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F. Duan



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    MINI 23 - Lung Cancer Risk: Genetic Susceptibility and Airway Biology (ID 135)

    • Event: WCLC 2015
    • Type: Mini Oral
    • Track: Screening and Early Detection
    • Presentations: 1
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      MINI23.02 - COPD Severity by GOLD Status and Lung Cancer Risk: Results from a Large Prospective Screening Study (NLST-ACRIN Cohort Analysis, N=18, 714) (ID 865)

      16:45 - 18:15  |  Author(s): F. Duan

      • Abstract
      • Slides

      Background:
      Epidemiological studies consistently show that chronic obstructive pulmonary disease (COPD) is associated with an increased risk of lung cancer among smokers. However, debate exists as to whether there is a linear relationship between the severity of COPD and risk of lung cancer. The National Lung Screening Study (NLST) and it’s sub-study by the American College of Radiology and Imaging Network (ACRIN), provides the means to re-examine these findings. We examined the effect of spirometry-defined COPD (according to GOLD status at baseline), on the risk of lung cancer in the NLST-ACRIN cohort (according to lung cancer incidence), in a large prospective lung cancer screening study of high risk smokers.

      Methods:
      In the NLST-ACRIN cohort of 18,475 screening participants eligible for the NLST, 6,436 screening participants had COPD (35%) according to baseline pre-bronchodilator spirometry and were followed for a mean of 6.4 years. From this group, 401 lung cancer cases were identified. The 6,436 screening participants with COPD were sub-grouped according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages 1 (N=1607), 2 (N=3528), 3 (N=1083) and 4 (211). Lung cancer incidence at the end of follow-up was compared between the GOLD subgroups and those with normal spirometry (N=12,039).

      Results:
      Compared to those with normal spirometry, where the lung cancer incident rate was 4.63/1000 person years, the lung cancer incident rate was 7.58/1000 person years for GOLD 1, 9.43/1000 person years for GOLD 2, 12.7/1000 person years for GOLD 3 and 15.55/1000 person years for GOLD 4 (all P<0.0001). The lung cancer histology was significantly different, with more squamous and non-small cell cancers in those with COPD but more adenocarcinoma and Bronchoalveolar carcinoma in those with normal lung function (P<0.004). Figure 1



      Conclusion:
      In a large prospective study of unselected high risk smokers with and without COPD, we report a strong linear association between increasing severity of COPD and increasing lung cancer risk (incidence). This suggests that the risk of lung cancer is greatest in those with the most severe COPD and 3-4 fold greater than those with normal lung function. We also report that lung cancers of more aggressive histology were more common in those with COPD. Funding This study was funded by a grant from Johnson and Johnson and grants U01-CA-80098 and U01-CA-79778 to the American College of Radiology Imaging Network

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    ORAL 24 - CT Detected Nodules - Predicting Biological Outcome (ID 122)

    • Event: WCLC 2015
    • Type: Oral Session
    • Track: Screening and Early Detection
    • Presentations: 1
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      ORAL24.06 - Stratification of Lung Adenocarcinomas in the National Lung Screening Trial (ID 102)

      10:45 - 12:15  |  Author(s): F. Duan

      • Abstract
      • Presentation
      • Slides

      Background:
      Screening for lung cancer with low-dose computed tomography (LDCT) was shown to reduce lung cancer mortality. However, lung cancer screening also detects indolent cancers of unclear clinical significance, which generally belong to the adenocarcinoma spectrum. The individualized management of these more indolent cancers may be facilitated by non-invasive risk stratification. We present our validation study of CANARY (Computer-Aided Nodule Assessment and Risk Yield), a novel LDCT-based software, used to stratify adenocarcinoma nodules in three groups with distinct outcomes.

      Methods:
      All individuals in the LDCT arm of the National Lung Screening Trial (NLST) with adenocarcinoma were identified. The last LDCT data available were analyzed blinded to clinical data. Using CANARY, all lung adenocarcinoma nodules were classified as Good (G), Intermediate (I) and Poor (P) based on previously established radiologic signatures. This classification was then used for survival analysis using progression-free survival

      Results:
      LDCT datasets of 294 patients with resected adenocarcinomas with available outcome data were included in the blinded CANARY analysis. Kaplan-Meier analysis of all the 294 adenocarcinoma nodules stratified into G, I and P CANARY classes yielded distinct progression-free survival curves (P < 0.0001). A similar separation was seen with adjusted progression-free survival curves, after adjustment for, age, gender, race and smoking status for all pathological stage I cases.

      Conclusion:
      CANARY allows the non-invasive risk stratification of lung adenocarcinomas into three groups with distinct post-surgical disease-free survival. Our results suggest that CANARY could facilitate individualized management of incidentally- or screen-detected lung adenocarcinomas.

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    P3.06 - Poster Session/ Screening and Early Detection (ID 220)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Screening and Early Detection
    • Presentations: 1
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      P3.06-002 - Favourable Stage-Shift Limited to Screening Participants with COPD in a Biomarker Sub-Study of the National Lung Screening Trial (NLST) (ID 873)

      09:30 - 17:00  |  Author(s): F. Duan

      • Abstract
      • Slides

      Background:
      Based on a 20% reduction in lung cancer deaths in participants of the National Lung Screening Trial (NLST), CT screening for lung cancer is now widely recommended in the US. However concerns remain regarding the cost-benefits of screening due to overall low detection rates, over-diagnosis and high false-positive rates. Using the spirometric data available from the ACRIN-biomarker sub-study of the NLST (n=18,714), we examined the effect of Chronic Obstrucitve Pulmonary Disease (COPD) status on lung cancer detection in the NLST screening participants. Specifically we compared lung cancer incidence, histology and stage shift in those with and without COPD based on baseline pre-bronchodilator spirometry.

      Methods:
      Baseline spirometry results were available for 18,475 (99%) of the total cohort of 18,714, (6,436 with COPD and 12,039 with no COPD). Spirometry results were available for 758 (99%) of the 768 histology-confirmed lung cancer cases diagnosed over the 7 year follow-up period. After lung cancer cases were sub-grouped by spirometry-defined COPD (GOLD 1-4, n=401) and no baseline COPD (n=357) it was possible to compare the number of cancers, histology and stage according to screening arm. Differences in lung cancer incidence rates were compared by incident rate ratios, while prevalence, histology and stage shift, were compared by chi-square frequency tables.

      Results:
      In this NLST-ACRIN Biomarker sub-study, we found the demographic variables were comparable to those from the full NLST study. Regardless of screening interval, we found the lung cancer incidence was 2 fold greater in those with COPD compared to no COPD (P<0.0001). In those with COPD, we found a signficant reduction in adenocarcinomas and bronchioloalveolar carcinomas. After stratification by COPD status, when comparing CT versus CXR screening arms, we found no excess lung cancers and comparable lung cancer histology. However, a clinically significant stage shift favouring increased early stage (+17) and reduced late stage cancers (-23) was found (P=0.05). In contrast, in cancer cases with no COPD, we found an 18% excess of lung cancers in the CT arm (+29) which were of a BAC/AC histology. After correction for this overdiagnosis from these excess cancers, the stage shift no longer favoured early stage over late stage. Figure 1



      Conclusion:
      These data suggest that in those with COPD at baseline, CT screening (vs CXR) was associated with no excess cancers, no histology shift but a clinically significant stage shift favouring early over late stage cancers. In those with no COPD, CT was associated with excess cancers and a marginal stage shift.

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