Association between lung cancer screening and smoking cessation

IntroductionAdults with high-risk smoking histories benefit from annual lung cancer screening. It is unclear if there is an association between lung cancer screening and smoking cessation among U.S. adults who receive screening.MethodsWe performed this population-based cross-sectional study using data from the Behavioral Risk Factor Surveillance System (2017–2020). We defined individuals eligible for lung cancer screening as adults 55–80 years old with ≥ 30 pack-year smoking history who were currently smoking or quit within the last 15 years. We assessed the association between lung cancer screening and current smoking status.ResultsBetween 2017 and 2020, 12,382 participants met screening criteria. Current smoking was reported by 5685 (45.9 %) participants, of whom 40.4 % (2298) reported a cessation attempt in the prior year. Lung cancer screening was reported by only 2022 (16.3 %) eligible participants. Lung cancer screening was associated with lower likelihood of currently smoking (odds ratio [OR] 0.705, 95 % CI 0.626–0.793) compared to individuals who did not receive screening. Screening was also associated with higher likelihood of reporting a cessation attempt in the prior year (OR 1.562, 95 % CI 1.345–1.815) compared to individuals who did not receive screening.ConclusionsReceipt of lung cancer screening was associated with lower smoking rates and more frequent cessation attempts among U.S. adults. Better implementation of lung cancer screening programs is critical and may profoundly increase smoking cessation in this population at risk of developing lung cancer.     

Screening baseline characteristics of early lung cancer on low-dose computed tomography with computer-aided detection in a Chinese population

ObjectivesThis study investigated appropriate baseline characteristics for screening a Chinese population at high risk of early lung cancer, assisted by low-dose computed tomography (LDCT) with computer-aided detection (CAD). Included is a discussion of the viability of using LDCT in the screening guideline and optimizing the guideline.MethodsIn 2014, 1016 individuals from Sichuan Province were enrolled who satisfied the criteria for high risk according to the 2013 National Comprehensive Cancer Network (NCCN) Guidelines for Non-Small Cell Lung Cancer. From 2014 to 2018, each subject was followed using LDCT with CAD, and pathologically confirmed lung cancers and baseline nodule characteristics (size and density) were recorded. Positive risk was considered a non-calcified solid or part-solid nodule on LDCT with diameter ≥5 mm and ground-glass nodule ≥8 mm, as newly recommended by the China National Lung Cancer Screening Guideline.ResultsFrom 2014–2018, 13 cases of lung cancer were detected; 5 of these were early stage (38.5%). According to the NCCN criteria, 54 women were included and one of these (1.8%) developed lung cancer. The prevalence of lung cancer was 0.7% at baseline. For the entire population (excluding subjects with a tumor mass at baseline, n = 4), the rate of positivity was 20.4% at baseline; applying the Chinese criteria, the false positive rate was 19.5% (197/1012).ConclusionsFurther studies are warranted to establish appropriate eligible criteria and management strategies for Chinese populations.     

Probability of lung cancer in a population excluded from screening due to low PLCOM2012 risk

BackgroundSeveral randomized trials demonstrated have reduced lung cancer mortality with screening using computed tomography. However, there remains debate about the optimal approach for determining screening eligibility, and no evidence yet exists reporting lung cancer rates in those excluded from screening due to too low of a personalized risk.MethodsThis study was based on the Alberta Lung Cancer Screening Study, which received 1737 applicants and enrolled 850 based on the NLST criteria or a PLCO_M2012 risk ≥ 1.5%. We excluded 887 applicants who were interested in screening but deemed ineligible. We report lung cancer rates in the screened and unscreened cohorts.ResultsWe observed 30 and 8 lung cancers in the screened and unscreened groups, respectively. Only 1 of 8 lung cancers were among those considered too low risk (0.14%), while the remaining 7 were among those excluded for other reasons, including symptoms requiring more immediate workup. No NLST eligible but PLCO risk < 1.5% screened individual had a lung cancer detected as part of the study, so that of all applicants contacting the program with risk estimates less than 1.5%, only 1/857 (0.12%) developed lung cancer.ConclusionOur findings indicate that a risk-based approach for screening eligibility is unlikely to miss many lung cancers.     

The value of blood-based measures of liver function and urate in lung cancer risk prediction: A cohort study and health economic analysis

BackgroundSeveral studies have reported associations between low-cost blood-based measurements and lung cancer but their role in risk prediction is unclear. We examined the value of expanding lung cancer risk models for targeting low-dose computed tomography (LDCT), including blood measurements of liver function and urate.MethodsWe analysed a cohort of 388,199 UK Biobank participants with 1873 events and calculated the c-index and fraction of new information (FNI) for models expanded to include combinations of blood measurements, lung function (forced expiratory volume in 1 s - FEV₁), alcohol status and waist circumference. We calculated the hypothetical cost per lung cancer case detected by LDCT for different scenarios using a threshold of ≥ 1.51 % risk at 6 years.ResultsThe c-index was 0.805 (95 %CI:0.794–0.816) for the model containing conventional predictors. Expanding to include blood measurements increased the c-index to 0.815 (95 %CI: 0.804–0.826;p < 0.0001;FNI:0.06). Expanding to include FEV₁, alcohol status, and waist circumference increased the c-index to 0.811 (95 %CI: 0.800–0.822;p < 0.0001;FNI: 0.04). The c-index for the fully expanded model containing all variables was 0.819 (95 %CI:0.808–0.830;p < 0.0001;FNI:0.09). Model expansion had a greater impact on the c-index and FNI for people with a history of smoking cigarettes relative to the full cohort. Compared with the conventional risk model, the expanded models reduced the number of participants meeting the criteria for LDCT screening by 15–21 %, and lung cancer cases detected by 7–8 %. The additional cost per lung cancer case detected relative to the conventional model was £ 1018 for adding blood tests and £ 9775 for the fully expanded model.ConclusionBlood measurements of liver function and urate made a modest improvement to lung cancer risk prediction compared with a model containing conventional risk factors. There was no evidence that model expansion would improve the cost per lung cancer case detected in UK healthcare settings.     

Should Nonsmokers Be Excluded from Early Lung Cancer Screening with Low-Dose Spiral Computed Tomography? Community-Based Practice in Shanghai

OBJECTIVE: We investigated the efficacy of early lung cancer screening with low-dose spiral computed tomography(LDCT) in both smokers and nonsmokers based on the current situation of community health service, with integration of superior resources of medical institutions at all levels in Shanghai. METHODS: From August 2013 to August 2014, we screened 11,332 (male 7144; female 4188) high-risk individuals in selected communities of Minhang, Shanghai City, for early diagnosis of lung cancer with LDCT combined with multidisciplinary comprehensive treatment pattern including minimally invasive surgery, exploring the medical service network covering prevention, diagnosis, treatment, rehabilitation, and follow-up. RESULTS: Screening resulted in a diagnosis of cancer in 29 participants. Of these participants, 27 had primary lung cancer, 1 had lung metastatic cancer, and 1 had breast cancer. The detection rate of primary lung cancer was 238.26 cases per 100,000 person-years among all the participants. Specifically, the incidence of primary lung cancer was 336.97 cases per 100,000 person-years among the nonsmoking participants, as compared with 159.06 cases per 100,000 person-years among the smoking participants (P = .054). Among the 27 primary lung cancers, 22 (81.48%) had stage 0 to I lung cancer. CONCLUSION: Based on community health service, screening with LDCT could improve the early diagnosis rate of lung cancer in both smokers and nonsmokers with feasibility and validity, which could be applicable in qualified eligible medical centers and communities in China. It is not reasonable to exclude nonsmokers from screening with LDCT.     

A Cost-Utility Analysis of Lung Cancer Screening and the Additional Benefits of Incorporating Smoking Cessation Interventions

Background

A 2011 report from the National Lung Screening Trial indicates that three annual low-dose computed tomography (LDCT) screenings for lung cancer reduced lung cancer mortality by 20% compared to chest X-ray among older individuals at high risk for lung cancer. Discussion has shifted from clinical proof to financial feasibility. The goal of this study was to determine whether LDCT screening for lung cancer in a commercially-insured population (aged 50–64) at high risk for lung cancer is cost-effective and to quantify the additional benefits of incorporating smoking cessation interventions in a lung cancer screening program.

Methods and Findings

The current study builds upon a previous simulation model to estimate the cost-utility of annual, repeated LDCT screenings over 15 years in a high risk hypothetical cohort of 18 million adults between age 50 and 64 with 30+ pack-years of smoking history. In the base case, the lung cancer screening intervention cost $27.8 billion over 15 years and yielded 985,284 quality-adjusted life years (QALYs) gained for a cost-utility ratio of $28,240 per QALY gained. Adding smoking cessation to these annual screenings resulted in increases in both the costs and QALYs saved, reflected in cost-utility ratios ranging from $16,198 per QALY gained to $23,185 per QALY gained. Annual LDCT lung cancer screening in this high risk population remained cost-effective across all sensitivity analyses.

Conclusions

The findings of this study indicate that repeat annual lung cancer screening in a high risk cohort of adults aged 50–64 is highly cost-effective. Offering smoking cessation interventions with the annual screening program improved the cost-effectiveness of lung cancer screening between 20% and 45%. The cost-utility ratios estimated in this study were in line with other accepted cancer screening interventions and support inclusion of annual LDCT screening for lung cancer in a high risk population in clinical recommendations.     

Implementing Direct Access to Low-Dose Computed Tomography in General Practice—Method,Adaption and Outcome

Background

Early detection of lung cancer is crucial as the prognosis depends on the disease stage. Chest radiographs has been the principal diagnostic tool for general practitioners (GPs), but implies a potential risk of false negative results, while computed tomography (CT) has a higher sensitivity. The aim of this study was to describe the implementation of direct access to low-dose CT (LDCT) from general practice.

Methods

We conducted a cohort study nested in a randomised study. A total of 119 general practices with 266 GPs were randomised into two groups. Intervention GPs were offered direct access to chest LDCT combined with a Continuing Medical Education (CME) meeting on lung cancer diagnosis.

Results

During a 19-month period, 648 patients were referred to LDCT (0.18/1000 adults on GP list/month). Half of the patients needed further diagnostic work-up, and 15 (2.3%, 95% CI: 1.3–3.8%) of the patients had lung cancer; 60% (95% CI: 32.3–83.7%) in a localised stage. The GP referral rate was 61% higher for CME participants compared to non-participants.

Conclusion

Of all patients referred to LDCT, 2.3% were diagnosed with lung cancer with a favourable stage distribution. Half of the referred patients needed additional diagnostic work-up. There was an association between participation in CME and use of CT scan. The proportion of cancers diagnosed through the usual fast-track evaluation was 2.2 times higher in the group of CME-participating GPs. The question remains if primary care case-finding with LDCT is a better option for patients having signs and symptoms indicating lung cancer than a screening program. Whether open access to LDCT may provide earlier diagnosis of lung cancer is yet unknown and a randomised trial is required to assess any effect on outcome.

Trial Registration

Clinicaltrials.gov NCT01527214     

Blood cadmium levels as a marker for early lung cancer detection

BackgroundWe assessed whether blood cadmium levels were associated with incident lung cancer and could be used in the context of a screening program for early-stage lung cancer.Material and methodsWe measured blood cadmium levels among 205 lung cancer patients and 205 matched controls. Cases and controls were matched for sex, age and smoking history (total pack-years, years since cessation for former smokers).ResultsThe odds ratio for those in the highest quartile of cadmium level (versus lowest) was four-fold (OR = 4.41, 95 % CI:2.01–9.67, p < 0.01). The association was present in former smokers (OR = 16.8, 95 % CI:3.96−71.2, p < 0.01), but not in current smokers (OR = 1.23, 95 % CI: 0.34–4.38) or in never smokers (OR not defined). Among former smokers, the association was present in both early- and late-stage lung cancer.ConclusionBlood cadmium levels may be a marker to help with the early detection of lung cancer among former smokers.     

Do Lung Cancer Eligibility Criteria Align with Risk among Blacks and Hispanics?

Background

Black patients have higher lung cancer risk despite lower pack years of smoking. We assessed lung cancer risk by race, ethnicity, and sex among a nationally representative population eligible for lung cancer screening based on Medicare criteria.

Methods

We used data from the National Health and Nutrition Examination Survey, 2007–2012 to assess lung cancer risk by sex, race and ethnicity among persons satisfying Medicare age and pack-year smoking eligibility criteria for lung cancer screening. We assessed Medicare eligibility based on age (55–77 years) and pack-years (≥30). We assessed 6-year lung cancer risk using a risk prediction model from Prostate, Lung, Colorectal and Ovarian Cancer Screening trial that was modified in 2012 (PLCO_m2012). We compared the proportions of eligible persons by sex, race and ethnicity using Medicare criteria with a risk cut-point that was adjusted to achieve comparable total number of persons eligible for screening.

Results

Among the 29.7 million persons aged 55–77 years who ever smoked, we found that 7.3 million (24.5%) were eligible for lung cancer screening under Medicare criteria. Among those eligible, Blacks had statistically significant higher (4.4%) and Hispanics lower lung cancer risk (1.2%) than non-Hispanic Whites (3.2%). At a cut-point of 2.12% risk for lung screening eligibility, the percentage of Blacks and Hispanics showed statistically significant changes. Blacks eligible rose by 48% and Hispanics eligible declined by 63%. Black men and Hispanic women were affected the most. There was little change in eligibility among Whites.

Conclusion

Medicare eligibility criteria for lung cancer screening do not align with estimated risk for lung cancer among Blacks and Hispanics. Data are urgently needed to determine whether use of risk-based eligibility screening improves lung cancer outcomes among minority patients.     

Variables altering the impact of respiratory gated CT simulation on planning target volume in radiotherapy for lung cancer

BackgroundRespiratory gated CT simulation (4D-simulation) has been evolved to estimate the internal body motion. This study aimed to evaluate the impact of tumor volume and location on the planning target volume (PTV) for primary lung tumor when 4D simulation is used.MethodsPatients who underwent CT simulation for primary lung cancer radiotherapy between 2012 and 2016 using a 3D- (free breathing) and 4D- (respiratory gated) technique were reviewed. For each patient, gross tumor volume (GTV) was contoured in a free breathing scan (3D-GTV), and 4D-simulation scans (4D-GTV). Margins were added to account for the clinical target volume (CTV) and internal target motion (ITV) in 3D and 4D simulation scans. Additional margins were added to account for planned target volume (PTV). Univariate and multivariate analyses were performed to test the impact of the volume of the GTV and location of the tumor (relative to the bronchial tree and lung lobes) on PTV changes by more than 10% between the 3D and 4D scans.ResultsA total of 10 patients were identified. 3D-PTV was significantly larger than the 4D-PTV; median volumes were 182.79 vs. 158.21 cc, p = 0.0068). On multivariate analysis, neither the volume of the GTV (p = 0.5027) nor the location of the tumor (peripheral, p = 0.5027 or lower location, p = 0.5802) had an impact on PTV differences between 3D-simulation and 4D-simluation.ConclusionThe use of 4D-simulation reduces the PTV for the primary tumor in lung cancer cases. Further studies with larger samples are required to confirm the benefit of 4D-simulation in decreasing PTV in lung cancer.     

Evaluation of the Lung Cancer Risks at Which to Screen Ever- and Never-Smokers: Screening Rules Applied to the PLCO and NLST Cohorts

BackgroundLung cancer risks at which individuals should be screened with computed tomography (CT) for lung cancer are undecided. This study''s objectives are to identify a risk threshold for selecting individuals for screening, to compare its efficiency with the U.S. Preventive Services Task Force (USPSTF) criteria for identifying screenees, and to determine whether never-smokers should be screened. Lung cancer risks are compared between smokers aged 55–64 and ≥65–80 y.ConclusionsThe USPSTF criteria for CT screening include some low-risk individuals and exclude some high-risk individuals. Use of the PLCO_m2012 risk ≥0.0151 criterion can improve screening efficiency. Currently, never-smokers should not be screened. Smokers aged ≥65–80 y are a high-risk group who may benefit from screening. Please see later in the article for the Editors'' Summary     

Association of arsenic exposure with lung cancer incidence rates in the United States

Background

Although strong exposure to arsenic has been shown to be carcinogenic, its contribution to lung cancer incidence in the United States is not well characterized. We sought to determine if the low-level exposures to arsenic seen in the U.S. are associated with lung cancer incidence after controlling for possible confounders, and to assess the interaction with smoking behavior.

Methodology

Measurements of arsenic stream sediment and soil concentration obtained from the USGS National Geochemical Survey were combined, respectively, with 2008 BRFSS estimates on smoking prevalence and 2000 U.S. Census county level income to determine the effects of these factors on lung cancer incidence, as estimated from respective state-wide cancer registries and the SEER database. Poisson regression was used to determine the association between each variable and age-adjusted county-level lung cancer incidence. ANOVA was used to assess interaction effects between covariates.

Principal Findings

Sediment levels of arsenic were significantly associated with an increase in incident cases of lung cancer (P<0.0001). These effects persisted after controlling for smoking and income (P<0.0001). Across the U.S., exposure to arsenic may contribute to up to 5,297 lung cancer cases per year. There was also a significant interaction between arsenic exposure levels and smoking prevalence (P<0.05).

Conclusions/Significance

Arsenic was significantly associated with lung cancer incidence rates in the U.S. after controlling for smoking and income, indicating that low-level exposure to arsenic is responsible for excess cancer cases in many parts of the U.S. Elevated county smoking prevalence strengthened the association between arsenic exposure and lung cancer incidence rate, an effect previously unseen on a population level.     

Application of radiography of computed tomography in non-small cell lung cancer using prognosis model

ObjectiveStudying the diagnostic value of CT imaging in non-small cell lung cancer (NSCLC), and establishing a prognosis model combined with clinical characteristics is the objective, so as to provide a reference for the survival prediction of NSCLC patients.MethodCT scan data of NSCLC 200 patients were taken as the research object. Through image segmentation, the radiology features of CT images were extracted. The reliability and performance of the prognosis model based on the optimal feature number of specific algorithm and the prognosis model based on the global optimal feature number were compared.Results30-RELF-NB (30 optimal features, RELF feature selection algorithm and NB classifier) has the highest accuracy and AUC (area under the subject characteristic curve) in the prognosis model based on the optimal features of specific algorithm. Among the prognosis models based on global optimal features, 25-NB (25 global optimal features, naive Bayes classification algorithm classifier) has the highest accuracy and AUC. Compared with the prediction model based on feature training of specific feature selection algorithm, the overall performance and stability of the prediction model based on global optimal feature are higher.ConclusionThe prognosis model based on the global optimal feature established in this paper has good reliability and performance, and can be applied to the CT radiology of NSCLC.     

Young adult cancer incidence trends in Taiwan and the U.S. from 2002 to 2016

BackgroundPrevious studies have not examined young adult cancer incidence trends in Taiwan, or comprehensively compared these trends at two nations with different population genetics, environmental exposures, and health care. Therefore, we compared the incidence rates and trends of the most common young adult cancers diagnosed at 20–39 years of age in Taiwan and the U.S.MethodsIncidence rates from 2002 to 2016 were calculated from the Taiwan National Health Insurance Research Datasets and the U.S. Surveillance, Epidemiology, and End Results Program. For trend assessment, average annual percent change (AAPC) values were calculated from 15 years of data using Joinpoint Regression Program. We also obtained sex or age of diagnosis stratified estimates.ResultsThe age-standardized overall young adult cancer incidence rate significantly increased from 2002 to 2016 in both Taiwan (AAPC=1.1%, 95% CI: 0.8–1.5%) and the U.S. (AAPC=1.8%, 95% CI: 1.1–2.4%). Cancers with significantly decreasing trends in Taiwan included cancers of the nasopharynx, liver, and tongue, which were not among the most common young adult cancers in the U.S. Cancers with significantly increasing trends in both Taiwan and the U.S. included colorectal, thyroid, and female breast cancers. Lymphoma, ovarian cancer, and lung and bronchus cancer had significantly increasing trends in Taiwan but not in the U.S. Although cervical cancer had significantly decreasing trends in both nations among those 30–39 years of age, its trend was significantly increasing in Taiwan but decreasing in the U.S. among those 20–29 years of age.ConclusionThe types of common young adult cancers as well as their incidence rates and trends differed in Taiwan and the U.S. Future studies should further understand the etiological factors driving these trends.     

Predictive value of vascular calcification identified in 4D planning CT of lung cancer patients treated with stereotactic body radiation therapy

PurposeThe aim was to identify vascular calcification in 4DCT scan of lung cancer patients and establish the association between overall survival (OS) and vascular calcification, as surrogate for vascular health.MethodsVascular calcification within the thoracic cavity were segmented in 334 lung cancer patients treated with stereotactic body radiation therapy (SBRT). This has been done automatically on 4D planning CT and average reconstruction scans. Correlation between cardiac comorbidity and calcification volumes was evaluated for patients with recorded Adult Co-Morbidity Evaluation (n = 303). Associations between the identified calcifications and OS were further investigated.ResultsThe volume of calcification from the average scan was significantly lower than from each phase (p < 0.001). The highest level of correlations between cardiac comorbidity and volume of the calcifications were found for one phase representing inhale and two phases representing exhale with the least motion blurring due to respiration (p < 0.005). The volume of the calcifications was subsequently averaged over these three phases. The average of calcification volumes over the three phases (denoted by inhale-exhale) showed the highest likelihood in univariate analysis and was chosen as vascular calcification measure. Cox-model suggested that tumor volume (Hazard Ratio [HR] = 1.46, p < 0.01) and inhale-exhale volume (HR = 1.05, p < 0.05) are independent factors predicting OS after adjusting for age, sex, and performance status.ConclusionIt was feasible to use. It 4DCT scan for identifying thoracic calcifications in lung cancer patients treated with SBRT. Calcification volumes from inhale-exhale phases had the highest correlation with overall cardiac comorbidity and the average of the calcification volume obtained from these phases was an independent predictive factor for OS.     

Diagnosis of chronic obstructive pulmonary disease in lung cancer screening Computed Tomography scans: independent contribution of emphysema,air trapping and bronchial wall thickening

Background

Beyond lung cancer, screening CT contains additional information on other smoking related diseases (e.g. chronic obstructive pulmonary disease, COPD). Since pulmonary function testing is not regularly incorporated in lung cancer screening, imaging biomarkers for COPD are likely to provide important surrogate measures for disease evaluation. Therefore, this study aims to determine the independent diagnostic value of CT emphysema, CT air trapping and CT bronchial wall thickness for COPD in low-dose screening CT scans.

Methods

Prebronchodilator spirometry and volumetric inspiratory and expiratory chest CT were obtained on the same day in 1140 male lung cancer screening participants. Emphysema, air trapping and bronchial wall thickness were automatically quantified in the CT scans. Logistic regression analysis was performed to derivate a model to diagnose COPD. The model was internally validated using bootstrapping techniques.

Results

Each of the three CT biomarkers independently contributed diagnostic value for COPD, additional to age, body mass index, smoking history and smoking status. The diagnostic model that included all three CT biomarkers had a sensitivity and specificity of 73.2% and 88.%, respectively. The positive and negative predictive value were 80.2% and 84.2%, respectively. Of all participants, 82.8% was assigned the correct status. The C-statistic was 0.87, and the Net Reclassification Index compared to a model without any CT biomarkers was 44.4%. However, the added value of the expiratory CT data was limited, with an increase in Net Reclassification Index of 4.5% compared to a model with only inspiratory CT data.

Conclusion

Quantitatively assessed CT emphysema, air trapping and bronchial wall thickness each contain independent diagnostic information for COPD, and these imaging biomarkers might prove useful in the absence of lung function testing and may influence lung cancer screening strategy. Inspiratory CT biomarkers alone may be sufficient to identify patients with COPD in lung cancer screening setting.     

不同放射剂量CT在早期非小细胞肺癌中筛检价值对比

摘要 目的：探讨与对比不同放射剂量计算机断层扫描(Computed Tomography,CT)在早期非小细胞肺癌中筛检价值。方法：2020年1月到2020年12月选择在本院经病理确诊为肺内磨玻璃样结节患者98例作为研究对象,所有患者都给予常规剂量正电子发射计算机断层扫描(Positron emission tomography,PET)/CT检查与低剂量PET/CT检查,记录成像特征、辐射剂量并判定筛检价值。结果：低剂量PET/CT对肺部增厚、边界不规则、钙化、囊变的检出率高于常规剂量PET/CT(P<0.05)。低剂量PET/CT与常规剂量PET/CT的图像质量优良率为98.0 %和96.9 %,对比差异无统计学意义(P>0.05)。低剂量PET/CT的有效放射剂量、剂量长度乘积低于常规剂量PET/CT(P<0.05)。低剂量PET/CT的最大标准摄取值(maximum standardized uptake value,SUVmax)值低于常规剂量PET/CT(P<0.05)。低剂量PET/CT与常规剂量PET/CT分别筛检非小细胞肺癌51例与37例,筛检敏感性分别为98.1 %和69.2 %,特异性分别为100.0 %和97.8 %。结论：低放射剂量PET/CT在肺结节中的应用不会影响图像质量,且能降低辐射剂量,提高对早期非小细胞肺癌患者的筛检效果。     

Short- and long-term survival outcomes among never smokers who developed lung cancer

BackgroundLung cancer is the leading cause of cancer death in the US. While an extensive literature exists detailing lung cancer risk factors and mortality among patients with a history of tobacco use, the data are more limited among individuals who have never smoked. The purpose of this investigation is to compare survival rates between the two groups and evaluate potential risk factors among never smokers.MethodsThis retrospective study included 3380 smokers and 334 never smokers who were diagnosed with lung cancer at Stony Brook University Hospital between 2003 and 2016. 1-, 3-, 5- and 10-year survival outcomes, stratified by smoking status, were compared and Kaplan-Meier curves for overall survival are provided. Cox Proportional Hazard models were used to evaluate factors influencing survival among never smokers.ResultsNever smokers with lung cancer were more likely to be female, be diagnosed with adenocarcinoma histology, and had fewer comorbidities than lung cancer patients who smoked. Although 60% of patients were diagnosed at a later stage of disease development, regardless of smoking status, overall short- and long-term survival was significantly higher among never smokers compared to those with a history of tobacco use. In addition to age and stage at diagnosis, a history of diabetes was found to be a significant prognostic factor for decreased survival among never smokers (HR=3.15, 95% CI (1.74, 5.71)).ConclusionsData from the present investigation suggest that, regardless of smoking status, approximately three of every five lung cancer patients are diagnosed at a later stage, and that both short- and long-term survival outcomes are significantly better among never smokers compared to those with a history of tobacco use. Additional studies are required to validate these findings and better explain the mechanistic drivers for the improved outcomes among never smokers.     

Longitudinal multistage model for lung cancer incidence, mortality, and CT detected indolent and aggressive cancers

It is currently not known whether most lung cancers detected by computerized tomography (CT) screening are aggressive and likely to be fatal if left untreated, or if a sizable fraction are indolent and unlikely to cause death during the natural lifetime of the individual. We developed a longitudinal biologically-based model of the relationship between individual smoking histories and the probability for lung cancer incidence, CT screen detection, lung cancer mortality, and other-cause mortality. The longitudinal model relates these different outcomes to an underlying lung cancer disease pathway and an effective other-cause mortality pathway, which are both influenced by the individual smoking history. The longitudinal analysis provides additional information over that available if these outcomes were analyzed separately, including testing if the number of CT detected and histologically-confirmed lung cancers is consistent with the expected number of lung cancers "in the pipeline". We assume indolent nodules undergo Gompertz growth and are detectable by CT, but do not grow large enough to contribute significantly to symptom-based lung cancer incidence or mortality. Likelihood-based model calibration was done jointly to data from 6878 heavy smokers without asbestos exposure in the control (placebo) arm of the Carotene and Retinol Efficacy Trial (CARET); and to 3,642 heavy smokers with comparable smoking histories in the Pittsburgh Lung Screening Study (PLuSS), a single-arm prospective trial of low-dose spiral CT screening for diagnosis of lung cancer. Model calibration was checked using data from two other single-arm prospective CT screening trials, the New York University Lung Cancer Biomarker Center (NYU) (n=1,021), and Moffitt Cancer Center (Moffitt) cohorts (n=677). In the PLuSS cohort, we estimate that at the end of year 2, after the baseline and first annual CT exam, that 33.0 (26.9, 36.9)% of diagnosed lung cancers among females and 7.0 (4.9,11.7)% among males were overdiagnosed due to being indolent cancers. At the end of the PLuSS study, with maximum follow-up of 5.8years, we estimate that due to early detection by CT and limited follow-up, an additional 2.2 (2.0,2.4)% of all diagnosed cancers among females and 7.1 (6.7,8.0)% among males would not have been diagnosed in the absence of CT screening. We also find a higher apparent cure rate for lung cancer among CARET females than males, consistent with the larger indolent fraction of CT detected and histologically confirmed lung cancers among PLuSS females. This suggests that there are significant gender differences in the aggressiveness of lung cancer. Females may have an inherently higher proportion of indolent lung cancers than males, or aggressive lung cancers may be brought into check by the immune system more frequently among females than males.     

Blood-based lung cancer biomarkers identified through proteomic discovery in cancer tissues,cell lines and conditioned medium

Background

Support for early detection of lung cancer has emerged from the National Lung Screening Trial (NLST), in which low-dose computed tomography (LDCT) screening reduced lung cancer mortality by 20 % relative to chest x-ray. The US Preventive Services Task Force (USPSTF) recently recommended annual screening for the high-risk population, concluding that the benefits (life years gained) outweighed harms (false positive findings, abortive biopsy/surgery, radiation exposure). In making their recommendation, the USPSTF noted that the moderate net benefit of screening was dependent on the resolution of most false-positive results without invasive procedures. Circulating biomarkers may serve as a valuable adjunctive tool to imaging.

Results

We developed a broad-based proteomics discovery program, integrating liquid chromatography/mass spectrometry (LC/MS) analyses of freshly resected lung tumor specimens (n = 13), lung cancer cell lines (n = 17), and conditioned media collected from tumor cell lines (n = 7). To enrich for biomarkers likely to be found at elevated levels in the peripheral circulation of lung cancer patients, proteins were prioritized based on predicted subcellular localization (secreted, cell-membrane associated) and differential expression in disease samples. 179 candidate biomarkers were identified. Several markers selected for further validation showed elevated levels in serum collected from subjects with stage I NSCLC (n = 94), relative to healthy smoker controls (n = 189). An 8-marker model was developed (TFPI, MDK, OPN, MMP2, TIMP1, CEA, CYFRA 21–1, SCC) which accurately distinguished subjects with lung cancer (n = 50) from high risk smokers (n = 50) in an independent validation study (AUC = 0.775).

Conclusions

Integrating biomarker discovery from multiple sample types (fresh tissue, cell lines and conditioned medium) has resulted in a diverse repertoire of candidate biomarkers. This unique collection of biomarkers may have clinical utility in lung cancer detection and diagnoses.

Electronic supplementary material

The online version of this article (doi:10.1186/s12014-015-9090-9) contains supplementary material, which is available to authorized users.