射波刀治疗非小细胞肺癌脑转移的近期临床效果和安全性及预后影响因素

Short-term clinical efficacy,safety and prognostic influencing factors of CyberKnife for treatment of brain metastases in non-small cell lung cancer

目的探讨射波刀治疗非小细胞肺癌(NSCLC)脑转移的近期临床效果和安全性及此类患者预后影响因素。方法回顾性病例系列研究。回顾性分析2020年7月至2022年1月在吉林省肿瘤医院接受射波刀治疗脑转移瘤的58例NSCLC患者临床资料。射波刀治疗后3个月,依据头部增强磁共振成像(MRI)检查的脑转移瘤变化评价放疗疗效。采用Kaplan-Meier法对58例患者进行总生存(OS)和局部无复发生存(LRRFS)分析;以患者随访期间生存状态为金标准,采用受试者工作特征(ROC)曲线分析依据累计脑转移瘤体积判断射波刀治疗的NSCLC脑转移患者生存情况的效果,并获得累计脑转移瘤体积最佳临界值;通过单因素和多因素Cox比例风险模型分析影响射波刀治疗的NSCLC脑转移患者OS和LRRFS的临床因素;评估射波刀治疗相关不良反应。结果58例患者中,男性26例(44.8%),女性32例(55.2%),中位年龄[M(Q1,Q3)]64岁(56岁,70岁);每例患者有1~7个脑转移病灶,58例患者共有98个脑转移病灶。射波刀治疗后3个月内死亡2例(3.4%);其余56例患者治疗后3个月,完全缓解3例(5.4%),部分缓解36例(64.3%),疾病稳定13例(23.2%),疾病进展4例(7.1%);ROC曲线分析显示,依据累计脑转移瘤体积判断射波刀治疗的NSCLC脑转移患者生存的曲线下面积为0.593(95%CI:0.423~0.763),累计脑转移瘤体积最佳临界值为15 cm^(3)。中位随访时间12.6个月(7.5个月,17.9个月)。6、12个月的OS率分别为91.3%、79.5%,6、12个月的LRRFS率分别为93.0%、89.2%。多因素Cox回归分析显示,Karnofsky功能状态评分(>70分比≤70分,HR=0.103,95%CI:0.019~0.545,P=0.007)、颅外肿瘤控制情况(已控制比未控制,HR=0.145,95%CI:0.049~0.429,P<0.001)、累计脑转移瘤体积(≤15 cm^(3)比>15 cm^(3),HR=0.105,95%CI:0.028~0.399,P=0.001)是OS不良的独立影响因素,颅外肿瘤控制情况(已控制比未控制,HR=0.062,95%CI:0.006~0.616,P=0.018)、累计脑转移瘤体积(≤15 cm^(3)比>15 cm^(3),HR=0.440,95%CI:0.007~0.292,P=0.001)、靶区总生物等效剂量(BED)(≤60 Gy比>60 Gy,HR=5.299,95%CI:1.020~27.530,P=0.047)是LRRFS不良的独立影响因素。治疗后仅出现1~2级头痛[53.5%(31/58)]、恶心呕吐[36.2%(21/58)]等不良反应,无≥3级不良反应发生。结论射波刀治疗NSCLC脑转移具有较高的局部控制率和近期生存率,不良反应轻微。Karnofsky功能状态评分、颅外肿瘤控制情况、累计脑转移瘤体积可能影响射波刀治疗的NSCLC脑转移患者的OS,颅外肿瘤控制情况、累计脑转移瘤体积、总BED可能影响局部复发。

Objective To explore the short-term clinical efficacy,safety and patients'prognostic influencing factors of CyberKnife for the treatment of brain metastases in non-small cell lung cancer(NSCLC).Methods A retrospective case series study was conducted.The clinical data of 58 NSCLC patients who received CyberKnife treatment for brain metastases at Jilin Cancer Hospital from July 2020 to January 2022 were retrospectively analyzed.At 3 months after CyberKnife treatment for brain metastases,and the efficacy of radiotherapy was evaluated on the basis of changes of brain metastases detected by contrast-enhanced magnetic resonance imaging(MRI)of the head.Overall survival(OS)and local recurrence-free survival(LRRFS)were analyzed in 58 patients by using the Kaplan-Meier method;the efficacy of cumulative brain metastasis volume for determining the survival of CyberKnife-treated NSCLC patients with brain metastases was analyzed by using the receiver operating characteristic(ROC)curve with the survival status of patients during the follow-up period as the gold standard,and the optimal cut-off value of cumulative brain metastasis volume was obtained;the clinical factors affecting OS and LRRFS of CyberKnife-treated NSCLC patients with brain metastases were analyzed by univariate and multivariate Cox proportional hazards models,and the adverse reactions associated with CyberKnife treatment were evaluated.Results Among the 58 patients,26(44.8%)were male and 32(55.2%)were female,with a median age[M(Q1,Q3)]of 64 years old(56 years old,70 years old);there were 1-7 brain metastatic lesions in each patient,and there were 98 brain metastatic lesions in the 58 patients.There were 2 deaths(3.4%)within 3 months after CyberKnife treatment.At 3 months after treatment,there were 3 cases(5.4%)in complete remission,36 cases(64.3%)in partial remission,13 cases(23.2%)in stable disease,and 4 cases(7.1%)in disease progression in the remaining 56 patients.ROC curve analysis showed that the area under the curve for determining the survival of CyberKnife-treated NSCLC patients with brain metastases based on the cumulative brain metastasis volume was 0.593(95%CI:0.423-0.763),and the optimal cut-off value of cumulative brain metastasis volume was 15 cm^(3).Median follow-up time was 12.6 months(7.5 months,17.9 months).The 6-and 12-month OS rates were 91.3% and 79.5%,respectively,and the 6-and 12-month LRRFS rates were 93.0% and 89.2%,respectively.Multivariate Cox regression analysis showed that the Karnofsky functional status score(>70 points vs.≤70 points,HR=0.103,95%CI:0.019-0.545,P=0.007),control of extracranial tumor(controlled vs.uncontrolled,HR=0.145,95%CI:0.049-0.429,P<0.001),cumulative brain metastasis volume(≤15 cm^(3) vs.>15 cm^(3),HR=0.105,95%CI:0.028-0.399,P=0.001)were independent influencing factors for poor OS,and the control of extracranial tumor(controlled vs.uncontrolled,HR=0.062,95%CI:0.006-0.616,P=0.018),cumulative brain metastasis volume(≤15 cm^(3) vs.>15 cm^(3),HR=0.440,95%CI:0.007-0.292,P=0.001),and target area total bioequivalent dose(BED)(≤60 Gy vs.>60 Gy,HR=5.299,95%CI:1.020-27.530,P=0.047)were independent influencing factors for poor LRRFS.Only grade 1-2 headache[53.5%(31/58)],nausea and vomiting[36.2%(21/58)]and other adverse reactions occurred after treatment,and no≥grade 3 adverse reactions occurred.Conclusions CyberKnife treatment for NSCLC brain metastases has high local control rate and short-term survival rate with mild adverse effects.Karnofsky functional status score,control of extracranial tumor and cumulative brain metastasis volume may affect OS of CyberKnife-treated NSCLC patients with brain metastases,and the control of extracranial tumor,cumulative brain metastasis volume and total BED may affect local recurrence.