Physical and Biological Characteristics of Particle Therapy for Oncologists

Abstract

Particle therapy is a promising and evolving modality of radiotherapy that can be used to treat tumors that are radioresistant to conventional photon beam radiotherapy. It has unique biological and physical advantages compared with conventional radiotherapy. The characteristic feature of particle therapy is the "Bragg peak," a steep and localized peak of dose, that enables precise delivery of the radiation dose to the tumor while effectively sparing normal organs. Especially, the charged particles (e.g., proton, helium, carbon) cause a high rate of energy loss along the track, thereby leading to high biological effectiveness, which makes particle therapy attractive. Using this property, the particle beam induces more severe DNA double-strand breaks than the photon beam, which is less influenced by the oxygen level. This review describes the general biological and physical aspects of particle therapy for oncologists, including non-radiation oncologists and beginners in the field.

Keywords: Neoplasms; Particle therapy; Radiation injuries; Radiotherapy.

Fig. 1

(A) Depth-dose distributions for photons, protons, and carbon ions. (B) A spread-out Bragg peak of a carbon ion beam (bold line) for a single-entry port.

Fig. 2

Screenshot of plan comparison between carbon ion therapy (A) and conventional X-ray intensity-modulated radiotherapy (B). Note that carbon ion beams can produce steeper dose gradients and a more conformal dose distribution without increasing the dose delivered to the normal tissue, with a smaller number of beams.

Fig. 3

Comparison of the lateral penumbra between protons and carbon ions. The penumbra of a carbon beam is much sharper than that of a proton beam of comparable range.

Fig. 4

Schematic designs of passive scattering beam (A) and active scanning beam (B) delivery systems used in particle therapy.

Fig. 5

Comparison of dose-averaged linear energy transfer (LET_d) between protons and carbon ions in water. The LET_d for each particle beam was calculated with the Geant 4 (ver. 10.06) simulation toolkit.

Fig. 6

Diagram illustrating why high-linear energy transfer (LET) radiation has the greatest relative biological effectiveness (RBE) for cell death, mutagenesis, or oncogenic transformation. High-LET radiation is most likely to produce a double-strand break from one track for an administered absorbed dose. Beyond the point at which the RBE reaches a peak, energy is wasted because the ionizing events are closer than the diameter of the DNA double helix.

Fig. 7

Physical, biological, and clinical depth-dose distributions for carbon beam spread-out Bragg peak (SOBP). The biological model was obtained using an in vitro model of a human salivary gland tumor cell line. The physical dose×relative biological effectiveness (RBE) is supposed to be constant within the SOBP. Note that the physical dose line is curved within the SOBP area. Accordingly, the RBE within the SOBP area is not a constant value but rather a function of depth.