Risk factors of postoperative recurrences in patients with clinical stage I NSCLC

Background

Despite advances in radiation therapy, chemotherapy, and newly developed molecular targeting therapies, long-term survival after resection for patients with NSCLC remains less than 50%. We investigated factors predicting postoperative locoregional recurrences and distant metastases in patients with clinical stage I non-small-cell lung cancer (NSCLC) after surgical resection.

Methods

All patients with clinical stage I NSCLC, who underwent surgical resection between January 2002 and June 2006, were reviewed retrospectively. Multiple logistic regression analyses were used to identify independent risk factors for patients with locoregional recurrences and distant metastases.

Results

A total of 261 patients were eligible. Overall survival was significant related to locoregional recurrences (P?=?0.03) and distant metastases (P <0.001). There were significant differences of locoregional recurrence in tumor differentiation (P?=?0.032) and advanced pathological stage (P?=?0.002). In the group of distant metastases, there were significant differences in tumor differentiation (P?=?0.035), lymphovascular space invasion (P?=?0.031). Among the relationship between pattern of distant metastasis and clinicopathologic variables in patients with clinical stage I NSCLC, SUVmax (P?=?0.02) and tumor size (P?=?0.001) had significant differences. According to multiple logistic regression analysis, tumor differentiation is the only risk factor of postoperative outcome for locoregional recurrence and serum CEA (>3.5 ng/mL) is the predictor of distant metastasis.

Conclusions

Tumor differentiation and serum CEA were predictors of postoperative relapse for clinical stage I NSCLC after surgical resection. Risk factors of postoperative recurrence in patients with clinical stage I NSCLC may enable us to optimize the patient selection for postoperative adjuvant therapies or neoadjuvant treatment before surgery.     

Increased CYFRA 21-1, CEA and NSE are Prognostic of Poor Outcome for Locally Advanced Squamous Cell Carcinoma in Lung: A Nomogram and Recursive Partitioning Risk Stratification Analysis

OBJECTIVES: This study aimed to: (1) assess the prognostic significance of serum tumor markers in locally advanced squamous cell carcinoma in lung (LA-SCCL); (2) generate a nomogram to predict the overall survival (OS) and (3) identify a prognostic stratification to assist the therapeutic decision-making. METHODS: LA-SCCL patients receiving definitive radiotherapy and baseline tumor marker measurement were eligible for this retrospective study. Cox proportional hazards regression was used to determine independent factors associated with various survival indexes and a nomogram was created to estimate the 5-year OS probability for individual patient. The identified prognostic factors were recruited into a recursive partitioning analysis (RPA) for OS to stratify patients with distinct outcome. RESULTS: A total of 224 patients were eligible for analysis. Increased cytokeratin-19 fragment (CYFRA 21-1) was independently associated with inferior OS, progression free survival (PFS) and a borderline decreased local-regional progression free survival (LRPFS). Elevated carcino-embryonic antigen (CEA) served as an unfavorable determinant for OS and increased neuron-specific enolase (NSE) was predictive of poor distant metastasis free survival (DMFS). A nomogram integrating KPS, TNM stage, CEA and CYFRA 21-1 was created, resulting in a c-index of 0.62. RPA identified 4 prognostic classifications, with median OS of 27.6, 19.9, 17.3 and 10.9?months for low, intermediate, high and very-high risk groups, respectively. CONCLUSIONS: Baseline tumor marker panel including CYFRA 21-1, CEA and NSE can be prognostic of outcome for LA-SCCL receiving definitive radiotherapy. The RPA identified four prognostic subgroups, which could assist personalized therapy and clinical trial design in LA-SCCL.     

Impact of Antiretroviral Therapy on Incidence of Pregnancy among HIV-Infected Women in Sub-Saharan Africa: A Cohort Study

Background

With the rapid expansion of antiretroviral therapy (ART) services in sub-Saharan Africa there is growing recognition of the importance of fertility and childbearing among HIV-infected women. However there are few data on whether ART initiation influences pregnancy rates.

Methods and Findings

We analyzed data from the Mother-to-Child Transmission-Plus (MTCT-Plus) Initiative, a multicountry HIV care and treatment program for women, children, and families. From 11 programs in seven African countries, women were enrolled into care regardless of HIV disease stage and followed at regular intervals; ART was initiated according to national guidelines on the basis of immunological and/or clinical criteria. Standardized forms were used to collect sociodemographic and clinical data, including incident pregnancies. Overall 589 incident pregnancies were observed among the 4,531 women included in this analysis (pregnancy incidence, 7.8/100 person-years [PY]). The rate of new pregnancies was significantly higher among women receiving ART (9.0/100 PY) compared to women not on ART (6.5/100 PY) (adjusted hazard ratio, 1.74; 95% confidence interval, 1.19–2.54). Other factors independently associated with increased risk of incident pregnancy included younger age, lower educational attainment, being married or cohabiting, having a male partner enrolled into the program, failure to use nonbarrier contraception, and higher CD4 cell counts.

Conclusions

ART use is associated with significantly higher pregnancy rates among HIV-infected women in sub-Saharan Africa. While the possible behavioral or biomedical mechanisms that may underlie this association require further investigation, these data highlight the importance of pregnancy planning and management as a critical but neglected component of HIV care and treatment services. Please see later in the article for the Editors'' Summary     

A Real-World Study in Advanced Non–Small Cell Lung Cancer with KRAS Mutations

BACKGROUND: KRAS gene mutations are well known as a key driver of advanced non–small cell lung cancer (NSCLC). The impact of KRAS-mutant subtypes on the survival benefit from salvage chemotherapy is controversial. Here, we present a real-world study in patients across China with advanced NSCLC with KRAS mutations using a website-based patient self-report system. METHODS: We identified a total of 75 patients diagnosed with KRAS-mutant (determined by molecular sequencing) advanced NSCLC between 2014/5/9 and 2019/5/30. KRAS mutation subtypes were divided into G12C and non-G12C groups for statistical analysis. The clinicopathological characteristics and treatment survival benefit in all patients with a KRAS mutation were evaluated. Programmed death-ligand 1 (PD-L1) expression data were collected from 30 patients in the same cohort. RESULTS: In this study, 23 patients with stage IIIB NSCLC and 52 patients with stage IV NSCLC were enrolled with 58 men and 17 women; the median age was 60 years (39–84). All patients received regular chemotherapy/radiotherapy/targeted therapy/immune therapy as per the disease condition. Four main KRAS mutation subtypes were detected: G12C (33%), G12V (19%), G12A (12%), and G12D (12%). Three predominant KRAS comutations were detected: TP53-KRAS (31%), EGFR-KRAS (11%), and STK11-KRAS (8%). Compared with the KRAS non-G12C mutation subtype, patients with the KRAS G12C mutation had potentially longer progression-free survival (PFS) after first-line chemotherapy (4.7 vs. 2.5 months, p < 0.05). Pemetrexed-based chemotherapy appeared to be superior to taxanes- and gemcitabine-based chemotherapies in all patients (PFS: 5.0 vs. 1.5 and 2.3 months, respectively, p > 0.05). Cox regression analysis showed that the KRAS G12C mutation and pemetrexed-based first-line chemotherapy were positive influencers for PFS after first-line (hazard ratios = 0.31 and 0.55, respectively, P < 0.05), but not second-line chemotherapies. CONCLUSION: The KRAS G12C mutation could be a predictive biomarker for better survival benefit from first-line chemotherapy in patients with advanced NSCLC and KRAS mutations. The first-line chemotherapy regimen could possibly influence the outcome in patients with KRAS mutations. Larger and prospective clinical trials are warranted to confirm our conclusions.     

Early CYFRA 21-1 variation predicts tumor response to chemotherapy and survival in locally advanced non-small cell lung cancer patients

We have evaluated CYFRA 21-1 serum level variations as an indicator of tumor response and survival in 44 consecutive patients with locally advanced non-small cell lung cancer (NSCLC) treated with induction chemotherapy (IC). Irrespective of the initial CYFRA 21-1 serum concentration, a more than 65% decrease in the serum level after the first chemotherapy course was significantly predictive of an objective tumor response (p = 0.0022). In addition, a more than 80% decrease in this level significantly predicted a better disease-free survival (p = 0.039). In patients with initial CYFRA 21-1 serum levels > 3.3 ng/mL (n = 29), a more than 80% decrease after the first IC course was the most significant predictor of overall survival (p = 0.025) in a Cox analysis including initial staging, tumor response and surgery. We conclude that early monitoring of CYFRA 21-1 serum levels may be a useful prognostic tool for tumor response and survival in stage III NSCLC patients treated by induction chemotherapy.     

Association of TERT Polymorphisms with Clinical Outcome of Non-Small Cell Lung Cancer Patients

TERT is of great importance in cancer initiation and progression. Many studies have demonstrated the TERT polymorphisms as risk factors for many cancer types, including lung cancer. However, the impacts of TERT variants on cancer progression and treatment efficacy have remained controversial. This study aimed to investigate the association of TERT polymorphisms with clinical outcome of advanced non-small cell lung cancer (NSCLC) patients receiving first-line platinum-based chemotherapy, including response rate, clinical benefit, progression-free survival (PFS), overall survival (OS), and grade 3 or 4 toxicity. Seven polymorphisms of TERT were assessed, and a total of 1004 inoperable advanced NSCLC patients treated with platinum-based chemotherapy were enrolled. It is exhibited that the variant heterozygote of rs4975605 showed significant association with a low rate of clinical benefit, and displayed a much stronger effect in never-smoking female subset, leading to the clinical benefit rate decreased from 82.9% (C/C genotype) to 56.4% (C/A genotype; adjusted OR, 3.58; P=1.40×10^-4). It is also observed that the polymorphism rs2736109 showed significant correlation with PFS (log-rank P=0.023). In age > 58 subgroup, patients carrying the heterozygous genotype had a longer median PFS than those carrying the wild-type genotypes (P=0.002). The results from the current study, for the first time to our knowledge, provide suggestive evidence of an effect of TERT polymorphisms on disease progression variability among Chinese patients with platinum-treated advanced NSCLC.     

全胸腔镜肺叶切除术治疗早期非小细胞肺癌患者的预后分析

目的:探讨全胸腔镜肺叶切除术治疗早期非小细胞肺癌(NSCLC)患者的疗效及预后状况。方法:选择2010年6月至2013年6月我院收治的早期NSCLC患者80例作为研究对象,随机分为对照组(n=40)和实验组(n=40)。对照组患者行常规开胸肺叶切除术,实验组患者行全胸腔镜肺叶切除术,所有患者于术后视具体情况给予化疗或放疗。记录两组患者术中及术后临床相关指标,术后并发症发生率,术后随访3年,比较两组患者3年生存率,并分析全胸腔镜肺叶切除术后患者预后影响因素。结果:实验组患者手术时间、术中出血量、胸腔引流时间及住院时间均明显低于对照组(P0.05)。实验组患者术后并发症发生率、术后3年生存率分别为12.50%、57.50%,与对照组的17.50%、50.00%相比,差异均无统计学意义(P0.05)。Cox多因素分析结果显示,肿瘤直径和术后是否放化疗是影响全胸腔镜肺叶切除术后患者预后的危险因素(P0.05)。结论:全胸腔镜肺叶切除术治疗早期NSCLC患者具有微创、安全及远期生存率较高的特点,术后辅以放化疗能够延长患者的生存率。     

Risk of a permanent work-related disability pension after incident venous thromboembolism in Denmark: A population-based cohort study

BackgroundLong-term complications of venous thromboembolism (VTE) hamper physical function and impair quality of life; still, it remains unclear whether VTE is associated with risk of permanent work-related disability. We aimed to assess the association between VTE and the risk of receiving a permanent work-related disability pension and to assess whether this association was explained by comorbidities such as cancer and arterial cardiovascular disease.Methods and findingsA Danish nationwide population-based cohort study consisting of 43,769 individuals aged 25 to 66 years with incident VTE during 1995 to 2016 and 218,845 birth year-, sex-, and calendar year-matched individuals from the general population, among whom 45.9% (N = 120,540) were women, was established using Danish national registries. The cohorts were followed throughout 2016, with permanent work-related disability pension as the outcome. Hazard ratios (HRs) with 95% confidence intervals (CIs) for disability pension were computed and stratified by sex and age groups (25 to 34, 35 to 44, 45 to 54, and 55 to 66 years of age) and adjusted for comorbidities and socioeconomic variables.Permanent work-related disability pensions were granted to 4,415 individuals with VTE and 9,237 comparison cohort members (incidence rates = 17.8 and 6.2 per 1,000 person-years, respectively). VTE was associated with a 3-fold (HR 3.0, 95% CI: 2.8 to 3.1) higher risk of receiving a disability pension. Adjustments for socioeconomic status and comorbidities such as cancer and cardiovascular diseases reduced the estimate (HR 2.3, 95% CI: 2.2 to 2.4). The risk of disability pension receipt was slightly higher in men than in women (HR 2.5, 95% CI: 2.3 to 2.6 versus HR 2.1, 95% CI: 2.0 to 2.3). As this study is based on medical and administrative registers, information on post-VTE care, individual health behavior, and workplace factors linked to disability pension in the general population are lacking. Furthermore, as disability pension schemes vary, our results might not be directly generalizable to other countries or time periods.ConclusionsIn this study, incident VTE was associated with increased risk of subsequent permanent work-related disability, and this association was still observed after accounting for comorbidities such as cancer and cardiovascular diseases. Our results emphasize the social consequences of VTE and may help occupational and healthcare professionals to identify vulnerable individuals at risk of permanent exclusion from the labor market after a VTE event.

In a population-based cohort study, Helle Jørgensen and colleagues investigate the risk of receiving a permanent work-related disability pension after incident venous thromboembolism in Denmark.     

Development of predictive models to identify advanced-stage cancer patients in a US healthcare claims database

BackgroundAlthough healthcare databases are a valuable source for real-world oncology data, cancer stage is often lacking. We developed predictive models using claims data to identify metastatic/advanced-stage patients with ovarian cancer, urothelial carcinoma, gastric adenocarcinoma, Merkel cell carcinoma (MCC), and non-small cell lung cancer (NSCLC).MethodsPatients with ≥1 diagnosis of a cancer of interest were identified in the HealthCore Integrated Research Database (HIRD), a United States (US) healthcare database (2010–2016). Data were linked to three US state cancer registries and the HealthCore Integrated Research Environment Oncology database to identify cancer stage. Predictive models were constructed to estimate the probability of metastatic/advanced stage. Predictors available in the HIRD were identified and coefficients estimated by Least Absolute Shrinkage and Selection Operator (LASSO) regression with cross-validation to control overfitting. Classification error rates and receiver operating characteristic curves were used to select probability thresholds for classifying patients as cases of metastatic/advanced cancer.ResultsWe used 2723 ovarian cancer, 6522 urothelial carcinoma, 1441 gastric adenocarcinoma, 109 MCC, and 12,373 NSCLC cases of early and metastatic/advanced cancer to develop predictive models. All models had high discrimination (C > 0.85). At thresholds selected for each model, PPVs were all >0.75: ovarian cancer = 0.95 (95% confidence interval [95% CI]: 0.94–0.96), urothelial carcinoma = 0.78 (95% CI: 0.70–0.86), gastric adenocarcinoma = 0.86 (95% CI: 0.83–0.88), MCC = 0.77 (95% CI 0.68–0.89), and NSCLC = 0.91 (95% CI 0.90 – 0.92).ConclusionPredictive modeling was used to identify five types of metastatic/advanced cancer in a healthcare claims database with greater accuracy than previous methods.     

The Frequency and Clinical Implication of ROS1 and RET Rearrangements in Resected Stage IIIA-N2 Non-Small Cell Lung Cancer Patients

To evaluate the frequency and clinicopathological features of ROS1 and RET rearrangements in N2 node positive stage IIIA (IIIA-N2) non-small cell lung cancer (NSCLC) patients, we retrospectively screened 204 cases with a tissue microarray (TMA) panel by fluorescent in situ hybridization (FISH), and confirmed by direct sequencing and immunohistochemistry (IHC). The relationship between ROS1 or RET rearrangements, clinicopathological features, and prognostic factors were analyzed in resected stage IIIA-N2 NSCLC. Of the 204 cases, 4 cases were confirmed with ROS1 rearrangement, but no RET rearrangement was detected. All 4 ROS1-rearranged cases were adenocarcinomas. The predominant pathological type was acinar pattern in ROS1-rearranged tumors, except for 1 case harboring a mixture acinar and mucous tumor cells. Variants of ROS1 rearrangement were SDC4-ROS1 (E2:E32), SDC4-ROS1 (E4:E32) and SDC4-ROS1 (E4:E34). There was no significant association between ROS1 rearrangement and clinicopathological characteristics. In this cohort, multivariate analysis for overall survival (OS) indicated that squamous cell carcinoma and lobectomy were independent predictors of poor prognosis; R0 surgical resection and non-pleural invasion were independent predictors of good prognosis. In resected stage IIIA-N2 NSCLC patients, ROS1-rearranged cases tended to occur in younger patients with adenocarcinomas. The prognosis of resected stage IIIA-N2 is generally considered poor, but patients with ROS1 rearrangement will benefit from the targeted therapy.     

红细胞分布宽度、中性粒细胞与淋巴细胞比值与晚期非小细胞肺癌患者临床病理特征及预后的关系研究

目的:探讨红细胞分布宽度(RDW)、中性粒细胞与淋巴细胞比值(NLR)与晚期非小细胞肺癌(NSCLC)患者临床病理特征及预后的关系。方法:选择2017年5月至2019年5月我院收治的106例确诊为晚期NSCLC患者(NSCLC组)和门诊接诊的102例体检正常者(对照组)作为研究对象。检测RDW、NLR,分析RDW、NLR与NSCLC患者临床病理特征以及预后的关系。结果:NSCLC组RDW、NLR高于对照组(P<0.05),年龄≥60岁、淋巴结转移NSCLC患者RDW高于年龄<60岁、无淋巴结转移NSCLC患者(P<0.05),TNM分期为Ⅳ期、淋巴结转移NSCLC患者NLR高于TNM分期为Ⅲ期、无淋巴结转移患者(P<0.05)。Kaplan-Meier生存曲线分析结果显示高RDW组、高NLR组NSCLC患者生存率低于低RDW组、低NLR组(P<0.05)。单因素COX回归分析显示分化程度、TNM分期、淋巴结转移、RDW、NLR与NSCLC预后有关(P<0.05),多因素COX回归分析显示淋巴结转移、RDW、NLR与NSCLC患者预后相关(P<0.05)。结论:晚期NSCLC患者RDW、NLR较高,RDW与年龄、淋巴结转移有关,NLR与TNM分期和淋巴结转移有关,高水平RDW、NLR预示着NSCLC预后不良,可作为预后评估的辅助指标。     

Tumor BRCA1, RRM1 and RRM2 mRNA Expression Levels and Clinical Response to First-Line Gemcitabine plus Docetaxel in Non-Small-Cell Lung Cancer Patients

Background

Overexpression of RRM1 and RRM2 has been associated with gemcitabine resistance. BRCA1 overexpression increases sensitivity to paclitaxel and docetaxel. We have retrospectively examined the effect of RRM1, RRM2 and BRCA1 expression on outcome to gemcitabine plus docetaxel in advanced non-small-cell lung cancer (NSCLC) patients.

Methodology and Principal Findings

Tumor samples were collected from 102 chemotherapy-naïve advanced NSCLC patients treated with gemcitabine plus docetaxel as part of a randomized trial. RRM1, RRM2 and BRCA1 mRNA levels were assessed by quantitative PCR and correlated with response, time to progression and survival. As BRCA1 levels increased, the probability of response increased (Odds Ratio [OR], 1.09: p = 0.01) and the risk of progression decreased (hazard ratio [HR], 0.99; p = 0.36). As RRM1 and RRM2 levels increased, the probability of response decreased (RRM1: OR, 0.97; p = 0.82; RRM2: OR, 0.94; p<0.0001) and the risk of progression increased (RRM1: HR, 1.02; p = 0.001; RRM2: HR, 1.005; p = 0.01). An interaction observed between BRCA1 and RRM1 allowed patients to be classified in three risk groups according to combinations of gene expression levels, with times to progression of 10.13, 4.17 and 2.30 months (p = 0.001). Low BRCA1 expression was the only factor significantly associated with longer time to progression in 31 patients receiving cisplatin-based second-line therapy.

Conclusions

The mRNA expression of BRCA1, RRM1 and RRM2 is potentially a useful tool for selecting NSCLC patients for individualized chemotherapy and warrants further investigation in prospective studies.     

早期非小细胞肺癌患者血清巨噬细胞抑制因子-1、趋化素与临床病理特征及预后的关系

目的:探讨早期非小细胞肺癌(NSCLC)患者血清巨噬细胞抑制因子-1(MIC-1)、趋化素(chemerin)水平与临床病理特征及预后的关系。方法:选择72例NSCLC患者(NSCLC组)、53例肺良性疾病患者(良性组)、50例体检健康人群(对照组),分别检测血清MIC-1、chemerin水平,分析血清MIC-1、chemerin水平与NSCLC患者临床病理参数的关系。Kaplan-Meier法分析不同血清MIC-1、chemerin水平NSCLC患者生存时间的差异,COX比例风险回归分析血清MIC-1、chemerin水平与NSCLC患者预后的关系。结果:NSCLC组患者血清MIC-1、chemerin水平高于良性组和对照组(P0.05)。血清MIC-1水平与NSCLC患者年龄、目前吸烟、肿瘤直径、TNM分期、分化程度、复发或转移、生存状态有关(P0.05),chemerin水平与NSCLC患者目前吸烟、TNM分期、复发或转移、生存状态有关(P0.05)。高MIC-1水平患者生存率低于低MIC-1水平患者(P0.05),高chemerin水平患者生存率低于低chemerin水平患者(P0.05)。COX比例风险回归分析结果显示:血清MIC-1、chemerin、TNM分期与NSCLC不良预后独立相关。结论:血清MIC-1、chemerin水平与NSCLC患者部分临床病理参数和预后相关,可作为早期NSCLC患者预后预测的潜在指标。     

Prognostic value of neuron-specific enolase in patients with advanced and metastatic non-neuroendocrine non-small cell lung cancer

Background: Increased serum neuron-specific enolase (NSE) level was found in a substantial proportion (30–69%) of patients with non-small-cell lung cancer (NSCLC), but little was known about the clinical properties of NSE in NSCLC.Objective: We aimed to assess the level of serum NSE to predict prognosis and treatment response in patients with advanced or metastatic non-neuroendocrine NSCLC.Methods: We retrospectively analyzed 363 patients with advanced and metastatic NSCLC between January 2011 and October 2016. The serum NSE level was measured before initiation of treatment.Results: Patients with high NSE level (≥26.1 ng/ml) showed significantly shorter progression-free survival (PFS) (5.69 vs 8.09 months; P=0.02) and significantly shorter overall survival (OS) than patients with low NSE level (11.41 vs 24.31 months; P=0.01).NSE level was an independent prognostic factor for short PFS (univariate analysis, hazard ratio [HR] = 2.40 (1.71–3.38), P<0.001; multivariate analysis, [HR] = 1.81 (1.28–2.56), P=0.001) and OS (univariate analysis, [HR] = 2.40 (1.71–3.37), P<0.001; multivariate analysis, [HR] = 1.76 (1.24–2.50), P=0.002).Conclusion: The survival of NSCLC patients with high serum NSE level was shorter than that of NSCLC patients with low serum NSE levels. Serum NSE level was a predictor of treatment response and an independent prognostic factor.     

The Role of NQO1 Polymorphisms in the Susceptibility and Chemotherapy Response of Chinese NSCLC Patients

To investigate whether the NAD(P)H:quinone oxidoreductase 1 (NQO1) gene polymorphisms determine the Platinum-based chemotherapy in advanced non-small cell lung cancer (NSCLC) in a Chinese cohort. A total of 391 patients with inoperable advanced stage of NSCLC, namely, stage III (A + B) and IV NSCLC, and 663 age-and sex-matched healthy were enrolled. The effects of chemotherapy were evaluated. NQO1 C609T polymorphism was determined. The NSCLC patients had a significantly higher prevalence of TT than control subjects (33.76 vs. 21.67 %, P < 0.001). For allele comparison, NSCLC subjects had lower T allele frequency than controls as well (55.63 vs. 44.42 %, P < 0.001). multivariate regression analyses showed the TT carriage had a significantly increased risk for development of NSCLC after adjustments with age, sex, smoke, and cancer family history (OR 1.681, 95 % CI 1.242–2.274, P = 0.001). The TT genotype distribution was significantly higher in non-responders than in responders (31.85 vs. 21.96 %, P = 0.003). Logistic regression analysis showed TT genotype carriers had less chance to gain chemotherapy response compared to CC genotype carriers (OR 0.399, P = 0.003) after adjustment with sex, age, tumor histology, disease stage, and chemotherapy regimens. The NQO1 C609T polymorphism is an important molecular marker for advanced NSCLC, since it is associated with the NSCLC risk as well as the response status of platinum-based chemotherapy.     

非小细胞肺癌的治疗方案及影响预后的重要因素

目的:回顾分析各种非小细胞肺癌(non-small cell lung cancer,NSCLC)的治疗方案及影响其治疗预后的因素,为合理制定个体化的综合治疗方案提供参考。方法:回顾分析近年来NSCLC治疗的研究报道,分析如病理分期、实验室检查结果(VEGF、WBC、Hg等)影响治疗预后的因素,建议相应的治疗对策。结果:1.Ⅰ期、Ⅱ期及部分Ⅲa期NSCLC的患者治疗措施首先以手术治疗为主,同步放化疗比单纯放、化疗及序贯放化疗更能有效改善晚期NSCLC的预后;2.个体相关因素、肿瘤相关因素和治疗相关因素影响NSCLC治疗预后。结论:同步放化疗在晚期NSCLC的治疗中有重要作用,肿瘤的病理分期、血浆VEGF浓度是影响NSCLC预后的独立因素。     

Role of EGFR SNPs in survival of advanced lung adenocarcinoma patients treated with Gefitinib

Aim

As a novel molecularly targeting agent for non-small-cell lung cancer (NSCLC), Gefitinib can block its tyrosine kinase activity of the epidermal growth factor receptor (EGFR). Genetic variations in EGFR may affect its protein function or expression and lead to diverse outcomes in NSCLC patients after Gefitinib therapy. Therefore, this prospective study examined whether EGFR single nucleotide polymorphisms (SNPs) are associated with different survival time in advanced lung adenocarcinoma patients treated with Gefitinib.

Methods

One hundred and twenty-eight patients with stage IIIB or IV lung adenocarcinoma receiving Gefitinib target therapy between 2008 and 2010 were recruited in this study. Six EGFR haplotype-tagging SNPs were genotyped by the Sequenom MassArray system. Survival by different genotypes was compared using Kaplan–Meier methods. Cox proportional hazards models were applied to estimate the effect of prognostic factors on overall survival (OS) and progression-free survival (PFS).

Results

After the median 16.6 months of follow-up, the unfavorable EGFR rs2293347AA or GA genotype was significantly correlated with shorter OS (AA vs. GG: 2.0 vs. 21.0 months; hazard ratio (HR) = 2.44, 95% confidence interval (CI) = 1.06–5.56; P = 0.036; GA vs. GG: 15.0 vs. 21.0 months; HR = 1.75, 95%CI = 1.08–2.86, P = 0.025) compared with the favorable rs2293347GG genotype. The prognostic significance of EGFR rs4947492 polymorphism on OS also existed (GG carriers vs. AA carriers: median OS = 24.6 vs. 14.9 months, HR = 0.29, 95%CI = 0.10–0.83, P = 0.021). No significant associations were found among other EGFR SNPs and survival.

Conclusion

EGFR rs2293347 and rs4947492 SNPs might be potential predictive markers of OS in advanced lung adenocarcinoma patients treated with Gefitinib.     

PD-L1 Expression and Survival among Patients with Advanced Non–Small Cell Lung Cancer Treated with Chemotherapy

BACKGROUND: Recent clinical trial results have suggested that programmed cell death ligand 1 (PD-L1) expression measured by immunohistochemistry may predict response to anti–programmed cell death 1 (PD-1) therapy. Results on the association between PD-L1 expression and survival among patients with advanced non–small cell lung cancer (NSCLC) treated with chemotherapy are inconsistent. MATERIAL AND METHODS: We evaluated the relationship between PD-L1 expression and overall survival (OS) among 204 patients with advanced NSCLC treated at Aarhus University Hospital, Aarhus, Denmark, from 2007 to 2012. PD-L1 expression was measured using a prototype immunohistochemistry assay with the anti–PD-L1 22C3 antibody (Merck). PD-L1 strong positivity and weak positivity were defined to be traceable to the clinical trial version of the assay. RESULTS: Twenty-five percent of patients had PD-L1 strong-positive tumors, and 50% had PD-L1 weak-positive tumors. No statistically significant association was found between PD-L1 expression and survival; adjusted hazard ratio of 1.34 (95% confidence interval, 0.88-2.03; median OS, 9.0 months) for the PD-L1 strong-positive group and 1.07 (0.74-1.55; median OS, 9.8 months) for the PD-L1 weak-positive group compared with the PD-L1–negative group (median OS, 7.5 months). No association was seen between PD-L1 expression and OS when PD-L1 expression levels were stratified by median or tertiles. CONCLUSIONS: In concordance with previous studies, we found PD-L1 measured by immunohistochemistry to be frequently expressed in patients with advanced NSCLC. However, PD-L1 expression is not a strong prognostic marker in patients with advanced NSCLC treated with chemotherapy.     

Decrease of PDSS2 expression,a novel tumor suppressor,in non-small cell lung cancer

Background: Prenyl diphosphate synthase subunit 2 (PDSS2) gene has recently been reported as a potential tumor suppressor. The association of PDSS2 and non-small cell lung cancer (NSCLC) has not been known. Methods: To investigate its association with NSCLC, we examined the expression level of PDSS2 in 28 paired clinical samples of non-small cell lung cancer tissues and surrounding normal tissues. Results: PDSS2 was constitutionally expressed in normal lung tissues regardless of sex, race and smoking history. An overall decreased PDSS2 expression was found in the tumor tissues compared to surrounding normal tissues. Decrease in PDSS2 expression was more severe in poorly and poor-to-moderately differentiated lung cancers, while the decrease was not significant in moderately to well-differentiated tumors. Moreover, the expression of PDSS2 decreased more in higher pathological stage, and in patients with lymph node metastasis. The decrease in PDSS2 expression in tumor tissues was not related to sex or histological type of NSCLC, but was related to smoking history. No correlation has been found between PDSS2 and the clinical factors of EGRF, Ki-67 and p53. Conclusion: Taken together, decreased expression of PDSS2 in NSCLC was evident. This is an initial report for the expression of PDSS2 in relation to different factors in lung cancer. Loss of PDSS2 could serve as a potential biomarker in NSCLC development. The role of PDSS2 as a tumor suppressor, and the mechanism of its potential anti-tumor action in NSCLC warrant further investigation.