13分(超高危)4例;8例患者均有肺转移,同时伴脑转移2例、肾及肠道转移各1例。(2)既往治疗:①化疗:8例GTN患者平均接受了21.1个疗程(5~30个疗程)的化疗;化疗途径主要为全身静脉化疗,有1例患者因脑转移接受了甲氨蝶呤鞘内注射。②手术:8例GTN患者中,7例接受了手术治疗,其中盆腔手术5例次,肺叶切除术6例次,右半结肠切除术1例次。③放疗:8例GTN患者中,2例接受了放疗,其中1例因肺转移行肺部放疗8次,另1例行肺部、右骶髂关节及头颅放疗共22次。(3)PD-1抑制剂治疗:8例GTN患者耐药复发后均接受了PD-1抑制剂治疗,平均9.0个疗程(2~12个疗程),治疗过程中有6例出现了不同程度的免疫相关不良反应,均为Ⅰ~Ⅱ级,无一例重度不良反应发生。(4)预后:8例耐药复发GTN患者中,4例患者在PD-1抑制剂治疗2~3个疗程后血清β-hCG水平降至正常,巩固治疗0~9个疗程,随访2~7个月均无复发;1例患者接受PD-1抑制剂治疗12个疗程,在第6个疗程后血清β-hCG水平降至正常,维持正常1个月后血清β-hCG水平升高,因疾病进展接受贝伐单抗治疗;3例患者PD-1抑制剂治疗期间疾病进展,更换其他化疗方案治疗。结论PD-1抑制剂可作为耐药复发GTN的补救治疗措施,其有效率较高,不良反应相对较轻。但本研究病例数较少,临�Objective To investigate the therapeutic effect of programmed cell death receptor 1(PD-1)inhibitor in drug-resistant recurrent gestational trophoblastic neoplasia(GTN).Methods Clinicopathological features,previous treatments,PD-1 inhibitor treatment and prognosis of 8 patients with drug-resistant recurrent GTN treated with PD-1 inhibitor pembrolizumab,in Peking Union Medical College Hospital of Chinese Academy of Medical Sciences from August 2018 to June 2019 were collected and retrospectively analyzed.Results(1)Clinicopathological features:the average age of onset of 8 GTN patients was 32.9 years old(31-39 years old);pathological types:choriocarcinoma in 7 cases,epithelioid trophoblastic tumor in 1 case.International Federation of Gynecology and Obstetrics(FIGO)stages:stageⅢin 5 cases,stageⅣin 3 cases;FIGO score:4 patients with 7-12 points(high-risk group)and 4 patients with≥13 points(ultra high-risk group).All the 8 patients had lung metastasis,2 patients with brain metastasis,1 patient with kidney and 1 patient with intestinal metastasis.(2)Previous treatments:①Chemotherapy:8 patients with GTN received an average of 21.1 courses(5-30 courses)of chemotherapy;the main route was systemic intravenous chemotherapy.One patient received intrathecal methotrexate chemotherapy due to brain metastasis.②Surgery:7 of 8 patients with GTN received surgical treatment,including 5 cases of pelvic surgury,6 cases of pulmonary lobectomy and 1 case of right hemicolectomy.③Radiotherapy:2 of 8 patients with GTN received radiotherapy,among which 1 patient received radiotherapy for lung for 8 times due to lung metastasis,and the other one received radiotherapy for lung,right sacroiliac joint and skull for a total of 22 times.(3)PD-1 inhibitor treatment:8 patients with GTN received PD-1 inhibitor treatment with a mean course of 9(2-12 courses).Six patients appearedⅠ-Ⅱgrade of immune related adverse events(AE),and no severe AE occurred.(4)Prognosis:after 2-3 courses of PD-1 inhibitor treatment,serumβ-hCG level came to n

关 键 词：妊娠滋养细胞肿瘤 程序性细胞死亡受体1 免疫抑制剂 抗体 单克隆 人 免疫疗法 

分 类 号：R737.33[医药卫生—肿瘤]