We present calculations and simulations on the role of the p+$^{11}$B$\to$3$α$ reaction in proton therapy. This reaction has been recently suggested to be responsible for a decrease in the survival probability of tumor cells, when they are irradiated with low-energy protons. However, at the concentration levels typical of the proposed boron carrier (sodium borocaptate, Na$_{2}$B$_{12}$H$_{11}$SH, in short BSH), i.e. less than 100 ppm, both calculations and Monte Carlo simulations suggest that the dose related to this reaction is orders of magnitude lower than the dose delivered by the primary proton beam inside the tissues. These calculations cast some doubts on the claim of an important role played by Proton Boron Capture in enhancing the therapeutic effectiveness of proton therapy, and suggest that other mechanisms should be investigated in order to explain the observed decrease in the survival probability.
Previous measurements have shown large cross sections for the 11B(p,$α$)8Be reaction and K-shell ionization of boron from H+ ions. Past publications have shown that this reaction will likely increase the efficacy of proton therapy. This study investigates the size of boron particles for optimum treatment enhancement in proton therapy. Simulations of protons passing through varying sized boron particles were developed to compare energy outputs for alpha particles and low energy electrons. The results for the boron particle radius that produced the largest radiation output are presented in graph…
The proton boron fusion reaction, 11B(p, 3α), is investigated using MCNP6 to assess the viability for potential use in radiation therapy. The 11B(p, 3α) is theoretically desirable because it could combine the localized dose delivery protons exhibit (Bragg peak) with the creation of three high LET α particles that locally deposit energy in tumor regions. Simple simulations of a proton pencil beam incident upon a water phantom and a water phantom with an axial region also containing boron were modeled using MCNP6 in order to determine the extent of the impact boron had upon the calculated energy…
Boron neutron capture therapy is a powerful anti-cancer treatment, the success of which depends heavily on the boron delivery agent. Enabling the real-time tracing of delivery agents as they move through the body is crucial to the further development of boron neutron therapy. In this study, we fabricate highly bio-compatible boron-10 embedded nanodiamonds using physical ion implantation in conjunction with a two-step annealing process. The red fluorescence of the nanodiamonds allows their use in fluorescence microscopy and in vivo imaging systems, thereby making it possible to conduct tracking…
Selective accumulation of B-10 compound in tumour tissue is a fundamental condition for the achievement of BNCT (Boron Neutron Capture Therapy), since the effectiveness of therapy irradiation derives just from neutron capture reaction of B-10. Hence, the determination of the B-10 concentration ratio, between tumour and healthy tissue, and a control of this ratio, during the therapy, are essential to optimise the effectiveness of the BNCT, which it is known to be based on the selective uptake of B-10 compound. In this work, experimental methods are proposed and evaluated for the determination i…
This manuscript provides a response to a recent report by Mazzone et al. available online on arXiv that, in turn, tentatively aims at demonstrating the inefficacy of proton boron capture in hadrotherapy. We clarify that Mazzone et al. do not add any scientific or technical insights to the points extensively discussed in the original manuscript by Cirrone et al., and/or in the series of iterations had with the Referee, which ultimately lead to the publication of our original and pioneering experimental work. Here we summarize some of the key points of the long scientific debate we had during th…
Neutron relative effectiveness factors in Boron Neutron Capture Therapy: estimation of their values from the secondary charged particles and evaluation of weighted kerma factors for a standard tissue
Quantum Mechanical Analysis of Neutron Wavefunction Overlap and Nuclear Interaction Probability with Carborane Cage ($^{10}$B10) in Boron Neutron Capture Therapy
Background and purpose: Accelerator-Based Boron Neutron Capture Therapy is a radiotherapy based on compact accelerator neutron sources requiring an epithermal neutron field for tumour irradiations. Neutrons of 10 keV are considered as the maximum optimised energy to treat deep-seated tumours. We investigated, by means of Monte Carlo simulations, the epithermal range from 10 eV to 10 keV in order to optimise the maximum epithermal neutron energy as a function of the tumour depth. Methods: A Snyder head phantom was simulated and mono-energetic neutrons with 4 different incident energies were use…
A work recently published experimentally demonstrates an increase in the radiobiological efficacy of clinical proton beams when a tumour is treated in the presence of a concentration of 11B. The paper, for the first time, demonstrates the potential role of the p+11B to 3α (for brevity, p-B) reaction in the biological enhancement of proton therapy effectiveness. The work reports robust experimental data in terms of clonogenic cell survival and chromosomal aberrations and unambiguously shows the presence of an enhancement when cells were exposed to a clinical proton beam subject to treatment wit…
Boron Neutron Capture Therapy (BNCT) is a neutron radiotherapy used to treat tumours cells previously doping with Boron-10. This therapy requires an epithermal neutron beam for the treatment of deep tumours and a thermal beam for shallow ones. Thanks to recent high-current commercial accelerators, Accelerator-Based Neutron Sources (ABNS) are competitive option for providing therapeutic neutron beams in hospitals. In this work, the neutron field generated by the $^7$Li(p,n)$^7$Be reaction at $1950~$keV is studied as neutron source in ABNS, being measured by the Time-Of-Flight (TOF) technique at…
In proton therapy both the energy, which determines the range, and the distal slope, which reflects the rate at which the protons decelerate, are of import if we are to ensure accurate dose deposition and maximum tissue sparing. This publication describes a Geant4 model and presents a two-dimensional polynomial relationship between energy, the energy spread and the distal slope for beams with Gaussian energy spectra for proton therapy. This simple polynomial relationship will be useful for non-invasive or minimally invasive near real-time monitoring of the energy and energy spread of a proton …
Bremsstrahlung photon beams produced by medical linear accelerators are currently the most commonly used method of radiation therapy for cancerous tumors. Photons with energies greater than 8-10 MeV potentially generate neutrons through photonuclear interactions in the accelerator's treatment head, patient's body, and treatment room ambient. Electrons impinging on a heavy target generate a cascade shower of bremsstrahlung photons, the energy spectrum of which shows an end point equal to the electron beam energy. By varying the target thickness, an optimum thickness exists for which, at the giv…
The HANARO ex-core neutron irradiation facility was developed for various applications in the boron neutron capture therapy (BNCT) field, and its characteristics have been investigated. In order to obtain a sufficient thermal neutron flux with a low level contamination of fast neutrons and gamma-rays, a radiation filtering method is adopted. The radiation filter has been designed by using a silicon single crystal cooled by liquid nitrogen and a bismuth crystal. The installation of the main components of the irradiation facility and the irradiation room are finished. Experimental measurements o…
Background and Objective: Recent experimental studies using ultra-high dose rate radiation therapy (FLASH-RT) have shown improved normal tissue sparing and comparable tumor control compared to conventional dose rate RT. Pencil beam scanning (PBS) proton therapy with superior dosimetry characteristics has begun to draw attention to the delivery of conformal FLASH-RT for preclinical studies. This review aims to provide recent updates on the development of PBS FLASH-RT. Methods: The information summarized in this review article is based on search results in databases such as PubMed and search eng…
Secondary radiation in a radiation therapy environment is considered a cause for post-treatment side effects including secondary carcinogenesis. In a proton-therapy setup, neutrons deliver a considerable extra dose to the patient. Various measurements and calculations of neutron dose suggest a wide range of values for this quantity. This paper provides a comparison between the previously published values and analyzes the Monte Carlo calculated neutron dose from the present work using the neutron cross-section data. The purpose is to provide a range for the convergence of several neutron-absorb…
The advanced imaging and delivery techniques in proton therapy allow conformal high-dose irradiation of the target volume with high accuracy using pencil beam scanning or beam shaping apertures. These irradiation methods increasingly include small radiation fields with large dose gradients, which require detector systems with high spatial resolution for quality assurance. In addition the measurement of all success parameters for daily quality assurance with only one proton field and one simple detector system would save a lot of time in clinical usage. Based on their good spatial resolution an…
Proton Pencil-Beam Scanning Stereotactic Body Radiation Therapy and Hypofractionated Radiation Therapy for Thoracic Malignancies: Patterns of Practice Survey and Recommendations for Future Development from NRG Oncology and PTCOG
PET imaging is a non-invasive technique for particle range verification in proton therapy. It is based on measuring the beta+ annihilations caused by nuclear interactions of the protons in the patient. In this work we present measurements for proton range verification in phantoms, performed at the CNAO particle therapy treatment center in Pavia, Italy, with our 10 x 10 cm^2 planar PET prototype DoPET. PMMA phantoms were irradiated with mono-energetic proton beams and clinical treatment plans, and PET data were acquired during and shortly after proton irradiation. We created 1-D profiles of the…
Cao et al (2018) published an article on inverse planning based on dose-averaged linear energy transfer (LET). Their claim that the problem can be cast as a linear optimization model relies on an incorrect application of the Charnes-Cooper transformation. In this comment we show that their linear model is simlar to one where dose-averaged LET is multiplied with dose, explaining why their model was nonetheless able to improve the LET distribution.
Physical and biological range uncertainties limit the clinical potential of Proton Beam Therapy (PBT). In this proceedings, we report on two research projects, which we are conducting in parallel and which both tackle the problem of range uncertainties. One aims at developing software tools and the other at developing detector instrumentation. Regarding the first, we report on our development and pre-clinical application of a GPU-accelerated Monte Carlo (MC) simulation toolkit Fred. Concerning the letter, we report on our investigations of plastic scintillator based PET detectors for particle …
To expedite the commissioning process of the proton therapy system at Samsung Medical Center (SMC), we have developed a Monte Carlo simulation model of the proton therapy nozzles using TOPAS. At SMC proton therapy center, we have two gantry rooms with different types of nozzles; a multi-purpose nozzle and a dedicated scanning nozzle. Each nozzle has been modeled in detail following the geometry information provided by the manufacturer, Sumitomo Heavy Industries, Ltd. For this purpose, novel features of TOPAS, such as the time feature or the ridge filter class, have been used. And the appropria…
This contribution describes general concepts for control and safety systems in proton therapy. These concepts are illustrated by concrete examples implemented in the Proscan facility at PSI.
Background: A relative biological effectiveness (RBE) of 1.1 is used for proton therapy though clinical evidence of varying RBE was raised. Clinical studies on RBE variability have been conducted for decades for carbon radiation, which could advance the understanding of the clinical proton RBE given an ion-independent RBE model. In this work, such a model, linear and simple, using the beam quantity Q = Z^2/E (Z = ion charge, E = kinetic energy per nucleon) was tested and compared to the commonly used, proton-specific and linear energy transfer (LET) based Wedenberg RBE model. Material and meth…
For the in vivo range verification in proton therapy, it has been tried to measure the spatial distribution of the prompt gammas generated by the proton-induced interactions with the close relationship with the proton dose distribution. However, the high energy of the prompt gammas and background gammas are still problematic in measuring the distribution. In this study, we suggested a new method determining the in vivo range by utilizing the time structure of the prompt gammas formed with the rotation of a range modulation wheel (RMW) in the passive scattering proton therapy. To validate the M…
The radiotherapy of malignant diseases has reached much progress during the past decade. Thus, intensity modulated radiation therapy (IMRT) and VMAT (Rapidarc) now belong to the standard modalities of tumor treatment with high energy radiation in clinical practice. In recent time, the particle therapy (protons and partially with heavy carbon ions) has reached an important completion of these modalities with regard to some suitable applications. In spite of this enrichment essential features need further research activities and publications in this field: Nuclear reactions and the role of the r…
The total nuclear cross-section Qtot(E) resulting from the interaction of protons with nuclei is decomposed in 3 different contributions: 1. elastic scatter at the complete nucleus, which adopts a part of the proton kinetic energy; 2. inelastic scatter at a nucleus, which changes its quantum numbers by vibrations, rotations, transition to highly excited states; 3. proper nuclear reactions with change of the mass and/or charge number. Then different particles leave the hit nucleus (neutrons, protons, etc.), which is now referred to as 'heavy recoil' nucleus. The scatter parts of Qtot(E) accordi…
Depth distributions of positron-emitting nuclei in PMMA phantoms are calculated within a Monte Carlo model for Heavy-Ion Therapy (MCHIT) based on the GEANT4 toolkit (version 8.0). The calculated total production rates of $^{11}$C, $^{10}$C and $^{15}$O nuclei are compared with experimental data and with corresponding results of the FLUKA and POSGEN codes. The distributions of e$^+$ annihilation points are obtained by simulating radioactive decay of unstable nuclei and transporting positrons in surrounding medium. A finite spatial resolution of the Positron Emission Tomography (PET) is taken in…
Therapeutic protons acting on O18-substituted thymidine increase cytotoxicity in radio-resistant human cancer cells. We consider here the physics behind the irradiation during proton beam therapy and diagnosis using O18-enriched thymine in DNA, with attention to the effect of the presence of thymine-18 on cancer cell death.
Introduction. Treatment planning systems (TPS) are an essential component for simulating and optimizing a radiation therapy treatment before administering it to the patient. It ensures that the tumor is well covered and the dose to the healthy tissues is minimized. However, the TPS provided by commercial companies often come with a large panel of tools, each implemented in the form of a black-box making it difficult for researchers to use them for implementing and testing new ideas. To address this issue, we have developed an open-source TPS. Approach. We have developed an open-source software…
In this study, two proton beam delivery designs, passive scattering proton therapy (PSPT) and pencil beam scanning (PBS), were quantitatively compared in terms of dosimetric indices. The GATE Monte Carlo code was used to simulate the proton beam system; and the developed simulation engines were benchmarked with respect to the experimental measurements. A water phantom was used to simulate system energy parameters using a set of depth-dose data in the energy range of 120-235 MeV. To compare the performance of PSPT against PBS, multiple dosimetric parameters including FWHM, peak position, range,…
Background and purpose: The relative biological effectiveness (RBE) varies along the treatment field. However, in clinical practice, a constant RBE of 1.1 is assumed, which can result in undesirable side effects. This study provides an accurate overview of current clinical practice for considering proton RBE in Europe. Materials and Methods: A survey was devised and sent to all proton therapy centres in Europe that treat patients. The online questionnaire consisted of 39 questions addressing various aspects of RBE consideration in clinical practice, including treatment planning, patient follow…
Beam modelling of Hitachi PROBEAT proton therapy system for a GPU-based Fast Monte Carlo dose engine
University of Nebraska Omaha（内布拉斯加大学奥马哈分校）；Rice University（莱斯大学）；The University of Texas MD Anderson Cancer（德克萨斯大学安德森癌症中心）；Mevion Medical System（美维医疗系统）；Emory University（埃默里大学）
The First Nozzle-Mounted Compton Camera Prompt Gamma Imaging System for In Vivo Proton Therapy Dose Verification
University of Maryland School of Medicine（马里兰大学医学院）；University of Cape Town（开普敦大学）；University of Wisconsin School of Medicine and Public Health（威斯康星大学医学院与公共卫生学院）；University of Maryland, Baltimore County（马里兰大学巴尔的摩县分校）；H3D, Inc.（H3D公司）
When using superconducting (SC) magnets in a gantry for proton therapy, the gantry will benefit from some reduction in size and a large reduction in weight. In this contribution we show an important additional advantage of SC magnets in proton therapy treatments. We present the design of a gantry with a SC bending section and achromatic beam optics with a very large beam momentum acceptance of $\pm15\%$. Due to the related very large energy acceptance, approximately 70% of the treatments can be performed without changing the magnetic field for synchronization with energy modulation. In our des…
Background and purpose: In-beam Positron Emission Tomography (PET) is one of the modalities that can be used for in-vivo non-invasive treatment monitoring in proton therapy. PET distributions obtained during various treatment sessions can be compared in order to identify regions that have anatomical changes. The purpose of this work is to test and compare different analysis methods in the context of inter-fractional PET image comparison for proton treatment verification. Methods: For our study we used the FLUKA Monte Carlo code and artificially generated CT scans to simulate in-beam PET distri…
Uncertainties in the proton range in tissue during proton therapy limit the precision in treatment delivery. These uncertainties result in expanded treatment margins, thereby increasing radiation dose to healthy tissue. Real-time range verification techniques aim to reduce these uncertainties in order to take full advantage of the finite range of the primary protons. In this paper, we propose a novel concept for real-time range verification based on detection of secondary neutrons produced in nuclear interactions during proton therapy. The proposed detector concept is simple; consisting of a h…
