早期放疗干预对非小细胞肺癌寡转移患者的有效性及安全性分析

Analysis of the effectiveness and safety of early radiotherapy intervention in oligometastatic non-small cell lung cancer

目的研究非小细胞肺癌(NSCLC)寡转移患者的预后影响因素及早期放疗干预的有效性和安全性。方法回顾性分析苏州大学附属第一医院放疗科2015年1月至2018年12月收治的159例NSCLC寡转移(转移灶≤5个、转移器官≤3个)患者的临床资料,其中,男107例,女52例;中位年龄63岁;放疗早期干预137例,放疗中晚期干预22例。以受试者工作特征曲线(ROC)确定无进展生存时间(PFS)/总生存时间(OS)判断肿瘤局部控制和患者预后的最佳截断值。生存分析采用Kaplan-Meier法,并行Log-rank检验,多因素生存分析采用Cox比例风险模型。结果159例患者的中位随访时间为28.2个月,随访期内,完全缓解16例(10.1%),部分缓解53例(33.3%),疾病稳定27例(17.0%),疾病进展63例(39.6%),3、6、12个月局部控制率分别为83.9%、59.7%和41.0%。159例患者的PFS为8.0个月,中位OS为35.0个月,1、2、3年生存率分别为77.3%、63.0%和45.1%。与放疗相关的不良反应较轻,多为1~2级。PFS/OS=0.3是判断肿瘤局部控制和患者预后的最佳截断值。单因素分析结果显示,患者性别、寡转移器官数、T分期、放疗干预模式、肿瘤靶体积吸收剂量(DT-GTVnx)、PFS/OS与中位PFS有关(χ^(2)=4.175、16.508、4.408、10.300、6.842、38.175,P<0.05);患者性别、病理类型、寡转移器官数、初诊分期、T分期、N分期、肺叶手术情况、放疗干预模式、肿瘤靶体积(V-GTVnx)、肿瘤负荷、肿瘤局部控制情况与中位OS有关(χ^(2)=6.672、8.330、21.299、5.398、6.874、6.893、5.611、115.206、4.017、5.110、21.299,P<0.05)。多因素分析结果显示,放疗中晚期干预(HR=3.728,95%CI 2.099~6.622,P<0.001)是影响NSCLC寡转移患者PFS的独立危险因素,PFS/OS>0.3(HR=0.123,95%CI 0.062~0.246,P<0.001)是影响NSCLC寡转移患者PFS的独立保护因素;男性(HR=1.665,95%CI 1.024~3.043,P=0.033)、高肿瘤负荷(HR=2.113,95%CI 1.088~4.107,P=0.027)、放疗中晚期干预(HR=15.076,95%CI 7.925~28.680,P<0.001)是影响NSCLC寡转移患者OS的独立危险因素。结论女性、低肿瘤负荷和放疗早期干预的NSCLC寡转移患者的OS明显延长,放疗早期干预可明显改善患者的预后,且放疗相关不良反应均可耐受,提示局部放疗是治疗NSCLC寡转移患者安全且有效的手段。

Objective To investigate the prognostic factors of oligometastatic(OM)non-small cell lung cancer(NSCLC)patients and the safety and effectiveness of early radiotherapy intervention.Methods A retrospective analysis was conducted,including 159 OM NSCLC cases(metastatic sites≤5,metastasis organs≤3)admitted to Department of Radiation Oncology in First Affiliated Hospital of Soochow University from January 2015 to December 2018.Among 159 cases,there were 107 males and 52 females,with the median age of 63 years.137 cases were administrated via early radiotherapy intervention,and 22 cases via delayed radiotherapy intervention.The receiver operating characteristic curve(ROC)was used to determine the progression-free survival time(PFS)/overall survival time(OS)to ascertain the best cut-off value for local control and prognosis.Survival analysis was calculated by Kaplan-Meier curves,and Log rank test was used for comparison of these curves.Cox proportional hazards regression model was used for multivariate survival analysis.Results The median follow-up time of 159 cases was 28.2 months.During the follow-up period,there were 16 cases with complete remission(10.1%),53 cases with partial remission(33.3%),27 cases with stable disease(17.0%),and 63 cases with progressed disease(39.6%).The local control rates at 3,6 and 12 months were 83.9%,59.7%and 41.0%,respectively.The median progression-free survival(PFS)of 159 patients was 8.0 months,the median survival time(OS)was 35.0 months,and 1,2,and 3-year survival rates were 77.3%,63.0%and 45.1%,respectively.Adverse reactions related to radiotherapy were relatively mild,mostly grade 1 and 2.PFS/OS=0.3 is the best cut-off value for determining the patient's local control and prognosis.The result of univariate analysis showed that gender,number of OM organs,T staging,radiotherapy intervention mode,tumor target volume absorbed dose(DT-GTVnx),PFS/OS were significantly related to median PFS(χ^(2)=4.175,16.508,4.408,10.300,6.842,38.175,P<0.05);gender,pathological type,number of OM organs,initial diagnosis stage,T stage,N stage,lobectomy,radiotherapy intervention mode,tumor target volume(V-GTVnx),tumor load,local control status were significantly related to median OS(χ^(2)=6.672,8.330,21.299,5.398,6.874,6.893,5.611,115.206,4.017,5.110,21.299,P<0.05).The result of multivariate analysis showed that delayed radiotherapy intervention(HR=3.728,95%CI 2.099-6.622,P<0.001)was an independent risk factor for PFS in patients with OM NSCLC,and PFS/OS>0.3(HR=0.123,95%CI 0.062-0.246,P<0.001)was an independent protective factor for PFS in patients with OM NSCLC;male(HR=1.665,95%CI 1.024-3.043,P=0.033),high tumor burden(HR=2.113,95%CI 1.088-4.107,P=0.027),delayed radiotherapy interventions(HR=15.076,95%CI 7.925-28.680,P<0.001)were independent risk factors for OS in patients with OM NSCLC.Conclusions OS of patients with OM NSCLC is significantly prolonged in female,low tumor burden and early radiotherapy intervention.Early radiotherapy intervention significantly improved the prognosis,and radiotherapy-related adverse reactions could be tolerated.These might suggest that local radiotherapy is safe and effective in the treatment of OM NSCLC patients.