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S. Couraud



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    O18 - Cancer Control and Epidemiology II (ID 133)

    • Event: WCLC 2013
    • Type: Oral Abstract Session
    • Track: Prevention & Epidemiology
    • Presentations: 2
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      O18.03 - The BioCAST / IFCT-1002 study: a comprehensive overview of demographic, risk exposure and somatic mutations of non-small cell lung cancer occurring among French never smokers (ID 3293)

      10:30 - 12:00  |  Author(s): S. Couraud

      • Abstract
      • Presentation
      • Slides

      Background
      Lung cancer occurring in never-smoker (LCINS) is a particular entity. Although the definition is strict (less than 100 cigarette in lifetime) never-smokers are frequently misclassified and no study gives a comprehensive analysis of this group, particularly in a European setting.

      Methods
      All consecutive never-smoker patients diagnosed with a non-small cell lung cancer in one of the 75 participating centers throughout France, between November 2011 and January 2013, were included in this prospective survey. All patients underwent a detailed questionnaire supported by a trained staff during a phone interview. Somatic mutations and cancer clinical and histological data were also recorded from medical charts.

      Results
      Overall, 384 never-smokers were included and 336 interviews were completed. Most of them were women (n=319, 83.1%). The mean age at diagnosis was 69.8 ± 12.02 and 10.9% were under 55 years-old. None reported alternative smoking (pipe, cigar, water-pipe, gum, or cannabis). Most of them originated from Western and Southern Europe (90.5%). Overall, 219 (65.6%) reported a passive smoking exposure in a domestic setting (n=198; 59.3%), and/or at workplace (n=60; 18.0%). Patients had a personal history of pneumonia in 6.2%, tuberculosis in 8.3%, COPD in 13.0%, and a cancer at another site in 16.6%. Eighty patients reported at least two relatives with lung cancer (24.0%). Definite occupational exposure was observed in 12.0% (n=44) for diesel, 7,1% (n=26) for asbestos, 3.3% (n=12) for poly-aromatic hydrocarbons, 2.4% (n=9) for silica, 0.8% (n=3) for chrome, and 0.5% (n=2) for painting. Exposure to cooking oil was noted in 123 patients (36.8%) with a mean of 49.4 ± 356.7 cooking-dish year. Moreover, 79.7% (n=259) patients were ever exposed to solid fuel fumes for cooking or heating (21.2% during more than 50% of their lifetime). Among women, 91.7% already reached menopause (mean age 49.3 ± 5.6 years-old), 115 (41.7%) were ever-exposed to oral contraceptive (mostly oestrogen-containing drugs), and 25.5% to post-menopause hormone replacement therapy (oral or transdermal). Most of lung cancers were adenocarcinoma (n=327, 85.2%) followed by squamous cell carcinoma (n=29, 7.6%) and large cell carcinoma (n=17; 4.4%). Among adenocarcinoma, 71% were invasive, 4% in-situ, 2% minimally-invasive, 2% variant of invasive, and 20.0% were NOS. Cancer stage was I in 9.2%, II in 5.8%, III in 11.8% and IV in 73.2%. At least one biomarker was tested in 359 patients (93.5%). We found 148 patients with EGFR mutations (43.5% out of the EGFR-tested patients), 20 with KRAS mutations (6.8%), 24 with ALK translocation (12.5%), 10 with BRAF mutation (4.5%), 8 with HER2 mutation (4.0%) and 4 with PIK3CA (2.1%). Overall, 27.0% samples remain wild type, 2.1% with multiple mutations, 71.0% with a single mutation, and 20.6% with missing data.

      Conclusion
      We provide here the largest cohort of LCINS in a European setting with reliable data on tobacco intoxication, occupational exposure, and hormonal treatments, since collected by a trained staff through phone interview. In this perfectly clinically characterized cohort, molecular analyses showed that 72% of tumors exhibited oncogenic targetable mutations.

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      O18.04 - Impact of Passive Smoking on molecular pattern in Never Smokers with Non-Small Cell Lung Cancer: Findings from the BioCAST / IFCT-1002 Study (ID 3305)

      10:30 - 12:00  |  Author(s): S. Couraud

      • Abstract
      • Presentation
      • Slides

      Background
      EGFR and HER2 mutations are usually associated with never-smokers while KRAS and BRAF mutations are thought to be link with smoking behavior in Non-Small Cell Lung Cancer (NSCLC). Passive smoking exposure is a well-known risk factor for lung cancer. Only EGFR and KRAS mutations were investigated in association with passive smoking and showed conflicting results. We aimed to investigate mutation rate of EGFR, HER2, KRAS, BRAF and ALK in a cohort of never smokers regarding their passive smoke exposure.

      Methods
      The BioCAST / IFCT-1002 study is a prospective cohort of NSCLC patients diagnosed in French never-smokers patients (less than 100 cigarettes in lifetime) between November 2011 and January 2013, Passive smoking exposure was evaluated through standardized questionnaire. We obtained biomarkers mutation results through routine testing. We used Fisher, Chi-square, median test and Mann-Whitney U test for comparisons as appropriate. We used logistic regression to calculate adjusted odds ratio for risk of each mutations.

      Results
      Out of the 384 patients included in the BioCAST database, 334 (87.0%) had available data on passive smoking exposure. Among them, 219 patients (65.6%) were ever exposed to passive smoking in their lifetime. 198 (59.3%) reported a domestic exposure (122 during childhood at least) and 60 (18.0%) a workplace exposure. Result of at least one biomarker mutation was available in 313 patients (93.7%). including 128 EGFR mutations in 297 patients, 8/174 HER2 mutations, 18/256 KRAS mutations, 10/196 BRAF mutations, and 20/171 ALK gene rearrangements. We found no difference in mutation rate according to passive smoke exposure (cf. Table 1). There was no difference when comparing cumulative year of exposure, smoker-year or passive-pack year (as continuous variable) to the mutation rate, for any biomarker. When considered as categorical variable – after division in quartiles – we found also no difference. Results were similar when focusing on domestic (childhood versus adulthood included) and workplace exposure only. Finally, we found no significant increased risk for mutation for any biomarker in logistic regression adjusted for most of other lung cancer risk factors.

      EGFR Mt (n=297) HER2 Mt (n=171) KRAS Mt (n=256) BRAF Mt (n=196) ALK Fusion (n=171)
      % % % % %
      Overall exposure Never 46.5 3.5 6.7 5.9 13.0
      Ever 41.3 5.1 7.2 4.7 11.1
      Domestic exposure Never 45.8 2.9 7.7 6.4 11.1
      Ever 41.3 5.7 6.6 4.2 12.0
      Exposure at workplace Never 43.3 5.5 7.0 5.4 12.2
      Ever 42.3 0 7.0 3.6 8.3
      Total 43.1 4.6 7.0 5.1 11.7
      Exposure in childhood Ever 40.5 3.0 6.5 2.7 14.7
      Only in adulthood 42.6 10.3 6.8 6.7 7.5

      Conclusion
      Although we report the largest and more comprehensive study focusing on this topic, we found no significant difference in the biomarker mutation profile of NSCLC occurring in French never-smokers regarding their exposure to passive smoking as compared with the pattern of mutations described never-smoker patients with any passive smoking.

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