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J. Margery



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    O18 - Cancer Control and Epidemiology II (ID 133)

    • Event: WCLC 2013
    • Type: Oral Abstract Session
    • Track: Prevention & Epidemiology
    • Presentations: 1
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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): J. Margery

      • 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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    P3.14 - Poster Session 3 - Mesothelioma (ID 197)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Mesothelioma
    • Presentations: 1
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      P3.14-001 - Assessing the role of chemotherapy for solitary fibrous tumors of the pleura in a routine practice setting (ID 306)

      09:30 - 16:30  |  Author(s): J. Margery

      • Abstract

      Background
      Solitary Fibrous Tumors of the Pleura (SFTP) refer as to a heterogeneous group of mesenchymal malignancies with various anatomic and histologic features. Upfront surgical resection is the standard approach, but the outcome of patients is unpredictable. Recurrences may be aggressive and difficult to treat.The most widely accepted staging system has been proposed by De Perrot et al., and is based on the anatomy of the tumor implantation (sessile/pedunculated), and the presence of histologic signs of aggressiveness, including cellularity with crowding and overlapping of nuclei, cellular pleomorphism, high mitotic count, necrosis, or stromal/vascular invasion. Given the rarity of the tumor, limited evidence is available about the role and the modalities of perioperative and definite chemotherapy for SFTP.

      Methods
      Multicenter retrospective study of patients (pts) with histologically-proven SFTP with complete follow-up from surgical diagnostic to tumor recurrence and death.

      Results
      68 pts (28 males/40 females) were included. Median age at diagnosis was 62 year-old. Tumor stage according to the De Perrot system was 0/I for 29 pts, II for 23 pts, III for 7 pts, and IV for 4 pts. Adjuvant chemotherapy was given to 7 patients, mostly with stage III/IV SFTP, consisting of doxorubicin-based regimen. Recurrence rate and median time-to-progression (TTP) after surgery were 3%, 52%, 71%, and 75% (p<0.001), and 107, 70, 29, 11 months (p=0.006) for stage 0/I, II, III, and IV tumors, respectively. Besides tumor stage, predictors of shorter TTP were incomplete resection (p<0.001) and a higher number of histologic signs of malignancy (p=0.009). At time of tumor recurrence, 12 pts received chemotherapy. Highest disease control rates were observed with trabectedine (7/9 pts; Disease Control Rate (DCR): 78%; median TTP: 3,4 months), and gemcitabine-dacarbazine combination (2/3 pts, DCR: 66%; median TTP: 1,9 months). Median overall survival of the whole cohort was 56 months.

      Conclusion
      This study 1) confirms the prognostic value of the De Perrot staging system, 2) indicates a high recurrence rate in patients with stage II tumors, for which perioperative chemotherapy may be considered, and 3) suggests an interest for trabectedine in the setting of recurrent tumors. Besides clinical data, further molecular characterization, including recently identified specific gene fusions, may help to better predict the outcome of patients with SFTP.