Annual Low-dose Computed Tomography Screening Research Articles

Selection of Sensitive Methylation Markers for the Detection of Non-small Cell Lung Cancer

Introduction: While early-stage lung cancer is curable by surgical resection, most patients are diagnosed with advanced- stage disease. Annual low-dose computed tomography screening decreases lung cancer mortality, however effective biomarkers to address the high false positive rate and to better define high risk individuals are lacking. This study was designed to identify potential DNA methylation markers for the detection of non-small cell lung cancer, the most common type of lung cancer. Methods: 152 candidate methylation genes were first investigated in lung cancer cell lines and a pilot set of lung tissues. Five promising methylated genes, DMRTA, HOXA9, ZIC4, HOXA7, and SIX3, were selected and further validated in 150 non-small cell lung cancers and 142 tumor-free surrounding lung tissues using the quantitative methylation-specific PCR. Results: Methylation levels of DMRTA2, HOXA9, ZIC4, HOXA7, and SIX3 were significantly higher in tumors compared to tumor-free surrounding lung tissues (P 0.05). Conclusion: We identified a group of highly sensitive and specific methylation markers in non-small cell lung cancer. These markers are potential valuable candidates to improve the performance of lung cancer screening.

Low-Dose Chest Computed Tomography for Lung Cancer Screening Among Hodgkin Lymphoma Survivors: A Cost-Effectiveness Analysis

Hodgkin lymphoma (HL) survivors face an increased risk of treatment-related lung cancer. Screening with low-dose computed tomography (LDCT) may allow detection of early stage, resectable cancers. We developed a Markov decision-analytic and cost-effectiveness model to estimate the merits of annual LDCT screening among HL survivors. Population databases and HL-specific literature informed key model parameters, including lung cancer rates and stage distribution, cause-specific survival estimates, and utilities. Relative risks accounted for radiation therapy (RT) technique, smoking status (>10 pack-years or current smokers vs not), age at HL diagnosis, time from HL treatment, and excess radiation from LDCTs. LDCT assumptions, including expected stage-shift, false-positive rates, and likely additional workup were derived from the National Lung Screening Trial and preliminary results from an internal phase 2 protocol that performed annual LDCTs in 53 HL survivors. We assumed a 3% discount rate and a willingness-to-pay (WTP) threshold of $50,000 per quality-adjusted life year (QALY). Annual LDCT screening was cost effective for all smokers. A male smoker treated with mantle RT at age 25 achieved maximum QALYs by initiating screening 12 years post-HL, with a life expectancy benefit of 2.1 months and an incremental cost of $34,841/QALY. Among nonsmokers, annual screening produced a QALY benefit in some cases, but the incremental cost was not below the WTP threshold for any patient subsets. As age at HL diagnosis increased, earlier initiation of screening improved outcomes. Sensitivity analyses revealed that the model was most sensitive to the lung cancer incidence and mortality rates and expected stage-shift from screening. HL survivors are an important high-risk population that may benefit from screening, especially those treated in the past with large radiation fields including mantle or involved-field RT. Screening may be cost effective for all smokers but possibly not for nonsmokers despite a small life expectancy benefit.

In Response

In Response

A cost-utility analysis of lung cancer screening and the additional benefits of incorporating smoking cessation interventions.

BackgroundA 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 FindingsThe 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.ConclusionsThe 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.

Screening for lung cancer.

This is an updated version of the original review published inThe Cochrane Library in 1999 and updated in 2004 and 2010. Population-based screening for lung cancer has not been adopted in the majority of countries. However it is not clear whether sputum examinations, chest radiography or newer methods such as computed tomography (CT) are effective in reducing mortality from lung cancer. To determine whether screening for lung cancer, using regular sputum examinations, chest radiography or CT scanning of the chest, reduces lung cancer mortality. We searched electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 5), MEDLINE (1966 to 2012), PREMEDLINE and EMBASE (to 2012) and bibliographies. We handsearched the journal Lung Cancer (to 2000) and contacted experts in the field to identify published and unpublished trials. Controlled trials of screening for lung cancer using sputum examinations, chest radiography or chest CT. We performed an intention-to-screen analysis. Where there was significant statistical heterogeneity, we reported risk ratios (RRs) using the random-effects model. For other outcomes we used the fixed-effect model. We included nine trials in the review (eight randomised controlled studies and one controlled trial) with a total of 453,965 subjects. In one large study that included both smokers and non-smokers comparing annual chest x-ray screening with usual care there was no reduction in lung cancer mortality (RR 0.99, 95% CI 0.91 to 1.07). In a meta-analysis of studies comparing different frequencies of chest x-ray screening, frequent screening with chest x-rays was associated with an 11% relative increase in mortality from lung cancer compared with less frequent screening (RR 1.11, 95% CI 1.00 to 1.23); however several of the trials included in this meta-analysis had potential methodological weaknesses. We observed a non-statistically significant trend to reduced mortality from lung cancer when screening with chest x-ray and sputum cytology was compared with chest x-ray alone (RR 0.88, 95% CI 0.74 to 1.03). There was one large methodologically rigorous trial in high-risk smokers and ex-smokers (those aged 55 to 74 years with ≥ 30 pack-years of smoking and who quit ≤ 15 years prior to entry if ex-smokers) comparing annual low-dose CT screening with annual chest x-ray screening; in this study the relative risk of death from lung cancer was significantly reduced in the low-dose CT group (RR 0.80, 95% CI 0.70 to 0.92). The current evidence does not support screening for lung cancer with chest radiography or sputum cytology. Annual low-dose CT screening is associated with a reduction in lung cancer mortality in high-risk smokers but further data are required on the cost effectiveness of screening and the relative harms and benefits of screening across a range of different risk groups and settings.

Lung Cancer Screening

Lung cancer is the leading cause of cancer death. Although smoking prevention and cessation programs have decreased lung cancer mortality, there remains a large at-risk population. Dismal long-term survival rates persist despite improvements in diagnosis, staging, and treatment. Early efforts to identify an effective screening test have been unsuccessful. Recent advances in multidetector computed tomography have allowed screening studies using low-dose computed tomography (LDCT) to be performed. This set the stage for the National Lung Screening Trial that found that annual LDCT screening benefits individuals at high risk for lung cancer. An understanding of the harmful effects of lung cancer screening is required to help maximize the benefits and decrease the risks of a lung cancer screening program. Although many questions remain regarding LDCT screening, a comprehensive lung cancer screening program of high-risk individuals will increase detection of preclinical and potentially curable disease, creating a new model of lung cancer surveillance and management.

Finding needles in a haystack: annual low-dose computed tomography screening reduces lung cancer mortality in a high-risk group

Evaluation of: Aberle DR, Adams AM, Berg CD et al.; National Lung Screening Trial Research Team. Reduced lung-cancer mortality with low-dose computed tomographic screening. N. Engl. J. Med. 365(5), 395–409 (2011).Lung cancer is a global health issue. Compared with other common malignancies, the prognosis is poor as many patients present with advanced disease. The National Lung Screening Trial (NLST) aimed to identify and treat early lung cancers using annual low-dose computed tomography (CT) screening in a high-risk group. When compared with chest x-ray screening, low-dose CT screening reduced lung cancer mortality by 20%; the NLST is the first lung cancer screening trial to demonstrate such a mortality benefit. However, we must wait for cost–effectiveness data from the NLST, as well as the results of ongoing European studies comparing low-dose CT with observation alone, before firm conclusions can be drawn regarding the overall benefits of introducing a CT screening program to clinical practice.

Computed tomography screening for lung cancer in Hodgkin's lymphoma survivors: decision analysis and cost-effectiveness analysis

Hodgkin's lymphoma patients have an elevated risk of developing lung cancer and may be targeted for lung cancer screening. We used a decision-analytic model to estimate the potential clinical benefits and cost-effectiveness of computed tomography (CT) screening for lung cancer in Hodgkin's lymphoma survivors. We developed a Markov decision-analytic model to compare annual low-dose CT screening versus no screening in a hypothetical cohort of patients diagnosed with stage IA-IIB Hodgkin's lymphoma at age 25, with screening starting 5 years after initial diagnosis. We derived model parameters from published studies and the Surveillance, Epidemiology and End Results (SEER) Program, and assumed that stage-shift produces a survival benefit. Annual CT screening increased survival by 0.64 years for smokers and 0.16 years for non-smokers. The corresponding benefits in quality-adjusted survival were 0.58 quality-adjusted life-years (QALYs) for smokers and 0.14 QALYs for non-smokers. The incremental cost-effectiveness ratios for annual CT screening compared with no screening were $34 100/QALY for smokers and $125 400/QALY for non-smokers. Our analysis suggests that if early promising results for lung cancer screening hold, CT screening for lung cancer may increase survival and quality-adjusted survival among Hodgkin's lymphoma survivors, with a benefit and incremental cost-effectiveness ratio for smokers comparable to that of other recommended cancer screening strategies.