- Email: [email protected]
EP receptors in NSCLC, and their regulation by epigenetic modifications
Posters, 6th Annual BTOG Meeting, 2008
S11
of downstream substrates, including FOXO3a, facilitating cell survival by blocking apoptosis. Evidence from patient tumour samples suggests that nuclear localization may be the most important aspect of the cell survival activity of pAkt. We have shown that nuclear pAkt expression is associated with more advanced disease or poor prognosis in non-small cell lung cancer (NSCLC) and malignant pleural mesothelioma (MPM). Carbonic Anhydrase (CA)-IX, a tumour-specific member of the carbonic anhydrase family, is a surrogate marker of hypoxia overexpressed in solid tumours. This study examines the expression of CA-IX and phosphorylated Akt (pAkt) in tumour samples from patients with MPM, correlating expression with established prognostic factors. Expression of Akt and pAkt as well as changes in the subcellular localisation of pAkt and FOXO3a, in a panel of MPM cells, over time under both normoxia and hypoxia were quantified. The role of pAkt in the survival of MPM cell lines exposed to both normoxic and hypoxic conditions was also examined. Methods: Tumour samples from 200 patients with MPM were stained using pAkt and CA-IX specific antibodies. Western blot analysis was used to examine the effect of hypoxia on Akt and pAkt expression in 4 MPM cell lines in the presence or absence of the phosphatidylinositol-3-kinase inhibitor, LY294002. Highcontent screening (HCS) analyses, using the Incell 1000, was used to quantify any changes in subcellular localisation of pAkt and FOXO3a in the cells. FACs and HCS were used to quantify levels of apoptosis. Results: There was a positive association between the level of CA-IX and pAkt staining, implying that intra-tumoural hypoxia may be a stimulus for Akt phosphorylation. On multivariate analysis increased expression of nuclear phospho-Akt (pAkt) was found to be associated with a poor survival. Hypoxia induced the activation of Akt in the panel of cell lines with CRL5915 cells showing very low levels of pAkt expression. Changes in the subcellular localisation of pAkt and FOXO3a were quantified. JU77 cells had a significant increase in the level of apoptosis under hypoxic conditions when the phosphorylation of Akt was blocked by LY294002. Conclusion: This work provides evidence for the anti-apoptotic role of pAkt in hypoxic conditions in solid human malignancies. Phospho-Akt may represent a novel therapeutic target in MPM.
FTIR to distinguish between primary lung cancer and non-cancer cases from sputum. Method: Patients: 5 (biopsy proven) non-small cell lung cancer (cases) and 26 non-cancer controls (mixture of stable COPD patients, ‘healthy’ smoking and non-smoking members of staff). Procedure: sputa was collected prior to bronchoscopy (cases) or in clinic (controls) and were frozen within 2 3 hours. Sputum cells were isolated by centrifugation and freeze dried. Bronchial cell presence in sputum was confirmed by microscopy. Freeze dried cell extracts were processed in triplicate for FTIR. FTIR spectra data processing and multivariate analysis were performed using Matlab© software. Results: The FTIR spectra show that the 5 lung cancer cases all have a significantly greater peak at certain wavenumbers in comparison to the non cancer cases. When this is data-mapped the lung cancer cases appear to group away from a large cluster in the middle of the map which is representative of the controls. There are some cases which fall in between these two subgroups which may represent patients who have premalignant lesions. All sputum samples contained bronchial cells and lung cancer patients did not have more bronchial component. This suggests the difference in metabolites is due to different expression rather than cases just producing more sputum (cells). Conclusion: This pilot suggests that i) sputum is suitable as a biofluid for easy/cost effective processing for FTIR and ii) FTIR can potentially distinguish between cancer and non-cancer cases in sputum. Greater recruitment and longer term (10 year) follow-up is now assessing combinations of biomarkers in not only diagnosing lung cancer, but detecting pre-cancerous lesions and monitoring response to treatment.
32 Using Fourier transform infrared (FTIR) spectroscopy to evaluate metabolic markers in sputum in patients with and without lung cancer
Introduction: PGE2 exerts its effects through binding to specific receptors. There are at least four subtypes of PGE2 receptor, designated as EP1, EP2, EP3, and EP4, according to their pharmacological profiles and signal transduction pathways. Although the role of each EP receptor in cancer biology remains complex, evidence is building that these receptors may be relevant therapeutic targets, and may also have predictive and or prognostic value in non-small cell lung cancer (NSCLC). Methods: A panel of normal and lung cancer cell lines were screened for expression of EP1 4, by RT-PCR under conditions of normoxia and hypoxia (0.5%). Their expression in matched tumor/normal samples from patients with NSCLC was also examined. Epigenetic mechanisms regulating their expression was examined using (a) two HDAC inhibitors Phenylbutyrate (PB, 10 mM) and Trichostatin A (TSA, 250 ng/ml), and (b) DNA methyltransferase inhibition using 5-aza-2-deoxycytidine (DAC1 mM). Results: Expression of all four EP receptors could be readily detected in all cell lines with the following exceptions; Beas-2B and A549 did not express EP3, and H1299 did not express any EP2. In primary NSCLC lung tumour samples (n = 20) with matched normal tissue, altered expression for EP receptors was observed in all tumours specimens. Epigenetics mechanisms regulating the expression EP1 4 were studied. A549 (adenocarcinoma) and SK-MES-1 (squamous cell carcinoma) cell lines were treated with 5-Aza-2-deoxycytidine. A clear upregulation of EP1 mRNA was observed. Bioinformatic analysis
R. Ghosal1,2 , K.E.L. Lewis1,2 , P. Kloer2 , R. Mehta3 , D. Parry3 , C. Llewllyn-Jones4 , L. Mur5 , J. Blaser5 , P.D. Lewis1 . 1 School of Medicine, Swansea University; 2 Respiratory Department, Prince Philip Hospital, Llanelli; 3 Respiratory Department, Princess of Wales Hospital, Bridgend; 4 Respiratory Department, West Wales General Hospital, Carmarthen; 5 Institute of Biological Sciences, University of Aberystwyth, UK Introduction: There are 1.3 million worldwide and over 37,000 new cases of lung cancer diagnosed in the UK each year. The incidence of lung cancer is higher in Wales than the UK average 2 . MEDLUNG is a long term study measuring different combinations of metabolic biomarkers for early detection of lung cancer. Biofluids, including sputum and serum, and biopsy tissue are being collected prospectively from people undergoing bronchoscopy for suspected lung cancer. A key objective of this project is to evaluate Fourier transform infrared (FTIR) spectroscopy for metabolic markers in sputum. FTIR is an established, cost effective technique that enables rapid, highthroughput analysis of different sample types. FTIR has great potential as a metabolic fingerprinting technique and has been applied in a wide variety of clinical settings. We have carried out a preliminary study to evaluate: (i) suitability of sputum as a biofluid for easy/cost effective processing for FTIR (ii) ability of
Reference(s) [1] http//www.cancerresearchuk.org. [2] Welsh Cancer Intelligence and Surveillance Unit. Trachea, Bronchus and Lung Cancer in Wales (Diagnosis Period 1995 2004), Occasional Report S0605.
33 EP receptors in NSCLC, and their regulation by epigenetic modifications S.G. Gray, N. Al-Sarraf, K.J. O’Byrne. Trinity Centre for Health Sciences, Institute of Molecular Medicine, St James’s Hospital, Dublin, Ireland
S12
Posters, 6th Annual BTOG Meeting, 2008 35 Lung cancer
the devil is in the detail
of the genomic DNA containing the EP1 gene, indicates that the exonsfor this gene are extremely CpG rich and may be a hot-spot for DNA CpG methylation. Cells were also treated with the histone deacetylase inhibitors TSA and PB. EP-2 and EP-3 were robustly inducible by histone deacetylase inhibition, while EP4 was slightly inducible. In contrast, EP1 expression was downregulated following treatment with TSA. When compared to cells grown under normoxic conditions, EP1 expression was induced in A549 cells following 24 hour exposure to hypoxia. We are currently evaluating the effect of hypoxia on the other EP receptors in these samples. Conclusions: Our data indicates that aberrant expression of the EP receptors is a common event in NSCLC. We show that EP receptors are epigenetically regulated via histone post-translational modifications and DNA CpG methylation. In addition, the expression of these receptors is affected by hypoxia. Further investigations are required to delineate the role of these receptors in NSCLC, and whether aberrant epigenetic regulation of these genes is important in NSCLC pathogenesis. Should this prove true, targeting the epigenetic mechanisms underpinning this pathway may be of therapeutic value in the treatment of NSCLC.
Category
No (%)
Delay median (range)
Networks & Pathways
Abnormality missed by radiologist
14 (6.25%)
Abnormality missed by clinician
8 (3.57%)
J. D. Lung Cancer CNS, University Hospital North Tees, UK, 2 Respiratory Oncology Nurse Specialist, Darlington Memorial Hospital, Darlington, UK
No action despite recommendation
3 (1.34%)
Imaging for other reasons, delayed referral Long interval between imaging and follow-up
1 (0.45%) 7 (3.13%)
Introduction: The authors deliver lessons to students in local secondary schools as part of a project organised by Durham Education Business Partnership (DEBP). This project is designed to promote different career pathways to students aged 14 years who are studying for NVQ qualifications. Method: The sessions focus on the role of the Lung Cancer Specialist Nurse, also smoking and lung cancer awareness. Studies have shown that 95% of smokers start in their childhood years and about 450 children start smoking every day in Great Britain 1 . One of the challenges in delivering the sessions is to maintain both the interest and attention of up to 30 students. This is achieved through various teaching strategies such as brainstorming, PowerPoint presentations and questions and answers. Results: An ongoing challenge is that of auditing the effectiveness of the education. However, comments from students, to date, suggest that they find sessions constructive and new information beneficial, with some students considering smoking cessation and others determined not to start. Conclusion: This project plays a small role in supporting the Government initiative to achieve a reduction in the number of children/adolescents who smoke 2 ; thus reducing the risk of developing lung cancer and other related illnesses. In addition, by raising lung cancer awareness, it is anticipated that these young people could become more proactive in recognising the signs and symptoms and thus be empowered to educate others on the importance of acting on early warning signs.
Malignancy not confirmed on initial tests
5 (2.23%)
Total (n = 224)
38 (16.96%)
334 days (15 1113) 168 days (46 1338) 114 days (87 470) 99 days 90 days (66 170) 135 days (84 497) 153 days
34 Promoting lung cancer awareness in secondary schools Draffan1 ,
Brown2 . 1 Macmillan
Reference(s) [1] Roy Castle: Kids Against Tobacco Smoke. 2007 [2] Saving Lives “Our Healthier Nation” DOH 2000
B.A. Khan1 , A.A. Lwin1 , D. Baker2 , E.H. Sawicka1 . Departments of Respiratory Medicine, Princess Royal University Hospital, Orpington, Kent, UK, 2 Departments of Radiology, Princess Royal University Hospital, Orpington, Kent, UK Introduction: Survival figures for lung cancer in the UK lag behind most of Europe. In our unit patients are usually diagnosed in 18 days, but most have advanced disease. We looked to see if an earlier diagnosis could have been reached. Method: We reviewed all patients diagnosed with lung cancer from March 2006 to August 2007, recording the date of MDT meeting as the date of diagnosis. All previous imaging prior to the index chest x-ray (CXR), defined as the CXR leading to referral, was reviewed for any abnormality that could have prompted earlier investigation. Causes of delay were categorised. The time from first abnormal CXR to index CXR was calculated as the delay. Results: 224 patients’ data was reviewed. 38 patients had abnormal images prior to the index CXR, of these 4 (10.5%) had small cell lung cancer (SCLC).
Conclusion: Significant radiological abnormalities often predate the index CXR in patients diagnosed with lung cancer, and in some cases co-morbidities may obscure the diagnosis. This contributes to a delay in treatment and poorer survival, especially in patients with SCLC. Radiological workload needs reviewing, as well as pathways prior to referral, to improve efficiency, accuracy of diagnosis, and outcomes for patients. However further work is needed to determine the precise impact of these delays. 36 An audit of patient and consultant satisfaction with a lung cancer nurse specialist follow up service H. Jones, A. Hickox. Macmillan Lung Cancer CNS’s Calderdale and Huddersfield NHS Foundation Trust, UK Introduction: In 2005 the NICE guidelines for the diagnosis and treatment of lung cancer recommended that patients should have the option of protocol driven nurse-led follow up. A local protocol was developed with the lung cancer multidisciplinary team and implemented from September 2006. Some or all routine visits to the consultant clinics were replaced by prearranged telephone calls or home visits by specialist nurses. The location of assessment was determined on an individual basis. 56 patients have been entered into the protocol so far. Method: There was a three-stage data collection process. (1) 45 patients with lung cancer were randomly selected and their notes reviewed. As few of these patients had experienced nurse-led follow up, a further10 were purposively selected. (2) An anonymous questionnaire was sent to patients currently on nurse-led follow up (n = 14). (3) Questionnaire to chest physicians and oncologists (n = 6). Findings: All patients were referred appropriately although not all consultants complied exactly with the protocol. 11 patients
S11
of downstream substrates, including FOXO3a, facilitating cell survival by blocking apoptosis. Evidence from patient tumour samples suggests that nuclear localization may be the most important aspect of the cell survival activity of pAkt. We have shown that nuclear pAkt expression is associated with more advanced disease or poor prognosis in non-small cell lung cancer (NSCLC) and malignant pleural mesothelioma (MPM). Carbonic Anhydrase (CA)-IX, a tumour-specific member of the carbonic anhydrase family, is a surrogate marker of hypoxia overexpressed in solid tumours. This study examines the expression of CA-IX and phosphorylated Akt (pAkt) in tumour samples from patients with MPM, correlating expression with established prognostic factors. Expression of Akt and pAkt as well as changes in the subcellular localisation of pAkt and FOXO3a, in a panel of MPM cells, over time under both normoxia and hypoxia were quantified. The role of pAkt in the survival of MPM cell lines exposed to both normoxic and hypoxic conditions was also examined. Methods: Tumour samples from 200 patients with MPM were stained using pAkt and CA-IX specific antibodies. Western blot analysis was used to examine the effect of hypoxia on Akt and pAkt expression in 4 MPM cell lines in the presence or absence of the phosphatidylinositol-3-kinase inhibitor, LY294002. Highcontent screening (HCS) analyses, using the Incell 1000, was used to quantify any changes in subcellular localisation of pAkt and FOXO3a in the cells. FACs and HCS were used to quantify levels of apoptosis. Results: There was a positive association between the level of CA-IX and pAkt staining, implying that intra-tumoural hypoxia may be a stimulus for Akt phosphorylation. On multivariate analysis increased expression of nuclear phospho-Akt (pAkt) was found to be associated with a poor survival. Hypoxia induced the activation of Akt in the panel of cell lines with CRL5915 cells showing very low levels of pAkt expression. Changes in the subcellular localisation of pAkt and FOXO3a were quantified. JU77 cells had a significant increase in the level of apoptosis under hypoxic conditions when the phosphorylation of Akt was blocked by LY294002. Conclusion: This work provides evidence for the anti-apoptotic role of pAkt in hypoxic conditions in solid human malignancies. Phospho-Akt may represent a novel therapeutic target in MPM.
FTIR to distinguish between primary lung cancer and non-cancer cases from sputum. Method: Patients: 5 (biopsy proven) non-small cell lung cancer (cases) and 26 non-cancer controls (mixture of stable COPD patients, ‘healthy’ smoking and non-smoking members of staff). Procedure: sputa was collected prior to bronchoscopy (cases) or in clinic (controls) and were frozen within 2 3 hours. Sputum cells were isolated by centrifugation and freeze dried. Bronchial cell presence in sputum was confirmed by microscopy. Freeze dried cell extracts were processed in triplicate for FTIR. FTIR spectra data processing and multivariate analysis were performed using Matlab© software. Results: The FTIR spectra show that the 5 lung cancer cases all have a significantly greater peak at certain wavenumbers in comparison to the non cancer cases. When this is data-mapped the lung cancer cases appear to group away from a large cluster in the middle of the map which is representative of the controls. There are some cases which fall in between these two subgroups which may represent patients who have premalignant lesions. All sputum samples contained bronchial cells and lung cancer patients did not have more bronchial component. This suggests the difference in metabolites is due to different expression rather than cases just producing more sputum (cells). Conclusion: This pilot suggests that i) sputum is suitable as a biofluid for easy/cost effective processing for FTIR and ii) FTIR can potentially distinguish between cancer and non-cancer cases in sputum. Greater recruitment and longer term (10 year) follow-up is now assessing combinations of biomarkers in not only diagnosing lung cancer, but detecting pre-cancerous lesions and monitoring response to treatment.
32 Using Fourier transform infrared (FTIR) spectroscopy to evaluate metabolic markers in sputum in patients with and without lung cancer
Introduction: PGE2 exerts its effects through binding to specific receptors. There are at least four subtypes of PGE2 receptor, designated as EP1, EP2, EP3, and EP4, according to their pharmacological profiles and signal transduction pathways. Although the role of each EP receptor in cancer biology remains complex, evidence is building that these receptors may be relevant therapeutic targets, and may also have predictive and or prognostic value in non-small cell lung cancer (NSCLC). Methods: A panel of normal and lung cancer cell lines were screened for expression of EP1 4, by RT-PCR under conditions of normoxia and hypoxia (0.5%). Their expression in matched tumor/normal samples from patients with NSCLC was also examined. Epigenetic mechanisms regulating their expression was examined using (a) two HDAC inhibitors Phenylbutyrate (PB, 10 mM) and Trichostatin A (TSA, 250 ng/ml), and (b) DNA methyltransferase inhibition using 5-aza-2-deoxycytidine (DAC1 mM). Results: Expression of all four EP receptors could be readily detected in all cell lines with the following exceptions; Beas-2B and A549 did not express EP3, and H1299 did not express any EP2. In primary NSCLC lung tumour samples (n = 20) with matched normal tissue, altered expression for EP receptors was observed in all tumours specimens. Epigenetics mechanisms regulating the expression EP1 4 were studied. A549 (adenocarcinoma) and SK-MES-1 (squamous cell carcinoma) cell lines were treated with 5-Aza-2-deoxycytidine. A clear upregulation of EP1 mRNA was observed. Bioinformatic analysis
R. Ghosal1,2 , K.E.L. Lewis1,2 , P. Kloer2 , R. Mehta3 , D. Parry3 , C. Llewllyn-Jones4 , L. Mur5 , J. Blaser5 , P.D. Lewis1 . 1 School of Medicine, Swansea University; 2 Respiratory Department, Prince Philip Hospital, Llanelli; 3 Respiratory Department, Princess of Wales Hospital, Bridgend; 4 Respiratory Department, West Wales General Hospital, Carmarthen; 5 Institute of Biological Sciences, University of Aberystwyth, UK Introduction: There are 1.3 million worldwide and over 37,000 new cases of lung cancer diagnosed in the UK each year. The incidence of lung cancer is higher in Wales than the UK average 2 . MEDLUNG is a long term study measuring different combinations of metabolic biomarkers for early detection of lung cancer. Biofluids, including sputum and serum, and biopsy tissue are being collected prospectively from people undergoing bronchoscopy for suspected lung cancer. A key objective of this project is to evaluate Fourier transform infrared (FTIR) spectroscopy for metabolic markers in sputum. FTIR is an established, cost effective technique that enables rapid, highthroughput analysis of different sample types. FTIR has great potential as a metabolic fingerprinting technique and has been applied in a wide variety of clinical settings. We have carried out a preliminary study to evaluate: (i) suitability of sputum as a biofluid for easy/cost effective processing for FTIR (ii) ability of
Reference(s) [1] http//www.cancerresearchuk.org. [2] Welsh Cancer Intelligence and Surveillance Unit. Trachea, Bronchus and Lung Cancer in Wales (Diagnosis Period 1995 2004), Occasional Report S0605.
33 EP receptors in NSCLC, and their regulation by epigenetic modifications S.G. Gray, N. Al-Sarraf, K.J. O’Byrne. Trinity Centre for Health Sciences, Institute of Molecular Medicine, St James’s Hospital, Dublin, Ireland
S12
Posters, 6th Annual BTOG Meeting, 2008 35 Lung cancer
the devil is in the detail
of the genomic DNA containing the EP1 gene, indicates that the exonsfor this gene are extremely CpG rich and may be a hot-spot for DNA CpG methylation. Cells were also treated with the histone deacetylase inhibitors TSA and PB. EP-2 and EP-3 were robustly inducible by histone deacetylase inhibition, while EP4 was slightly inducible. In contrast, EP1 expression was downregulated following treatment with TSA. When compared to cells grown under normoxic conditions, EP1 expression was induced in A549 cells following 24 hour exposure to hypoxia. We are currently evaluating the effect of hypoxia on the other EP receptors in these samples. Conclusions: Our data indicates that aberrant expression of the EP receptors is a common event in NSCLC. We show that EP receptors are epigenetically regulated via histone post-translational modifications and DNA CpG methylation. In addition, the expression of these receptors is affected by hypoxia. Further investigations are required to delineate the role of these receptors in NSCLC, and whether aberrant epigenetic regulation of these genes is important in NSCLC pathogenesis. Should this prove true, targeting the epigenetic mechanisms underpinning this pathway may be of therapeutic value in the treatment of NSCLC.
Category
No (%)
Delay median (range)
Networks & Pathways
Abnormality missed by radiologist
14 (6.25%)
Abnormality missed by clinician
8 (3.57%)
J. D. Lung Cancer CNS, University Hospital North Tees, UK, 2 Respiratory Oncology Nurse Specialist, Darlington Memorial Hospital, Darlington, UK
No action despite recommendation
3 (1.34%)
Imaging for other reasons, delayed referral Long interval between imaging and follow-up
1 (0.45%) 7 (3.13%)
Introduction: The authors deliver lessons to students in local secondary schools as part of a project organised by Durham Education Business Partnership (DEBP). This project is designed to promote different career pathways to students aged 14 years who are studying for NVQ qualifications. Method: The sessions focus on the role of the Lung Cancer Specialist Nurse, also smoking and lung cancer awareness. Studies have shown that 95% of smokers start in their childhood years and about 450 children start smoking every day in Great Britain 1 . One of the challenges in delivering the sessions is to maintain both the interest and attention of up to 30 students. This is achieved through various teaching strategies such as brainstorming, PowerPoint presentations and questions and answers. Results: An ongoing challenge is that of auditing the effectiveness of the education. However, comments from students, to date, suggest that they find sessions constructive and new information beneficial, with some students considering smoking cessation and others determined not to start. Conclusion: This project plays a small role in supporting the Government initiative to achieve a reduction in the number of children/adolescents who smoke 2 ; thus reducing the risk of developing lung cancer and other related illnesses. In addition, by raising lung cancer awareness, it is anticipated that these young people could become more proactive in recognising the signs and symptoms and thus be empowered to educate others on the importance of acting on early warning signs.
Malignancy not confirmed on initial tests
5 (2.23%)
Total (n = 224)
38 (16.96%)
334 days (15 1113) 168 days (46 1338) 114 days (87 470) 99 days 90 days (66 170) 135 days (84 497) 153 days
34 Promoting lung cancer awareness in secondary schools Draffan1 ,
Brown2 . 1 Macmillan
Reference(s) [1] Roy Castle: Kids Against Tobacco Smoke. 2007 [2] Saving Lives “Our Healthier Nation” DOH 2000
B.A. Khan1 , A.A. Lwin1 , D. Baker2 , E.H. Sawicka1 . Departments of Respiratory Medicine, Princess Royal University Hospital, Orpington, Kent, UK, 2 Departments of Radiology, Princess Royal University Hospital, Orpington, Kent, UK Introduction: Survival figures for lung cancer in the UK lag behind most of Europe. In our unit patients are usually diagnosed in 18 days, but most have advanced disease. We looked to see if an earlier diagnosis could have been reached. Method: We reviewed all patients diagnosed with lung cancer from March 2006 to August 2007, recording the date of MDT meeting as the date of diagnosis. All previous imaging prior to the index chest x-ray (CXR), defined as the CXR leading to referral, was reviewed for any abnormality that could have prompted earlier investigation. Causes of delay were categorised. The time from first abnormal CXR to index CXR was calculated as the delay. Results: 224 patients’ data was reviewed. 38 patients had abnormal images prior to the index CXR, of these 4 (10.5%) had small cell lung cancer (SCLC).
Conclusion: Significant radiological abnormalities often predate the index CXR in patients diagnosed with lung cancer, and in some cases co-morbidities may obscure the diagnosis. This contributes to a delay in treatment and poorer survival, especially in patients with SCLC. Radiological workload needs reviewing, as well as pathways prior to referral, to improve efficiency, accuracy of diagnosis, and outcomes for patients. However further work is needed to determine the precise impact of these delays. 36 An audit of patient and consultant satisfaction with a lung cancer nurse specialist follow up service H. Jones, A. Hickox. Macmillan Lung Cancer CNS’s Calderdale and Huddersfield NHS Foundation Trust, UK Introduction: In 2005 the NICE guidelines for the diagnosis and treatment of lung cancer recommended that patients should have the option of protocol driven nurse-led follow up. A local protocol was developed with the lung cancer multidisciplinary team and implemented from September 2006. Some or all routine visits to the consultant clinics were replaced by prearranged telephone calls or home visits by specialist nurses. The location of assessment was determined on an individual basis. 56 patients have been entered into the protocol so far. Method: There was a three-stage data collection process. (1) 45 patients with lung cancer were randomly selected and their notes reviewed. As few of these patients had experienced nurse-led follow up, a further10 were purposively selected. (2) An anonymous questionnaire was sent to patients currently on nurse-led follow up (n = 14). (3) Questionnaire to chest physicians and oncologists (n = 6). Findings: All patients were referred appropriately although not all consultants complied exactly with the protocol. 11 patients