ALLEGRO: understanding the risks of normal tissue complications and second cancers following radiotherapy

How can we optimise radiotherapy treatments now in order to minimise the risk to the patient of long-term normal tissue damage or a second cancer in the following decades? The ALLEGRO Project has been funded by EURATOM for two years to provide some initial answers and pointers for new research. The ALLEGRO consortium is made up of 13 partners from 8 European countries. All are leading research institutes, hospitals, and university medical departments. The project covers every aspect of radiation damage to normal tissue from current and emerging treatment modalities. Radiation doses to normal tissue. Measurements have been taken of the out-of-field radiation scattered from radiotherapy beams, including protons and carbon ions. The results are being modelled using Monte Carlo to obtain energy spectra for assessment of the biological effectiveness of heavy particles and neutrons. Results will be used to verify the dose estimates reconstructed from clinical databases. The project is also undertaking an investigation of the risk from concomitant patient doses received during position verification for IGRT.Risk of normal tissue complications. The ALLEGRO project has been testing the validity and accuracy of current state-of-the-art NTCP models in order to provide either advice concerning their clinical application, or recommendations for further research and development. This has involved testing the accuracy with which the dose data can be recovered from clinical databases used for model fitting, the validation of NTCP models in three major tumour sites (i.e., head and neck, lung and prostate cancer), and an exploration of ways to improve NTCP models through an understanding of the underlying radiobiological mechanisms leading to specific endpoints. Risk of second cancers. In order to gain a better understanding of the likelihood of second cancers following radiotherapy, and their relationship to the dose distribution around the treated volume, case-control studies are being undertaken on four major European cancer databases. The doses are reconstructed using software validated by measurements. The results are being used to develop a predictive model that can potentially assist treatment planning optimisation to minimise second cancer risk. Interim results and recommendations. The presentation will discuss the results to date and provisional recommendations for current clinical practice of the optimisation of radiotherapy treatments, and further research that is required.