New Ions for Therapy

Abstract

Purpose: Charged particle therapy (CPT) is currently based on the use of protons or carbon ions for the treatment of deep-seated and/or radioresistant tumors, which are known to return poor prognosis in photon treatments. A renovated interest has recently been observed in the possibility of extending the spectrum of ions used in CPT. The potential and limitations of different particle species will be discussed in this work, with special regard to ¹H, ⁴He, ¹²C, and ¹⁶O, that is, those presently available in the most advanced particle therapy clinical centers.

Materials and methods: Literature information has been screened, as well as additional analysis has been performed, aimed at the comparison of basic physical and biological properties of several ions. The research treatment planning system TRiP98 is also employed to compare the dose distribution resulting from exposure to the different ions in different configurations, including the irradiation of hypoxic targets.

Results: Particles of intermediate charge, such as helium and lithium, offer an increased physical selectivity compared with protons, while having reduced biological effectiveness compared with carbon. The latter aspect translates into a less sensitive biological optimization of CPT treatments, though still more effective than protons in killing cancer cells. At the same time, in view of their increased linear energy transfer, heavier ions, like oxygen, are considered attractive, especially for the treatment of hypoxic tumors. While the higher biological dose released in the entrance dose represents in general a drawback for ions heavier than carbon, for oxygen beam this effect may be balanced by the lower dose increase requested to overcome hypoxia.

Conclusions: The possibility of delivering radiation quality-optimized CPT treatments seems to be the new challenge in heavy ion therapy. The potential and limitations of different particle species, according to different sensitivity and morphological scenarios, makes combined treatments of different ions an intriguing option. New ions could open new scenarios in cancer therapy, but would represent as well an opportunity for the treatment of specific non-cancer disease such as atrial fibrillation.

Keywords: Bragg peak; OER; RBE; charged particle therapy; heavy ions; light ions.

Figure 1.

Physical properties of different ion beams propagating in water. (A) Width of lateral dose falloff (σ) due to multiple scattering. (B) Absolute dose per unit fluence. (C) Profiles of dose-averaged linear energy transfer for the irradiation of an extended target of 2.5 × 2.5 × 2.5 cm³ centered at 8 cm depth in water, with a field optimized on a uniform physical dose (2 Gy). The horizontal line in (C) indicates a linear energy transfer level that can be associated to a significant reduction in the oxygen enhancement ratio. (See also Figure 5A.)

Figure 2.

Biological characteristics (relative biological effectiveness at 10% survival level) of different particles as a function of the linear energy transfer, grouped in different sensitivity ranges. All data are extracted from the Particle Irradiation Data Ensemble [27] database and refer to monoenergetic beam irradiation.

Figure 3.

Single-field extended target irradiation of an idealized geometry resembling a head and neck tumor (25 × 25 × 25 mm³) centered at 80-mm depth; the plan was calculated with a relative biological effectiveness (RBE)–weighted dose optimization in the target. RBE profiles for 2 different sensitivity scenarios are shown in (A) and (B). For the first configuration, the resulting biological dose profile (C) is also shown for a better understanding, and the dose average linear energy transfer profiles (D) are compared with those resulting from a physical dose optimization (dashed, from Figure 1C) .

Figure 4.

Double opposed field irradiation of an idealized geometry simulating a typical case of head and neck cancer. The tumor (25 × 25 × 25 mm³) is centered in an irradiation volume of 16-cm length. Physical dose optimization was performed (A), as opposed to relative biological effectiveness–weighted dose optimization for different sensitivity scenarios in (B) and (C).

Figure 5.

(A) Oxygen enhancement ratio (OER) in full anoxia (0% O₂) and 10% survival as a function of dose averaged linear energy transfer for mono-energetic irradiation with different ion species, as measured in Furusawa et al [36] and Ma et al [37] for CHO and V79 cell lines, and including experimental data fit for carbon and neon with the formula in Scifoni et al [12]. (B) double opposed field irradiation for a fully normoxic and (C) partially hypoxic idealized tumor of 4 × 4 × 6 cm³ with oxygen and carbon beams. In the hypoxic case, the plan accounts for OER in the different regions with different oxygen concentrations and optimizes the fields accordingly.