晚期非鳞非小细胞肺癌应用贝伐单抗疗效的预测因素分析

发布时间：2018-09-14 10:35

【摘要】：研究背景非小细胞肺癌(NSCLC)是最常见的恶性肿瘤之一,也是世界范围内最常见的癌症相关死因。大多数NSCLC患者在诊断时已是晚期(ⅢB期或Ⅳ期),预后极差。近年来,表皮生长因子受体酪氨酸激酶受体抑制剂(EGFR-TKI)、间变性淋巴瘤激酶酪氨酸(ALK)激酶受体抑制剂的应用为晚期NSCLC的治疗开启了新的篇章。然而只有部分NSCLC患者具有EGFR或ALK等驱动基因,对于驱动基因阴性的病人,含铂两药化疗仍是其标准治疗。贝伐单抗为抗血管内皮生长因子单克隆抗体,多项研究证实贝伐单抗可进一步提高含铂两药化疗在晚期非鳞NSCLC中的疗效,但是其客观反应率(Objective Resonse Rate,ORR)也仅为35%-54%,也就意味着并不是所有的患者均可以从贝伐单抗治疗中获益。许多研究者对贝伐单抗的疗效预测因素进行了探索和分析,包括影像学参数、血浆VEGF水平、TP53突变等,但是结果尚存在争议,对临床的指导作用不足。因此,寻找贝伐单抗在晚期非磷NSCLC中疗效的预测因素仍是亟待解决的问题。研究目的本研究以应用贝伐单抗的晚期非鳞NSCLC患者为研究对象,通过对患者的基本特征、病理特征、肿瘤标志物、中性粒细胞淋巴细胞比值及血生化等血液学参数进行分析,探索晚期非鳞NSCLC应用贝伐单抗的疗效预测因素,筛选贝伐单抗的最大获益人群,以指导贝伐单抗的临床应用,为晚期非鳞NSCLC患者带来更精准的治疗。研究方法本研究回顾性分析了 2011年6月至2017年1月于山东省肿瘤医院接受贝伐单抗治疗的112例晚期非鳞NSCLC患者的临床资料,对其基本特征、病理学特征、肿瘤标志物、中性粒细胞淋巴细胞比值及血生化等血液学参数特征及生存进行分析。运用Kaplan-Meier、log-rank检验、单因素Cox回归分析进行单因素分析,p0.1纳入多因素分析;多因素Cox回归进一步分析相关因素对贝伐单抗治疗后无进展生存时间(PFS)的影响,p0.05有统计学意义。研究结果随访截止至2017年1月20日,随访时间为2-36个月,中位随访时间为11月。所有应用贝伐单抗患者的中位PFS为11月。从应用贝伐单抗后的近期疗效来看,女性患者(ORR37%,P =0.364,p=0.024)、周围型肺癌(ORR40%,χ2=8.370,p=0.04)、贝伐单抗应用前无骨转移(ORR 35.5%,χ2 =0.483,p=0.028)、双肺转移(ORR 37.1%,χ2=9.455,p=0.002)、应用前转移部位数目≤2个(ORR41.2%,χ2=5.216,p=0.022)、中性粒细胞淋巴细胞比值(Neutrophil lymphocyte ratio,NLR)≤2.29(ORR37.0%,χ2 =5.099,p=0.024)、血小板淋巴细胞比值(Platelet lymphocyte ratio,PLR)≤150(ORR 43.5%,χ2=10.468,p=0.001)、血小板平均体积(Medianplateletvolume,MPV)≤9.9fL(ORR36.7%,χ2=5.873,p=0.015)、乳酸脱氢酶(Lactate dehydrogenase,LDH)≤179.5 U/L(ORR 43.8%,χ2=18.223,p=0.000)的患者应用贝伐单抗后有效率高,且有统计学意义。从应用贝伐单抗的远期疗效来看,年龄(χ2=3.557,p=0.059)、所在肺叶(χ2=34.987,p=0.000)、解剖分型(χ2=12.853,p=0.000)、贝伐单抗同步化疗方案(χ2 =14.602,p=0.000)、贝伐单抗应用时机(χ2=14.577,p=0.001)、贝伐单抗应用前 T分期(χ2=4.389,p=0.036)、N分期(χ2=3.149,p=0.0076)、转移部位的数目(χ2=3.141,p=0.076)、是否有肝转移(χ2=7.758,p=0.005)、是否有骨转移(χ2 =4.34,p=0.037)、血红蛋白(Hemoglobin,HGB)(χ2=3.288,p=0.070)、LDH水平(χ2=4.266,p=0.039)、白蛋白(Albumin,ALB)水平(χ2=7.324,p=0.007)、D2聚体(χ2=7.403,p=0.007)与应用贝伐单抗后的疗效相关。我们又对其进行了多因素分析,结果显示:应用贝伐单抗前年龄(HR=4.133,p=0.007),所在肺叶(HR=37.206,p=0.000),原发肿瘤 T 分期(HR=0.114,p=0.000),骨转移(HR=2.685,p=0.044),LDH 水平(HR=0.245,p=0.012),ALB水平(HR=7.670,p=0.001),为应用贝伐单抗的独立预后因素。研究结论晚期非鳞NSCLC人群中,年龄60岁、下叶肿瘤、应用贝伐单抗前T1-T2期肿瘤、无骨转移、贝伐单抗前ALB42.1g/L、LDH≤179.5U/L为应用贝伐单抗的独立预后因素。
[Abstract]:Background Non-small cell lung cancer (NSCLC) is one of the most common malignancies and the most common cause of cancer-related deaths worldwide. Most patients with NSCLC are diagnosed at advanced stage (stage III B or IV) and have poor prognosis. In recent years, epidermal growth factor receptor tyrosine kinase receptor inhibitor (EGFR-TKI), anaplastic lymphoma kinase The use of tyrosine kinase receptor inhibitors (ALK) opens a new chapter in the treatment of advanced NSCLC. However, only a few patients with NSCLC have EGFR or ALK-driven genes. For patients with negative driving genes, chemotherapy with platinum is still the standard treatment. Bevacizumab is a monoclonal antibody against vascular endothelial growth factor, which has been proved by many studies. Bevacizumab can further improve the efficacy of platinum-based chemotherapy in advanced NSCLC, but its objective Resonse Rate (ORR) is only 35% - 54%, which means that not all patients can benefit from bevacizumab treatment. Many researchers have explored predictors of the efficacy of bevacizumab. Objective To investigate the predictors of bevacizumab efficacy in advanced non-phosphorus NSCLC. Objective: To explore the predictors of the efficacy of bevacizumab in advanced NSCLC by analyzing the basic characteristics, pathological features, tumor markers, neutrophil lymphocyte ratio and blood biochemical parameters of patients, and to screen the most beneficiary population of bevacizumab so as to guide the clinical application of bevacizumab in advanced NSCLC. Methods The clinical data of 112 advanced NSCLC patients treated with bevacizumab in Shandong Cancer Hospital from June 2011 to January 2017 were analyzed retrospectively. The basic features, pathological features, tumor markers, neutrophil lymphocyte ratio and blood biochemistry were analyzed. Kaplan-Meier test, log-rank test, univariate Cox regression analysis were used for univariate analysis, and P0.1 was included in multivariate analysis; multivariate Cox regression was used to further analyze the effect of related factors on progression-free survival (PFS) after bevacizumab treatment, with statistical significance at p0.05. The median follow-up time was 2-36 months on January 20, 2017, with a median follow-up time of 11 months. The median PFS of all patients treated with bevacizumab was 11 months. 3, P = 0.028, double lung metastases (ORR 37.1%, 967 2 = 9.455, P = 0.002), pre-application metastasites (< 2 (ORR 41.2%, 962 = 5.216, P = 0.022), neutrophil lymphocyte ratio (NLR) (< 2.29 (ORR 37.0%, 962 = 5.099, P = 0.024), platelet lymphocyte ratio (96let, PLlet, lymphocyte ratio 962 = 5.216, P = 5.216, P = 0.022, P = 0.022), neutrophil lymphocyte lymphocyte ratio (NLR), NLR < 2.29 (ORR 37.0%, 967 2 = 1 Patients with mean platelet volume (MPV) less than 9.9 fL (ORR 36.7%, 2 = 5.873, P = 0.015) and lactate dehydrogenase (LDH) less than 179.5 U/L (ORR 43.8%, 2 = 18.223, P = 0.000) had a high response rate and a statistically significant difference in the long-term efficacy of bevacizumab. 9672 = 3.557, P = 0.057, P = 0.059, lobe (962 = 34.987, P = 0.000), lobe (962 = 34.987, P = 0.000), anatomtyping (962 = 12.853, P = 0.000), concurrentchemotherapy regimen (962 = 14.602, P = 0.000), time of application of bevacizum (962 = 14.577, P = 0.001), T stage (962 = 4.382 = 4.389, P = 0.N6, N stage (962 = 4.Nstage = 4.Nstage (962 = 4.Nstage), N stage (962 = 3.Nstage (962 = 3.962 = 3.Nstage 149, P = 0.0076, number of metastatic sites (_2 = 3.141, P = 0.076) Liver metastasis, liver metastasis (962 = 7.758, P = 0.005), bone metasta (962 = 4.34, P = 0.037), hemoglobin (HGB) (962 = 3.288, P = 0.070), LDH (962 = 4.266, P = 0.039), albumin (Albumin, ALB) levels (962 = 7.324, P = 0.004, P = 0.007), D2aggregate (962 = 7.2 = 7.403, P = 2 = 7.3, P = 3, P = P = 0.003, P = 0.007) and the use of albumin (albumin, albumin, albumin, albumin, albumin, There is a correlation between the efficacy of Vamvastatin. We have multiple reasons for this. The results showed that age (HR = 4.133, P = 0.007), lobe (HR = 37.206, P = 0.000), primary tumor T stage (HR = 0.114, P = 0.000), bone metastasis (HR = 2.685, P = 0.044), LDH level (HR = 0.245, P = 0.012), ALB level (HR = 7.670, P = 0.001) were independent prognostic factors. In this population, 60 years of age, lower lobe tumors, T1-T2 tumors before bevacizumab administration, no bone metastasis, ALB42.1g/L before bevacizumab, LDH < 179.5U/L were independent prognostic factors for bevacizumab administration.
【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R734.2

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