Optimization of beam arrangements in proton minibeam radiotherapy by cell survival simulations

Abstract

Purpose: Proton minibeam radiotherapy using submillimeter beam dimensions allows to enhance tissue sparing in the entrance channel by spatial fractionation additionally to advantageous proton depth dose distribution. In the entrance channel, spatial fractionation leads to reduced side effects compared to conventional proton therapy. The submillimeter sized beams widen with depth due to small angle scattering and enable therefore, in contrary to x-ray microbeam radiation therapy (MRT), the homogeneous irradiation of a tumor. Proton minibeams can either be applied as planar minibeams or pencil shaped with an additional possibility to vary between a quadratic and a hexagonal arrangement for pencil minibeams.The purpose of this work is to deduce interbeam distances to achieve a homogeneous dose distribution for different tumor depths and tumor thicknesses. Furthermore, we aim for a better understanding of the sparing effect on the basis of surviving cells calculated by the linear-quadratic model. Methods: Two-dimensional dose distributions are calculated for proton minibeams of different shapes and arrangements. For a tumor in 10-15 cm depth, treatment plans are calculated with initial beam size of r 0 = 0.2 mm in a water phantom. Proton minibeam depth dose distributions are finally converted into cell survival using a linear-quadratic model. Results: Inter proton beam distances are maximized under the constraint of dose homogeneity in the tumor for tumor depths ranging from 4 to 15 cm and thickness ranging from 0.5 to 10 cm. Cell survival calculations for a 5 cm thick tumor covered by 10 cm healthy tissue show less cell death by up to 85%, especially in the superficial layers, while keeping the cell death in the tumor as in conventional therapy. In the entrance channel, the pencil minibeams result in higher cell survival in comparison to the planar minibeams while all proton minibeam irradiations show higher cell survival than conventional broadbeam irradiation. Conclusion: The deduced constraints for interbeam distances simplify treatment planning for proton minibeam radiotherapy applications in future studies. The cell survival results indicate that proton minibeam radiotherapy reduces side effects but keeps tumor control as in conventional proton therapy. It makes proton minibeam, especially pencil minibeam radiotherapy a potentially attractive new approach for radiation therapy.

Implementation of planar proton minibeam radiation therapy using a pencil beam scanning system: A proof of concept study

“…Results illustrate that the lateral homogeneity of the dose at the Bragg peak is closely correlated with the center‐to‐center (ctc) value and the initial energy of the beam, thereby influencing the design of the multislit collimator, as increasing the ctc significantly increases the PVDR in normal tissues. Very recently, the beam size variations as well as lateral and in‐depth‐dose homogeneity were characterized as a function of the inter‐slit distance for theoretically focused high‐energy proton pencil beams and various beam arrangements. Using initial beam size of σ = 0.2 mm, these authors found optimal ctc values comparable to those reported in the present study.…”

Spatially fractionated proton minibeams

“…72 Alternative materials that have been proposed to reduce the neutron dose by approximately 30% include nickel, iron and brass. 73 The most sophisticated framework to obtain optimal irradiation geometry was recently presented by Sammer et al 63 They defined the incident beam geometry and energy within an elegant inverse planning approach and evaluated the effectiveness of different beam geometries in terms of survival fractions. The overall aim was to optimize the geometry and distances between the minibeams to minimize overall cell killing outside the target, while maintaining uniform dose coverage at depth.…”

Optimization of hexagonal‐pattern minibeams for spatially fractionated radiotherapy using proton beam scanning

“…1 The aim in SFRT was to spare normal tissue by depositing dose in spatially fractionated manner, but at the same time deliver homogeneous dose to tumor volume. 2 One of the metrics of how good SFRT is achieved is the peak-tovalley-dose ratio (PVDR), of which the "peak dose" refers to the radiation dose of an exposed region and the "valley dose" refers to the dose of the adjacent unexposed region. It has been shown that high PVDRs and low valley doses tend to increase normal tissue sparing.…”