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1.局部晚期非小细胞肺癌放疗或化放综合治疗预后因素分析 2.MicroRNA在小细胞肺癌中的预后价值
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摘要
第一部分:三维适形放疗提高局部晚期非小细胞肺癌的生存率
     目的比较局部晚期非小细胞肺癌(NSCLC)三维适形放疗(3 DCRT)与常规放疗(2DRT)疗效。方法2000年1月至2006年12月间527例局部晚期NSCLC患者纳入分析。其中,253例接受3 DCRT,274例接受2 DRT。3 DCRT组中,62.8%患者接受化放综合治疗,30.4%接受放疗剂量>60Gy,19.4%接受剂量50~60Gy;常规放疗组中,46.4%患者接受化放综合治疗,17.5%接受放疗剂量>60Gy,27.4%接受剂量50~60Gy。毒性评价依据CTC 3.0。观察指标:总生存率、肿瘤专项生存率。统计方法:生存分析采用Kaplan-Meier法及COX回归分析。结果3 DCRT组1、3、5年总生存率(OS)及中位生存时间分别为73.3%,、26.1%,、14.4%和20.1个月,2 DRT组为61.0%,、13.8%,、8.0%和15.6个月(P=0.002)。3 DCRT组1、3、5年肿瘤专项生存率(CSS)分别为79.0%,、33.3%,、20.8%,2 DRT组为65.1%,、16.7%,、11.2%(P=0.000)。3 DCRT组1、3、5年局部区域控制率分别为71.6%、34.3%、31.0%,2 DRT组为57.3%、22.1%、19.2%(P=0.002)。多因素分析显示:三维适形放疗较常规放疗显著提高患者OS和CSS。同时发现KPS评分、近期疗效及疗前血红蛋白也是独立相关因素。两组放疗并发症无显著统计学差异。结论采用三维适形放疗技术能够提高局部晚期非小细胞肺癌的生存率。第二部分:局部晚期非小细胞肺癌三维适形放射治疗结果
     目的回顾性分析局部晚期非小细胞肺癌(NSCLC)三维适形放射治疗疗效及预后因素。方法2000年1月至2006年12月,共有253例局部晚期NSCLC符合条件患者纳入分析。其中ⅢA期82例,ⅢB期171例。治疗方法包括单纯放疗(96例)、同步放化疗(93例)、序贯化放疗(64例)。放射治疗中位总剂量60(50~76)Gy。观察指标:总生存率、肿瘤专项生存率。统计方法:生存分析采用Kaplan-Meier法及COX回归分析。结果全组1、3、5年总生存率分别为73.3%、26.1%、14.4%,中位生存时间20.1个月。1、3、5年肿瘤专项生存率分别为79.0%、33.3%、20.8%。肿瘤体积80cm~3是评价预后的最佳界值。单因素分析显示:肿瘤体积(≤80 vs>80cm~3)、KPS评分(≥80 vs<80分)、近期疗效(CR+PR vs SD+PD)显著影响总生存率及肿瘤专项生存率;多因素分析显示:肿瘤体积、KPS评分和近期疗效是总生存率及肿瘤相关生存率独立相关因素;治疗失败原因包括局部失败(49.0%)和远处转移(48.6%),全组2级以上放射性肺炎和放射性食管炎的发生率分别为26.5%和35.2%。结论肿瘤体积、疗前KPS评分、近期疗效与总生存率和肿瘤相关生存率显著相关。肿瘤体积80cm~3是影响局部晚期NSCLC治疗预后的最佳分界点。第三部分:疗前肿瘤标记物(CEA、NSE、CA-125、Cyfra 21-1)在非小细胞肺癌放射治疗中的预后价值
     目的回顾性分析疗前血清肿瘤标记物(CEA、NSE、CA-125、Cyfra 21-1)对接受放射治疗或放化疗的Ⅰ-Ⅲ期非小细胞肺癌预后价值。方法对2001年1月至2006年12月间符合以下入组条件的190例患者纳入分析:病理或细胞学证实非小细胞癌;治疗前经过详细的分期检查确认为Ⅰ-Ⅲ期;接受单独放疗或化放综合治疗;放射治疗总剂量≥50Gy;有完整的治疗前血清肿瘤标记物检测数据。肿瘤标记物测定采用酶联免疫吸附实验。观察指标:总生存率、无病生存率。统计方法:生存分析采用Kaplan-Meier法及COX回归分析。结果全组1、3、5年总生存率,中位生存时间分别为70.1%、25.3%、19.2%,19.4个月;1、3、5年无病生存率分别为48.4%,18.2%,15.5%。单因素分析:Cyfra 21-1(≥3.3 vs<3.3 ng/ml)、CA-125(≥35 vs<35 ng/ml)、放疗总剂量(≥60 vs<60Gy)、治疗技术(二维vs三维)对总生存率影响达到统计学显著性差异水平(P<0.05)。多因素分析:Cyfra 21-1≥3.3ng/ml(HR=1.708,1.176-2.478),CA-125≥35ng/ml(HR=1.444,1.024-2.035),三维适形放疗(HR=0.657,0.454-0.952),放疗总剂量≥60Gy(HR=0.664,0.451-0.978)是总生存率独立预后因素;结论疗前血清肿瘤标记物Cyfra21-1、CA-125是接受放射治疗非小细胞肺癌患者独立预后因素。第四部分:MicroRNAs在小细胞肺癌中的预后价值
     目的研究MicroRNAs与小细胞肺癌预后之间关系。方法收集42例接受手术±化疗±放疗患者福尔马林固定石蜡包埋小细胞肺癌标本,进行microRNA微阵列芯片检测。利用COX回归模型评价每个microRNA表达水平同生存之间相关性。将每个和生存相关显著的microRNA表达值乘以其回归系数(B值),之后线型相加建立模型,计算每个患者危险分数,预测患者治疗结果。另外收集40例标本,采用qRT-PCR进行验证。结果芯片组发现,microRNA1、microRNA2与小细胞肺癌患者预后具有显著相关性。基于危险分数中位值分为低危和高危两组,两组3年无进展生存率分别为76.2%、42.9%(P=0.045),3年生存率分别为76.3%、47.6%(P=0.02)。验证组结果同芯片组一致,3年无进展生存率分别为64.3%、40.0%(P=0.017),3年生存率分别为74.1%、40.0%(P=0.005)。结论microRNA1、microRNA2预后模型显著影响小细胞肺癌无进展生存率及生存率。
PartⅠ:3 DCRT improved overall survival for locally advanced non-small-cell lung cancer patients comparing to conventional radiotherapy
     Purpose To compare treatment results of three-dimensional(3D)conformal radiotherapy and conventional radiotherapy(2D)for patients with locally advanced non-small-cell lung cancer(NSCLC).Methods and Materials Between Jan 2000 and Dec 2006,527 patients with stageⅢNSCLC were reviewed.253 cases were treated with 3D conformal radiotherapy,274 with conventional radiotherapy.In the 3D group,62.8%patients with chemoradiotherapy,30.4%with total radiotherapy dose of>60Gy,19.4%with 50~60Gy;In the 2D group,46.4%patients with chemoradiotherapy,17.5%with total radiotherapy dose of>60Gy,27.4%with 50~60Gy.Toxicity was scored accorcing to CTC 3.0.The observed endpoints were overall survival(OS)and cancer-specific survival(CSS).Kaplan-Meier estimation and Cox regression models were used for survival analyses.Results 1-,3-,5-year overall survival rates(OS)and median survival time for patients who received 3D were 73.3%,26.1%,14.4%and 20.1 months respectively;61.0%,13.8%,8.0%and 15.6 months in patients who received 2D radiotherapy(P=0.002).1-,3-,5-year cancer-special survival rates(CSS)were 79.0%, 33.3%,20.8%for the 3D group and 65.1%,16.7%,11.2%for the 2D group, respectively(P=0.000).Locoregional control rates at 1-,3-,and 5-year were 71.6%, 34.3%and 31.0%for patients who received 3D radiotherapy and 57.3%,22.1%and 19.2%in patients who received 2D treatment,respectively(P=0.002).On multivariate analysis,3D radiotherapy was independently associated with increased OS and CSS.In addition,KPS,clinical tumor response and pretreatment haemoglobin level also were independently associated with OS and CSS.No statistically differences of radiation complication were found in the two groups.Conclusion This study demonstrates that 3D conformal radiotherapy improves survival rate in patients with stageⅢNSCLC compared with 2D treatment.
     PartⅡ:Treatment results of 3DCRT for locally advanced non-small cell lung cancer
     Purpose To retrospectively analyze treatment results of Three-Dimensional conformal Radiotherapy(3 DCRT)for locally advanced non-small cell lung cancer(LD NSCLC) patents.Methods and Materials Between Jan 2000 and Dec 2006,253 patients with locally advanced NSCLC were reviewed.Among them,82 with stageⅢA,171 with stageⅢB.Patents were treated with radiotherapy alone(n=96),concurrent chemoradiotherapy(n=93),Sequential chemoradiotherapy(n=64).The median total radiotherapy dose were 60(range,50~76)Gy.The observed endpoints were overall survival(OS)and cancer-specific survival(CSS).KapIan-Meier estimation and Cox regression models were used for survival analyses.Results The 1-,3-,5-year overall OS and the median survival time were 73.3%,26.1%,14.4%and 20.1 months for the whole group,respectively;79.0%,33.3%,20.8%for CSS.Tumor volume of 80cm~3 was selected as the cutoff point which optimally predict the prognosis.In univariate analysis,the following variables were significantly associated with OS and CSS:gross tumor volume(>80 vs≤80cm),performance status(≥80 vs<80)and clinical tumor response(CR+PR vs SD+PD).In multivariate analysis,gross tumor volume, performance status and clinical tumor response were independently associated factors on OS and CSS.Failure sites included the local recurrence(49.0%)and distant metastasis (48.6%).Radiation pneumonitis and esophagitis of GradeⅡor higher were 26.5%and 35.2%,respectively.Conclusion Gross tumor volume,performance status and clinical tumor response were the independent factors on OS and CSS.Tumor volume of 80cm~3 was the cutoff point which optimally predict the prognosis for patients with LD NSCLC.
     PartⅢ:The prognostic value of serum tumor markers(CEA,NSE,CA-125 and Cyfra 21-1)in patients with non-small cell lung cancer undergoing radiotherapy alone or chemoradiotherapy
     Purpose To study the prognostic value of serum tumor markers(CEA,CA-125,NSE and Cyfra 21-1)in patients with stageⅠ-Ⅲnon-small cell lung cancer(NSCLC)undergoing radiotherapy alone or chemoradiotherapy.Methods and Materials Between Jan,2001 and Dec,2006,190 patients were analyzed who met the following criteria:histologically or cytologically NSCLC,clinical stageⅠ-Ⅲ,definitive thoracic radiotherapy alone or chemoradiotherapy and a total dose of≥50 Gy;completed medical data of pretreatment biological markers.All assays were measured by ELISA.Serum levels of CEA,CA-125, NSE and Cyfra 21-1 less than 5.0 ng/ml,35 U/ml,12 ng/ml and 3.3 ng/ml,respectively, were considered as normal.The observed endpoints were overall survival(OS)and diease free survival(DFS).Kaplan-Meier estimation and Cox regression models were used for survival analyses.Results The overall 1,3,5-year survival rate(OS)and the median survival time were 70.1%、25.3%、19.2%and 19.4 months for the whole group, respectively,and 48.4%,18.2%,15.5%for disease free survival(DFS).In univariate analysis,Cyfra 21-1(≥3.3 vs<3.3 ng/ml),CA-125(≥35 vs<35 ng/ml),radiotherapy technique(2D vs 3D)and total dose(<60 vs≥60Gy)were correlated with OS. Multivariate analysis demonstrated that Cyfra 21-1≥3.3 ng/ml(HR=1.708,1.176-2.478), CA-125≥35 ng/ml(HR=1.444,1.024-2.035),Three-Dimensional conformal radiotherapy(HR=0.657,0.454-0.952)and total dose≥60Gy(HR=0.664, 0.451-0.978)were independent prognostic factors.Conclusion Cyfra 21-1,CA-125 are independent prognostic factors for patients with NSCLC treated with radiotherapy alone or chemoradiotherapy..
     PartⅣ:The prognostic value of microRNAs in small cell lung cancer
     Purpose To study the association between microRNAs and prognosis for small cell lung cancer.Methods and Materials MicroRNA microarray expression profiling of Archived formalin-fixed,paraffin-embedded tumor tissues was performed on a cohort of 42 patients with SCLC receiving surgery±chemotherapy±radiotherapy.Association between the level of each microRNA expression and survival was evaluated by cox regression analysis.A model was developed according to a linear combination of the expression level of the microRNAs,weighted by the regression coefficients for the prediction of the outcome of treatment of SCLC.We validated the model in another cohort of 40 patients,using quantitative reverse transcription polymerase chain reaction assays(qRT-PCR).Results In the microchip group,MicroRNA1 and microRNA2 that significantly correlated with survival among patients with SCLC were identified. According to the median risk score computed by model,high risk and low risk group were divided.The low risk group had higher 3-year progression free(76.2%vs 42.9%, P=0.045)and overall survival rate(76.3%vs 47.6%,P=0.02)than high risk group.The model was validated in the qRT-PCR group,3-year progression free survival rates were 64.3%,40.0%(P=0.017),3-year overall survival rates were 74.1%,40.0% (P=0.005).Conclusion Two-mcroRNA signature is closely associated with progression free and overall survival among patients with small cell lung cancer.
引文
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