Early Detection of Lung Cancer: Metabolic Biomarkers for High Risk Screening

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1 Early Detection of Lung Cancer: Metabolic Biomarkers for High Risk Screening Dr Paul Lewis Senior Lecturer in Biomedical Informatics PI, Pathology & Toxicology Informatics Group

2 MEDLUNG study Metabolic biomarkers for the Detection of Lung Cancer Observational study Involves Trusts across Wales and England Hywel Dda ABM Collaboration with Aberystwyth University Collecting sputum from patients who have lung cancer or deemed high risk for lung cancer Using Infrared technology to detect metabolic changes in sputum Velindre Royal Derby Royal Cornwall Great western Milton Keynes

3 MEDLUNG Why Lung Cancer? Most common cancer in the world 1.3 million deaths each year (WHO, 2009). 2 nd most common cancer in the UK most common cause of cancer mortality with 34,500 deaths per annum (Cancer Research UK, 2006) Survival time is poor > 90% of patients dying within 5 yrs of diagnosis. Why should there be a screening programme for lung cancer? 2/3 patients are diagnosed at a late stage that is currently not amenable to potentially curative treatment.

4 Screening for early detection of lung cancer WHO Requirements The condition should be an important health problem The disease has significant mortality and morbidity Intervention earlier in the disease process can improve outcomes The screening test should: be sensitive and specific involve little risk of harm be cost effective detect cancer subtypes (non-small cell and small cell) Target Population People deemed high risk : over the age of 60 with a history of smoking those with a previous history of cancer patients with chronic obstructive pulmonary disease (COPD)

5 Existing Diagnostic Technologies computerized tomography (CT) bronchoscopy chest X-ray, Common diagnostic methods are not suitable for high risk screening

6 Fourier Transform Infrared Spectroscopy (FTIR) Cheap molecular based high-throughput technology FTIR detects the absorbance of infrared light by bonds in molecules By measuring the absorbance of a certain wavelength we can determine the level of a molecule in tissue FTIR provides a spectrum of wavenumber Absorbance is usually between 4000 to 400 cm -1 Wavelengths especially in fingerprint region (1800 to 950 cm -1 )

7 FTIR and other cancers FTIR has already shown promise as a sensitive diagnostic tool to distinguish neoplastic from normal cells in cancers such as: colon (Lasch et al., 2002) prostate (Baker et al., 2009) breast (Gao et al., 1999) cervical (El-Tawil et al., 2008) gastric (Fujioka et al., 2004) oral (Fukuyama et al., 1999) oesophageal (Wang et al., 2003) BUT...there have been surprisingly few attempts to apply FTIR for diagnostic purposes using lung cancer tissue......and NONE using sputum as the tissue source Only application to sputum has been for COPD diagnosis

8 FTIR in the MEDLUNG Study Cancer patients 3 arms Normal, healthy donors High Risk (smokers etc)? Cancer Normal High Risk

9 Preliminary Findings 25 Cancer spectra Statistical test Control spectra 25 < 100 significant wavenumbers Select most significant that have biological interpretation A B C D E.. Submitted to BMC Cancer Patent Application

10 How good are our panel of wavenumbers at distinguishing cancer from normal sputum? Multivariate statistical analysis -Hierarchical Cluster Analysis- C = Cancer, N = Normal healthy control

11 Generate a Diagnostic Model Cancer & Healthy Control Wavenumbers Logistic regression B Cancer? = ax + by + c Cancer, Healthy Control & High Risk D

12 Conclusions... FTIR can distinguish cancer from healthy controls using sputum and a small panel of infrared wavenumbers Accuracy is potentially much greater than existing methods of detection Wavenumbers show which High Risk cases group with cancer Maybe potential for recognizing lung tumours that have metastasized from breast tumours Future... We will be collecting hundreds of samples over the next few years Looking to develop FTIR technology for evaluation in Hospitals/ GP Surgeries etc p.d.lewis@swansea.ac.uk