{\bf Introduction}: To revisit the formulation of the mean chord length in microdosimetry and replace it by the particle mean free path appropriate for modelings in radio-biology. {\bf Methods}: We perform a collision-by-collision following by event-by-event Geant4 Monte Carlo simulation and calculate double-averaged stepping-length, $\langle\langle l \rangle\rangle$, for a range of target sizes from mm down to $μ$m and depth in water. We consider $\langle\langle l \rangle\rangle$ to represent the particle mean free path. {\bf Results}: We show that $\langle\langle l \rangle\rangle$ continuously drops as a function of depth and asymptotically saturates to a minimum value in low energies, where it exhibits a universal scaling behavior, independent of particle nominal beam energy. We correlate $\langle\langle l \rangle\rangle$ to linear density of DNA damage, complexities of initial lethal lesions and illustrate a relative difference between predictive RBEs in model calculations using mean chord length vs. the proposed mean free path. We demonstrate consistency between rapid increase in RBE within and beyond the Bragg peak and $\langle\langle l \rangle\rangle$, a decreasing function of depth. {\bf Discussion and conclusion}: An interplay between localities in imparted energy at nano-meter scale and subsequent physio-chemical processes, causalities and pathways in DNA damage requires substitution of geometrical chord length of cell nuclei by mean-free path of proton and charged particles to account for a mean distance among sequential collisions in DNA materials.
Integrating microdosimetric in vitro RBE models for particle therapy into TOPAS MC using the MicrOdosimetry-based modeling for RBE Assessment (MONAS) tool
Experimental studies of microdosimetry in therapeutic ion beams have been performed using several detectors. The differences among them lie on the shapes, the site sizes, and the material. Coin-shaped solid-state detectors made of silicon or diamond with thickness varying from 0.3 to 10 microns, as well as proportional counters with spherical and cylindrical sensitive volumes filled with tissue-equivalent gas are the microdosimeters used in therapeutic proton and carbon-ion beams. One goal of microdosimetry in the clinical environment is providing repeatable specification of the radiation qual…
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.
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 …
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.
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 …
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…
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…
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
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…
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…
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…
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…
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…
Radiotherapy is one of the main methods in the successful treatment of cancer. The tumor is irradiated with photons or charged particles (e.g. protons), and in the case of massive charged particles, the treatment results in less unnecessary dose outside the tumor and therefore less side effects for the patient and a faster recovery. However, the dose planning of hadron therapy is calculated from photon CT measurements, which results in large uncertainties in the planning and therefore in a necessary enlargement of the treatment area. This uncertainty can be reduced by performing the CT scan us…
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…
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…
The performance of the energy degrader in terms of beam properties directly impacts the design and cost of cyclotron-based proton therapy centers. The aim of this study is to evaluate the performances of different existing and novel degrader materials. The quantitative estimate is based on detailed GEANT4 simulations that analyze the beam-matter interaction and provide a determination of the beam emittance increase and transmission. Comparisons between existing (aluminum, graphite, beryllium) and novel (boron carbide and diamond) degrader materials are provided and evaluated against semi-analy…
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…
The determination of relative stopping power (RSP) via proton computed tomography (pCT) of a patient is dependent in part on the knowledge of the incoming proton kinetic energies; the uncertainty in these energies is in turn determined by the proton source -- typically a cyclotron. Here we show that reducing the incident proton beam energy spread may significantly improve RSP determination in pCT. We demonstrate that the reduction of beam energy spread from the typical 1.0% (at 70MeV) down to 0.2%, can be achieved at the proton currents needed for imaging at the Paul Scherrer Institut 230MeV c…
In microdosimetry, lineal energies y are calculated from energy depositions $ε$ inside the microdosimeter divided by the mean chord length, whose value is based on geometrical assumptions on both the detector and the radiation field. This work presents an innovative two-stages hybrid detector (HDM: hybrid detector for microdosimetry) composed by a Tissue Equivalent Proportional Counter (TEPC) and a silicon tracker made of 4 Low Gain Avalanche Diode (LGAD). This design provides a direct measurement of energy deposition in tissue as well as particles tracking with a submillimeter spatial resolut…
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）
Charged particle therapy (CPT) is an advanced modality of radiation therapy which has grown rapidly worldwide, driven by recent developments in technology and methods of delivery. To ensure safe and high quality treatments, various instruments are used for a range of different measurements such as for quality assurance, monitoring and dosimetry purposes. With the emergence of new and enhanced delivery techniques, systems with improved capabilities are needed to exceed existing performance limitations of conventional tools. The Medipix3 is a hybrid pixel detector able to count individual proton…
{\bf Purpose}: To develop a first principle and multi-scale model for normal tissue complication probability (NTCP) as a function of dose and LET for proton and in general for particle therapy with a goal of incorporating nano-scale radio-chemical to macro-scale cell biological pathways, spanning from initial DNA damage to tissue late effects. {\bf Methods}: The method is combination of analytical and multi-scale computational steps including (1) derivation of functional dependencies of NTCP on DNA driven cell lethality in nanometer and mapping to dose and LET in millimeter, and (2) 3D-surface…
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）
