Using Breath, Cell Free DNA and Image Analysis to PRedIct Normal TissUe and Tumour Response During Prostate Cancer SBRT

Radiotherapy scheduling and prescription dose does not take into account individual patient heterogeneity in normal tissue response or tumour response. Personalisation of radiotherapy dose based on real-time assessments of normal tissue and tumour response would maximise cure and minimise treatment related toxicity. During a 5 fraction course of prostate Stereotactic Body Radiotherapy (SBRT) this pilot study will assess whether a number of different biomarker approaches can predict for normal tissue and tumour response. Firstly the investigators will analyse volatile organic compounds released within the breath with each fraction of treatment using Gas Chromatography Ion Mobility Spectroscopy (GC-IMS). The investigators have extensive experience in this area within the TOXI-Triage research program (www.toxi-triage.eu/) including deep learning and machine learning techniques to interrogate the metabolomics data generated. Secondly the investigators will analyse cell free normal tissue and tumour DNA released during treatment to assess both tumour and normal tissue response. Radiotherapy releases large amounts in to the blood stream allowing easier quantitative analysis. Thirdly the investigators will look for imaging biomarkers of rectal wall toxicity using imaging analysis algorithms of on-treatment cone beam verification CT images taken before and after each radiotherapy treatment. The RayPilot® system made by Micropos Medical Ltd tracks prostate motion throughout the SBRT delivery to ensure that the treatment dose is delivered with great precision. The potential of each biomarker approach for predicting normal tissue and tumour response will be assessed against PSA and CTCAE v 4.0 toxicity criteria and EPIC-26 patient reported outcome measures after 24 months of patient follow up.