肿瘤M2型丙酮酸激酶在非小细胞肺癌疗效监测中的应用价值

目的研究非小细胞肺癌手术前后血清肿瘤M2型丙酮酸激酶(tumor M2-PK)的应用价值。方法用酶联免疫吸附试验(ELISA)检测56例不同分期的非小细胞肺癌患者手术前后的Tu M2-PK含量的变化并进行分析。结果非小细胞肺癌患者血浆中Tu M2-PK明显高于正常人(P<0.01);非小细胞肺癌患者手术切除和不完全切除血浆中Tu M2-PK均明显低于手术前,无论手术前后,手术切除组血浆Tu M2-PK均显著低于不完全切除组(P<0.01);TNMⅢ期者明显高于Ⅰ、Ⅱ期,有淋巴结转移者显著高于无转移者(P<0.01);而非小细胞肺癌患者的性别、年龄对血浆Tu M2-PK影响无明显差别(P>0.05)。结论血浆Tu M2-PK可成为非小细胞肺癌患者病情监测及预后评估的有效指标。     

核苷酸还原酶M1表达对老年晚期非小细胞肺癌化疗疗效的影响

目的探讨核苷酸还原酶M1(RRM1)的表达对老年晚期非小细胞肺癌(NSCLC)化疗疗效的影响。方法分为治疗组和对照组,每组40例。治疗组通过免疫组织化学法检测肺癌组织RRM1的表达,根据RRM1的表达选择化疗药物,RRM1低表达选择吉西他滨(1 000 mg/m2第1、8天,每21 d为1个周期)化疗,RRM1高表达选择紫杉醇(175 mg/m2第1天,每21 d为1个周期)化疗;对照组只需根据医生的意愿选择吉西他滨或紫杉醇化疗。结果治疗组中不同性别、组织类型及分期患者的RRM1表达差异无统计学意义(P0.05);治疗组的疗效及疾病控制率明显优于对照组(P0.05);两组的治疗方式与不良反应均无明显差异。结论根据RRM1的表达对老年晚期NSCLC患者进行选择性用药。     

艾迪注射液联合化疗治疗晚期非小细胞肺癌临床观察

2004年3月～2005年3月,我科用艾迪注射液联合化疗治疗晚期非小细胞肺癌（NSCLC）33例,并与单纯化疗进行比较。现报告如下。     

老年晚期非小细胞肺癌每周化疗近期疗效观察

目的 评价每周使用去甲长春花碱(NVB)和顺铂(PDD)治疗老年晚期非小细胞肺病(NSCLC)的疗效。方法 治疗70岁以上NSCLC32例，分析其治疗后的近期疗效、毒性反应及治疗前后的机能状况。结果 部分缓解(PR)14例(43.8％)，无进展(NC)15例(46．3％)，进展(PD)3例(9．4％)。用药前KPS评分80分13例，70分19例；用药后90分14例，80分16例。毒性反应主要为骨髓抑制，白细胞下降占81．3％。结论 每周化疗治疗老年晚期NSCLC能提高生活质量，毒性可以耐受。     

盖诺联合放疗治疗晚期非小细胞肺癌的临床研究

目的　观察以盖诺加顺铂联合放疗治疗晚期非小细胞肺癌的临床疗效及毒副作用。方法　 38例晚期非小细胞肺癌患者接受盖诺加顺铂方案联合放疗 ,与同期单纯接受化疗的 36例对比。结果　客观近期有效率 ,中位生存期和 1年、2年、3年生存率 :放化疗组分别为 6 5 .8% ,14个月和 6 3.1%、39.4 %、2 8.9% ;而化疗组为 4 4 .4 % ,11个月和 4 1.6 %、2 7.7%、11.1% ,两组近期有效率有显著性差异 (P<0 .0 5 )。毒副作用可耐受 ,无治疗相关性死亡。结论　以盖诺加顺铂联合放疗治疗晚期非小细胞肺癌有效率较高 ,安全性较好的综合治疗方案 ,值得采用。     

肿瘤标记物在非小细胞肺癌化疗中的应用价值

近年来关于肿瘤标记物在不同组织类型肺癌诊断中应用的研究报道甚多 ,但对其在化疗疗程中的变化及其疗效评判中的应用报道不多。本文对 130例晚期非小细胞肺癌患者以化疗前后的主要血清肿瘤标记物浓度进行了检测 ,并对其化疗前后的变化及其与临床疗效之间的关系进行了分析研究。1　材料与方法1.1　本文 130例研究对象均为 1998年 12月至 2 0 0 1年 11月在上海肺科医院住院诊治的肺癌患者 ,其中男 98人 ,女 32人 ,年龄 37～ 80岁 ,平均年龄 6 2± 10 .0岁 ,其肺癌的诊断均达病理诊断 ,其中鳞癌 5 8例 ,腺癌 72例 ,其临床分期按 1997年 UICC…     

得力生辅助化疗治疗晚期非小细胞肺癌30例疗效观察

1996年10月～2001年10月，我们采用得力生注射液配合DFEP(顺铂、5-尿嘧啶、足叶乙甙、平阳霉素)方案治疗非小细胞肺癌(NSCLC)30例，疗效满意，现报告如下。     

晚期非小细胞肺癌免疫治疗预后评分在免疫联合化疗治疗晚期非小细胞肺癌中的临床意义

目的 回顾性分析基线晚期非小细胞肺癌(NSCLC)免疫治疗预后(EPSILoN)评分与免疫联合化疗治疗晚期NSCLC患者预后之间的关系。方法 纳入应用免疫检查点抑制剂(ICIs)联合含铂双药化疗的晚期NSCLC患者112例为研究组,同期仅接受含铂双药化疗的NSCLC患者120例为对照组。根据EPSILoN评分将患者分为好组(0分)、中间组(1～2分)及差组(3～5分)。收集所有患者一般资料及临床资料并分组进行比较。采用Cox比例风险回归模型分析不同因素与免疫联合化疗治疗NSCLC患者预后的关系。生存分析比较采用log-rank检验。结果 Cox多因素分析结果显示,EPSILoN分组差、有肝脏转移及中性粒细胞与淋巴细胞比值(NLR)>4为影响NSCLC患者无进展生存期(PFS)的独立预后不良因素,EPSILoN分组差、NLR>4为影响NSCLC患者总生存期(OS)的独立预后不良因素(P<0.05)。研究组中EPSILoN评分好组、中间组及差组PFS和OS均依次降低(P<0.001)。结论 EPSILoN评分与晚期NSCLC患者接受免疫联合化疗治疗的疗效和预后呈负相...     

自体细胞生物化疗在晚期非小细胞肺癌治疗中的临床应用

目的探讨树突状细胞(dendritic cells,DCs)和细胞因子诱导的杀伤细胞(cytokine-induced killers,CIKs)联合化疗对晚期非小细胞肺癌(NSCLC)患者的疗效。方法 DC-CIK细胞治疗联合化疗的ⅢB期、Ⅳ期非小细胞肺癌患者为治疗组,同期相同入组标准的单纯化疗者作为对照组。治疗组和对照组各40例,比较两组患者治疗前后外周血T细胞亚群、临床疗效、生活质量变化等。结果两组的一般资料基线水平一致。与对照组相比,治疗组T细胞亚群变化无统计学意义(P>0.05)。治疗组疾病控制率[DCR(90%)]明显高于对照组DCR(72.5%),差异具有统计学意义(P<0.05)。两组中位无进展生存期(progression free survival,PFS)分别为275 d vs.212 d,治疗组PFS长于对照组(P<0.05)。但两组间客观缓解率(objective response rate,ORR)、总生存期(overall survival,OS)无统计学意义(P>0.05)。治疗后生活质量(KPS)评分下降者,治疗组较对照组少(P<0.05),未见不可耐受不良反应。结论自体DC-CIK联合化疗的生物化疗模式,可提高晚期NSCLC患者疾病控制率、延长无进展生存期,改善患者生活质量。     

老年晚期非小细胞肺癌的临床特点及对化疗的耐受性和疗效

目的分析老年晚期非小细胞肺癌(NSCLC)的临床特点,探讨采用化疗治疗后的患者的耐受性与临床疗效。方法选取200例晚期NSCLC患者,并根据患者的年龄,将60~80岁的100例患者设为观察组,将50~59岁的100例患者设为对照组,给予观察组患者采用吉西他滨联合顺铂,给予对照组采用盖诺联合顺铂进行治疗。在治疗结束后对两组患者的临床疗效、毒副反应进行分析。并对两组患者治疗后血清VEGF浓度进行检测。结果观察组的临床疗效与对照组相比并无显著差异(P0.05);观察组中位生存期优于对照组;观察组毒副反应明显高于对照组,但是均可以耐受化疗。治疗前观察组与对照组VEGF水平无明显差异,治疗后观察组较对照组VEGF水平明显降低且两组治疗后均较治疗前明显降低。结论对于老年患者,顺铂的剂量可降低三分之一,降低毒副反应的作用。     

联合检测肿瘤M2型丙酮酸激酶、CEA对并发胸腔积液的肺癌的诊断价值

目的检测胸腔积液中肿瘤M2型丙酮酸激酶（TumorM2-Pyruvate kinase,Tu M2-PK）和癌胚抗原（carcinoembbry-onicantigen,CEA）,探讨M2-PK和CEA在并发胸腔积液的肺癌患者的临床诊断价值。方法利用夹心ELISA法测定44例良性胸液和35例并发胸腔积液的肺癌患者的M2-PK,CEA值。比较两组之间的差异。结果肺癌并胸腔积液组M2-PK、CEA值分别为（28.45±8.63）U/m l,（19.55±12.93）ng/ml;良性胸液组M2-PK、CEA值分别为（19.48±6.75）U/mL,（7.79±4.47）ng/m l,恶性胸液组中M2-PK和CEA值均明显高于良性胸液组（P〈0.05）。联合检测的灵敏度为82.86%,特异度为63.64%,阳性预测值为64.44%及阴性预测值为82.35%。联合检测胸腔积液中的M2-PK和CEA能够显著提高并发胸腔积液患者的肺癌诊断水平。结论 M2-PK和CEA在恶性胸液组中明显升高,联合检测胸液中M2-PK和CEA可提高对并发胸腔积液的肺癌患者的诊断水平。     

肺癌相关抗原检测对非小细胞肺癌的诊断意义

目的探讨肺癌相关抗原（lung tumor antigen LTA）在纤维支气管镜支气管肺泡灌洗液、胸水和血清中的检测结果对肺癌的临床诊断意义。方法收集72例非小细胞肺癌（non-small cell lung cancerNSCLC）伴胸腔积液患者和对照组68例肺部良性病变（benign lungdisease BLD）患者的支气管肺泡灌洗液、胸水及血清样本,运用LTA检测试剂用快速乳胶凝集法分别检测,并对所得数据进行统计分析。结果肿瘤组病人支气管肺泡灌洗液、胸水和血清的LTA检测阳性率分别为58％、67％和75％,对照组三者的阳性检出率分别为22％、17％和20％,两组比较均有明显差异（P〈0．05）。LTA阳性检出率以肿瘤组的血清样本最高,达75％。特异性以胸水样本最高,为82％。结论支气管肺泡灌洗液、胸水和血清IJTA检测对肺癌的诊断有一定的临床参考意义。     

112例非小细胞肺癌淋巴结转移规律分析

目的分析112例非小细胞肺癌淋巴结的转移规律。方法对112例肺癌患者施行手术切除并行广泛肺门、叶间及纵隔淋巴结清扫术。术后病理资料进行统计分析。结果在共清除898组淋巴结中,单纯N1淋巴结转移率为24.1%,N2(包括N1+N2)淋巴结转移率30.4%。原发肺癌(T)分期T1、T2、T3间淋巴结转移率差异有统计学意义(P0.01)。跳跃式转移占N2转移的35.3%。结论非小细胞肺癌的淋巴结转移与T分期有关,具有较多的跳跃性纵隔淋巴结转移发生,肿瘤部位及肺癌的病理学类型与淋巴结的转移无明显关系。外科治疗中应注意广泛清扫肺内、同侧纵隔淋巴结才有可能达到根治目的。     

培美曲塞治疗晚期非小细胞肺癌近期疗效及毒性反应研究

目的研究多靶点叶酸拮抗剂培美曲塞治疗晚期非小细胞肺癌(NSCLC)的近期疗效和毒性反应。方法收集我院2008年1月至2010年1月资料完整的晚期非小细胞肺癌患者共18例,男10例,女8例,中位年龄51岁(范围32～68岁),均经组织学和/或细胞学证实,因化疗后出现复发或进展而采用培美曲塞化疗。化疗方案为培美曲塞500mg/m2单药或联合顺铂75mg/m2,每3周重复;对接受两个或两个以上化疗周期的患者进行化疗效果及副反应评价。结果 18例可评价疗效,无完全缓解(CR)病例,部分缓解(PR)仅2例,稳定者(SD)共12例,4例疾病进展(PD)。全组有效率(CR+PR)为11.1%(2/18),疾病控制率(DCR)为77.8%(14/18)。中位生存时间9.2个月,中位疾病进展时间2.8个月,1年生存率为31.2%。未出现化疗相关死亡,毒副反应主要为I～Ⅲ度胃肠道反应和骨髓抑制。结论培美曲塞治疗复治晚期NSCLC安全有效,耐受性良好。     

Clinical adjustability of radiological tools in patients with surgically resected cT1N0-staged non-small-cell lung cancer from the long-term survival evaluation

BackgroundVarious radiological tools have been introduced to determine the malignancy or prognosis of lung carcinomas. We retrospectively summarized the clinical outcomes to evaluate whether radiological tools such as consolidation-to-tumor ratio (CTR), tumor disappearance ratio (TDR), and mediastinal diameter (MD) are suitable for surgically resected non-small-cell lung cancer (NSCLC).MethodsThis retrospective study included 260 patients (128 men and 132 women; median age, 64 years) with cT1N0-staged NSCLC who underwent thoracotomy. Disease-free survival (DFS) and overall survival (OS) outcomes were analyzed using the Kaplan-Meier method and Cox proportional hazards model.ResultsWhen the adjusted hazard ratios (HRs) with reference to cT1a/1 mi were calculated, significant differences were observed in cT1b and cT1c for DFS (P=0.04 and P<0.01, respectively) and in cT1c for OS (P=0.01). For HRs with reference to CTR (≤0.5), a significant difference was only observed in CTR (>0.5) for DFS (P=0.01). For HRs with reference to TDR (≤25%), significant differences were observed in TDR (>75%) for DFS (P=0.02) and OS (P=0.02). For HRs with reference to MD (≤5 mm), significant differences were observed in 6–20 mm (P=0.04) and >20 mm (P=0.02) for DFS and in >20 mm (P=0.02) for OS.ConclusionsAll radiological tools revealed significant correlations with prognosis in the patients with cT1N0-staged NSCLCs. We recommend the use of MD in a clinical context. However, further investigation of this issue is needed.     

High serum C-reactive protein levels predict survival in patients with treated advanced lung adenocarcinoma

BackgroundThe prognosis of non-small cell lung cancer (NSCLC) varies greatly depending on whether or not it can receive molecular-targeted drug treatment including epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). We investigated the clinical utility of C-reactive protein (CRP) levels measured at the time of diagnosis in EGFR-mutant and wild-type NSCLC patients who had undergone first-line therapy.MethodsSerum CRP levels were analyzed in 213 patients, of whom 89 patients had advanced EGFR-mutated NSCLC who underwent first-line EGFR-TKI treatment. We used Cox proportional hazards models to study the relationship between CRP and overall survival (OS). CRP cutoff values were obtained from the receiver operating characteristic curve.ResultsMean serum CRP level in treated NSCLC patients were not significantly different in patients with or without EGFR mutations. The optimal CRP cutoff values were 8.1 mg/L for EGFR-mutated NSCLC and 16.7 mg/L for EGFR-wild NSCLC. Based on multivariate analysis, high CRP level (EGFR-mutated, HR: 2.479, 95% CI: 1.331–4.619, P=0.004; EGFR-wild, HR: 3.625, 95% CI: 2.149–6.116, P<0.001) was a significant and independent negative prognostic factor for OS in patients with or without EGFR mutations.ConclusionsHigh CRP levels predicted a lack of response to treatment in patients with advanced lung adenocarcinoma with or without EGFR mutations. Thus, the CRP level is a good and easy to use prognostic factor and objective indicator for clinical practice.     

Plasma thymidylate synthase and dihydrofolate reductase mRNA levels as potential predictive biomarkers of pemetrexed sensitivity in patients with advanced non-small cell lung cancer

BackgroundHigh levels of thymidylate synthase (TS) and dihydrofolate reductase (DHFR) expression in tumour tissues are an indicator of ineffective responses to pemetrexed-based chemotherapy in various tumours, including non-small cell lung cancer (NSCLC). However, tumour tissues are highly heterogeneous, so a single biopsy may not reflect genetic alterations during disease progression. This study investigated the potential use of plasma TS and DHFR mRNA levels as biomarkers for predicting sensitivity to pemetrexed-based chemotherapy.MethodsPlasma samples were obtained from 245 patients with advanced NSCLC and 30 healthy donors. Total RNA was extracted from the plasma samples, and TS and DHFR mRNA levels were determined via real-time PCR. TS and DHFR mRNA levels between cancer patients and healthy controls were compared. The association between plasma TS and DHFR mRNA levels and tumour response to pemetrexed/cisplatin chemotherapy was analysed.ResultsThe plasma TS and DHFR mRNA levels decreased in patients with advanced NSCLC compared with healthy controls. Moreover, plasma TS and DHFR mRNA levels negatively correlated with tumour response to pemetrexed/cisplatin chemotherapy in patients with advanced NSCLC. Overall survival time was prolonged in patients with low TS mRNA expression compared with those with high TS mRNA expression, although the difference was not statistically significant.ConclusionsLow expression levels of plasma TS and DHFR mRNA confer increased tumour sensitivity to pemetrexed/cisplatin chemotherapy in patients with advanced NSCLC. The results suggested that plasma TS and DHFR mRNA levels are promising biomarkers for choosing patients who are likely to respond and benefit the most from pemetrexed-based chemotherapy.     

A narrative review of advances in treatment and survival prognosis of HER2-positive malignant lung cancers

Human epidermal growth factor receptor 2 (HER2), as a receptor tyrosine kinase of EGF receptor family, whose mutation is often associated with even if less frequency but poor prognosis and shorter survival in pulmonary malignant tumor. HER2 status include mutation, overexpression, amplification and also some rare genotypes, detected by next generation sequencing (NGS), immunohistochemistry (IHC), and also fluorescence in situ hybridization (FISH). Different genotypes represent different therapeutic targets and indicate different clinical prognosis concluded by previous studies. Unfortunately, no standard guidelines for first-line treatment are widely recognized, and current therapeutic schedules include chemotherapy, radiotherapy, targeted therapy, and immunotherapy. Especially for patients with advanced metastasis, chemotherapy is based as a systemic therapy using studies of breast cancer or EGFR-positive lung adenocarcinoma as a template. Studies already explored treatment including EGFR tyrosine kinase inhibitors (TKIs) such as gefitinib and afatinib, and also trastuzumab and its conjugation like HER2-targeted antibody-drug conjugate trastuzumab emtansine (T-DM1) and conjugate trastuzumab deruxtecan (T-DXd). Also, he researches explored combination therapy with chemotherapy and TKIs or monoclonal antibodies. This review describes commonly used therapies for HER2-positive/HER2-overexpression patients and general relationship between genotypes of HER2, drug selection and final prognosis in order to provide suggestions for future diagnosis and treatment.     

A study of weekly docetaxel and carboplatin as first-line chemotherapy for advanced non-small cell lung cancer

Background

Weekly docetaxel demonstrated similar efficacy but better tolerability than standard triweekly docetaxel, and carboplatin was less nephrotoxic, neurotoxic and emetogenic than cisplatin. This study aimed to evaluate the efficacy and safety of weekly docetaxel with carboplatin as first-line chemotherapy for advanced non-small cell lung cancer (NSCLC).

Methods

Forty-three Chinese patients have been included. Patients were administered docetaxel at a dose of 35 mg/m² on days 1, 8, 15 and carboplatin at an area under the curve (AUC) 5 on day 1 every 28-day cycle (maximum six cycles).

Results

Of the 43 eligible patients, the assessed overall response rate (RR) was 30.2% with 30.2% partial response (PR) in 13 patients, 48.8% stable disease (SD) in 21 patients and 20.9% progressive disease (PD) in 9 patients. The estimated median progression free survival and median overall survival (OS) time were respectively, 120 days (95% CI: 80-160 days) and 340 days (95% CI: 224-456 days) with the patients surviving of 46.5% (95% CI: 31.6-61.4%) at one year and 20.0% (95% CI: 7.1-33.3%) at two years. The major grade 3/4 hematological toxicities were included leucocytopenia in 6 patients (13.9%) and neutropenia in 8 patients (18.6%). One patient (2.3%) suffered grade 1 febrile neutropenia. All grade of the nonhematological toxicities, such as nausea, vomiting, alopecia and fatigue held the proportion of 48.8% (grade 3/4 4.6%), 27.9%, 55.8% and 53.5% (grade 3/4 9.3%), respectively.

Conclusions

The combination of weekly docetaxel and carboplatin showed feasible efficacy with acceptable hematologic toxicities for advanced lung cancer.