Biological Effectiveness Of Ion Beams for Cancer Therapy

Cancer radiotherapy employing charged particles (i.e. protons and carbon ions) is currently the fastest growing cancer treatment approach with over 30 centres worldwide and an extra 30 (including 3 in the UK) planned to be operational in the next 3-5 years. Compared to conventional photon based approaches, the energy deposition profiles of ion beams are such that their destructive power can be better confined to the tumour volume with minimal damage to surrounding healthy tissues. However, despite the impressive tumour control probabilities reported, there are still uncertainties on the biological effects caused by ion beams especially related to late effects in healthy tissues which prevent further optimization of cancer particle therapy. Ultimately, it is normal tissue effects, including risks of secondary cancers, which will determine the treatment outcome. The main issue is related to the change of biological effectiveness as the ions penetrate into the tissue and a higher probability of inducing late effects when compared to X-rays. Current lack of experimental data is forcing treatment plans to adopt broadly averaged parameters for estimating tumour cell killing and neglect late effects. This project aims to investigate in parallel DNA damage, acute and late cellular effect in a variety of normal and cancerous cell lines induced by therapeutically relevant ion beams across and around their trajectory. Our central hypothesis is that damage and cellular response will vary greatly along and around the ion path as a function of depth, energy deposited, cell line and ion characteristics. Data collected will help improving current knowledge of the biological effectiveness along the ion path and how it varies with physical and biological parameters. Attention will be focused on late effects and how biological depth curves for radiation risks need to be further investigated and included in existing models in order to design optimal cancer treatment strategies. Additionally, we anticipate DNA damage caused by secondary electrons and cell signalling to have non-negligible effects whose contribution to the cancer treatment plans has still to be fully investigated.

Cancer radiotherapy employing charged particles (i.e. protons and carbon ions) is currently the fastest growing cancer treatment approach with over 30 centres worldwide and an extra 30 (including 3 in the UK) planned to be operational in the next 3-5 years. Despite the impressive results so far reported, there are still uncertainties on the biological effects caused by ion beams especially related to non-lethal and late effects in healthy tissues which prevent further optimization of cancer particle therapy. The main issue is related to the change of biological effectiveness as the ions penetrate into the tissue and a higher probability of inducing late effects when compared to X-rays. Ultimately, it is normal tissue effects, including risks of secondary cancers, which will determine the treatment outcome. Current lack of experimental data is forcing treatment plans to adopt broadly averaged parameters for estimating tumour cell killing and neglect late effects. More accurate investigations are therefore essential to develop a rigorous theory of ion radiation action at cellular and molecular level to further improve tumour hadrontherapy. Experimental studies investigating the biological response of charged particles have focused mainly on the cell killing effect of tumour cells or tissues at the Bragg peak. Damage caused at the beam entrance channel, beyond the Bragg peak and indeed in the immediate proximity of the ion path is unavoidable and needs to be addressed. Our central hypothesis is that damage and cellular response will vary greatly along and around the ion path as a function of both physics and biological parameters (i.e. depth, physical dose, cell line, ion characteristics). Using a variety of approaches, the present proposal aims to investigate in parallel DNA damage, acute and sub-lethal cellular response caused by therapeutically relevant ion beams (mainly protons but also carbon ions) on a range of normal and cancerous cell lines along the ion path and in its proximity. Data collected will help evaluating more accurate RBE values to be included in new and existing models to design optimal cancer treatment strategies. Determination of biological Bragg curves for radiation risks including late effects will provide critical information for the development and improvement of biological models aimed to improve the therapeutic use of ion beams. Additionally, we anticipate DNA damage caused by secondary electrons and cell signalling between exposed and un-exposed samples to play a non-negligible role whose contribution to cancer treatment plans has still to be fully investigated.