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A. McWilliams



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    MTE 21 - Early Detection of Central Airway Lesions: Biology and Practical Clinical Approaches (Ticketed Session) (ID 73)

    • Event: WCLC 2015
    • Type: Meet the Expert (Ticketed Session)
    • Track: Screening and Early Detection
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/08/2015, 07:00 - 08:00, 703
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      MTE21.01 - Early Detection of Central Airway Lesions: Biology and Practical Clinical Approaches (ID 2007)

      07:00 - 08:00  |  Author(s): A. McWilliams

      • Abstract
      • Presentation

      Abstract:
      Introduction: Lung cancer is highly curable if detected at an early stage. Screening with low dose CT (LDCT) has been shown to reduce lung cancer mortality, but largely detects peripheral tumours. Due to limitation of resolution, LDCT currently cannot detect early pre-invasive central lung cancers. Evaluation of the central bronchial tree remains important in populations where central squamous carcinoma remains a significant contributor to lung cancer incidence or in patients at high risk of developing synchronous or metachronous squamous cell cancers. Imaging Technology: The imaging modality most commonly used for evaluation of the central airways is white light flexible bronchoscopy (WLB). The ability of routine white light examination to detect small pre-invasive central lung cancer remains limited. A number of technological advances and development of alternative in vivo optical imaging modalities improve the detection and evaluation of central pre-invasive lesions. These techniques include high magnification WLB, autofluorescence imaging (AFB), narrow band imaging (NBI), optical coherence tomography (OCT), confocal microendoscopy/endocystoscopy and raman spectroscopy (RS). Management: There are multiple tools available to be used with a flexible bronchoscopic approach to treat pre-invasive central lung cancers once detected. These include endobronchial electrocautery, argon plasma coagulation, cryotherapy, photodynamic therapy, brachytherapy and laser therapy. Therapeutic outcomes are dependent on multiple factors but curative rates of >85-90% are achievable. Patients are at risk of recurrence or the development of metachronous lesions and require close surveillance. Summary: The detection of early central lung cancers often requires more sophisticated tools than conventional white light bronchoscopy. The multimodality utilisation of different technologies will enable the rapid detection and diagnosis of early curable central lung cancers in selected high-risk populations. There are multiple tools available for curative treatment of early central lung cancers. References 1. Sun J, Garfield DH, Lam B, et al. The value of autofluorescence bronchoscopy combined with white light bronchoscopy compared with white light alone in the diagnosis of intraepithelial neoplasia and invasive lung cancer: a meta-analysis. J Thorac Oncol 2011;6(8):1336-1344. 2. Lee P, van den Berg RM, Lam S, Gazdar A, Grunberg K, McWilliams A, LeRiche J, Postmus P, Sutedja T. Color fluorescence ratio for detection of bronchial dysplasia and carcinoma in situ. Clin Cancer Res 2009; 15:4700-4705. 3. Herth F, Eberhardt R, Anantham D, Gompelmann D, Zakaria M, Ernst A. Narrow-band imaging bronchoscopy increases the specificity of bronchoscopic early lung cancer detection. J Thorac Oncol, 2009;4:1060-1065. 4. Lam S, Standish B, Baldwin C, et al. In vivo optical coherence tomography imaging of preinvasive bronchial lesions. Clin Cancer Res. 2008; 14: 2006–2011. 5. Thiberville L, Salaun M, Lachkar S, Dominique S, Moreno-Swirc S, Vever-Bizet C, Bourg-Heckly G. Confocal fluorescence endomicroscopy of the human airways. Proc Am Thorac Soc, 2009;6:444-449. 6. Shibuya K, Fujiwara T, Yasufuku K, Mohamed Alaa RM, Chiyo M, Nakajima T, Hoshino H, Hiroshima K, Nakatani Y, Yoshino I. In vivo microscopic imaging of the bronchial mucosa using an endo-cystoscopy system. Lung Cancer, 2011;72:184-190. 7. Short M, Lam S, McWilliams A, Ionescu D, Zeng H. Using laser Raman spectroscopy to reduce false positives of autofluorescence bronchoscopy: A pilot study. JTO, 2011;6:1206-1214. 8. McWilliams A, Shaipanich T, Lam S. Fluorescence and Navigational Bronchoscopy. Thoracic Surgery Clinics, May 2013. 9. Wisnivesky J, Yung R, Mathur P, Zulueta J. Diagnosis and Treatment of Bronchial Intraepithelial Neoplasia and Early Lung Cancer of the Central Airways. Diagnosis and Management of Lung Cancer, 3[rd] Edition, ACCP Guidelines. Chest, 2013;143 (5)(Suppl):e263S-e277S. 10. McWilliams. Clinical Applications in the Lung. In: Diagnostic Endsocopy: Series in Medical Physics and Biomedical Engineering. Eds. Zeng, H. Taylor & Francis Group 2014:pp209-220.

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    ORAL 23 - Prevention and Cancer Risk (ID 121)

    • Event: WCLC 2015
    • Type: Oral Session
    • Track: Prevention and Tobacco Control
    • Presentations: 1
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      ORAL23.01 - A Randomized Phase IIb Trial of Myo-Inositol in Smokers with Bronchial Dysplasia (ID 856)

      10:45 - 12:15  |  Author(s): A. McWilliams

      • Abstract
      • Presentation
      • Slides

      Background:
      Previous preclinical studies and a phase I clinical trial suggested myo-inositol may be a safe and effective lung cancer chemopreventive agent. We conducted a randomized, double blind, placebo-controlled, phase IIb study to determine the chemopreventive effects of myo-inositol in smokers with bronchial dysplasia.

      Methods:
      Smokers with ≥1 site of dysplasia identified by autofluorescence bronchoscopy-directed biopsy were randomly assigned to receive oral placebo or myo-inositol, 9 g once/day for two weeks, and then twice/day for 6 months. The primary endpoint was change in dysplasia rate after six months of intervention on a per participant basis. Other trial endpoints reported herein include Ki-67 labeling index and pro-inflammatory, oxidant/anti-oxidant biomarker levels in blood and bronchoalveolar lavage fluid (BAL).

      Results:
      Seventy four (n=38 myo-inositol, n=36 placebo) participants with a baseline and 6-month bronchoscopy were included in all efficacy analyses. The complete response and the progressive disease rates were 26.3% versus 13.9% and 47.4% versus 33.3%, respectively, in the myo-inositol and placebo arms (p=0.76). The mean percent change in Ki67 labeling index in bronchial biopsies with dysplasia was -22.8% and -6.2%, respectively, in the myo-inositol and placebo arms (p=0.34). Compared with placebo, myo-inositol intervention significantly reduced IL-6 levels in BAL over 6 months (p=0.03) and had borderline significant effects on BAL myeloperoxidase (p= 0.06) level.

      Conclusion:
      The heterogeneous response to myo-inositol suggests a targeted therapy approach based on molecular alterations is needed in future clinical trials to determine the efficacy of myo-inositol as a chemopreventive agent.

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