老年广泛期小细胞肺癌患者化疗与预后的分析

目的:在老年人群中,小细胞肺癌的治疗难度大,缺乏有临床指导意义的研究数据,本文旨在通过对老年广泛期小细胞肺癌患者预后因素的分析寻找适合老年患者的化疗策略.方法:回顾性分析106例老年广泛期小细胞肺癌患者资料,应用SPSS13.0统计软件对数据进行单因素及COX回归多因素分析,探讨年龄、PS评分、化疗周期、化疗方案、血液学毒性等因素对生存的影响.结果:①单因素分析显示PS评分、化疗与否、化疗周期数、血液学毒性等因素对预后有影响,单药化疗与联合用药预后无明显差别.②COX回归多因素分析显示PS评分(P＜0.001)、化疗周期数(P=0.002)是影响预后的因素.③单药化疗的血液学毒性明显低于联合用药,化疗周期数更多.结论:老年广泛期小细胞肺癌患者可从化疗中受益,四周期以上的化疗可明显延长生存时间,对于PS评分较差的患者,单药化疗可能是一个好的选择.     

电视胸腔镜术在老年小结节非小细胞肺癌患者治疗中的应用研究

目的:研究电视胸腔镜术在老年小结节非小细胞肺癌(Small nodules in non small cell lung cancer,sn NSCLC)患者治疗中的应用。方法:回顾2009年1月-2011年6月在我院接受电视胸腔镜术治疗的老年sn NSCLC88例患者的临床资料,按照手术方式将所有患者分为电视胸腔镜组与常规开胸组两个小组。电视胸腔镜组行电视胸腔镜术,常规开胸组行常规开胸术。观察两组患者手术指标、疼痛程度评分、手术前后1 d CRP、TNF-α、IL-6等炎性因子水平、术后并发症、1-3年生存率以及复发率等指标。结果:两组患者一般资料比较无统计学上的差异(P0.05)。电视胸腔镜组术中出血量、术后引流时间、下床活动时间以及疼痛程度评分及术后1 d CRP、TNF-α、IL-6等炎性因子水平及术后并发症发病率均显著低于常规开胸组(P0.05)。电视胸腔镜组术后1、2、3年生存率显著高于常规开胸组(P0.05),且术后复发率显著低于常规开胸组(P0.05)。结论:电视胸腔镜术治疗老年sn NSCLC创口小、恢复快,且有效避免过度激活炎性细胞,降低术后并发症发病率,值得应用于临床。     

老年晚期非小细胞肺癌患者对放化疗的耐受性研究现况

近年多组大规模的随机对照研究已经证实:放化疗对于老年晚期NSCLC患者好于最佳支持治疗(BSC),放化疗组的有效率、中位生存期、一年生存率显著高于BSC组,但老年人伴随着年龄的增长器官功能衰退、药代酶活性下降等生理因素,常合并其他疾病等原因,其药效学和药动学也随之发生变化,老年NSCLC放化疗的潜在毒性危险可能增加,治疗耐受性较差,综合治疗可能带来较多的并发症,甚至高的治疗相关死亡率。中医学认为化疗副反应主要表现为气血亏损、脾胃失调及肝肾虚损等症候群,放疗副反应的症候群以热象较重,属热毒之邪耗气伤阴,进而灼津烁血以致气血、肌肤、脏腑受损的火郁、燥结、热毒症候较多。中医药在减轻放化疗的毒副作用、提高老年患者对放化疗的耐受性等方面有明显优势。     

老年晚期非小细胞肺癌患者对放化疗的耐受性研究现况

近年多组大规模的随机对照研究已经证实：放化疗对于老年晚期NSCLC患者好于最佳支持治疗（BSC）,放化疗组的有效率、中住生存期、一年生存率显著高于BSC组,但老年人伴随着年龄的增长器官功能衰退、药代酶活性下降等生理因素,常合并其他疾病等原因,其药效学和药动学也随之发生变化,老年NSCLC放化疗的潜在毒性危险可能增加,治疗耐受性较差,综合治疗可能带来较多的并发症,甚至高的治疗相关死亡率。中医学认为化疗副反应主要表现为气血亏损、脾胃失调及肝肾虚损等症候群,放疗副反应的症候群以热象较重,属热毒之邪耗气伤阴,进而灼津烁血以致气血、肌肤、脏腑受损的火郁、燥结、热毒症候较多。中医药在减轻放化疗的毒副作用、提高老年患者对放化疗的耐受性等方面有明显优势。     

全胸腔镜肺叶切除联合淋巴结清扫术治疗老年非小细胞肺癌患者的临床研究

目的:了解全胸腔镜肺叶切除联合淋巴结清扫术治疗老年非小细胞肺癌病人的临床效果。方法:选取我院2009年2月到2011年2月接受全胸腔镜肺叶切除联合淋巴结清扫术治疗的老年非小细胞肺癌患者共102例,其中高龄组(≧70岁)24例;非高龄组(70岁)78例。观察两组手术时间、手术中的出血量、术后的住院时间、术后的输血量、胸液总量、胸管放置时间、术后并发症、止痛药使用的次数等情况,并对两组患者进行随访了解其早期生存情况。结果:两组手术时间、术中出血量、术后输血量、术后住院时间、胸液的总量、胸管放置的时间、止痛药的使用次数、术后的并发症、平均的淋巴结数和淋巴结转移情况比较均无统计学差异(P0.05)。非高龄组1年生存率为98.1%,2年生存率为80.3%,高龄组1年生存率为95.3%,2年生存率为73.1%,非高龄组与高龄组早期生存状况比较无统计学意义差异(P0.05)。结论:采用全胸腔镜肺叶切除联合淋巴结清扫术治疗非小细胞肺癌病人,与非高龄病人进行比较,高龄病人能获得同样的治疗疗效和早期预后,所以,可在临床上采纳。     

图像引导放射治疗老年非小细胞肺癌30例

目的:分析图像引导放射治疗(IGRT)对老年非小细胞肺癌患者的临床疗效.方法:30例老年非小细胞肺癌患者,全部采用医科达图像引导放射治疗系统,GTV:60Gy,参考剂量线为95%～98%,分割方式3～4Gy/次.结果:肿瘤完全缓解率为33%(10/30),部分缓解率为50%(15/30),总有效率为83%(25/30).1、2、3年生存率为85%、70%、67%.结论:图像引导放射治疗(IGRT)对老年非小细胞肺癌有较好的局部控制率,是治疗老年非小细胞肺癌患者的有效方法之一.     

新辅助化疗对局部晚期非小细胞肺癌患者术后生存质量的影响

目的:探讨新辅助化疗对局部晚期非小细胞肺癌患者术后生存质量的影响。方法:选取2011年5月至2012年5月于本院胸腔外科接受治疗的ⅢA~ⅢB期非小细胞肺癌患者240例并将其随机分成2组,即新辅助化疗组(A组)和单纯手术组(B组),每组120例。A组患者在临床确诊后接受2个周期的新辅助化疗,化疗结束2~3周后接受手术治疗;对照组患者临床确诊后直接行手术治疗。术后,两组患者均给予4周期常规放化疗。采用QLQ-C30量表对两组患者术前与术后第1、3、6个月的生存质量进行评估,并比较两组患者生存质量评分的差异。结果:术后1、3、6个月时,两组患者的各项功能分值均较术前显著升高(P0.05);术后第3、6个月,患者的总体健康状况得分较术前显著升高(P0.05);术后1个月时,A组患者的呼吸困难评分较术前明显增加(P0.05),术后第3个月后,该分值与术前比较无显著性差异;术后第1、3个月时,两组患者的疼痛评分均较术前明显升高(P0.05),但第6个月时,该评分与术前无显著性差异;术后第6个月时,两组患者的疲乏得分较术前明显降低(P0.05);术后第1、3、6个月时,两组患者的经济困难评分明显较术前升高(P0.05)。术后1、3、6个月时,A组患者的总体状况得分均显著高于B组(P0.05),呼吸困难评分和疲乏评分明显低于B组(P0.05),经济困难评分均显著高于B组(P0.05)。结论:新辅助化疗可以提高局部晚期非小细胞肺癌患者术后半年内的生存质量。     

非小细胞肺癌患者肠道微生物特征分析

[目的]分析非小细胞肺癌患者与肺部良性病变患者肠道微生物的构成差异,探究特异肠道菌群对非小细胞肺癌发生发展的影响.[方法]收集63例患者粪便样本,非小细胞肺癌患者39例,其中肺腺癌(ADC) 32例,肺鳞癌(SCC)7例,肺部良性病变患者24例,进行16S rDNA测序.[结果]毛螺菌属(Lachnospira)、瘤胃...     

非小细胞肺癌患者K-ras基因突变与预后的相关性分析

目的:探讨非小细胞肺癌(NSCLC)患者K-ras基因突变与预后的相关性。方法:回顾分析2006年3月~2008年7月江西省肿瘤医院收治的92例NSCLC患者的临床资料,所有患者均采用蝎形探针扩增阻遏突变系统(ARMS)法行K-ras基因突变检测。结果:92例NSCLC患者中,11例K-ras基因突变阳性,阳性率为11.96%,包括Gly12Cys(GGTTGT)突变3例、Gly12Val(GGTGTT)突变2例、Gly12Ala(GGTGCT)突变2例、Gly12Arg(GGTCGT)突变2例、Gly12Cys(GGTTGT)突变与Gly12Val(GGTGTT)突变并存1例、Gly12Cys(GGTTGT)突变与Gly12Ala(GGTGCT)突变并存1例;K-ras基因突变阳性组与阴性组之间的患者性别、年龄、病理类型、吸烟史相比,差异无统计学意义(P0.05);K-ras基因突变阳性组Ⅲa~Ⅳ期患者中位生存期显著低于K-ras基因突变阴性组Ⅲa~Ⅳ期患者,差异有统计学意义(P0.05)。结论:NSCLC患者K-ras基因突变阳性率较低,但它可以对NSCLC患者预后产生负性影响。     

榄香烯治疗非小细胞肺癌的作用机制研究进展

榄香烯注射液是从天然中草药姜科植物温郁金中提取获得的萜烯类化合物,其主要生物学活性为降低肿瘤细胞有丝分裂能力,诱导肿瘤细胞凋亡,抑制肿瘤细胞的生长,从而改善NSCLC患者的临床症状,增强患者免疫力.本文主要从杀灭癌细胞、诱导癌细胞凋亡、抑制癌细胞血管形成、增强患者免疫力等几方面综述榄香烯注射液对非小细胞肺癌的作用机制.     

Synergistic interaction between cisplatin and PARP inhibitors in non-small cell lung cancer

The antineoplastic agent cis-diammineplatinum(II) dichloride (cisplatin, CDDP) is part of the poorly effective standard treatment of non-small cell lung carcinoma (NSCLC). Here, we report a novel strategy to improve the efficacy of CDDP. In conditions in which CDDP alone or either of two PARP inhibitors, PJ34 hydrochloride hydrate or CEP 8983, used as standalone treatments were inefficient in killing NSCLC cells, the combination of CDDP plus PJ34 or that of CDDP plus CEP 8983 were found to kill a substantial fraction of the cells. This cytotoxic synergy could be recapitulated by combining CDDP and the siRNA-mediated depletion of the principal PARP isoform, PARP1, indicating that it is mediated by on-target effects of PJ34 or CEP 8983. CDDP and PARP inhibitors synergized in inducing DNA damage foci, mitochondrial membrane permeabilization leading to cytochrome c release, and dissipation of the inner transmembrane potential, caspase activation, plasma membrane rupture and loss of clonogenic potential in NSCLC cells. Collectively, our results indicate that CDDP can be advantageously combined with PARP inhibitors to kill several NSCLC cell lines, independently from their p53 status. Combined treatment with CDDP and PARP inhibitors elicits the intrinsic pathway of apoptosis.     

外周血T淋巴细胞亚群及早期炎症标志物表达对老年非小细胞肺癌化疗预后的影响分析

目的评估外周血T淋巴细胞亚群及早期炎症标志物表达对老年非小细胞肺癌(NSCLC)化疗预后的影响。方法入选2015年1月至2018年12月在武汉科技大学附属孝感医院接受化疗的NSCLC患者86例为NSCLC组,另选本院常规体检的健康人群82名作为对照组,分析两组人群外周血T淋巴细胞亚群与炎症细胞的分布差异。采用Kaplan-Meier单因素生存分析不同临床参数及化疗后不同T细胞亚群和炎症细胞水平患者的生存期,采用Cox比例回归风险模型分析影响NSCLC患者预后的独立影响因素。结果与对照组比较,NSCLC组患者CD3^+(71.31±6.02比68.22±7.09)、CD4^+(40.20±5.79比36.61±7.11)、CD4^+/CD8+(1.49±0.37比1.30±0.56),CD8+(28.43±6.37比31.79±9.88)均降低,而PLT(229.73±58.84比211.32±54.18)、淋巴细胞计数(LY)(1.67±0.61比30.01±8.45)及淋巴细胞百分比(LY﹪)(25.65﹪±6.87﹪比30.01﹪±8.45﹪)均升高,差异具有统计学意义(P均<0.05)。Kaplan-Meier单因素生存分析结果显示,是否淋巴转移、远处转移及不同TNM分期的患者生存期相比,差异具有统计学意义(P均<0.05);CD8+T细胞≥31.8﹪、CD4/CD8<1.28、中性粒细胞与淋巴细胞比值(NLR)<3.16及血小板与淋巴细胞比值(PLR)<197的患者生存期较长,差异具有统计学意义(P均<0.05);Cox多因素生存分析结果显示,伴远处转移(HR=9.310)、TNM分期ⅢB-Ⅳ期(HR=1.059)、CD8+T细胞<31.8﹪(HR=2.697)、NLR≥3.16(HR=1.887)及PLR≥197(HR=2.869)是影响老年NSCLC患者预后的独立影响因素(P均<0.05)。结论外周血CD8+T细胞、CD4/CD8比值、NLR及PLR水平是影响老年NSCLC预后的独立影响因素,可作为评估老年NSCLC患者化疗预后的简易生物标志物。     

Drug-induced cell cycle perturbation in chemotherapy of patients with non-small cell lung cancer

To observe in vivo cell cycle perturbation in the chemotherapy of lung cancer, tumour cell kinetics during the first course of chemotherapy were measured in seven patients with histologically-verified non-small cell lung cancer. The tumour cells were aspirated from six lymph nodes and one subcutaneous nodule both prior to treatment and twice weekly after the administration of chemotherapeutic agents. The nuclear DNA content of aspirated tumour cells was measured with a scanning microdensitometer at a wavelength of 550 nm after the modified Feulgen reaction. The cell population in cell cycle was estimated with a cumulated percentage scale. Marked cell cycle perturbation occurred within one week after initiation of chemotherapy. There was a decrease in the G1 cell population, from 70.6 +/- 9.1% to 26.1 +/- 11.4%, and a corresponding increase of cells in G2-M phase, from 21.4 +/- 8.7% to 63.7 +/- 10.0%. The proportion of cells in S phase was slightly increased from 8.0 +/- 1.5% to 10.1 +/- 3.2% during this period. The degree of cell cycle changes was unrelated to the clinical response to chemotherapy.     

Comparison between morphometry and immunostaining of malignant cells in non-small cell lung cancer

OBJECTIVE: To investigate the morphometric properties of tumor cells in combination with the expression of 5 immunomarkers, quantitatively evaluated by image analysis, in a series of 60 non-small cell lung carcinomas (NSCLCs) and to assess their prognostic significance. STUDY DESIGN: Tissue sections from 60 NSCLCs were assessed for the expression of p53, Ki-67, bcl-2, bax and FasL using immunohistochemistry and antibodies. Correlations between morphometric features and clinicopathologic variables, including overall survival and the expression of the above markers, were statistically investigated. RESULTS: Major and minor axis nuclear values, as well as nuclear area and perimeter values, were positively interrelated. No statistically significant correlations were observed between nuclear morphometry and any of the clinicopathologic parameters. p53 Accumulation, when quantitatively estimated, displayed a positive correlation with major axis (P = .008), minor axis (P = .06), nuclear perimeter (P = .006) and mainly nuclear area values (P = .003). Bcl-2- and bax-quantified immunostaining demonstrated a weak negative correlation with shape factor values (P = .039 and P = .025, respectively). Univariate and multivariate analysis showed that stage was the only significant predictor of survival in all patients. In univariate statistical analysis there was a trend between worse survival and shape factor values < 0.8 (P = .0791); this trend almost reached statistical significance in the subgroup of squamous cell carcinomas (P = .0570). CONCLUSION: p53 Accumulation, when quantified, appears to be positively linked with nuclear morphometric values. The prognostic significance of shape factor in NSCLC warrants further investigation.     

Initial medical attention on patients with early-stage non-small cell lung cancer

Background

Detection of early stage non-small cell lung cancer (NSCLC) is commonly believed to be incidental. Understanding the reasons that caused initial detection of these patients is important for early diagnosis. However, these reasons are not well studied.

Methods

We retrospectively reviewed medical records of patients diagnosed with stage I or II NSCLC between 2000 and 2009 at UT MD Anderson Cancer Center. Information on suggestive LC-symptoms or other reasons that caused detection were extracted from patients'' medical records. We applied univariate and multivariate analyses to evaluate the association of suggestive LC-symptoms with tumor size and patient survival.

Results

Of the 1396 early stage LC patients, 733 (52.5%) presented with suggestive LC-symptoms as chief complaint. 347 (24.9%) and 287 (20.6%) were diagnosed because of regular check-ups and evaluations for other diseases, respectively. The proportion of suggestive LC-symptom-caused detection had a linear relationship with the tumor size (correlation 0.96; with p<.0001). After age, gender, race, smoking status, therapy, and stage adjustment, the symptom-caused detection showed no significant difference in overall and LC-specific survival when compared with the other (non-symptom-caused) detection.

Conclusion

Symptoms suggestive of LC are the number one reason that led to detection in early NSCLC. They were also associated with tumor size at diagnosis, suggesting early stage LC patients are developing symptoms. Presence of symptoms in early stages did not compromise survival. A symptom-based alerting system or guidelines may be worth of further study to benefit NSCLC high risk individuals.     

Correlation between immunotherapy biomarker PD-L1 expression and genetic alteration in patients with non-small cell lung cancer

Programmed death-ligand 1 (PD-L1) has been widely used in immunotherapy evaluation of patients with non-small cell lung cancer (NSCLC). However, the effect is not particularly ideal, and the association between PD-L1 and genetic alterations requires more exploration. Here, we performed targeted next-generation sequencing and PD-L1 immunohistochemistry (IHC) testing for PD-L1 expression on both tumor cells (TCs) and tumor-infiltrating immune cells (ICs) in 1549 patients. Our studies showed that surgical method of resection was positively correlated with IC+, and a low tumor mutation burden (TMB) was negatively correlated with TC+. Furthermore, we found that EGFR was mutually exclusive with both ALK and STK11. In addition, the features between PD-L1 expression status and genomic alterations were characterized. These results suggest that clinical characteristics and molecular phenotypes are associated with PD-L1 expression signatures, which may provide novel insights for improving the efficiency of immune checkpoint inhibitors (ICIs) in immunotherapy.