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Annette Maree McWilliams



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    IBS30 - Risk Assessment in CT Screening (Ticketed Session) (ID 61)

    • Event: WCLC 2019
    • Type: Interactive Breakfast Session
    • Track: Screening and Early Detection
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/10/2019, 07:00 - 08:00, Seoul (2007)
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      IBS30.01 - Risk Assessment to Establish Screening Programs: The Australian Point of View (Now Available) (ID 3408)

      07:00 - 08:00  |  Presenting Author(s): Annette Maree McWilliams

      • Abstract
      • Presentation
      • Slides

      Abstract

      AustraIia has a multicultural community of 25 million people. (1) The ethnic background of Australians is predominantly Caucasian (83.6%) with 5.2% Chinese ancestry and 2.8% Indigenous Australian in 2016 census data.(1) It has one of the lowest current smoking rates in the world with only 14% of people >18 years being current smokers in 2017-2018.(2) Despite this, lung cancer remains the greatest cause of cancer death for women and men and is the fourth leading cause of all deaths in Australia. (2,3) Lung cancer cases continue to increase due to a variety of reasons including our growing and ageing population and the lag time between the tobacco epidemic and lung cancer occurrence.(4) Lung cancer rates in Indigenous Australians are approximately double compared to non-Indigenous Australians.(4)

      Overall, the majority of lung cancer in Australia is attributable to tobacco exposure but 20% of lung cancer occurs in never smokers.(4) There are known gender differences with ~90% of lung cancer in men attributable to tobacco exposure but only ~75% in women. (4) Other occupational exposures play an important role in lung cancer in Australia, with asbestos being one of the most important toxins contributing to lung cancer incidence.(1) A large longitudinal screening program in asbestos exposed individuals (>1700 participants) is ongoing in Western Australia, the Asbestos Review Project. The project has been utilising low dose chest computed tomography (CT) screening since 2012. Lung cancer rates in this cohort are similar to a high-risk smoking cohort despite lower tobacco exposures. The use of current screening enrolment criteria (USPSTF/NCCN) would have resulted in most lung cancer cases being missed. (5)

      Population based screening programs in Australia have been implemented for cervical, breast and bowel cancers but currently there is no national screening program for lung cancer. A proposed screening program must meet the Australian Screening Framework established in 2008 and be endorsed by the Standing Committee on Screening and the Australian Health Minister’s Advisory Council. (6) In their last published statement in 2015, implementation of a national program has not been supported.(7) The definition of the appropriate population to screen and the likely uptake of screening requires further evaluation in the Australian population.The reduction in mortality from lung cancer screening only occurs in those at high risk so the delineation of this cohort is crucial for minimisation of harm and a cost-effective program.(8) International work evaluating various risk prediction models to define the population that would most benefit from lung cancer screening have been published. (8,9)

      The performance of one of the most well validated models, the PLCOM2012 , has been retrospectively evaluated in the Australian population in a subset of the 45 and Up study.(10) In this large longitudinal cohort, 95 882 ever smokers, >45 years were included in the analysis. The predictive power of the PLCOM2012 risk model was assessed compared to other potential lung cancer screening enrolment criteria (NLST, USPSTF). This study showed that the risk model, although derived from a North American population, performed equally as well in the Australian population. It would reduce the proportion of ever smokers >55 years, potentially eligible for screening to ~29%. However, only 2% of the cohort were of Asian ancestry and 1.6% Indigenous Australian.

      The PLCO risk prediction model has been utilised prospectively in the PanCanadian study and further prospective validation is ongoing in Australia, Canada and Hong Kong in the International LungScreen Trial (ILST). The further refinement of a risk prediction model incorporating occupational/environmental carcinogen exposures such as asbestos and ethnicity is needed to further improve risk assessment for lung cancer screening.

      Supported by National Health and Medical Research Council and Cancer Australia.

      References:

      1. Australian Bureau of Statistics. 3101.0-Australian Demographic Statistics, Sep 2018. Dataset: 2016 Census-Cultural Diversity in Australia. Cited 7 June 2019

      2. Cancer in Australia 2019. https://www.aihw.gov.au/reports/cancer/cancer-in-australia-2019

      3. Deaths in Australia, Leading causes of death. https://www.aihw.gov.au/reports/life-expectancy-death/deaths-in-australia/contents/leading-causes-of-death

      4. Making Lung Cancer a fair fight: a blueprint for reform. Lung Foundation Australia, October 2018. https://lungfoundation.com.au/wp-content/uploads/2018/10/Information-paper-Making-Lung-Cancer-A-Fair-Fight-A-Blueprint-for-Reform-Oct2018.pdf

      5. Harris E, Murray C, Adler B, Ho A, Kong K, Reid A, Franklin P, De Klerk N, Musk A, Brims F. Malignant and non-malignant findings from 5 years of Low dose CT scans screening for lung cancer in the Western Australian Asbestos Review Program. American Thoracic Society Meeting 2019, Dallas, Texas, USA: Abstract 1001.

      6. http://www.cancerscreening.gov.au/internet/screening/publishing.nsf/Content/population-based-screening-framework

      7. http://www.cancerscreening.gov.au/internet/screening/publishing.nsf/Content/lung-cancer-screening

      8. Kovalchik SA, Tammemagi M, Berg CD, et al. Targeting of low-dose CT screening according to the risk of lung-cancer death. The New England journal of medicine2013;369(3): 245-54.

      9. Tammemagi MC, Katki HA, Hocking WG, Church T, Caporaso N, Kvale P, et al. Selection criteria for lung-cancer screening. N Engl J Med 2013;368:728-36.

      10. Weber M, Yap S, Goldsbury D, Manners D, Tammemagi M, Marshal H, Brims F, McWilliams A, Fong K, Kang, YJ, Carauna M, Banks E, Canfell K. Identifying high risk individuals for targeted lung cancer screening: independent validation of the PLCOm2012risk prediction tool. Int Journal of Cancer, 2017;141(2):242-253.

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    MA10 - Emerging Technologies for Lung Cancer Detection (ID 129)

    • Event: WCLC 2019
    • Type: Mini Oral Session
    • Track: Screening and Early Detection
    • Presentations: 2
    • Now Available
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      MA10.01 - Invasive Adenocarcinoma in Screen Detected Pure Ground-Glass Nodules (GGN) (Now Available) (ID 2736)

      15:15 - 16:45  |  Author(s): Annette Maree McWilliams

      • Abstract
      • Presentation
      • Slides

      Background

      A major criticism of lung cancer screening initiatives is their propensity to instigate enhanced surveillance and over-treatment of otherwise indolent disease, including adenocarcinoma-in-situ (AIS). These nodules present radiographically as GGN. There are wide variations in the recommendations for surveillance (repeat imaging), diagnosis (biopsy) and therapeutic intervention (resection) for these lesions. To further our understanding of the optimal management of screen detected GGN, we used data from two screening studies in Canada with up to 17 years of follow-up to determine the proportion of persistent GGN that are invasive adenocarcinomas.

      Method

      Two lung cancer screening studies data sets were reviewed: the BC Lung Health Study (BCLHS) with 1365 participants and the Pan-Canadian Early Detection of Lung Cancer Study (PanCan) with 2537 participants. BCLHS enrolled ever smokers 45-74 years of age with >30-year smoking history. The median follow-up in this cohort was 12 years (0.1-17.6) The PanCan study screened participants age 50-75 years with a PLCOm2008 6-year lung cancer risk > 2%. The median follow-up was 5.5 years (3.2-6.1). The nodules were followed until they resolved, demonstrated stability for >2 yrs or were surgically resected. All pure GGO resected were re-reviewed and classified by two pulmonary pathologists according to the revised 2015 World Health Organization classification of lung tumours. Cancers were staged using the 8th edition of the AJCC/UICC cancer staging manual.

      Result

      A total of 18,589 nodules in 3902 participants were reviewed. 2392 (13% of all nodules) were classified as pure GGN. 1073 of the 2392 were > 5mm at the baseline scan. Of these 1073 GGN, 156 (15%) resolved, 879 (82%) remained pure GGN, 38 (3.5%) became part-solid or solid. 32(3%) of the GGN from 29 patients that demonstrated growth were resected. The median size prior to resection was 16 mm (range 7 to 33 mm). The histopathology distribution included: 19 invasive adenocarcinomas, 7 minimally invasive adenocarcinomas, 6 adenocarcinoma-in-situ. The TNM stage distribution and average size of the GGN on the CT prior to resection are listed in Table 1. Sixty-one percent of the invasive cancers (Stage IA1 to IIIA) were less than 20 mm. Eleven percent of the invasive adenocarcinomas had lymph node metastasis.

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      Conclusion

      A high proportion of pure GGN that demonstrate growth are invasive cancers. The majority were < 20mm in size when they were resected. This has significant implication in the development of recommendations to manage screen detected GGN.

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      MA10.09 - Evaluation of the Clinical Utility of the PanCan, EU-NELSON and Lung-RADS Protocols for Management of Screen Detected Lung Nodules at Baseline (Now Available) (ID 2137)

      15:15 - 16:45  |  Author(s): Annette Maree McWilliams

      • Abstract
      • Presentation
      • Slides

      Background

      Several protocols are available to guide management of lung nodules identified by the first (baseline) low-dose screening CT. It is important to objectively assess their clinical utility, health care resource utilization and potential harms. We aim to compare the PanCan (NEJM 2013;369:908 & J Thorac Oncol 2018; 13(10): S362-S363), EU-NELSON (Lancet Oncol. 2017 Dec;18(12):e754-e766 & Lung Cancer 2006;54:177-184) and Lung-RADS(https://www.acr.org/Clinical-Resources/Reporting-and-Data-Systems/Lung-Rads) lung nodule management protocols on our data set from two sites of the International Lung Screen Trial (ILST), in Vancouver, Canada and Perth, Western Australia.

      Method

      Ever smokers age 55 to 80 years were enrolled into ILST if they had a ≥30 pack-years smoking history and smoked within 15 years or if their PLCO m2012 6 year lung cancer risk was ≥1.51%. The participants were managed via the PanCan lung nodule risk based protocol. The NELSON and Lung-RADS nodule protocols were applied to the ILST data set. The potential difference in the proportion of the participants having an early recall CT scan (< 1 year) or referral to a clinical diagnostic pathway was compared between the PanCan, NELSON, Lung-RADS protocols. The participants were divided into 3 groups: Group 1 (next scheduled annual/biennial CT) included PanCan CAT 1, 2, NELSON NODCAT I, II, Lung-RADS CAT 1, 2. Group 2 (early recall CT <1 year) included PanCan CAT 3, NELSON NODCAT III, Lung-RADS CAT 3, 4A and Group 3 (Diagnostic Pathway) included PanCan CAT 4, 5, NELSON NODCAT IV (solid nodule), Lung-RADS CAT 4B, 4X. The number of participants and the lung cancer rate in each group was compared between the three protocols.

      Result

      A total of 1386 participants with a median follow-up of 10 months (ranging from 4-31 mos) were evaluated. The results are shown in Table 1.

      PanCan selected the fewest individuals to early recall (Group 2 & 3) versus NELSON p=0.004 and detected the same number of lung cancers as did the NELSON and more than by Lung-RADS.

      In addition, 81% of the PanCan group 1 participants were triaged to biennial repeat screening instead of annual screening in the NELSON and Lung-RADS protocols, which has substantial resource utilization and radiation exposure implications.

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      Conclusion

      The personalized risk-based PanCan Protocol may decrease resource utilization and potentially minimize risk of screening for participants.

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    PL02 - Presidential Symposium including Top 7 Rated Abstracts (ID 89)

    • Event: WCLC 2019
    • Type: Plenary Session
    • Track:
    • Presentations: 1
    • Now Available
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      PL02.02 - Lung Cancer Screenee Selection by USPSTF Versus PLCOm2012 Criteria – Interim ILST Findings (Now Available) (ID 2804)

      08:00 - 10:15  |  Author(s): Annette Maree McWilliams

      • Abstract
      • Presentation
      • Slides

      Background

      The National Lung Screening Trial showed that lung cancer screening of high-risk individuals with low dose computed tomography can reduce lung cancer mortality by 20%. Critically important is enrolling high-risk individuals. Most current guidelines including the United States Preventive Services Task Force (USPSTF) and Center for Medicare and Medicaid Services (CMS) recommend screening using variants of the NLST eligibility criteria: smoking ≥30 pack-years, smoking within 15 years, and age 55-80 and 55-77 years. Many studies indicate that using accurate risk prediction models is superior for selecting individuals for screening, but these findings are based on retrospective analyses. The International Lung Screen Trial (ILST) was implemented to prospectively identify which approach is superior.

      Method

      ILST is a multi-centred trial enrolling 4000 participants. Individuals will be offered screening if they are USPSTF criteria positive or have PLCOm2012 model 6-year risk ≥1.5%. Participants will receive two annual screens and will be followed for six years for lung cancer outcomes. Individuals not qualifying by either criteria will not be offered screening, but samples of them will be followed for lung cancer outcomes. Outcomes in discordant groups, USPSTF+ve/PLCOm2012-ve and PLCOm2012+ve/USPSTF-ve, are informative. Numbers of lung cancers and individuals enrolled, sensitivity, specificity and positive predictive values (PPV) of the two criteria will be compared.

      Result

      As of March 2019, ILST centers in Canada (British Columbia), Australia, Hong Kong, and the United Kingdom had enrolled and scanned 3673 individuals. Study results are summarized in Figure 1.

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      Conclusion

      Interim analysis of ILST data, indicates that classification accuracy of lung cancer screening outcomes support the PLCOm2012 criteria over the USPSTF criteria. The PLCOm2012 criteria detected significantly more lung cancers. Individuals who are USPSTF+ve and PLCOm2012-ve appear to be at such low baseline risk (0.2%) that they may be unlikely to benefit from screening.

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