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14 Lung cancer diagnosis, EGFR testing and their implications
Poster abstracts, 11th Annual British Thoracic Oncology Group Conference, 2013: Chemotherapy Stratification of patients according to smoking status revealed EGFR mutations in approximately 44% of non-smokers, 7% of current smokers, and 10% of ex-smokers. This finding is independent of gender. KRAS mutation was detected in 11% non-smokers, 29% of current smokers and 40% of ex-smokers. Further subdivision of the exsmoker patient group according to number of years stopped revealed an EGFR positive rate of 18% in ex>15 years and 6% of ex<15 years. The most common KRAS mutation detected was c.34G>T; p.Gly12Cys. This was found in 44% and 39% of KRAS positive never and current smoking groups respectively. 2.2% of samples completely failed to produce an EGFR result. The combined fail/partial fail rate for EGFR ranged from 4.4% to 20.7% according to referral centre. Conclusion: EGFR mutations are found in a significant proportion of Adenocarcinoma NSCLC tumours arising in current and ex smokers. It is therefore important that these patient groups are not excluded from testing. 13 Acquired resistance to EGFR inhibition: evolution from adenocarcinoma to small cell lung cancer (SCLC) C. Moss1 *, P. Cane1 , E. Mclean1 , G. Santis1,2 , K. Tobal1 , J. Spicer1,2 . 1 Guy’s and St Thomas’ NHS Foundation Trust, 2 King’s College London, UK Background: All patients with EGFR-mutated lung cancer who initially respond to treatment with first generation EGFR tyrosine kinase inhibitors (TKIs) eventually progress due to acquired resistance. Recent advances have been made in the understanding of mechanisms driving this acquired resistance, and specific therapies targeted at some of these resistance events are available. Methods: Re-biopsy on progression for patients who have benefited from EGFR TKIs has become a standard of care at our institution. We report a case of EGFR inhibitor resistance with morphological transformation from EGFR-mutated adenocarcinoma to SCLC. Results: A 79-year-old male Vietnamese ex-smoker, with background emphysema, was diagnosed in 2008 with a T2N1 right upper lobe lung adenocarcinoma. An EGFR exon 19 deletion was detected. Initial treatment was with radical radiotherapy; upon relapse 2 years later, he commenced erlotinib and enjoyed a partial response which was maintained for a further 2 years. In May 2012, progressive disease was noted at the right hilum, with small volume liver and brain metastases. Endobronchial ultrasound-guided sampling demonstrated small cell lung carcinoma. He received whole brain radiotherapy and 3 cycles of carboplatin/etoposide chemotherapy to partial response. Conclusion: A previous systematic study of the molecular and histological changes associated with EGFR inhibitor resistance in 37 patients found 5 (14%) with SCLC transformation. In this series, the original EGFR mutation was maintained in all 5 cases, refuting the possibility of a co-incidental second primary. Our case illustrates the importance in routine practice of reassessing EGFR-driven lung cancers following the development of resistance to TKIs. 14 Lung cancer diagnosis, EGFR testing and their implications K. Lodge *, L. Lok, T. Win. East and North Hertfordshire NHS Trust, UK Introduction: Targeted treatment with tyrosine kinase inhibitors (TKI) is recommended for patients with non-small cell lung cancers (NSCLC) positive for epidermal growth factor receptor (EGFR) mutations. However, this treatment is relatively new and EGFR mutation testing has not been uniformly available due to funding issues. We undertook an audit of patients diagnosed with lung cancer in a district general hospital in 2011, reviewing their tissue diagnosis and EGFR testing status.
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Methods: All patients diagnosed with lung cancer in 2011 were selected from the local lung cancer database in our district general hospital. Data were collected from electronic records of clinic letters and histocytological results. Results: A total of 228 patients were audited, 135 males and 93 females. 128 (56.1%) patients had histological or cytological confirmation of diagnosis. Of these 128 patients, 37 (28.9%) had adenocarcinomas, 33 (25.8%) squamous cell carcinomas, 5 (3.9%) adenosquamous carcinomas, 11 (8.6%) NSCLC not otherwise specified (NOS), 4 (3.1%) neuroendocrine tumours, 23 (18.0%) small cell carcinomas and 15 (11.7%) mesotheliomas. In total 24 patients were tested for EGFR mutations: 17 with adenocarcinomas, 3 with adenosquamous carcinomas, 2 with NSCLC NOS and 2 with squamous cell carcinomas. 53 cases should have been tested for EGFR mutations according to current national guidelines; however only 22 (41.5%) out of 53 cases were tested. 4 out of 22 (18%) patients tested had EGFR mutations and received TKI. Conclusion: In our cohort only 41.5% of patients eligible for EGFR testing were tested. Reasons such as clinical suitability for treatment are not enough to explain the shortfall in testing. With current national efforts at improving lung cancer survival, it is important to focus resources on improving EGFR testing to maximise treatment options with survival benefit for patients with NSCLC. 15 Non-invasive KRAS and EGFR mutation testing of primary lung cancer via peripheral blood circulating tumour cells M.B. Freidin *, A. Tay, D. Chudasama, A.G. Nicholson, A. Rice, O. Bamsey, A. Higgins, S. Popat, V. Anikin, E. Lim. The Royal Brompton Hospital, London, UK Background: As circulating tumour cells (CTCs) are present in the blood stream of a proportion of patients with lung cancer, we sought to determine if it is possible (as a proof of concept) to predict the underlying mutation status of the primary tumour through capture and real-time polymerase chain reaction (RT-PCR) of CTC DNA. Methods: From 24/01/12 to 20/09/2012 peripheral blood CTCs were captured in 67 patients using ScreenCell™ Cyto and 82 patients using the ScreenCellTM MB devices from patients who underwent surgery for lung cancer at The Royal Brompton Hospital. Captured cells were stained using H&E and independently assessed by two pathologists (AGN, AR) for the presence of atypical cells suspicious for cancer. In a sample of 23 patients who were eligible and consented for the CRUK Stratified Medicines Program (SMP), the primary tumour KRAS and EGFR status was determined using Roche cobas® 4800 system and SSCA approach, and mutation detection of the extracted CTC undertaken with RT-PCR using Panagene PNAClamp™ KRAS and EGFR mutation detection kits after whole genome amplification. Results: In specimens obtained with Cyto devices suspicious atypical cells were diagnosed in 57.7% by both pathologists with a concordance of 66.7%. For 23 patients who participated in the CRUCK SMP CTCs were identified in 9 and 11 patients by each pathologist, respectively, with same concordance rate. Overall mutation rate in codons 12/13 of the KRAS gene was 32.1%, and concordance with CRUK SMP KRAS mutation testing for primary tumours for 23 patients was 70%. Six mutations were detected in CTCs but not in primary tumours, and 1 mutation in primary tumour was not found in corresponding CTC sample. Overall mutation rate in EGFR gene was 11%. The eligible mutations were G719X, exon 19 deletion, S768I, and L858R or L861Q, and concordance with CRUK SMP testing for EGFR mutations was 78%. Three mutations in CTCs were not present in primary tumours, and 2 mutations in primary tumours were not present in corresponding CTC samples. Conclusion: The result of our study indicates that it is possible to extract DNA from CTCs to screen for primary tumour mutations with reasonable concordance. Differences in the mutation results from the CTC and primary tumours needs to be explored in more detail
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Methods: All patients diagnosed with lung cancer in 2011 were selected from the local lung cancer database in our district general hospital. Data were collected from electronic records of clinic letters and histocytological results. Results: A total of 228 patients were audited, 135 males and 93 females. 128 (56.1%) patients had histological or cytological confirmation of diagnosis. Of these 128 patients, 37 (28.9%) had adenocarcinomas, 33 (25.8%) squamous cell carcinomas, 5 (3.9%) adenosquamous carcinomas, 11 (8.6%) NSCLC not otherwise specified (NOS), 4 (3.1%) neuroendocrine tumours, 23 (18.0%) small cell carcinomas and 15 (11.7%) mesotheliomas. In total 24 patients were tested for EGFR mutations: 17 with adenocarcinomas, 3 with adenosquamous carcinomas, 2 with NSCLC NOS and 2 with squamous cell carcinomas. 53 cases should have been tested for EGFR mutations according to current national guidelines; however only 22 (41.5%) out of 53 cases were tested. 4 out of 22 (18%) patients tested had EGFR mutations and received TKI. Conclusion: In our cohort only 41.5% of patients eligible for EGFR testing were tested. Reasons such as clinical suitability for treatment are not enough to explain the shortfall in testing. With current national efforts at improving lung cancer survival, it is important to focus resources on improving EGFR testing to maximise treatment options with survival benefit for patients with NSCLC. 15 Non-invasive KRAS and EGFR mutation testing of primary lung cancer via peripheral blood circulating tumour cells M.B. Freidin *, A. Tay, D. Chudasama, A.G. Nicholson, A. Rice, O. Bamsey, A. Higgins, S. Popat, V. Anikin, E. Lim. The Royal Brompton Hospital, London, UK Background: As circulating tumour cells (CTCs) are present in the blood stream of a proportion of patients with lung cancer, we sought to determine if it is possible (as a proof of concept) to predict the underlying mutation status of the primary tumour through capture and real-time polymerase chain reaction (RT-PCR) of CTC DNA. Methods: From 24/01/12 to 20/09/2012 peripheral blood CTCs were captured in 67 patients using ScreenCell™ Cyto and 82 patients using the ScreenCellTM MB devices from patients who underwent surgery for lung cancer at The Royal Brompton Hospital. Captured cells were stained using H&E and independently assessed by two pathologists (AGN, AR) for the presence of atypical cells suspicious for cancer. In a sample of 23 patients who were eligible and consented for the CRUK Stratified Medicines Program (SMP), the primary tumour KRAS and EGFR status was determined using Roche cobas® 4800 system and SSCA approach, and mutation detection of the extracted CTC undertaken with RT-PCR using Panagene PNAClamp™ KRAS and EGFR mutation detection kits after whole genome amplification. Results: In specimens obtained with Cyto devices suspicious atypical cells were diagnosed in 57.7% by both pathologists with a concordance of 66.7%. For 23 patients who participated in the CRUCK SMP CTCs were identified in 9 and 11 patients by each pathologist, respectively, with same concordance rate. Overall mutation rate in codons 12/13 of the KRAS gene was 32.1%, and concordance with CRUK SMP KRAS mutation testing for primary tumours for 23 patients was 70%. Six mutations were detected in CTCs but not in primary tumours, and 1 mutation in primary tumour was not found in corresponding CTC sample. Overall mutation rate in EGFR gene was 11%. The eligible mutations were G719X, exon 19 deletion, S768I, and L858R or L861Q, and concordance with CRUK SMP testing for EGFR mutations was 78%. Three mutations in CTCs were not present in primary tumours, and 2 mutations in primary tumours were not present in corresponding CTC samples. Conclusion: The result of our study indicates that it is possible to extract DNA from CTCs to screen for primary tumour mutations with reasonable concordance. Differences in the mutation results from the CTC and primary tumours needs to be explored in more detail