Download Early Detection of Lung Cancer: Metabolic

Early Detection of Lung Cancer: Metabolic
Biomarkers for High Risk Screening
Dr Paul Lewis
Senior Lecturer in Biomedical Informatics
PI, Pathology & Toxicology Informatics Group
[email protected]
01792 295222
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
MEDLUNG
Why Lung Cancer?
• Most common cancer in the world
• 1.3 million deaths each year (WHO, 2009).
• 2nd 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.
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)
Existing Diagnostic Technologies
computerized tomography (CT)
bronchoscopy
chest X-ray,
Common diagnostic methods are not suitable for high risk screening
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)
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
prostate
breast
cervical
gastric
oral
oesophageal
(Lasch et al., 2002)
(Baker et al., 2009)
(Gao et al., 1999)
(El-Tawil et al., 2008)
(Fujioka et al., 2004)
(Fukuyama et al., 1999)
(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
FTIR in the MEDLUNG Study
3 arms
Cancer patients
Normal, healthy donors
High Risk (smokers etc)
?
Cancer
Normal
High Risk
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
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
Generate a Diagnostic Model
Cancer & Healthy Control
Wavenumbers
B
Logistic regression
Cancer? = aX + bY + c
D
Cancer, Healthy Control & High Risk
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
[email protected]
01792 295222