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J.R. Gosney



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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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      P1.18-014 - An analysis of mRNA and long non-coding RNA (lncRNA) expression during the progression from pre-invasive lesions (PL) to invasive squamous cell carcinoma (SqCC) of the bronchus. (ID 2251)

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

      • Abstract

      Background
      Lung cancer is a common disease, with a poor 5-year survival rate often attributed to late diagnosis where curative treatment is uncommon. SqCC account for ~40% of non-small cell lung cancer (NSCLC) that possess a clinically detectable preinvasive phase. Intervention following early diagnosis of NSCLC using low-dose CT and autofluorescence bronchoscopy can significantly reduce mortality. PL are histological changes of bronchial epithelium that can be classified into squamous metaplasia (M), mild dysplasia (MID), moderate dysplasia (MOD), severe dysplasia (SD), carcinoma in-situ (CIS). They are found with varying prevalence, in high-risk cohorts such as smokers or individuals exposed to occupational carcinogens. MID and MOD are more frequently identified but only a minority progress to a SqCC. SD and CIS more commonly progress to SqCC but this is not universal.

      Methods
      The natural history of PL is not sufficiently understood. In order to address this, we have used exon arrays to profile mRNA and lncRNA levels in total RNA samples derived from formalin fixed wax embedded bronchial biopsies subject to laser microdissection. Three thoracic pathologists (KK, JG, LJ) reviewed all biopsies and agreed the morphological classification. We will report changes in differential expression of mRNA and lncRNA levels when we compare the transcriptome profiles of 5 categories of PL (M, miD, moD, sD, CIS) and 2 categories of SqCC (node negative and node positive), with those of matched normal bronchial epithelial cells. We believe this analysis provides an unprecedented insight into the molecular events that drive progression towards invasive malignancy, and may aid the identification of novel tools for the management of early squamous cell lung cancer.

      Results
      not applicable

      Conclusion
      not applicable

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    P1.20 - Poster Session 1 - Early Detection and Screening (ID 172)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Imaging, Staging & Screening
    • Presentations: 1
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      P1.20-004 - UK lung Cancer Screening trial (UKLS): Base line data (ID 1796)

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

      • Abstract

      Background
      Lung Cancer causes over 35,000 UK deaths per year: early detection by CT screening has been shown to reduce mortality in the USA by 20%.

      Methods
      UKLS is a pilot randomised controlled trial, screening individuals at a high risk of developing lung cancer (>5% over 5yrs) with low-dose CT. UKLS is population-based, approaching people of 50-75yrs identified through local primary care records and using a validated lung cancer risk prediction model to identify high risk individuals from the target group (Raji Annals of Int. Med 2012). We report observations made from the initial recruitment to the trial. 250,000 individuals were approached in Liverpool and Cambridgeshire, 30% responded positively to the first questionnaire. 4000 individuals were recruited and randomised to receive either a low-dose CT scan or usual care. All CTs were double read according to UKLS protocol. Nodules were reported as category 1, 2, 3 or 4 depending on size and volume (Baldwin et al. Thorax 2011). Participants with category 4 nodules (>500mm3) were referred to the lung cancer multi-disciplinary team (MDT) for further workup. Individuals with a category 3 nodule (50-500 mm3) underwent a repeat CT within 3 months, whereas category 2 nodules (15-50mm3) were followed up at 12 months. The trial is currently in follow-up and some participants are still in the 3 and 12 month phases.

      Results
      1991 high risk UKLS participants underwent baseline CT by June 2013. 1044/1991(52.4%) individuals had nodules requiring further imaging or work-up. 79/1991 (4.0%) had nodules which required referral to the MDT clinics at the pilot sites for further workup. At this time 31/1991(1.6%) had a prevalent lung cancer. 27/31 lung cancers (87.1%) were non-small cell lung cancer and 25/31 lung cancers (80.6%) were Stage I or II (based on pathological staging or clinical staging where the pathology staging was not available).

      Conclusion
      UKLS has already demonstrated 1.6% prevalence, utilising the LLP risk prediction model to identify high risk individuals, which compares favourably with the NELSON and other European trials. The Pilot UKLS is due to provide an interim report in 2014.

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    P2.18 - Poster Session 2 - Pathology (ID 176)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Pathology
    • Presentations: 1
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      P2.18-005 - Morphological and genetic classification of lung cancer: variation in practice and implications for tailored treatment (ID 956)

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

      • Abstract

      Background
      The rational use of tailored therapy for lung cancer depends crucially on high quality pathology. Not only must subtyping of the tumour be achieved consistently and with accuracy, but as much material as possible from increasingly small specimens must be preserved for the genetic analysis upon which such treatment is increasingly predicated. Although there is a general presumption that pathologists have risen to this challenge, reliable data is sparse and the nature and degree of variation in practice and quality is unknown.

      Methods
      We collected and scrutinised anonymised information, including pathology reports, on all consecutive, newly-diagnosed patients with lung cancer referred to 19 lung cancer units across the UK for a period of 6 months commencing late 2011, a total of 1507 cases. Centres surveyed ranged from district general hospitals to specialist regional cardiothoracic units.

      Results
      Achievement of a positive tissue diagnosis of malignancy ranged from 53 to 88%, figures accompanied by ‘suspicious but non-diagnostic’ rates of 10 and 2% respectively. Despite apparent adherence to the diagnostic criteria and terminology of the WHO classification of tumours of the lung, variation in proportions of tumour subtypes was wide, the prevalence of squamous carcinoma, for example, varying from less than 10 to greater than 50%. The proportion of tumours unclassified beyond ‘non-small cell lung cancer not otherwise specified’ varied from 3 to 20% despite the almost universal use of immunochemistry (most often TTF-1, class 7 cytokeratins and p63) to aid in this differential diagnosis. Testing for EGFR gene mutations was directly instigated by the pathologist at diagnosis in only 4 of the 19 centres and the proportion of tumours tested ranged from 12 to 92%.

      Conclusion
      Variations in practice amongst pathologists and arguably in the quality of pathology ranged widely across the centres surveyed, raising important questions about variable expertise of pathologists, adherence to guidelines, applicability and rigour of external quality assessment and, ultimately, the reliability of the pathology that crucially underpins the management of lung cancer.

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    P3.21 - Poster Session 3 - Diagnosis and Staging (ID 171)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Prevention & Epidemiology
    • Presentations: 1
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      P3.21-003 - The LungPath Study: Variation in lung cancer diagnostics in England. Does the availability of PET scanning and EBUS affect patient care? (ID 1429)

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

      • Abstract

      Background
      The LungPath study is a national multi-centre survey of lung cancer diagnosis and staging practice in England. As part of the project, we looked for variation in access to key investigations such as EBUS and PET-CT scanning and linked this to how likely these studies were used to be in different centres and the impact these differences may have on patient care.

      Methods
      Twenty willing English lung cancer centres were randomly selected to participate in the LungPath study. Participating centres agreed to submit data on each new lung cancer patient seen during the study period of six months from January to June 2012. Data collected included clinical information such as age, gender and performance status, the dates of all radiological investigations performed and anonymised pathology reports from all other investigations performed. The data collected was used to map each individual patient’s diagnostic pathway. In addition, we collected information about typical waiting times for key investigations and whether these investigations were available on-site or at other institutions. We analysed the patient data to see if the availability of investigations such as EBUS and PET-CT impacted the patient pathways in each centre.

      Results
      There were significant differences between centres in the availability of EBUS and PET-scanning. Approximately half of the units surveyed reported waiting times for EBUS and PET-scanning of one week or less while the other half reported longer waits, typically two weeks and sometimes longer. There were large differences in the proportions of patients that underwent EBUS or PET-scanning from centre to centre with patients up to six times more likely to receive an EBUS and four times more likely to receive a PET-scan in some centres than others. There was a clear relationship between the use of the investiagtion and the waiting time. We also found that the point in the diagnostic pathways that these investigations were used varied and in many cases differed from best practice guidelines; several centres routinely performed EBUS as a separate procedure after a bronchoscopy had already been performed.

      Conclusion
      There are marked differences in the availability and use of EBUS and PET-scanning within different lung cancer units involved in diagnosing and staging lung cancer in England. There is a need for commissioners to ensure fairer service provision across England and opportunities for education of clinicians to make best use of the available resources.