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Title: The performance of faecal and plasma biomarkers with a local population based bayesian prior risk model as a potential screening programme for oesophago-gastric cancer
Author: Hornby , Steven Thomas
Awarding Body: Exeter and Plymouth Peninsula Medical School
Current Institution: Exeter and Plymouth Peninsula Medical School
Date of Award: 2013
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Oesophago-gastric cancer is a devastating disease associated with 5 year survival rate of 11 %. It frequently presents in the later stages of the disease when curative treatment is not possible, and there is currently no screening test available. 8ayes' theorem has been used in prenatal screening for trisomy 21 and pre-eclampsia, to derive a patient-specific risk of disease. This study aimed to determine if a screening process for oesophago-gastric cancer could be developed using a combination of biomarkers and a 8ayesian prior risk model. METHODS 53 patients with established oesophago-gastric cancer were recruited along with 275 control patients. A medical history was recorded from each patient and blood taken for measurement of Plasma M2-Pyruvate Kinase (M2-PK) and two cancer antigens (CA 19-9 and 72-4). The subjects then returned a faecal sample for analysis of Faecal M2-PK. A comprehensive literature search of the risk factors for oesophago-gastric cancer was used to inform a prior risk model. The biomarkers were then combined with the prior risk model and the screening performance assessed with receiver operator characteristic curves. RESULTS The median value of all the biomarkers was higher in the cancers than the controls. A combination of prior risk model and all 4 biomarkers provided the best test performance, although the improvement seen from the addition of the prior risk model was not statistically significant. For a fixed detection rate of 60% the false positive rate (FPR) was 4.9% and 22.5% respectively for gastric and oesophageal cancers. Despite the relatively low false positive rate for gastric cancer, the low estimated prevalence in the population means that the number of endoscopies required to detect 60% of cancers would likely prove practically preclusive. The test would require a FPR of 1.3% for both cancers in order to generate the equivalent extra number of endoscopies that have been seen with colorectal screening. CONCLUSION 8ayesian Prior risk models combined with biomarker measurement can in theory be used to screen for oesophago-gastric cancer. More work is required to identify better performing biomarkers and to refine the prior risk model in order to minimize the false positive rate.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available