中国老年人群恶性间皮瘤临床病理学特征与疗效生存分析

Clinicopathologic characteristics and survival analysis of malignant mesothelioma in the Chinese elderly population

目的探讨中国老年人群恶性间皮瘤(MM)患者的临床病理学特征与疗效、预后相关影响因素。方法回顾性分析2007年11月至2024年7月就诊于北京医院、北京大学肿瘤医院和中国医学科学院肿瘤医院的115例65岁及以上老年MM患者的临床资料,根据不同年龄(高龄组≥75岁、低龄组<75岁)、组织学分型及治疗方式分组,Kaplan-Meier法进行生存曲线分析,并进行Log-rank检验,Cox风险比例回归模型分析预后影响因素。结果中国老年人群MM患者钙视网膜结合蛋白(Calretinin)阳性表达率与国外报道一致,细胞角蛋白5/6(CK5/6)、肾母细胞瘤蛋白1(WT-1)、抗胎儿蛋白M2A抗体(D2-40)阳性率明显低于既往研究。一线治疗的总有效率(ORR)为17.3%(9/52),疾病控制率(DCR)为92.3%(48/52)。二线治疗的ORR为7.7%(1/13),DCR为76.9%(10/13)。一线免疫治疗组ORR和DCR均高于化疗组,分别为50.0%比14.6%(P=0.134)和100.0%比91.7%(P=1.000),差异无统计学意义。二线免疫治疗组ORR高于化疗组,分别为25.0%比0,DCR两组相同,均为75.0%。接受一线治疗的患者总体中位无进展生存期(mPFS)为9.2个月,中位总生存期(mOS)为19.0个月,接受二线治疗的患者总体mPFS为3.3个月,mOS为11.0个月。一线免疫治疗组mPFS短于化疗组(1.6个月比9.2个月,P=0.081),mOS延长(未达到比18.1个月,P=0.147)。低龄组mPFS较高龄组延长(9.7个月比7.2个月,P=0.305),mOS较高龄组缩短(18.1个月比23.9个月,P=0.289),但差异均无统计学意义。上皮样亚型mPFS和mOS均较非上皮样亚型延长,分别为10.4个月比1.6个月(P<0.001)和20.3个月比4.6个月(P=0.803);二线化疗组mPFS和mOS均较免疫组延长分别为7.1个月比4.7个月(P=0.583)和18.3个月比6.3个月(P=0.134)。多因素Cox回归分析结果显示,性别、美国东部肿瘤协作组体力状况评分(ECOGPS)和CK5/6阳性是一线治疗PFS的独立预测因子,组织学分型是一线治疗OS的独立预后因素。结论中国老年人群MM具有独特的临床病理学特征。患者一线使用免疫治疗能提高ORR、DCR并延长mOS,二线使用免疫治疗能提高ORR,但DCR、mPFS和mOS无获益。低龄组接受一线治疗较高龄组mPFS延长;多因素Cox回归提示性别、ECOGPS评分和CK5/6表达阳性是患者一线治疗疗效预测标志物,组织学亚型是患者生存独立预后因素。

Objective To explore the clinicopathological characteristics and the related influencing factors of efficacy and prognosis of elderly patients with malignant mesothelioma(MM)in Chinese population.Methods We retrospectively analyzed the clinical data of 115 patients aged 65 years and above who were diagnosed with MM in Beijing Hospital,Peking University Cancer Hospital,and Cancer Hospital of Chinese Academy of Medical Sciences between November 2007 and July 2024,and the patients were grouped according to age(≥75 years in the older group and<75 years in the younger group),histological types and therapy regimens.Kaplan-Meier curve and Log-rank test were performed.Cox regression was used in prognostic analysisR.IesultsThe positive expression rate of Calretinin in the Chinese elderly population with MM was consistent with previous reports,while the positive rates of Cytokeratin 5/6(CK5/6),WT-1,and D2-40 were much lower.The overall response ratio(ORR)for first-line treatment was 17.3%(9/52),and the disease control rate(DCR)was 92.3%(48/52).The ORR for second-line treatment was 7.7%(1/13)and the DCR was 76.9%(10/13).The ORR and DCR were higher in the first-line immunotherapy group than in the chemotherapy group,50.0%vs.14.6%(P=0.134)and 100.0%us.91.6%(P=1.000),respectively.The ORR in the second-line immunotherapy group was higher than that in the chemotherapy group,25.0%vs.0,respectively,and the DCR were both 75.0%in two groups.The median progression free survival(mPFS)was 9.2 months and median overall survival(mOS)was 19.O months for patients receiving first-line treatment,and the mPFS was 3.3 months and mOS was 11.O months for second-line therapy.The first-line immunotherapy provided more shorter mPFS(1.6 months us.9.2 months,P-0.081)and longer mOS(not reached s.18.1 months,P=0.147)than the chemotherapy group.The younger group had prolonged mPFS(9.7 months us.7.2 months,P=0.305)while shorter mOS(18.1 months vs.23.9 months,P=0.289)compared with the older group,and none of them reached statistical differences.Both mPFS and mOS were prolonged in the epithelioid subtype compared with the non-epithelioid subtypes,10.4 months us.1.6 months(P<0.001)and 20.3 months us.4.6 months(P=0.803),respectively.Both mPFS(7.1 months us.4.7 months,P=0.583)and mOS(18.3 months us.6.3 months,P=0.134)were prolonged in the second-line chemotherapy group compared with the immunotherapy group.The Cox regression analysis showed that gender,Eastern Cooperative Oncology Group,Performance Status(ECOG PS)and positive CK5/6 were both the independent predictors for the first-line PFS.Histological type was an independent prognostic factor for the firstline OS.Conclusions MM in the Chinese elderly population exhibits unique clinicopathologic characteristics.The immunotherapy improves ORR,DCR and prolongs mOS in first-line use,and improves ORR in second-line.First-line treatment improves mPFS in the younger group compared with the older group.Multivariate Cox regression demonstrates that gender,ECOG PS and CK5/6 expression are both predictors of efficacy,and histological type is an independent prognostic factor for survival of the Chinese elderly population with MM.