Showing papers by "Bo Lu published in 2018"

The surgical safety checklist and patient outcomes after surgery: a prospective observational cohort study, systematic review and meta-analysis

Abstract: Background The surgical safety checklist is widely used to improve the quality of perioperative care. However, clinicians continue to debate the clinical effectiveness of this tool. Methods Prospective analysis of data from the International Surgical Outcomes Study (ISOS), an international observational study of elective in-patient surgery, accompanied by a systematic review and meta-analysis of published literature. The exposure was surgical safety checklist use. The primary outcome was in-hospital mortality and the secondary outcome was postoperative complications. In the ISOS cohort, a multivariable multi-level generalized linear model was used to test associations. To further contextualise these findings, we included the results from the ISOS cohort in a meta-analysis. Results are reported as odds ratios (OR) with 95% confidence intervals. Results We included 44 814 patients from 497 hospitals in 27 countries in the ISOS analysis. There were 40 245 (89.8%) patients exposed to the checklist, whilst 7508 (16.8%) sustained ≥1 postoperative complications and 207 (0.5%) died before hospital discharge. Checklist exposure was associated with reduced mortality [odds ratio (OR) 0.49 (0.32–0.77); P Conclusions Patients exposed to a surgical safety checklist experience better postoperative outcomes, but this could simply reflect wider quality of care in hospitals where checklist use is routine.

Targeting Myeloid-derived Suppressor Cells and Programmed Death Ligand 1 Confers Therapeutic Advantage of Ablative Hypofractionated Radiation Therapy Compared With Conventional Fractionated Radiation Therapy

Abstract: Purpose Ablative hypofractionated radiation therapy (AHFRT) presents a therapeutic advantage compared with conventional fractionated radiation therapy (CFRT) for primary and oligometastatic cancers. However, the underlying mechanisms remain largely unknown. In the present study, we compared the immune alterations in response to AHFRT versus CFRT and examined the significance of immune regulations contributing to the efficacy of AHFRT. Methods and Materials We established subcutaneous tumors using syngeneic lung cancer and melanoma cells in both immunocompetent and immunocompromised mice and treated them with AHFRT and CFRT under the same biologically equivalent dose. Results Compared with CFRT, AHFRT significantly inhibited tumor growth in immunocompetent, but not immunocompromised, mice. On the cellular level, AHFRT reduced the recruitment of myeloid-derived suppressor cells (MDSCs) into tumors and decreased the expression of programmed death-ligand 1 (PD-L1) on those cells, which unlashed the cytotoxicity of CD8+ T cells. Through the downregulation of vascular endothelial growth factor (VEGF), AHFRT inhibited VEGF/VEGF receptor signaling, which was essential for MDSC recruitment. When combined with anti-PD-L1 antibody, AHFRT presented with greater efficacy in controlling tumor growth and improving mouse survival. By altering immune regulation, AHFRT, but not CFRT, significantly delayed the growth of secondary tumors implanted outside the irradiation field. Conclusions Targeting MDSC recruitment and enhancing antitumor immunity are crucial for the therapeutic efficacy of AHFRT. When combined with anti-PD-L1 immunotherapy, AHFRT was more potent for cancer treatment.

mTORC1 signaling suppresses Wnt/β-catenin signaling through DVL-dependent regulation of Wnt receptor FZD level

Abstract: Wnt/β-catenin signaling plays pivotal roles in cell proliferation and tissue homeostasis by maintaining somatic stem cell functions. The mammalian target of rapamycin (mTOR) signaling functions as an integrative rheostat that orchestrates various cellular and metabolic activities that shape tissue homeostasis. Whether these two fundamental signaling pathways couple to exert physiological functions still remains mysterious. Using a genome-wide CRISPR-Cas9 screening, we discover that mTOR complex 1 (mTORC1) signaling suppresses canonical Wnt/β-catenin signaling. Deficiency in tuberous sclerosis complex 1/2 (TSC1/2), core negative regulators of mTORC1 activity, represses Wnt/β-catenin target gene expression, which can be rescued by RAD001. Mechanistically, mTORC1 signaling regulates the cell surface level of Wnt receptor Frizzled (FZD) in a Dishevelled (DVL)-dependent manner by influencing the association of DVL and clathrin AP-2 adaptor. Sustained mTORC1 activation impairs Wnt/β-catenin signaling and causes loss of stemness in intestinal organoids ex vivo and primitive intestinal progenitors in vivo. Wnt/β-catenin–dependent liver metabolic zonation gene expression program is also down-regulated by mTORC1 activation. Our study provides a paradigm that mTORC1 signaling cell autonomously regulates Wnt/β-catenin pathway to influence stem cell maintenance.

Beyond Concurrent Chemoradiation: The Emerging Role of PD-1/PD-L1 Inhibitors in Stage III Lung Cancer

Abstract: Concurrent chemoradiation (cCRT) with platinum-based chemotherapy is standard-of-care therapy for patients with stage III unresectable non-small cell lung cancer (NSCLC). Although cCRT is potentially curative, 5-year overall survival has hovered around 20%, despite extensive efforts to improve outcomes with increasing doses of conformal radiation and intensification of systemic therapy with either induction or consolidation chemotherapy. PD-1/PD-L1 immune checkpoint inhibitors have demonstrated unprecedented efficacy in patients with stage IV NSCLC. In addition, preclinical and early clinical evidence suggests that chemotherapy and radiation may work synergistically with anti-PD-1/PD-L1 therapy to promote antitumor immunity, which has led to the initiation of clinical trials testing these drugs in patients with stage III NSCLC. A preliminary report of a randomized phase III trial, the PACIFIC trial, demonstrated an impressive increase in median progression-free survival with consolidative durvalumab, a PD-L1 inhibitor, compared with observation after cCRT. Here, we discuss the clinical and translational implications of integrating PD-1/PD-L1 inhibitors in the management of patients with unresectable stage III NSCLC. Clin Cancer Res; 24(6); 1271-6. ©2018 AACR.

Attitudes toward Tobacco, Alcohol, and Non-Alcoholic Beverage Advertisement Themes among Adolescent Boys.

Abstract: Background: Previous studies have examined what adolescents find appealing in tobacco and alcohol advertisements and how different themes in advertisements are used to manipulate consumer behaviors...

Ohio's Medicaid Expansion and Unmet Health Needs Among Low-Income Women of Reproductive Age.

Abstract: Objective To examine changes in the prevalence and odds of unmet healthcare needs and healthcare utilization among low-income women of reproductive age (WRA) after Ohio’s 2014, ACA-associated Medicaid expansion, which extended coverage to non-senior adults with a family income ≤ 138% of the federal poverty level. Methods We analyzed publically available data from the 2012 and 2015 Ohio Medicaid Assessment Survey (OMAS), a cross-sectional telephone survey of Ohio’s non-institutionalized adult population. The study included 489 low-income women in 2012 and 1273 in 2015 aged 19–44 years who were newly eligible for Medicaid after expansion in January 2014. Four unmet healthcare need and three healthcare utilization measures were examined. We fit survey-weighted logistic regression models adjusted for race/ethnicity, working status, and educational attainment to determine whether the odds of each measure differed between 2012 and 2015. Results In 2015, low-income WRA had a significantly lower odds of reporting an unmet dental care need (ORadj = 0.72, 95% CI 0.54, 0.95), unmet vision care need (ORadj = 0.68, 95% CI 0.50, 0.93), unmet mental health need (ORadj = 0.57, 95% CI 0.39, 0.83), and unmet prescription need (ORadj = 0.39, 95% CI 0.45, 0.80) compared to 2012. There were no significant differences in the odds of seeing a doctor or dentist in the past year or of having a usual source of care for low-income WRA in 2012 and 2015. Conclusions for Practice After Ohio’s 2014 Medicaid expansion the odds of low-income WRA having unmet healthcare needs was reduced. Future research should examine outcomes after a longer period of follow-up and include additional measures, such as self-rated health status.

Warning Size Affects What Adolescents Recall From Tobacco Advertisements.

Abstract: Objectives In the U.S., print advertisements for smokeless tobacco (SLT) feature a large black-and-white text warning covering 20% of the advertisement space. Cigarette and e-cigarette advertisements feature a small warning covering approximately 4% of advertisement space. We explored how warning size affects adolescent boys' spontaneous recollection of the warning, brand-relevant advertisement features, and product risks. Methods 1,220 adolescent males (ages 11-16) viewed SLT, cigarette, and e-cigarette advertisements. After each advertisement, boys were asked to recall what they remembered most. Coders identified recalls of the warning label, brand-relevant advertisement features, and risks associated with the product in responses. Results Participants were less likely to recall warnings in the cigarette vs. SLT (OR=0.30, p 3.50, p's<0.001). Conclusions Youth are more likely to recall large SLT warnings than small cigarette and e-cigarette warnings. Warning recall is associated with lower likelihood of recalling brand-relevant advertisement features and greater likelihood of mentioning product risks.

Testing causal effects in observational survival data using propensity score matching design.

Abstract: Time-to-event data are very common in observational studies. Unlike randomized experiments, observational studies suffer from both observed and unobserved confounding biases. To adjust for observed confounding in survival analysis, the commonly used methods are the Cox proportional hazards (PH) model, the weighted logrank test, and the inverse probability of treatment weighted Cox PH model. These methods do not rely on fully parametric models, but their practical performances are highly influenced by the validity of the PH assumption. Also, there are few methods addressing the hidden bias in causal survival analysis. We propose a strategy to test for survival function differences based on the matching design and explore sensitivity of the P-values to assumptions about unmeasured confounding. Specifically, we apply the paired Prentice-Wilcoxon (PPW) test or the modified PPW test to the propensity score matched data. Simulation studies show that the PPW-type test has higher power in situations when the PH assumption fails. For potential hidden bias, we develop a sensitivity analysis based on the matched pairs to assess the robustness of our finding, following Rosenbaum's idea for nonsurvival data. For a real data illustration, we apply our method to an observational cohort of chronic liver disease patients from a Mayo Clinic study. The PPW test based on observed data initially shows evidence of a significant treatment effect. But this finding is not robust, as the sensitivity analysis reveals that the P-value becomes nonsignificant if there exists an unmeasured confounder with a small impact.

A new weighted injury severity scoring system: Better predictive power for pediatric trauma mortality.

Abstract: BACKGROUND An accurate injury severity measurement is essential for the evaluation of pediatric trauma care and outcome research. The traditional Injury Severity Score (ISS) does not consider the differential risks of the Abbreviated Injury Scale (AIS) from different body regions nor is it pediatric specific. The objective of this study was to develop a weighted ISS (wISS) system for pediatric blunt trauma patients with better predictive power than ISS. METHODS Based on the association between mortality and AIS from each of the six ISS body regions, we generated different weights for the component AIS scores used in the calculation of ISS. The weights and wISS were generated using the National Trauma Data Bank. The Nationwide Emergency Department Sample (NEDS) was used to validate our main results. Pediatric blunt trauma patients younger than 16 years were included, and mortality was the outcome. Discrimination (areas under the receiver operating characteristic curve, sensitivity, specificity, positive predictive value, negative predictive value, concordance) and calibration (Hosmer-Lemeshow statistic) were compared between the wISS and ISS. RESULTS The areas under the receiver operating characteristic curves from the wISS and ISS are 0.88 versus 0.86 in ISS of 1 to 74 and 0.77 versus 0.64 in ISS of 25 to 74 (p < 0.0001). The wISS showed higher specificity, positive predictive value, negative predictive value, and concordance when they were compared at similar levels of sensitivity. The wISS had better calibration (smaller Hosmer-Lemeshow statistic) than the ISS (11.6 vs. 19.7 for ISS = 1-74 and 10.9 vs. 12.6 for ISS = 25-74). The wISS showed even better discrimination with the Nationwide Emergency Department Sample. CONCLUSION By weighting the AIS from different body regions, the wISS had significantly better predictive power for mortality than the ISS, especially in critically injured children. LEVEL OF EVIDENCE AND STUDY TYPE Prognostic/epidemiological, level IV.

Model assisted sensitivity analyses for hidden bias with binary outcomes.

Abstract: In medical and health sciences, observational studies are a major data source for inferring causal relationships. Unlike randomized experiments, observational studies are vulnerable to the hidden bias introduced by unmeasured confounders. The impact of unmeasured covariates on the causal effect can be assessed by conducting a sensitivity analysis. A comprehensive framework of sensitivity analyses has been developed for matching designs. Sensitivity parameters are introduced to capture the association between the missing covariates and the exposure or the outcome. Fixing sensitivity parameter values, it is possible to compute the bounds of the p-value of a randomization test on causal effects. We propose a model assisted sensitivity analysis with binary outcomes for the general 1:k matching design, which provides results equivalent to the conventional nonparametric approach in large sample. By introducing a conditional logistic outcome model, we substantially simplify the implementation and interpretation of the sensitivity analysis. More importantly, we are able to provide a closed form representation for the set of sensitivity parameters for which the maximum p-values are non-significant. This methodology can be easily extended to matching designs with multilevel treatments. We illustrate our method using a U.S. trauma care database to examine mortality difference between trauma care levels.

Feasibility of photon beam profile deconvolution using a neural network.

Abstract: Purpose Ionization chambers are the detectors of choice for photon beam profile scanning. However, they introduce significant volume averaging effect (VAE) that can artificially broaden the penumbra width by 2-3 mm. The purpose of this study was to examine the feasibility of photon beam profile deconvolution (the elimination of VAE from ionization chamber-measured beam profiles) using a three-layer feedforward neural network. Methods Transverse beam profiles of photon fields between 2 × 2 and 10 × 10 cm2 were collected with both a CC13 ionization chamber and an EDGE diode detector on an Elekta Versa HD accelerator. These profiles were divided into three datasets (training, validation and test) to train and test a three-layer feedforward neural network. A sliding window was used to extract input data from the CC13-measured profiles. The neural network produced the deconvolved value at the center of the sliding window. The full deconvolved profile was obtained after the sliding window was moved over the measured profile from end to end. The EDGE-measured beam profiles were used as reference for the training, validation, and test. The number of input neurons, which equals the sliding window width, and the number of hidden neurons were optimized with a parametric sweeping method. A total of 135 neural networks were fully trained with the Levenberg-Marquardt backpropagation algorithm. The one with the best overall performance on the training and validation dataset was selected to test its generalization ability on the test dataset. The agreement between the neural network-deconvolved profiles and the EDGE-measured profiles was evaluated with two metrics: mean squared error (MSE) and penumbra width difference (PWD). Results Based on the two-dimensional MSE plots, the optimal combination of sliding window width of 15 and 5 hidden neurons was selected for the final neural network. Excellent agreement was achieved between the neural network-deconvolved profiles and the reference profiles in all three datasets. After deconvolution, the mean PWD reduced from 2.43 ± 0.26, 2.44 ± 0.36, and 2.46 ± 0.29 mm to 0.15 ± 0.15, 0.04 ± 0.03, and 0.14 ± 0.09 mm for the training, validation, and test dataset, respectively. Conclusions We demonstrated the feasibility of photon beam profile deconvolution with a feedforward neural network in this work. The beam profiles deconvolved with a three-layer neural network had excellent agreement with diode-measured profiles.

A social-contextual investigation of smoking among rural women: multi-level factors associated with smoking status and considerations for cessation.

Abstract: Introduction The social-contextual model of tobacco control and the potential mechanisms of the maintenance or cessation of smoking behavior among disadvantaged women, including rural residents, have yet to be comprehensively studied. The purpose of this study was to determine the association between selected individual, interpersonal, workplace, and neighborhood characteristics and smoking status among women in Appalachia, a US region whose residents experience a disproportionate prevalence of tobacco-related health disparities. These findings may assist in efforts to design and test scientifically valid tobacco control interventions for this and other disadvantaged populations. Methods Women, 18 years of age and older, residing in three rural Ohio Appalachian counties, were recruited using a two-phase address-based sampling methodology for a cross-sectional interview-administered survey between August 2012 and October 2013 (N=408). Multinomial logistic regression was employed to determine associations between select multilevel factors (independent variables) and smoking status (dependent variable). The sample included 82 (20.1%) current smokers, 92 (22.5%) former smokers, and 234 (57.4%) women reporting never smoking (mean age 51.7 years). Results In the final multivariable multinomial logistic regression model, controlling for all other significant associations, constructs at multiple social-contextual levels were associated with current versus either former or never smoking. At the individual level, for every additional year in age, the odds of being a former or never smoker increased by 7% and 6% (odds ratio (OR) (95% confidence interval(CI)): 1.07 (1.0-1.11) and 1.06 (1.02-1.09)), respectively, as compared to the odds of being a current smoker. With regard to depression, for each one unit increase in the Center for Epidemiologic Studies Depression Scale score, the odds of being a former or never smoker were 5% and 7% lower (OR(95%CI): 0.95(0.91-0.999) and 0.93(0.88-0.98)), respectively. Five interpersonal factors were associated with smoking status. As the social influence injunctive norm score increased by one unit, indicating perception of smoking to be more acceptable, the odds of being a former or never smoker decreased by 23% and 30%, respectively. For every one unit increase in the social participation score, indicating past-year engagement in one additional activity type, the odds of being a former or never smoker increased by 17% and 36%, respectively. For every 10% increase in the percentage of social ties in the participant's advice network who smoked, the odds of being a former or never smoker were 24% and 28% less, respectively. For every 0.1 unit increase in the E/I index, indicating increasing homophily on smoking in one's social network, the odds of being a former or never smoker were 20% and 24% less, respectively, in the time network, and 18% and 20% less, respectively, in the advice network. At the neighborhood level, for every one unit increase in neighborhood cohesion score, indicating increasing cohesion, the odds of being a former smoker or never smoker were 12% and 14% less, respectively. Conclusions These findings indicate that a social-contextual approach to tobacco control may be useful for narrowing a widening trajectory of smoking disparity for rural women. Interpersonal context, in particular, must be considered in the development of culturally targeted cessation interventions for Ohio Appalachian women.

A new inverse planning formalism with explicit DVH constraints and kurtosis-based dosimetric criteria

Abstract: In inverse planning processes of radiotherapy, dose-volume histograms (DVH) have been commonly used as a measure of plan quality. The exact mathematical formulation of DVHs involves binary variables and is therefore intrinsically nonconvex. In view of the resulting computational intractability, existing treatment planning systems adopt convex surrogate models that involve many parameters. Manual parameter tweaking is then required to determine reasonable values for those parameters in order to generate plans that meet the target DVHs. However, conventional convex formulations for inverse planning entails non-trivial differences from an exact formulation and, therefore, provide only very limited control over the DVHs. In view of this limitation, this paper presents a new formulation that combines a novel folded concave penalty (FCP)-based constraint and a new kurtosis-based optimization criterion. The former presents a much sharper approximation to the exact DVH constraints than the existing counterparts, and the latter penalizes the occurrence of hot and cold spots in dose distributions. We investigated the effectiveness of the proposed planning formulations on three head-and-neck cases in comparison with conventional DVH-based formulations. Significant outperformance in terms of better distributed doses-at-volume was achieved through the proposed scheme.

Tobacco and Alcohol on Television: A Content Analysis of Male Adolescents' Favorite Shows.

Abstract: Introduction Media tobacco and alcohol portrayals encourage adolescent substance use. Preventing adolescent initiation with these substances is critical, as they contribute to leading causes of morbidity and mortality in the United States. Television tobacco and alcohol portrayals have not been examined for more than 7 years. This study analyzed tobacco and alcohol portrayals on adolescents' favorite television shows and evaluated the rate of portrayals by parental rating. Methods Adolescent males (N = 1,220) from Ohio reported 3 favorite television shows and how frequently they watch them. For each of the 20 most-watched shows in the sample, 9 episodes were randomly selected and coded for visual and verbal tobacco and alcohol incidents. Demographics of characters who used or interacted with the substances were recorded. Negative binomial regression modeled rates of tobacco and alcohol incidents per hour by parental rating. Results There were 49 tobacco and 756 alcohol portrayals across 180 episodes. Characters using the products were mostly white, male, and adult. The rate of tobacco incidents per hour was 1.2 for shows rated TV-14 (95% CI, 0.4-3.6) and 1.1 for shows rated TV-MA (95% CI, 0.3-4.5). The estimated rate of alcohol incidents per hour was 20.9 for shows rated TV-14 (95% CI, 6.3-69.2) and 7.2 for shows rated TV-MA (95% CI, 1.5-34.1). Conclusions Adolescent males' favorite television shows rated TV-14 expose them to approximately 1 tobacco incident and 21 alcohol incidents per hour on average. Limiting tobacco and alcohol incidents on television could reduce adolescents' risk of substance use.

Inference for proportional hazard model with propensity score

Abstract: Since the publication of the seminal paper by Cox (1972), proportional hazard model has become very popular in regression analysis for right censored data. In observational studies, treatment assignment may depend on observed covariates. If these confounding variables are not accounted for properly, the inference based on the Cox proportional hazard model may perform poorly. As shown in Rosenbaum and Rubin (1983), under the strongly ignorable treatment assignment assumption, conditioning on the propensity score yields valid causal effect estimates. Therefore we incorporate the propensity score into the Cox model for causal inference with survival data. We derive the asymptotic property of the maximum partial likelihood estimator when the model is correctly specified. Simulation results show that our method performs quite well for observational data. The approach is applied to a real dataset on the time of readmission of trauma patients. We also derive the asymptotic property of the maximum partial...

Address-Based Sampling for Recruiting Rural Subpopulations: A 2-Phase, Multimode Approach.

Abstract: Purpose This article describes recruitment of a subpopulation of women in a rural area, extending an existing method of a 2-phase address-based sampling protocol to include a mixed-mode approach. Methods Phase 1 included a household enumeration questionnaire mailed to randomly selected households (n = 1,950) in 3 Ohio Appalachian counties to identify members of the eligible subgroup. The second phase of recruitment involved contacting 1 randomly selected eligible woman enumerated by each household, based on return of the questionnaire. These women (n = 599) were invited by field interviewers to participate in a one-time in-person health survey. Findings Of the women invited to participate, a total of 408 completed the interview. Based on American Association for Public Opinion Research Response Rate 1 calculations, the response rates were 44.4% and 70.3% for phases 1 and 2, respectively. Response rates in this study were encouraging, especially for the second phase in-person interview. Conclusion We discuss implications for future research using a mixed-mode approach in this subpopulation.

Utility of stereotactic ablative radiotherapy/stereotactic body radiation therapy in the setting of oligometastatic non-small cell lung cancer.

Abstract: Oligometastatic disease treatment has become one of the highlights of radiation treatment in recent years. Phase II study results from UT Southwestern published in September 2017 in JAMA Oncol showed a near threefold benefit to progression-free survival favoring local ablative radiation therapy, leading to a stopping in accrual earlier than anticipated (1). The study directly compared stereotactic ablative radiotherapy (SABR), also known as stereotactic body radiation therapy (SBRT), with maintenance chemotherapy versus maintenance chemotherapy alone, both arms after receiving induction chemotherapy. The study population was limited to patients with non-small cell lung cancer (NSCLC), including up to five metastatic lesions with no targetable mutations and no disease progression after induction chemotherapy.

Nivolumab plus cisplatin/pemetrexed or cisplatin/gemcitabine as induction in resectable NSCLC.

Abstract: TPS8582Background: For patients (pts) with stage IB (≥4cm)-IIIA Non-small-cell lung cancer (NSCLC), multi-modality therapy yields a modest improvement in 5 year post-surgical overall survival (OS),...

Routine Adaptive Replanning of p16-Positive Stage N2b Oropharyngeal Cancer: Quality Improvement or Waste of Time?

Abstract: PURPOSE/OBJECTIVE(S) To determine if routinely replanning patients treated for oropharyngeal cancer that is p16-positive and clinical neck stage N2b (AJCC 7th edition) is likely to result in dose changes that will improve patient outcomes to a meaningful degree. METHODS In 10 consecutive patients treated with primary radiotherapy (RT) and concurrent weekly chemotherapy for p16-positive N2b oropharyngeal carcinoma, we prospectively evaluated dose changes from replanning for the final 4 or 2 weeks of RT of a 7-week RT program. RESULTS Replanning for the final 4 or 2 weeks improved planning target volume coverage by an average of 4 and 2 percentage points, respectively. For all normal structures, the dose change was small (<1 Gy) with replanning. CONCLUSIONS In patients with p16-positive N2b oropharynx cancer, the value of replanning RT is a small improvement in target coverage with minimal improvement in normal tissue sparing. In response to our study, some of the physicians in our group replan most node-positive oropharyngeal cancer cases while others think routine replanning is not valuable.

Neoadjuvant PD-1 blockade in non-small cell lung cancer: what else do we need to do?

Abstract: For decades, systemic therapy for non-small cell lung cancer (NSCLC) was subjected to cytotoxic agents. For patients with locally advanced NSCLC (stages IIIA–B) not suitable to surgical resection, the current standard of regimen is concurrent chemoradiotherapy, which induces median survival time in excess of 2- and 5-year survival of 15–20% (1). For advanced NSCLC patients, the application of third-generation of chemotherapy drugs such as docetaxel, paclitaxel and gemcitabine, had improved the overall survival to 8 months (2).