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J. Brown



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    P1.18 - Poster Session 1 - Pathology (ID 175)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Pathology
    • Presentations: 1
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      P1.18-022 - The natural history of bronchial pre-invasive disease (ID 3433)

      09:30 - 09:30  |  Author(s): J. Brown

      • Abstract

      Background
      Bronchial pre-invasive lesions represent the earliest stages of the stepwise progression of squamous carcinogenesis, they predominantly affect the large airways and are readily detectable using autofluoresence bronchoscopy (AFB) however very little is known about the natural history of these lesions and no randomised data exists to determine whether intervention before progression to invasion improves outcome.

      Methods
      A total of 94 patients with bronchial dysplasia were enrolled into an on-going surveillance cohort at University College London Hospital running prospectively since 1999. Lesions were biopsied longitudinally and kept under regular surveillance with AFB and low dose annual CT scanning until resolution or progression to invasive disease occurred. Retrospective analysis of lesional destiny was undertaken to determine the proportions of progressive vs. regressive lesions that occur in low grade dysplasia (LGD- squamous metaplasia, mild and moderate dysplasia) vs. high grade dysplasia (HGD- severe dysplasia (SD) and carcinoma-in-situ). A lesion was considered to have progressed/ regressed if it crossed between groups (LGD, HGD, invasive cancer).

      Results
      A total of 117 separate lesions that were biopsied on more than one occasion were identified of which 61 were HGD and 56 LGD. Of the low grade lesions 54/56 (96%) regressed or remained static, 1 (2%) progressed to CIS and 1 (2%) to invasive carcinoma both of these lesions progressed from moderate dysplasia. Of the high grade lesions there were 13 SD and 48 CIS, overall 35/61 (57%) of HGD progressed to invasive cancer 9/61 (15%) regressed and 17/61 (28%) remained static. There was a trend toward higher progression to cancer (62% vs 56%) and lower rates of regression (8% vs. 17%) for SD versus CIS in the HGD cohort although the numbers are too small to be statistically significant (see fig. 1). In the HGD group median time to invasion was 9.5 months (range 3-49), static lesions were documented to have remained as such for a median of 17 months (range 4-60). Figure 1

      Conclusion
      In our cohort we see very few lesions following the traditional stepwise progression and LGD remains relatively indolent. There is a significant proportion of HGD that progresses to invasive cancer and further studies are required to test the role of endobronchial intervention to prevent progression and to determine the most efficacious modality of treatment.

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    P2.21 - Poster Session 2 - Diagnosis and Staging (ID 170)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Prevention & Epidemiology
    • Presentations: 1
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      P2.21-004 - Infrared spectral cytopathology of the respiratory tract:<br /> a pilot study (ID 2250)

      09:30 - 09:30  |  Author(s): J. Brown

      • Abstract

      Background
      Background: Vibrational infrared (IR) spectroscopy is a powerful chemical analytical tool that can be used to detect and analyse many types of chemicals and materials including complex mixtures. Absorptions in this region arise from molecular vibrational properties and most molecules have characteristic IR spectra. There is a growing literature on its possible medical diagnostic use to distinguish cell types and states by characterising their IR ‘molecular fingerprints’ in the 1800 -900 cm[-1 ]range. Such spectra are complex since they represent an overlapping mixture of proteins, lipids, carbohydrates, DNA and cellular metabolites. Hypothesis: IR spectroscopy will differentiate histological grade of bronchial biopsies by identifying spectral changes corresponding to the stepwise progression from dysplasia to invasive cancer.

      Methods
      Methods: 52 biopsy specimens were obtained bronchoscopically from 38 patients representing 21 normal, 9 low grade dysplasia, 18 high grade dysplasia and 7 invasive squamous cell carcinomas. Matched histopathological samples were examined by H&E staining and microscopy for pathological classification. In all cases, IR data were collected in the 4000 – 900cm[-1] region using a Bruker IFS66s FTIR spectrometer, both absolute absorbance spectra and their second derivatives were calculated. Biopsies are analysed fresh; time taken to capture each reading is approximately 1 minute.

      Results
      Results: There were minimal changes to differentiate low grade changes from normal epithelial cells however there were significant and reproducible changes corresponding to high grade dysplasia and cancer (Fig 1). We have developed an algorithm analysing the relative size of IR peaks in the 1290-1270cm[-1 ]range that differentiates with 100% accuracy between normal/ low grade and high grade/ cancer in this small pilot study. We have observed differences in regions suggesting changes in intracellular glycoproteins and lipids and work continues to define the exact cause of the observed differences. More subtle spectral changes also discriminate between high grade dysplasia and cancer and are the subject of further algorithm development and validation.Figure 1

      Conclusion
      Conclusions: High quality mid-IR spectra of ex-vivo biopsies do reveal differences between normal and dysplastic/ cancerous cells in bronchial tissues. This technology has the potential to provide real-time near patient cytopathological diagnosis for the bronchoscopist or thoracic surgeon for instance to confirm clear resection margins at surgery. Identification of the chemical changes occurring at a cellular level may lead to reverse translation and better understanding of the processes driving progression to malignant transformation. Future work will refine and validate the observed changes.

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    P3.12 - Poster Session 3 - NSCLC Early Stage (ID 206)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P3.12-022 - Patterns of disease recurrence and modality of detection following surgery for early stage lung cancer (ID 3413)

      09:30 - 09:30  |  Author(s): J. Brown

      • Abstract

      Background
      There is a significant risk of disease recurrence following surgery with curative intent for non-small cell lung cancer (NSCLC). However, limited data is available on the patterns of recurrence and best practice for follow up imaging after lung cancer surgery. Current practice in the United Kingdom (UK) is to perform interval chest x-ray for 5 year following surgery. We aimed to determine the incidence, anatomical site, modality of detection and percentage of patient requiring acute admission as a harbinger of disease recurrence post thoracotomy for NSCLC

      Methods
      Records of consecutive patients with NSCLC who underwent thoracotomy and resection of early stage lung cancer at 5 institutions situated in the South East of the UK between October 2007 and September 2012 were interrogated. Data collection was completed in Jan 2013.

      Results
      A total of 314 patients were included; 59 (18.8%) patients died from disease recurrence during the study period, the site of recurrence was lung, central nervous system, bone/ soft tissue, abdominal and lymph node respectively in 24 (40.7%), 17 (28.8%), 10 (16.9%), 4 (6.8%) and 4 (6.8%) cases. In 45 (76.2%) patients disease recurrence was detected during outpatient consultation, modality of detection for routine chest x-ray, CT and other modalities were respectively 7 (15.5% ), 28 (62.2%) and 10 (22.3%) in every case CT was prompted by change in symptoms, a clinically palpable mass lesion or clinical suspicion. Other modalities used were MRI, ultrasound and lymph node aspiration in 4, 3 and 3 cases respectively. Emergency admission accounted for 14 (23.8%) patients pathway to detection of recurrence, of these 9 (64.3%) were admitted with symptoms relating to cerebral metastases, 4 (28.6%) with symptomatic breathlessness and 1 (7.1%) with a pathological fracture.

      Conclusion
      Almost a quarter of patients with relapsed lung cancer following surgery present with acute symptoms requiring emergency admission. Standard chest x-ray follow-up detects very few recurrences with most cases being detected once reported symptoms direct further investigation. It is currently unknown whether earlier detection of recurrence may offer symptomatic or survival gains however avoidance of emergency admissions is likely to have a positive impact on quality of life. Further studies to investigate which patients are at highest risk of recurrence and the most appropriate post-surgical follow-up strategies are required.