Sensitivity of a mini-TEPC to radiation quality variations in clinical proton beams.

PURPOSE: This work aims at studying the sensitivity of a miniaturized Tissue-Equivalent Proportional Counter to variations of beam quality in clinical radiation fields, to further investigate its performances as radiation quality monitor. METHODS: Measurements were taken at the CATANA facility (INFN-LNS, Catania, Italy), in a monoenergetic and an energy-modulated proton beam with the same initial energy of 62 MeV. PMMA layers were placed in front of the detector to measure at different depths along the depth-dose profile. The frequency- and dose-mean lineal energy were compared to the track- and dose-averaged LET calculated by Monte Carlo simulations. A microdosimetric evaluation of the Relative Biological Effectiveness (RBE) was performed and compared with cell survival experiments. RESULTS: Microdosimetric distributions measured at identical depths in the two beams show spectral differences reflecting their different radiation quality. Discrepancies are most evident at depths corresponding to the Spread-Out Bragg Peak, while spectra at the entrance and in the dose fall-off regions are similar. This can be explained by the different energy components that compose the pristine and spread-out peaks at each depth. The trend of microdosimetric mean values matches that of calculated LET averages along the entire penetration depth, and the microdosimetric estimation of RBE is consistent with radiobiological data not only at 2 Gy but also at lower dose levels, such as those absorbed by healthy tissues. CONCLUSIONS: The mini-TEPC is sensitive to differences in radiation quality resulting from different modulations of the proton beam, confirming its potential for beam quality monitoring in proton therapy.

Microdosimetry of a 62-MeV clinical proton beam with five detectors.

In proton therapy, most treatment planning systems (TPS) use a fixed relative biological effectiveness (RBE) of 1.1 all along the depth-dose profile. Innovative TPS are now investigated considering the variability of RBE with radiation quality. New TPS need an experimental verification in the quality assurance (QA) routine in clinics, but RBE data are usually obtained with radiobiological measurements that are time consuming and not suitable for daily QA. Microdosimetry is a useful tool based on physical measurements which can monitor the radiation quality. Several microdosimeters are available in different research institutions, which could potentially be used for the QA in TPS. In this study, the response functions of five detectors in the same 62-MeV proton Spread Out Bragg Peak is compared in terms of spectral distributions and their average values and microdosimetric RBE. Their different response function has been commented and must be considered in the clinical practice.

4He dose- and track-averaged linear energy transfer: Monte Carlo algorithms and experimental verification.

Objective.In the present hadrontherapy scenario, there is a growing interest in exploring the capabilities of different ion species other than protons and carbons. The possibility of using different ions paves the way for new radiotherapy approaches, such as the multi-ions treatment, where radiation could vary according to target volume, shape, depth and histologic characteristics of the tumor. For these reasons, in this paper, the study and understanding of biological-relevant quantities was extended for the case of4He ion.Approach.Geant4 Monte Carlo based algorithms for dose- and track-averaged LET (Linear Energy Transfer) calculations, were validated for4He ions and for the case of a mixed field characterised by the presence of secondary ions from both target and projectile fragmentation. The simulated dose and track averaged LETs were compared with the corresponding dose and frequency mean values of the lineal energy,yD¯andy¯F, derived from experimental microdosimetric spectra. Two microdosimetric experimental campaigns were carried out at the Italian eye proton therapy facility of the Laboratori Nazionali del Sud of Istituto Nazionale di Fisica Nucleare (INFN-LNS, Catania, I) using two different microdosimeters: the MicroPlus probe and the nano-TEPC (Tissue Equivalent Proportional Counter).Main results.A good agreement ofL¯dTotalandL¯tTotalwithy¯Dandy¯Texperimentally measured with both microdosimetric detectors MicroPlus and nano-TEPC in two configurations: full energy and modulated4He ion beam, was found.Significance.The results of this study certify the use of a very effective tool for the precise calculation of LET, given by a Monte Carlo approach which has the advantage of allowing detailed simulation and tracking of nuclear interactions, even in complex clinical scenarios.

Experimental investigation at CATANA facility of n-10B and p-11B reactions for the enhancement of proton therapy.

The aim of the NEPTUNE (Nuclear process-driven Enhancement of Proton Therapy UNravEled) project is to investigate in detail both the physical and radiobiological phenomena that could justify an increase of the proton-induced cytogenetic effects in cells irradiated in presence of an agent containing natural boron. In this work, a double-stage silicon telescope coupled to different boron converters was irradiated at the CATANA proton therapy facility (INFN-LNS) for studying the proton boron fusion and the neutron boron capture reactions by discriminating secondary particles from primary protons. Different boron targets were developed by depositing boric acid, enriched with a higher than 99% content of 10B or 11B, on a 50 µm thick PolyMethilMetacrylate (PMMA) substrate. The 10B target allows to evaluate the contribution of lithium and alpha particles produced by the boron neutron capture reaction triggered by secondary thermal neutrons, while the 11B target is exploited for studying the effect of the p + 11B → 3α nuclear reaction directly triggered by primary protons. Experimental results clearly show the presence of alpha particles from both the reactions. The silicon telescope is capable of discriminating, by means of the so-called "scatter plots", the contribution of alpha particles originated by thermal neutrons on 10B with respect to the ones produced by protons impinging on 11B. Although a reliable quantitative study of the alpha production rate has not been achieved yet, this work demonstrates that low energy and, therefore, high-LET particles from both the reactions can be measured.

Microdosimetry of a therapeutic proton beam with a mini-TEPC and a MicroPlus-Bridge detector for RBE assessment.

Proton beams are widely used worldwide to treat localized tumours, the lower entrance dose and no exit dose, thus sparing surrounding normal tissues, being the main advantage of this treatment modality compared to conventional photon techniques. Clinical proton beam therapy treatment planning is based on the use of a general relative biological effectiveness (RBE) of 1.1 along the whole beam penetration depth, without taking into account the documented increase in RBE at the end of the depth dose profile, in the Bragg peak and beyond. However, an inaccurate estimation of the RBE can cause both underdose or overdose, in particular it can cause the unfavourable situation of underdosing the tumour and overdosing the normal tissue just beyond the tumour, which limits the treatment success and increases the risk of complications. In view of a more precise dose delivery that takes into account the variation of RBE, experimental microdosimetry offers valuable tools for the quality assurance of LET or RBE-based treatment planning systems. The purpose of this work is to compare the response of two different microdosimetry systems: the mini-TEPC and the MicroPlus-Bridge detector. Microdosimetric spectra were measured across the 62 MeV spread out Bragg peak of CATANA with the mini-TEPC and with the Bridge microdosimeter. The frequency and dose distributions of lineal energy were compared and the different contributions to the spectra were analysed, discussing the effects of different site sizes and chord length distributions. The shape of the lineal energy distributions measured with the two detectors are markedly different, due to the different water-equivalent sizes of the sensitive volumes: 0.85 µm for the TEPC and 17.3 µm for the silicon detector. When the Loncol's biological weighting function is applied to calculate the microdosimetric assessment of the RBE, both detectors lead to results that are consistent with biological survival data for glioma U87 cells. Both the mini-TEPC and the MicroPlus-Bridge detector can be used to assess the RBE variation of a 62 MeV modulated proton beam along its penetration depth. The microdosimetric assessment of the RBE based on the Loncol's weighting function is in good agreement with radiobiological results when the 10% biological uncertainty is taken into account.

Microdosimetric measurements of a monoenergetic and modulated Bragg Peaks of 62 MeV therapeutic proton beam with a synthetic single crystal diamond microdosimeter.

PURPOSE: The purpose of this study was to investigate for the first time the performance of a synthetic single crystal diamond detector for the microdosimetric characterization of clinical 62 MeV ocular therapy proton beams. METHODS: A novel diamond microdosimeter with a well-defined sensitive volume was fabricated and tested with a monoenergetic and spread-out Bragg peak (SOBP) of the CATANA therapeutic proton beam in Catania, Italy. The whole sensitive volume of the detector has an active planar-sectional area of 100 µm × 100 µm and a thickness of approximately 6.3 um. Microdosimetric measurements were performed at several water equivalent depths, corresponding to positions of clinical relevance. From the measured spectra, microdosimetric quantities such as the frequency mean lineal energy ( y ¯ F ), dose mean lineal energy ( y ¯ D ) as well as microdosimetric relative biological effectiveness (RBEµ ) values were derived for each depth along both a pristine Bragg curve and SOBP. Finally, Geant4 Monte Carlo simulations were performed modeling the detector geometry and CATANA beamline in order to calculate the average linear energy transfer (LET) values in the diamond active layer and water. RESULTS: The microdosimetric spectra acquired by the diamond microdosimeter show different shapes as a function of the water equivalent depths. No spectral distortion, due to pile-up events and polarization effects, was observed. The experimental spectra have a very low detection threshold due to the electronic noise during the irradiation of about 1 keV/µm. The y ¯ F and y ¯ D values were in agreement with expected trends, showing a sharp increase in mean lineal energy at the distal edge of the Bragg peak. In addition, a good agreement between the mean lineal energy values and the calculated average LET ones was also observed. Finally, the RBE values evaluated with the diamond microdosimeter were in excellent agreement with those obtained with a mini tissue equivalent proportional counter as well as with radiobiological measurements in the same proton beam field. CONCLUSIONS: The microdosimetric performance of the tested synthetic single crystal diamond microdosimeter clearly indicates its suitability for quality assurance in clinical proton therapy beam.

Preliminary results in using Deep Learning to emulate BLOB, a nuclear interaction model.

PURPOSE: A reliable model to simulate nuclear interactions is fundamental for Ion-therapy. We already showed how BLOB ("Boltzmann-Langevin One Body"), a model developed to simulate heavy ion interactions up to few hundreds of MeV/u, could simulate also 12C reactions in the same energy domain. However, its computation time is too long for any medical application. For this reason we present the possibility of emulating it with a Deep Learning algorithm. METHODS: The BLOB final state is a Probability Density Function (PDF) of finding a nucleon in a position of the phase space. We discretised this PDF and trained a Variational Auto-Encoder (VAE) to reproduce such a discrete PDF. As a proof of concept, we developed and trained a VAE to emulate BLOB in simulating the interactions of 12C with 12C at 62 MeV/u. To have more control on the generation, we forced the VAE latent space to be organised with respect to the impact parameter (b) training a classifier of b jointly with the VAE. RESULTS: The distributions obtained from the VAE are similar to the input ones and the computation time needed to use the VAE as a generator is negligible. CONCLUSIONS: We show that it is possible to use a Deep Learning approach to emulate a model developed to simulate nuclear reactions in the energy range of interest for Ion-therapy. We foresee the implementation of the generation part in C++ and to interface it with the most used Monte Carlo toolkit: Geant4.

High-current stream of energetic α particles from laser-driven proton-boron fusion.

The nuclear reaction known as proton-boron fusion has been triggered by a subnanosecond laser system focused onto a thick boron nitride target at modest laser intensity (∼10^{16}W/cm^{2}), resulting in a record yield of generated α particles. The estimated value of α particles emitted per laser pulse is around 10^{11}, thus orders of magnitude higher than any other experimental result previously reported. The accelerated α-particle stream shows unique features in terms of kinetic energy (up to 10 MeV), pulse duration (∼10 ns), and peak current (∼2 A) at 1 m from the source, promising potential applications of such neutronless nuclear fusion reactions. We have used a beam-driven fusion scheme to explain the total number of α particles generated in the nuclear reaction. In this model, protons accelerated inside the plasma, moving forward into the bulk of the target, can interact with ^{11}B atoms, thus efficiently triggering fusion reactions. An overview of literature results obtained with different laser parameters, experimental setups, and target compositions is reported and discussed.

Transversal dose profile reconstruction for clinical proton beams: A detectors inter-comparison.

PURPOSE: The main purpose of this work is the inter-comparison between different devices devoted to the transversal dose profile recostruction for daily QA tests in proton therapy. METHODS: The results obtained with the EBT3 radiochromic films, used as a reference, and other common quality control devices, have been compared with those obtained with a beam profiling system developed at the "Laboratori Nazionali del Sud" of Italian Institute for Nuclear Physics (INFN-LNS, Catania, Italy). It consists of a plastic scintillator screen (thickness 1 mm), mounted perpendicularly to the beam axis and coupled with a highly sensitive CCD detector in a light-tight box. RESULTS AND CONCLUSION: The tests, carried out both at the INFN-LNS and Trento Proton Therapy Center facilities, show, in general, a good agreement between the different detectors. The beam profiling system, in particular, appears to be a promising quality control device for 2-D relative dosimetry, because of its linear response in a dose rate range useful for proton therapy treatments, its high spatial resolution and its short acquisition and processing time.

Three-voltage linear method to determine ion recombination in proton and light-ion beams.

A new practical method to determine the ion recombination correction factor (k s ) for plane-parallel and Farmer-type cylindrical chambers in particle beams is investigated. Experimental data were acquired in passively scattered and scanned particle beams and compared with theoretical models developed by Boag and/or Jaffé. The new method, named the three-voltage linear method (3VL-method), is simple and consists of determining the saturation current using the current measured at three voltages in a linear region and dividing it by the current at the operating voltage (V) (even if it is not in the linear region) to obtain k s . For plane-parallel chambers, comparing k s -values obtained by model fits to values obtained using the 3VL-method, an excellent agreement is found. For cylindrical chambers, recombination is due to volume recombination only. At low voltages, volume recombination is too large and Boag's models are not applicable. However, for Farmer-type chambers (NE2571), using a smaller voltage range, limited down to 100 V, we observe a linear variation of k s with 1/V 2 or 1/V for continuous or pulsed beams, respectively. This linearity trend allows applying the 3VL-method to determine k s at any polarizing voltage. For the particle beams used, the 3VL-method gives an accurate determination of k s at any polarizing voltage. The choice of the three voltages must to be done with care to ensure to be in a linear region. For Roos-type or Markus-type chambers (i.e. chambers with an electrode spacing of 2 mm) and NE2571 chambers, the use of the 3VL-method with 300 V, 200 V and 150 V is adequate. A difference with the 2V-method and some 3V-methods in the literature is that in the 3VL-method the operational voltage does not have to be one of the three voltages. An advantage over a 2V-method is that the 3VL-method can inherently verify if the linearity condition is fulfilled.

Preliminary results coupling "Stochastic Mean Field" and "Boltzmann-Langevin One Body" models with Geant4.

PURPOSE: Monte Carlo (MC) simulations are widely used for medical applications and nuclear reaction models are fundamental for the simulation of the particle interactions with patients in ion therapy. Therefore, it is of utmost importance to have reliable models in MC simulations for such interactions. Geant4 is one of the most used toolkits for MC simulation. However, its models showed severe limitations in reproducing the yields measured in the interaction of ion beams below 100 MeV/u with thin targets. For this reason, we interfaced two models, SMF ("Stochastic Mean Field") and BLOB ("Boltzmann-Langevin One Body"), dedicated to simulate such reactions, with Geant4. METHODS: Both SMF and BLOB are semi-classical, one-body approaches to solve the Boltzmann-Langevin equation. They include an identical treatment of the mean-field propagation, on the basis of the same effective interaction, but they differ in the way fluctuations are included. Furthermore, we tested a correction to the excitation energy calculated for the light fragments emerging from the simulations and a simple coalescence model. RESULTS: While both SMF and BLOB have been developed to simulate heavy ion interactions, they show very good results in reproducing the experimental yields of light fragments, up to alpha particles, obtained in the interaction of 12C with a thin carbon target at 62 MeV/u. CONCLUSIONS: BLOB in particular gives promising results and this stresses the importance of integrating it into the Geant4 toolkit.

Dose intercomparison at Italian hadrontherapy centers.

PURPOSE: To perform the first dosimetric intercomparison for proton beams in Italy using ionization chambers, according to the IAEA TRS-398 code of practice. METHODS: Measurement sites included: National Center for Oncological Hadron Therapy (CNAO, Pavia), Center for Proton Therapy (CTP, Trento) and Center for Hadron Therapy and for advanced Nuclear Applications (CATANA, Catania). For comparison we also included a 6 MV photon beam produced at Istituti Clinici Scientifici Maugeri (ICSM, Pavia). For proton beams, both single pseudo-monoenergetic layers (in order to obtain a planned dose of 2 Gy at the reference depth of 2 cm in a water phantom) and Spread-out Bragg peaks (SOBP) have been delivered. Measurements were performed with a PTW Farmer 30010-1 and a PTW Advanced Markus type 34,045 ionization chamber. RESULTS: Data obtained at CATANA, CNAO and CPT in terms of absorbed dose to water depth show good consistency within the experimental uncertainties, with a weighted mean of 1.99 ± 0.01 Gy and a standard error of 0.003 Gy, with reference to a nominal dose of 2 Gy as designed by the treatment planning system. CONCLUSIONS: The results showed a standard deviation of less than 1% for single layer and SOBP beams, for all chambers and a percent deviation less than 1.5% for single layer measurements. The weighted means of the absorbed doses for clinical proton beams (118.19 MeV and 173.61 MeV) are consistent within less than 1%. These results agree within the 1.5% difference considered acceptable for national dose intercomparison.

Microdosimetry at the CATANA 62 MeV proton beam with a sealed miniaturized TEPC.

A new mini-TEPC with cylindrical sensitive volume of 0.9 mm in diameter and height, and with external diameter of 2.7 mm, has been developed to work without gas flow. With such a mini counter we have measured the physical quality of the 62 MeV therapeutic proton beam of CATANA (Catania, Italy). Measurements were performed at six precise positions along the Spread-Out Bragg Peak (SOBP): 1.4, 19.4, 24.6, 29.0, 29.7 and 30.8 mm, corresponding to positions of clinical relevance (entrance, proximal, central, and distal-edge of the SOBP) or of high lineal energy transfer (LET) increment (distal-dose drop off). Without refilling the microdosimeter with new gas, the measurements were repeated at the same positions 4 months later, in order to study the stability of the response in sealed-mode operation. From the microdosimetric spectra the frequency-mean lineal energy y-F and the dose-mean lineal energy y-D were derived and compared with average LET values calculated by means of Geant4 simulations. The comparison points out, in particular, a good agreement between microdosimetric y-D and the total dose-average LET¯d, which is the average LET of the mixed radiation field, including the contribution by nuclear reactions.

A new energy spectrum reconstruction method for time-of-flight diagnostics of high-energy laser-driven protons.

The Time-of-Flight (TOF) technique coupled with semiconductorlike detectors, as silicon carbide and diamond, is one of the most promising diagnostic methods for high-energy, high repetition rate, laser-accelerated ions allowing a full on-line beam spectral characterization. A new analysis method for reconstructing the energy spectrum of high-energy laser-driven ion beams from TOF signals is hereby presented and discussed. The proposed method takes into account the detector's working principle, through the accurate calculation of the energy loss in the detector active layer, using Monte Carlo simulations. The analysis method was validated against well-established diagnostics, such as the Thomson parabola spectrometer, during an experimental campaign carried out at the Rutherford Appleton Laboratory (UK) with the high-energy laser-driven protons accelerated by the VULCAN Petawatt laser.

Radiobiological quantities in proton-therapy: Estimation and validation using Geant4-based Monte Carlo simulations.

PURPOSE: The Geant4 Monte Carlo simulation toolkit was used to reproduce radiobiological parameters measured by irradiating three different cancerous cell lines with monochromatic and clinical proton beams. METHODS: The experimental set-up adopted for irradiations was fully simulated with a dedicated open-source Geant4 application. Cells survival fractions was calculated coupling the Geant4 simulations with two analytical radiobiological models: one based on the LEM (Local Effect Model) approach and the other on a semi-empirical parameterisation. Results was evaluated and compared with experimental data. RESULTS AND CONCLUSIONS: The results demonstrated the Geant4 ability to reproduce radiobiological quantities for different cell lines.

MICRODOSIMETRY AT NANOMETRIC SCALE WITH AN AVALANCHE-CONFINEMENT TEPC: RESPONSE AGAINST A HELIUM ION BEAM.

The tissue-equivalent proportional counter (TEPC) is the most accurate device for measuring the microdosimetric properties of a particle beam but, since the lower operation limit of common TEPCs is ~0.3 µm, no detailed information on the track structure of the impinging particles can be obtained. The pattern of particle interactions at the nanometric level is measured directly by only three different nanodosimeters worldwide: practical instruments are not yet available. In order to partially fill the gap between microdosimetry and track-nanodosimetry, a low-pressure avalanche-confinement TEPC was designed and constructed for simulating tissue-equivalent sites down to the nanometric region. The present paper aims at describing the response of this TEPC in the range 0.3 µm-25 nm to a 62 MeV/n 4He ion beam. The experimental results, for depths near the Bragg peak, show good agreement with FLUKA simulations and suggest that, for smaller depths, the distribution is highly influenced by secondary electrons.

Miniaturized microdosimeters as LET monitors: First comparison of calculated and experimental data performed at the 62 MeV/u 12C beam of INFN-LNS with four different detectors.

PURPOSE: The aim of this paper is to investigate the limits of LET monitoring of therapeutic carbon ion beams with miniaturized microdosimetric detectors. METHODS: Four different miniaturized microdosimeters have been used at the 62 MeV/u 12C beam of INFN Southern National Laboratory (LNS) of Catania for this purpose, i.e. a mini-TEPC and a GEM-microdosimeter, both filled with propane gas, and a silicon and a diamond microdosimeter. The y-D (dose-mean lineal energy) values, measured at different depths in a PMMA phantom, have been compared withLET¯D (dose-mean LET) values in water, calculated at the same water-equivalent depth with a Monte Carlo simulation setup based on the GEANT4 toolkit. RESULTS: In these first measurements, no detector was found to be significantly better than the others as a LET monitor. The y-D relative standard deviation has been assessed to be 13% for all the detectors. On average, the ratio between y-D and LET¯D values is 0.9 ±â€¯0.3, spanning from 0.73 ±â€¯0.08 (in the proximal edge and Bragg peak region) to 1.1 ±â€¯0.3 at the distal edge. CONCLUSIONS: All the four microdosimeters are able to monitor the dose-mean LET with the 11% precision up to the distal edge. In the distal edge region, the ratio of y-D to LET¯D changes. Such variability is possibly due to a dependence of the detector response on depth, since the particle mean-path length inside the detectors can vary, especially in the distal edge region.

Transversal dose distribution optimization for laser-accelerated proton beam medical applications by means of Geant4.

The main purpose of this paper is to quantitatively study the possibility of delivering dose distributions of clinical relevance with laser-driven proton beams. A Monte Carlo application has been developed with the Geant4 toolkit, simulating the ELIMED (MEDical and multidisciplinary application at ELI-Beamlines) transport and dosimetry beam line which is being currently installed at the ELI-Beamlines in Prague (CZ). The beam line will be used to perform irradiations for multidisciplinary studies, with the purpose of demonstrating the possible use of optically accelerated ion beams for therapeutic purposes. The ELIMED Geant4-based application, already validated against reference transport codes, accurately simulates each single element of the beam line, necessary to collect the accelerated beams and to select them in energy. Transversal dose distributions at the irradiation point have been studied and optimized to try to quantitatively answer the question if such kind of beam lines, and specifically the systems developed for ELIMED in Prague, will be actually able to transport ion beams not only for multidisciplinary applications, such as pitcher-catcher nuclear reactions (e.g. neutrons), PIXE analysis for cultural heritage and space radiation, but also for delivering dose patterns of clinical relevance in a future perspective of possible medical applications.

Monte Carlo GEANT4-based application for in vivo RBE study using small animals at LNS-INFN preclinical hadrontherapy facility.

Preclinical studies represent an important step towards a deep understanding of the biological response to ionizing radiations. The effectiveness of proton therapy is higher than photons and, for clinical purposes, a fixed value of 1.1 is used for the relative biological effectiveness (RBE) of protons considered 1.1. Recent in vitro studies have reported that the RBE along the spread-out Bragg peak (SOBP) is not constant and, in particular, the RBE value increases on the distal part of SOBP. The present work has been carried-out in the perspective of a preclinical hadrontherapy facility at LNS-INFN and was focused on the experimental preparation of an in vivo study concerning the RBE variation along the SOBP. The main purpose of this work was to determine, using GEANT4-based Monte Carlo simulations, the best configuration for small animal treatments. The developed GEANT4 application simulates the proton-therapy beam line of LNS-INFN (CATANA facility) and allows to import the DICOM-CT images as targets. The RBE will be evaluated using a deterministic radiation damage like myelopathy as end-point. In fact, the dose at which the 50% of animals will show the myelopathy is supposed to be LET-dependent. In this work, we studied different treatment configurations in order to choose the best two that maximize the LET difference reducing as much as possible the dose released to healthy tissue. The results will be useful to plan hadrontherapy treatments for preclinical in vivo studies and, in particular, for the future in vivo RBE studies.

First experimental proof of Proton Boron Capture Therapy (PBCT) to enhance protontherapy effectiveness.

Protontherapy is hadrontherapy's fastest-growing modality and a pillar in the battle against cancer. Hadrontherapy's superiority lies in its inverted depth-dose profile, hence tumour-confined irradiation. Protons, however, lack distinct radiobiological advantages over photons or electrons. Higher LET (Linear Energy Transfer) 12C-ions can overcome cancer radioresistance: DNA lesion complexity increases with LET, resulting in efficient cell killing, i.e. higher Relative Biological Effectiveness (RBE). However, economic and radiobiological issues hamper 12C-ion clinical amenability. Thus, enhancing proton RBE is desirable. To this end, we exploited the p + 11B → 3α reaction to generate high-LET alpha particles with a clinical proton beam. To maximize the reaction rate, we used sodium borocaptate (BSH) with natural boron content. Boron-Neutron Capture Therapy (BNCT) uses 10B-enriched BSH for neutron irradiation-triggered alpha particles. We recorded significantly increased cellular lethality and chromosome aberration complexity. A strategy combining protontherapy's ballistic precision with the higher RBE promised by BNCT and 12C-ion therapy is thus demonstrated.