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ES08 - Critical Concerns in Screening (ID 11)
- Event: WCLC 2019
- Type: Educational Session
- Track: Screening and Early Detection
- Presentations: 7
- Now Available
- Moderators:Ugo Pastorino, John Kirkpatrick Field
- Coordinates: 9/08/2019, 13:30 - 15:00, Copenhagen (1980)
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ES08.01 - Participation of the Target Population in Lung Cancer Screening (Now Available) (ID 3191)
13:30 - 15:00 | Presenting Author(s): Robin Cornelissen
- Abstract
- Presentation
Abstract
Participation of the Target Population in Lung Cancer Screening
Robin Cornelissen, MD, PhD.
Erasmus MC cancer institute
Rotterdam, The Netherlands
The two largest randomized controlled trials performed, The National Lung Screening Trial (NLST) and the Nederlands-Leuvens Longkanker ScreeningsONderzoek (NELSON) 1,2, proved that lung cancer screening using low dose CT scan, resulted in a significant reduction in lung cancer mortality. Following the results of the NLST trial, lung cancer screening was initiated in the United States and Canada. However, the uptake of lung cancer screening is poor, with only 3% to 4% of all eligible persons participating in the implemented screening program 3. Given more recent positive results of the NELSON study that were presented at the World Conference on Lung Cancer last year in Toronto, lung cancer screening is now considered in many countries across the globe. This low uptake of lung cancer screening is however a cause of concern.
The reasons for the low participation rate are multi-factorial. The novelty of the lung cancer screening program is such a factor, resulting in lower uptake and might be the easiest one to address. The identification of the target population is more challenging due to the fact that the population to be screened is more defined than just age and sex. In addition, the lower socioeconomic status, which presents a significant portion of the to be screened population, and those who face barriers to care present a major challenge for implementing a successful screening program with a satisfactory uptake rate.
Several strategies have been proposed to improve lung cancer screening uptake.
In the socioeconomically deprived and heavy smoking communities, lung cancer is perceived as an uncontrollable disease 4, while cure rates in yearly screening programs lead to a cure in the majority of patients when lung cancer is detected 5,6. Therefore, public awareness of the curability of lung cancer when screening programs are implemented could boost the participation rate.
Mobile lung cancer testing in supermarket car parks proved to be a successful pilot 7. This strategy avoids difficulties relating to the distance of travel, lack of public transport available, and the cost of either the journey itself or hospital parking. This strategy is currently explored in a larger cohort.
One potential intervention that is being evaluated in clinical trials to improve the uptake and implementation of lung cancer screening is a patient navigator. A navigator can be a layperson, a medical assistant, or a nurse who will directly contact potential candidates for lung cancer screening for enrollment 3.
The Accelerate, Coordinate, Evaluate (ACE) Programme, initiated in the United Kingdom, is an early diagnosis of cancer initiative focused on testing innovations that either identify individuals at high risk of cancer earlier 8. This program consists of several individual programs in different regions of the UK, of which The Liverpool Healthy Lung Programme is a participant. Among other goals, this initiative tries to improve uptake in the hard to reach cohort. They used general practitioners’ records to invite participants meeting the criteria to a ‘Lung Health Check’. This ‘Lung Health Check’ is a novel approach that may overcome or minimize the emotional barriers associate with the term “lung cancer screening”. This method resulted in an uptake level up to 40% 9. This initiative is an example that a higher uptake rate is indeed possible, even in the hard to reach population.
At the IASLC World Conference on Lung Cancer in Barcelona, the issues regarding participation of the target population in lung cancer screening will be addressed and possible strategies will be discussed to overcome these challenges. As lung cancer screening is yet to be implemented in the majority of countries worldwide, we now have a unique opportunity to test and apply these strategies to successfully implement lung cancer screening in order to reduce lung cancer mortality.
References
1. The National Lung Screening Trial Research Team. Reduced Lung-Cancer Mortality with Low-Dose Computed Tomographic Screening. N Engl J Med. 2011;365(5):395-409. doi:10.1056/NEJMoa1102873
2. Koning HD, Aalst CVD, Haaf KT, Oudkerk M. PL02.05 Effects of Volume CT Lung Cancer Screening: Mortality Results of the NELSON Randomised-Controlled Population Based Trial. J Thorac Oncol. 2018;13(10):S185. doi:10.1016/j.jtho.2018.08.012
3. Triplette M, Thayer JH, Pipavath SN, Crothers K. Poor Uptake of Lung Cancer Screening: Opportunities for Improvement. J Am Coll Radiol JACR. 2019;16(4 Pt A):446-450. doi:10.1016/j.jacr.2018.12.018
4. Quaife SL, Marlow LAV, McEwen A, Janes SM, Wardle J. Attitudes towards lung cancer screening in socioeconomically deprived and heavy smoking communities: informing screening communication. Health Expect Int J Public Particip Health Care Health Policy. 2017;20(4):563-573. doi:10.1111/hex.12481
5. Survival of Patients with Stage I Lung Cancer Detected on CT Screening. N Engl J Med. 2006;355(17):1763-1771. doi:10.1056/NEJMoa060476
6. Jonnalagadda S, Bergamo C, Lin JJ, et al. Beliefs and attitudes about lung cancer screening among smokers. Lung Cancer Amst Neth. 2012;77(3):526-531. doi:10.1016/j.lungcan.2012.05.095
7. Wise J. Mobile lung cancer testing in supermarket car parks is to be expanded. BMJ. 2017;359:j5450. doi:10.1136/bmj.j5450
8. Proactive Approaches to Individuals at High Risk of Lung Cancer; Accelerate, Coordinate, Evaluate (ACE) Programme. V1.1a.; 2018. https://www.cancerresearchuk.org/sites/default/files/ace_proactive_lung_report_with_economic_evaluation_final_version_1.1a.pdf. Accessed July 9, 2019.
9. Ghimire B, Maroni R, Vulkan D, et al. Evaluation of a health service adopting proactive approach to reduce high risk of lung cancer: The Liverpool Healthy Lung Programme. Lung Cancer. 2019;134:66-71. doi:10.1016/j.lungcan.2019.05.026
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ES08.02 - Nodule Growth Assessment (Now Available) (ID 3192)
13:30 - 15:00 | Presenting Author(s): Matthijs Oudkerk
- Abstract
- Presentation
Abstract
In the past 15 years several lung cancer screening trials have been performed in Europe1. Experts involved in these trials recently published a position paper in the Lancet Oncology2.
Several conclusions and recommendations were drawn to enable a smooth and timely implementation of lung cancer screening in Europe. The experts made a strong and conditional argument on the methodology of lung cancer screening by low-dose computed tomography (CT). Quality control by regular CT phantom testing enabling standardization of CT data acquisition as well as benchmarking of CT software post processing and data analysis are mandatory. It is promoted to execute the CT screening Q/A control through national reference centers similar to the organizational structure of breast screening programs. In this manner the CT screening programs can be implemented in a responsible way avoiding the detrimental side effects of too high false positive CT outcome rates on the one hand and keeping up the most effective lung cancer early detection rate on the other hand.
Apart from the acquisition protocol, the CT lung nodule analysis methodology is a critical factor for successful implementation of CT lung cancer screening 3. The diameter based NLST protocol used a 4 mm threshold (~ 30 mm3) as significant suspicion for malignancy. This approach yielded a positive rate of approximately 27% in the baseline round with a very low positive predictive value for lung cancer of 3.8%4. The NELSON study introduced a nodule volume analysis and a volume doubling time methodology with 2 CT measurements with a 3-month interval to calculate the volume doubling time as a biomarker for growth rate in indeterminate nodules. This approach resulted in a 2.6% positive rate in the baseline round with a high positive predictive value for lung cancer of approximately 36%, which is within the criteria needed for lung cancer screening implementation3. In the meantime, a ten times higher threshold of 8 mm (~300 mm3) was recommended to correct the high false positive rate of the NLST diameter methodology by several international societies5. After the publications of the NELSON data on increased lung cancer probability in baseline nodules at a threshold of 100 mm3the US guideline recommendations shifted from 300 mm3to 100 mm3(~ 6mm)6. A direct comparison of diameter and volume protocols cannot be performed through the assumption that all nodules are spherical. While this approach was chosen in a recent publication of the IELCAP investigators7, even the slightest correction for the assumption of sphericity reveals the substantial inferiority of diameter protocols. At follow-up CT examination at annual incident screen new nodules represent a high lung cancer probability at lower volumes than at baseline screen8,9. The upper threshold is at 200 mm3as indication for further clinical workup while new nodule at incident screen between the 30-200 mm3are classified as indeterminate and need a repeat scan at 3 months to calculate the volume doubling time. Lung cancer screening should be integrated in a defined national program and therefore opportunistic screening is not recommended. Calcium scoring as a screening methodis not yet established as a validated tool for early detection of coronary artery disease and the outcomes of the ROBINSCA study (risk or benefit in screening for cardiovascular disease www.robinsca.nl) are being awaited. Thus, so far, it is not indicated as a combined clinical routine screening methodology since ECG triggering is mandatory10. Non-triggered CT coronary artery calcium scoring will result in high false negative percentages. A lower CT radiation exposure threshold at a DLP of 50 mGy or 0.6 mSv is defined to assure the calibration of the quantitative imaging biomarkers for lung nodule detection. Lower radiation doses will induce false negative and unreliable growth rate results.
References
1 An update on the European Lung Cancer Screening Trials and Comparison of the Lung Cancer Screening Recommendations in Europe . Han et alJournal of Thoracic Imaging 2019; 34(1): 65–71.
2 European position statement on lung cancer screening Oudkerk M Devaraj ALancet Oncology 2017 Dec;18(12):e754-e766.
3 Management of lung nodules detected by volume CT scanning van Klaveren R Oudkerk M et al N Engl J Med. 2009 Dec 3;361(23):2221-9.
4 Reduced lung-cancer mortality with low-dose computed tomographic screening Aberle DR et al N Engl J Med 2011 Aug 4;365(5):395-409.
5 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 Yip R Henschke CI Radiology 2014 Nov;273(2):591-6.
6 Guidelines for Management of Incidental Pulmonary Nodules Detected on CT Images: From the Fleischner Society 2017 Mac Mahon H Radiology: Volume 284: Number 1—July 2017
7 CT screening for lung cancer: comparison of three baseline screening protocol Henschke CI et al Eur Rad 2018 Dec 3
8 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 Walter JE Heuvelmans MA et al Lancet Oncology 2016 Jul;17(7):907-916.
9.Persisting new nodules in incidence rounds of the NELSON CT lungcancer screening study Walter JE Heuvelmnans MA Thorax. 2018 Dec 27
10 Can nontriggered thoracic CT be used for coronary artery calcium scoring? A phantom study Xueqian Xie et al Medical Physics, Vol. 40, No. 8, August 2013
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ES08.03 - The Magnitude of the Benefit (Now Available) (ID 3193)
13:30 - 15:00 | Presenting Author(s): David F. Yankelevitz
- Abstract
- Presentation
Abstract
Why do people get screened? The obvious answer is so that cancer can be detected early with a view towards a higher chance of cure with early treatment. Therefore the critical questions that must be addressed relate to the risk of cancer over time and then, how likely cure will be when screen-detected versus clinically detected. Current approaches to evaluate screening have relied on randomized controlled trials with a view towards demonstrating that a benefit actually exists but are not designed to quantify the magnitude of the benefit. Current trial designs have limited rounds of screening and long-term follow up after screening has stopped. When these parameters change, the results of the trial will also change. Several approaches currently exist to estimate that critical parameter regarding the curability of screen detected lung cancer. This includes modeling approaches which can use data extracted from a variety of sources, they can also be measured directly as was done in the I-ELCAP study which measures directly the reduction in case fatality rate by using long term survival as a measure of cure, and an additional approach would be to screen continuously in the context of a clinical trial and measure the reduction in mortality after several years of screening where the benefit of screening reaches its maximum and becomes equivalent to the reduction in case fatality rate. When applied to lung cancer it can be shown that this benefit is far greater than the 20% so commonly reported and instead is in the 60=80% range for cure. Were this to be fully understood the entire rationale behind requiring shared decision making would be called into question as it was thought that the balance between benefits and harms was so tenuous that shared decision making was necessary.
When considering whether a particular type of screening is to be considered beneficial there is also a tendency to compare different types of screening and seeing how many screens are necessary to save a life. Here to, this approach suffers from the same mistake. Each of those screening exams estimates this number based on their own randomized trial and each of these differ in terms of the design parameters, therefore the comparisons are essentially meaningless.
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ES08.04 - Management Algorithms (Now Available) (ID 3194)
13:30 - 15:00 | Presenting Author(s): Claudia I Henschke | Author(s): Rowena Yip, Teng Ma, Samuel Miguel Aguayo, Javier Zulueta, David Yankelevitz
- Abstract
- Presentation
Abstract
Introduction
Clinical management decisions arising from the first, baseline round of screening for lung cancer are most challenging, as nodules that are seen for the first time may have accumulated over a lifetime and almost all of them are of no clinical concern [1]. In contrast, new or changing findings on subsequent annual repeat low-dose CT scans (LDCTs) have much greater clinical significance.
Efficiency is particularly important in the baseline round in order to minimize unnecessary harms caused by work-up within the 12 months after the baseline LDCT. Potential workup includes surgery, biopsies, and diagnostic tests requiring intravenous injection (e.g., PET scans, contrast CT). Biopsies and surgery have greater risks than LDCT, and thus the management protocols should aim to minimize these higher risk procedures as much as possible [2]. It is also important not to discourage participants undergoing the baseline round from future participation in annual rounds as these provide the real benefit of annual LDCT screening.
Methods
We compared the efficiency of three published baseline LDCT screening protocols [2], the International Early Lung Cancer Action Program (I-ELCAP) [3], American College of Radiology (ACR)-LungRADS [4], and the European Consortium protocols [5] for participants 50 years of age or older with at least 20 pack-years of smoking.
The three protocols provide recommendations for immediate workup, 3-month and 6-month LDCT as shown in Table 1 [1]. The three protocols use the diameter of the entire solid and nonsolid non-calcified nodule (NCN), but differ for part-solid NCNs. For part-solid NCNs, I-ELCAP uses the diameter of the solid component [6], while ACR-LungRADS uses both the entire diameter of the part-solid NCN as well as the diameter of its solid component. The European Consortium protocol determines the volume of a solid NCN using their software [5], but also specifies the equivalent diameter values for the entire part-solid and nonsolid NCNs as volumetric measurements for these are problematic as was recognized [5]. Measurement error and rounding of measurements are also an important consideration [7,8].
Efficiency was defined as an efficiency ratio (ER): the number of participants recommended for a particular workup divided by the resulting number of participants diagnosed with lung cancer [2]. An ER of 1 would mean that each recommended workup resulted in a diagnosis of lung cancer. An optimum ER has not been established for lung cancer, but it has been suggested that for lung surgery, a rate of 10% for non-malignant resections is desirable (9), this would be an ER of 1.1. In breast cancer biopsies which have a much lower risk than lung biopsies, it is recommended that 40% of biopsies should be negative to ensure sufficient workup to diagnose breast cancers early enough this would represent an ER of 1.4
Results
Table 1 provides the frequency of following the recommendations, the number of cancers diagnosed and the ER for each protocol. In summary, I-ELCAP recommendations had the lowest ER values for overall, immediate and delayed workup, and for potential biopsies.
Discussion
All three protocols used LDCT to guide evaluation of NCNs, particularly for the smaller NCNs. LDCT is a very low risk test as it requires no injection of contrast, the radiation dose is deemed “small” and “hypothetical” by the American Association of Physicists in Medicine [10], and the charge for a LDCT is 10-20 times lower than for a PET scan. This underscores the recognition that LDCT is a very useful tool for identifying growth at a malignant rate prior to further invasive testing.
The main point is that the definition of a “positive result” needs to be continually reevaluated and updated in light of emerging technology and evidence from ongoing screening programs with the goal of reducing unnecessary invasive procedures for non-malignant pulmonary NCNs, which will markedly reduce the concerns about potential harms and increase the benefit by early diagnosis and treatment of small, early curable lung cancers.
References
1. Henschke CI, Salvatore M, Cham M, Powell CA, DiFabrizio L, Flores R, et al. Baseline and annual repeat rounds of screening: implications for optimal regimens of screening. Eur Radiol. 2018; 28:1085-1094.
2. Henschke CI, Yip R, Ma T, Aguayo SM, Zulueta J, Yankelevitz DF, for the I-ELCAP Investigators. CT screening for lung cancer: comparison of three baseline screening protocols. Eur Radiol 2018; 29:3321-3322.
3. International Early Lung Cancer Action Program protocol. (2016) www.IELCAP.org/sites/default/files/I-ELCAP-protocol.pdf Accessed June 27, 2019
4. American College of Radiology (ACR). Lung CT screening reporting & data system (Lung-RADS Version 1.0). https://www.acr.org/Quality-Safety/Resources/LungRADS
5. Oudkerk M, Devaraj A, Vliegenthart R, Henzler T, Prosch H, Heussel CP, et al. European position statement on lung cancer screening. Lancet Oncology 2017; 18: e754-e766.
6. Henschke CI, Yip R, Wolf A, Flores R, Liang M, Salvatore M, et al. CT screening for lung cancer: part-solid nodules in baseline and annual repeat rounds. AJR Am J Roentgenol 2016; 11:1-9.
7. Radiologic Society of North America Quantitative Imaging Biomarkers Alliance (QIBA) Calculator. (2017) http://accumetra.com/solutions/qiba-lung-nodule-calculator. Accessed May 1, 2018.
8. Li K, Yip R, Avila R, Henschke CI, Yankelevitz DF. Size and growth assessment of pulmonary nodules: consequence of the rounding. J Thorac Oncol 2016; 12: 657-62.
9. Flores R, Bauer T, Aye R, et al. Balancing curability and unnecessary surgery in the context of computed tomography screening for lung cancer. J Thorac Cardiovasc Surg. 2014; 147:1619-26.
10. American Association of Physicists in Medicine. AAPM Position Statement on Radiation Risks from Medical Imaging Procedures. https://www.aapm.org/org/policies/details.asp?id=406&type=PP Accessed June 27, 2019
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ES08.05 - Advances in Artificial Intelligence - How Lung Cancer CT Screening Will Progress? (Now Available) (ID 3195)
13:30 - 15:00 | Presenting Author(s): Debora Gil | Author(s): Antoni Rosell
- Abstract
- Presentation
Abstract
Predictive models for personalized medicine (also known as radiomics) is a recent discipline that uses sophisticated image analysis and artificial intelligence (AI) methods to obtain quantitative image-based features that correlate to final diagnosis and treatment outcome [1].
The application of radiomics in lung cancer screening can represent a critical shift in this field. Some recent studies, like [2-3], show that radiomic features (including tumor shape descriptors and texture analysis) extracted from CT scans have significantly better predictive value than volumetry alone (AUC= 0.9 vs 0.74). Texture analysis reflects tumour heterogeneity and has recently introduced in PET images. In fact, PET texture analysis has demonstrated its value in establishing survival [4], predicting distant metastasis [5], detecting mutations and establishing radiotherapy doses [6]. However, and despite the promising results, there are some limitations like the low reliability of heterogeneity parameters in tumours with small volume, the low repeatability and reproducibility of textural features in the clinical setting and the limitation of the analytic methods.
A multi-radiomic model that could integrate morphological features from the CT together with biological characteristics from the PET and clinical risk factors (age, smoking history, contact with asbestos or family cancer background), would become a highly accurate diagnostic and prognostic method and, thus, make lung cancer screening programs cost-effective. However, in order that radiomics become the cornerstone for clinical decision-making, new machine learning and statistical strategies adapted to the specific requirements of clinical applications should be formulated.
A main pitfall in current state of the art AI methods is the use of generic machine learning and statistical tools borrowed from other fields of application which fall short under clinical conditions [7]. Predictive radiomic models for personalized medicine should address several specific challenges different from the ones common to other application areas of artificial intelligence. First, models should collect and integrate diverse multimodal data sources in a quantitative manner that delivers unambiguous clinical predictions. Second, models should also be easily interpreted from a clinical point of view to allow the analysis of the clinical factors that have an impact on the clinical decision. Third, predictions should be robust concerning data uncertainties due to the impact of collection conditions (like acquisition parameters or variability in manual annotations) and the presence of rare and/or outlying cases, which become highly influential for minority classes lead to overfitting.
This work reviews state-of-the-art AI methods for radiomics, the specific challenges that they must face in medical imaging applications and the latest advances for reliable personalized early diagnosis of lung cancer.
References
[1] P Lambin, et al, Radiomics: the bridge between medical imaging and personalized medicine, Nature Reviews,12, 749-53, 2017.
[2] Hawkins et al. Prediction of pathological nodal involvement by CT-based Radiomic features of the primary tumor in patients with clinically node-negative peripheral lung adenocarcinomas, Med. Phys. 45 (6), 2018.
[3] Peikert T et al. Novel high-resolution computed tomography-based radiomic classifier for screen-identified pulmonary nodules in the National Lung Screening Trial, PLOS ONE 13(10), 2018.
[4] Ohri N, Duan F, Snyder BS, Wei B, Machtay M, Alavi A, et al. Pretreatment 18F-FDG PET textural features in locally Advanced non-small cell lung cancer: secondary analysis of ACRIN 6668/RTOG 0235. J Nucl Med.57:842–8, 2016.
[5] Wu J,Aguilera, et al. Early-stage non-small cell lung cancer: quantitative imaging characteristics of (18)F fluorodeoxyglucose PET/CT allow prediction of distant metastasis. Radiology, 281:270–8, 2016.
[6] Yip SS, et al. Associations between somatic mutations and metabolic imaging phenotypes in non-small cell lung cancer. J Nucl Med. 58:569–76, 2017.
[7] JP. Cohen et al, Distribution matching losses can hallucinate features in medical image translation, MICCAI 2018.
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ES08.06 - Cost Effectiveness of Comprehensive Screening and Smoking Cessation Programmes (Now Available) (ID 3196)
13:30 - 15:00 | Presenting Author(s): Bruce Pyenson
- Abstract
- Presentation
Abstract
There is broad consensus that lung cancer screening with low-dose CT is cost-effective. However, there has been slow take-up in the US where it is covered by commercial insurance and by the federal Medicare program.
One way to optimize LC screening is to consider screening as part of an integrated program that specializes in population health for the cluster of smoking-related illness. There are four components of this,
LC screening centers can provide high-quality screening and systematic follow-up and appropriate referrals
Imaging for LC screening can quantify cardiac calcification, COPD, and osteoporosis, all of which may be associated with smoking
LC screening centers can operate as a center for smoking cessation, exercise counseling, and adherence support
For the 1.5 million annual indeterminant pulmonary nodules in the US, LC screening centers can provide appropriate follow-up. The vast majority of such cases receive no follow-up.
There are both economic and financial consequences for integrated screening. The economic consequences are measured in cost-effectiveness. The financial consequences are attracting high-utilizing people away from lower-quality providers, which can offset the loss of income from treating late stage lung cancers.
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ES08.07 - System Approach to Screening Management (Now Available) (ID 3197)
13:30 - 15:00 | Presenting Author(s): Anthony P Reeves
- Abstract
- Presentation
Abstract
IASLC ES08 - Critical Concerns in Screening 2019
System Approach to Screening Management
Anthony P. Reeves
School of Electrical and Computer Engineering
Cornell University
Screening seeks to identify a specific disease or set of diseases at an early stage where therapy can be most effective. It involves application of a medical test or tests to a group of asymptomatic individuals at-risk for the disease. Only a very small fraction of the tested population will be expected to have the target disease. Thus, a system for managing the screening process focuses on a single complex protocol and differs significantly from the more traditional medical practice that has a focus on symptomatic diseases and medical conditions. Very high compliance with the protocol and timeliness in follow up actions are critical to extract the maximum benefit of the screening process and avoid unnecessary actions on the majority of the participants that do not have the disease.
System requirements for Lung Cancer Screening
Screening involves detection of early stage asymptomatic disease and timely follow-up to provide the maximum therapeutic benefit of early stage detection. This requires a system to track participants throughout the screening process, from initial contact to documentation of screening results to follow-up. To maintain the highest degree of quality and timeliness, the screening management system should be comprehensive for all the digital data in the screening program and incorporate the screening protocol in its design.
For lung cancer screening (LCS), the web-based I-ELCAP management system was implemented in 2000 [1] with integration of all screening functions into a single system, including: scheduling, data collection, follow-up, patient reports and QA reports. This system includes structured reports for all patient interactions and medical events. The screening protocol is built in to the system; hence, there are real-time checks on adherence to the screening protocol. Any deviations from the protocol, such as a missing report or appointment schedule are flagged for attention. In addition, the management system includes all acquired digital images linked to the patient records; physicians may review images from within the system. Finally, the system includes computer image analysis methods for automated pulmonary nodule detection and for nodule growth rate assessment.
Additional findings and Computer Aided Diagnosis
Since that early system implementation in 2000, the importance of additional findings for other organs visible in the chest CT scans have become apparent. The radiological structured reporting requirements have been increased to include findings of the heart, and the lungs (emphysema, COPD) which, with lung cancer, covers the three main causes of death for the high-risk screening population. The detailed reporting of the CT scan reading, especially once the initial baseline scan has been read, places an increased burden on the radiologist. To improve the program quality and to address the reading issues a number of additional automated computer analysis functions have been integrated into the system, Reeves et. al. (2017) [2]. These include measures for: coronary calcium, heart size, the aorta, pulmonary hypertension, emphysema, major airways, bone mineral density from thoracic vertebra, breast density, and liver density. In addition, an automated quality assessment of the CT scan itself is reported.
The role for AI in screening management
Recent advances in AI technology, including deep learning with convolutional neural networks, have increased the capabilities of computer aided diagnostics. A landmark paper by Gulshan et. al. (2016) [3] showed that an automated end-to-end review of eye fundus images for diabetic retinopathy to determine if a follow-up action was indicated could be effectively accomplished without requiring a human read of the images. Following this work a commercial product for this task is now available. A recent paper by Ardila et. al. (2019) [4] showed that, for LCS CT scans, a similar approach with a more complex system could be used for predicting cancer events in a manner similar to LungRADS. A challenge with this LCS study, compared to Gulshan diabetic retinopathy study, is the cost and reporting complexity of the former for training data. While the Gulshan study was prospective and trained on over 120,000 cases, the Ardila study was retrospective with a subset of the NLST data of around 10,000 cases and only considered lung cancer. These methods employ the natural advantage of computer analysis with respect to human readers in attention to detail and lack of fatigue. Further, modern AI methods when appropriately designed, can assimilate data from millions of cases, far beyond human capacity. Efficient large-scale documentation methods have been developed to address the data issue for LCS [2] in which over 25,000 cases have been documented for multiple diseases.
These studies move us closer to the point where the majority of the CT image report for LCS could be automatically completed and the role of the physician focused to reviewing a small number of the most significant findings.
References
1. Reeves, A. P., Kostis, W. J., Yankelevitz, D. F., and Henschke, C. I. A web-based database system for multi-institutional research studies on lung cancer. RSNA 87th Scientific Meeting 221 (Nov. 2001), 372
2. Reeves, A. P., Xie, Y., and Liu, S. Large-scale image region documentation for fully automated image biomarker algorithm development and evaluation. Journal of Medical Imaging 4, 2 (2017), 024505.
3. Gulshan, V., Peng, L., Coram, M., Stumpe, M. C., Wu, D., Narayanaswamy, A., ... & Kim, R. (2016). Development and validation of a deep learning algorithm for detection of diabetic retinopathy in retinal fundus photographs. Jama, 316(22), 2402-2410.
4. Ardila, D., Kiraly, A. P., Bharadwaj, S., Choi, B., Reicher, J. J., Peng, L., ... & Naidich, D. P. (2019). End-to-end lung cancer screening with three-dimensional deep learning on low-dose chest computed tomography. Nature medicine, 1.
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S01 - IASLC CT Screening Symposium: Forefront Advances in Lung Cancer Screening (Ticketed Session) (ID 96)
- Event: WCLC 2019
- Type: Symposium
- Track: Screening and Early Detection
- Presentations: 20
- Now Available
- Moderators:John Kirkpatrick Field, James L Mulshine
- Coordinates: 9/07/2019, 07:00 - 12:00, Colorado Springs (1994)
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S01.02 - Introductions & Welcome (ID 3628)
07:00 - 12:00 | Presenting Author(s): James L Mulshine, John Kirkpatrick Field
- Abstract
Abstract
The Five-year Vision for Lung Cancer Screening
The goal of lung cancer screening is to increase the detection of asymptomatic, localized cancers that can more frequently be cured. Given this prospect, it is with a sense of urgency that we explore strategies that allow us to benefit as many willing candidates to receive this service. In addition, there is an obligation to ensure that this cancer detection service is delivered in a fashion that conveys maximal benefit while minimizing harms. Thinking strategically, what steps and in what sequence should we pursue implementation of lung cancer screening to optimize improvement of lung cancer outcome in the five-year window?
First, we expect results from a number of currently ongoing studies of smoking cessation studies integrated into lung cancer screening to be completed which may provide insight how to enhance cessation rates long-term smokers. This would be critical information to rapidly disseminate as risk of smoking harms rise so steeply in later life and since tobacco causes not only premature death but also profound economic costs (1, 2).
Resources to accelerate screening research are currently an intense focus of developmental efforts. Over the next five years, collaborative mechanisms such as the IASLC’s Early Lung Imaging Confederation will be fully functional and providing imaging cases with associated metadata to allow a robust number of research questions to be rapidly addressed (3).
Many believe that from an outcome’s perspective that “you get what your measure”. Currently, there are no established panel of metrics that define excellence in screening. This must be rapidly addressed. A strong measure of screening success would be the reality within five years that clinicians and subjects have easy access to information regarding critical outcomes at a lung cancer screening facility. Such annual metrics for a screening facility may include, screening number, rate of lung cancers detected in screening, frequency of Stage I/II/III/IV, frequency of symptom-detected lung cancer, frequency of true positive lung case detection, operability rate, non-malignant thoracic resection rate, surgical morbidity/mortality rate, compliance with subject follow-up and smoking cessation rate. Armed with such information, subjects as well as clinicians can make well-informed decision about selection of site of care.
Five years from now the clinical community may also come to consensus on a reliable and economical approach to access the biological potential of a resected tumor from a screen-identified cancer patient. The goal being to identify aggressive Stage I lung cancers based on mechanistic signatures derived from molecular analysis of the resected tumors identifying cancers that are unlikely to be cured with surgery alone. Appropriate target therapy can be match based on tumor characteristics so that immediate adjuvant therapy may be administered to preserve the possibility of a curative option for that subset of screen-detected cancers.
The key to the remarkable progress in lung cancer screening outcomes has been fueled by the rapid advances in reliably imaging of small non calcified lung nodules. Further progress in improving the efficiency of lung cancer screening management has been made possible by actually measuring changes in the volume of lung nodules over time to specifically identify clinically aggressive lung nodules. Reliably measuring lung nodule volume in the range of 6 mm in diameter is a challenging task, but the work of the Quantitative Imaging Biomarker Alliance (QIBA) has worked out a quality conformance process that greatly improved the reliability of using imaging as a quantitative biomarker in this context (3). As screening is rolled out, the QIBA quantitative measurement can be disseminated through a cloud-based infrastructure such as the environment being developed by IASLC to support the imaging quality aspect of lung cancer screening (4, 5). A key to sustain innovation in this regard is to continue to cultivate collaborative efforts in an open research environment so that investigators from many nations can participate and innovate, as IASLC has demonstrated with its impressive contributions to both lung cancer pathology and staging.
References:
1. Vineis P, Alavanja M, Buffler P, et al. Tobacco and cancer: recent epidemiological evidence. J Natl Cancer Inst. 2004 Jan 21;96(2):99-106. Review. No abstract available. PMID: 14734699
2. Ekpu VU, Brown AK.The Economic Impact of Smoking and of Reducing Smoking Prevalence: Review of Evidence. Tob Use Insights. 2015 Jul 14;8:1-35. doi: 10.4137/TUI.S15628. eCollection 2015.
3. Rydzak CE, Armato SG, Avila RS, Mulshine JL, Yankelevitz DF, Gierada DS. uality assurance and quantitative imaging biomarkers in low-dose CT lung cancer screening.Br J Radiol. 2018 Oct;91(1090):20170401. doi: 10.1259/bjr.20170401. Epub 2017 Oct 27. Review.PMID: 28830225
4. https://www.ascopost.com/issues/december-25-2018/low-dose-ct-lung-screening/
5. https://www.eurekalert.org/pub_releases/2018-12/iaft-isp121918.php -
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S01.03 - Session I: 2019 Status of the International Maturity of CT Trial Outcomes and Their Implications (ID 3629)
07:00 - 12:00 | Presenting Author(s): John Kirkpatrick Field, James L Mulshine
- Abstract
Abstract
Outstanding issues in lung cancer screening: Implementation Research Programmes
The Lung cancer community now have the results from two large international RCTs, NLST and NELSON (1, 2) , recent confirmatory data from the MILD trial (3), as well as from large international cohort studies (4-7) and smaller RCTs in Europe (8), all of which provide evidence to start the implementing lung cancer. The recent European consensus statement on lung cancer screening provides a very strong argument for the implementation of lung cancer screening (9).
However, the actual implementation a cancer screening modality quite often only occurs 10-15 years after the large clinical trials, due to a range of issue which includes the allocation of long term funding, approval from national organisations, clinical agreement regarding the screening protocol and design of the implementation programmes, as well as national service delivery and staffing issues.
All the evidence indicates that one would start to save lives now if lung cancer screening was implemented and even though there are acknowledged harms, the benefits outweigh the harms, as recently demonstrated in the NLST infographic (10). The number of deaths per year from lung cancer is still a major public health issue and has to be tackled with a well -structured and integrated smoking cessation and lung cancer screening programmes.
This does not infer we are currently in a position to undertake lung cancer screening to its optimum, we still have a great deal to learn and we need to plan for future ‘Implementation Research Programmes‘. Figure 1 provides the basis for continued improvements in screening over the next 20 years and are the subject of this presentation.”
We need to have conversations with the public, as to who benefits from lung cancer screening and discuss the basic concept of ‘early detection with early treatment, saves lives’.
Future Implementation Projects.
• Patient engagement /compliance.
• Identification of patients in primary care- availability of risk data, integrated
Information technology development.
• Quality assurance of imagining CT platforms.
• Use of liquid biopsies / breath tests in remote populations.
• Patient selection utilising risk prediction models – optimising risk models.
• Risk of lung cancer in females – re-evaluate based on NELSON mortality data.
• Lung cancer Risk in non-smokers, new approaches required.
• LDCT scans utilising volume & VDT – improve methodology / reporting.
• Coronary Calcium assessment, working with cardiology on treatment pathways.
• Use of AI reading of scans - quality control and future Radiology reporting.
• Central CT Screening scans reading nationally / internationally.
• Identification of the Indeterminate nodules – care pathway utilising integrated radiomics and biomarkers.
• Referral to MDT in centers of excellence – potential for spoke & hub care with far- reach communities.
• Treatment options / non-surgical – required clinical trials for small CT Screen detected nodules.
• Developing new innovative interventive treatment trials in the lung cancer screening pathway, which will be required over the future 20-year screening programmes.
• Continuously monitor mortality and cost effectiveness to improve the service.
• Significant other findings/ unexpected findings, integrated pathway of care with primary care for CT screened patients.
• Annual / biannual repeat screening based on initial CT Scan reports and patient underlying risks – re-evaluate with new data.
• Smoking cessation programmes – review success and adapt for differing populations.1. National Lung Screening Trial Research T, Aberle DR, Adams AM, et al. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med 2011; 365(5): 395-409.
2. de Koning DB, van Aalst CM, Ten Haaf K, oudkerk M. Effects of volumetric CT lung cancer screening: Mortality results of the NELSON randomised-controlled population based trail. WCLC2018; 2018; Toronto: IASLC; 2018. p. 2.
3. Pastorino U, Silva M, Sestini S, et al. Prolonged lung cancer screening reduced 10-year mortality in the MILD trial: new confirmation of lung cancer screening efficacy. Ann Oncol 2019.
4. International Early Lung Cancer Action Program I, Henschke CI, Yankelevitz DF, et al. Survival of patients with stage I lung cancer detected on CT screening. N Engl J Med 2006; 355(17): 1763-71.
5. Sagawa M, Sugawara T, Ishibashi N, Koyanagi A, Kondo T, Tabata T. Efficacy of low-dose computed tomography screening for lung cancer: the current state of evidence of mortality reduction. Surg Today 2017; 47(7): 783-8.
6. Tammemagi MC, Schmidt H, Martel S, et al. Participant selection for lung cancer screening by risk modelling (the Pan-Canadian Early Detection of Lung Cancer [PanCan] study): a single-arm, prospective study. Lancet Oncol 2017; 18(11): 1523-31.
7. Lee J, Lim J, Kim Y, et al. Development of Protocol for Korean Lung Cancer Screening Project (K-LUCAS) to Evaluate Effectiveness and Feasibility to Implement National Cancer Screening Program. Cancer Res Treat 2019.
8. Field JK, van Klaveren R, Pedersen JH, et al. European randomized lung cancer screening trials: Post NLST. J Surg Oncol 2013; 108(5): 280-6.
9. Oudkerk M, Devaraj A, Vliegenthart R, et al. European position statement on lung cancer screening. Lancet Oncol 2017; 18(12): e754-e66.
10. Robbins HA, Callister M, Sasieni P, et al. Benefits and harms in the National Lung Screening Trial: expected outcomes with a modern management protocol. Lancet Respir Med 2019.
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S01.04 - Lung Cancer Screening: 2019 – Taking Global Implementation Forward (Now Available) (ID 3630)
07:00 - 12:00 | Presenting Author(s): Harry J. de Koning | Author(s): Carlijn van der Aalst
- Abstract
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Abstract
With 338,000 EU-deaths annually, lung cancer is a devastating problem. Computed Tomography (CT) screening has the potential to prevent ten-thousands of lung cancer deaths annually. The positive results of the Dutch-Belgian screening trial (NELSON), with relatively low referral rates, and the NLST in the USA provided conclusive evidence. However, implementation is likely to be limited, slow and of variable quality throughout Europe, and current guidelines could easily require up to 25 million CT screens annually. The most optimal strategy in risk-based lung and thoracic screening is still unknown regarding the optimal and most cost-effective (e.g., targeted) strategy 1) to recruit, 2) to include smoking cessation and co-morbidity-reducing services in the context of screening, and 3) to determine the (risk-based) screening interval. Personalised regimens based on the baseline CT result can potentially retain 85% of the mortality reduction achievable through screening at 45% less screens, thus potentially saving much unnecessary harm associated with screening, and 0.5-1 billion Euros per year. But we do not know whether it is safe to have risk-based less intensive screening intervals after a negative baseline CT. Various methods to improve participation of hard-to-reach individuals have to be assessed in different healthcare settings. Innovative co-morbidity reducing strategies have to be tested including other markers on CT imaging, as Calcium Score and COPD. Such implementation research is needed to form the evidence base for risk-based lung cancer screening with huge benefits for the EU, on health outcomes, cost savings, and innovation in the long run.
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S01.05 - Panel Discussion (Now Available) (ID 3631)
07:00 - 12:00 | Presenting Author(s): Choon-Taek Lee, Motoyasu Sagawa, Charis Stacey, Karen Redmond, Witold Rzyman, Stephen Lam, Ugo Pastorino | Author(s): Ning Wu
- Abstract
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Abstract not provided
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S01.06 - Session II: U19 – Implications for the Future Integration of Biomarkers in the Selection of High Risk Individuals for Lung Cancer Screening (ID 3632)
07:00 - 12:00 | Author(s): Paul Brennan, Rayjean J. Hung On Behalf Of The International Lung Cancer Consortium
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Abstract not provided
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S01.07 - The U19 Plans for Integration of Biomarkers Into Future Lung Cancer Screening (Now Available) (ID 3633)
07:00 - 12:00 | Presenting Author(s): Christopher Ian Amos | Author(s): Rayjean J. Hung On Behalf Of The International Lung Cancer Consortium, Paul Brennan
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Abstract
The goal of the U19 Integrative analysis of Lung Cancer Etiology and Risk (INTEGRAL) consortium is to develop biomarkers that characterize individual risk for development and progression from lung cancer. We are using a comprehensive strategy, depicted below in Figure 1, for this analysis and we are drawing on world-wide resources and expertise.
There are three projects focusing on i) genetics of smoking behavior and lung cancer risk, ii) biomarker discovery and validation for identifying individuals at highest risk for developing lung cancer and iii) evaluation of these biomarkers in screening cohorts along with radiographic analaysis to evaluate risk for lung cancer development and nodule behavior. There are also administrative and biostatistics cores.
We will discuss strategies and novel findings from these projects. For Project 1, to assist in genetic analysis, we have reimputed all the available data from lung cancer cases and controls using the haplotype reference consortium to bring together a data lake comprising data from over 100,000 individuals. The consortium provides data to its members and to collaborators who would like to evaluate hypotheses related to lung cancer by providing access for analyses and we currently are supporting 107 projects evaluating lung cancer risk. Additionally, consortium members from the University of Laval have performed transcriptomic analysis of normal lung tissue from over 500 participants undergoing surgery for lung cancer treatment. We are also studying the role that genetic factors have in influencing smoking behavior by collaborating with other large consortia and by studying multiethnic variation using Hawaiian multiethnic populations.
Analyses of the genetic data and further extension to the UK Biobank have identified novel genetic loci that contribute to risk. Interaction analysis of the CHRNA3/A5/B4 cluster with all other genomic regions identifies interactions with the 15q25.1 nicotinic receptors that influence lung cancer risk. Results identified genes in the neuroactive ligand receptor interaction pathway as playing a key role in increasing lung cancer risk. A cross-ethnicity analysis identified genetic factors in the major histocompatibility complex (MHC) that affect risk for lung cancer. We imputed sequence variation for 26,044 cases and 20,836 controls in classical HLA genes, fine-mapped MHC associations for lung cancer risk with major histologies and compared results among ethnicities. Independent and novel associations within HLA genes were identified in Europeans primarily affecting risk for squamous cell histology including amino acids in the HLA-B*0801 peptide binding groove and an independent HLA-DQB1*06 loci group. In Asians, associations are driven by two independent HLA allele sets affecting adenocarcinoma risk primarily that both increase risk in HLA-DQB1*0401 and HLA-DRB1*0701; the latter was better represented by the amino acid Ala-104. These results implicate several HLA-tumor peptide interactions as the major MHC factor modulating lung cancer susceptibility. A rare variant analysis yielded a mutation of the ATM gene that is rare in all populations except individuals of Jewish descent that primarily increase risk for adenocarcinoma and has highest risk in nonsmoking women. Analyses of smoking and genetic data have identified gene-smoking interactions that contribute to lung cancer risk, and particularly several genes that protect at-risk smokers from lung cancer development. Mendelian randomization and mediation analyses are underway to evaluate novel biomarkers that can be further studied in project 2. This effort found a surprising result that elevated levels of vitamin B12 increase risk for lung cancer development.
Project 2 has been bringing together an approach to analyzing biomarkers using data from existing cohort consortia, which have collected samples prior to the clinical presentation of lung cancers. Results of an initial study showed that analysis of 4 circulating proteins (CEA125, CEA, CYFRA 21-1 and pro-SFTB) yielded an area under the receiver operator curve accuracy of 83%. This level of accuracy is sufficient to consider the panel for recruitment of individuals for screening studies, but we anticipate that adding additional biomarkers will further improve the accuracy of risk prediction. Biomarkers that are being further considered include additional protein markers along with micoRNA species, the inclusion of polygenic risk scores and additional serum-derived biomarkers like vitamins B-6 and B-12 that have been shown in mendelian randomization studies to help in identifying high risk subjects.
Project 3 is focused on the establishment and validation of the models in the LDCT screening programs. In collaboration with National Lung Screening Trial, Canadian LDCT screening programs, NELSON and United Kingdom Lung Study (UKLS), we have begun the data harmonization across LDCT studies, including clinic-epidemiological data as well as nodule characteristics. We have established a pipeline of feature extractions for the radiomics analysis and compared the inter-reader variability. The intraclass correlation coefficients are >0.75 for the majority of the radiomics features extracted. We will conduct cross-study validation for the model building to ensure the maximum generalizability of the model. We will start the work on biomarkers and assess their added values in these models.
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S01.10 - Session III: Global Prospective on Evolving Issues with CT Imaging in Lung Cancer Screening Populations (ID 3636)
07:00 - 12:00 | Author(s): Heidi Schmidt, John Kirkpatrick Field
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Abstract not provided
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S01.11 - Framing Current Status (Now Available) (ID 3637)
07:00 - 12:00 | Presenting Author(s): David F. Yankelevitz
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Abstract
CT screening has gained increased acceptance due to results from recently reported randomized controlled trials. Nevertheless, there continues to be concerns regarding the benefits. Articles continue to appear describing a very marginal benefit versus harms. This concern has likely impacted its uptake both in the US and globally. There is a strong need to rethink what is the relevant information to provide to a person interested in screening. The most obvious answer would related to their frequency of being diagnosed with a potentially life threatening cancer and then how curable it would be if found early by screening versus later when symptom prompted. Without knowing these specifics there is no rational way to make a decision. Nevertheless, this type of information is not routinely available and is commonly misrepresented in the literature. It is vital that people understand that lung cancer can be found early in the majority of cases and that surgery is curative in the majority of them as well. Another aspect of screening that directly affects the overall usefulness relates to the management of screen detected findings. Currently there are several different protocols that are being used. It will be important to be able to learn from each of these how well they perform and in particular, which aspects of the protocols work best. Some standardized measure that compares their efficiency would be useful. This not only would apply to the management schemes but also to the various software that is being applied. The use of volumetrics has been gaining continued acceptance, but it has different roles, it can be used for setting size thresholds and also looking for change over time. Each of these represent important areas that can have a large impact and both aspects need to be studied separately. Finally there is continued advancement in our ability to look for other findings on the same basic scan. The overall benefits that are likely to come about as a result of the screening process will extend to other illnesses and how this will be integrated into an overall assessment of benefit should be a high priority for those interested in screening.
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S01.12 - Panel Discussion (Now Available) (ID 3638)
07:00 - 12:00 | Presenting Author(s): Matthijs Oudkerk, Ella A Kazerooni, Claudia I Henschke, Mario Silva, Mat Callister, Javier Zulueta
- Abstract
- Presentation
Abstract
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S01.13 - Session IV: What Do We Do Next? Group Discussion Behind Implementing Lung Cancer Screening (ID 3639)
07:00 - 12:00 | Author(s): Dan Sullivan, Matthijs Oudkerk
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Abstract not provided
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S01.14 - Lung Cancer MDT (Now Available) (ID 3640)
07:00 - 12:00 | Presenting Author(s): David R. Baldwin
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Abstract
The Lung Cancer MDT
David R Baldwin
Consultant Respiratory Physician and Honorary Professor of Medicine
Nottingham University Hospitals and University of Nottingham, UK
Multidisciplinary Team (MDT) meetings or “Tumour Boards” are increasingly becoming a central component of lung cancer services. Management of lung cancer patients through diagnosis, staging, fitness assessment and treatment is a multidisciplinary endeavour. Good communication between disciplines means that the goal of personalised treatment can be realised because of the complexity of modern management, not least the rapid change in treatments. Many lung cancer services have a meeting of professionals at key points along the clinical pathway that is commonly at the point of decision to treat and where diagnosis and/or staging is complex. There are a number of documents that describe the membership of the MDT and how the meetings should function. Key is that all relevant professional groups are represented and that there is a clear record of the discussion. Despite the widespread adoption of MDT meetings, there remains limited evidence for their effectiveness. This is because the integration of MDTs into the lung cancer services has evolved as management has become increasingly complex. It would be difficult to devise an experiment to test the efficacy of the MDT as they are now so embedded in services.
With respect to lung cancer screening, it is important that MDTs adhere to guideline-driven management so as to reduce the harms that may accrue. The place of the lung cancer MDT is in relation to a high probability of cancer. In screening it is probably better to have a separate MDT to advise on the management of nodules and incidental findings, again using guideline-driven management. All MDTs should record data for audit, quality improvement and research.
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S01.15 - Service Requirements; Staff and Platforms Availability (Now Available) (ID 3641)
07:00 - 12:00 | Presenting Author(s): Heidi Schmidt
- Abstract
- Presentation
Abstract
Lung cancer screening encompasses a pathway that includes several integral elements. It starts with the active recruitment of individuals and their risk assessment. The pathway continues into radiology, with the actual scanning using low dose computed tomography (LDCT), as well as standardized reporting that focuses on the follow up of both lung nodules and incidental findings. At the end of the pathway is the seamless integration into a diagnostic assessment program for confirmation and timely and appropriate treatment of the detected lung cancer.
High quality, and quality assurance of the radiology performance is the central piece in this pathway, to decrease the harm from radiation and false positives. Since lung cancer screening is most often a newly established program in an institution, this presents a unique opportunity to build robust quality standards for radiology. Radiology quality assurance comes with requirements regarding acquisition, interpretation and reporting of the low-dose computed tomography (LDCT) scans.
The facility standards need to provide equipment that does allow low dose data acquisition. Scanning protocols need to be defined, and protocol compliance needs to be assured, radiation exposure needs to be regularly measured with phantoms, and image storage needs to be properly identified.
Personnel requirements cover both the technologists and the reporting radiologists. Both have to provide the necessary training and certification. Radiologists need to document their ongoing experience in chest reporting, participate in a workshop or alternative training regarding nodule follow up, and get familiar with the respective reporting template. Radiologists training programs have received positive feedback on content, their goal is to increase confidence in reading lung cancer screening LDCTs and appropriate recommend follow up for screen-detected nodules. Complex cases are collected and their discussion fosters mutual learning.
Ongoing quality assurance measures include peer review and double reads, to minimize false positive. An adjudication process can provide expert opinion and support learning where consensus can not initially be reached. Report completeness should be confirmed with regular audits.
All these requirements should be available and met by a facility planning to engage in lung cancer screening using LDCT. All above standards are available; they need to be monitored, must be met at baseline and during tailored annual assessments, ensuring compliance across screening sites.
In summary, the implementation of a robust quality assurance program assures a high standard around the radiology workflow, from LDCT scanning to image interpretation and follow up recommendations. Radiologist training programs, centre minimum requirements, and standardized reporting can ensure that quality standards are consistently highOnly Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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S01.16 - Surgical Services (Now Available) (ID 3848)
07:00 - 12:00 | Presenting Author(s): Nasser K Altorki
- Abstract
- Presentation
Abstract not provided
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S01.17 - Smoking Cessation (Now Available) (ID 3642)
07:00 - 12:00 | Presenting Author(s): Rachael L Murray
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Abstract
More than 85% of cases of lung cancer are caused by tobacco smoking, and stopping smoking, at any age, significantly reduces lung cancer risk. Despite positive findings reported by the National Lung Screening Trial (NLST) and the Dutch-Belgian Randomised Lung Cancer Screening Trial (NELSON), a number of important questions remain regarding the best way to implement lung cancer screening (LCS), including how most effectively to embed smoking cessation interventions (SCI) into these programmes. One concern that has been raised around LCS for current smokers is the potential ‘moral hazard’ arising from a negative (i.e. reassuring) screening result, which may reduce motivation to quit. Conversely, attendance at a lung cancer screening programme offers a ‘teachable moment’ for smoking cessation, occurring at a time when participating smokers may be particularly receptive to offers of help to quit. Indeed, a negative screen result has been reported as being perceived as a ‘clean slate’ as a motivator to stop smoking.
Evidence suggests that smoking cessation and low dose computed tomography (LDCT) screening have additive effects on survival; an analysis of participants in the NLST reported a 38% reduction in lung cancer mortality with the combination of smoking abstinence at 15 years with LDCT screening. Further, research has indicated that adding SCIs to LCS improves the cost effectiveness of such programmes. It is, therefore, essential that any lung cancer screening programme provides smoking cessation support for participants.
Clinical guidelines regarding delivery of smoking cessation interventions in the context of LCS have been produced by the Association for the Treatment of Tobacco Use and Dependence and The Society for Research on Nicotine and Tobacco, but this document acknowledges the paucity of data and need for future research specific to this patient population. Participants in LCS are unlikely to be representative of the general population of smokers, and evidence regarding smoking cessation outcomes in a lung cancer screening (LCS) context is variable.
There is some evidence to suggest that participation in LCS alone may increase smoking cessation rates above that of the general population, influenced by screening outcomes. However, comparisons between smoking cessation outcomes in screened and control populations in a number of studies have reported inconsistent findings. There is limited proven effectiveness of low intensity SCIs delivered as part of LCS programmes. When comparing such interventions delivered to smokers attending for LCS, there appears to be no difference between standard written advice, internet resources, quitline details or brief advice. However, more intensive interventions such as telephone-based counselling sessions have been shown to be more effective than self-help cessation resources and a combination of cognitive behavioural therapy and pharmacotherapy have shown further promise. Little research exists as to the potential benefits of e-cigarettes for cessation in this setting but given their increasing popularity as a cessation aid this requires further attention. Delivery of a more intensive intervention at the time of screening may be viable; one recent study reported that it was feasible to deliver a single tailored session of motivational interviewing counselling on the day of screening.
Smoking cessation studies from other settings mayprovide learnings transferrable to the LCS setting. Personalised interventions for smoking cessation are generally more effective than standard approaches. the presence of emphysema and coronary artery calcification may be incidental findings from LDCT scans that could be used as part of an SCI in the LCS setting. This may be particularly pertinent where participants are fit, relatively asymptomatic and hence potentially more susceptible to a message that lung damage had already occurred but clinical impact could be reduced by stopping smoking (as may be the case in LCS attendees).
Relatively few studies have tested interventions for smoking cessation in LCS settings, and are subject to large variations in timing, setting, participants, SCI and outcome measures which does not allow direct comparison between studies and makes it difficult to draw conclusions regarding optimal interventions. However, it is likely that higher intensity interventions will be more effective and the use of incidental scan findings should be considered. Much research into the best way to integrate SCIs into LCS is now ongoing in an attempt to answer the outstanding implementation questions. The SCALE (Smoking Cessation within the Context of Lung Cancer Screening) collaboration in the US consists of eight clinical trials which seek to build an evidence base for effective interventions in LCS, using a common core of data collection measures to allow pooling of data and comparison across studies. In the UK, the Yorkshire Enhanced Stop Smoking study (YESS) seeks to test the delivery of an intensive SCI, co-located with the Yorkshire Lung Screening Trial (YLST) and personalised to the LCS result. Data from these studies will hopefully add clarity to the question of how best to reduce morbidity and mortality amongst those presenting for LCS.
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S01.18 - Cost Effectiveness (Now Available) (ID 3643)
07:00 - 12:00 | Presenting Author(s): Bruce Pyenson
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- Presentation
Abstract
There is broad consensus that lung cancer screening with low-dose CT is cost-effective. However, there has been slow take-up in the US where it is covered by commercial insurance and by the federal Medicare program.
One way to optimize LC screening is to consider screening as part of an integrated program that specializes in population health for the cluster of smoking-related illness. There are four components of this,
LC screening centers can provide high-quality screening and systematic follow-up and appropriate referrals
Imaging for LC screening can quantify cardiac calcification, COPD, and osteoporosis, all of which may be associated with smoking
LC screening centers can operate as a center for smoking cessation, exercise counseling, and adherence support
For the 1.5 million annual indeterminant pulmonary nodules in the US, LC screening centers can provide appropriate follow-up. The vast majority of such cases receive no follow-up.
There are both economic and financial consequences for integrated screening. The economic consequences are measured in cost-effectiveness. The financial consequences are attracting high-utilizing people away from lower-quality providers, which can offset the loss of income from treating late stage lung cancers.
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S01.19 - Biomarkers (Now Available) (ID 3644)
07:00 - 12:00 | Presenting Author(s): Paul Brennan | Author(s): Mattias Johansson, Hilary Robbins
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Abstract
Improved risk stratification has the potential to enhance the ratio of benefit to harm for lung cancer screening. Risk biomarkers for lung cancer have been identified that have the potential to contribute to risk stratification, and efforts in this area are ongoing, although whether they are practical or cost-effective remains to be clarified. Recent progress in the use of biomarkers for lung cancer risk stratification and their cost-effectiveness will be discussed.
References
Guida F, et al. .Integrative Analysis of Lung Cancer Etiology and Risk (INTEGRAL) Consortium for Early Detection of Lung Cancer, Assessment of Lung Cancer Risk on the Basis of a Biomarker Panel of Circulating Proteins. JAMA Oncol. 2018 Oct 1;4(10)
Robbins HA, et al. .Benefits and harms in the National Lung Screening Trial: expected outcomes with a modern management protocol. Lancet Respir Med. 2019 May 7
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S01.20 - How Will Success Will Be Judged (Now Available) (ID 3645)
07:00 - 12:00 | Presenting Author(s): Kwun M Fong | Author(s): Henry Marshall
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- Presentation
Abstract
How will success be judged will vary according to the context of the evaluation.
For instance, for a screening proponent, the implementation of a population based CT screening program may signify success, whereas the opposite conclusion will be drawn by those not swayed by the available evidence on lung cancer screening.
From a technical viewpoint, as screening refers to the application of a test to a population which has no overt signs or symptoms of the disease in question, to detect disease at a stage when treatment is more effective. The technical effectiveness of CT screening can be viewed as its ability to detect the presence or absence of lung cancer, sensitivity, specificity, True and False positives, True and False negatives.
From a CT screening program perspective, the metrics may include:
· Participation (where it relates to an appropriate level of access and participation of people in the target and eligible population)
· Cancer detection rates
· Safety and harm minimisation (potential harm, either physical or emotional, is minimised)
· Timeliness (providing access to screening and assessment services in a timely and efficient manner)
· Client focused
From an economic point of view, success may be a measure of the balance of the costs of screening (costs of the test and subsequent diagnostic tests and the costs associated with any hazard of the test as well as the costs of over-treatment) to reduced costs of therapy (costs associated with less expenditure on the treatment of the advanced disease, and the economic value of the additional years of life gained)
For the policy maker, the metrics of success will include budgetary management, degree of realised benefit for the population targeted in the context of health care funding for other conditions (eg incidence and mortality), opportunity costs and population health measures, and adherence with their national screening policy
Here we discuss the nuances of selecting metrics for lung cancer CT screening to inform our considerations for the multiple circumstances that make up the pragmatisim of real life.
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S01.22 - Session V - IASLC Leads the International Collaboration on Data Sharing (ELIC) (ID 3647)
07:00 - 12:00 | Author(s): Norihiko Ikeda, John Kirkpatrick Field
- Abstract
Abstract not provided
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S01.23 - Evolution of ELIC (Now Available) (ID 3648)
07:00 - 12:00 | Presenting Author(s): Ricardo Avila
- Abstract
- Presentation
Abstract
The Early Lung Imaging Confederation (ELIC) Hub & Spoke Environment (H&SE) is a new globally distributed and open source lung cancer imaging database and computational analysis environment designed to significantly improve the cost, time, and quality of lung cancer imaging research. This IASLC led initiative and computational infrastructure project, when fully deployed, will allow clinical research groups (Spokes) to securely make their locally stored de-identified lung cancer imaging collections available for computational analysis by other research groups (Clients), all coordinated by a central IASLC managed server (Hub). Clinical sites will be able to make lung cancer imaging data available for specific types of computational analysis without transmitting the imaging data over national boundaries to other groups and losing control over how the data is used and further distributed. This allows lung cancer screening research groups to more easily make available datasets to large global lung cancer imaging research studies with far more control over data use. This federated data storage and analysis approach will allow the ELIC H&SE to scale to much larger data sizes than a traditional centralized database, one day allowing lung cancer imaging researchers to quickly and easily perform quantitative analysis on global lung cancer imaging studies with larger collections of high quality, standardized data than is attainable today. This is viewed as a critical next step for the development of next generation Artificial Intelligence algorithms for lung cancer imaging, which require large amounts of data for algorithm development and performance evaluation.
In preparation for the 2018 IASLC WCLC meeting in Toronto, Canada, a proof-of-concept ELIC Hub and Spoke Environment was developed and set up using Amazon Web Services (AWS) cloud resources. A hub was set up on a Virginia AWS cloud instance and 10 spokes, each pre-populated with an identical set of 100 de-identified CT lung scans, were set up at 10 globally distributed AWS cloud locations including Mumbai, London, Frankfurt, Montreal, Sydney, Tokyo, Paris, Seoul, Sao Paulo, and Virginia (on a separate cloud instance). Two open source lung cancer imaging algorithms, one that automatically computes lung volume for a thoracic CT scan and another for volumetric measurement of small lung nodules, were made available for use by the 10 spoke instances. Live demonstrations of the proof-of-concept system were shown at the 2018 WCLC meeting including the ability to launch computational experiments and receive back quantitative results from the 10 globally distributed spokes. Figure 1 shows the global distribution of the hub and spokes for the 2018 WCLC ELIC proof of concept demonstrations. The live demonstrations showed that the ELIC H&SE could be used to select globally distributed datasets available on the spokes for analysis, run specific computational algorithms on those datasets, and have all of the results aggregated in real-time for viewing on the hub, as shown in Figure 2.
The ELIC H&SE infrastructure is now undergoing further development in 2019 to bring it from a proof-of-concept demonstration to a functional globally distributed database and computational environment capable of performing useful quantitative lung cancer imaging studies. References to tools and resources for performing data de-identification and encryption are being added to support research groups that will be uploading lung imaging datasets and metadata into the ELIC H&SE. Standards for lung cancer screening data representation, starting with a lung cancer screening data dictionary developed by the VA-Partnership to increase Access to Lung Screening (VA-PALS) project, are also being added to ensure that global analyses can be performed with common terminology and data formats. In addition, the Radiological Society of North America’s Quantitative Imaging Biomarker Alliance (QIBA) small lung nodule conformance certification phantom, specifications, and methods are being used to help lung cancer screening sites prospectively collect, monitor, and optimize lung cancer imaging studies for high quality volume measurements. All of these resources and formats are planned to be reviewed with all ELIC stakeholders on a quarterly basis to receive feedback and refine the systems and methods.
There are numerous functionality advantages for spokes that use local cloud computing resources including significantly improved security for both clients and spokes, improved computational efficiency through on-demand cloud resourcing, and continuously updated hardware and infrastructure. Additional software development is underway that will allow ELIC to achieve these advantages for cloud-based deployments.
Live demonstrations are again planned for the 2019 IASLC WCLC meeting in Barcelona, Spain showing an early demonstration of a new iaslc-elic.org website capable of supporting both spokes and clients performing globally distributed lung cancer imaging research studies.
Figure 1: The global distribution of the hub and spokes for the 2018 WCLC ELIC proof-of-concept demonstrations.
Figure 2: ELIC H&SE live demonstration screenshots showing the ability to view spoke status, select globally distributed datasets for analysis, and view a list of completed experiments (left) as well as drill down and view statistical experiment results including computationally generated images (right).
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S01.24 - Closing Statements (Now Available) (ID 3649)
07:00 - 12:00 | Presenting Author(s): John Kirkpatrick Field, James L Mulshine
- Abstract
- Presentation
Abstract not provided
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Author of
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EP1.11 - Screening and Early Detection (ID 201)
- Event: WCLC 2019
- Type: E-Poster Viewing in the Exhibit Hall
- Track: Screening and Early Detection
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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EP1.11-02 - Implementation Planning of Lung Cancer Screening in China (Now Available) (ID 961)
08:00 - 18:00 | Author(s): John Kirkpatrick Field
- Abstract
Background
Lung cancer is the leading cause of cancer-related deaths in China, with approximately 690,000 lung cancer deaths estimated in 2018; this has increased about fivefold from the mid-1970s. Lung cancer low-dose CT (LDCT) screening in smokers was shown to improve the survival in the US National Lung Screening Trial and more recently in the European NELSON trial. However, the predominant risk factor smoking contributes to a lower fraction of lung cancers in China than in Europe and the US. Therefore, it is necessary to establish Chinese-specific screening strategies.
Method
To curate data on Chinese lung cancer screening programmes, we searched four Chinese and four English databases, and other sources including references in papers, policies or news from government websites and personal communications with principal investigators. We reviewed the current evidence for the implementation of lung cancer screening in China to generate Chinese-targeted recommendations.
Result
There are 23 associated programmes completed or ongoing in China since the 1980s, mainly after 2000; and one has recently been planned. Municipal or city-level screening programmes are increasing, particularly after two central government-supported feasibility programmes: the Rural Cancer Screening Programme in 2009 and the Cancer Screening Programmes in Urban China in 2012. Some institutes have established collaborations with international lung cancer screening research groups, i.e. I-ELCAP and NELSON. Most of the programmes targeted community-based high-risk urban residents. Generally, their entry criteria are not smoking-stringent but involve other risk factors, e.g. second-hand smoking, family history of cancer, occupational exposures and air pollution. Some programmes have reported their preliminary results, which demonstrated a different high-risk subpopulation of lung cancer in China and the potential importance of risk-based selection. Evidence concerning LDCT screening implementation is mainly based on randomised controlled trials outside China, which indicates population recruitment, screening protocol and nodule management need more delicate considerations. In addition, LDCT screening programmes combining tobacco control would produce more benefits. Targeting populations to support cost-effectiveness will be important, especially in China where almost half of the lung cancer sufferers are non-smokers.
Conclusion
In China, the high-risk subpopulation eligible for lung cancer screening has not as yet been confirmed, as all the risk parameters have not yet been determined. Though evidence on best practice for implementation of lung cancer screening has been accumulating in other countries, further research in China is urgently required, as China is now facing a lung cancer epidemic.
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P1.11 - Screening and Early Detection (ID 177)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Screening and Early Detection
- Presentations: 3
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.11-21 - Liverpool Health Lung Project: Significant Incidental Findings in a Smoker-Predominant Cohort (Now Available) (ID 1879)
09:45 - 18:00 | Author(s): John Kirkpatrick Field
- Abstract
Background
The Liverpool Healthy Lung Project (LHLP) is a prospective screening cohort which recruits ever-smokers or subjects with COPD aged 58-75 with a lung cancer risk of ≥5% in 5 years by the LLPv2 model. It aims to identify lung cancers at a treatable stage. On chest computed tomography scans, it is common to detect incidental findings with the frequency ranging 36% - 55%, but most of them are minor findings requiring no further management. Thus, it is presumed to be cost-effective if the most significant incidental findings are managed as appropriate in lung cancer screening programmes.
Method
In the LHLP, radiologists alert a significant incidental finding (SIF, not relevant to suspicious lung cancer or indeterminate lung nodule) in the radiological reports if the Radiologist considers an urgent intervention is required; it’s referred to a specialist or general practitioner outside the project. This paper reviewed the alerted reports with SIFs and followed up their final diagnosis and corresponding interventions in three hospital clinical databases.
Result
Among a total of 3336 eligible participants who have completed the baseline scans during Apr 2016 - Feb 2019, 124 SIFs have been identified in 122 individuals (3.7%). The most frequently reported SIFs at baseline are possible extra-pulmonary cancers (45 of 124, 36.3%), followed by lung infections (39 of 124, 31.5%) which often need (post-antibiotic) follow-up to confirm resolution. Nine extra-pulmonary malignancies (7.4% in SIFs, 0.3% in the LHLP) have been pathologically or radiologically confirmed, including 5 lymphomas/leukaemias (4.1%), 2 renal cancers (1.6%), 1 breast cancers (0.8%) and 1 liver metastasis with unknown origin (0.8%). Two lymphoma/leukaemia patients have been treated with chemotherapy and/or radiotherapy, and the other three are currently under active monitoring. Both of the two renal cancer patients have undergone laterally radical nephrectomy, without recurrence in 6 and 20 months after surgery, respectively. The remaining two established cancer patients are still under further investigation. Other common SIFs included 14 interstitial lung diseases (11.3%), three of which have progressed during a post-baseline follow-up time of 6 months - 2 years, and 10 aneurysms/dilated aortas (8.0%), of which two patients have undergone surgical repair and another one has commenced a preventive therapy of statin and anti-plate agent.
Conclusion
Identification by radiology of these SIFs in 3.7% of our screened population facilitates urgent clinical review, and appropriate management of these important, but unexpected findings.
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P1.11-32 - The UKLS Nodule Risk Model (UKLS-NRM): Utilising Nodule Volumetry (ID 728)
09:45 - 18:00 | Presenting Author(s): John Kirkpatrick Field
- Abstract
Background
Estimating the clinical probability of malignancy in patients with pulmonary nodules will facilitate early diagnosis, determine optimum patient management strategies and reduce overall costs.
Currently there are two risk prediction models, which are recommended by BTS; the Brock University model, for nodules ≥300mm3 or ≥8mm diameter, and where the risk is estimated at >10%, the Herder model after PET-CT. However, none of these models employ volumetry and all were developed for use at baseline
Method
The UK Lung Cancer Screening (UKLS) trial data were analysed, utilising multivariable logistic regression models to identify independent predictors and develop a parsimonious model to estimate the probability of lung cancer in lung nodules detected at baseline, three month and twelve months repeat screening.
Result
Conclusion
1994 UKLS participants had a CT scan; 1013 had a total of 5063 lung nodules and 52 (2.6%) developed lung cancer during a 4 year median follow-up. Covariates that predict lung cancer included: female gender, asthma, bronchitis, asbestos exposure, history of previous cancer, early and late onset of family history of lung cancer, smoking duration, forced vital capacity, nodule type and volume. The final model had excellent discrimination; area under the receiver-operating characteristic curve (AUC [95% CI] = 0.885 [0.880 to 0.889]). Internal validation indicated that the model will discriminate well when applied to new data (optimism-corrected AUC = 0.882 [0.848-.907]). The risk model had a good calibration (goodness-of-fit χ 8.13, P = 0.42).
The UKLS Nodule Risk Model (UKLS-NRM) estimates the probability of lung cancer in nodules detected at baseline, three months and twelve months from baseline. The model is based on readily available, strong, and plausible covariates that have been implicated in the aetiology of lung cancer. The application of UKLS-NRM has the potential to be used in both the research and clinical setting.
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P1.11-34 - The Liverpool Healthy Lung Project – Championing the Importance of Lung Health (Now Available) (ID 802)
09:45 - 18:00 | Author(s): John Kirkpatrick Field
- Abstract
Background
Liverpool has high levels of deprivation and one of the highest rates of respiratory morbidity in England with double the incidence of lung cancer, most prevalent in the lower socioeconomic groups. To tackle this health inequality, in February 2016 in partnership with Liverpool CCG, Liverpool University, and primary care, we embarked on the 4-year Liverpool Healthy Lung Project.
Method
Based on primary care records, individuals aged 58-75 with COPD, a history of smoking or asbestos exposure were invited to a face-to-face lung health check conducted by an experienced respiratory nurse. At this interview positive lifestyle messages were promoted and their 5-year personal lung cancer risk calculated (www.MyLungRisk.org) using the LLPv2 risk model. Those without a diagnosis of COPD underwent spirometry, and those who triggered the 5% threshold lung cancer risk threshold were offered a low dose thoracic CT scan. We now report our results to January 2019.
Result
8350 of 21409 (40%) patients invited to the lung health check had attended. Of these, 5501 (59%) underwent spirometry and 10% were diagnosed with COPD. A further 2947 (35%) underwent the CT scan and of these 98 (3.3%) were suspicious of malignancy. Lung cancer was ultimately diagnosed in 55 (1.9%) and 45 of these (81%) were offered radical treatment. Of the remaining 43 patients, 10 underwent an invasive test and there was 1 benign resection. 265 patients (9%) needed repeat scans for lung nodules.
Conclusion
These early results show that this innovative project is already improving access to respiratory healthcare in a deprived area of Liverpool, has identified new COPD patients, and over time should improve outcomes for lung cancer in this disadvantaged population.
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P2.03 - Biology (ID 162)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Biology
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.03-18 - Pathogenic Germline Rare Variants and Risk of Lung Cancer (Now Available) (ID 2699)
10:15 - 18:15 | Author(s): John Kirkpatrick Field
- Abstract
Background
Recent studies suggest that rare variants, with minor allele frequencies (MAFs) of less than 0.01, exhibit stronger effect sizes than common variants, might play a crucial role in the etiology of complex traits and could account for missing heritability unexplained by common variants.
Method
Germline DNA from 1059 lung cancer cases and 899 controls from the Transdisciplinary Research in Cancer of the Lung and International Lung Cancer Consortium study were sequenced, utilizing the Agilent SureSelect XT Custom ELID and Whole Exome v5 capture. To unveil the inherited rare causal variants, allelic association analysis of single variant and gene-based collapsing tests of multiple variants were performed, including variants per gene association test, the Kernel-based adaptive cluster test, and SNP-set Kernel association test. Odds ratio (OR), 95% confidence intervals (CIs), and false discovery rate (FDR) adjusted P values were calculated.
Result
Conclusion
We identified 32 highly deleterious rare heterozygotes, including 14 rare and 18 novel variants -- absent from prior databases of genetic variation (Table 1). The top candidate substitutions including NEBstop gain p.Q7971* (nine cases versus zero control carriers, P = 0.0056), OGG1 upstream Chr 3:9816129(11 cases versus one control carriers, P = 0.0087),CDKN2B transcription end site (16 cases versus three controls carriers, P = 0.0081), ATP6V0A2 regulatory Chr 12:124242486 (eight cases versus zero control carriers, P = 0.0089), KCNN4 transcription factor binding site (15 cases versus two controls carriers, P = 0.0044), and TEX28P1 regulatory rs1445670979 (11 cases versus one control carriers, P = 0.0087). We also identified candidates in known genes which have been previously implicated in lung cancer risk, i.e., HLA, TP53, POT1, PTEN, ERC, GPC, RGS17, and LAMC1. Among the candidate genes with multiple rare deleterious SNVs, the top five genes with strong association (FDR adjusted P < 0.01 in burden tests) are NBPF20 (OR5.69, 95% CI 2.4-13.5), ERC1 (OR 4.49, 95% CI 2.19-9.23), LOC440434 (OR 1.85, 95% CI 1.32-2.59), GPC5 (OR 1.55, 95% CI 1.21-1.99), and NOTCH2NL(OR 5.46, 95% CI 1.61-18.5). The KEGG pathway analysis shown the 1st and 4th significant pathways are from small cell and non-small cell lung cancer, respectively.
Our analyses led to identification of 32 pathogenic germline rare variants associated with lung cancer susceptibility. However, replication in additional populations is necessary to confirm potential genetic differences in lung cancer risk.
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S01 - IASLC CT Screening Symposium: Forefront Advances in Lung Cancer Screening (Ticketed Session) (ID 96)
- Event: WCLC 2019
- Type: Symposium
- Track: Screening and Early Detection
- Presentations: 5
- Now Available
- Moderators:John Kirkpatrick Field, James L Mulshine
- Coordinates: 9/07/2019, 07:00 - 12:00, Colorado Springs (1994)
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S01.02 - Introductions & Welcome (ID 3628)
07:00 - 12:00 | Presenting Author(s): John Kirkpatrick Field
- Abstract
Abstract
The Five-year Vision for Lung Cancer Screening
The goal of lung cancer screening is to increase the detection of asymptomatic, localized cancers that can more frequently be cured. Given this prospect, it is with a sense of urgency that we explore strategies that allow us to benefit as many willing candidates to receive this service. In addition, there is an obligation to ensure that this cancer detection service is delivered in a fashion that conveys maximal benefit while minimizing harms. Thinking strategically, what steps and in what sequence should we pursue implementation of lung cancer screening to optimize improvement of lung cancer outcome in the five-year window?
First, we expect results from a number of currently ongoing studies of smoking cessation studies integrated into lung cancer screening to be completed which may provide insight how to enhance cessation rates long-term smokers. This would be critical information to rapidly disseminate as risk of smoking harms rise so steeply in later life and since tobacco causes not only premature death but also profound economic costs (1, 2).
Resources to accelerate screening research are currently an intense focus of developmental efforts. Over the next five years, collaborative mechanisms such as the IASLC’s Early Lung Imaging Confederation will be fully functional and providing imaging cases with associated metadata to allow a robust number of research questions to be rapidly addressed (3).
Many believe that from an outcome’s perspective that “you get what your measure”. Currently, there are no established panel of metrics that define excellence in screening. This must be rapidly addressed. A strong measure of screening success would be the reality within five years that clinicians and subjects have easy access to information regarding critical outcomes at a lung cancer screening facility. Such annual metrics for a screening facility may include, screening number, rate of lung cancers detected in screening, frequency of Stage I/II/III/IV, frequency of symptom-detected lung cancer, frequency of true positive lung case detection, operability rate, non-malignant thoracic resection rate, surgical morbidity/mortality rate, compliance with subject follow-up and smoking cessation rate. Armed with such information, subjects as well as clinicians can make well-informed decision about selection of site of care.
Five years from now the clinical community may also come to consensus on a reliable and economical approach to access the biological potential of a resected tumor from a screen-identified cancer patient. The goal being to identify aggressive Stage I lung cancers based on mechanistic signatures derived from molecular analysis of the resected tumors identifying cancers that are unlikely to be cured with surgery alone. Appropriate target therapy can be match based on tumor characteristics so that immediate adjuvant therapy may be administered to preserve the possibility of a curative option for that subset of screen-detected cancers.
The key to the remarkable progress in lung cancer screening outcomes has been fueled by the rapid advances in reliably imaging of small non calcified lung nodules. Further progress in improving the efficiency of lung cancer screening management has been made possible by actually measuring changes in the volume of lung nodules over time to specifically identify clinically aggressive lung nodules. Reliably measuring lung nodule volume in the range of 6 mm in diameter is a challenging task, but the work of the Quantitative Imaging Biomarker Alliance (QIBA) has worked out a quality conformance process that greatly improved the reliability of using imaging as a quantitative biomarker in this context (3). As screening is rolled out, the QIBA quantitative measurement can be disseminated through a cloud-based infrastructure such as the environment being developed by IASLC to support the imaging quality aspect of lung cancer screening (4, 5). A key to sustain innovation in this regard is to continue to cultivate collaborative efforts in an open research environment so that investigators from many nations can participate and innovate, as IASLC has demonstrated with its impressive contributions to both lung cancer pathology and staging.
References:
1. Vineis P, Alavanja M, Buffler P, et al. Tobacco and cancer: recent epidemiological evidence. J Natl Cancer Inst. 2004 Jan 21;96(2):99-106. Review. No abstract available. PMID: 14734699
2. Ekpu VU, Brown AK.The Economic Impact of Smoking and of Reducing Smoking Prevalence: Review of Evidence. Tob Use Insights. 2015 Jul 14;8:1-35. doi: 10.4137/TUI.S15628. eCollection 2015.
3. Rydzak CE, Armato SG, Avila RS, Mulshine JL, Yankelevitz DF, Gierada DS. uality assurance and quantitative imaging biomarkers in low-dose CT lung cancer screening.Br J Radiol. 2018 Oct;91(1090):20170401. doi: 10.1259/bjr.20170401. Epub 2017 Oct 27. Review.PMID: 28830225
4. https://www.ascopost.com/issues/december-25-2018/low-dose-ct-lung-screening/
5. https://www.eurekalert.org/pub_releases/2018-12/iaft-isp121918.php -
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S01.03 - Session I: 2019 Status of the International Maturity of CT Trial Outcomes and Their Implications (ID 3629)
07:00 - 12:00 | Presenting Author(s): John Kirkpatrick Field
- Abstract
Abstract
Outstanding issues in lung cancer screening: Implementation Research Programmes
The Lung cancer community now have the results from two large international RCTs, NLST and NELSON (1, 2) , recent confirmatory data from the MILD trial (3), as well as from large international cohort studies (4-7) and smaller RCTs in Europe (8), all of which provide evidence to start the implementing lung cancer. The recent European consensus statement on lung cancer screening provides a very strong argument for the implementation of lung cancer screening (9).
However, the actual implementation a cancer screening modality quite often only occurs 10-15 years after the large clinical trials, due to a range of issue which includes the allocation of long term funding, approval from national organisations, clinical agreement regarding the screening protocol and design of the implementation programmes, as well as national service delivery and staffing issues.
All the evidence indicates that one would start to save lives now if lung cancer screening was implemented and even though there are acknowledged harms, the benefits outweigh the harms, as recently demonstrated in the NLST infographic (10). The number of deaths per year from lung cancer is still a major public health issue and has to be tackled with a well -structured and integrated smoking cessation and lung cancer screening programmes.
This does not infer we are currently in a position to undertake lung cancer screening to its optimum, we still have a great deal to learn and we need to plan for future ‘Implementation Research Programmes‘. Figure 1 provides the basis for continued improvements in screening over the next 20 years and are the subject of this presentation.”
We need to have conversations with the public, as to who benefits from lung cancer screening and discuss the basic concept of ‘early detection with early treatment, saves lives’.
Future Implementation Projects.
• Patient engagement /compliance.
• Identification of patients in primary care- availability of risk data, integrated
Information technology development.
• Quality assurance of imagining CT platforms.
• Use of liquid biopsies / breath tests in remote populations.
• Patient selection utilising risk prediction models – optimising risk models.
• Risk of lung cancer in females – re-evaluate based on NELSON mortality data.
• Lung cancer Risk in non-smokers, new approaches required.
• LDCT scans utilising volume & VDT – improve methodology / reporting.
• Coronary Calcium assessment, working with cardiology on treatment pathways.
• Use of AI reading of scans - quality control and future Radiology reporting.
• Central CT Screening scans reading nationally / internationally.
• Identification of the Indeterminate nodules – care pathway utilising integrated radiomics and biomarkers.
• Referral to MDT in centers of excellence – potential for spoke & hub care with far- reach communities.
• Treatment options / non-surgical – required clinical trials for small CT Screen detected nodules.
• Developing new innovative interventive treatment trials in the lung cancer screening pathway, which will be required over the future 20-year screening programmes.
• Continuously monitor mortality and cost effectiveness to improve the service.
• Significant other findings/ unexpected findings, integrated pathway of care with primary care for CT screened patients.
• Annual / biannual repeat screening based on initial CT Scan reports and patient underlying risks – re-evaluate with new data.
• Smoking cessation programmes – review success and adapt for differing populations.1. National Lung Screening Trial Research T, Aberle DR, Adams AM, et al. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med 2011; 365(5): 395-409.
2. de Koning DB, van Aalst CM, Ten Haaf K, oudkerk M. Effects of volumetric CT lung cancer screening: Mortality results of the NELSON randomised-controlled population based trail. WCLC2018; 2018; Toronto: IASLC; 2018. p. 2.
3. Pastorino U, Silva M, Sestini S, et al. Prolonged lung cancer screening reduced 10-year mortality in the MILD trial: new confirmation of lung cancer screening efficacy. Ann Oncol 2019.
4. International Early Lung Cancer Action Program I, Henschke CI, Yankelevitz DF, et al. Survival of patients with stage I lung cancer detected on CT screening. N Engl J Med 2006; 355(17): 1763-71.
5. Sagawa M, Sugawara T, Ishibashi N, Koyanagi A, Kondo T, Tabata T. Efficacy of low-dose computed tomography screening for lung cancer: the current state of evidence of mortality reduction. Surg Today 2017; 47(7): 783-8.
6. Tammemagi MC, Schmidt H, Martel S, et al. Participant selection for lung cancer screening by risk modelling (the Pan-Canadian Early Detection of Lung Cancer [PanCan] study): a single-arm, prospective study. Lancet Oncol 2017; 18(11): 1523-31.
7. Lee J, Lim J, Kim Y, et al. Development of Protocol for Korean Lung Cancer Screening Project (K-LUCAS) to Evaluate Effectiveness and Feasibility to Implement National Cancer Screening Program. Cancer Res Treat 2019.
8. Field JK, van Klaveren R, Pedersen JH, et al. European randomized lung cancer screening trials: Post NLST. J Surg Oncol 2013; 108(5): 280-6.
9. Oudkerk M, Devaraj A, Vliegenthart R, et al. European position statement on lung cancer screening. Lancet Oncol 2017; 18(12): e754-e66.
10. Robbins HA, Callister M, Sasieni P, et al. Benefits and harms in the National Lung Screening Trial: expected outcomes with a modern management protocol. Lancet Respir Med 2019.
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S01.10 - Session III: Global Prospective on Evolving Issues with CT Imaging in Lung Cancer Screening Populations (ID 3636)
07:00 - 12:00 | Author(s): John Kirkpatrick Field
- Abstract
Abstract not provided
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S01.22 - Session V - IASLC Leads the International Collaboration on Data Sharing (ELIC) (ID 3647)
07:00 - 12:00 | Author(s): John Kirkpatrick Field
- Abstract
Abstract not provided
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S01.24 - Closing Statements (Now Available) (ID 3649)
07:00 - 12:00 | Presenting Author(s): John Kirkpatrick Field
- Abstract
- Presentation
Abstract not provided
Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
