UNASSIGNED: To compare plan quality among photon volumetric arc therapy (VMAT), Gamma Knife, and three different proton beam modalities.
UNASSIGNED: Fifty-five brain lesions from 20 patients were planned with three different proton spot size ranges of cyclotron-generated proton beams, CPBs (spot size σ: 2.7-7.0 mm), linear accelerator proton beams, LPBs (σ: 2.9-5.5 mm), and linear accelerator proton minibeams, LPMBs (σ: 0.9-3.9 mm), with and without apertures and compared against photon VMAT and Gamma Knife plans. Dose coverage to each lesion for each proton and photon plan was set to 99% of the GTV receiving the prescription (Rx) dose. All proton plans used ±2 mm setup uncertainty and ±2% range uncertainty in robust evaluation to achieve V100%Rx > 95% of the GTV. Apertures were applied to proton beams irradiating tumors <1 cm3 volume and located <2.5 cm depth. Conformity index (CI), gradient index (GI), V12 Gy, V4.5 Gy, and mean brain dose were compared across all plan types. The Wilcoxon signed rank test was utilized to determine statistical significance of dosimetric results compared between photon and proton plans.
UNASSIGNED: When compared to CPB generated plans, average CI and GI were significantly better for the LPB and LPMB plans. Aperture-based IMPT plans showed improvement from Gamma Knife for all dosimetric metrics. Aperture-based IMPT plans also showed improvement in all dosimetric metrics for shallow tumors (d < 2.5 cm) when compared with non-aperture-based plans.
UNASSIGNED: The LPB and LPMB stand as excellent alternatives to CPB or photon therapy and significantly increase the preservation of normal tissue.

OBJECTIVE: Preclinical data demonstrated that the use of proton minibeam radiotherapy reduces the risk of toxicity in healthy tissue. Ventricular tachycardia radioablation is an area under clinical investigation in proton beam therapy. We sought to simulate a ventricular tachycardia radioablation with proton minibeams and to demonstrate that it was possible to obtain a homogeneous coverage of an arrhythmogenic cardiac zone with this technique.
METHODS: An arrhythmogenic target volume was defined on the simulation CT scan of a patient, localized in the lateral wall of the left ventricle. A dose of 25Gy was planned to be delivered by proton minibeam radiotherapy, simulated using a Monte Carlo code (TOPAS v.3.7) with a collimator of 19 0.4 mm-wide slits spaced 3mm apart. The main objective of the study was to obtain a plan ensuring at least 93% of the prescription dose in 93% of the planning target volume without exceeding 110% of the prescribed dose in the planning target volume.
RESULTS: The average dose in the planning treatment volume in proton minibeam radiotherapy was 25.12Gy. The percentage of the planning target volume receiving 93% (V93%), 110% (V110%), and 95% (V95%) of the prescribed dose was 94.25%, 0%, and 92.6% respectively. The lateral penumbra was 6.6mm. The mean value of the peak-to-valley-dose ratio in the planning target volume was 1.06. The mean heart dose was 2.54Gy versus 5.95Gy with stereotactic photon beam irradiation.
CONCLUSIONS: This proof-of-concept study shows that proton minibeam radiotherapy can achieve a homogeneous coverage of an arrhythmogenic cardiac zone, reducing the dose at the normal tissues. This technique, ensuring could theoretically reduce the risk of late pulmonary and breast fibrosis, as well as cardiac toxicity as seen in previous biological studies in proton minibeam radiotherapy.

(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.

BACKGROUND: In reference dosimetry, radiation quality correction factors are used in order to account for changes in the detector\'s response among different radiation qualities, improving dosimetric accuracy.
OBJECTIVE: Reference dosimetry radiation quality corrections factors for the PTW microDiamond were calculated for preclinical X-ray and proton minibeams, and their impact in dosimetric accuracy was evaluated.
METHODS: A formalism for the calculation of radiation quality correction factors for absolute dosimetry in minibeam fields was developed. Following our formalism, radiation quality correction factors were calculated for the PTW microDiamond detector, using the Monte Carlo method. Models of the detector, and X-ray and proton irradiation platform, were imported into the TOPAS Monte Carlo simulation toolkit. The radiation quality correction factors were calculated in the following scenarios: (i) reference dosimetry open field to minibeam center of the central peak, (ii) different positions at the minibeam profile (along the peaks and valleys direction) to the center of the central minibeam, and (iii) some representative depth positions. In addition, the radiation quality correction factors needed for the calculation of the peak-to-valley dose ratio at different depths were calculated.
RESULTS: An important overestimation of the dose (about 10%) was found in the case of the open to minibeam field for both X-rays and proton beams, when the correction factors were used. Smaller differences were observed in the other cases.
CONCLUSIONS: The usage of the PTW microDiamond detector requires radiation quality correction factors in order to be used in minibeam reference dosimetry.

Proton therapy has advantages and pitfalls comparing with photon therapy in radiation therapy. Among the limitations of protons in clinical practice we can selectively mention: uncertainties in range, lateral penumbra, deposition of higher LET outside the target, entrance dose, dose in the beam path, dose constraints in critical organs close to the target volume, organ movements and cost. In this review, we combine proposals under study to mitigate those pitfalls by using individually or in combination: (a) biological approaches of beam management in time (very high dose rate \"FLASH\" irradiations in the order of 100 Gy/s) and (b) modulation in space (a combination of mini-beams of millimetric extent), together with mechanical approaches such as (c) rotational techniques (optimized in partial arcs) and, in an effort to reduce cost, (d) gantry-less delivery systems. In some cases, these proposals are synergic (e.g., FLASH and minibeams), in others they are hardly compatible (mini-beam and rotation). Fixed lines have been used in pioneer centers, or for specific indications (ophthalmic, radiosurgery,…), they logically evolved to isocentric gantries. The present proposals to produce fixed lines are somewhat controversial. Rotational techniques, minibeams and FLASH in proton therapy are making their way, with an increasing degree of complexity in these three approaches, but with a high interest in the basic science and clinical communities. All of them must be proven in clinical applications.

Prescription and delivery of protons are somewhat different compared to photons and may influence outcomes (tumour control and toxicity). These differences should be taken into account to fully exploit the clinical potential of proton therapy. Innovations in proton therapy treatment are also required to widen the therapeutic window and determine appropriate populations of patients that would benefit from new treatments. Therefore, strategies are now being developed to reduce side effects to critical normal tissues using alternative treatment configurations and new spatial or temporal-driven optimisation approaches. Indeed, spatiotemporal optimisation (based on flash, proton minibeam radiation therapy or hypofractionated delivery methods) has been gaining some attention in proton therapy as a mean of improving (biological and physical) dose distribution. In this short review, the main differences in planning and delivery between protons and photons, as well as some of the latest developments and methodological issues (in silico modelling) related to providing scientific evidence for these new techniques will be discussed.