International Early Lung Cancer Action Program Research Articles

A 20-year Follow-up of the International Early Lung Cancer Action Program (I-ELCAP).

Background The low-dose CT (≤3 mGy) screening report of 1000 Early Lung Cancer Action Program (ELCAP) participants in 1999 led to the International ELCAP (I-ELCAP) collaboration, which enrolled 31 567 participants in annual low-dose CT screening between 1992 and 2005. In 2006, I-ELCAP investigators reported the 10-year lung cancer-specific survival of 80% for 484 participants diagnosed with a first primary lung cancer through annual screening, with a high frequency of clinical stage I lung cancer (85%). Purpose To update the cure rate by determining the 20-year lung cancer-specific survival of participants diagnosed with first primary lung cancer through annual low-dose CT screening in the expanded I-ELCAP cohort. Materials and Methods For participants enrolled in the HIPAA-compliant prospective I-ELCAP cohort between 1992 and 2022 and observed until December 30, 2022, Kaplan-Meier survival analysis was used to determine the 10- and 20-year lung cancer-specific survival of participants diagnosed with first primary lung cancer through annual low-dose CT screening. Eligible participants were aged at least 40 years and had current or former cigarette use or had never smoked but had been exposed to secondhand tobacco smoke. Results Among 89 404 I-ELCAP participants, 1257 (1.4%) were diagnosed with a first primary lung cancer (684 male, 573 female; median age, 66 years; IQR, 61-72), with a median smoking history of 43.0 pack-years (IQR, 29.0-60.0). Median follow-up duration was 105 months (IQR, 41-182). The frequency of clinical stage I at pretreatment CT was 81% (1017 of 1257). The 10-year lung cancer-specific survival of 1257 participants was 81% (95% CI: 79, 84) and the 20-year lung cancer-specific survival was 81% (95% CI: 78, 83), and it was 95% (95% CI: 91, 98) for 181 participants with pathologic T1aN0M0 lung cancer. Conclusion The 10-year lung cancer-specific survival of 80% reported in 2006 for I-ELCAP participants enrolled in annual low-dose CT screening and diagnosed with a first primary lung cancer has persisted, as shown by the updated 20-year lung cancer-specific survival for the expanded I-ELCAP cohort. © RSNA, 2023 See also the editorials by Grenier and by Sequist and Olazagasti in this issue.

Prospective Cohort Study to Compare Long-Term Lung Cancer-Specific and All-Cause Survival of Clinical Early Stage (T1a–b; ≤20 mm) NSCLC Treated by Stereotactic Body Radiation Therapy and Surgery

IntroductionWe aimed to compare outcomes of patients with first primary clinical T1a-bN0M0 NSCLC treated with surgery or stereotactic body radiation therapy (SBRT). MethodsWe identified patients with first primary clinical T1a-bN0M0 NSCLCs on last pretreatment computed tomography treated by surgery or SBRT in the following two prospective cohorts: International Early Lung Cancer Action Program (I-ELCAP) and Initiative for Early Lung Cancer Research on Treatment (IELCART). Lung cancer-specific survival and all-cause survival after diagnosis were compared using Kaplan-Meier analysis. Propensity score matching was used to balance baseline demographics and comorbidities and analyzed using Cox proportional hazards regression. ResultsOf 1115 patients with NSCLC, 1003 had surgery and 112 had SBRT; 525 in I-ELCAP in 1992 to 2021 and 590 in IELCART in 2016 to 2021. Median follow-up was 57.6 months. Ten-year lung cancer-specific survival was not significantly different: 90% (95% confidence interval: 87%–92%) for surgery versus 88% (95% confidence interval: 77%–99%) for SBRT, p = 0.55. Cox regression revealed no significant difference in lung cancer-specific survival for the combined cohorts (p = 0.48) or separately for I-ELCAP (p = 1.00) and IELCART (p = 1.00). Although 10-year all-cause survival was significantly different (75% versus 45%, p < 0.0001), after propensity score matching, all-cause survival using Cox regression was no longer different for the combined cohorts (p = 0.74) or separately for I-ELCAP (p = 1.00) and IELCART (p = 0.62). ConclusionsThis first prospectively collected cohort analysis of long-term survival of small, early NSCLCs revealed that lung cancer-specific survival was high for both treatments and not significantly different (p = 0.48) and that all-cause survival after propensity matching was not significantly different (p = 0.74). This supports SBRT as an alternative treatment option for small, early NSCLCs which is especially important with their increasing frequency owing to low-dose computed tomography screening. Furthermore, treatment decisions are influenced by many different factors and should be personalized on the basis of the unique circumstances of each patient.

Efficacy of Low Dose Computed Tomography Using Adaptive Statistical Iterative Reconstruction in Lung Cancer Screening

Abstract Background: Lung cancer is the most common malignant tumor and the leading cause of cancer-related deaths all over the world. Early detection and treatment are important to increase survival rate. Therefore, screening of lung cancer should target those individuals at high risk. Aim of Study: To detect the efficacy of low dose computed tomography (LDCT) of the chest with adaptive statistical iterative reconstruction (ASIR) algorithmas a screening method in diagnosing early stages of lung cancer and thus decrease the disease related morbidity and mortality as itminimizes exposure to ionizing radiation while maintaining sufficient image quality. Material and Methods: Ninety-six high risk cases (current smokers or ex-smokers), 94 males and 2 females, withage range from 50-78 yearswere included in this study. All cases underwent CT of the chest using low dose protocol with-ASIR algorithm with different blending levels of reconstruction (40%, 60%) for lung cancer screening. All images were interpreted using the International Early Lung Cancer Action Program (I-ELCAP) diagnostic protocol for lung nodule diagnosis and management. Results: From 96 cases included in the study, 82 cases had normal chest CT and 14 cases showed abnormal findings in chest CT (4 of them showed nodular lung lesions and the other 10 cases showed other findings related to smoking as bullae, bronchial wall thickening, emphysema, honey combing and bronchiectasis). Among the 6 nodules detected in the 4 cases, one nodule was >!15mm, and 5 nodules were <15mm. According to I-ELCAP diagnostic protocol, one nodule was considered positive and 5 nodules were considered semi-positive. LDCT chest using ASIR algorithm for lung cancer screening revealed high sensitivity and specificity for detecting lesions at cut off point size 6 mm (84.9% and 100% respec-tively). The area under receiver operating characteristic (ROC) curve for prediction of nodule with cutoff point size 6mm was 0.938 with 95% confidence interval (0.887-0.990). Conclusion: LDCT of the chest using ASIR algorithm is a promising and efficient tool for lung cancer screening with significant minimization of ionizing radiation exposure as well as preserved optimum image quality.

Retrospective assessment of Lung-RADS® performance in the Silesian Lung Cancer Screening Pilot Study

Background. A high percentage of false positive results, observed in lung cancer screening studies with low-dose computed tomography (LDCT), caused the modification of radiological assessment methods. According to the International Early Lung Cancer Action Program (IELCAP) all non-calcified nodules with a dimension ≥ 4 mm were considered as positive. Implementation of classification the Lung CT screening Reporting and Data System (Lung-RADS®) recommends additional testing only for nodules ≥ 6 mm, which reduced of false positive results. Methods. We provided a retrospective analysis of 601 LDCT scans, in asymptomatic volunteers of Pilot Silesian Study of Early Lung Cancer Detection, with at least 20 pack-years of cigarette smoking. The analysis of non- and invasive interventions was done. Assessment of nodules according to the Lung-RADS® system was done. Then the percentage of interventions that could be avoided using the Lung-RADS® criteria was estimated. Results. In total, 1016 nodules were identified in 265 participants. The positive result of screening was defined as a presence of solid or part-solid nodule ≥ 5 mm and ≥ 8 mm in the case of a nonsolid nodule in line with the IELCAP protocol. Screening based on the IELCAP protocol resulted in 200 positive results and based on Lung-RADS® in the 116 positives. The frequency of lung cancers among participants with a positive result was 7 of 200 (4.0%) (95% CI: 1.0%, 6.0%) for IELCAP and 7 of 116 (6.0%) (95% CI: 2.7%, 9.3%) for Lung-RADS®. The Lung-RADS® criteria reduced number of non- and invasive procedures by 48.8% and 24.1%, compared to IELCAP protocol. Conclusions. Adopting the Lung-RADS® classification system may reduce harms and improve the efficiency of lung cancer screening programs.

MTE 27.02 Pulmonary Nodule Guidelines: How Do We Decide Between the IELCAP, ACCP, NCCN, Fleischner Society, BTS, and Lung-RADS?

In the era of multidetector CT and lung cancer screening with low-dose CT, there are increasing number of incidentally or screen detected pulmonary nodules. Because a pulmonary nodule is an important finding of lung cancer, how to manage these nodules has become an essential issue in dealing with lung cancer, which explains why many guidelines on this topic are available. In this talk, overview of several well-established guidelines or protocols of International Early Lung Cancer Action Program (IELCAP), the American College of Chest Physicians (ACCP), National Comprehensive Cancer Network (NCCN), Fleischner Society, British Thoracic Society (BTS), and Lung CT screening Reporting and Data System (Lung-RADS) will be introduced. Nodule management protocols are different whether nodules are detected at screening programs or incidentally. Screening programs target high-risk subjects who need consistent monitoring, whereas incidentally detected lung nodules represent a different population that needs a varied clinical management. ACCP, BTS, and Fleischner Society guidelines deal with incidental nodules, while IELCAP and Lung-RADS are protocols for screening programs. NCCN guidelines state both issues with separate algorithms. Most pulmonary nodule guidelines have common components: risk factor assessment, nodule size, and nodule consistency. Baseline and annual repeat protocols are different at screening programs. Risk factors include age, smoking history, family history, previous cancer history, occupation exposure, etc. Nodules smaller than certain thresholds (NCCN, < 4 mm; ACCP and BTS, < 5 mm; Fleischner, IELCAP, and Lung-RADS, < 6 mm) do not require routine follow-up. The management for larger nodules varies with guidelines, but 8 mm and/or 15 mm are frequently recommended thresholds for more workups. Nodules can be classified into solid, part-solid, and pure ground-glass nodule according to their consistency. Because the likelihood of malignancy and growth rates are quite different depending on the nodule consistency, this classification is important in nodule management. Nodule volumetry and risk-prediction models such as the Brock University tool, currently employed in BTS guidelines, may be used more frequently in future guidelines. While the Fleischner Society, IELCAP, and Lung-RADS guidelines are relatively straightforward focused on the initial workup, ACCP, NCCN, and BTS guidelines also deal with the further workup and treatment. Some studies have shown that there is high awareness and adoption of these guidelines, but there are varying degrees of conformance with these recommendations. With the accumulation of large data, these guidelines will be more meticulous and evidence-based. Computerized tools that can assess both clinical and radiologic information will facilitate handling the issue of nodule management. 1. I-ELCAP protocol documents at http://www.ielcap.org/protocols Gould MK, 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 May;143(5 Suppl):e93S-e120S. 2. NCCN guidelines at https://www.nccn.org/professionals/physician_gls/f_guidelines.asp. 3. Callister ME, et al. British Thoracic Society guidelines for the investigation and management of pulmonary nodules. Thorax. 2015 Aug;70 Suppl 2:ii1-ii54. 4. MacMahon H, et al. Guidelines for Management of Incidental Pulmonary Nodules Detected on CT Images: From the Fleischner Society 2017. Radiology. 2017 Jul;284(1):228-243. Lung-RADS at https://www.acr.org/Quality-Safety/Resources/LungRADS. guidelines, lung cancer, lung nodule management

P2.16-023 Changes of the Pulmonary Artery After Resection of Stage I Lung Cancer

Radiologists focus on the anatomic changes in the lung itself when interpreting postoperative surveillance CT scans, but the anatomic and physiologic effects of lung resection on the other organs of the thorax, specifically the pulmonary artery (PA), have not been well studied. Potential variations in PA size over time have been recognized as predictors of post-surgical complications and the development of pulmonary hypertension. The International Early Lung Cancer Action Program (I-ELCAP) database was queried for lung cancer patients who underwent lobectomy and had both preoperative and postoperative CT imaging. Case-specific details were previously recorded in the database as per I-ELCAP protocol. All surgeries were performed by general thoracic surgeons. All CT imaging for each patient was reviewed by a fellowship-trained chest radiologist. Among the 142 subjects who underwent lobectomy, the median follow-up time from the pre-surgical CT to the last reviewable CT was 53.2 months (IQR: 27.9-100.4 months). The average increase in the size of the main pulmonary artery (mPA) was 1.5 mm (19.9 mm to 21.4 mm, P < 0.0001). There was also a significant increase between the pre-surgical CT and the initial postoperative CT which was on average 12.6 months later from 19.9 mm to 20.7 mm (P = 0.0002). Considering patients with and without CT evidence of emphysema, the 82 with emphysema had a smaller average change of the main PA between the pre-surgical and the last reviewable CT than the 60 without emphysema (1.0 mm vs. 1.8 mm, P = 0.08). Patients undergoing lobectomy appear to be at increased risk for enlargement of their pulmonary artery diameters after surgery. These results show that a focus on all the organs in the thorax, not just the lungs themselves, is important when evaluating postoperative lung resection CTs.

International Early Lung Cancer Action Program: update on lung cancer screening and the management of CT screen-detected findings

CT screening for lung cancer is a complex undertaking requiring specifications of all of its components. This includes questions as to who should be screened, how frequently screening should be performed, and an optimal regimen of screening. The regimen of screened defines who requires further workup during the year the screening is performed in addition to the specification of the CT acquisition parameters, how the readings are performed, and the results communicated to the participants being screened. In addition to looking for suspicious pulmonary nodules, the CT scan also shows the heart, mediastinum thyroid, and the organs in the upper abdomen. The recommendations for abnormal findings in all these organs and the workup also need to be interpreted in light of the fact that they are found in asymptomatic people at risk of lung cancer and not that they presented for clinical care because of symptoms. This report provides the International Early Lung Cancer Action Program (I-ELCAP) protocol for screening and also provides the references that provide the basis for the protocol. This protocol has been continually updated in light of advancing CT and diagnostic technology and knowledge that has emerged as a result of screening, particularly large databases that have been developed.

Four percent matters

Studies like the International Early Lung Cancer Action Program (I-ELCAP) (1) have revolutionized our understanding of early-stage lung cancer and its management. In their recent article (2), Flores and colleagues challenge us with the notion that sublobar resection without mediastinal lymph node sampling may be an adequate treatment for clinical stage IA non-small cell lung cancer (NSCLC). Drawing on the database of the I-ELCAP project (1), they were able to stratify patients into two propensity matched cohorts who received mediastinal lymph node resection (MLNR) and those who did not. A solid statistical and survival analysis methodology failed to demonstrate any significant difference in overall survival between patients who received MLNR during their operation, and those who did not. The authors conclude that subsolid nodules less than 30 mm in diameter, and peripheral solid nodules less than 20 mm in diameter should be treated with sublobar resection without MLNR.

Lung cancer screening.

Lung cancer screening.

The importance of the regimen of screening in maximizing the benefit and minimizing the harms.

In CT screening for lung cancer, the regimen of screening is critical in diagnosing lung cancer early while limiting unnecessary tests and invasive procedures. The International Early Lung Cancer Action Program (I-ELCAP) has developed a regimen based on evidence collected in the I-ELCAP cohort of more than 70,000 participants. Important in the development of the regimen is the recognition of the profound difference between the first, baseline round of screening and all subsequent rounds of repeat screening. For each person undergoing screening, the baseline round happens only once while repeat rounds will be performed annually for many years. This difference needs to be clearly recognized as it is these annual rounds which allow for identification of small, early, yet aggressive, lung cancers which have high cure rates despite their aggressiveness. The importance of nodule consistency and size are key factors in the regimen. The regimen needs to be continuously updated by incorporating advances in technology and knowledge. The use of the I-ELCAP regimen reduces the workup of participants in the screening program to less than 10% in the baseline round and less than 6% in the annual repeat rounds. By use of this regimen, estimated cure rate of lung cancers diagnosed under screening is 80% or higher in both baseline and annual repeat rounds. The I-ELCAP collaboration provides a new paradigm that answers the 2002 NCI call for multiple approaches to address relevant questions about screening and the Institute of Medicine (IOM) Roundtable on Evidence-based Medicine from the National Academy of Science's call for a "new clinical research paradigm that takes better advantage of data generated in the course of healthcare delivery would speed and improve the development of evidence for real-world decision making".

Low-dose Computed Tomography Screening for Lung Cancer in a Clinical Setting

The purpose of this article is to review clinical computed tomography (CT) lung screening program elements essential to safely and effectively manage the millions of Americans at high risk for lung cancer expected to enroll in lung cancer screening programs over the next 3 to 5 years. To optimize the potential net benefit of CT lung screening and facilitate medical audits benchmarked to national quality standards, radiologists should interpret these examinations using a validated structured reporting system such as Lung-RADS. Patient and physician educational outreach should be enacted to support an informed and shared decision-making process without creating barriers to screening access. Programs must integrate smoking cessation interventions to maximize the clinical efficacy and cost-effectiveness of screening. At an institutional level, budgets should account for the necessary expense of hiring and/or training qualified support staff and equipping them with information technology resources adequate to enroll and track patients accurately over decades of future screening evaluation. At a national level, planning should begin on ways to accommodate the upcoming increased demand for physician services in fields critical to the success of CT lung screening such as diagnostic radiology and thoracic surgery. Institutions with programs that follow these specifications will be well equipped to meet the significant oncoming demand for CT lung screening services and bestow clinical benefits on their patients equal to or beyond what was observed in the National Lung Screening Trial.

Lung Cancer Screening: A Comprehensive Review of the Literature with Detailed Data

Lung cancer still has a big proportion of cancer related deaths inspite of improvements in chemotherapeutic and surgical treatment approaches. It has a strong relationship with tobacco comsumption so that it can be regard as a common health problem. The survival rates of lung cancer at earlier stages are higher than later stages, so it is worth to effort detect lung cancer at an early stages which can cause mortality reduction and survival improvement. Some screening methods were used in screening trials to achieve a satisfactory mortality reduction with increased survival rates. We discussed about the results of important big trials which have different methods and qualities. There are two important screening tools to discuss about including; chest x-ray and low dose computed thomography (CT). Although there were many randomized or non-randomized trials used these tools for screening programs, few studies have enough power and quality to interpret the results. In this review, we discuss about the latest and detailed data of screening trials including, The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, Mayo Lung Project, The National Lung Screning Trial (NLST), The NELSON trial, The International Early Lung Cancer Action Program (I-ELCAP). Among the results of the trials we discussed about, only screening with low dose CT showed a statistically significant reduction of lung cancer deaths with increased early detection in high risk patients. Of these trials, the NLST which showed 20% mortality reduction in lung cancer and 6.7% mortality reduction from any cause has enough power to achieve this target and this results have affected nearly all of guidelines and recommendations of experts. The results of studies with low dose CT, especially of the NLST, changed thoughts about lung cancer screening. According to these results, the high risk individuals are suggested to be screened with low dose CT by almost experts and societies. In contrast, there should be further evaluations to clarify costs, harm effects of screening with low dose CT programs or related consequence procedures. Smoke cessation is still the most important strategy for reducing the burden of lung cancer, despite the promising results of screening trials.

Radiation therapy for stage I lung cancer detected on computed tomography screening: results from the international early lung cancer action program

Objective The International Early Lung Cancer Action Program (I-ELCAP) is a collaborative group designed to demonstrate reduction in lung cancer mortality by using low-dose computed tomography (CT) screening to identify early stage disease in high-risk individuals. While the majority of patients with stage I non-small cell lung cancer (NSCLC) were treated with surgical resection, some patients were treated with definitive radiation. This study explores the characteristics and outcomes of this population.

Balancing curability and unnecessary surgery in the context of computed tomography screening for lung cancer

Surgical management is a critical component of computed tomography (CT) screening for lung cancer. We report the results for US sites in a large ongoing screening program, the International Early Lung Cancer Action Program (I-ELCAP). We identified all patients who underwent surgical resection. We compared the results before (1993-2005) and after (2006-2011) termination of the National Lung Screening Trial to identify emerging trends. Among 31,646 baseline and 37,861 annual repeat CT screenings, 492 patients underwent surgical resection; 437 (89%) were diagnosed with lung cancer; 396 (91%) had clinical stage I disease. In the 54 (11%) patients with nonmalignant disease, resection was sublobar in 48 and lobectomy in 6. The estimated cure rate based on the 15-year Kaplan-Meier survival for all 428 patients (excluding 9 typical carcinoids) with lung cancer was 84% (95% confidence interval [CI], 80%-88%) and 88% (95% CI, 83%-92%) for clinical stage I disease resected within 1month of diagnosis. Video-assisted thoracoscopic surgery and sublobar resection increased significantly, from 10% to 34% (P<.0001) and 22% to 34% (P=.01) respectively; there were no significant differences in the percentage of malignant diagnoses (90% vs 87%, P=.36), clinical stage I (92% vs 89%, P=.33), pathologic stage I (85% vs 82%, P=.44), tumor size (P=.61), or cell type (P=.81). The frequency and extent of surgery for nonmalignant disease can be minimized in a CT screening program and provide a high cure rate for those diagnosed with lung cancer and undergoing surgical resection.

Avoiding overdiagnosis in lung cancer screening: the volume doubling time strategy

It has been 2 years since the breakthrough publication of the National Lung Cancer Screening Trial (NLST) results, yet there are still unresolved questions about cancer screening. Despite the possibility of reducing lung cancer-related mortality, the risk of detecting indolent lesions that are not life threatening, especially in advanced-age patients, still exists. Another problem is the number of false-positive findings leading to unnecessary diagnostic work-ups. In the NSLT study, for example, 27.2% of computed tomography participants were false positives, leading to follow-up diagnostic procedures in 90% of cases and to surgery in 4.2% [1]. Of course, computed tomography protocols and criteria for screening positivity should ensure accurate detection of all potentially malignant lesions, but this goal alone is not sufficient. Ideally, screening protocols should allow us to detect only true lung cancers, leaving out benign lesions, and among the malignant lesions detected, we should only be identifying those that are sufficiently aggressive to be potentially life threatening. This issue of the European Respiratory Journal includes two articles addressing precisely these problems. The paper by Infante et al. [2] is a review article dedicated to the slow-growing lung cancer entity, whereas the paper from Horeweg et al. [3] gives an overview of the NELSON strategy’s performance, especially its rate of false positives. Infante et al . [2] provide evidence of slow-growing lung cancers by analysing tumour volume doubling times (VDTs) in different lung cancer series. Considering a VDT >400 days to define slow-growing lung cancers, they report a highly variable proportion, ranging from 3% in the International Early Lung Cancer Action Program (I-ELCAP) [4] to 45% in some Japanese series [5]. The authors emphasise that only a minority of baseline VDTs were assessed in I-ELCAP, but …

CT Scans for Lung Cancer Screening

Frederic W Grannis Jr is clinical professor of thoracic surgery at the City of Hope National Medical Center in Duarte (CA, USA). Grannis has spent most of his adult life treating diseases caused by tobacco products, including lung cancer. He has served as a principal investigator in the International Early Lung Cancer Action Program (IELCAP) consortium and is a panel member of the National Comprehensive Cancer Network Non-Small-Cell Lung Cancer Guideline Committee and the Scientific Advisory Committee of the Tobacco Related Disease Projects at the University of California (CA, USA). His career is based upon the premise that reduction of lung cancer morbidity and mortality can be achieved by a tripartite combination of tobacco control policy reform, smoking cessation interventions and screening of tobacco-caused disease in high-risk individuals.

Lung Cancers Diagnosed at Annual CT Screening: Volume Doubling Times

To empirically address the distribution of the volume doubling time (VDT) of lung cancers diagnosed in repeat annual rounds of computed tomographic (CT) screening in the International Early Lung Cancer Action Program (I-ELCAP), first and foremost with respect to rates of tumor growth but also in terms of cell types. All CT screenings in I-ELCAP from 1993 to 2009 were performed according to HIPAA-compliant protocols approved by the institutional review boards of the collaborating institutions. All instances of first diagnosis of primary lung cancer after a negative screening result 7-18 months earlier were identified, with symptom-prompted diagnoses included. Lesion diameter was calculated by using the measured length and width of each cancer at the time when the nodule was first identified for further work-up and at the time of the most recent prior screening, 7-18 months earlier. The length and width were measured a second time for each cancer, and the geometric mean of the two calculated diameters was used to calculate the VDT. The χ(2) statistic was used to compare the VDT distributions. The median VDT for 111 cancers was 98 days (interquartile range, 108). For 56 (50%) cancers it was less than 100 days, and for three (3%) cancers it was more than 400 days. Adenocarcinoma was the most frequent cell type (50%), followed by squamous cell carcinoma (19%), small cell carcinoma (19%), and others (12%). Lung cancers manifesting as subsolid nodules had significantly longer VDTs than those manifesting as solid nodules (P < .0001). Lung cancers diagnosed in annual repeat rounds of CT screening, as manifest by the VDT and cell-type distributions, are similar to those diagnosed in the absence of screening.

Expression of concern

Cancer is publishing an Editorial Expression of Concern regarding the following articles: “Early Lung Cancer Action Project: Overall Design and Findings From Baseline Screening” by Claudia I. Henschke (Cancer. 2000;89(suppl 11):2474-2482). “Early Lung Cancer Action Project: Initial Findings on Repeat Screenings” by Claudia I. Henschke, David P. Naidich, David F. Yankelevitz, Georgeann McGuinness, Dorothy I. McCauley, James P. Smith, Daniel Libby, Mark Pasmantier, Madeline Vazquez, June Koizumi, Douglas Flieder, Nasser Altorki, and Olli S. Miettinen (Cancer. 2001;92:153-159). This Expression of Concern is based on an April 29, 2011, article in The New York Times as well as the April 29, 2011, issue of The Cancer Letter, both of which disclosed details of a report of an Independent Scientific Review Committee (Review Committee) convened by Weill Cornell Medical College to investigate the scientific research conducted as part of the International Early Lung Cancer Action Program (I-ELCAP). The Review Committee reported, among other things, that the I-ELCAP lacked positive confirmation of valid informed consent for all subjects at all sites by the coordinating center. The information contained in the Review Committee's report raises issues that cannot be fully investigated by the journal. We have therefore referred this matter to the Department of Health and Human Services Office for Human Research Protections. Based on the information we have received thus far, we are issuing this Expression of Concern to alert our readers. In addition, we would like to point readers to the Publisher's Note published in Cancer online on April 11, 2008 (available at: http://onlinelibrary.wiley.com/doi/10.1002/cncr.23540/pdf), which included additional disclosures made by Dr. Henschke that directly relate to these articles.

Radiation Therapy for Early Stage Lung Cancer Detected on CT Screening: Results from the I-ELCAP

The International Early Lung Cancer Action Program (I-ELCAP) is an international collaborative group that investigates CT screening as a means of early detection of lung cancer. I-ELCAP has shown that CT screening frequently leads to the diagnosis of Stage I lung cancer. While the majority of patients were treated surgically, we performed a subgroup analysis of the patients who were treated with radiation or chemoradiation as their primary treatment modality after the diagnosis of lung cancer.

Reducing the risk of overdiagnosis in lung cancer: A support from molecular biology

Early detection and swift treatment, when achievable, may significantly affect prognosis in lung cancer patients. Therefore, individuals with a high risk for lung cancer are invited to participate into international screening programs, such as the International Early Lung Cancer Action Program (I-ELCAP). An undesirable consequence of such massive enterprises is the detection of pulmonary nodules also in subjects who are unlikely to ultimately die from lung cancer. Nevertheless, the individuals with pulmonary nodule undergo stringent diagnostic procedures to assess the nature of the lesion. This implies a noticeable (physical and emotional) stress for our patients and the likelihood of overdiagnosis and, potentially, consequent overtreatment. Molecular markers, more specifically, microRNAs, might significantly add value to the workup process aiming at the distinction between benign and malignant lesions and, among the malignant ones, those concretely threatening for the patients' survival. We are confident that such a multidisciplinary approach would better suit our patients' diagnostic and/or therapeutic, actual needs.