Research Interest

Prediction and measurement of normal tissue response

We aim to produce predictive tests for the development of normal tissue toxicities

An important part of our programme is to support the analysis of the physical data arising from clinical trials aiming to produce robust validated normal tissue constraints to embed in national treatment guidelines. The limitations of physician-based scoring systems of toxicity (usually RTOG) are well-known.  

The RT01 and CHHiP studies together with the pelvic IMRT trial provide an important resource as we have collected both physician-based (RTOG, LENT-SOM) and patient-completed quality of life scores (FACT-P and UCLA prostate cancer index). Detailed analysis of these parameters in the RT01 trial is underway in a collaboration between the ICR CTSU and MRC which will produce more precise instruments for definition of normal tissue constraints for our future radiotherapy trials.

We have analysed dose cube data from 388 men in the RT01 trial showing correlation between composite rectal toxicity from patient/physician assessments and a novel set of dose constraints.

Investigation of the spatial component of dose response will be explored using dose surface maps generated using the GUINESS and VODCA software (www.vodca.ch) particularly relating to the anal region. NTCP models will be fitted to the data to acquire up-to-date parameters.  

Additionally, new approaches to the prediction of normal tissue complications will be proposed accepting that reducing the dose-distribution to an organ to a single number is insufficient to describe the dose-volume response. Novel statistical and machine learning techniques will also be investigated; particular interest will be the development of methods for studying correlations between spatial aspects of applied dose and clinical outcomes.  

Normal-tissue complications will also continue to be studied using cellular automata models describing radiation damage and repair mechanisms. The current epithelial cell model will be extended to other normal tissues.

Analysis of RT01 Trial: Number of dose constraints failed and development of toxicity.