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    S01 - IASLC CT Screening Symposium: Forefront Advances in Lung Cancer Screening (Ticketed Session) (ID 853)

    • Event: WCLC 2018
    • Type: Symposium
    • Track: Screening and Early Detection
    • Presentations: 7
    • Moderators:
    • Coordinates: 9/23/2018, 07:00 - 12:00, Room 203 BD
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      S01.04 - Lung Cancer Screening: 1999 to Date – What Have We Learnt? (ID 11885)

      07:35 - 07:50  |  Presenting Author(s): David F Yankelevitz

      • Abstract
      • Presentation
      • Slides

      Abstract

      In 1999, ELCAP published their initial results from baseline screening. It found that in a cohort of 1000 participants approximately 85% of the cancers could be diagnosed as clinical Stage I, and that compared with chest radiography found many more of the cancers. In a subsequent study the expanded I-ELCAP found that the long term survival as a measure of cure rate approached 80%. The publicity associated with this initial study was quite large and led to the initiation of several other trials including the NLST. The NLST published their results in 2011 and based this, screening was endorsed by insurers in the US and now other countries are similarly following suit. However, despite the positive result of the NLST, and reimbursement from insurers, screening has had extremely limited uptake in the US, with only approximately 2% of those eligible (among a restricted population) are being screened. Thus, we face a situation where the most common cancer killer has been studied in the most expensive screening trial ever performed which had a positive result, insurers are reimbursing for it, and few people are having it done.

      With lung cancer screening being touted as a major breakthrough in the war on cancer the question naturally arises as to why it is not being performed more frequently. There have been many reasons to explain the poor uptake, ranging from merely a slow start but expected steady increase, lack of awareness by the clinician or potential screenee, obstacles such as the shard decision making requirement, too many potential harms, and lack of significant benefits.

      This lack of perceived significant benefit is perhaps the most important aspect, since without a substantial benefit, even if the harms were minimized, why would anyone get screened and why would a clinician recommend it. It seems that this is clearly influencing the decision not to be screened as many experts and even guideline organizations consider the benefits to not be sufficient enough so as to recommend the screening. Even CMS considered the balance of the risks and benefits so tenuous that they took the unique step of requiring a shared decision making process to be included as necessary for reimbursement so that a person could balance the risks and benefits.

      It is this aspect of benefit that needs to be considered more carefully when explaining it to a potential screenee. Current decision aids, which are required as part of a shared decision making process, in the US and Canada rely almost exclusively on the NLST result and attempt to convert its findings into more visual aids. However, in translating those NLST results, it needs to be understood that they were highly dependent on the design parameters of the study itself, namely 3 rounds of screening and 6.5 years of follow-up. When these parameters change so do the benefits. In the US, current recommendations for screening include annual screening over the period of eligibility for the participant (although for Canada it is restricted to 3 years). Under the circumstance of continued annual screening, the reduction in mortality begins to approach the estimated cure rate for the cancer. It is this feature of cure rate that is really what is most important to any person interested in being screened, and it is substantially higher than the mortality reduction seen in a randomized trial where by necessity the mortality reduction is diluted by the time interval after screening has stopped and cancers are still being followed, and also by not including those cancers that are relatively slow growing and cured as a result of early treatment but not counted towards the mortality reduction because the trial has concluded before their counterpart in the control arm has died. Based on these considerations, it is possible to have a cancer that is 100% curable when screen detected, yet the trial may only show a 20% (or even lower) mortality reduction. Thus, there is inherently no incompatibility between the 80% cure rate seen in the I-ELCAP compared with the 20% mortality reduction seen in the NLST. The simple conversion of the 20% mortality reduction found in NLST into a cure rate as is so commonly done when explaining the benefit to a person interested in screening is highly misleading. The cure rate, which is the clinically relevant feature, is higher. This coupled with the way in which harms are currently expressed, based again almost solely on those NLST results has the effect of amplifying harms at the same time the benefits are being underestimated and surely affect the perception of overall value of CT screening both for physicians as well as people who might be interested.

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      S01.07 - The U19 Plans for Integration of Biomarkers into Future Lung Cancer Screening (ID 11888)

      08:00 - 08:50  |  Presenting Author(s): Rayjean J. Hung, Paul Brennan, Christopher Ian Amos

      • Abstract
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      Abstract not provided

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      S01.10 - EU Position Statement on Lung Cancer Screening (ID 11891)

      09:00 - 09:20  |  Presenting Author(s): Matthijs Oudkerk

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      Abstract not provided

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      S01.14 - Coordination of the Lung Cancer CT Screening Experience (ID 11895)

      09:50 - 10:05  |  Presenting Author(s): Joelle Thirsk Fathi

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      S01.15 - Integration of Smoking Cessation into Lung Cancer Screening (ID 11896)

      10:05 - 10:20  |  Presenting Author(s): Kate Brain

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      S01.17 - Session V: Panel Discussion: Next Steps for Lung Screening? (ID 11898)

      10:30 - 11:30  |  Presenting Author(s): Claudia I Henschke, Kwun M Fong, Motoyasu Sagawa, Matthew Eric Callister, Nasser Altorki, Bruce Pyenson, Andrea Katalin Borondy Kitts

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      Abstract not provided

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      S01.18 - IASLC Leads the International Collaboration on Data Sharing (IASLC- ELIC-CCTRR) (ID 11899)

      11:30 - 11:50  |  Presenting Author(s): John Kirkpatrick Field, James L Mulshine

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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
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      S01.02 - Introductions & Welcome (ID 3628)

      07:00 - 12:00  |  Presenting Author(s): James L Mulshine, John Kirkpatrick Field

      • Abstract
      • Slides

      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.

      jk field figure for wclc ct symposium 2019 draft 11-6-19.jpg

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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.

      figure4lungrunwlc.jpg

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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

      • Abstract

      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

      • Abstract
      • Presentation
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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

      • Abstract

      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

      • Abstract
      • Presentation
      • Slides

      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
      • Slides

      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

      • Abstract

      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

      • Abstract
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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

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      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 high

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      S01.16 - Surgical Services (Now Available) (ID 3848)

      07:00 - 12:00  |  Presenting Author(s): Nasser K Altorki

      • Abstract
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      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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      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

      • Abstract
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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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      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

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      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.

      figure1.png

      Figure 1: The global distribution of the hub and spokes for the 2018 WCLC ELIC proof-of-concept demonstrations.

      figure2.png

      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

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      Abstract not provided

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