Biologically optimized helium ion plans: calculation approach and itsin vitrovalidation

Abstract

Treatment planning studies on the biological effect of raster-scanned helium ion beams should be performed, together with their experimental verification, before their clinical application at the Heidelberg Ion Beam Therapy Center (HIT). For this purpose, we introduce a novel calculation approach based on integrating data-driven biological models in our Monte Carlo treatment planning (MCTP) tool. Dealing with a mixed radiation field, the biological effect of the primary (4)He ion beams, of the secondary (3)He and (4)He (Z = 2) fragments and of the produced protons, deuterons and tritons (Z = 1) has to be taken into account. A spread-out Bragg peak (SOBP) in water, representative of a clinically-relevant scenario, has been biologically optimized with the MCTP and then delivered at HIT. Predictions of cell survival and RBE for a tumor cell line, characterized by [Formula: see text] Gy, have been successfully compared against measured clonogenic survival data. The mean absolute survival variation ([Formula: see text]) between model predictions and experimental data was 5.3% ± 0.9%. A sensitivity study, i.e. quantifying the variation of the estimations for the studied plan as a function of the applied phenomenological modelling approach, has been performed. The feasibility of a simpler biological modelling based on dose-averaged LET (linear energy transfer) has been tested. Moreover, comparisons with biophysical models such as the local effect model (LEM) and the repair-misrepair-fixation (RMF) model were performed. [Formula: see text] values for the LEM and the RMF model were, respectively, 4.5% ± 0.8% and 5.8% ± 1.1%. The satisfactorily agreement found in this work for the studied SOBP, representative of clinically-relevant scenario, suggests that the introduced approach could be applied for an accurate estimation of the biological effect for helium ion radiotherapy.

A comparison of mechanism‐inspired models for particle relative biological effectiveness (RBE)

“…As of 2018, there are 11 carbon ion facilities (5 in Japan, 2 in Germany, 2 in China, 1 in Austria, and 1 in Italy) and 69 proton therapy centers (27 in the USA, 13 in Japan, 6 in Germany, and remainder spread among 14 countries) . Hadron therapy with helium and other ions has been used in the past and is still of potential interest in cancer therapy . To fully exploit the potential of high‐linear energy transfer (LET) hadron therapy and leverage the many decades of experience treating cancer with low‐LET radiations, such as 60 Co γ rays or megavoltage (MV) x rays, an understanding of the biological effectiveness of higher LET particles relative to a low LET reference radiation is essential.…”

“…The three mechanism‐inspired RBE models considered here are the local effect model (LEM), the microdosimetric‐kinetic (MK) model, and the repair‐misrepair‐fixation (RMF) model . The original version of LEM, referred to as LEM I, as well as the MK model are in routine clinical use for carbon ion treatment planning and have been implemented in commercially available treatment planning systems (LEM: Syngo RT, Siemens, Erlangen, Germany, and LEM + MK: RayStation, RaySearch Laboratories AB, Stockholm, Sweden).…”

Radiobiological issues in prospective carbon ion therapy trials

“…In the future, other ion species may become available for clinical use. Helium ions are currently being investigated because they compare favorably with protons in terms of lateral penumbra and spot size . However, the independent role of the LET is assumed to be comparable to that of protons rather than carbon ions.…”

A phenomenological biological dose model for proton therapy based on linear energy transfer spectra

“…The relative LET quantities, LET*, were calculated according to Eq. for the database using the LET x values calculated by Mairani et al The LET x values were found for all reference radiation types used, besides for 300 kV and 6 MV X‐rays. For 300 kV and 6 MV X‐rays, the LET d values were assumed to correspond to 250 kV x‐rays and 60 Co γ ‐rays, respectively.…”