A Potential Renewed Use of Very Heavy Ions for Therapy: Neon Minibeam Radiation Therapy

Prezado, Yolanda; Hirayama, Ryochi; Matsufuji, Naruhiro; Inaniwa, Taku; Martínez-Rovira, I.; Seksek, Olivier; Bertho, Annaïg; Koike, Sachiko; Labiod, Dalila; Pouzoulet, Frédéric; Polledo, Laura; Warfving, Nils; Liens, Aléthéa; Bergs, Judith; Shimokawa, Tetsuya

doi:10.3390/cancers13061356

Cited by 16 publications

(15 citation statements)

References 46 publications

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“…Despite the advantages that MBRT offers in terms of normal tissue sparing, [3][4][5] tumor control, [9][10][11]64 and seeming flexibility in the types of particles/energies able to be used in conjunction with this technique, 42,49,60,65 the exact biological mechanisms of action are still not fully understood, 25 and therefore warranted further investigation. These investigations were performed through the lens of radical and molecular species produced from water radiolysis, where the interest was two-fold.…”

Section: Discussionmentioning

confidence: 99%

“…The primary yields of · OH,

{\rm e}^{-}_{\rm aq}

, and H 2 O 2 , were calculated for photon, proton, 4 He ion, and 12 C ion MBs and BBs, and each radiation modality was compared. While the majority of publications detailing the advantages of MBRT have focused on photon and proton beams due to their vastly increased clinical prevalence, these heavier ions were included in this study as there has been a renewed interest in their combination with MBRT in order to take advantage of their dosimetric properties 42 . This work was therefore carried out in order establish a baseline level of knowledge on the presence of free radicals in MBRT, thus aiding future experiments/simulation studies.…”

Section: Introductionmentioning

confidence: 99%

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Monte Carlo study of the free radical yields in minibeam radiation therapy

Masilela

Prezado

2023

Medical Physics

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BackgroundMinibeam radiation therapy (MBRT) is a novel technique which has been shown to widen the therapeutic window through significant normal tissue sparing. Despite the heterogeneous dose distributions, tumor control is still ensured. Nevertheless the exact radiobiological mechanisms responsible for MBRT efficacy are not fully understood.PurposeReactive oxygen species (ROS) resulting from water radiolysis were investigated given their implications not only on targeted DNA damage, but also for their role in the immune response and non‐targeted cell signalling effects: two potential drivers of MBRT efficacy.MethodsMonte Carlo simulations were performed using TOPAS‐nBio to carry out the irradiation of a water phantom with beams of protons (pMBRT), photons (xMBRT), 4He ions (HeMBRT), and 12C ions (CMBRT). Primary yields at the end of the chemical stage were calculated in spheres of 20 μm diameter, located in the peaks and valleys at various depths up to the Bragg peak. The chemical stage was limited to 1 ns to approximate biological scavenging, and the yield of · OH, H2O2, and was recorded.ResultsBeyond 10 mm, there were no substantial differences in the primary yields between peaks and valleys of the pMBRT and HeMBRT modalities. For xMBRT, there was a lower primary yield of the radical species · OH and at all depths in the valleys compared to the peaks, and a higher primary yield of H2O2. Compared to the peaks, the valleys of the CMBRT modality were subject to a higher · OH and yield, and lower H2O2 yield. This difference between peaks and valleys became more severe in depth. Near the Bragg peak, the increase in the primary yield of the valleys over the peaks was 6% and 4% for · OH and respectively, while there was a decrease in the yield of H2O2 by 16%. Given the similar ROS primary yields in the peaks and valleys of pMBRT and HeMBRT, the level of indirect DNA damage is expected to be directly proportional to the peak to valley dose ratio (PVDR). The difference in the primary yields implicates a lower level of indirect DNA damage in the valleys compared to the peaks than what would be suggested by the PVDR for xMBRT, and a higher level for CMBRT.ConclusionsThese results highlight the notion that depending on the particle chosen, one can expect different levels of ROS in the peaks and valley that goes beyond what would be expected by the macroscopic PVDR. The combination of MBRT with heavier ions is shown to be particularly interesting as the primary yield in the valleys progressively diverges from the level observed in the peaks as the LET increases. While differences in the reported · OH yields of this work implicated the indirect DNA damage, H2O2 yields particularly implicate non‐targeted cell signalling effects, and therefore this work provides a point of reference for future simulations in which the distribution of this species at more biologically relevant timescales could be investigated.

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Section: Discussionmentioning

confidence: 99%

“…The primary yields of · OH,

{\rm e}^{-}_{\rm aq}

Section: Introductionmentioning

confidence: 99%

Monte Carlo study of the free radical yields in minibeam radiation therapy

Masilela

Prezado

2023

Medical Physics

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“…A deterrent for clinical application of higher‐LET particles like neon ions is the potential for increased normal tissue toxicity given conventional delivery methods 69 . Recent in vivo studies however demonstrate promising results for normal tissue sparing with neon ion mini‐beam delivery 70 . Investigations of dosimetric and biophysical distributions of helium, carbon, oxygen, and neon ion arc therapy delivery in combination with mini‐beam collimation and ultra‐high dose‐rate are anticipated 71 …”

Section: Discussionmentioning

confidence: 99%

“…69 Recent in vivo studies however demonstrate promising results for normal tissue sparing with neon ion mini-beam delivery. 70 Investigations of dosimetric and biophysical distributions of helium,carbon,oxygen,and neon ion arc therapy delivery in combination with mini-beam collimation and ultra-high dose-rate are anticipated. 71 Aside from arc therapies, beam rotation via gantry or treatment chair enables possible ion imaging and beam monitoring applications (particularly for centers with multiple ion sources) such as CT/radiography,range verification, or beam monitoring.…”

Section: Discussionmentioning

confidence: 99%

Spot‐scanning hadron arc (SHArc) therapy: A proof of concept using single‐ and multi‐ion strategies with helium, carbon, oxygen, and neon ions

et al. 2022

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Purpose To present particle arc therapy treatments using single and multi‐ion therapy optimization strategies with helium (4He), carbon (12C), oxygen (16O), and neon (20Ne) ion beams. Methods and materials An optimization procedure and workflow were devised for spot‐scanning hadron arc therapy (SHArc) treatment planning in the PRECISE (PaRticle thErapy using single and Combined Ion optimization StratEgies) treatment planning system (TPS). Physical and biological beam models were developed for helium, carbon, oxygen, and neon ions via FLUKA MC simulation. SHArc treatments were optimized using both single‐ion (12C, 16O, or 20Ne) and multi‐ion therapy (16O+4He or 20Ne+4He) applying variable relative biological effectiveness (RBE) modeling using a modified microdosimetric kinetic model (mMKM) with (α/β)x values of 2, 5, and 3.1 Gy, respectively, for glioblastoma, pancreatic adenocarcinoma, and prostate adenocarcinoma patient cases. Dose, effective dose, linear energy transfer (LET), and RBE were computed with the GPU‐accelerated dose engine FRoG and dosimetric/biophysical attributes were evaluated in the context of conventional particle and photon‐based therapies (e.g., volumetric modulated arc therapy [VMAT]). Results All SHArc plans met the target optimization goals (3GyRBE) and demonstrated increased target conformity and substantially lower low‐dose bath to surrounding normal tissues than VMAT. SHArc plans using a singleion species (12C, 16O, or 20Ne) exhibited favorable LET distributions with the highest‐LET components centralized in the target volume, with values ranging from ∼80–170 keV/μm, ∼130–220 keV/μm, and ∼180–350 keV/μm for 12C, 16O, or 20Ne, respectively, exceeding mean target LET of conventional particle therapy (12C:∼55, 16O:∼75 20Ne:∼95 keV/μm). Multi‐ion therapy with SHArc delivery (SHArcMIT) provided a similar level of target LET enhancement as SHArc compared to conventional planning, however, with additional benefits of homogenous physical dose and RBE distributions. Conclusion Here, we demonstrate that arc delivery of light and heavy ion beams, using either a single‐ion species (12C, 16O, or 20Ne) or combining two ions in a single fraction (16O+4He or 20Ne+4He) affords enhanced physical and biological distributions (e.g., LET) compared with conventional delivery with photons or particle beams. SHArc marks the first single‐ and multi‐ion arc therapy treatment optimization approach using light and heavy ions.

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“…Firstly, the patterns of peak-and-valleys are not dependent on the cardio synchronous pulsations, and the technique could be implemented into conventional and low-cost equipment [117]. In addition, MBRT is not limited to the use of low energy X-rays beams but it can be implemented with higher energy X-rays [118], protons [119], carbon [120] and some other heavier ions [121]. The excellent results (71 % pathological complete remission without toxicity) of the first de novo brain tumor dog MBRT trial [122] opens the door to the transition towards clinical trials.…”

Section: Tablementioning

confidence: 99%