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Martin Ledson



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    P3.05 - Early Stage NSCLC (ID 721)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Early Stage NSCLC
    • Presentations: 1
    • Now Available
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      P3.05-001 - Breath Analysis for Early Detection of Lung Cancer: The LuCID Study (Now Available) (ID 10067)

      09:30 - 09:30  |  Author(s): Martin Ledson

      • Abstract
      • Slides

      Background:
      There is an urgent need for methods to detect lung cancer earlier. If detected early, over half of lung cancer patients could be cured with existing treatments. Therefore, our greatest opportunity lies in increasing rates of early diagnosis through improved cancer screening. Exhaled breath contains over 1,000 Volatile Organic Compounds (VOCs), which are the products of metabolic activity, hence they directly reflect the current state of cells and represent a valuable source of information about the health of an individual. As the earliest stages of tumour development are characterized by profound changes in cellular metabolic activity, VOCs are potential non-invasive biomarkers for early detection of lung cancer. The LuCID study aims to collect breath samples and evaluate VOCs in exhaled breath as non-invasive biomarkers for early detection of lung cancer.

      Method:
      LuCID is an international multi-centre prospective case-control cohort study (ClinicalTrials.gov ID NCT02612532) currently in progress, evaluating breath VOCs in patients with a clinical suspicion of lung cancer. A clinical suspicion is based on symptoms and/or suspicious finding on incidental imaging. Using tidal breathing, patients breathe into the ReCIVA Breath Sampler for 7 minutes to collect alveolar- and bronchial-enriched breath fractions on stable sorbent tubes for later analysis by Gas Chromatography-Mass Spectrometry and Field Asymmetric Ion Mobility Spectrometry (FAIMS, Owlstone Medical Ltd). A classification algorithm will be constructed from chemical spectral data, and undergo internal and external blinded validation to provide a ROC-curve detailing diagnostic accuracy. The LuCID study has an adaptive trial design, recruiting up to 2,600 patients depending on interim results.

      Result:
      The LuCID study has recruited 980 patients to date from 20 centres (mean age 67.5, SD 12.0). Of patients with completed follow-up (n=802), 33% have histologically confirmed lung cancer (of those with lung cancer: 40% early stage 1a-2b, 60% advanced stage 3a-4). Non Small Cell Lung Cancer (NSCLC) comprised 87% of these cancers, and Small Cell Lung Cancer 9%. NSCLC were further categorized as adenocarcinoma (50%), squamous cell carcinoma (38%), with the remaining 12% belonging to other categories.

      Conclusion:
      The LuCID study is evaluating the analysis of exhaled VOC biomarkers as a new diagnostic modality for early detection of lung cancer. Successful completion of the LuCID study will pave the way for the development of a non-invasive, easy-to-implement test that could markedly improve screening and early detection rates, reducing lung cancer morbidity and mortality.

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    WS 01 - IASLC Supporting the Implementation of Quality Assured Global CT Screening Workshop (By Invitation Only) (ID 632)

    • Event: WCLC 2017
    • Type: Workshop
    • Track: Radiology/Staging/Screening
    • Presentations: 2
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      WS 01.05 - How Do We Engage the High Risk Population in Lung Cancer Screening? - Primary Care Perspective in UK (ID 10643)

      09:10 - 09:17  |  Presenting Author(s): Martin Ledson

      • Abstract
      • Slides

      Abstract:
      Lung cancer is the commonest cancer and cause of cancer death in the UK, and Liverpool has over twice the national incidence. In addition, the city has high rates of socioeconomic deprivation, smoking, and respiratory morbidity. Most lung cancer patients present through clinical routes, but symptoms are poor at defining the disease: risk scores have low predictive values, and in Liverpool 75% of cases present at stage 3 or 4. National guidance (NICE) suggests clinical referral with a risk score >3%. Although screening is well established for breast, colon and cervical cancer (which are less prevalent and cause fewer deaths) there is no lung cancer screening program. Liverpool was one of the pilot sites for the United Kingdom Lung Screening Trial (UKLS), where 2.4% of patients entered locally had lung cancer with a resection rate of 83%. Following this, 2 local proposals were developed for risk-stratified case finding. The first, involving CT scans for the high risk cohort already attending secondary care sector clinics, was refused funding. The second, the ‘Liverpool Healthy Lung Project’ (LHLP) secured funding (£3.3M), started in April 2016, and is described below. Firstly, a series of coordinated focused public engagement ‘Healthy Lung Events’ were arranged in areas with a high lung cancer incidence, aimed at promoting positive messages around lung health, and addressing the fear and fatalism surrounding lung cancer Secondly, in localities of the highest lung cancer risk, from GP records all those age 58-70 with COPD, who smoke, or had asbestos exposure were invited to a face to face lung health check by a respiratory nurse who promotes positive lifestyle messages and calculates a 5-year personal lung cancer risk (www.MyLungRisk.org): those > 5% threshold were offered a low dose CT scan. In the first year 87 Healthy Lung Events attracted 1943 interactions and 813 completed spirometry of which 146 (18%) were abnormal, triggering a primary care consultation. 2911 (40%) of 7274 eligible individuals attended the lung health check, where 1107 (38%) were offered a CT scan: of 1064 performed, 414 (39%) were abnormal (102 [9.6%] lung nodules and 17 [1.6%] lung cancer (65% resected). 726 (44%) of the 1658 (57%) without previously diagnosed COPD had abnormal spirometry. In the UK the cost/benefit ratio is paramount and provisional analysis suggests that the LHLP costs £4000 per QUALY (COPD 63%, 22% Lung cancer, 15% smoking cessation). Extending the CT scan screen to include cardiac disease may improve this further. What has been learned so far from LHLP? The 40% uptake was lower than anticipated, but disadvantaged groups are the hardest to engage. “Ownership” of the project is important: eligible patients receive letters from their own GP, who also manages abnormal findings. The use of existing community networks, events and resources, and local advertising and promotion aids recruitment: although 25% attended after the first letter, a further 48% attended after a second letter and 27% after a follow-up telephone call, increasing participation by 300%. Texting is being introduced, and social marketing strategies (used in commercial marketing), with client profiling to determine the best ways to achieve contact are being considered. Lung health checks are face to face with the project nurse, occur locally (often in patient’s own GP practice), and are invaluable in health promotion (smoking cessation, diet, exercise), and defining spirometry and cancer risk score and often facilitate onward referral. Some of the targeted areas had high levels of mental illness and foreign language speakers, and the approach has been modified to engage more with these groups. The eligible age range has been extended to 75 years for the second year. Radiology report need to be clear: potential cancers are automatically managed by the local lung cancer team, and pulmonary nodules are managed within the project. Other reported abnormalities are referred back to the GP - a not insubstantial workload. Conclusions This innovative project has improved access to respiratory healthcare in a deprived area of Liverpool. Screening for both lung cancer and COPD, linked with health promotion has shown that economic viability is achievable. Fear and fatalism is common in respiratory disease, and this disadvantaged population is hard to engage. Lessons re engagement have been learned. The positive health messaging, and promotion of early diagnosis and curability of lung cancer can only bring benefits to both patients and the health care community.

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      WS 01.18 - Lung Cancer Indicator Detection Trial (LuCID) (ID 10656)

      11:45 - 12:00  |  Author(s): Martin Ledson

      • Abstract
      • Slides

      Abstract:
      Background There is an urgent need for methods to detect lung cancer earlier. If detected early, over half of lung cancer patients could be cured with existing treatments. Therefore, our greatest opportunity lies in increasing rates of early diagnosis through improved cancer screening. Exhaled breath contains over 1,000 Volatile Organic Compounds ﴾VOCs﴿, which are the products of metabolic activity, hence they directly reflect the current state of cells and represent a valuable source of information about the health of an individual. As the earliest stages of tumour development are characterized by profound changes in cellular metabolic activity, VOCs are potential non‐invasive biomarkers for early detection of lung cancer. The LuCID study aims to collect breath samples and evaluate VOCs in exhaled breath as non‐invasive biomarkers for early detection of lung cancer. Method LuCID is an international multi‐centre prospective case‐control cohort study ﴾ClinicalTrials.gov ID NCT02612532﴿ currently in progress, evaluating breath VOCs in patients with a clinical suspicion of lung cancer. A clinical suspicion is based on symptoms and/or suspicious finding on incidental imaging. Using tidal breathing, patients breathe into the ReCIVA Breath Sampler for 7 minutes to collect alveolar‐ and bronchial enriched breath fractions on stable sorbent tubes for later analysis by Gas Chromatography‐Mass Spectrometry and Field Asymmetric Ion Mobility Spectrometry ﴾FAIMS, Owlstone Medical Ltd﴿. A classification algorithm will be constructed from chemical spectral data, and undergo internal and external blinded validation to provide a ROC‐curve detailing diagnostic accuracy. The LuCID study has an adaptive trial design, recruiting up to 2,600 patients depending on interim results. Figure 1 Results The LuCID study has recruited 980 patients to date from 20 centres ﴾mean age 67.5, SD 12.0﴿. Of patients with completed follow‐up ﴾n=802﴿, 33% have histologically confirmed lung cancer ﴾of those with lung cancer: 40% early stage 1a‐2b, 60% advanced stage 3a‐4﴿. Non Small Cell Lung Cancer ﴾NSCLC﴿ comprised 87% of these cancers, and Small Cell Lung Cancer 9%. NSCLC were further categorized as adenocarcinoma ﴾50%﴿, squamous cell carcinoma ﴾38%﴿, with the remaining 12% belonging to other categories. Most recent data on study progress and results will be presented at the conference. Conclusion The LuCID study is evaluating the analysis of exhaled VOC biomarkers as a new diagnostic modality for early detection of lung cancer. Successful completion of the LuCID study will pave the way for the development of a non‐invasive, easy‐to‐implement test that could markedly improve screening and early detection rates, reducing lung cancer morbidity and mortality.



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