Lorenzo Manti (Università di Napoli)
Knowledge of the cellular response to charged particles is crucial for human health. Aside from accounting for a substantial portion of the collective dose from environmental exposure (e.g. indoor radon), their adoption in cancer radiotherapy (hadrontherapy) is escalating [1]. The physical pillar of hadrontherapy is the unprecedented ballistic precision granted by the inverted dose-depth profile of the accelerated ions. However, normal cells that compose the tissues and organs along the particle track and/or proximal to the tumour are nevertheless exposed. In fact, charged particle radiobiology is affected by uncertainties, one major source of which is represented by poor experimental data on the effectiveness with which sublethal cytogenetic damage is induced along the Bragg curve in normal cells. This impacts risk of healthy tissue morbidity, secondary cancers, metastasization and cardiovascular failure. Thus, in spite of an evident lack of severe acute side effects, reliable assessment of long-term sequelae in hadrontherapy patients must still await evidence-based clinical follow-up. Hence, in vitro studies may provide timely insights in the possible late-occurring effects due to particle radiation exposure.
To this end, some experimental results obtained with clinically relevant proton and carbon ion beams will be discussed, including preliminary data from the INFN-funded project ETHICS (pre-clinical Experimental and THeoretical studies to Improve treatment and protection by Charged particleS), which focuses on the integrity of healthy tissues for specific disease scenarios (breast, pancreas and bone) and their interplay with the irradiated tumour. Emphasis will be laid upon the induction of premature normal cell senescence, which appears to be very effectively induced by low doses of particle radiation, akin to those absorbed by healthy tissues [2]. Accumulation of senescing cells undermine tissue/organ homeostasis and functions, and by altering the tumour microenvironment via paracrine signalling, may promote tumour progression and invasiveness [3,4], thus thwarting the unarguable clinical advantages of hadrontherapy.