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S. Knight



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    O28 - Endoscopy (ID 124)

    • Event: WCLC 2013
    • Type: Oral Abstract Session
    • Track: Pulmonology + Endoscopy/Pulmonary
    • Presentations: 1
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      O28.07 - Intra-operative scanning confocal endomicroscopy of pleural disease: in vivo diagnosis of malignancy (ID 2977)

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

      • Abstract
      • Presentation
      • Slides

      Background
      The intra-operative diagnosis of pleural malignancy may facilitate surgical decision-making including the need for pleurodesis. A scanning laser confocal endomicroscopy device has been developed which allows histological-detail optical imaging of subsurface tissues in vivo. Confocal laser microscopy illuminates and detects light from a fixed point of a specimen which is scanned across a tissue plane and adjustable depths, providing a 3D structural view in a living body. Applied to screening of mucosal lesions in patients undergoing GI endoscopy, endomicroscopy obviates the need for many tissue biopsies and operators can rapidly learn to identify malignant tissues.

      Methods
      We performed the first intra-operative examination of pleural tissues using this equipment which is a thoracoscope-mounted endomicroscope device in patients administered iv fluorescein prior to imaging. Intra-operative endomicroscopic images were correlated with biopsies of pleural tissues.

      Results
      Sixteen patients were imaged: including mesothelioma 5 (2 biphasic) and pleural metastases from malignancies of lung 2, ovary 2 and one case each of breast, adenoidcystic (see figure), thyroid, colorectal, carcinoid and non-Hodgkin’s lymphoma, and also one benign case. We were able to image and identify normal mesothelium, sub-mesothelium, connective tissues and blood vessels (including RBC). Malignant cells and clusters of cells had a characteristic appearance including poor uptake of fluorescein and cellular pleomorphism. Appearances of mesothelioma correlated closely with histology. Glandular and papillary structures were identified in metastatic pleural tumour. In ovarian cancer calcification was readily identified as were psammoma bodies, while the typical cystic spaces surrounded by small dark cells mirrored closely the histological appearances of adenoidcystic carcinoma.

      Conclusion
      Images obtained on scanning confocal endomicroscopy of pleural malignancy generally correlated well with the histological appearance on biopsies. We plan now to extend our experience of malignancy and also the ability to discriminate between benign disease and malignancy of the pleura. Supported by a Tumour Stream Grant from the Victorian Cancer Agency. Figure: Endomicroscopy image of pleural metastases from adenoidcystic carcinoma of the parotid. Figure 1

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    P1.12 - Poster Session 1 - NSCLC Early Stage (ID 203)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P1.12-018 - Overall Survival and Smoking Status in Resectable Non-Small Cell Lung Cancer (ID 2662)

      09:30 - 16:30  |  Author(s): S. Knight

      • Abstract

      Background
      Although the carcinogenic effects of cigarette smoking are important in the pathogenesis of lung carcinoma, the impact of quantitative smoking history on survival in resectable tumours has not been well described. Using a comprehensive database in which smoking was quantitatively documented, we analysed the impact of increasing number of pack years of smoking on stage, histology, mutation status and overall survival in an Australian population. We focused on patients without nodal involvement (N0) as they were less likely to have received neoadjuvant or adjuvant therapy.

      Methods
      Data was extracted from a large single institution database containing information on patients who underwent curative resection of non-small cell lung cancer from 1992 to 2012. Cigarette smoking history was documented in pack years. DNA was isolated and analysed using Sequenom’s LungCarta panel which interrogates 214 mutations in 26 genes. Statistical analysis was performed using Chi-square tests and the Kaplan Meier method for survival.

      Results
      Information on pack year smoking status was available for 470 patients, 70% of whom were male. This included 311 (66%) pathological N0 (pN0), 64 (14%) pN1 and 95 (20%) pN2. Smoking history ranged between 0 (never smokers N=32, 7%) and 180 pack years, with a median of 45 and mean of 48. Patients were divided into quartiles based on their smoking history: never- and < 10 pack year smokers (N=43; 9%), 11-25 pack years (N=74; 16%), 26-50 pack years (N=180; 38%) and >50 pack years (N=173; 37%). Adequate DNA was isolated in 425 samples. Frequencies of mutations were as follows: KRAS 21%, TP53 10%, EGFR 5%, PIK3CA 4%; other mutations occurred at lower frequencies. In 44% no mutation was found. Increased pack year history of smoking was not associated with overall survival. In the pN0 wild type population, no association with smoking and survival was seen. In the pN0 mutation group (Figure 1) those with a <25 pack year history had significantly better overall survival than heavier smokers (HR 0.61, 95% CI 0.40-0.92). Figure 1: Overall Survival by smoking status in pN0 tumours with a mutationFigure 1

      Conclusion
      Smoking status was not associated with overall survival across the entire cohort. In patients whose tumour harboured a mutation, increased smoking was associated with a less favourable mutation profile including in KRAS, TP53 and PIK3CA. In patients with pN0 disease a significant difference in overall survival was observed favouring light smokers. The presence of mutations in association with heavy smoking negatively impacts overall survival.