Infrared Imaging for Diagnosis and Prediction of the Biopotental of Low and Intermediate Risk Prostate Cancer

More than a quarter of a million people are diagnosed with cancer annually in the UK and the four most common ones, breast, lung, bowel and prostate cancer, make up over half of all these cases. Many, such as prostate cancer correlate strongly with age, 77% of cases being diagnosed in men over the age of 55. This produces a compound problem, as Western populations are ageing rapidly and the number of people diagnosed with cancer in European countries is inevitably going to rise. This will put a considerable strain on all parts of the health care systems and will have dramatic effects on health care costs. The problem is particularly prescient in certain cancers such as prostate cancer and breast cancer, which are endemic in the older population and whose natural history is uncertain in many cases. There is a clear clinical need for a robust and preferably automated system which can not only facilitate the pathological diagnosis but also to discriminate between tumours of low risk, which require surveillance or less aggressive treatment, and those of high risk, which will progress more rapidly and which need aggressive intervention to prevent morbidity and death. We have shown previously in small scale studies that infra red spectral markers used in conjunction with algorithmic models can be utilised not only to provide tumour grading data but also to provide staging and prognostic information. The attraction of infrared spectroscopy to aid clinical diagnosis is that it is a widely known technology which is readily available, reliable, simple to use and relatively inexpensive. It also allows further post scanning interrogation because it does not destroy the tissue under investigation. However, introduction into the clinical environment has been hampered by a lack of understanding of some of the fundamental principles. We have successfully addressed many of the fundamental issue with single cells and aim to utilize this knowledge to address scanning of tissue biopsiesThe aim of this proposal is to develop techniques using spectroscopic analysis of cancer tissue, which build on a strong scientific base developed by our collaborative research group and by others working in this field. We propose to develop rapid and accurate systems of analysis, which can be applied to the identification and characterisation of biological tissues and we will use prostate cancer as the primary model.Using prostate cancer as our model of low and high risk disease we will adapt existing technologies and protocols to enable rapid high throughput infra red screening of tissue samples which could be transferred from the research laboratory into a standard pathology laboratory. We will then use this system to develop a model, which can distinguish between low and high risk prostate cancers in samples that have been previously graded as low or intermediate grade prostate cancers and of known outcome. This model will then be blind tested using a large set of low and intermediate grade prostate cancers to assess the ability of the model to predict disease outcome. An added benefit of spectral screening is that interrogation of the spectral differences between high and low risk disease will direct research towards novel molecular markers that may shed light on tumour progression as well as generating new molecular diagnostic markers for use in the clinic. As the technique is non destructive any new markers identified can be tested back on the original tissue it was discovered from.We envision that development and robust testing of the system will lead to a powerful diagnostic and prognostic tool that may be incorporated in to oncological practice both in the laboratory and the clinic and that it will potentially describe new techniques with utility in other areas of bio-health and biological science.

Cancer is becoming an increasingly large burden, not just on the NHS but also on health provision worldwide. This is exemplified by the urological malignancies which are the most common group of malignancies diagnosed in the UK, resulting in over 18000 deaths. They are also the most expensive to treat. However not all of these cancers when diagnosed, will go on to cause significant clinical morbidity and mortality: these are deemed low-risk . Other, high risk cases, will progress more rapidly, causing morbidity and cancer related death. It is not currently possible to make this distinction accurately or reliably. There is therefore an urgent need to tailor therapeutic regimes whereby low risk patients will have their disease followed, with intervention on progression, whilst high-risk patients will undergo more radical therapy. For example men diagnosed with low-grade localised prostate cancer with a good prognosis may be offered active surveillance to monitor their disease, with radical therapy being used if the disease is observed to progress. However, because there are no biological markers within urology (or indeed in many other malignancies) which accurately predict disease progression, treatment rather than surveillance is commonly initiated. Development of a new biometric technology, which would ultimately be incorporated with oncology histopathology laboratories, is required to enable tailored therapeutic regimes. The aim is to treat each patient individually and not just by application of class based parameters of disease. FTIR spectroscopy offers such a potential biometric technology. It is a non-destructive procedure, enabling the same sample to be re-analysed and verified by other histopathological techniques, with the potential to offer a simple prognostic readout based on the complex cellular biochemistry of the biopsy. It is perceived that verification of such a system would rapidly lead to it's incorporation within existing histopathological regimes for diagnosis and prognostication providing a clear benefit to the patient and the healthcare system in terms of diagnosis and treatment planning. The project will also take a significant step towards translating spectral technologies in to the routine histopathology laboratories, providing a powerful tool for the histopathologist. Another potential use of this technology within the medical fields would be the utilisation of spectral markers in following therapeutic responses. For tailored therapeutic regimes to make a significant impact on disease treatment and management it is necessary to determine the effect of a regime on the tumour, which requires robust biomarkers for that disease. Large Pharmaceutical companies as they trial new agents also require these biomarkers. However active surveillance of therapy is hampered by the lack of biomarkers. FTIR can detect the chemical changes within a tissue in response to a therapeutic agent a provide novel biomarkers based on key chemical changes. This would be of significant scientific and financial benefit to both healthcare providers, academic researchers and to pharmaceutical companies running developmental programmes for new agents. The project partner's benefit from developing a method to combine clinical metrics and analytical data from high throughput IR imaging and a method which could be applied to any other analytical method or biological system. The project will give rise to novel metric marker of tumour bio-potential which could be further data mined to give rise to novel bio-markers in cancer, providing insight in to carcinogenesis and providing novel pathological biomarkers. The academic community will benefit from a validated, high throughput spectral system able to rapid follow chemical changes within any biological system (microbial to mammalian cell) and generate novel biomarkers based on response to external events.