Abstract
Proton radiotherapy using minibeams of sub-millimeter dimensions reduces side effects in comparison to conventional proton therapy due to spatial fractionation. Since the proton minibeams widen with depth, the homogeneous irradiation of a tumor can be ensured by adjusting the beam distances to tumor size and depth to maintain tumor control as in conventional proton therapy. The inherent advantages of protons in comparison to photons like a limited range that prevents a dosage of distal tissues are maintained by proton minibeams and can even be exploited for interlacing from different beam directions. A first animal study was conducted to systematically investigate and quantify the tissue-sparing effects of proton pencil minibeams as a function of beam size and dose distributions, using beam widths between σ = 95, 199, 306, 411, 561 and 883 μm (standard deviation) at a defined center-to-center beam distance (ctc) of 1.8 mm. The average dose of 60 Gy was distributed in 4x4 minibeams using 20 MeV protons (LET ~ 2.7 keV/μm). The induced radiation toxicities were measured by visible skin reactions and ear swelling for 90 days after irradiation. The largest applied beam size to ctc ratio (σ/ctc = 0.49) is similar to a homogeneous irradiation and leads to a significant 3-fold ear thickness increase compared to the control group. Erythema and desquamation was also increased significantly 3–4 weeks after irradiation. With decreasing beam sizes and thus decreasing σ/ctc, the maximum skin reactions are strongly reduced until no ear swelling or other visible skin reactions should occur for σ/ctc < 0.032 (extrapolated from data). These results demonstrate that proton pencil minibeam radiotherapy has better tissue-sparing for smaller σ/ctc, corresponding to larger peak-to-valley dose ratios PVDR, with the best effect for σ/ctc < 0.032. However, even quite large σ/ctc (e.g. σ/ctc = 0.23 or 0.31, i.e. PVDR = 10 or 2.7) show less acute side effects than a homogeneous dose distribution. This suggests that proton minibeam therapy spares healthy tissue not only in the skin but even for dose distributions appearing in deeper layers close to the tumor enhancing its benefits for clinical proton therapy.
Highlights
Radiotherapy with highly energetic protons, light or heavy ions is one of the strongest growing fields in cancer therapy
Heavy ions (e.g. He-ions, boron, carbon or oxygen ions) are suitable for minibeam therapy just as protons, but the beams have to be initially smaller since the lower scattering of heavier ions requires smaller ctc distances to form a homogenous tumor dose, while sparing healthy tissue
The results show that larger σ/ctc ratios are still beneficial compared to homogeneous irradiations, but side effects increase with increasing σ/ctc-ratios
Summary
Radiotherapy with highly energetic protons, light or heavy ions is one of the strongest growing fields in cancer therapy. The inherent physical advantages such as a limited range as well as the increasing dose deposition with depth (Bragg curve) are highly attractive for oncologists. Cancer treatment with protons and ions is beneficial compared to photons, side effects are still the limiting factor for the applied dose. A novel technique, unidirectional proton minibeam radiotherapy, was recently introduced by Zlobinskaya et al [2] and mentioned by Prezado et al [3]: Sub-millimeter sized pencil or planar proton beams, called proton minibeams, are applied in a pattern that covers the tumor volume laterally with center-to-center-distances (ctc) in the millimeter range. Due to small-angle scattering of the protons in the traversed tissue, minibeams increase in size with depth. The tumor dimensions were chosen such that the calculations fit the experimental setup of this work
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