International Early Lung Cancer Action Research Articles

Lung Cancer Screening in People With COPD: The Pamplona-IELCAP Experience

IntroductionThe Global Initiative for Obstructive Lung Disease (GOLD) recommends lung cancer screening for patients with Chronic Obstructive Pulmonary Disease (COPD), but data is lacking regarding results of screening in this high-risk population. The main goal of the present work is to explore if lung cancer screening with Low Dose Chest Tomography (LDCT) in people with COPD, allows lung cancer (LC) diagnosis in early stages with survival compatible with curative state. MethodsThis is a post hoc exploratory analysis. Pamplona International Early Lung Cancer Action Program (P-IELCAP) participants with a GOLD defined obstructive pattern (post bronchodilator FEV1/FVC<0.70) were selected for analysis. The characteristics of those who developed LC and their survival are described. A Cox proportional analysis explored the factors associated with LC diagnosis. ResultsEight hundred and sixty-five patients (77% male, 93% in spirometric GOLD stage 1+2) were followed for 102±63 months. LC prevalence was 2.6% at baseline, with an annual LC diagnosis rate of 0.68%. Early-stage tumors predominated (74%) with a median survival (25–75th percentiles) of 139 (76–185) months. Cumulative tobacco exposure, FEV1%, and emphysema were the main predictors of an LC diagnosis. Eight (11%) patients with COPD had a second LC, most of them in early stage (92%), and 6 (8%) had recurrence. Median survival (25–75th percentiles) in these patients was 168 (108–191) months. ConclusionsLung cancer screening of selected high-risk participants with COPD allowed the LC diagnosis in early stages with survival compatible with curative state.

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.

Impact of Duration of Diagnostic Workup on Prognosis for Early Lung Cancer.

Growth assessment for pulmonary nodules is an important diagnostic tool; however, the impact on prognosis due to time delay for follow-up diagnostic scans needs to be considered. Using the data between 2003 and 2019 from the International Early Lung Cancer Action Program, a prospective cohort study, we determined the size-specific, 10-year Kaplan-Meier lung cancer (LC) survival rates as surrogates for cure rates. We estimated the change in LC diameter after delays of 90, 180, and 365 days using three representative LC volume doubling times (VDTs) of 60 (fast), 120 (moderate), and 240 (slow). We then estimated the decrease in the LC cure rate resulting from time between computed tomography scans to assess for growth during the diagnostic workup. Using a regression model of the 10-year LC survival rates on LC diameter, the estimated LC cure rate of a 4.0 mm LC with fast (60-d) VDT is 96.0% (95% confidence interval [CI]: 95.2%-96.7%) initially, but it would decrease to 94.3% (95% CI: 93.2%-95.0%), 92.0% (95% CI: 90.5%-93.4%), and 83.6%(95% CI: 80.6%-86.6%) after delays of 90, 180, and 365 days, respectively. A 20.0-mm LC with the same VDTs has a lower LC cure rate of 79.9% (95% CI: 76.2%-83.5%) initially and decreases more rapidly to 71.5% (95% CI: 66.4%-76.7%), 59.8% (95% CI: 52.4%-67.1%), and 17.9% (95% CI: 3.0%-32.8%) after the same delays of 90, 180, and 365 days, respectively. Time between scans required to measure growth of lung nodules affects prognosis with the effect being greater for fast growing and larger cancers. Quantifying the extent of change in prognosis is required to understand efficiencies of different management protocols.

Evaluation and Management of Indeterminate Pulmonary Nodules on Chest Computed Tomography in Asymptomatic Subjects: The Principles of Nodule Guidelines.

With the rapidly increasing number of chest computed tomography (CT) examinations, the question of how to manage lung nodules found in asymptomatic patients has become increasingly important. Several nodule management guidelines have been developed that can be applied to incidentally found lung nodules (the Fleischner Society guideline), nodules found during lung cancer screening (International Early Lung Cancer Action Program protocol [I-ELCAP] and Lung CT Screening Reporting and Data System [Lung-RADS]), or both (American College of Chest Physicians guideline [ACCP], British Thoracic Society guideline [BTS], and National Comprehensive Cancer Network guideline [NCCN]). As the radiologic nodule type (solid, part-solid, and pure ground glass) and size are significant predictors of a nodule's nature, most guidelines categorize nodules in terms of these characteristics. Various methods exist for measuring the size of nodules, and the method recommended in each guideline should be followed. The diameter can be manually measured as a single maximal diameter or as an average of two-dimensional diameters, and software can be used to obtain volumetric measurements. It is important to properly evaluate and measure nodules and familiarize ourselves with the relevant guidelines to appropriately utilize medical resources and minimize unnecessary radiation exposure to patients.

New or enlarging hiatal hernias after thoracic surgery for early lung cancer

ObjectiveThe study objective was to determine the relationship between lung resection and the development of postoperative hiatal hernia. MethodsPreoperative and postoperative computed tomography imaging from 373 patients from the International Early Lung Cancer Action Program and the Initiative for Early Lung Cancer Research on Treatment were compared at a median of 31.1 months of follow-up after resection of clinical early-stage non–small cell lung cancer. Incidence of new hiatal hernia or changes to preexisting hernias were recorded and evaluated by patient demographics, surgical approach, extent of resection, and resection site. ResultsNew hiatal hernias were seen in 9.6% of patients after lung resection (5.6% after wedge or segmentectomy and 12.4% after lobectomy; P = .047). The median size of new hernias was 21 mm, and the most commonly associated resection site was the left lower lobe (24.2%; P = .04). In patients with preexisting hernias, 53.5% demonstrated a small but significant increase in size from 21 to 22 mm (P < .0001). All hernias persisted through the latest postoperative computed tomography scan. When 110 surgical patients without preexisting hernia were matched by sex, age, and smoking to nonoperative controls, the incidence of new hernia at follow-up was significantly higher among those who underwent surgery (17.3% vs 2.7%, P = .0003). ConclusionsBoth open and minimally invasive lung resection for clinical early-stage lung cancer are associated with new or enlarging postoperative hiatal hernia, especially after resections involving the left lower lobe.

Characterization of Newly Detected Costal Pleura-attached Noncalcified Nodules at Annual Low-Dose CT Screenings.

Background Solid costal pleura-attached noncalcified nodules (CP-NCNs) less than 10.0 mm with lentiform, oval, or semicircular (LOS) or triangular shapes and smooth margins on baseline low-dose CT scans from the Mount Sinai Early Lung and Cardiac Action Program (MS-ELCAP) were reviewed, and it was determined that they can be followed up at the first annual screening rather than having a shorter-term work-up. Purpose To determine whether the same criteria could be used for solid CP-NCNs newly identified at annual screening examinations. Materials and Methods With use of the same MS-ELCAP database, all new solid CP-NCNs measuring 30.0 mm or less were identified at 4425 annual screening examinations between 2010 and 2019. In addition, to ensure that no malignant CP-NCNs met the criteria, all solid malignant CP-NCNs of 30.0 mm or less in the International Early Lung Cancer Action Program, or I-ELCAP, database of 111 102 annual screening examinations from the 76 participating institutions between 1992 and 2019 were identified; Mount Sinai is one of these institutions. All identified solid CP-NCNs were reviewed-with the radiologists blinded to diagnosis-for shape (triangular, LOS, polygonal, round, or irregular), margin (smooth or nonsmooth), pleural attachment (broad or narrow), and the presence of emphysema and/or fibrosis within 10.0 mm of each CP-NCN. Intra- and interreader readings were performed, and agreements were determined by using the B-statistic. Results Of the 76 new solid CP-NCNs, 21 were lung cancers. Benign CP-NCNs were smaller than malignant ones (median diameter, 4.2 mm vs 11 mm; P < .001), had a different shape distributions, more frequently had smooth margins (67% vs 14%; P < .001), and less frequently had emphysema (38% vs 81%; P = .003) or fibrosis (3.6% vs 19%; P = .045) within a 10.0 mm radius. All 22 solid CP-NCNs less than 10.0 mm in average diameter with triangular or LOS shapes and smooth margins were benign, and none of the 21 solid malignant CP-NCNs had these characteristics. Intra- and interobserver agreement for triangular or LOS-shaped CP-NCNs with smooth margins was almost perfect (0.77 and 0.69, respectively). Conclusion The same follow-up recommendation developed for baseline costal pleura-attached noncalcified nodules (CP-NCNs) can be used for CP-NCNs newly identified at annual screening rounds. © RSNA, 2021.

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.

The importance of low-dose CT screening to identify emphysema in asymptomatic participants with and without a prior diagnosis of COPD

PurposeChronic Obstructive Pulmonary Disease (COPD) includes chronic bronchitis, small airways disease, and emphysema. Diagnosis of COPD requires spirometric evidence and may be normal even when small airways disease or emphysema is present. Emphysema increases the risk of exacerbations, and is associated with all-cause mortality and increased risk of lung cancer. We evaluated the prevalence of emphysema in participants with and without a prior history of COPD. MethodsWe reviewed a prospective cohort of 52,726 subjects who underwent baseline low dose CT screening for lung cancer from 2003 to 2016 in the International Early Lung Cancer Action Program. ResultsOf 52,726 participants, 23.8%(12,542) had CT evidence of emphysema. Of these 12,542 participants with emphysema, 76.5%(9595/12,542) had no prior COPD diagnosis even though 23.6% (2258/9595) had moderate or severe emphysema. Among 12,542 participants, significant predictors of no prior COPD diagnosis were: male (OR = 1.47, p < 0.0001), younger age (ORage10 = 0.72, p < 0.0001), lower pack-years of smoking (OR10pack-years = 0.90, p < 0.0001), completed college or higher (OR = 1.54, p < 0.0001), no family history of lung cancer (OR = 1.12, p = 0.04), no self-reported cardiac disease (OR = 0.76, p = 0.0003) or hypertension (OR = 0.74, p < 0.0001). The severity of emphysema was significantly lower among the 9595 participants with no prior COPD diagnosis, the OR for moderate emphysema was ORmoderate = 0.58(p = 0.0007) and for severe emphysema, it was ORsevere = 0.23(p < 0.0001). ConclusionEmphysema was identified in 23.8% participants undergoing LDCT and was unsuspected in 76.5%. LDCT provides an opportunity to identify emphysema, and recommend smoking cessation.

ES10.06 Putting It Together: Current Best Practices in the Evaluation and Follow-Up of the Indeterminate Pulmonary Nodule

In a sense, all pulmonary nodules are indeterminate until there has been a definitive diagnosis or long-term follow-up. Which nodules are included in the “indeterminate” category is determined by the definition applied, and this can differ between established guidelines. For the purposes of this talk, which relates specifically to the context of LDCT screening for lung cancer, the recommendations from five key guidelines on the management of pulmonary nodules have been reviewed1 - 5. A further key guideline, the Fleischner Society 2017 update refers only to nodules detected incidentally, rather than in a screening setting so is not included in the comparisons6. Most comparisons of recommendations concentrate on the approach to nodules according to size categories because this is one of the major determinants of the probability that a nodule is both malignant and harmful. This is a useful approach but can produce some complicated tables. This talk approaches the subject from a slightly different and patient-centred angle. For participants in screening, it is important to think of the impact of management strategies and there are 3 key outcomes after either a prevalence or incident screen: return to the screening programme for the next scheduled screen; have additional low dose CT(s) before the next screen is due; and be referred to the hospital for further clinical work-up. The chance of harming the participant, both physically and psychologically, increases as we progress through these categories. It is thus important to avoid both additional LDCT and clinical work-up, unless beneficial. Guidelines aim to do this by managing the vast majority of nodules with minimal chance of harm whilst promptly investigating those nodules likely to be both malignant and harmful. It is important to appreciate that nodules that are malignant are not always harmful because they may be very slow growing and treating them may cause more harm. This can be the case for sub-solid nodules. Comparisons are made for four situations: baseline (prevalence) detection, new nodules (incidence screen), subsolid nodules and growing nodules. The table shows an example of a comparison for baseline detection. The Lung RADS 1.1 and NCCN guidelines essentially make the same recommendations. Guidelines generally agree on the threshold for returning to the screening programme but specify an annual screen (1 year interval) except for the British Thoracic Society (BTS), where the interval can be longer. Guidelines differ somewhat on the management of the nodules that require a shorter interval. It can be seen that there is the potential for a stage shift from T1a (≤10mm) for some of the recommendations although caveats are added such as the option for PET-CT or very short interval CT for larger nodules. Another potentially important difference is the use of semi-automated volumetry, which is the preferred method to measure nodules and their growth in both the BTS guideline and the European Position Statement (EUPS). Both of these documents make a case for the better accuracy of volumetry as compared with manual diameter measurements. This also has implications for some of the other recommendations for growing nodules where management is recommended on the basis of volume doubling time (VDT). For example, both BTS and the EUPS recommend work-up on the basis of specific VDTs, with less invasive options for participants who have nodules with a VDT of 400-600 days. I-ELCAP defines growth sufficient to prompt work-up as a VDT of 180 days, in contrast to BTS and EUPS where it is 400 days. BTS is the only guideline that firmly recommends the use of multivariable models in the management of people with nodules. The Brock / PanCan model is recommended at baseline to assist in deciding who should undergo PET-CT. This avoids this high-radiation dose scan in people who have low risk nodules. The Herder model is then used to classify nodules further. The use of PET-CT is generally recommended in the further assessment of nodules and the cut-off size is broadly >8-10mm diameter, reflecting the limitations of PET in nodules smaller than this. Guidelines are cautious with the management of sub-solid nodules, reflecting their often indolent nature and therefore the potential to harm participants by over-zealous treatment. The is particularly the case for pure ground glass / non-solid nodules; most guidelines only recommend an invasive approach if there is a solid component. Much progress has been made on the management of pulmonary nodules, and this is reflected in the much lower frequency of complications and invasive approaches in participants who do not have cancer. It will be important that screening centres adhere to guidelines to ensure participants experience the maximum benefit with least arm. 1. Callister ME, Baldwin DR, Akram AR, Barnard S, Cane P, Draffan J, et al. British Thoracic Society guidelines for the investigation and management of pulmonary nodules. Thorax. 2015;70 Suppl 2:ii1-ii54 2. Matthijs Oudkerk AD, Rozemarijn Vliegenthart, Thomas Henzler, Helmut Prosch, Claus P Heussel, Gorka Bastarrika, Nicola Sverzellati, Mario Mascalchi SD, David R Baldwin, Matthew E Callister, Nikolaus Becker, Marjolein A Heuvelmans, Witold Rzyman, Maurizio V Infante UP, Jesper H Pedersen, Eugenio Paci, Stephen W Duffy, Harry de Koning, John K Field. European position statement on lung cancer screening. Lancet Oncology. 2017;18(12): e754–e66. 3. American College Radiology. Lung RADS v 1.1 2019 [Available from: https://www.acr.org/-/media/ACR/Files/RADS/Lung-RADS/LungRADSAssessmentCategoriesv1-1.pdf?la=en. 4. National Comprehensive Cancer Network. NCCN Lung Cancer Screening Version 1 2021 [Available from: https://www.nccn.org/professionals/physician_gls/pdf/lung_screening.pdf. 5. International Early Lung Cancer Action Program Investigators Group. Protocol Documents 2016 [Available from: https://www.ielcap.org/sites/default/files/I-ELCAP-protocol-summary.pdf. 6. MacMahon H, Naidich DP, Goo JM, Lee KS, Leung ANC, Mayo JR, et al. Guidelines for Management of Incidental Pulmonary Nodules Detected on CT Images: From the Fleischner Society 2017. Radiology. 2017;284(1):228-43.

The Regimen of Computed Tomography Screening for Lung Cancer: Lessons Learned Over 25 Years From the International Early Lung Cancer Action Program.

We learned many unanticipated and valuable lessons since we started planning our study of low-dose computed tomography (CT) screening for lung cancer in 1991. The publication of the baseline results of the Early Lung Cancer Action Project (ELCAP) in Lancet 1999 showed that CT screening could identify a high proportion of early, curable lung cancers. This stimulated large national screening studies to be quickly started. The ELCAP design, which provided evidence about screening in the context of a clinical program, was able to rapidly expand to a 12-institution study in New York State (NY-ELCAP) and to many international institutions (International-ELCAP), ultimately working with 82 institutions, all using the common I-ELCAP protocol. This expansion was possible because the investigators had developed the ELCAP Management System for screening, capturing data and CT images, and providing for quality assurance. This advanced registry and its rapid accumulation of data and images allowed continual assessment and updating of the regimen of screening as advances in knowledge and new technology emerged. For example, in the initial ELCAP study, introduction of helical CT scanners had allowed imaging of the entire lungs in a single breath, but the images were obtained in 10 mm increments resulting in about 30 images per person. Today, images are obtained in submillimeter slice thickness, resulting in around 700 images per person, which are viewed on high-resolution monitors. The regimen provides the imaging acquisition parameters, imaging interpretation, definition of positive result, and the recommendations for further workup, which now include identification of emphysema and coronary artery calcifications. Continual updating is critical to maximize the benefit of screening and to minimize potential harms. Insights were gained about the natural history of lung cancers, identification and management of nodule subtypes, increased understanding of nodule imaging and pathologic features, and measurement variability inherent in CT scanners. The registry also provides the foundation for assessment of new statistical techniques, including artificial intelligence, and integration of effective genomic and blood-based biomarkers, as they are developed.

Early Lung Cancer Detection using Deep Learning Optimization

This paper proposes a Computer Aided Detection (CADe) system for early detection of lung nodules from low dose computed tomography (LDCT) images. The proposed system initially pre-process the raw data to improve the contrast of the low dose images. Compact deep learning features are then extracted by investigating different deep learning architectures, including Alex, VGG16, and VGG19 networks. To optimize the extracted set of features, a genetic algorithm (GA) is trained to select the most relevant features for early detection. Finally, different types of classifiers are tested in order to accurately detect the lung nodules. The system is tested on 320 LDCT images from 50 different subjects, using an online public lung database, i.e., the International Early Lung Cancer Action Project, I-ELCAP. The proposed system, using VGG19 architecture and SVM classifier, achieves the best detection accuracy of 96.25%, sensitivity of 97.5%, and specificity of 95%. Compared to other state-of-the-art methods, the proposed system shows a promising results.

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.

3D local circular difference patterns for biomedical image retrieval

In this paper, three-dimensional local circular difference patterns (3D LCDP) and three-dimensional local circular difference wavelet patterns (3D LCDWP) are proposed for retrieval of biomedical images. The standard patterns are used to correlate gray value of center pixel with neighboring pixels. In the proposed approach, 3D volume is generated for calculating local circular difference patterns with the help of three planes obtained from original image. In case of color image, RGB channels are used as three planes and Gaussian filter banks of different resolution for gray level image. From this 3D volume, LCDP values are obtained by calculating relationship between center pixel and neighboring pixels in five different directions. Finally, feature vector is generated using histogram. The performance is evaluated using different medical databases: (i) open access series of imaging studies MRI database, (ii) International early lung cancer action program and vision and image analysis research groups CT scans, (iii) MESSIDOR-Retinal image database. The results are compared with existing biomedical image retrieval techniques by considering average retrieval precision and average retrieval rate as evaluation parameters.

Outcomes of Long-term Interval Rescreening With Low-Dose Computed Tomography for Lung Cancer in Different Risk Cohorts

IntroductionWe hypothesize that the incidence of screen-detected lung cancer (LC), in participants with previously negative scans, will be highest in the cohort with the highest baseline risk score. MethodsIndividuals with negative baseline screening results from the Princess Margaret International Early Lung Cancer Action Program before 2009 underwent low-dose computed tomography rescreening from 2015 to 2018. Individuals were contacted in order of descending risk, as determined by the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial's PLCOM2012 6-year LC risk-prediction model, and then categorized into three risk cohorts according to their baseline risks. The incidence of LC in each risk cohort was determined and compared. Chi-square testing was used for categorical variables and one-way analysis of variance on ranks was used for continuous variables. ResultsOf the 1261 participants we attempted to re-contact, 359 participants returned for a rescreening scan (mean of 7.6 years between scans). Participants were divided into low (<2%), moderate (≥2% to <3.5%), and high baseline risk (≥3.5%) cohorts. On average, those in the high-risk cohort compared to the moderate- and low-risk cohorts were older (66 years versus 62 and 59 years) and had a greater smoking history (54 pack-years versus 47 and 29 pack-years). The incidence of cancer in the high-risk cohort was significantly higher than in the moderate-risk cohort (11% versus 1.7%, p = 0.002). ConclusionsThere was a significantly higher incidence of LC in the high-risk cohort than in the moderate-risk cohort. The cut-point between the high- and moderate-risk was determined to be greater than or equal to 3.5% of the 6-year baseline risk.

Definitive Radiation for Stage I Lung Cancer in a Screened Population: Results From the I-ELCAP

The International Early Lung Cancer Action Program is a cohort study to assess the cure rate of participants undergoing annual low-dose computed tomography screening for lung cancer. This study compares the characteristics and outcomes of patients who received a diagnosis of clinical stage I non-small cell lung carcinoma (NSCLC) treated with definitive radiation therapy and surgical resection. Patient information was drawn from the International Early Lung Cancer Action Program database from 1992 to 2017. All instances in which treatment was performed for histologically proven stage I NSCLC using definitive radiation therapy and surgery were identified. The home institution determined radiation plans. Patient characteristics and Kaplan-Meier lung cancer-specific (LCS) long-term survival rates were compared for both types of treatment. Follow-up time was calculated from time of diagnosis until death from lung cancer, loss to follow-up, or December 31, 2017, whichever came earlier. Among 82,628 baseline and 109,250 annual repeat screenings, 853 patients received a diagnosis of clinical stage I NSCLC, of whom 31 (3.6%) were treated by definitive radiation therapy and 702 (82.3%) by surgical resection alone. Radiation therapy prescription information was obtainable for 24 of the 31 patients: The median dose was 54.5Gy, the median number of fractions was 5, and 17 patients were treated using stereotactic body radiation therapy. LCS survival rates were not significantly different for radiation therapy compared with surgery: 90.0% (95% confidence interval, 84.9%-100.0%) versus 94.8% (95% confidence interval, 93.0%-96.6%) (P=.09). Median follow-up time was 9.7years for all, but it was shorter for those treated by radiation therapy than for those who underwent surgery (4.3 vs 10.0years, P<.0001). The majority of patients identified by computed tomography screening were treated with surgical resection. Despite being older and having more comorbidities, LCS long-term survival rates of patients treated with definitive radiation therapy were not significantly different compared with survival rates of patients treated with surgery alone. Radiation therapy appears to be a viable alternative to surgery for screen-diagnosed patients with lung cancer.

Importance of Long-term Low-Dose CT Follow-up after Negative Findings at Previous Lung Cancer Screening.

Purpose To assess the incidence of lung cancer in a cohort of patients with negative findings at previous lung cancer screening. Materials and Methods In this prospective cohort study, the authors first identified 4782 individuals who had negative screening results as part of the International Early Lung Cancer Action Program (1993-2005). Subjects were assigned a lung cancer risk score by using a validated risk model. Starting with those at highest risk, subjects were interviewed by phone and invited to undergo low-dose CT between March 2013 and October 2016. Subjects with a diagnosis of lung cancer and those who had died of lung cancer were determined. Descriptive statistics were used to summarize data. The independent samples t test and Fisher exact test were used to compare age, sex, and risk scores. Results A total of 327 study participants were contacted, and 200 subjects participated in this study. The average age was 74 years (range, 57-88 years), and the median time since previous CT was 7 years. The incidence rate of developing lung cancer during the next 6 years was estimated at 5.6%. The period prevalence of lung cancer was 20.8% (new and preexisting lung cancer, 68 of total cohort of 327). The detection rate of low-dose CT was 7% (14 of 200 subjects). Of the 14 screening-detected cancers, 12 were stage I or II. Conclusion High-risk individuals have a high incidence of lung cancer after previous negative lung cancer screening. Early-stage lung cancer can be successfully detected in older high-risk individuals. © RSNA, 2018 Online supplemental material is available for this article.

(P38) Radiation Therapy for Stage I Lung Cancer Detected on Computed Tomography Screening: Results from the International Early Lung Cancer Action Program

(P38) Radiation Therapy for Stage I Lung Cancer Detected on Computed Tomography Screening: Results from the International Early Lung Cancer Action Program

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.

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