Document Type

Theses, Ph.D

Rights

Available under a Creative Commons Attribution Non-Commercial Share Alike 4.0 International Licence

Disciplines

1.3 PHYSICAL SCIENCES, 3. MEDICAL AND HEALTH SCIENCES

Publication Details

Submitted for the award of PhD, Radiation and Environmental Science Centre, Technological University Dublin, February 2022.

Abstract

The success of radiotherapy in tumour control depends on the total dose given. However, the tolerance of the normal tissues surrounding the tumour limits this dose. It is not known why some patients develop radiation toxicity and, currently, it is not possible to predict before treatment which patients will experience adverse effects. Thus, there is an unmet clinical need for a new test to identify patients at risk of radiation toxicity. The aim of this study was to determine if spectral variations in blood lymphocytes from PCa patients may suggest Raman spectral bands that could be used in future research to identify spectral features associated with radiosensitivity.

Blood samples were collected retrospectively from 42 patients enrolled on the Cancer Trials Ireland ICORG 08-17 study who had undergone radiotherapy for prostate cancer and had shown either severe or no/minimal late radiation toxicity in follow-up. Radiation response was assessed following in-vitro irradiation using Raman micro-spectroscopy in addition to the G2 chromosomal radiosensitivity assay and the γH2AX DNA damage assay. A partial least squares discriminant analysis model was developed to classify patients using known radiation toxicity scores. Following this retrospective study, blood samples were collected prospectively from 51 patients also enrolled on the ICORG 08- 17 study. These samples were collected prior to radiotherapy and these patients were categorised based on severe or no/minimal late radiation toxicity in follow-up. Radiation response was assessed following in-vitro irradiation using Raman micro-spectroscopy in addition to the G2 chromosomal radiosensitivity assay and the γH2AX DNA damage assay.

A partial least squares discriminant analysis model was developed to predict radiation toxicity. Finally, blood samples were collected prospectively prior to radiotherapy from another 30 patients enrolled on the Northern Ireland Cancer Trials Centre SPORT study for prostate cancer and these patients were also categorised based on severe or no/minimal late radiation toxicity in follow-up. Radiation response was assessed following in-vitro irradiation using Raman micro-spectroscopy in addition to the citrulline assay. A partial least squares discriminant analysis model was again developed to predict radiation toxicity.

Prediction of radiation toxicity outcome could not be achieved based on late radiation toxicity in the cohort of prostate cancer patients enrolled on the ICORG 08-17 study, but some success in predicting radiation toxicity could be achieved based on late radiation toxicity in the cohort of prostate cancer patients enrolled on the Northern Ireland Cancer Trials Centre SPORT study. The patients from the ICORG 08-17 study will be followed up at 6 monthly intervals until Year 9 however, and those from the SPORT study will be followed up every 6 months for up to 5 years with a minimum annual follow-up from 5- 10 years, allowing the models to be updated as patient clinical status changes. In the future, this technology may have potential to lead to individualized patient radiotherapy by identifying patients that are at risk of radiation toxicity.

DOI

https://doi.org/10.21427/Y7QN-AZ43

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