Project Funding Details

Colorectal cancer continues to present at an advanced stage (55% stage III/IV), often as an emergency (24%), with associated worse survival. Current screening and diagnostic methods are invasive, have low specificity for cancer and do not have widespread patient acceptance. As such there is a pressing need to develop alternative non-invasive acceptable methods for detecting bowel cancer at an early stage. Raman spectroscopy is a technique that involves analysis of in-elastically scattered laser-light for changes that reflect the molecular and structural composition of biological samples. The resultant Raman spectrum may be considered unique for individual disease states and cancer types. The capability to analyse ?liquid biopsies? provides advantages over solid state techniques such as FTIR. This innovative study aims to definitively establish if unique Raman spectral signatures are associated with defined stages of colorectal cancer with the ultimate goal of developing diagnostic, prognostic and treatment care pathways for colorectal cancer patients. Training set data from a secondary care patient cohort has shown unique Raman spectral changes in confirmed cancer patients when compared with matched controls with high sensitivity(91%) and specificity(86%). This result now requires prospective validation in a larger patient cohort from both the primary and secondary care setting. Aims: The research will be split into two work plans (WP). The aim of the first WP will address whether Raman spectroscopy has sufficient discriminatory power to distinguish between colorectal cancer and controls at each AJCC-UICC stage. The second WP will involve primary care trials to determine if the result from a Raman spectroscopy based blood test will reduce the number of referrals to secondary care by GPs. Methods: Work Plan1: Serum samples will be obtained from 300 patients with colorectal cancer at defined stages through the Wales Cancer Bank infrastructure and 100 matched controls. Samples will be subject to a robust vibrational spectroscopic diagnostic method using Raman spectroscopy with the aim of optimising excitation wavelength and spectral reproducibility. Utilising the previously developed multivariate analysis routine and Leave One Out Cross Validation (LOOCV) tools we will test the strength of association between Raman waveforms and various cancer stages. The work will focus on patients undergoing chemo-radiotherapy (CRT) and the spectral differences between cancers at each AJCC-UICC stage. This work will also expand on promising spectral differences in pilot data from cancer types including pancreatic cancer. There will be an assessment of specificity and sensitivity of the test for future clinical utility. Work Plan 2: Serum samples from 300 patients will be collected from a primary care patient population who are presenting with symptoms/ signs suspicious of colorectal cancer. Samples will be subjected to the Raman spectroscopy method of cancer detection. The results of these tests will be used to determine the positive and negative predictive values of the Raman based method by comparing the test results to clinical outcomes. There will then be a period of interim analysis wherein the analysis routine for the primary care cohort of patients will be optimised for this patient population and results disseminated to participating GP practices in preparation for the next trial phase. After this period a validation cohort of 150 patients will be recruited, in this population the GP will have results of the Raman test before making the decision to refer the patient or not. The results from this validation cohort will then be used to evaluate if the Raman based test reduces colorectal cancer referrals under the urgent suspected cancer pathway (USC). How the results of this research will be used: Results from this work will allow the assay to be developed to appropriate reproducible laboratory grade diagnostic standards suitable for prospective patient testing, and inform a clinical trial of assay performance against the gold standard. A parallel drive towards commercialisation of the assay platform with industry partners will begin to deliver clinical utility for the NHS.

This research will investigate if bowel cancer can be diagnosed by a simple blood test. Colorectal (bowel) cancer is the third commonest cancer worldwide. It remains a leading cause of cancer- related death in the Western World. Current diagnostic tests, such as colonoscopy or faecal blood detection kits, can be invasive, unpleasant and expensive, so alternative tests are needed. We aim to be able to make it easier to diagnose bowel cancer using a simple blood test. The test uses a technique called Raman spectroscopy to detect cancer related changes in patient blood samples. The test works by shining laser light onto a sample and measuring how much light is scattered off chemicals and molecules in that sample. By measuring the scattered light we can create a unique ?fingerprint? result that is specific for colorectal cancer. Firstly, we will test the technique on 600 patients recruited by their GPs and nurses and evaluate how effective the test is at diagnosing cancer. The results will be used to define the accuracy of the blood test. Provided the results are effective a trial with 150 patients will be conducted to see if giving the blood test results to GPs will reduce the number of suspected cancer referrals.