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T1 Figure 1ConclusionsOverall, this largest paediatric single cell COVID-19 study to date showed significant differences in response to SARS-CoV-2 between children and adults, reflecting the changes of the immune landscape over developmental time, which in children are dominated by naive and innate responses.

P100 Table 1Factors influencing reduced utilisation of healthcare services during the covid-19 pandemicConclusions40% of individuals in a cohort at high risk of lung cancer and respiratory comorbidities reported reduced utilisation of health care services due to the COVID-19 pandemic.Limitations to our data include the lung health check questions not distinguishing between primary and secondary care or routine and urgent visits, and self-reported co-morbidity data limited to selected respiratory conditions. Nevertheless, we provide evidence for the scale of the problem and highlight that individuals with chronic respiratory conditions are particularly likely to be impacted.Please refer to page A193 for declarations of interest related to this abstract.

Introduction Lung cancer remains the leading cause of cancer related death globally. Low-dose CT (LDCT) screening of high-risk individuals reduces lung cancer specific mortality. An important requirement for any screening programme is to minimise harms, especially in those who do not have cancer. Data from randomised controlled trials is often used as the primary source from which to extrapolate risks of harm but they do not reflect modern, real-world practice. In this paper we present cumulative data on screening harms from five UK-based lung cancer screening programmes. Methods In the UK, several implementation pilots and research studies have demonstrated that screening can be successfully delivered within or aligned to the NHS. These include: UK Lung Cancer Screening Trial (UKLS), Lung Screen Uptake Trial, Manchester Lung Health Checks, Liverpool Healthy Lung Project and Nottingham Lung Health MOT.Most sites used BTS nodule management guidelines. Positive results were defined as those referred for more than a repeat LDCT. False positives were those positive screens without an eventual diagnosis of lung cancer. Harms were categorised according to the need for further imaging, invasive investigations and/or surgery. Complications were categorised as per the National Lung Screening Trial (NLST). Results A total of 11,815 screening LDCTs were performed across the five programmes (2016–2020). Overall, 85.5% of screening scans were categorised as negative, 10.5% as indeterminate and 4% as positive. Lung cancer detection was 2.1%, ranging from 1.7% to 4.4% across sites. The surgical resection rate was 66.0%. Details of the cumulative reported harms are summarised in table 1. Discussion This collaborative work provides up-to-date data on lung cancer screening performance and harms. The rate of positive (4%) and false positive (1.9%) screening results were significantly lower than NLST and the majority of European screening trials. Harms from investigation and treatment of non-malignant disease was minimised with no reported major complications or deaths. This provides reassurance that with the use of evidence-based practice and experienced MDTs, harms from false positive results can be minimised within screening. This information is important in the planning of larger scale implementation of lung cancer screening within the UK and beyond.

Introduction The SUMMIT Study aims to assess the implementation of Low-Dose Computed Tomography (LDCT) for lung cancer screening in a high-risk population and to validate a multi-cancer early detection blood test. LDCT results are communicated to participants and their GPs by standardised letter. We aim to evaluate the turnaround time from the scan report to the subsequent management and communication of results via letter. Methods Results are automatically sent to participants and GPs according to pre-defined management plans based on findings collected via proformatised radiology report. Possible outcomes from these reports are: urgent referrals for suspicious findings, nodule surveillance LDCT at 3 months, 12 month surveillance LDCT, or suitable for randomisation at Year 1 to annual or biennial LDCT (see figure 1). Participants with suspicious findings are reviewed by the study clinicians. Where appropriate an urgent referral to the participant’s local hospital is completed manually after discussion with the participant; the automated letters in these cases are delayed until contact is made with the participant and a clinical plan confirmed. Results We report outcomes from the first 11,551 SUMMIT Study participants with completed baseline LDCT reports. We aim to action results within 5 days: 11,319 (98.0%) of all results letters were mailed to participants and 11,423 (98.9%) to their GPs within 5 days. 645 (5.6%) participants required further review and consideration of an urgent referral. For these, 84.6% of results letters were mailed within 5 days, and 95.5% within 12 days. As expected, increased mailing times were observed in cases that were more complex, requiring liaison with an external clinical team or review of imaging at our internal weekly radiology meeting. Discussion Timely reporting of results is crucial in establishing wider roll-out of lung cancer screening in the UK. The vast majority of results are automated and are reliably sent as programmed. A minority require further clinical input and image review, prior to completion of an onwards referral. We demonstrate a scalable and feasible approach to feeding back results following LDCT.

Introduction Recent work has shown that tobacco smoke exposure increases the mutational burden and cell-to-cell mutational heterogeneity of the normal bronchial epithelium. However, smoking cessation allows the preferential expansion of low-mutant epithelial cells, which could be responsible for the decline in lung cancer risk on quitting smoking. Although less is understood about the nasal epithelium, the incidence of squamous cell cancer (SCC) in the nose is much lower than in the bronchi. Whether a difference in function or mutational burden underlies this variation is unknown. Methods Nasal brushings and endobronchial biopsies were enzymatically dissociated and underwent initial analysis by flow cytometry for expression of CK5, ITGA6, PDPN and NGFR (basal cell markers). Subsequently, single bronchial (n=152) and nasal epithelial (n=47) cells were flow-sorted and cultured from an ex-smoker to permit more detailed study of regional inter-cell variability and functionality. Index sorting was performed on the most relevant basal cell subpopulation marker PDPN. Single cells were clonally expanded in vitro and colony-forming efficiency and colony size were calculated. After expansion, DNA and RNA were isolated for downstream analysis. Results Flow cytometric analysis showed that CK5-positive basal cells constituted a similar proportion of the epithelial cell population in the nose and the bronchus (35% v. 30%, respectively, p=0.8). CK5-positive nasal basal cells compared with CK5-positive bronchial basal cells differed most in their expression of PDPN (6% v. 64% PDPN-positive, respectively, p=0.2). This was coupled with a lower median intensity of PDPN expression in nasal basal cells compared with bronchial basal cells (2437 v. 8434, respectively). Nasal epithelial cells showed lower colony-forming efficiency (15%) than bronchial epithelial cells (35%). In addition, the nasal clones that grew were significantly smaller in area than the bronchial clones (9.84 mm2 v. 13.26 mm2, respectively, p=0.0002). Conclusions The lower colony-forming efficiency, smaller colony size and lower expression of PDPN in the nasal epithelial population suggests nasal basal cells may have a lower stem cell capacity than their bronchial counterparts. Analysis of the mutational burden and transcriptomic profile of both populations is a crucial next step to understand the difference in incidence of SCC in these compartments.

Background Lung cancer is the leading cause of cancer related deaths worldwide. The value of targeting early stage disease has been widely recognised to improve survival. Oncogene-induced senescence (OIS) is a stress response instigated following the activation of oncogenes and is a well-known tumour suppressor mechanism. OIS is abundant in pre-invasive lesions in murine lung cancer models, however is lost during the progression to malignancy. We previously identified a regulatory role for Toll-like receptor 2 (TLR2) in OIS and expression of the senescence-associated secretory phenotype (SASP), however the functional relevance of this has yet to be established. Methods We used genetically engineered mouse (GEM) models of lung cancer (KrasLSL-G12D/+ and KrasLSL-G12D/+;TP53fl/fl) on both wild-type and Tlr2 null backgrounds. Lung specific activation of mutant KrasG12D and TP53 loss was achieved upon intranasal infection with Cre-recombinase expressing adenovirus. Tumour burden, senescence markers and SASP expression were assessed by immunohistochemistry. Immune cell recruitment was measured using flow cytometry on whole lung single cell suspensions from tumour bearing mice. The expression of Tlr2 and associated SASP components were measured in human pre-invasive lung cancer samples that either progressed to invasive malignancy or regressed to normal epithelium. Results Tlr2 loss was associated with an increased tumour burden and reduced survival in our GEM model. Furthermore, Tlr2 loss caused significantly reduced epithelial expression of key senescence markers and SASP factors. However, immune cell recruitment was not affected suggesting this effect was cell intrinsic. Inhalational administration of a synthetic TLR2 agonist (Pam2CSK4) significantly reduced tumour burden in our GEM model. Molecular profiling of bronchoscopic biopsies of human pre-invasive lung lesions revealed increased TLR2 and SASP expression in samples that did not progress to invasive malignancy, suggesting a tumour suppressor role for TLR2-SASP signalling in human lung cancer. Conclusions We have identified TLR2 as a potential tumour suppressor in lung cancer via regulation of the SASP. Furthermore, we have highlighted a novel therapeutic strategy for the treatment of early stage lung cancer. SASP factors are released into the bloodstream and are ideal candidate biomarkers of pre-invasive disease and thus could potentially aid in stratifying lung cancer screening populations.

Introduction and Objectives The SUMMIT Study aims to assess the implementation of low-dose Computed Tomography (LDCT) for lung cancer screening (LCS) in a high-risk population and to validate a multi-cancer early detection blood test. Invitees are identified via primary care records and invited to attend a Lung Health Check (LHC), where if eligible, LDCT is offered. Uptake of LCS has been low, whilst UK studies have demonstrated higher rates, these are still lower than other screening programmes. Research in other cancer screening settings suggests that re-invitation strategies improve uptake among non-responders, with recall routine practice in existing national screening programmes. We aim to quantify the uptake to re-invitation, something not previously tested in the LDCT screening context. Methods Re-invitation and re-invitation reminder letters were sent to individuals who had not responded to the initial series of invitation letters (pre-invitation, invitation, reminder) within four months or longer. The content of the letters was designed using behavioural science evidence for strategies effective for non-responders in the colorectal cancer screening context, including the principles of scarcity, social norms for participation so far, personalisation to local London borough and GP endorsement. Responses from the first ten re-invited practices were analysed. Re-invitations were sent between 22nd January and 5th February 2020 and reminders between 5th and 19th February 2020. Data were analysed 21 days after the last reminder was sent. Results 2,000 non-responders were sent re-invitation letters. 310 (15.5%) of those re-invited responded (range: 8.3%–21.2% per practice). The average response time was 19 days. Of those who responded, 186 (60.0%) were eligible for a LHC and 182 (97.8%) of those eligible booked a LHC appointment. Four people (2.2%), did not attend their booked appointment. Of those attending, 154 (86.5%) were eligible, of which 133 (86.4%) consented. Conclusions The re-invitation strategy impacted positively on screening uptake and participation by non-responders. These results may be an underrepresentation of the true effect, as invitees could contact the study team after the date of analysis. Work continues to assess the demographic and smoking-related characteristics of those who respond to re-invitation and how it interacts with the overall invitation strategy.

Introduction The NLST and NELSON studies demonstrated lung cancer mortality reduction from low-dose CT (LDCT) lung cancer screening. Local implementation pilots of ‘Lung Health Checks’ indicate feasibility in the NHS. NHS England will now fund 10 aligned projects for a national Lung Health Check pilot as a major centre-piece of the early diagnosis agenda of the NHS Long Term Plan. We report on methodological approaches to deliver this project and progress towards deployment. Methods Sites selected from Clinical Commissioning Groups in 10 Cancer Alliances had highest incidence and mortality from lung cancer, excluding those where screening pilots or research projects were already underway. Approximately 600,000 individuals will be invited with an expected 200,000 scans over the next four years, including baseline and 24 month incident round scanning. To support quality and governance, NHS England published a National Protocol (January 2019), are developing a Quality Assurance Framework, minimum dataset, Incidental Findings Protocol and Research Standard (assisted by CRUK). NHSE are supported by the CT Screening Advisory Committee, a sub-group of the Clinical Expert Group for Lung Cancer, NHSE. Cancer Alliances are being assisted in developing detailed delivery plans by the National Cancer Programme team. Results Detailed delivery plans have been provided by all regions. 47 radiologists will attend a national education program with clearly defined metrics for a national quality assurance training standard including volumetry and computer-aided detection. Standard participant materials are in production and QA evaluator appointed. Data on infrastructure readiness, progress against delivery milestones and final supporting documents relating to quality and governance will be presented. Conclusions The Lung Health Check program will be a major national flagship for respiratory medicine and a key component of the Long Term Plan aspirations to achieve early stage diagnosis in 75% of cancer cases. The program will inform the international literature on implementation of potentially revolutionary lung cancer screening but careful adherence to QA and demonstration of efficacy through appropriate evaluation is critical. Potential barriers include participant uptake; workforce capacity and data flow/information governance. The Standard Protocol is already being used by several European countries as a template for local protocol development. On behalf of the CT Screening Advisory Group, Clinical Expert Group for Lung Cancer and NHS England National Cancer Team.

Introduction and objectives The success of lung cancer screening (LCS) with low-dose CT (LDCT) depends critically on delivering timely, accurate radiology reports. Its anticipated widespread introduction will place a significant burden on current thoracic radiologist capacity, mandating innovative solutions. We explored the role that trained radiographers, using computer-assisted nodule detection (CADe) software, might have in LCS reporting pathways. Methods 770 LDCTs performed as part of the Lung Screen Uptake trial (LSUT) were retrospectively reported by two radiographers (R1 and R2) using the Veolity™ CADe software. Radiographers could request the opinion of the study radiologist about uncertain findings. The original radiologists’ reports (read without CADe) were considered the reference standard. Studies were categorised as ‘positive’ (nodule or mass requiring nodule surveillance or MDT referral), ‘negative’ (no intrapulmonary findings requiring further imaging) or ‘ill-defined’ (indistinct focal abnormality requiring surveillance, e.g. consolidation). Reported outcomes were compared to the reference standard, with any discrepant (i.e. radiographer-only reported) nodules re-reviewed by both study radiologist and a second independent radiologist, and verified as either ‘true’ or ‘false positive’ (figure 1). Secondary outcomes included scan-reading times and identification of incidental findings. Results The reference standard dataset included 163 ‘positive’, 35 ‘ill-defined’, and 572 ‘negative’ studies, and 34 confirmed lung cancers. R1 and R2 requested radiologist confirmation for 6.5% and 10.4% of studies respectively. Following verification of discrepant nodules, reporting sensitivity varied significantly between radiographers at 67.3% (R1) and 74.0% (R2) for all ‘positive’ studies (OR 2.27, p=0.03): 77.4% and 93.9% for confirmed cancers. The majority of ‘missed’ lesions arose from inappropriate rejection of CADe-detected findings rather than being missed altogether. The radiographer plus CADe reading combination highlighted ten nodules previously dismissed by the study radiologist, that were subsequently recalled for further surveillance. Allowing for these, the rates of false positive reporting were 7.9% (R1) and 6.2% (R2). Conclusions Individual performance varied significantly between the two radiographers, but the overall results suggest inadequate sensitivity to recommend this strategy. As per previous observations elsewhere, using CADe software in LCS reporting pathways is likely to reduce reporting times whilst increasing reader sensitivity.

Introduction Malignant mesothelioma (MM) has no biomarker driven therapies in routine clinical use. We used a drug screen of molecularly characterised MM lines to identify novel genomic biomarker driven therapy. This led to the discovery of a subset of MMs, defined by loss of function (LOF) of the nuclear deubiquitinase BRCA associated protein 1 (BAP1), that demonstrate heightened sensitivity to tumour necrosis factor related apoptosis inducing ligand (TRAIL). We then validated this association across in vitro, in vivo and ex vivo models and delineated the underlying mechanism. Methods 15 MM lines were characterised for mutations in five MM tumour driver genes and screened for response to 95 compounds. The identified BAP1-TRAIL association was validated in an extended panel of MM lines with apoptosis and cell viability assays. 25 early passage MM cultures, mouse xenograft and human tumour explant models were used to further validate the association. Knock-in and knock-out models in BAP1 mutant and wild type lines confirmed the effect of loss of BAP1 expression on TRAIL sensitivity. 6 mutant BAP1 constructs were generated and identified which functional BAP1 sites modulate TRAIL sensitivity. The effect of BAP1 function on the downstream death receptor/apoptosis pathway components was determined using microarray and immunoblot analysis. Results BAP1 LOF significantly correlated with TRAIL sensitivity in established MM lines (p=0.015) and primary MM cultures (p Conclusions We identify loss of BAP1 as a novel biomarker for TRAIL sensitivity in MM. BAP1 LOF is observed in up to 67% of MM tumours and BAP1 immunohistochemistry is in use as a diagnostic tool; hence this approach is validated and ready for immediate and actionable clinical use for this disease.

Introduction Lung cancer is the leading cause of cancer death worldwide with over 70% presenting with incurable disease and few effective treatments. We previously demonstrated that mesenchymal stem cells (MSCs) transduced to express TNF-related apoptosis inducing ligand (TRAIL), will home to and induce apoptosis of tumour cells in vitro and reduce tumour growth in multiple in vivo models. We are now undertaking a clinical trial to assess the therapeutic efficacy of this genetically modified cell therapy. Aim To evaluate the safety and anti-tumour activity of MSCTRAIL in combination with chemotherapy in patients with metastatic lung adenocarcinoma. Manufacturing Methods MSCs were isolated from unrelated umbilical cord donors and characterised as MSCs according to international criteria. Cells from individual donors were thawed and transduced with a lentiviral vector encoding for TRAIL. Successful transduction was confirmed by flow cytometry and cells were subsequently pooled and seeded into a multilayer bioreactor. Once confluent, cells were harvested to form the primary seed stock (PSS). PSS vials underwent further expansion rounds to form a working cell stock (WCC) and subsequent investigational medicinal product (IMP) ready for patient dosing. Trial Design Patients with stage IIIB/IV adenocarcinoma of the lung (EGFR and EML4-ALK negative) will be eligible for enrolment Phase I is a dose de-escalation study (figure 1A) where patients will receive pemetrexed and cisplatin on day 1 then 4 × 108 MSC-TRAIL cells on day 2 of a 21 day cycle for 3 cycles. Dose limiting toxicities will be recorded. Phase II is a single blinded, randomised, placebo controlled trial consisting of standard chemotherapy and either MSC-TRAIL or placebo (figure 1B). Safety data will be collected and efficacy will be assessed using CT with RECIST (v1.1) criteria at 12 weeks. All patients will be monitored for up to 2 years. Outcomes Phase I primary outcome is safety and tolerability of MSC-TRAIL. Phase II is tumour response rate by RECIST (v 1.1) criteria at 12 weeks. Conclusion We have produced a viable working bank of genetically modified stem cells, If therapy is effective we will plan to expand into larger phase III trials.

Introduction Lung Cancer screening by Low-Dose CT (LDCT) has been shown to reduce mortality, though exactly how best to implement this is unclear. Uptake to screening trials has generally been low, particularly in those at highest risk of lung cancer. The Lung Screen Uptake Trial is a UK based dual centre LDCT randomised controlled screening trial of a modified invitation strategy versus a standard approach in a population with high levels of socioeconomic deprivation. Methods Patients were identified as ‘high-risk’ primarily by age and smoking history on a predesigned EMIS-Web search and subsequently invited on behalf of their general practitioner (GP) to a ‘lung health check’ appointment. Those attending were offered enrolment into the study and a LDCT if they met the required threshold of lung cancer risk. This abstract focuses on the mode of recruitment via general practice. Results Potentially eligible participants were recruited from 16 GP surgeries serving a population of 1 55 034. Of these, 8.7% were in the required age range of 60–75% and 98.9% of those had smoking status recorded. A mean of 32.2% (SD 3.8) of those aged 60–75 had been recorded as a current smoker in the preceding 15 years. A total of 1997 patients, who had been recorded as current smokers within the past 5 years were invited. Uptake to the study was 50.3% (n=1005) of all those invited. 765 underwent a LDCT examination (figure 1). In 10.3% of patients the smoking history was confirmed to be too light for CT screening, despite GP records suggesting otherwise. Conclusions Smoking status was found to be very well recorded in primary care records, providing a feasible method for initial selection of those eligible for screening. However we also showed the importance of confirmation of smoking history, something that might be done prior to invitation in screening programmes. This study observed a high rate of attendance when compared to previous LDCT screening trials. The explanation for this observed difference is likely to be multifactorial, though one key factor, unique to this study, is that the invitation to participate came from patients’ own GP.

Rationale Recent data have demonstrated the superiority of Pembroluzimab over chemotherapy for patients with advanced NSCLC and high (≥50% expression) of PD-L1.1 This has resulted in NICE approving Pembroluzimab as a first line treatment option for patients with advanced NSCLC in June 2017. The original trial however excluded patients with PD-L1 testing on EBUS samples. We therefore conducted a large, multicentre study to clarify whether specimens obtained by EBUS-TBNA were suitable for testing PD-L1 in patients with NSCLC. Methods NSCLC samples acquired by EBUS-TBNA (29.4%), percutaneous biopsy (31.2%), endobronchial biopsy (13.8%), surgical (21.4%) or other techniques (4.1%) were recorded from 435 consecutive patients with known or suspected lung cancer across 5 centres in England between January 2015 and December 2016. Results PD-L1 assessment (using the 22 C3 assay in all cases) was possible in 92.2% of patients undergoing EBUS and there was no difference in success of PD-L1 testing according to modality of tissue acquisition (p=0.18). The frequency of complications from EBUS-TBNA was similar to endobronchial or percutaneous techniques but lower than surgical procedures (5.0% vs 13.8%; p=0.03). PD-L1 expression in the cohort was high (≥50%) in 28.5%, weak (≥1%–50%) in 28.2%, whilst 43.3% of patients were PD-L1 negative. The only statistically significant predictor for PD-L1 expression in multivariate analysis was the presence of brain metastasis at diagnosis (OR 2.02; CI 1.04–3.90). 47 patients (11.4%) were treated with immunotherapy and the response rate was 16.2%. All patients that responded to immunotherapy had high (≥50%) expression of PD-L1. Conclusions This large multicentre study demonstrates for the first time that samples obtained by EBUS-TBNA in routine practice are suitable for PD-L1 testing in patients with NSCLC. The presence of brain metastases at diagnosis predicts high PD-L1 expression in this cohort and this new finding should be tested in future clinical trials. Reference Reck M, Rodrguez-Abreu D, Robinson AG, et al. Pembrolizumab versus Chemotherapy for PD-L1Positive NonSmall-Cell Lung Cancer. N Engl J Med 2016;375(19):1823-33. doi:10.1056/NEJMoa1606774

Introduction Lung cancer is the leading cause of cancer death worldwide with over 70% of patients presenting with incurable disease and few effective treatments. We previously demonstrated that mesenchymal stem cells transduced to express TNF-related apoptosis inducing ligand (TRAIL), will home to and induce apoptosis of tumour cells in vitro and reduce tumour growth in multiple in vivo models. A key unknown of cellular therapy is the location and duration of cells following intravenous delivery. 111 Indium-oxine is established for lymphocyte tracking but it has low sensitivity and is toxic to cells. 89 Zirconium-oxine is a novel PET tracer which has better sensitivity and lower toxicity. Our study aimed to label MSCTRAIL with 89 Zr with the aim of tracking cells in patients enrolled in the TACTICAL trial – an early phase trial delivering MSCTRAIL to patients with metastatic lung adenocarcinoma. Methods MSC-TRAIL cells were incubated with multiple doses of 89 Zr-oxine and label retention measured using a gamma counter. Cells were assessed for cell viability using cell proliferation assays, TRAIL expression was determined using flow cytometry and ELISA and apoptosis was determined using co-culture experiments with luciferase expressing cancer cell lines and bioluminescent readout. DNA damage and cellular stress was assessed using western blotting. To determine whether radiolabelled cells could be detected in vivo , 2 × 10 5 89 Zr-Oxine MSC-TRAIL cells were delivered intravenously and imaging was performed at multiple time points (Mediso PET-CT, AMI-X). Results 89 Zr-oxine labelling at clinically relevant doses did not affect cell proliferation and therapeutic efficacy was maintained in co-culture experiments. There was no evidence of DNA damage and cell stress response and cellular phenotype was maintained. CT/PET imaging after labelling and delivery of the cells into mice showed good correlation with bioluminescent signal confirming its use a high sensitivity tracking tool. Conclusion 89 Zr-oxine can be used to successfully radiolabel genetically modified stem cells without effecting cell viability or therapeutic efficacy. We are currently performing in vivo studies to enable further translation into a clinical trial and will ultimately track MSC-TRAIL after patient administration via radiolabelling with 89 Zr-oxine.

Objectives Genomic studies of malignant pleural mesothelioma (MPM) have identified frequent mutations in the nuclear deubiquitinase BRCA Associated Protein 1 (BAP1). Previous studies have identified 100% correlation between BAP1 nuclear staining and wild type BAP1 status, pointing to immunohistochemistry (IHC) as a reliable technique to detect BAP1 molecular status. The objective of this study is to assess BAP1 expression and infer molecular status using IHC in a cohort from a prospective UK based clinical trial (MSO1). Furthermore, we aim to evaluate the effect of BAP1 status on treatment outcomes. Methods BAP1 expression was evaluated by IHC in 79 biopsies independently by two consultant histopathologists. Cases were considered positive (wild type BAP1) if strong nuclear staining was present and negative (mutant BAP1) if absent. Results Assessment of BAP1 expression was concordant in 77 of 79 cases (97%). BAP1 expression was negative in 66 of these 77 cases (86%). Patient characteristics and the effect of BAP1 expression on treatment outcomes are in Table 1. Conclusions BAP1 expression was negative in 86% of MPM tumours suggesting a high frequency of BAP1 mutations in this UK cohort. No significant differences in clinical characteristics or outcomes were noted between cases with positive or negative BAP1 expression overall. When analysed by treatment subgroup, there was a trend towards a survival benefit in cases with negative BAP1 expression (BAP1 mutants) in the ASC plus vinorelbine arm, but no statistically significant difference in outcomes within any treatment arm. We plan to further validate our findings by correlating BAP1 expression directly with BAP1 molecular status in this cohort using laser capture microdissection and sequencing.

Introduction Lung cancer screening by Low-Dose CT (LDCT) has been shown to reduce mortality, and the harm-benefit balance of screening is optimised by screening those at higher risk. The Lung Screen Uptake Trial is a UK based randomised controlled trial of standard versus enhanced invitation methods for LDCT screening in more deprived communities. Methods Patients aged 60 to 75, at higher risk of lung cancer by virtue of their recorded smoking history, were invited to a ‘lung health check appointment’ on behalf of their GP. Attendees at one of two secondary care sites, underwent a nurse consultation that included a lung cancer risk assessment. Participants were eligible for LDCT if they met any of the following three criteria: NLST-like criteria* (≥30 pack-year smoking history and given up ≤15 years ago); PLCO m2012 score ≥1.51%; or LLP score ≥2.5%. This abstract focuses on the performance of the different eligibility criteria. Results At the time of analysis, 1997 individuals had been invited to screening and 936 attended and were enrolled into the study. 854 participants were eligible for LDCT by fulfilling any of the 3 criteria above, and 718 went on to have LDCT. The mean age of participants was 66.0 (SD 4.16), 54.4% were male and the mean smoking pack-year history was 39.7 (SD 24.9). After a median of 9.7 months follow up, 17 lung cancers were confirmed. Ten suspicious pulmonary nodules are undergoing diagnostic work up under the lung cancer multidisciplinary team (MDT) and 80 indeterminate nodules are under CT surveillance. The distribution of these cancers and nodules by eligibility criteria is shown in Table 1. Conclusions Using the NLST-like* criteria to determine eligibility would mean the fewest number screened, with 4 fewer cancers detected. The PLCO m2012 score was the most reliable way to detect cancers and resulted in less individuals screened than with use of the LLP score. Further follow up and review of the data is required to fully establish the most effective tool for determining eligibility into LDCT screening though the PLCO m2012 score shows the most promise with the available data.