Analysis: Since the discovery of X-rays in 1895, radiotherapy has been applied as a cancer treatment yet the major challenge is to develop predictive tests that can help individualise patient treatment.
Since the discovery of X-rays in 1895, radiotherapy has been applied as a cancer treatment and is used in the treatment of approximately 50% of all cancer patients. It aims to maximise tumour cell death while at the same time minimising damage to normal cells and tissues surrounding the tumour.
In the early days, this treatment was imperfect because of its severe side effects. Radiation induced leukaemia, loss of fingers, malignant skin changes and thickening or scarring of tissue were reported soon after radiation began to be used in the clinical setting.
Additionally, several radiotherapy reports have described acute effects such as nausea, fatigue, diarrhoea, hair loss and skin reactions or late adverse effects like rectal bleeding, lung tissue damage and low thyroid following treatment.
To deal with this, new technologies such as 3D conformal radiotherapy, intensity modulated radiotherapy, and image-guided radiotherapy were developed to minimise the exposure of normal tissue to the radiation while maximising the delivery of the radiation dose to the tumour cells.
These technologies have helped reduce the severity and the occurrence of normal tissue damage but adverse effects of radiotherapy still occur and can vary greatly from patient to patient. These effects can be harmful to some radiotherapy patients and may severely affect the patient's quality of life.
To date, there are no tests in use that can predict which patients are most at risk of severe side effects. Development of such predictive tests could lead to individualised patient treatment and avoidance of unnecessary radiotherapy in radiosensitive patients.
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Research is ongoing to develop predictive tests for normal tissue radiosensitivity but so far, none have translated into the clinical setting.
Although research methods such as assays (an analysis done to determine the presence of a substance and the amount of that substance) based on cell growth or DNA damage were developed previously to analyse individual radiosensitivity, translating these methods to clinical settings were not successful.
The possible reasons for these failures might be due to the time-consuming, labour-intensive nature of these assays which are prone to error and require significant technical expertise. This makes them unrealistic methods for routine clinical use meaning there's an unmet clinical need for new assays to identify patients at risk of radiation toxicity.
Changes in the structure and molecular composition of pathologically-altered biological samples provide opportunities for the development of tools for the prediction of treatment response prior to radiotherapy.
Vibrational spectroscopic techniques have been shown to be promising for the characterisation of various biological samples (cells, tissues and biofluids) and may be useful for the development of a predictive assay for radiation toxicity.
Vibrational spectroscopy techniques such as Raman and infrared spectroscopy provide biochemical profiles of cells, tissues, and biofluids. Infrared spectroscopy is based on the absorption of infrared radiation by the sample under study and the fact that molecules absorb specific frequencies of the incident light which are characteristic of their structure.
Raman spectroscopy is based on inelastic scattering of light by chemical bonds and therefore can show molecular specificity. These techniques can detect those changes and identify variations that occur between healthy and diseased specimens.
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Recent studies have applied these techniques for radiobiological analysis and demonstrated them to be sensitive to molecular events occurring in cells, tissues and biofluids after exposure to ionising radiation.
My PhD research, funded by the Irish Research Council, involved the development of vibrational spectroscopy techniques for liquid biopsies for monitoring and prediction of radiotherapeutic treatment outcome in prostate cancer patients.
This work demonstrated that a spectral measurement from liquid biofluids may be used for monitoring treatment response and for the prediction of severe side effects prior to radiotherapy. Also, this technology has the potential to identify important analytes and metabolites involved in the radiation toxicity.
Compared to other biochemical methods, biofluid-based vibrational spectroscopy offers several advantages - its non-destructive, non-invasive, reagent free, label free, cost-effective, and rapid - and can be used to identify multiple analytes in a single measurement.
Further research is ongoing as a part of my postdoctoral research, funded by the Health Research Board, to evaluate this technology on a larger sample number and develop further; the ultimate goal of translating into a clinical setting as a novel predictive tool for radiotherapy.
The views expressed here are those of the author and do not represent or reflect the views of RTÉ
