Ions heavier than protons, especially carbon ions, offer additional physical advantages over protons
Due to their increased mass, heavier ions have limited lateral scattering and maintain their direction when aimed at a tumor
Sharp lateral dose deposition edges
Physical range uncertainty mostly stems from patient imaging uncertainties and therefore is similar to that of protons
Heavy ions exhibit a much sharper dose fall off than protons in the longitudinal direction
Nuclear interactions activate the atomic nuclei of the irradiated tissue to induce localized radioactivity that can be externally imaged and used for in vivo tumor and normal tissue dose deposition verification
Heavy charged particles initially traversing normal tissues are only slightly more deleterious than x-rays in causing adverse effects in normal tissue
As they reach the end of their range and come to a stop in the tumor target, their biological effectiveness is greatly (up to 3 or 4 times) enhanced
This unique feature may allow heavy ions to effectively kill radioresistant tumors and potentially overcome therapeutic resistance due to hypoxia within the tumor, leading to an increase in the therapeutic ratio
The exact magnitude and quality of the biological effects of heavy ions along their path still carries uncertainties and is an active area of research
The uncertainty is caused by the special radiobiological properties of the densely ionizing heavy ion track, which can be a concern for normal tissue toxicity and an advantage for tumor ablation and for eliciting immune response
Only a few pediatric patients, typically treated with protons, have received carbon ion therapy so far, because of the potential risk of secondary cancers
Similarly to protons, irradiation of moving targets, as well as irradiation of static targets but through moving tissue, is technologically challenging with heavy ions because of the uncertainty and danger that the Bragg peak of incoming ions will be placed in healthy tissue
Robust treatment planning and motion management techniques were developed to mitigate the effect of these uncertainties, and clinical trials are being designed to study survival improvements while avoiding significant toxic effects
