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R.C. Rintoul



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    P1.02 - Poster Session 1 - Novel Cancer Genes and Pathways (ID 144)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P1.02-013 - SDHB is overexpressed and may be a candidate target for therapeutic intervention in Malignant Pleural Mesothelioma (ID 3287)

      09:30 - 09:30  |  Author(s): R.C. Rintoul

      • Abstract

      Background
      Malignant pleural mesothelioma (MPM) is a rare aggressive cancer of the pleura. Asbestos exposure (through inhalation) is the most well established risk factor for mesothelioma. The current standard of care for patients suffering from MPM is a combination of cisplatin and pemetrexed (or alternatively cisplatin and raltitrexed). Most patients however, die within 24 months of diagnosis. New therapies are therefore urgently required for this disease. The Succinate Dehydrogenase Complex, Subunit B, IronSulfur Protein (SDHB), is a subunit of the Succinate dehydrogenase or succinate-coenzyme Q reductase (SQR) or respiratory Complex II, and has recently been identified by us as an important element in MPM.

      Methods
      A panel of MPM cell lines inluding the normal pleural cells LP9 & Met5A were screened for expression of SDHB by RT-PCR. Levels were subsequently examined in a cohort of snap-frozen patient samples isolated at surgery comprising benign, epithelial, biphasic, and sarcomatoid histologies by RT-PCR and western blot. Finally the expression of SDHB in a large cohort of MPM specimens with clinical data was asessed by IHC.

      Results
      Expression of SDHB occurs in all cell lines. Significantly higher expression of SDHB is observed in the malignant tumour material versus benign pleura. There was a trend towards better survival for patients expressing higher levels of SDHB, but this was not statistically significant.

      Conclusion
      SDHB, a key member of oxidative energy metabolism is significantly altered in MPM. This may have important future implications for the management of MPM.

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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 - 09:30  |  Author(s): R.C. Rintoul

      • 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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    P2.14 - Poster Session 2 - Mesothelioma (ID 196)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Mesothelioma
    • Presentations: 1
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      P2.14-011 - MesobanK: A UK based bioresource for malignant pleural mesothelioma (ID 1314)

      09:30 - 09:30  |  Author(s): R.C. Rintoul

      • Abstract

      Background
      Availability of quality assured, fully annotated mesothelioma tissue collected to rigorous standard operating procedures will facilitate better understanding of mesothelioma biology. Currently, few bioresources of mesothelioma tissue exist, the largest being the National Mesothelioma Virtual Bank hosted by the University of Pittsburgh (http://www.mesotissue.org/). A few other clinical/research groups hold fresh tissue from small numbers of mesothelioma patients but these collections are not formally linked and often do not involve collection of tissue and data to Standard Operating Procedures. The British Lung Foundation/Mick Knighton Mesothelioma Research Fund has recently funded MesobanK, a UK based bioresource of malignant mesothelioma tissue samples.

      Methods
      Tissue Microarray: MesobanK will construct a tissue microarray (circa 1000 cases) using historical formalin fixed paraffin embedded blocks of tissue taken at thoracoscopy/surgical resection. Inclusion criteria requires sufficient tissue to permit multiple 0.5 mm cores (to allow for tumour heterogeneity) and a clinical minimum data set. Fresh tissue: Fresh frozen mesothelioma tissue (300 cases over 3 years) will be collected prospectively from multiple centres across the UK together with parallel pleural fluid, whole blood, serum and plasma. Each case will have a detailed anonymised linked clinical data set with follow up data. Cell lines: MesobanK plans to create 20 new fully annotated mesothelioma primary cell lines. The bioresource will be supported by a web-based IT infrastructure for annotating and searching the collection. Clinical data will be collected on each case and supplemented by laboratory and pathology results, Hospital Episode Statistics data and UK Cancer Registry data in order to achieve as complete a data set as possible. MesobanK will follow the Guiding Principles laid out by the NCRI Confederation of Cancer Biobanks and the UK Medical Research Council Operational and Ethical Guidelines on Human Tissue and Biological Materials for Use in Research. It will also be managed within the scope of all relevant regulatory frameworks and quality management/quality assurance systems. In addition, we share the aim of the US National Cancer Institute (NCI) National Biospecimen Network Blueprint: to create a comprehensive framework for sharing and comparing research results through a robust, flexible, scalable and secure bioinformatics system that supports the collection, processing, storage, annotation and distribution of biospecimens and data using standard operating procedures based on best practices. A steering committee will have overall control of MesobanK. An independent scientific advisory board will review applications for samples and advise the steering committee. Prioritisation for access to samples will be based solely on scientific merit. All researchers, whether in the UK National Health Service, universities, charities, government agencies or commercial companies, and whether based in the UK or abroad will be subject to the same application process and approval criteria.

      Results
      Not applicable

      Conclusion
      It is anticipated that initial tissue (TMA and cell lines) will be available in 2014.

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    PL03 - Presidential Symposium Including Top Rated Abstracts (ID 85)

    • Event: WCLC 2013
    • Type: Plenary Session
    • Track:
    • Presentations: 1
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      PL03.03 - MesoVATS: A multi-centre randomised controlled trial of video assisted thoracoscopic pleurectomy versus talc pleurodesis in malignant pleural mesothelioma (ID 2423)

      08:37 - 08:49  |  Author(s): R.C. Rintoul

      • Abstract
      • Slides

      Background
      Malignant pleural mesothelioma (MPM) incidence is increasing and has no known cure. Non randomised studies suggest that video assisted thoracoscopic (VAT) pleurectomy is effective in controlling pleural effusion and may be associated with increased survival compared to talc pleurodesis.

      Methods
      A multicentre randomised controlled trial of VAT pleurectomy versus talc pleurodesis was undertaken for patients > 18 years with any sub-type confirmed or suspected MPM with a pleural effusion who were fit enough to undergo VAT pleurectomy. Exclusion criteria included previous pleurodesis by any approach. Previous malignancy was permitted if there was no evidence of active disease and MPM had been confirmed. Participants were risk stratified using a modified EORTC prognostic scoring system. Talc pleurodesis was performed via tube thoracostomy or by poudrage at thoracoscopy. VAT pleurectomy involved partial parietal pleurectomy and decortication of the visceral pleura, where appropriate, to achieve lung re-expansion. A total of 196 patients was required to show a survival difference at 1 year of 59% (VAT pleurectomy) versus 37% (talc pleurodesis). Ethical approval was granted by Huntingdon, Cambridge (UK) Research Ethics committee: H02/809; ISRCTN: 34321019; ClinicalTrials.gov NCT00821860.

      Results
      Between 2003 and 2012, 196 patients (120 confirmed, 76 suspected) were randomised across 9 UK centres. 21 cases suspected MPM were subsequently found not to have MPM and excluded (pre-planned in protocol), leaving 87 VAT pleurectomy and 88 talc pleurodesis for the main analysis. Baseline characteristics were similar between the two groups; overall mean age 69 years, 86% men and 75% had known asbestos exposure. Eighty four per cent showed epithelioid disease, 78% were IMIG stage 3/4 and 49% were high risk as per EORTC criteria. The allocated procedure was completed for 73 (83%) talc and 78 (90%) VAT pleurectomy patients. One year survival rates (primary outcome measure) were 57% for the talc group and 52% in the pleurectomy group (hazard ratio 1.03 (95% CI: 0.76, 1.42), p=0.83). Of the secondary outcome measures, pleural effusion was controlled in 37% of talc and 59% pleurectomy patients at one month (p=0.008) and in 57% of talc and 76% pleurectomy patients at 6 months (p=0.04). At 9 and 12 months control of pleural effusion was similar between groups. Median hospital stay was longer in pleurectomy patients (8 days (range 1-31) vs. 6 (range 1-15), p<0.001) and this group had significantly more complications, predominantly prolonged air leak (26% vs. 8%, p=0.009). Based on patients with complete data there was a significant benefit in EQ5D quality of life at 6 months (mean difference 0.08 (95%CI 0.003,0.16), p=0.042) and 12 months (mean difference 0.19 (95%CI 0.05,0.32), p=0.006) in favour of the pleurectomy group. Adjusting for bias due to missing data prior to death reduced the difference in 12 month EQ5D to 0.09 (95%CI -0.04,0.22), p=0.16.

      Conclusion
      MesoVATS showed that VAT pleurectomy significantly improved control of pleural effusion versus talc pleurodesis and improved quality of life. However, overall survival was not increased and the pleurectomy group experienced more complications. Subgroup analyses will investigate which patients benefit most from which intervention. Funded by the BUPA Foundation

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