Heavy charged particle radiobiology: using enhanced biological effectiveness and improved beam focusing to advance cancer therapy

Abstract

Ionizing radiation causes many types of DNA damage, including base damage and single- and double-strand breaks. Photons, including X-rays and γ-rays, are the most widely used type of ionizing radiation in radiobiology experiments, and in radiation cancer therapy. Charged particles, including protons and carbon ions, are seeing increased use as an alternative therapeutic modality. Although the facilities needed to produce high energy charged particle beams are more costly than photon facilities, particle therapy has shown improved cancer survival rates, reflecting more highly focused dose distributions and more severe DNA damage to tumor cells. Despite early successes of charged particle radiotherapy, there is room for further improvement, and much remains to be learned about normal and cancer cell responses to charged particle radiation.

Fig. 1

Depth dose distributions for 6MV photons, stopping protons and carbon ions. The plots are normalized to 100% at the depth corresponding to maximum dose. Adapted from ref. [3].

Fig 2

RBE (a) and OER (b) of X-rays, protons, and carbon ions. Adapted from refs. [11,12,18]. Improved therapeutic outcomes are achieved with high RBE and low OER values.

Fig. 3

Equi-dose and equi-effect SOBP dose distributions. (a) A 4 cm equi-dose SOBP beginning at a depth of 6 cm incident carbon ions (solid circles). The SOBP is created from multiple beams with variable energy (shown by the set of thin lines); the Bragg peak for the highest incident energy ions is shown with gray circles. The SOBP is designed to deliver equal dose across the tumor volume. (b) A 4 cm equi-effect SOBP beginning at a depth of 6 cm for incident carbon ions. The dose to achieve equal cell killing in the SOBP is reduced at distal sites because LET and RBE increase with depth.

Fig. 4

Changing LET spectrum of carbon ion radiation. (a) Distribution of LET within a 4 cm equi-dose SOBP for incident carbon ions. (b) Distribution of fragments at a depth of 3 cm in water from an incident carbon ion beam at 230 MeV/nucleon. The data are plotted as the frequency of particles as a function of LET. The main peak is from carbon ions after penetrating 3 cm of water. The lower LET particles are fragments with certain ion peaks identified.