肺癌脑转移患者容积旋转调强放疗剂量学及预后分析

Dosimetric and prognostic analysis of VMAT in the treatment with brain metastases of lung cancer

目的脑转移瘤是颅内最常见的恶性肿瘤,其中肺癌转移风险最高,本研究分析应用容积旋转调强(volumetric modulated arc therapy,VMAT)技术行全脑+病灶同步推量放疗肺癌脑转移瘤的剂量学优势及预后。方法回顾性分析2016-01-01-2018-04-30郑州大学附属肿瘤医院接受VMAT放疗的40例肺癌脑转移患者临床资料。全脑放疗(whole brain radiotherapy,WBRT)剂量为30~40Gy,肿瘤靶区(gross tumor volume,GTV)同步推量至35~60Gy,分10~20次。随机选取10例患者,做调强适形放疗(intensity modulated radiation therapy,IMRT)9野同步推量计划,评估其适形指数(conformity index,CI)、均匀指数(homogeneity index,HI)。采用Kaplan-Meier法计算颅内无进展生存期(intracranial progression-free survival,IPFS)和总生存期(overall survival,OS),并采用Log-rank检验行单因素分析和Cox回归模型多因素分析。结果VMAT在脑转移瘤靶区的CI(t=4.255,P=0.002)、HI(t=-2.404,P=0.040)及全脑靶区中CI(t=7.384,P<0.001)均优于IMRT,且随着脑转移瘤个数的增加,VMAT计划的优势更加明显。1年IPFS为52.3%,1和2年OS分别为56.8%和36.7%。单因素分析显示,靶向治疗(χ^2=4.084,P=0.043)、KPS(χ^2=10.072,P=0.0002)、RPA分级(χ^2=10.102,P=0.006)与IPFS有关联,靶向治疗(χ^2=4.246,P=0.039)、KPS(χ^2=5.329,P=0.021)、RPA分级(χ^2=6.608,P=0.037)、GPA评分(χ^2=4.001,P=0.045)、中性粒细胞/淋巴细胞比值(neutrophil to lymphocyte ratio,NLR)(χ^2=4.081,P=0.043)与OS有关联。多因素分析显示,靶向治疗(HR=0.218,95%CI:0.054~0.873,P=0.031)是IPFS的独立影响因素,KPS(HR=2.317,95%CI:0.171~31.376,P=0.047)和靶向治疗(HR=0.309,95%CI:0.113~0.851,P=0.023)是OS的独立预后因素。结论脑转移数目越多VMAT技术剂量学优势越显著;KPS高、NLR值低的患者预后更佳。靶向治疗有助于延长IPFS和OS。

OBJECTIVE Brain metastases are the most common intracranial malignancy.Among them,the risk of lung cancer metastasis is the highest.This study aimed to analyze the dosimetric advantages and the prognosis of wholebrain irradiation(WBRT)with simultaneous integrated boost(SIB)in the treatment of brain metastases from lung cancer by volumetric modulated arc therapy(VMAT).METHORDS Totally 40 patients with brain metastases from lung cancer treated with VMAT in the Affiliated Tumor Hospital of Zhengzhou University from January 1,2016 to April 30,2018 were analyzed retrospectively.A dose of 30 to 40 Gy was delivered to the whole brain in 10 to 20 fractions,while a dose of 35 to 60 Gy was delivered to the gross target volume(GTV)in 10 to 20 fractions.Ten patients were randomly selected to make IMRT plan.Conformity index(CI)and homogeneity index(HI)were assessed.The overall survival(OS)and intracranial progression-free survival(IPFS)were estimated by Kaplan-Meier analysis.The univariate analysis was performed by Log-rank test and the multivariate analysis was evaluated by the Cox regression analysis.RESULTS VMAT was superior to IMRT,of which CI(t=4.255,P=0.002),HI(t=-2.404,P=0.040)in GTV and CI(t=7.384,P<0.001)in whole brain were better in VMAT.With the increase of the number of brain metastases,the advantage of VMAT program was more obvious.The 1-year and 2-year OS were 56.8%and 36.7%respectively,and the 1-year IPFS was 52.3%.Univariate analysis showed that target therapy(χ^2=4.084,P=0.043),KPS(χ^2=10.072,P=0.0002),RPA(χ^2=10.102,P=0.006)were associated with IPFS,target therapy(χ^2=4.246,P=0.039),KPS(χ^2=5.329,P=0.021),RPA(χ^2=6.608,P=0.037),GPA score(χ^2=4.001,P=0.045)and neutrophil to lymphocyte ratio(NLR)(χ^2=4.081,P=0.043)were correlated with OS.Multivariate analysis showed that target therapy(HR=0.218,95%CI:0.054-0.873,P=0.031)was the independent influence factors of IPFS,KPS(HR=2.317,95%CI:0.171-31.376,P=0.047)and target therapy(HR=0.309,95%CI:0.113-0.851,P=0.023)was independent prognostic factors for survival.CONCLUSIONS The more the number of brain metastases is,the more significant the dosimetric advantage of VMAT is.Patients with higher KPS and lower NLR have better prognosis.Targeted therapy helps prolong IPFS and OS.