Orthovoltage X-ray Minibeam Radiation Therapy for the Treatment of Ocular Tumours-An In Silico Evaluation

Abstract

(1) Background: Radiotherapeutic treatments of ocular tumors are often challenging because of nearby radiosensitive structures and the high doses required to treat radioresistant cancers such as uveal melanomas. Although increased local control rates can be obtained with advanced techniques such as proton therapy and stereotactic radiosurgery, these modalities are not always accessible to patients (due to high costs or low availability) and side effects in structures such as the lens, eyelids or anterior chamber remain an issue. Minibeam radiation therapy (MBRT) could represent a promising alternative in this regard. MBRT is an innovative new treatment approach where the irradiation field is composed of multiple sub-millimetric beamlets, spaced apart by a few millimetres. This creates a so-called spatial fractionation of the dose which, in small animal experiments, has been shown to increase normal tissue sparing while simultaneously providing high tumour control rates. Moreover, MBRT with orthovoltage X-rays could be easily implemented in widely available and comparably inexpensive irradiation platforms. (2) Methods: Monte Carlo simulations were performed using the TOPAS toolkit to evaluate orthovoltage X-ray MBRT as a potential alternative for treating ocular tumours. Dose distributions were simulated in CT images of a human head, considering six different irradiation configurations. (3) Results: The mean, peak and valley doses were assessed in a generic target region and in different organs at risk. The obtained doses were comparable to those reported in previous X-ray MBRT animal studies where good normal tissue sparing and tumour control (rat glioma models) were found. (4) Conclusions: A proof-of-concept study for the application of orthovoltage X-ray MBRT to ocular tumours was performed. The simulation results encourage the realisation of dedicated animal studies considering minibeam irradiations of the eye to specifically assess ocular and orbital toxicities as well as tumour response. If proven successful, orthovoltage X-ray minibeams could become a cost-effective treatment alternative, in particular for developing countries.

Keywords: MBRT; Monte Carlo simulation; X-rays; cost-effective; in silico; minibeams; ocular tumours; orthovoltage.

Figure 1

Schematic of the collimator used for minibeam generation illustrating the slit widths and divergence angles listed in Table 1.

Figure 2

Illustration of the four different irradiation positions (P1–P4): For each row, the left and right panels show sagittal and axial sections, respectively, of the same dose distribution, while the orange arrows indicate the beam direction. The dashed yellow lines in the left panels indicate the position of the dose slices mentioned in Section 2.2, while the dashed yellow rectangles in the right panels outline the region within the slices that were considered in the dose analysis.

Figure 3

Dose analysis for the three P1 cases: The ROIs are shown and the sampling positions of the lateral profiles are indicated (red lines).

Figure 4

The ROIs and the lateral profile sampling positions (red lines) for the P2, P3 and P4 cases.

Figure 5

Regions of the dose distributions used for global uncertainty calculation. Only the voxels inside the regions delineated by the yellow dashed lines were considered.

Figure 6

Minibeam dose patterns obtained with the three collimator geometries A, B and C.