NCCN Categories of Evidence and Consensus
Category 1: Based upon high-level evidence, there is uniform NCCN consensus that the intervention is appropriate.
Category 2A: Based upon lower-level evidence, there is uniform NCCN consensus that the intervention is appropriate.
Category 2B: Based upon lower-level evidence, there is NCCN consensus that the intervention is appropriate.
Category 3: Based upon any level of evidence, there is major NCCN disagreement that the intervention is appropriate.
All recommendations are category 2A unless otherwise noted.
Clinical trials: NCCN believes that the best management for any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.
Overview
Lung cancer is the leading cause of cancer-related mortality in the United States and worldwide.1–5 In 2018, it is estimated that 154,050 deaths from lung cancer will occur in the United States.6 Five-year survival rates for lung cancer are only 18%, partly because most patients have advanced-stage lung cancer at initial diagnosis.7 Currently, most lung cancer is diagnosed clinically when patients present with symptoms such as persistent cough, pain, and weight loss; unfortunately, patients with these symptoms usually have advanced lung cancer. These facts—combined with the success of cervical, colon, and breast cancer screening—have been the impetus for developing an effective lung cancer screening (LCS) test.8–10 Ideally, effective screening will lead to earlier detection of lung cancer—before patients have symptoms and when treatment is more likely to be effective—and will decrease mortality.11 Data support using low-dose computed tomography (LDCT) of the chest to screen select patients who are at high risk for lung cancer.11–15 Chest x-ray is not recommended for LCS.11,16,17
The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for LCS were developed in 2011 and have been updated every year.11,18,19 The NCCN Guidelines 1) describe risk factors for lung cancer; 2) recommend criteria for selecting individuals with high-risk factors for screening; 3) provide recommendations for evaluation and follow-up of lung nodules found during screening; 4) discuss the accuracy of chest LDCT screening; and 5) discuss the benefits and risks of LDCT screening. The “Summary of the Guidelines Updates” section in the algorithm (available at NCCN.org) briefly describes the new changes for 2018. For example, the NCCN cutoff thresholds for lung nodules have been revised to harmonize with the Lung Imaging Reporting and Data System (Lung-RADS) cutoffs.20–22 The complete version of the NCCN Guidelines for Lung Cancer Screening provides recommendations for initial and subsequent LDCT screening and provides more detail about LDCT screening than this manuscript (see
NCCN Clinical Practice Guidelines in Oncology: Lung Cancer Screening, Version 3.2018
Version 3.2018, 01-18-18 ©2018 National Comprehensive Cancer Network, Inc. All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.
Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 16, 4; 10.6004/jnccn.2018.0020
NCCN Clinical Practice Guidelines in Oncology: Lung Cancer Screening, Version 3.2018
Version 3.2018, 01-18-18 ©2018 National Comprehensive Cancer Network, Inc. All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.
Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 16, 4; 10.6004/jnccn.2018.0020
NCCN Clinical Practice Guidelines in Oncology: Lung Cancer Screening, Version 3.2018
Version 3.2018, 01-18-18 ©2018 National Comprehensive Cancer Network, Inc. All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.
Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 16, 4; 10.6004/jnccn.2018.0020
NCCN Clinical Practice Guidelines in Oncology: Lung Cancer Screening, Version 3.2018
Version 3.2018, 01-18-18 ©2018 National Comprehensive Cancer Network, Inc. All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.
Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 16, 4; 10.6004/jnccn.2018.0020
The goal of screening is to detect disease at a stage when it is not causing symptoms and when treatment will be most successful. Screening should benefit the individual by increasing life expectancy and increasing quality of life. False-positive results should be low to prevent unnecessary additional testing. The screening test should 1) improve outcomes; 2) be scientifically validated; and 3) be low risk, reproducible, accessible, and cost-effective. LCS is not a substitute for smoking cessation.23 Smokers, including those undergoing LCS, should always be encouraged to quit smoking tobacco (see the NCCN Guidelines for Smoking Cessation, available at NCCN.org).24–26 Likewise, former smokers should be encouraged to remain abstinent. Programs using behavioral counseling combined with medications that promote smoking cessation (approved by the FDA) can help individuals to quit smoking.23,27,28
Literature Search Criteria and Guidelines Update Methodology
An electronic search of the PubMed database was performed to obtain key literature in LCS, The search results were narrowed by selecting studies in humans published in English. Results were confined to the following article types: clinical trial, phase 2; clinical trial, phase 3; clinical trial, phase 4; guideline; meta-analysis; randomized controlled trial; systematic reviews; and validation studies. The data from key PubMed articles have been included in this discussion. If high-level evidence is lacking, recommendations are based on the panel's review of lower-level evidence and expert opinion. The complete details of the development and update of the NCCN Guidelines are available on the NCCN webpage (NCCN.org).
LDCT as Part of a Lung Screening Program
LCS with LDCT should be part of a program of care and should not be performed in isolation as a free-standing test.20,29–31 Trained personnel and a system to contact patients to achieve compliance with recommended follow-up studies are required for an effective lung screening program.30,32,33 The NCCN-recommended follow-up intervals assume compliance with follow-up recommendations. To help ensure good image quality, all chest LDCT screening programs should use CT scanners that meet the standards of the American College of Radiology (ACR). The ACR has developed Lung-RADS to standardize the reporting and management of LDCT lung examinations.20,34 The Lung-RADS protocol has been shown to improve the detection of lung cancer and to decrease the false-positive rate.22,30,32,34,35
When assessing scans, the most important radiologic factor is change or stability of nodules when compared with a previous imaging study. The risks and benefits of LCS should be discussed with the individual before a screening LDCT scan is performed.36–39 Shared patient/physician decision-making is recommended before LDCT lung screening, especially for patients with comorbid conditions.16,40,41 Institutions performing LCS should use a multidisciplinary approach, such as chest radiology, pulmonary medicine, and thoracic surgery.42 Only centers with considerable expertise in LCS should perform LDCT.43
Randomized Trials
Multiple randomized trials have assessed LDCT screening for lung cancer among high-risk groups.10,12,44–58 The National Lung Screening Trial (NLST) showed that LDCT decreased the relative risk (RR) of death from lung cancer by 20% (95% CI, 6.8–26.7; P=.004) when compared with chest radiography alone.11 Although the NLST also reported a significant decrease in all-cause mortality of 7%, the apparent decrease is not significant after lung cancer mortality has been subtracted. Analyses of some LCS studies using LDCT scans suggest that overdiagnosis (ie, diagnosis of cancer that would never be life-threatening) and false-positive results are significant concerns.59–61 A phase 3 randomized trial (The Prostate, Lung, Colorectal, and Ovarian [PLCO] trial) reported that annual screening with chest radiography is not useful for LCS in individuals at low risk for lung cancer.62
Lung Cancer Screening Guidelines
NCCN was the first major organization to develop LCS guidelines using LDCT based on the NLST data.18 The U.S. Preventive Services Task Force (USPSTF) recommends lung screening with LDCT; their B recommendation means that lung screening is covered under the Affordable Care Act for individuals with high-risk factors who are 55 to 80 years of age.16 The Centers for Medicare & Medicaid Services (CMS) covers annual screening LDCT for appropriate Medicare beneficiaries at high risk for lung cancer (ie, smokers and former smokers ages 55–77 years with a 30 pack-year smoking history) if they also receive counseling and participate in shared decision-making before screening. The American College of Chest Physicians and ASCO also recommend LCS with LDCT for individuals at high risk if they meet the criteria of the NLST (ie, smokers and former smokers ages 55–74 years with a 30 pack-year smoking history).43 Other organizations have also developed guidelines for LCS with LDCT.16,63–65
Risk Factors for Lung Cancer
An essential goal of any LCS protocol is to identify the populations that are at a high risk for developing the disease. Although smoking tobacco is a well-established risk factor for lung cancer, other environmental and genetic factors also seem to increase risk.34,66–69 This section reviews the currently known risk factors for the development of lung cancer to identify populations with high-risk factors that should be targeted for screening. Individuals with high-risk factors who are candidates for screening should not have any symptoms suggestive of lung cancer (eg, cough, pain, weight loss).
Tobacco Smoke
Active Tobacco Use: Tobacco smoking is a major modifiable risk factor in the development of lung cancer and accounts for 85% of all lung cancer-related deaths.3,8,9 Approximately 36.5 million adults in the United States smoke cigarettes.70 Smoking tobacco is also associated with other cancers and diseases, such as kidney, bladder, pancreatic, gastric, or cervical cancer or acute myeloid leukemia.3 It is estimated that about 443,000 United States adults die from smoking-related illnesses each year; cigarette smoking is estimated to cause about 30% of deaths due to cancer.71,72 Globally, experts estimate that deaths from smoking tobacco will increase to 10 million by 2020.73 The risk of developing lung cancer from smoking tobacco has been firmly established. Tobacco smoke contains more than 50 known carcinogens.74–77
A dose–response relationship exists between smoking tobacco and the risk of developing lung cancer; however, there is no risk-free level of tobacco exposure. The RR for lung cancer is approximately 20-fold higher for smokers than for nonsmokers.3,78 Cessation of tobacco smoking decreases the risk for lung cancer.74,79–82 Former smokers have a higher risk for lung cancer compared with never-smokers. Current or past history of tobacco smoking is considered a risk factor for the development of lung cancer, irrespective of the magnitude of exposure and the time since smoking cessation. In the NCCN Guidelines, individuals aged 55 to 74 years with a 30 or more pack-year history of smoking tobacco are selected as the highest-risk group for lung cancer and are recommended for LDCT screening (category 1) based on NLST criteria.10,11 Individuals with a 30 pack-year smoking history who quit smoking fewer than 15 years ago are still in this highest-risk group. Pack-years of smoking history is defined as the number of packs of cigarettes smoked every day multiplied by the number of years of smoking. Data for determining whether patients are at high risk for cancer are based on cigarette smoking and not on other kinds of tobacco products.83,84
Exposure to Second-Hand Smoke: Studies have suggested that second-hand smoke (also known as environmental tobacco smoke, passive smoke, and involuntary smoke) causally increases the risk for lung cancer among nonsmokers.85,86 The NCCN Panel does not feel that second-hand smoke is an independent risk factor, because the association is either weak or variable. Second-hand smoke does not confer a great enough risk for exposed individuals to be candidates for LCS. An analysis of 37 studies found an RR of 1.24 (95% CI, 1.13–1.36) for adult nonsmokers who live with a smoker.87 An estimate from 25 studies found an RR of 1.22 (95% CI, 1.13–1.33) for lung cancer risk from exposure to second-hand smoke at the workplace.85 The pooled estimate for 6 studies suggests a dose–response relationship between number of years of second-hand smoke exposure and lung cancer risk.85 Data are inconsistent for second-hand smoke exposure during childhood and subsequent lung cancer risk in adulthood.85
Occupational Exposure to Carcinogens
Carcinogens targeting the lungs include arsenic, chromium, asbestos, nickel, cadmium, beryllium, silica, diesel fumes, coal smoke, and soot.67,88–93 The calculated mean RR for development of lung cancer is 1.59 for individuals in the United States who have a known occupational exposure to these carcinogens.67,93 Among those who are exposed to these carcinogens, data suggest that smokers have a greater risk for lung cancer than nonsmokers.88,90,94–96
Residential Radon Exposure
Radon (a gaseous decay product of uranium-238 and radium-226) has been implicated in the development of lung cancer.97 The risk for lung cancer from occupational exposure among uranium miners is well established.98 The risk associated with residential radon is uncertain. A meta-analysis in 1997 of 8 studies yielded an estimated RR of 1.14 (95% CI, 1.0–1.3).99 A 2005 meta-analysis of 13 studies (using individual data from patients) reported a linear relationship between the amount of radon detected in a home and the risk of developing lung cancer.100 Among those exposed to radon, smokers have a greater risk for lung cancer than nonsmokers.100 The NCCN Panel feels that radon is a risk factor if there is a documented sustained and substantially elevated radon exposure.
History of Cancer
Evidence shows an increased risk for new primary lung cancers among patients who survive lung cancer, lymphomas, cancers of the head and neck, or smoking-related cancers, such as bladder cancer.101 Patients who survive small cell lung cancer have a 3.5-fold increase in the risk for developing a new primary cancer, predominantly non-small cell lung cancer (NSCLC).102 Risk for second lung cancers is increased if survivors continue smoking.103 Patients previously treated with chest irradiation have a 13-fold increase in risk for developing new primary lung cancer, and those previously treated with alkylating agents have an estimated RR of 9.4. In patients previously treated for Hodgkin lymphoma, the RR for new primary lung cancer is 4.2 if previously treated with alkylating agents and 5.9 if previously treated with 5 Gy or more of radiation therapy.104 In patients with laryngeal or hypopharyngeal cancer, the lung is the most common site of second primary cancers.105 Evidence suggests that patients who are successfully treated (ie, cured) for an initial smoking-related lung cancer and who stop smoking will have a decreased risk for a subsequent smoking-related cancer compared with those who continue smoking.106,107
Family History of Lung Cancer
Several studies have suggested an increased risk for lung cancer among first-degree relatives of patients with lung cancer, even after adjustment for age, gender, and smoking habits.74,108,109 A meta-analysis of 28 case-control studies and 17 observational cohort studies showed an RR of 1.8 (95% CI, 1.6–2.0) for individuals with a sibling/parents or a first-degree relative with lung cancer.110 The risk is greater in individuals with multiple affected family members or who had a cancer diagnosis at a young age. Although no high-penetrance inherited syndrome has been described for lung cancer (either small cell lung cancer or NSCLC), several groups have identified genetic loci that may be associated with an increased risk of developing lung cancer.111–115 Patients with classic familial cancer susceptibility syndromes (such as retinoblastoma and Li-Fraumeni syndrome) have a substantially increased risk for lung cancer if they also smoke tobacco.116–118
History of Lung Disease
A history of chronic obstructive pulmonary disease (COPD) is associated with lung cancer risk,119–125 which may be largely caused by smoking.115 COPD is associated with 12% of lung cancer cases among heavy smokers.126 Data suggest that lower pack-year thresholds may be useful to trigger LDCT screening in individuals with COPD.127 Evidence suggests that the association between COPD and lung cancer may not be entirely caused by smoking.128–130 For example, 1) family history of chronic bronchitis and emphysema is associated with increased risk for lung cancer; 2) COPD is associated with lung cancer among never-smokers; and 3) COPD appears to be an independent risk factor for lung cancer.126,130–132 COPD accounts for 10% of lung cancer cases among never-smokers.126 When analyses are restricted to adenocarcinoma (which is more common among nonsmokers, particularly women), COPD was still associated with an increased risk for lung cancer.130 Patients with diffuse pulmonary fibrosis seem to be at a higher risk for lung cancer even after age, gender, and a history of smoking are taken into consideration (RR, 8.25; 95% CI, 4.7–11.48).133,134 Among patients with a history of exposure to asbestos, those who develop interstitial fibrosis are at a higher risk of developing lung cancer than those without fibrosis.135
Selection of Individuals for Lung Screening
Well-known risk factors exist for the development of lung cancer, especially smoking tobacco.3,8,9 Results from the NLST support screening select individuals who are at high risk for lung cancer.11 The NCCN Panel recommends that individuals at high risk for lung cancer should be screened using LDCT; individuals at moderate or low risk should not be screened. Screening with LDCT should only be recommended for select individuals at high risk if they are potential candidates for definitive treatment (ie, curative intent therapy). Chest radiography is not recommended for LCS.11,17
The NCCN Panel recommends using the following criteria to determine whether individuals are at high, moderate, or low risk for lung cancer.
Individuals with High-Risk Factors
There are 2 groups of individuals who qualify as high risk:
Group 1: Individuals aged 55 to 74 years with a 30 or more pack-year history of smoking tobacco who currently smoke or, if former smoker, have quit within 15 years (category 1).10,11 Initial screening with LDCT is a category 1 recommendation for group 1, because these individuals are selected based on the NLST inclusion criteria.10,11 Annual screening LDCT is recommended until individuals are no longer candidates for definitive treatment. The appropriate duration of screening and the age at which screening is no longer appropriate are uncertain.36,136
Group 2: Individuals aged 50 years or older with a 20 or more pack-year history of smoking tobacco and with one additional risk factor (category 2A). Panel members expanded screening beyond the NLST criteria to a larger group of individuals at risk for lung cancer. LDCT screening is a category 2A recommendation for group 2 based on lower level evidence (eg, nonrandomized studies, observational data).137 These additional risk factors include personal history of cancer or lung disease, family history of lung cancer, radon exposure, and occupational exposure to carcinogens.66,67,69,100,104,110,130 Exposure to second-hand smoke is not an independent risk factor.
Panel members believe that individuals in group 2 are also at high risk for lung cancer based on data from the NLST and other studies. The NCCN Panel believes that limiting use to the NLST criteria is arbitrary and naïve, because the NLST only used age and smoking history for inclusion criteria and did not consider other well-known risk factors for lung cancer. Others share this opinion.64,138,139 The NCCN Panel feels that it is important to expand screening beyond the NLST criteria to a larger group of individuals at risk for lung cancer.137,140 Using just the narrow NLST criteria, only 27% of patients currently being diagnosed with lung cancer would be candidates for LDCT screening.140 Data suggest that the lung cancer risk for individuals with a 20 to 29 pack-year smoking history is similar to that of individuals with a 30 or more pack-year history.141 Expanding the groups at high risk who are candidates for screening—by including individuals aged 50 or more years with a 20 or more pack-year smoking history and one additional risk factor—may save thousands of additional lives.21,137,142–144
The NLST included both low-risk and high-risk individuals.138,143 Only 1% of the prevented deaths occurred among individuals whose risk was 0.55% or less; almost 90% of prevented deaths were observed among individuals with a baseline risk of at least 1.24%.138 The true risks and benefits of screening these group 2 individuals are uncertain. A risk calculator may be useful to assist in quantifying the risk for individuals in group 2 for use in a shared decision-making process.143,145,146 Individuals in group 2 may be considered at high risk if they have additional risk factors that increase the lung cancer risk above a threshold of 1.3%.145
In the NCCN Guidelines, the age range for LDCT was extended for individuals in group 2 (ie, ≥50 years and >74 years) for several reasons. Panel Members believe that younger and older individuals in group 2 are also at high risk for lung cancer based on data from the NLST and other studies. Three phase 3 randomized trials assessed screening in younger patients ages 50 to 55 years of age. The NELSON screening and UKLS trials assessed LDCT in individuals 50 to 75 years of age.45,46,49,50,52,53,55,58,147 The Danish Lung Cancer Screening Trial screened individuals 50 to 70 years of age.48,148,149 Several studies have assessed LDCT using an extended age range of 50 to 85 years.150–152
What the age cutoff should be, at which screening is no longer appropriate, is uncertain.43 At diagnosis of lung cancer, the median age of patients is 70 years.7 Approximately 54% of lung cancer is diagnosed in patients aged 55 to 74 years; about 27% of lung cancer is diagnosed in older patients aged 75 to 84 years.7,153 Screening may benefit older patients who are 75 to 84 years.154 The USPSTF recommends LDCT for individuals aged 55 to 80 years with high-risk factors.16 The American Association for Thoracic Surgery recommends LDCT for individuals aged 55 to 79 years with high-risk factors.64 Annual screening LDCT is recommended in the NCCN Guidelines for individuals older than 74 years with high-risk factors who are candidates for definitive treatment, generally defined as curative intent therapy (eg, surgery, chemoradiation, stereotactic body radiation therapy [SBRT]). Screening can be considered for individuals older than 74 years if they have good functional status, do not have serious comorbidities that would impede curative treatment, and are willing to undergo treatment.
For individuals at high risk with negative LDCT scans or those whose nodules do not meet the size cutoff for more frequent scanning or other intervention, the NCCN Guidelines suggest annual screening LDCT until individuals are no longer candidates for definitive treatment. The appropriate duration of screening is uncertain.43 After the 3 rounds of LDCT in the NLST, new cases (367 cases) of lung cancer were frequently diagnosed during the 3.5 years of follow-up (median of 6.5 years).11,155 The NLST data show that lung cancer continues to occur over time in individuals with high-risk factors. The incidence of lung cancer and the death rate from lung cancer did not change during the 7 years of the NLST.156 The NLST data support annual screening LDCT for at least 2 years but do not define a time limit on efficacy.
Individuals with Moderate-Risk Factors and Low-Risk Factors
NCCN defines individuals with moderate-risk factors as those aged 50 years or older and with a 20 or more pack-year history of smoking tobacco or second-hand smoke exposure but no additional lung cancer risk factors. The NCCN Panel does not recommend (category 2A) LCS for individuals at moderate risk for lung cancer based on nonrandomized studies and observational data.43,157 NCCN defines individuals with low-risk factors as those younger than 50 years and/or with a smoking history of fewer than 20 pack-years. The NCCN Panel does not recommend (category 2A) LCS for individuals at low risk for lung cancer based on nonrandomized studies and observational data.43,157
Accuracy of LDCT Protocols and Imaging Modalities
LDCT is recommended for detecting noncalcified nodules that may be suspicious for lung cancer depending on their type and size (eg, solid, part-solid, and nonsolid nodules). Most noncalcified nodules are solid.158 Solid and subsolid nodules are the 2 main types of pulmonary nodules. Subsolid nodules include 1) nonsolid nodules, also known as ground-glass opacities or ground-glass nodules; and 2) part-solid nodules (also known as mixed nodules), which contain both ground-glass and solid components.159–163 Nonsolid nodules are mainly adenocarcinoma in situ (AIS) or minimally invasive adenocarcinoma (MIA), formerly known as bronchioloalveolar carcinoma (BAC); patients have 5-year disease-free survival rates of 100% if these nonsolid nodules are completely resected.160-162,164–167 Data suggest that many nonsolid nodules can resolve, although they need to be followed.158,168,169 Solid and part-solid nodules are more likely to be invasive and faster-growing cancers, factors that are reflected in the increased suspicion and follow-up of these nodules.170–173 Data suggest that long-term survival is excellent if part-solid nodules are resected.159 When assessing subsequent LDCT scans, the most important radiologic factor is change or stability of nodules compared with a previous imaging study.
Multidetector CT (MDCT) of the chest has made it possible to detect very small lung nodules, both benign and malignant. The ability to acquire thinner slices, the use of maximum intensity projection (MIP) or volume-rendered images, and computer-aided diagnosis (CAD) software have increased the sensitivity of small-nodule detection.174–188 The use of thinner images has also improved the characterization of small lung nodules.189 For LCS, LDCT without intravenous contrast is currently recommended (instead of standard-dose CT) to decrease the dose of radiation. LDCT of the chest is usually approximately 10% to 30% of standard-dose CT. LDCT has been shown to be as accurate as standard-dose CT for detecting solid pulmonary nodules, although nodule detection with LDCT may be limited in larger patients.190,191 LDCT seems to be less sensitive for detecting very low-density nonsolid nodules or nonsolid nodules.192 Decreasing the radiation dose does not significantly affect the measurement of nodule size when using 1-mm thick slices.193 Studies suggest that some variation occurs in interpretation of LDCT scans among radiologists.194–200
Studies using MDCT have reported that lung cancer mortality is decreased when compared with unscreened cohorts or those receiving chest radiographs.11,201 Studies using multidetector LDCT screening for lung cancer in individuals with high-risk factors have used different protocol algorithms for detection and follow-up of pulmonary nodules/lesions.10,149,150,202–206 These protocols are based on 1) nodule size and/or nodule consistency/density and likelihood of malignancy; 2) nodule size and tumor stage; and 3) tumor stage and survival. They also take into account the average growth rate of lung cancer (ie, doubling time).207–214 Most of these protocols recommend that dynamic contrast-enhanced CT and/or PET/CT be considered for nodules that are at least 7 to 10 mm, because these technologies have been shown to increase specificity for malignancy.215–222 PET has low sensitivity for nodules with less than 8 mm of solid component and for small nodules near the diaphragm.
Patients who live in areas endemic for fungal disease may have granulomatous disease; the false-positive rate for PET/CT is higher for granulomas.223–225 Solitary pulmonary nodules pose unique challenges.215,226–230 Nodule risk calculators have been published, which may be helpful when assessing solitary pulmonary nodules.227,231 The risk of cancer is increased if a nodule is located in the upper lobes.226 Geographic and other risk factors can influence the accuracy of nodule risk calculators. LDCT screening programs (with multiple years of follow-up) report that 65% to 85% of their detected lung cancers are stage I.52,142,205,222,232 The I-ELCAP (International Early Lung Cancer Action Program) and NLST are the largest series examining lung cancer detection using LDCT in individuals with high-risk factors.10,209
The NCCN recommendations are an adaptation of the Fleischner guidelines for solid and subsolid nodules, NLST data, I-ELCAP protocol guidelines, and LungRADS guidelines.20,34,161,173 Studies suggested that the definition of a positive result from an LDCT scan should be revised, because the original definition from the NLST was associated with a high percentage of false-positives.11,49,233,234 In Version 1.2014 of the NCCN Guidelines, the recommended cutoff sizes for assessing solid and part-solid lung nodules on initial LDCT screening were increased to 6 mm in diameter rather than the 4 mm originally used in the NLST and in earlier versions of the NCCN Guidelines for LCS.18,34,234,235 The NCCN-recommended cutoff sizes for solid, part-solid, and nonsolid nodules detected on LDCT scans are shown in the algorithm (LSC-3–LSC-5, pages 416–418; also online, in these guidelines, at NCCN.org). The cutoff sizes differ for nodules detected on initial screening LDCT when compared with new or growing nodules detected on follow-up and annual screening LDCT scans (see the complete version of the NCCN Guidelines for Lung Cancer Screening, available at NCCN.org). There is a higher degree of suspicion for new or growing nodules and hence lower cutoff sizes are used.44 If there is a high suspicion of lung cancer, recommendations include biopsy or surgical excision. For nodules of borderline concern, assessment with interval LDCT scans is often recommended to determine if the nodule is changing to a suspicious form by increasing in size and/or by having a new or growing solid component.
The ACR developed Lung-RADS to standardize LDCT lung examinations.20,34,236 Lung-RADS has been shown to improve the detection of lung cancer and to decrease false-positives to approximately 1 in 10 screened individuals compared with more than 1 in 4 in NLST.22,30,34,35 For subsequent LDCT scans after baseline, the false-positive result for Lung-RADS was also decreased when compared with NLST (5.3% [95% CI, 5.1%–5.5%] vs 21.8% [95% CI, 21.4%–22.2%]).22 The NCCN Panel has harmonized Lung-RADS with the NCCN Guidelines by revising the definitions of positive scans for initial screening, follow-up, and annual screening LDCT.22 For the 2018 update, the NCCN threshold cutoffs for solid, part-solid, and nonsolid nodules have been rounded to the nearest whole number to harmonize with the Lung-RADS cutoffs.20,21 For solid or part-solid nodules, the NCCN definition of a positive initial screening scan is a nodule measuring 6 mm in mean diameter.12,22,52,170,237 For nonsolid nodules, the NCCN definition of a positive initial screening scan is 20 mm in diameter; nodules of this size require a short-term follow-up LDCT scan in 6 months to assess for malignancy. Specific recommendations for other types of nodules, other size ranges, and different types of LDCT scans (ie, initial, follow-up, annual) are provided in the NCCN Guidelines (available at NCCN.org).
If a new or growing nodule is detected on follow-up interim scans or subsequent annual screening LDCT scans, the definition of a positive scan is different because these nodules are associated with higher risk.44 If a new solid nodule is detected on follow-up or subsequent annual screening LDCT scans, the cutoff threshold is decreased to 4 mm. For new part-solid nodules with a solid component of 4 mm, an immediate chest CT with or without contrast and/or PET/CT is recommended to assess for malignancy. Again, if a new or growing nonsolid nodule is detected on follow-up interim scans or subsequent annual LDCT scans, follow-up recommendations are different. Nodules should be measured on lung windows and reported as the average diameter rounded to the nearest whole number; only a single diameter measurement is necessary for round nodules. The NCCN Guidelines emphasize that nonsolid lesions must be evaluated using thin slices (<1.5 mm) to increase the sensitivity for a solid component and to detect subtle changes over time.160,161,179,180,189
In Lung-Rads, growth is defined as an increase in size of more than 1.5 mm.19,196 Mean diameter is the mean of the longest diameter of the nodule and its perpendicular diameter. This definition of nodule growth is based on intraobserver and interobserver variability when measuring small pulmonary nodules, and on the minimum change in diameter that can be reliably detected using conventional methods (excluding volumetric analysis software).238 If endobronchial nodules are suspected, then LDCT is recommended after 1 month. The technician should ask the patient to cough vigorously, then the LDCT should be immediately done. If findings suggest infection or inflammation, a follow-up LDCT is suggested in 1 to 3 months.
A table on recommended LDCT acquisition parameters is included in the algorithm (see LCSA, page 420). Use of MIP, volume rendered, and/or CAD software is highly recommended in addition to evaluation of conventional axial images for increased sensitivity of small nodule detection. A detector collimation of 1.5 mm or less is necessary for optimal use of these 3-dimensional applications. Measurement and evaluation of small nodules are more accurate and consistent on 1-mm thick images compared with 5-mm images.189
The preferred slice width is 1 mm or less, and the acceptable slice width is 2.5 mm or less based on Lung-RADS.22,34,161,179 Nonsolid lesions must be evaluated at thin slices (<1.5 mm) to exclude solid components.161 Part-solid nodules have higher malignancy rates than either solid nodules or pure non-solid nodules and, therefore, require rigorous evaluation.161 Because slice thickness, reconstruction algorithms, and postprocessing filters affect nodule size measurement, the same technical parameters should be used for each screening LDCT (eg, the same window/width and window/level settings).239,240 Ultra-low-dose chest CT currently produces lower sensitivity for nodule detection, especially in larger patients.191
Multiple Nonsolid Nodules
Subsolid nodules may contain part-solid or solid components, which increase the possibility of malignancy. When multiple subsolid nodules occur, the dominant lesion should be assessed.170 Careful assessment is needed to determine whether patients have 1) a malignant nodule and several benign nodules, 2) several synchronous lung cancers, or 3) dominant malignant nodule with metastases.241 Multiple nodules may also be due to inflammation or infection, especially if they are rapidly expanding in size.170
The following increase the degree of suspicion that nonsolid or part-solid nodules may be malignant: 1) part-solid nodules with solid components larger than 5 mm; 2) pure nonsolid nodules larger than 10 mm; 3) atypical subsolid nodules with spiculated contours, bubbly appearance, or reticulation; 4) pure nonsolid nodules or part-solid nodules with solid components smaller than 5 mm that show interval change in size or attenuation; or 5) solid lesions with characteristics that are suspicious for invasive carcinoma.161,171,226 All nonsolid nodules should be reviewed at thin (<1.5 mm) slices to exclude any solid components.161 If the nodule contains any solid components, then the nodule should be managed using the recommendations from the NCCN Panel for part-solid nodules.215,242
Benefits and Risks of Lung Cancer Screening
The goal of screening is to identify disease at an early stage while it is still treatable and curable. The potential huge benefits of LCS include a reduction in mortality and improvement in quality of life.38,243 The risks of lung screening include false-negatives and false-positives, radiation exposure, overdiagnosis of incidental findings, futile detection of aggressive disease, anxiety, unnecessary testing, complications from diagnostic workup, and financial costs.243–249 Most lung nodules found on LDCT are benign; if possible, these nodules should be assessed using noninvasive procedures to avoid the morbidity of invasive procedures in patients who may not have cancer.246,250 The risks and benefits of LCS should be discussed with the individual before an LDCT scan is done.
Benefits
Benefits of screening for lung cancer using LDCT scans include 1) decreased lung cancer mortality, or improvement in other oncologic outcomes; 2) quality-of life benefits from screening and early detection of cancer (compared with standard clinical detection); and 3) detection of disease, other than lung cancer, that requires treatment.14,36,39,43,156 Effective lung screening may prevent more than 12,000 premature deaths due to lung cancer per year.251
Oncology Outcomes: After a clinical diagnosis of NSCLC, survival is directly related to stage at diagnosis.252 Although patients with earliest-stage disease (IA) may have a 5-year survival rate of approximately 75% with surgery, the outcomes quickly decrease with increasing stage.253 A new edition of the AJCC Cancer Staging Manual (8th edition) will be effective for all cancer cases recorded on or after January 1, 2018.254,255 Although it is intuitively appealing to conclude that earlier detection of disease will improve outcome, screen-detected lung cancers may have a different natural history from that of clinically detected cancers,256,257 and an apparent improvement in survival from early detection itself (lead-time bias). Pathology results of resected lung cancers detected through prior screening trials suggest that screening increases the detection of indolent cancer. Randomized trial data from the NLST show that LDCT screening decreases lung cancer mortality.11
To address the concerns of bias and overdiagnosis from nonrandomized screening studies, the NCI launched the NLST in 2002.10 The NLST was a prospective, randomized LCS trial comparing annual screening LDCT scans with annual chest radiographs for 2 years The NLST results showed that annual screening LDCT decreased the RR of death from lung cancer by 20%.11 In the NLST, 356 participants died of lung cancer in the LDCT arm and 443 participants died of lung cancer in the chest radiograph arm.11 Thus, annual screening LDCT decreased the RR of death by 20%. The NLST results indicate that to prevent 1 death from lung cancer, 320 individuals with high-risk factors must be screened with LDCT. Approximately 8.6 million individuals were eligible for LDCT lung screening in 2010 using the NLST definitions of high risk. It was estimated that 12,250 deaths would be averted if these high-risk individuals received LDCT screening.251 If NCCN group 2 criteria were also used to identify high-risk individuals, then an additional 2 million individuals would also receive lung screening. An additional 3,000 deaths would be averted.137
Quality of Life: The NLST assessed quality of life among participants at the time of each annual screening study.258 Possible quality-of-life benefits from early lung cancer detection (as opposed to detection at the time of clinical symptoms) include 1) reduction in disease-related morbidity, 2) reduction in treatment-related morbidity, 3) alterations in health-affecting lifestyles, and 4) reduction in anxiety and psychological burden. Presumably, quality of life is also improved with negative LDCT findings, although the need for continued follow-up may increase anxiety. In the NLST trial, patients with either a false-positive result or significant incidental finding did not report increased anxiety or differences in quality of life at 1 or 6 months after screening.258 LCS may identify other clinical conditions unrelated to lung cancer that require follow-up (eg, coronary artery calcification, COPD, other cancers); presumably, treatment of these other conditions will decrease the overall disease burden.11,170,259–262
The NLST found that 40% of the cancers detected in the CT-screening group were stage IA, 12% were stage IIIB, and 22% were stage IV.11 Conversely, 21% of the cancers detected in the chest radiograph group were stage IA, 13% were stage IIIB, and 36% were stage IV. These results suggest that LDCT screening decreases the number of cases of advanced lung cancer, and therefore may decrease treatment-related morbidity. Data from the NELSON and UKLS trials also suggest that CT screening detects more early-stage lung cancer.46,52
Risks
LCS with LDCT has inherent risks and benefits.36,38,43,155,263 The risks must be understood to determine whether screening is beneficial. The possible or projected risks of screening for lung cancer using LDCT scans include 1) false-positive results, leading to unnecessary testing, unnecessary invasive procedures (including surgery), increased cost, and decreased quality of life because of mental anguish; 2) false-negative results, which may delay or prevent diagnosis and treatment because of a false sense of good health; 3) futile detection of small aggressive tumors (which have already metastasized, preventing meaningful survival benefit from screening); 4) futile detection of indolent disease (ie, overdiagnosis), which would never have harmed the patient who subsequently undergoes unnecessary therapy; 5) indeterminate results, leading to additional testing; 6) radiation exposure; and 7) physical complications from diagnostic workup. Patients with several comorbid conditions may be at greater risk than those with few or none.
False-Positive Results: LCS studies (which have included only high-risk populations) have found a high rate of noncalcified nodules larger than 4 mm on LDCT screening, with false-positives ranging from 10% to 43%.151,264–268 In the NLST, the false-positive rate was 96.4% for the CT screening group.11 The cumulative risk of a false-positive result was 33% for a person undergoing LCS with 2 sequential annual examinations.264 Thus, LDCT had a high rate of sensitivity but a low rate of specificity in the NLST. These false-positive results in the NLST were probably due to benign intrapulmonary lymph nodes and noncalcified granulomas.11,216 Use of the Lung-RADS protocol has been shown to decrease false-positive results and increase the detection of lung cancer.21,22,34 False-positive and indeterminate results require follow-up, which may include surveillance with chest LDCT scans, percutaneous needle biopsy, or even surgical biopsy. Each of these procedures has its own risks and potential harms.269 Approximately 7% of individuals with a false-positive result will undergo an invasive procedure (typically bronchoscopy).264 In the NLST, the rate of major complications after an invasive procedure was very low (only 0.06%) after workup for a false-positive result in the CT screening group.11
The NCCN recommendations for LCS may avoid much of the most invasive follow-up for non-calcified nodules that are detected on baseline screening with LDCT. The NCCN recommendations use the Lung-RADS, NLST, and I-ELCAP protocols/recommendations and the Fleischner Society guidelines and are based on expert opinion from NCCN Panel Members.11,161,173,270 Repeat chest LDCT scanning is associated with risk for 1) increased radiation exposure; 2) increased cost of follow-up scans and clinic visits; and 3) ongoing anxiety to the individual, who must wait for the results of repeat chest LDCT scans.37,271
Bach et al272 also provide insight into the potential harms of LDCT screening, which results in a 3-fold increase in lung cancer diagnosis and a 10-fold increase in lung cancer surgery; this represents substantial psychological and physical burdens. Although the I-ELCAP investigators reported a surgical mortality rate of only 0.5% (when surgery is performed by board-certified thoracic surgeons at cancer centers), the average surgical mortality rate for major lung surgery across the United States is 5%, and the frequency of serious complications is greater than 20%.273 These potential harms associated with thoracic surgery273–275 mandate that the effectiveness of LDCT screening be accurately assessed. Methods of decreasing potential harms with thoracic surgery include using treatment with less morbidity (eg, sublobar resection, VATS lobectomy, SBRT), using minimally invasive diagnostics (endobronchial ultrasound and navigational bronchoscopy), and using multidisciplinary teams to minimize unnecessary testing and morbidity.
False-Negative Results: Sone et al276 reported on lung cancers missed at screening.277,278 Of 88 lung cancers diagnosed, 32 were missed on 38 LDCT scans: 23 from detection errors and 16 from interpretation errors. Detection errors included 1) subtle lesions (91%) appearing as nonsolid nodules; and 2) lesions (83%) that were overlapped with, obscured by, or similar in appearance to normal structures (such as blood vessels). Interpretation errors (87%) were seen in patients who had underlying lung disease, such as tuberculosis, emphysema, or fibrosis.228 The second report revealed that 84% of missed cancers were subsequently detected using an automated lung nodule detection method. The CAD method involved the use of gray-level thresholding techniques to identify 3-dimensionally contiguous structures within the lungs, which were possible nodule candidates. A database of lung nodules on CT scans provides an imaging resource for radiologists, which may help to decrease false-negative and false-positive results.176
Futile Detection of Small Aggressive Tumors: Early detection using LCS may not be beneficial if a small tumor is very aggressive and has already metastasized, with a loss of opportunity for effective treatment. Studies show that a 5-mm lung cancer has undergone approximately 20 doublings yielding 108 cells, whereas patient death typically occurs with a tumor burden of 1012 cells.279 Even small tumors may have already metastasized. Studies have also shown that metastases can occur at the time of angiogenesis, when lesions are approximately 1 to 2 mm.280
The NLST trial results show that LCS is effective in select individuals with high-risk factors.11 The data show that detecting and treating lung lesions leads to a reduction in lung cancer–specific mortality. Therefore, the likelihood of futile therapy in patients with screen-detected tumors is much less. Because the natural history of lung cancer is heterogeneous,281 the potential remains for futile treatment in patients with an aggressive tumor that is already incurable at the time of screening diagnosis.
Futile Detection of Indolent Disease: Although lung cancer specialists generally have a strong opinion of the uniform fatality of untreated lung cancer, studies of some low-grade lung cancers (ie, AIS or MIA, formerly known as BAC) show a potential for prolonged survival in some patients with NSCLC, even without therapy.282,283 AIS and MIA, which are likely to present as nonsolid nodules, have a 100% 5-year disease-free survival rate if completely resected.166,282 A greater percentage of the lepidic pattern (formerly BAC pattern), which corresponds with the nonsolid component in a part-solid nodule, is correlated with a more favorable prognosis.166,282,283
Furthermore, experience in LCS has raised the question of increased identification of indolent tumors in the screened population, which is termed overdiagnosis.272,284 These indolent tumors may not cause symptoms or cancer mortality; therefore, patients do not benefit from screening and subsequent workup and treatment. A percentage of these patients will be exposed to the risk, morbidity, and mortality of surgical resection that, in retrospect, will not increase their life expectancy. As the entities of AIS and MIA, with excellent survival, have been separated from overtly invasive adenocarcinomas, the potential exists to minimize surgical intervention for pure nonsolid nodules through CT screening studies and long-term follow-up.166 Overdiagnosis is difficult to measure.158,285 An analysis of the NLST data reported that 18% of all lung cancers detected by LDCT seemed to be indolent.59 Bach et al272 found an increase in the number of patients with lung cancer detected through screening, yet found no evidence of a decline in the number of deaths from lung cancer. Their nonrandomized study raised concern that LDCT screening may lead to overdiagnosis of indolent cases and to the morbidity of treatment, without a survival benefit. However, the randomized NLST found that LDCT does decrease lung cancer mortality.11
Quality of Life: The effect of LCS on the quality of life is not fully known. van den Bergh et al286 found no measured adverse effects, although approximately half of the participants reported discomfort while waiting for the results. Several studies (including the NLST and NELSON trial) have measured quality-of-life issues.287,288 Data from the NLST and NELSON trials suggest that lung screening did not adversely affect quality of life.258,288 False-positive and indeterminate results may decrease quality of life because of mental anguish and additional testing.249 During the NLST, 3 rounds of LDCT screening were done (ie, baseline, year 1, year 2) and then individuals were followed for an additional 3.5 years. Lung cancer was diagnosed between annual screens in some patients (ie, interval cancers); lung cancer was also diagnosed during follow-up.11,289 Thus, individuals should be cautioned that LDCT may not identify all lung cancers or prevent death from lung cancer.11 They should be informed that a positive test result does not mean they have lung cancer because many false-positive results occur with LDCT.37
Unnecessary Testing: Any LCS program will result in additional testing. The NLST was a carefully supervised randomized controlled trial. In a less-controlled environment, the rate of additive studies may be higher. Sistrom et al290 reviewed the recommendations for additional imaging in more than 5.9 million radiology reports; they reported an additional imaging rate of 35.8% for chest LDCT. The issue of incidental findings on screening examinations is problematic.291
Radiation Exposure with LDCT: Current MDCT scanners provide a significantly enhanced capability for detecting small nodules through allowing thinner slice images. Using low-dose techniques, the mean effective radiation dose is 1.5 mSv (standard deviation [SD], 0.5 mSv) compared with an average of 7 mSv for conventional CT.11,14,158,292 The radiation dose of LDCT is 10 times that of chest radiography. Brenner293 estimated a 1.8% increase in lung cancer cases if 50% of all current and former smokers in the United States between 50 and 75 years of age were to undergo annual screening LDCT. Lower doses of radiation are now used for LDCT scans, and these lower doses may be less dangerous.294,295 The risk of radiation exposure over long periods will have to be considered when screening guidelines are developed, especially when recommending how frequently the scans should be performed.271 Radiation exposure from LCS using LDCT and PET/CT is greater for woman than for men.244 For men, the median cumulative effective dose was 9.3 mSv after 10 years of screening; the dose was 13.0 mSv for women. These doses are equivalent to one standard CT of the chest (7–8 mSv).
Increased Cost: Many experts are concerned about the effect of LCS on medical resources, including the cost of LDCT screening and additional testing. The cost of an LDCT scan was estimated to be about $527 (in 2011 U.S. dollars).296 Approximately 15% of the adult population in the United States (about 36.5 million people) are active smokers; approximately 11% are daily smokers.70,72,297 In 2015, the number of individuals at high risk who were candidates for LCS was approximately 6 million (using NLST criteria).11,298 Depending on the screening rate (50% or 75%), the annual cost in the United States is estimated at $1.7 to $3.4 billion.296,298 If 75% of the eligible population has screening, it is estimated that it will cost $240,000 to prevent one lung cancer death.39 About $12.1 billion is spent each year on lung cancer care in the United States.296
LDCT screening will lead to false-positive results, detection of indeterminate nodules, and detection of potential disease other than lung cancer.258 In the NLST, although 24.2% of the LDCT scans were positive, most of these were false-positive (96.4%).11 Follow-up for positive nodules typically involves further imaging.11 Assuming a 50% screening rate, a conservative estimate of the annual cost of working up false-positive nodules is about $800 million (3.5 million × 23% × $1,000). Use of Lung-RADS will probably decrease this cost because the false-positive rate will decrease. This estimate does not include costs of workup for other potential abnormalities detected during screening, such as cardiac and upper abdominal pathology. Of individuals with false-positives, approximately 7% will undergo an invasive procedure (typically bronchoscopy).264 Limiting screening to only individuals with high-risk factors not only helps avoid unnecessary risks in individuals with a lower risk for cancer but also is important for decreasing the costs of the screening program. Prescreening based on age, smoking history, appropriate medical history, family history, and occupational history is important to determine which patients are at high risk.
Lack of well-defined guidelines can lead to overuse of screening. Excessive screening and/or interpretations of studies by unskilled individuals may occur without strict guidelines. Other factors, such as the interval at which screening should be performed, will also affect calculations of cost. In screening studies using LDCT, 23% of the ELCAP and 69% of the 1999 Mayo Clinic study had at least 1 indeterminate nodule. Depending on the size and characteristics of the indeterminate nodule, further evaluation may include serial follow-up LDCT, dynamic contrast-enhanced nodule densitometry, PET, or biopsy. False-positives also lead to additional unnecessary testing and increased cost.
Lung screening also leads to detection of disease other than lung cancer, such as infection; coronary artery calcification; COPD; and renal, adrenal, and liver lesions.170,228,260–262,299,300 Although detection of other diseases may frequently provide a clinical benefit to the patient, costs will be further increased with additional testing and treatment. It is important to rule out infection; however, antimicrobials are not indicated for chronic lesions.228 Inappropriate use of antimicrobials may cause adverse side effects and will increase cost. Incidental lesions may also be detected, which may require further testing (eg, intrapulmonary lymph nodes, noncalcified granulomas, thyroid incidentalomas, upper abdominal lesions).11,301
Cost-Effectiveness and Cost-Benefit Analyses
The cost-effectiveness of LCS is also important to consider.302 LDCT imaging is more expensive than many other screening programs, and therefore it is important to validate the effectiveness of screening.303 Currently, Medicare reimburses $285 for a CT scan.296,302 Note that cost-benefit analysis provides dollar values for the outcomes, whereas cost-effectiveness analysis provides cost per health outcome (eg, cost per life-year gained). Seven analyses have reported a cost effectiveness ratio of $100,000 (in U.S. dollars) or less per quality adjusted life years gained for LDCT, which indicates that screening is cost effective.304 A threshold level of $100,000 per quality-adjusted life year gained is what some experts consider to be a reasonable value in the United States.
A fundamental flaw with cost–benefit analyses for LCS is that the true benefit of screening requires more years of follow-up and more years of screening to realize the full potential; this crucial factor has been arbitrarily assigned or assumed in prior analyses.305 The types of assumptions made can significantly affect the conclusions of the analysis. Many cost–benefit analyses do not adequately represent the detrimental effects of false-positives on screening. For a person undergoing LCS with 2 sequential annual examinations, the cumulative risk of a false-positive was 33%.264 The cost of false-positives has been estimated to be at least $1,000 per incident.306 The ELCAP investigators documented that diagnostic procedure costs and hospital/physician costs in the first year after the diagnosis of lung cancer proportionally increased with increasing stage.307
Shared Decision-Making
Given the high percentage of false-positive results and the downstream management that ensues for many patients, the risks and benefits of LCS should be discussed with the individual before a screening LDCT scan is performed.36–39,233,308,309 Individuals should be cautioned that LDCT may not identify all lung cancers or prevent death from lung cancer.11 They should be informed that a positive test result does not mean they have lung cancer because false-positives occur with LDCT.37 Shared patient/physician decision-making may be the best approach before deciding whether to perform LDCT lung screening, especially for elderly patients with comorbid conditions.16,40,41,310 Smoking cessation counseling is recommended.24,311
Lung screening is not recommended for patients who are not able or willing to undergo curative therapy, because of health problems or other major concerns.16 Shared decision-making aids may assist when determining if screening should be recommended. Risk calculators may assist with decision-making for group 2 in the NCCN Guidelines (ie, individuals ≥50 years with a ≥20 pack-year smoking history).145 The Tammemagi risk calculator includes additional variables that can be used to help determine whether individuals in group 2 are candidates for screening. Using this risk calculator, the threshold for screening is 1.3%. Previous LCS results can also be used for risk stratification.147
Individual Disclosures for Lung Cancer Screening Panel
References
- 1.↑
Torre LA, Siegel RL, Ward EM, Jemal A. Global cancer incidence and mortality rates and trends—an update. Cancer Epidemiol Biomarkers Prev 2016;25:16–27.
- 2.
Torre LA, Bray F, Siegel RL et al.. Global cancer statistics, 2012. CA Cancer J Clin 2015;65:87–108.
- 3.↑
The Health Consequences of Smoking: A Report of the Surgeon General (ed 2010/07/30). Atlanta: US Department of Health and Human Services; 2004.
- 4.
Thun MJ, Henley SJ, Burns D et al.. Lung cancer death rates in lifelong nonsmokers. J Natl Cancer Inst 2006;98:691–699.
- 7.↑
Howlader N, Noone AM, Krapcho M et al.. SEER Cancer Statistics Review, 1975–2014, based on November 2016 SEER data submission, posted to the SEER web site, April 2017. Bethesda, MD: National Cancer Institute; 2017.
- 8.↑
Jemal A, Ward EM, Johnson CJ et al.. Annual report to the nation on the status of cancer, 1975-2014, featuring survival. J Natl Cancer Inst 2017;109.
- 9.↑
Jemal A, Thun MJ, Ries LA et al.. Annual report to the nation on the status of cancer, 1975-2005, featuring trends in lung cancer, tobacco use, and tobacco control. J Natl Cancer Inst 2008;100:1672–1694.
- 10.↑
National Lung Screening Trial Research Team Aberle DR, Berg CD et al.. The National Lung Screening Trial: overview and study design. Radiology 2011;258:243–253.
- 11.↑
National Lung Screening Trial Research Team Aberle DR, Adams AM et al.. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med 2011;365:395–409.
- 12.↑
Aberle DR, DeMello S, Berg CD et al.. Results of the two incidence screenings in the National Lung Screening Trial. N Engl J Med 2013;369:920–931.
- 13.
National Lung Screening Trial Research Team Church TR, Black WC et al.. Results of initial low-dose computed tomographic screening for lung cancer. N Engl J Med 2013;368:1980–1991.
- 14.↑
Kramer BS, Berg CD, Aberle DR, Prorok PC. Lung cancer screening with low-dose helical CT: results from the National Lung Screening Trial (NLST). J Med Screen 2011;18:109–111.
- 16.↑
Moyer VAForce USPST. Screening for lung cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 2014;160:330–338.
- 17.↑
Detterbeck FC, Mazzone PJ, Naidich DP, Bach PB. Screening for lung cancer: diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2013;143:e78S–92S.
- 18.↑
Wood DE, Eapen GA, Ettinger DS et al.. Lung cancer screening. J Natl Compr Canc Netw 2012;10:240–265.
- 20.↑
Kazerooni EA, Armstrong MR, Amorosa JK et al.. ACR CT accreditation program and the lung cancer screening program designation. J Am Coll Radiol 2016;13:R30–34.
- 21.↑
McKee BJ, Regis SM, McKee AB, Flacke S, Wald C. Performance of ACR Lung-RADS in a clinical CT lung screening program. J Am Coll Radiol 2016;13:R25–29.
- 22.↑
Pinsky PF, Gierada DS, Black W et al.. Performance of Lung-RADS in the National Lung Screening Trial: a retrospective assessment. Ann Intern Med 2015;162:485–491.
- 23.↑
Leone FT, Evers-Casey S, Toll BA, Vachani A. Treatment of tobacco use in lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2013;143:e61S–77S.
- 24.↑
Fucito LM, Czabafy S, Hendricks PS et al.. Pairing smoking-cessation services with lung cancer screening: a clinical guideline from the Association for the Treatment of Tobacco Use and Dependence and the Society for Research on Nicotine and Tobacco. Cancer 2016;122:1150–1159.
- 25.
Sitas F, Weber MF, Egger S, Yap S, Chiew M, O'Connell D. Smoking cessation after cancer. J Clin Oncol 2014;32:3593–3595.
- 26.↑
Taylor KL, Cox LS, Zincke N, Mehta L, McGuire C, Gelmann E. Lung cancer screening as a teachable moment for smoking cessation. Lung Cancer 2007;56:125–134.
- 27.↑
Cataldo JK, Dubey S, Prochaska JJ. Smoking cessation: an integral part of lung cancer treatment. Oncology 2010;78:289–301.
- 28.↑
Hays JT, McFadden DD, Ebbert JO. Pharmacologic agents for tobacco dependence treatment: 2011 update. Curr Atheroscler Rep 2012;14:85–92.
- 29.↑
Wiener RS, Gould MK, Arenberg DA et al.. An official American Thoracic Society/American College of Chest Physicians policy statement: implementation of low-dose computed tomography lung cancer screening programs in clinical practice. Am J Respir Crit Care Med 2015;192:881–891.
- 30.↑
Mazzone P, Powell CA, Arenberg D et al.. Components necessary for high-quality lung cancer screening: American College of Chest Physicians and American Thoracic Society Policy Statement. Chest 2015;147:295–303.
- 32.↑
Fintelmann FJ, Bernheim A, Digumarthy SR et al.. The 10 pillars of lung cancer screening: rationale and logistics of a lung cancer screening program. Radiographics 2015;35:1893–1908.
- 33.↑
Armstrong K, Kim JJ, Halm EA et al.. Using lessons from breast, cervical, and colorectal cancer screening to inform the development of lung cancer screening programs. Cancer 2016;122:1338–1342.
- 34.↑
Kazerooni EA, Austin JH, Black WC et al.. ACR-STR practice parameter for the performance and reporting of lung cancer screening thoracic computed tomography (CT): 2014 (Resolution 4). J Thorac Imaging 2014;29:310–316.
- 35.↑
McKee BJ, Regis SM, McKee AB et al.. Performance of ACR Lung-RADS in a clinical CT lung screening program. J Am Coll Radiol 2015;12:273–276.
- 36.↑
de Koning HJ, Meza R, Plevritis SK et al.. Benefits and harms of computed tomography lung cancer screening strategies: a comparative modeling study for the U.S. Preventive Services Task Force. Ann Intern Med 2014;160:311–320.
- 37.↑
Wiener RS, Gould MK, Woloshin S et al.. What do you mean, a spot?: A qualitative analysis of patients' reactions to discussions with their physicians about pulmonary nodules. Chest. 2013;143:672–677.
- 38.↑
Aberle DR, Abtin F, Brown K. Computed tomography screening for lung cancer: has it finally arrived? Implications of the national lung screening trial. J Clin Oncol 2013;31:1002–1008.
- 39.↑
Goulart BH, Ramsey SD. Moving beyond the national lung screening trial: discussing strategies for implementation of lung cancer screening programs. Oncologist 2013;18:941–946.
- 40.↑
Sox HC. Implementing lung cancer screening under Medicare: the last chance to get it right? JAMA 2014;312:1206–1207.
- 41.↑
Volk RJ, Hawk E, Bevers TB. Should CMS cover lung cancer screening for the fully informed patient? JAMA 2014;312:1193–1194.
- 42.↑
Field JK, Smith RA, Aberle DR et al.. International Association for the Study of Lung Cancer Computed Tomography Screening Workshop 2011 report. J Thorac Oncol 2012;7:10–19.
- 43.↑
Bach PB, Mirkin JN, Oliver TK et al.. Benefits and harms of CT screening for lung cancer: a systematic review. JAMA 2012;307:2418–2429.
- 44.↑
Walter JE, Heuvelmans MA, de Jong PA et al.. Occurrence and lung cancer probability of new solid nodules at incidence screening with low-dose CT: analysis of data from the randomised, controlled NELSON trial. Lancet Oncol 2016;17:907–916.
- 45.↑
Field JK, Duffy SW, Baldwin DR et al.. The UK Lung Cancer Screening Trial: a pilot randomised controlled trial of low-dose computed tomography screening for the early detection of lung cancer. Health Technol Assess 2016;20:1–146.
- 46.↑
Field JK, Duffy SW, Baldwin DR et al.. UK Lung Cancer RCT Pilot Screening Trial: baseline findings from the screening arm provide evidence for the potential implementation of lung cancer screening. Thorax 2016;71:161–170.
- 47.
Patz EF Jr., Greco E, Gatsonis C et al.. Lung cancer incidence and mortality in National Lung Screening Trial participants who underwent low-dose CT prevalence screening: a retrospective cohort analysis of a randomised, multicentre, diagnostic screening trial. Lancet Oncol 2016;17:590–599.
- 48.↑
Wille MM, Dirksen A, Ashraf H et al.. Results of the randomized Danish Lung Cancer Screening Trial with focus on high-risk profiling. Am J Respir Crit Care Med 2016;193:542–551.
- 49.↑
Horeweg N, van Rosmalen J, Heuvelmans MA et al.. Lung cancer probability in patients with CT-detected pulmonary nodules: a prespecified analysis of data from the NELSON trial of low-dose CT screening. Lancet Oncol 2014;15:1332–1341.
- 50.↑
Horeweg N, Scholten ET, de Jong PA et al.. Detection of lung cancer through low-dose CT screening (NELSON): a prespecified analysis of screening test performance and interval cancers. Lancet Oncol 2014;15:1342–1350.
- 51.
Prosch H, Schaefer-Prokop C. Screening for lung cancer. Curr Opin Oncol 2014;26:131–137.
- 52.↑
Horeweg N, van der Aalst CM, Thunnissen E et al.. Characteristics of lung cancers detected by computer tomography screening in the randomized NELSON trial. Am J Respir Crit Care Med 2013;187:848–854.
- 53.↑
McRonald FE, Yadegarfar G, Baldwin DR et al.. The UK Lung Screen (UKLS): demographic profile of first 88,897 approaches provides recommendations for population screening. Cancer Prev Res (Phila) 2014;7:362–371.
- 54.
Field JK, van Klaveren R, Pedersen JH et al.. European randomized lung cancer screening trials: post NLST. J Surg Oncol 2013;108:280–286.
- 55.↑
Ru Zhao Y, Xie X, de Koning HJ et al.. NELSON lung cancer screening study. Cancer Imaging 2011;11 Spec No A:S79–84.
- 56.
Xu DM, Gietema H, de Koning H et al.. Nodule management protocol of the NELSON randomised lung cancer screening trial. Lung Cancer 2006;54:177–184.
- 57.
Nair A, Hansell DM. European and North American lung cancer screening experience and implications for pulmonary nodule management. Eur Radiol 2011;21:2445–2454.
- 58.↑
van Iersel CA, de Koning HJ, Draisma G et al.. Risk-based selection from the general population in a screening trial: selection criteria, recruitment and power for the Dutch-Belgian randomised lung cancer multi-slice CT screening trial (NELSON). Int J Cancer 2007;120:868–874.
- 59.↑
Patz EF Jr., Pinsky P, Gatsonis C et al.. Overdiagnosis in low-dose computed tomography screening for lung cancer. JAMA Intern Med 2014;174:269–274.
- 60.
Reich JM. A critical appraisal of overdiagnosis: estimates of its magnitude and implications for lung cancer screening. Thorax 2008;63:377–383.
- 61.↑
Black WC. Computed tomography screening for lung cancer: review of screening principles and update on current status. Cancer 2007;110:2370–2384.
- 62.↑
Oken MM, Hocking WG, Kvale PA et al.. Screening by chest radiograph and lung cancer mortality: the Prostate, Lung, Colorectal, and Ovarian (PLCO) randomized trial. JAMA 2011;306:1865–1873.
- 63.↑
Wender R, Fontham ET, Barrera E Jr. et al.. American Cancer Society lung cancer screening guidelines. CA Cancer J Clin 2013;63:107–117.
- 64.↑
Jaklitsch MT, Jacobson FL, Austin JH et al.. The American Association for Thoracic Surgery guidelines for lung cancer screening using low-dose computed tomography scans for lung cancer survivors and other high-risk groups. J Thorac Cardiovasc Surg 2012;144:33–38.
- 65.↑
Roberts H, Walker-Dilks C, Sivjee K et al.. Screening high-risk populations for lung cancer: guideline recommendations. J Thorac Oncol 2013;8:1232–1237.
- 66.↑
Alberg AJ, Brock MV, Ford JG et al.. Epidemiology of lung cancer: diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2013;143:e1S–29S.
- 67.↑
Driscoll T, Nelson DI, Steenland K et al.. The global burden of disease due to occupational carcinogens. Am J Ind Med 2005;48:419–431.
- 68.
de Groot P, Munden RF. Lung cancer epidemiology, risk factors, and prevention. Radiol Clin North Am 2012;50:863–876.
- 69.↑
Youlden DR, Cramb SM, Baade PD. The international epidemiology of lung cancer: geographical distribution and secular trends. J Thorac Oncol 2008;3:819–831.
- 70.↑
Jamal A, King BA, Neff LJ et al.. Current cigarette smoking among adults - United States, 2005-2015. MMWR Morb Mortal Wkly Rep 2016;65:1205–1211.
- 71.↑
Jacobs EJ, Newton CC, Carter BD et al.. What proportion of cancer deaths in the contemporary United States is attributable to cigarette smoking? Ann Epidemiol 2015;25:179–182 e171.
- 72.↑
Centers for Disease Control and Prevention. Current cigarette smoking among adults—United States, 2011. MMWR Morb Mortal Wkly Rep 2012;61:889–894.
- 73.↑
Jha P, Peto R. Global effects of smoking, of quitting, and of taxing tobacco. N Engl J Med 2014;370:60–68.
- 74.↑
Chen LS, Baker T, Hung RJ et al.. Genetic risk can be decreased: quitting smoking decreases and delays lung cancer for smokers with high and low CHRNA5 risk genotypes - a meta-analysis. EBioMedicine 2016;11:219–226.
- 75.
Hecht SS. Tobacco smoke carcinogens and lung cancer. J Natl Cancer Inst 1999;91:1194–1210.
- 76.
Secretan B, Straif K, Baan R et al.. A review of human carcinogens--Part E: tobacco, areca nut, alcohol, coal smoke, and salted fish. Lancet Oncol 2009;10:1033–1034.
- 77.↑
Sakoda LC, Loomis MM, Doherty JA et al.. Germ line variation in nucleotide excision repair genes and lung cancer risk in smokers. Int J Mol Epidemiol Genet 2012;3:1–17.
- 78.↑
Centers for Disease Control and Prevention. Smoking-attributable mortality, years of potential life lost, and productivity losses--United States, 2000-2004. MMWR Morb Mortal Wkly Rep 2008;57:1226–1228.
- 79.↑
Jha P, Ramasundarahettige C, Landsman V et al.. 21st-century hazards of smoking and benefits of cessation in the United States. N Engl J Med 2013;368:341–350.
- 80.
Doll R, Peto R, Boreham J, Sutherland I. Mortality in relation to smoking: 50 years' observations on male British doctors. BMJ 2004;328:1519.
- 81.
Moolgavkar SH, Holford TR, Levy DT et al.. Impact of reduced tobacco smoking on lung cancer mortality in the United States during 1975-2000. J Natl Cancer Inst 2012;104:541–548.
- 82.↑
Peto R, Darby S, Deo H et al.. Smoking, smoking cessation, and lung cancer in the UK since 1950: combination of national statistics with two case-control studies. BMJ 2000;321:323–329.
- 83.↑
Kasza KA, Ambrose BK, Conway KP et al.. Tobacco-product use by adults and youths in the United States in 2013 and 2014. N Engl J Med 2017;376:342–353.
- 84.↑
Hu SS, Neff L, Agaku IT et al.. Tobacco product use among adults - United States, 2013-2014. MMWR Morb Mortal Wkly Rep 2016;65:685–691.
- 85.↑
Office on Smoking and Health (US). The Health Consequences of Involuntary Exposure to Tobacco Smoke: A Report of the Surgeon General (ed 2010/07/30). Atlanta: Centers for Disease Control and Prevention; 2006.
- 86.↑
Garfinkel L. Time trends in lung cancer mortality among nonsmokers and a note on passive smoking. J Natl Cancer Inst 1981;66:1061–1066.
- 87.↑
Hackshaw AK, Law MR, Wald NJ. The accumulated evidence on lung cancer and environmental tobacco smoke. BMJ 1997;315:980–988.
- 88.↑
Delva F, Margery J, Laurent F et al.. Medical follow-up of workers exposed to lung carcinogens: French evidence-based and pragmatic recommendations. BMC Public Health 2017;17:191.
- 89.
Straif K, Benbrahim-Tallaa L, Baan R et al.. A review of human carcinogens--part C: metals, arsenic, dusts, and fibres. Lancet Oncol 2009;10:453–454.
- 90.↑
Silverman DT, Samanic CM, Lubin JH et al.. The Diesel Exhaust in Miners study: a nested case-control study of lung cancer and diesel exhaust. J Natl Cancer Inst 2012;104:855–868.
- 91.
Nelson DI, Concha-Barrientos M, Driscoll T et al.. The global burden of selected occupational diseases and injury risks: methodology and summary. Am J Ind Med 2005;48:400–418.
- 92.
Nurminen M, Karjalainen A. Epidemiologic estimate of the proportion of fatalities related to occupational factors in Finland. Scand J Work Environ Health 2001;27:161–213.
- 93.↑
Steenland K, Loomis D, Shy C, Simonsen N. Review of occupational lung carcinogens. Am J Ind Med 1996;29:474–490.
- 94.↑
Markowitz SB, Levin SM, Miller A, Morabia A. Asbestos, asbestosis, smoking, and lung cancer. New findings from the North American insulator cohort. Am J Respir Crit Care Med 2013;188:90–96.
- 95.
Frost G, Darnton A, Harding AH. The effect of smoking on the risk of lung cancer mortality for asbestos workers in Great Britain (1971-2005). Ann Occup Hyg 2011;55:239–247.
- 96.↑
Reid A, de Klerk NH, Ambrosini GL et al.. The risk of lung cancer with increasing time since ceasing exposure to asbestos and quitting smoking. Occup Environ Med 2006;63:509–512.
- 97.↑
El Ghissassi F, Baan R, Straif K et al.. A review of human carcinogens--part D: radiation. Lancet Oncol 2009;10:751–752.
- 98.↑
Leuraud K, Schnelzer M, Tomasek L et al.. Radon, smoking and lung cancer risk: results of a joint analysis of three European case-control studies among uranium miners. Radiat Res 2011;176:375–387.
- 99.↑
Lubin JH & Boice JD Jr. Lung cancer risk from residential radon: meta-analysis of eight epidemiologic studies. J Natl Cancer Inst 1997;89:49–57.
- 100.↑
Darby S, Hill D, Auvinen A et al.. Radon in homes and risk of lung cancer: collaborative analysis of individual data from 13 European case-control studies. BMJ 2005;330:223.
- 101.↑
Wu GX, Nelson RA, Kim JY, Raz DJ. Non-small cell lung cancer as a second primary among patients with previous malignancy: who is at risk? Clin Lung Cancer 2017;18:543–550.
- 102.↑
Tucker MA, Murray N, Shaw EG et al.. Second primary cancers related to smoking and treatment of small-cell lung cancer. Lung Cancer Working Cadre. J Natl Cancer Inst 1997;89:1782–1788.
- 103.↑
Shiels MS, Gibson T, Sampson J et al.. Cigarette smoking prior to first cancer and risk of second smoking-associated cancers among survivors of bladder, kidney, head and neck, and stage I lung cancers. J Clin Oncol 2014;32:3989–3995.
- 104.↑
Travis LB, Gospodarowicz M, Curtis RE et al.. Lung cancer following chemotherapy and radiotherapy for Hodgkin's disease. J Natl Cancer Inst 2002;94:182–192.
- 105.↑
Morris LG, Sikora AG, Patel SG et al.. Second primary cancers after an index head and neck cancer: subsite-specific trends in the era of human papillomavirus-associated oropharyngeal cancer. J Clin Oncol 2011;29:739–746.
- 106.↑
Kawaguchi T, Matsumura A, Iuchi K et al.. Second primary cancers in patients with stage III non-small cell lung cancer successfully treated with chemo-radiotherapy. Jpn J Clin Oncol 2006;36:7–11.
- 107.↑
Richardson GE, Tucker MA, Venzon DJ et al.. Smoking cessation after successful treatment of small-cell lung cancer is associated with fewer smoking-related second primary cancers. Ann Intern Med 1993;119:383–390.
- 108.↑
Jonsson S, Thorsteinsdottir U, Gudbjartsson DF et al.. Familial risk of lung carcinoma in the Icelandic population. JAMA 2004;292:2977–2983.
- 109.↑
Li X, Hemminki K. Familial multiple primary lung cancers: a population-based analysis from Sweden. Lung Cancer 2005;47:301–307.
- 110.↑
Matakidou A, Eisen T, Houlston RS. Systematic review of the relationship between family history and lung cancer risk. Br J Cancer 2005;93:825–833.
- 111.↑
Bailey-Wilson JE, Amos CI, Pinney SM et al.. A major lung cancer susceptibility locus maps to chromosome 6q23-25. Am J Hum Genet 2004;75:460–474.
- 112.
Thorgeirsson TE, Geller F, Sulem P et al.. A variant associated with nicotine dependence, lung cancer and peripheral arterial disease. Nature 2008;452:638–642.
- 113.
Hung RJ, McKay JD, Gaborieau V et al.. A susceptibility locus for lung cancer maps to nicotinic acetylcholine receptor subunit genes on 15q25. Nature 2008;452:633–637.
- 114.
Amos CI, Wu X, Broderick P et al.. Genome-wide association scan of tag SNPs identifies a susceptibility locus for lung cancer at 15q25.1. Nat Genet 2008;40:616–622.
- 115.↑
Yang IA, Holloway JW, Fong KM. Genetic susceptibility to lung cancer and co-morbidities. J Thorac Dis 2013;5 Suppl 5:S454–462.
- 116.↑
Hwang SJ, Cheng LS, Lozano G et al.. Lung cancer risk in germline p53 mutation carriers: association between an inherited cancer predisposition, cigarette smoking, and cancer risk. Hum Genet 2003;113:238–243.
- 117.
Sanders BM, Jay M, Draper GJ, Roberts EM. Non-ocular cancer in relatives of retinoblastoma patients. Br J Cancer 1989;60:358–365.
- 118.↑
Fletcher O, Easton D, Anderson K et al.. Lifetime risks of common cancers among retinoblastoma survivors. J Natl Cancer Inst 2004;96:357–363.
- 119.↑
Mayne ST, Buenconsejo J, Janerich DT. Previous lung disease and risk of lung cancer among men and women nonsmokers. Am J Epidemiol 1999;149:13–20.
- 120.
Samet JM, Humble CG, Pathak DR. Personal and family history of respiratory disease and lung cancer risk. Am Rev Respir Dis 1986;134:466–470.
- 121.
Alavanja MC, Brownson RC, Boice JD Jr., Hock E. Preexisting lung disease and lung cancer among nonsmoking women. Am J Epidemiol 1992;136:623–632.
- 122.
Wu-Williams AH, Dai XD, Blot W et al.. Lung cancer among women in north-east China. Br J Cancer 1990;62:982–987.
- 123.
Gao YT, Blot WJ, Zheng W et al.. Lung cancer among Chinese women. Int J Cancer 1987;40:604–609.
- 124.
Brenner AV, Wang Z, Kleinerman RA et al.. Previous pulmonary diseases and risk of lung cancer in Gansu Province, China. Int J Epidemiol 2001;30:118–124.
- 125.↑
Skillrud DM, Offord KP, Miller RD. Higher risk of lung cancer in chronic obstructive pulmonary disease: a prospective, matched, controlled study. Ann Intern Med 1986;105:503–507.
- 126.↑
Yang P, Sun Z, Krowka MJ et al.. Alpha1-antitrypsin deficiency carriers, tobacco smoke, chronic obstructive pulmonary disease, and lung cancer risk. Arch Intern Med 2008;168:1097–1103.
- 127.↑
Lowry KP, Gazelle GS, Gilmore ME et al.. Personalizing annual lung cancer screening for patients with chronic obstructive pulmonary disease: a decision analysis. Cancer 2015;121:1556–1562.
- 128.↑
Young RP, Hopkins RJ. How the genetics of lung cancer may overlap with COPD. Respirology 2011;16:1047–1055.
- 129.
El-Zein RA, Young RP, Hopkins RJ, Etzel CJ. Genetic predisposition to chronic obstructive pulmonary disease and/or lung cancer: important considerations when evaluating risk. Cancer Prev Res (Phila) 2012;5:522–527.
- 130.↑
Koshiol J, Rotunno M, Consonni D et al.. Chronic obstructive pulmonary disease and altered risk of lung cancer in a population-based case-control study. PLoS One 2009;4:e7380.
- 131.
Young RP, Hopkins RJ, Christmas T et al.. COPD prevalence is increased in lung cancer, independent of age, sex and smoking history. Eur Respir J 2009;34:380–386.
- 132.↑
Turner MC, Chen Y, Krewski D et al.. Chronic obstructive pulmonary disease is associated with lung cancer mortality in a prospective study of never smokers. Am J Respir Crit Care Med 2007;176:285–290.
- 133.↑
Turner-Warwick M, Lebowitz M, Burrows B, Johnson A. Cryptogenic fibrosing alveolitis and lung cancer. Thorax 1980;35:496–499.
- 134.↑
Hubbard R, Venn A, Lewis S, Britton J. Lung cancer and cryptogenic fibrosing alveolitis: a population-based cohort study. Am J Respir Crit Care Med 2000;161:5–8.
- 135.↑
Hughes JM, Weill H. Asbestosis as a precursor of asbestos related lung cancer: results of a prospective mortality study. Br J Ind Med 1991;48:229–233.
- 136.↑
Han SS, Ten Haaf K, Hazelton WD et al.. The impact of overdiagnosis on the selection of efficient lung cancer screening strategies. Int J Cancer 2017;140:2436–2443.
- 137.↑
McKee BJ, Hashim JA, French RJ et al.. Experience with a CT screening program for individuals at high risk for developing lung cancer. J Am Coll Radiol 2015;12:192–197.
- 138.↑
Kovalchik SA, Tammemagi M, Berg CD et al.. Targeting of low-dose CT screening according to the risk of lung-cancer death. N Engl J Med 2013;369:245–254.
- 139.↑
Berg CD. Formidable challenges ahead for lung cancer screening. Oncology (Williston Park) 2012;26:182, 185.
- 140.↑
Pinsky PF, Berg CD. Applying the National Lung Screening Trial eligibility criteria to the US population: what percent of the population and of incident lung cancers would be covered? J Med Screen 2012;19:154–156.
- 141.↑
Pinsky PF, Kramer BS. Lung cancer risk and demographic characteristics of current 20-29 pack-year smokers: implications for screening. J Natl Cancer Inst 2015;107.
- 142.↑
Miller DL, Mayfield WR, Luu TD et al.. Community-based multidisciplinary computed tomography screening program improves lung cancer survival. Ann Thorac Surg 2016;101:1864–1869.
- 143.↑
Katki HA, Kovalchik SA, Berg CD et al.. Development and validation of risk models to select ever-smokers for CT lung cancer screening. JAMA 2016;315:2300–2311.
- 144.↑
Li K, Husing A, Sookthai D et al.. Selecting high-risk individuals for lung cancer screening: a prospective evaluation of existing risk models and eligibility criteria in the German EPIC cohort. Cancer Prev Res (Phila) 2015;8:777–785.
- 145.↑
Tammemagi MC, Church TR, Hocking WG et al.. Evaluation of the lung cancer risks at which to screen ever- and never-smokers: screening rules applied to the PLCO and NLST cohorts. PLoS Med 2014;11:e1001764.
- 146.↑
Ten Haaf K, Jeon J, Tammemagi MC et al.. Risk prediction models for selection of lung cancer screening candidates: a retrospective validation study. PLoS Med 2017;14:e1002277.
- 147.↑
Yousaf-Khan U, van der Aalst C, de Jong PA et al.. Risk stratification based on screening history: the NELSON lung cancer screening study. Thorax 2017;72:819–824.
- 148.↑
Saghir Z, Dirksen A, Ashraf H et al.. CT screening for lung cancer brings forward early disease. The randomised Danish Lung Cancer Screening Trial: status after five annual screening rounds with low-dose CT. Thorax 2012;67:296–301.
- 149.↑
Pedersen JH, Ashraf H, Dirksen A et al.. The Danish randomized lung cancer CT screening trial--overall design and results of the prevalence round. J Thorac Oncol 2009;4:608–614.
- 150.↑
Menezes RJ, Roberts HC, Paul NS et al.. Lung cancer screening using low-dose computed tomography in at-risk individuals: the Toronto experience. Lung Cancer 2010;67:177–183.
- 151.↑
Swensen SJ, Jett JR, Hartman TE et al.. CT screening for lung cancer: five-year prospective experience. Radiology 2005;235:259–265.
- 152.↑
Wilson DO, Weissfeld JL, Fuhrman CR et al.. The Pittsburgh Lung Screening Study (PLuSS): outcomes within 3 years of a first computed tomography scan. Am J Respir Crit Care Med 2008;178:956–961.
- 153.↑
Pinsky PF, Gierada DS, Hocking W et al.. National Lung Screening Trial findings by age: Medicare-eligible versus under-65 population. Ann Intern Med 2014;161:627–633.
- 154.↑
Varlotto JM, Decamp MM, Flickinger JC et al.. Would screening for lung cancer benefit 75- to 84-year-old residents of the United States? Front Oncol 2014;4:37.
- 156.↑
Jett JR, Midthun DE. Screening for lung cancer: for patients at increased risk for lung cancer, it works. Ann Intern Med 2011;155:540–542.
- 157.↑
Berrington de Gonzalez A, Kim KP, Berg CD. Low-dose lung computed tomography screening before age 55: estimates of the mortality reduction required to outweigh the radiation-induced cancer risk. J Med Screen 2008;15:153–158.
- 158.↑
Marshall HM, Bowman RV, Yang IA et al.. Screening for lung cancer with low-dose computed tomography: a review of current status. J Thorac Dis 2013;5 Suppl 5:S524–539.
- 159.↑
Yip R, Henschke CI, Xu DM et al.. Lung cancers manifesting as part-solid nodules in the National Lung Screening Trial. AJR Am J Roentgenol 2017;208:1011–1021.
- 160.↑
Gardiner N, Jogai S, Wallis A. The revised lung adenocarcinoma classification-an imaging guide. J Thorac Dis 2014;6:S537–546.
- 161.↑
Naidich DP, Bankier AA, MacMahon H et al.. Recommendations for the management of subsolid pulmonary nodules detected at CT: a statement from the Fleischner Society. Radiology 2013;266:304–317.
- 162.↑
Seidelman JL, Myers JL, Quint LE. Incidental, subsolid pulmonary nodules at CT: etiology and management. Cancer Imaging 2013;13:365–373.
- 163.↑
Hansell DM, Bankier AA, MacMahon H et al.. Fleischner Society: glossary of terms for thoracic imaging. Radiology 2008;246:697–722.
- 164.↑
Travis WD, Asamura H, Bankier AA et al.. The IASLC lung cancer staging project: proposals for coding T categories for subsolid nodules and assessment of tumor size in part-solid tumors in the forthcoming eighth edition of the TNM classification of lung cancer. J Thorac Oncol 2016;11:1204–1223.
- 165.
Travis WD, Brambilla E, Noguchi M et al.. Diagnosis of lung cancer in small biopsies and cytology: implications of the 2011 International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification. Arch Pathol Lab Med 2013;137:668–684.
- 166.↑
Travis WD, Brambilla E, Noguchi M et al.. International association for the study of lung cancer/american thoracic society/european respiratory society international multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol 2011;6:244–285.
- 167.↑
Kim HY, Shim YM, Lee KS et al.. Persistent pulmonary nodular ground-glass opacity at thin-section CT: histopathologic comparisons. Radiology 2007;245:267–275.
- 168.↑
Yip R, Yankelevitz DF, Hu M et al.. Lung cancer deaths in the National Lung Screening Trial attributed to nonsolid nodules. Radiology 2016;281:589–596.
- 169.↑
Fukui M, Suzuki K, Matsunaga T et al.. Surgical intervention for ground glass dominant lesions: observation or outright resection? Jpn J Clin Oncol 2017:1–6.
- 170.↑
Gould MK, Donington J, Lynch WR et al.. Evaluation of individuals with pulmonary nodules: when is it lung cancer? Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2013;143:e93S–120S.
- 171.↑
Chang B, Hwang JH, Choi YH et al.. Natural history of pure ground-glass opacity lung nodules detected by low-dose CT scan. Chest 2013;143:172–178.
- 172.
Lindell RM, Hartman TE, Swensen SJ et al.. Five-year lung cancer screening experience: CT appearance, growth rate, location, and histologic features of 61 lung cancers. Radiology 2007;242:555–562.
- 173.↑
MacMahon H, Austin JH, Gamsu G et al.. Guidelines for management of small pulmonary nodules detected on CT scans: a statement from the Fleischner Society. Radiology 2005;237:395–400.
- 174.↑
Jacobs C, van Rikxoort EM, Murphy K et al.. Computer-aided detection of pulmonary nodules: a comparative study using the public LIDC/IDRI database. Eur Radiol 2016;26:2139–2147.
- 175.
Zhao Y, de Bock GH, Vliegenthart R et al.. Performance of computer-aided detection of pulmonary nodules in low-dose CT: comparison with double reading by nodule volume. Eur Radiol 2012;22:2076–2084.
- 176.↑
Armato SG 3rd, McLennan G, Bidaut L et al.. The Lung Image Database Consortium (LIDC) and Image Database Resource Initiative (IDRI): a completed reference database of lung nodules on CT scans. Med Phys 2011;38:915–931.
- 177.
Clark TJ, Flood TF, Maximin ST, Sachs PB. Lung CT screening reporting and data system speed and accuracy are increased with the use of a semiautomated computer application. J Am Coll Radiol 2015;12:f1301–1306.
- 178.
Jacobs C, van Rikxoort EM, Scholten ET et al.. Solid, part-solid, or non-solid?: classification of pulmonary nodules in low-dose chest computed tomography by a computer-aided diagnosis system. Invest Radiol 2015;50:168–173.
- 179.↑
Valencia R, Denecke T, Lehmkuhl L et al.. Value of axial and coronal maximum intensity projection (MIP) images in the detection of pulmonary nodules by multislice spiral CT: comparison with axial 1-mm and 5-mm slices. Eur Radiol 2006;16:325–332.
- 180.↑
Fischbach F, Knollmann F, Griesshaber V et al.. Detection of pulmonary nodules by multislice computed tomography: improved detection rate with reduced slice thickness. Eur Radiol 2003;13:2378–2383.
- 181.
Kawel N, Seifert B, Luetolf M, Boehm T. Effect of slab thickness on the CT detection of pulmonary nodules: use of sliding thin-slab maximum intensity projection and volume rendering. AJR Am J Roentgenol 2009;192:1324–1329.
- 182.
Peloschek P, Sailer J, Weber M et al.. Pulmonary nodules: sensitivity of maximum intensity projection versus that of volume rendering of 3D multidetector CT data. Radiology 2007;243:561–569.
- 183.
Park EA, Goo JM, Lee JW et al.. Efficacy of computer-aided detection system and thin-slab maximum intensity projection technique in the detection of pulmonary nodules in patients with resected metastases. Invest Radiol 2009;44:105–113.
- 184.
Jankowski A, Martinelli T, Timsit JF et al.. Pulmonary nodule detection on MDCT images: evaluation of diagnostic performance using thin axial images, maximum intensity projections, and computer-assisted detection. Eur Radiol 2007;17:3148–3156.
- 185.
Rubin GD, Lyo JK, Paik DS et al.. Pulmonary nodules on multi-detector row CT scans: performance comparison of radiologists and computer-aided detection. Radiology 2005;234:274–283.
- 186.
Fraioli F, Bertoletti L, Napoli A et al.. Computer-aided detection (CAD) in lung cancer screening at chest MDCT: ROC analysis of CAD versus radiologist performance. J Thorac Imaging 2007;22:241–246.
- 187.
Sahiner B, Chan HP, Hadjiiski LM et al.. Effect of CAD on radiologists' detection of lung nodules on thoracic CT scans: analysis of an observer performance study by nodule size. Acad Radiol 2009;16:1518–1530.
- 188.↑
Das M, Muhlenbruch G, Heinen S et al.. Performance evaluation of a computer-aided detection algorithm for solid pulmonary nodules in low-dose and standard-dose MDCT chest examinations and its influence on radiologists. Br J Radiol 2008;81:841–847.
- 189.↑
Lee HY, Goo JM, Lee HJ et al.. Usefulness of concurrent reading using thin-section and thick-section CT images in subcentimetre solitary pulmonary nodules. Clin Radiol 2009;64:127–132.
- 190.↑
Kubo T, Lin PJ, Stiller W et al.. Radiation dose reduction in chest CT: a review. AJR Am J Roentgenol 2008;190:335–343.
- 191.↑
Lee JY, Chung MJ, Yi CA, Lee KS. Ultra-low-dose MDCT of the chest: influence on automated lung nodule detection. Korean J Radiol 2008;9:95–101.
- 192.↑
Funama Y, Awai K, Liu D et al.. Detection of nodules showing ground-glass opacity in the lungs at low-dose multidetector computed tomography: phantom and clinical study. J Comput Assist Tomogr 2009;33:49–53.
- 193.↑
Hein PA, Romano VC, Rogalla P et al.. Linear and volume measurements of pulmonary nodules at different CT dose levels - intrascan and interscan analysis. Rofo 2009;181:24–31.
- 194.↑
van Riel SJ, Sanchez CI, Bankier AA et al.. Observer variability for classification of pulmonary nodules on low-dose CT images and its effect on nodule management. Radiology 2015;277:863–871.
- 195.
Ridge CA, Yildirim A, Boiselle PM et al.. Differentiating between subsolid and solid pulmonary nodules at CT: inter- and intraobserver agreement between experienced thoracic radiologists. Radiology 2016;278:888–896.
- 196.↑
Kim H, Park CM, Song YS et al.. Measurement variability of persistent pulmonary subsolid nodules on same-day repeat CT: what is the threshold to determine true nodule growth during follow-up? PLoS One 2016;11:e0148853.
- 197.
Penn A, Ma M, Chou BB et al.. Inter-reader variability when applying the 2013 Fleischner guidelines for potential solitary subsolid lung nodules. Acta Radiol 2015;56:1180–1186.
- 198.
Pinsky PF, Gierada DS, Nath PH et al.. National lung screening trial: variability in nodule detection rates in chest CT studies. Radiology 2013;268:865–873.
- 199.
Singh S, Pinsky P, Fineberg NS et al.. Evaluation of reader variability in the interpretation of follow-up CT scans at lung cancer screening. Radiology 2011;259:263–270.
- 200.↑
Gierada DS, Pilgram TK, Ford M et al.. Lung cancer: interobserver agreement on interpretation of pulmonary findings at low-dose CT screening. Radiology 2008;246:265–272.
- 201.↑
Henschke CI, Boffetta P, Gorlova O et al.. Assessment of lung-cancer mortality reduction from CT Screening. Lung Cancer 2011;71:328–332.
- 202.↑
van Klaveren RJ, Oudkerk M, Prokop M et al.. Management of lung nodules detected by volume CT scanning. N Engl J Med 2009;361:2221–2229.
- 203.
Lopes Pegna A, Picozzi G, Mascalchi M et al.. Design, recruitment and baseline results of the ITALUNG trial for lung cancer screening with low-dose CT. Lung Cancer 2009;64:34–40.
- 204.
Veronesi G, Bellomi M, Scanagatta P et al.. Difficulties encountered managing nodules detected during a computed tomography lung cancer screening program. J Thorac Cardiovasc Surg 2008;136:611–617.
- 205.↑
Infante M, Cavuto S, Lutman FR et al.. A randomized study of lung cancer screening with spiral computed tomography: three-year results from the DANTE trial. Am J Respir Crit Care Med 2009;180:445–453.
- 206.↑
Swensen SJ, Jett JR, Hartman TE et al.. Lung cancer screening with CT: Mayo Clinic experience. Radiology 2003;226:756–761.
- 207.↑
Henschke CI, Yankelevitz DF, Naidich DP et al.. CT screening for lung cancer: suspiciousness of nodules according to size on baseline scans. Radiology 2004;231:164–168.
- 208.
Henschke CI, Yankelevitz DF, Miettinen OSInternational Early Lung Cancer Action Program Investigators. Computed tomographic screening for lung cancer: the relationship of disease stage to tumor size. Arch Intern Med 2006;166:321–325.
- 209.↑
International Early Lung Cancer Action Program Investigators Henschke CI, Yankelevitz DF et al.. Survival of patients with stage I lung cancer detected on CT screening. N Engl J Med 2006;355:1763–1771.
- 210.
Steele JD, Buell P. Asymptomatic solitary pulmonary nodules. Host survival, tumor size, and growth rate. J Thorac Cardiovasc Surg 1973;65:140–151.
- 211.
Galante E, Reduzzi D, Gallus G et al.. The growth rate in the interpretation of the natural history of lung cancer. Tumori 1984;70:427–432.
- 212.
Usuda K, Saito Y, Sagawa M et al.. Tumor doubling time and prognostic assessment of patients with primary lung cancer. Cancer 1994;74:2239–2244.
- 213.
Arai T, Kuroishi T, Saito Y et al.. Tumor doubling time and prognosis in lung cancer patients: evaluation from chest films and clinical follow-up study. Japanese Lung Cancer Screening Research Group. Jpn J Clin Oncol 1994;24:199–204.
- 214.↑
Weiss W, Boucot KR, Cooper DA. The histopathology of bronchogenic carcinoma and its relation to growth rate, metastasis, and prognosis. Cancer 1970;26:965–970.
- 215.↑
Patel VK, Naik SK, Naidich DP et al.. A practical algorithmic approach to the diagnosis and management of solitary pulmonary nodules: part 2: pretest probability and algorithm. Chest 2013;143:840–846.
- 216.↑
Murrmann GB, van Vollenhoven FH, Moodley L. Approach to a solid solitary pulmonary nodule in two different settings-”Common is common, rare is rare”. J Thorac Dis 2014;6:237–248.
- 217.
Allen TL, Kendi AT, Mitiek MO, Maddaus MA. Combined contrast-enhanced computed tomography and 18-fluoro-2-deoxy-D-glucose-positron emission tomography in the diagnosis and staging of non-small cell lung cancer. Semin Thorac Cardiovasc Surg 2011;23:43–50.
- 218.
Swensen SJ, Viggiano RW, Midthun DE et al.. Lung nodule enhancement at CT: multicenter study. Radiology 2000;214:73–80.
- 219.
Yi CA, Lee KS, Kim BT et al.. Tissue characterization of solitary pulmonary nodule: comparative study between helical dynamic CT and integrated PET/CT. J Nucl Med 2006;47:443–450.
- 220.
Christensen JA, Nathan MA, Mullan BP et al.. Characterization of the solitary pulmonary nodule: 18F-FDG PET versus nodule-enhancement CT. AJR Am J Roentgenol 2006;187:1361–1367.
- 221.
Schillaci O, Travascio L, Bolacchi F et al.. Accuracy of early and delayed FDG PET-CT and of contrast-enhanced CT in the evaluation of lung nodules: a preliminary study on 30 patients. Radiol Med 2009;114:890–906.
- 222.↑
Bastarrika G, Garcia-Velloso MJ, Lozano MD et al.. Early lung cancer detection using spiral computed tomography and positron emission tomography. Am J Respir Crit Care Med 2005;171:1378–1383.
- 223.↑
Sebro R, Aparici CM, Hernandez-Pampaloni M. FDG PET/CT evaluation of pathologically proven pulmonary lesions in an area of high endemic granulomatous disease. Ann Nucl Med 2013;27:400–405.
- 224.
Reyes N, Onadeko OO, Luraschi-Monjagatta Mdel C et al.. Positron emission tomography in the evaluation of pulmonary nodules among patients living in a coccidioidal endemic region. Lung 2014;192:589–593.
- 225.↑
Huber H, Hodolic M, Stelzmuller I et al.. Malignant disease as an incidental finding at (1)(8)F-FDG-PET/CT scanning in patients with granulomatous lung disease. Nucl Med Commun 2015;36:430–437.
- 226.↑
McWilliams A, Tammemagi MC, Mayo JR et al.. Probability of cancer in pulmonary nodules detected on first screening CT. N Engl J Med 2013;369:910–919.
- 227.↑
Herder GJ, van Tinteren H, Golding RP et al.. Clinical prediction model to characterize pulmonary nodules: validation and added value of 18F-fluorodeoxyglucose positron emission tomography. Chest 2005;128:2490–2496.
- 228.↑
Patel VK, Naik SK, Naidich DP et al.. A practical algorithmic approach to the diagnosis and management of solitary pulmonary nodules: part 1: radiologic characteristics and imaging modalities. Chest 2013;143:825–839.
- 229.
Gould MK, Fletcher J, Iannettoni MD et al.. Evaluation of patients with pulmonary nodules: when is it lung cancer?: ACCP evidence-based clinical practice guidelines (2nd edition). Chest 2007;132:108S–130S.
- 230.↑
Madsen PH, Holdgaard PC, Christensen JB, Hoilund-Carlsen PF. Clinical utility of F-18 FDG PET-CT in the initial evaluation of lung cancer. Eur J Nucl Med Mol Imaging 2016;43:2084–2097.
- 231.↑
Al-Ameri A, Malhotra P, Thygesen H et al.. Risk of malignancy in pulmonary nodules: a validation study of four prediction models. Lung Cancer 2015;89:27–30.
- 232.↑
Infante M, Cavuto S, Lutman FR et al.. Long-term follow-up results of the DANTE trial, a randomized study of lung cancer screening with spiral computed tomography. Am J Respir Crit Care Med 2015;191:1166–1175.
- 233.↑
Gierada DS, Pinsky P, Nath H et al.. Projected outcomes using different nodule sizes to define a positive CT lung cancer screening examination. J Natl Cancer Inst 2014;106.
- 234.↑
Yip R, Henschke CI, Yankelevitz DF, Smith JP. CT screening for lung cancer: alternative definitions of positive test result based on the National Lung Screening Trial and International Early Lung Cancer Action Program databases. Radiology 2014;273:591–596.
- 235.↑
Wood DE, Kazerooni E, Baum SL et al.. Lung cancer screening, version 1.2015: featured updates to the NCCN Guidelines. J Natl Compr Canc Netw 2015;13:23–34; quiz 34.
- 236.↑
Kazerooni EA, Armstrong MR, Amorosa JK et al.. ACR CT accreditation program and the lung cancer screening program designation. J Am Coll Radiol 2015;12:38–42.
- 237.↑
Henschke CI, Yip R, Yankelevitz DF, Smith JPInternational Early Lung Cancer Action Program Investigators. Definition of a positive test result in computed tomography screening for lung cancer: a cohort study. Ann Intern Med 2013;158:246–252.
- 238.↑
Revel MP, Bissery A, Bienvenu M et al.. Are two-dimensional CT measurements of small noncalcified pulmonary nodules reliable? Radiology 2004;231:453–458.
- 239.↑
Rampinelli C, Origgi D, Bellomi M. Low-dose CT: technique, reading methods and image interpretation. Cancer Imaging 2013;12:548–556.
- 240.↑
Donnelly EF. Technical parameters and interpretive issues in screening computed tomography scans for lung cancer. J Thorac Imaging 2012;27:224–229.
- 241.↑
Kozower BD, Larner JM, Detterbeck FC, Jones DR. Special treatment issues in non-small cell lung cancer: diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2013;143:e369S–399S.
- 242.↑
Kim H, Park CM, Koh JM et al.. Pulmonary subsolid nodules: what radiologists need to know about the imaging features and management strategy. Diagn Interv Radiol 2014;20:47–57.
- 243.↑
Detterbeck FC. Overdiagnosis during lung cancer screening: is it an overemphasised, underappreciated, or tangential issue? Thorax 2014;69:407–408.
- 244.↑
Rampinelli C, De Marco P, Origgi D et al.. Exposure to low dose computed tomography for lung cancer screening and risk of cancer: secondary analysis of trial data and risk-benefit analysis. BMJ 2017;356:j347.
- 245.
Wiener RS. Balancing the benefits and harms of low-dose computed tomography screening for lung cancer: Medicare's options for coverage. Ann Intern Med 2014;161:445–446.
- 246.↑
Ettinger DS. Lung cancer screening: has its time come? Oncology (Williston Park) 2014;28:342, 448.
- 247.
Braillon A. Bronchioalveolar lung cancer: screening and overdiagnosis. J Clin Oncol 2014;32:3575.
- 248.
Johnson DH, Schiller JH, Bunn PA. Reply to A. Braillon. J Clin Oncol 2014;32:3575.
- 249.↑
Slatore CG, Sullivan DR, Pappas M, Humphrey LL. Patient-centered outcomes among lung cancer screening recipients with computed tomography: a systematic review. J Thorac Oncol 2014;9:927–934.
- 250.↑
Brawley OW, Flenaugh EL. Low-dose spiral CT screening and evaluation of the solitary pulmonary nodule. Oncology (Williston Park) 2014;28:441–446.
- 251.↑
Ma J, Ward EM, Smith R, Jemal A. Annual number of lung cancer deaths potentially avertable by screening in the United States. Cancer 2013;119:1381–1385.
- 252.↑
Goldstraw P, Crowley J, Chansky K et al.. The IASLC Lung Cancer Staging Project: proposals for the revision of the TNM stage groupings in the forthcoming (seventh) edition of the TNM Classification of malignant tumours. J Thorac Oncol 2007;2:706–714.
- 253.↑
Rami-Porta R, Ball D, Crowley J et al.. The IASLC Lung Cancer Staging Project: proposals for the revision of the T descriptors in the forthcoming (seventh) edition of the TNM classification for lung cancer. J Thorac Oncol 2007;2:593–602.
- 254.↑
Amin MB, Greene FL, Edge SB et al., eds. AJCC Staging Manual, 8th ed. New York: Springer International Publishing; 2017.
- 255.↑
Rami-Porta R, Asamura H, Travis WD, Rusch VW. Lung cancer - major changes in the American Joint Committee on Cancer eighth edition cancer staging manual. CA Cancer J Clin 2017;67:138–155.
- 256.↑
Flieder DB, Vazquez M, Carter D et al.. Pathologic findings of lung tumors diagnosed on baseline CT screening. Am J Surg Pathol 2006;30:606–613.
- 257.↑
Hall FM. Identification, biopsy, and treatment of poorly understood premalignant, in situ, and indolent low-grade cancers: are we becoming victims of our own success? Radiology 2010;254:655–659.
- 258.↑
Gareen IF, Duan F, Greco EM et al.. Impact of lung cancer screening results on participant health-related quality of life and state anxiety in the National Lung Screening Trial. Cancer 2014;120:3401–3409.
- 259.↑
Mets OM, de Jong PA, Prokop M. Computed tomographic screening for lung cancer: an opportunity to evaluate other diseases. JAMA 2012;308:1433–1434.
- 260.↑
Mets OM, Buckens CF, Zanen P et al.. Identification of chronic obstructive pulmonary disease in lung cancer screening computed tomographic scans. JAMA 2011;306:1775–1781.
- 261.
Jacobs PC, Gondrie MJ, Mali WP et al.. Unrequested information from routine diagnostic chest CT predicts future cardiovascular events. Eur Radiol 2011;21:1577–1585.
- 262.↑
Sekikawa A, Curb JD, Edmundowicz D et al.. Coronary artery calcification by computed tomography in epidemiologic research and cardiovascular disease prevention. J Epidemiol 2012;22:188–198.
- 263.↑
Silvestri GA. Screening for lung cancer: it works, but does it really work? Ann Intern Med 2011;155:537–539.
- 264.↑
Croswell JM, Baker SG, Marcus PM et al.. Cumulative incidence of false-positive test results in lung cancer screening: a randomized trial. Ann Intern Med 2010;152:505–512, W176–580.
- 265.
Diederich S, Wormanns D, Semik M et al.. Screening for early lung cancer with low-dose spiral CT: prevalence in 817 asymptomatic smokers. Radiology 2002;222:773–781.
- 266.
Gohagan JK, Marcus PM, Fagerstrom RM et al.. Final results of the Lung Screening Study, a randomized feasibility study of spiral CT versus chest X-ray screening for lung cancer. Lung Cancer 2005;47:9–15.
- 267.
Henschke CI, McCauley DI, Yankelevitz DF et al.. Early Lung Cancer Action Project: overall design and findings from baseline screening. Lancet 1999;354:99–9105.
- 268.↑
Kaneko M, Eguchi K, Ohmatsu H et al.. Peripheral lung cancer: screening and detection with low-dose spiral CT versus radiography. Radiology 1996;201:798–802.
- 269.↑
Wiener RS, Schwartz LM, Woloshin S, Welch HG. Population-based risk for complications after transthoracic needle lung biopsy of a pulmonary nodule: an analysis of discharge records. Ann Intern Med 2011;155:137–144.
- 270.↑
Henschke CI, Yip R, Yankelevitz DF, Miettinen OS. Computed tomography screening for lung cancer: prospects of surviving competing causes of death. Clin Lung Cancer 2006;7:323–325.
- 271.↑
McCunney RJ, Li J. Radiation risks in lung cancer screening programs: a comparison with nuclear industry workers and atomic bomb survivors. Chest 2014;145:618–624.
- 272.↑
Bach PB, Jett JR, Pastorino U et al.. Computed tomography screening and lung cancer outcomes. JAMA 2007;297:953–961.
- 273.↑
Bach PB, Cramer LD, Schrag D et al.. The influence of hospital volume on survival after resection for lung cancer. N Engl J Med 2001;345:181–188.
- 274.
Silvestri GA, Handy J, Lackland D et al.. Specialists achieve better outcomes than generalists for lung cancer surgery. Chest 1998;114:675–680.
- 275.↑
Stephan F, Boucheseiche S, Hollande J et al.. Pulmonary complications following lung resection: a comprehensive analysis of incidence and possible risk factors. Chest 2000;118:1263–1270.
- 276.↑
Sone S, Takashima S, Li F et al.. Mass screening for lung cancer with mobile spiral computed tomography scanner. Lancet 1998;351:1242–1245.
- 277.↑
Li F, Sone S, Abe H et al.. Lung cancers missed at low-dose helical CT screening in a general population: comparison of clinical, histopathologic, and imaging findings. Radiology 2002;225:673–683.
- 278.↑
Armato SG 3rd, Li F, Giger ML et al.. Lung cancer: performance of automated lung nodule detection applied to cancers missed in a CT screening program. Radiology 2002;225:685–692.
- 279.↑
DeVita VT Jr., Young RC, Canellos GP. Combination versus single agent chemotherapy: a review of the basis for selection of drug treatment of cancer. Cancer 1975;35:98–110.
- 280.↑
Folkman J. Seminars in Medicine of the Beth Israel Hospital, Boston. Clinical applications of research on angiogenesis. N Engl J Med 1995;333:1757–1763.
- 281.↑
Patz EF, Black WC, Goodman PC. CT screening for lung cancer: not ready for routine practice. Radiology 2001;221:587–591.
- 282.↑
Yoshizawa A, Motoi N, Riely GJ et al.. Impact of proposed IASLC/ATS/ERS classification of lung adenocarcinoma: prognostic subgroups and implications for further revision of staging based on analysis of 514 stage I cases. Mod Pathol 2011;24:653–664.
- 283.↑
Russell PA, Wainer Z, Wright GM et al.. Does lung adenocarcinoma subtype predict patient survival?: a clinicopathologic study based on the new International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society international multidisciplinary lung adenocarcinoma classification. J Thorac Oncol 2011;6:1496–1504.
- 284.↑
Jett JR, Midthun DE. Commentary: CT screening for lung cancer--caveat emptor. Oncologist 2008;13:439–444.
- 285.↑
Bach PB. Reduced lung-cancer mortality with CT screening. N Engl J Med 2011;365:2036; author reply 2037–2038.
- 286.↑
van den Bergh KA, Essink-Bot ML, Bunge EM et al.. Impact of computed tomography screening for lung cancer on participants in a randomized controlled trial (NELSON trial). Cancer 2008;113:396–404.
- 287.↑
van den Bergh KA, Essink-Bot ML, Borsboom GJ et al.. Short-term health-related quality of life consequences in a lung cancer CT screening trial (NELSON). Br J Cancer 2010;102:27–34.
- 288.↑
van den Bergh KA, Essink-Bot ML, Borsboom GJ et al.. Long-term effects of lung cancer computed tomography screening on health-related quality of life: the NELSON trial. Eur Respir J 2011;38:154–161.
- 289.↑
Gierada DS, Pinsky PF, Duan F et al.. Interval lung cancer after a negative CT screening examination: CT findings and outcomes in National Lung Screening Trial participants. Eur Radiol 2017;27:3249–3256.
- 290.↑
Sistrom CL, Dreyer KJ, Dang PP et al.. Recommendations for additional imaging in radiology reports: multifactorial analysis of 5.9 million examinations. Radiology 2009;253:453–461.
- 291.↑
Berland LL, Silverman SG, Gore RM et al.. Managing incidental findings on abdominal CT: white paper of the ACR incidental findings committee. J Am Coll Radiol 2010;7:754–773.
- 292.↑
Larke FJ, Kruger RL, Cagnon CH et al.. Estimated radiation dose associated with low-dose chest CT of average-size participants in the National Lung Screening Trial. AJR Am J Roentgenol 2011;197:1165–1169.
- 293.↑
Brenner DJ. Radiation risks potentially associated with low-dose CT screening of adult smokers for lung cancer. Radiology 2004;231:440–445.
- 294.↑
Frank L, Christodoulou E, Kazerooni EA. Radiation risk of lung cancer screening. Semin Respir Crit Care Med 2013;34:738–747.
- 295.↑
Mascalchi M, Belli G, Zappa M et al.. Risk-benefit analysis of X-ray exposure associated with lung cancer screening in the Italung-CT trial. AJR Am J Roentgenol 2006;187:421–429.
- 296.↑
Goulart BH, Bensink ME, Mummy DG, Ramsey SD. Lung cancer screening with low-dose computed tomography: costs, national expenditures, and cost-effectiveness. J Natl Compr Canc Netw 2012;10:267–275.
- 297.↑
Centers for Disease Control and Prevention. Vital signs: current cigarette smoking among adults aged ≥18 years--United States, 2005-2010. MMWR Morb Mortal Wkly Rep 2011;60:1207–1212.
- 298.↑
Mauchley DC, Mitchell JD. Current estimate of costs of lung cancer screening in the United States. Thorac Surg Clin 2015;25:205–215.
- 299.↑
Schweigert M, Dubecz A, Beron M et al.. Pulmonary infections imitating lung cancer: clinical presentation and therapeutical approach. Ir J Med Sci 2013;182:73–80.
- 300.↑
Jacobs PC, Gondrie MJ, van der Graaf Y et al.. Coronary artery calcium can predict all-cause mortality and cardiovascular events on low-dose CT screening for lung cancer. AJR Am J Roentgenol 2012;198:505–511.
- 301.↑
Morgan L, Choi H, Reid M et al.. The frequency of incidental findings and subsequent evaluation in low-dose CT scans for lung cancer screening. Ann Am Thorac Soc 2017;14:1450–1456.
- 302.↑
Black WC, Gareen IF, Soneji SS et al.. Cost-effectiveness of CT screening in the National Lung Screening Trial. N Engl J Med 2014;371:1793–1802.
- 303.↑
Duke SL, Eisen T. Finding needles in a haystack: annual low-dose computed tomography screening reduces lung cancer mortality in a high-risk group. Expert Rev Anticancer Ther 2011;11:1833–1836.
- 304.↑
Puggina A, Broumas A, Ricciardi W, Boccia S. Cost-effectiveness of screening for lung cancer with low-dose computed tomography: a systematic literature review. Eur J Public Health 2016;26:168–175.
- 305.↑
Tabar L, Vitak B, Chen TH et al.. Swedish two-county trial: impact of mammographic screening on breast cancer mortality during 3 decades. Radiology 2011;260:658–663.
- 306.↑
Lafata JE, Simpkins J, Lamerato L et al.. The economic impact of false-positive cancer screens. Cancer Epidemiol Biomarkers Prev 2004;13:2126–2132.
- 307.↑
Wisnivesky JP, Mushlin AI, Sicherman N, Henschke C. The cost-effectiveness of low-dose CT screening for lung cancer: preliminary results of baseline screening. Chest 2003;124:614–621.
- 308.↑
Lillie SE, Fu SS, Fabbrini AE et al.. What factors do patients consider most important in making lung cancer screening decisions? Findings from a demonstration project conducted in the Veterans Health Administration. Lung Cancer 2017;104:38–44.
- 309.↑
Woloshin S, Schwartz LM, Black WC, Kramer BS. Cancer screening campaigns--getting past uninformative persuasion. N Engl J Med 2012;367:1677–1679.
- 310.↑
Smith RA, Andrews KS, Brooks D et al.. Cancer screening in the United States, 2017: a review of current American Cancer Society guidelines and current issues in cancer screening. CA Cancer J Clin 2017;67:100–121.
- 311.↑
Tammemagi MC, Berg CD, Riley TL et al.. Impact of lung cancer screening results on smoking cessation. J Natl Cancer Inst 2014;106:dju084.
