Difference between revisions of "FLUKA"

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== Local FLUKA projects ==
 
== Local FLUKA projects ==
 +
 +
===2020:===
 +
==== Implementation of a double scattering nozzle for Monte Carlo recalculation of proton plans with variable relative biological effectiveness ====
 +
<small>''Fjæra, Lars Fredrik et al. Physics in Medicine and Biology (2020)''</small>
 +
 +
A constant relative biological effectiveness (RBE) of 1.1 is currently used in clinical proton therapy. However, the RBE varies with factors such as dose level, linear energy transfer (LET) and tissue type. Multiple RBE models have been developed to account for this biological variation. To enable recalculation of patients treated with double scattering (DS) proton therapy, including LET and variable RBE, we implemented and commissioned a Monte Carlo (MC) model of a DS treatment nozzle.
 +
 +
The article is available in pdf format [https://doi.org/10.1088/1361-6560/abc12d here].
 +
 +
==== Spatial agreement of brainstem dose distributions depending on biological model in proton therapy of pediatric brain tumors ====
 +
<small>''Fjæra, Lars Fredrik et al. Advances in Radiation Oncology (2020)''</small>
 +
 +
During radiotherapy of paediatric brain tumours, the brainstem is a critical organ at risk, possibly with different radio-sensitivity across its substructures. In proton therapy, treatment planning is currently performed using a constant relative biological effectiveness (RBE) of 1.1, whereas preclinical studies point toward spatial variability of this factor. To shed light on this biological uncertainty, we investigated the spatial agreement between isodose maps produced by different RBE models, with emphasis on (smaller) substructures of the brainstem.
 +
 +
The article is available in pdf format [https://doi.org/10.1016/j.adro.2020.08.008 here].
 +
 +
==== The FLUKA Monte Carlo code coupled with an OER model for biologically weighted dose calculations in proton therapy of hypoxic tumors ====
 +
<small>''Dahle, Tordis J. et al. Physica Medica (2020)''</small>
 +
 +
The increased radioresistance of hypoxic cells compared to well-oxygenated cells is quantified by the oxygen enhancement ratio (OER). In this study we created a FLUKA Monte Carlo based tool for inclusion of both OER and relative biological effectiveness (RBE) in biologically weighted dose (ROWD) calculations in proton therapy and applied this to explore the impact of hypoxia.
 +
 +
The article is available in pdf format [https://www.sciencedirect.com/science/article/pii/S1120179720301630 here].
 +
 +
==== Models for the relative biological effectiveness in proton therapy: on the impact of cell-irradiation design - Master thesis by Odin Nødset Alvestad ====
 +
 +
In clinical practice, a constant Relative Biological Effectiveness (RBE) of 1.1 is used in treatment planning for protons, to account for the difference in biological effects between photon and proton irradiation. The RBE is, however, known to vary with variables such as physical dose levels, tissue type and Linear Energy Transfer (LET). RBE models are generally based on data derived from in vitro experiments. The aim of this study was to investigate how the restrictions of input data affect the estimates of RBE for protons predicted by such models.
 +
 +
The thesis is available in pdf format [http://bora.uib.no/handle/1956/23341 here].
 +
 +
==== Comparison of relative biological effectiveness in passive scattering- and pencil beam scanning proton therapy of pediatric cancer - Master thesis by Lars Sandnes ====
 +
 +
In proton radiation therapy, the vast majority of patients have been treated using the passive scattering (PS) beam delivery technique. Increasingly, new proton therapy centers apply the pencil beam scanning (PBS) delivery technique instead of PS. PBS is generally considered to provide an increased sparing of surrounding healthy tissue and organs at risk (OARs). While a lot of clinical data is available for the PS modality, the original treatment plans does not take the linear energy transfer (LET) into account when calculating the relative biological effectiveness (RBE). Although the physical dose distributions for PBS and PS proton plans may be similar, the LET and RBE distributions could differ leading to potential different outcome from PBS compared to predictions based on clinical data from PS. The aim of this project was therefore to investigate whether or not a variable RBE negates the dosimetric benefits of PBS over PS. 
 +
 +
The thesis is available in pdf format [http://bora.uib.no/handle/1956/23140 here].
 +
 +
==== Studies of the Relative Biological Effectiveness and Biological Dose in Proton and Carbon Ion Therapy - PhD thesis by Tordis J. Dahle ====
 +
 +
Protons and heavier ions have an increased relative biological effectiveness (RBE) compared to photons. While variable RBE models are applied clinically in carbon ion therapy, the RBE in proton therapy is accounted for clinically by applying a constant RBE of 1.1. However, an increasing amount of experimental and clinical data show that also the proton RBE varies spatially within the patient. In addition, the existing carbon ion RBE models give substantially different RBE-weighted dose (often referred to as biological dose) distributions for the same irradiation scenarios. In this thesis, variables affecting the RBE and biological dose models were studied using the FLUKA Monte Carlo code. Overall, this thesis has contributed to knowledge on the RBE and biological dose calculations in proton and carbon ion therapy. Monte Carlo studies of an experimental or clinical proton or carbon ion beam may help reducing the uncertainties in the RBE and biological dose.
 +
 +
The thesis is available in pdf format [http://bora.uib.no/handle/1956/21963 here].
 +
 +
==== Inter-patient variations in relative biological effectiveness for cranio-spinal irradiation with protons ====
 +
<small>''Ytre-Hauge, Kristian S. et al. Scientific Reports (2020)''</small>
 +
 +
Cranio-spinal irradiation (CSI) using protons has dosimetric advantages compared to photons and is expected to reduce risk of adverse effects. The proton relative biological effectiveness (RBE) varies with linear energy transfer (LET), tissue type and dose, but a variable RBE has not replaced the constant RBE of 1.1 in clinical treatment planning. We examined inter-patient variations in RBE for ten proton CSI patients.
 +
 +
The article is available in pdf format [https://www.nature.com/articles/s41598-020-63164-8 here].
 +
 +
===2019:===
 +
 +
==== Variations in biological doses to cognitive brain structures following pediatric proton therapy by using different models for the relative biological effectiveness - Master thesis by Ole Marius Otterlei ====
 +
 +
In clinical practice, a constant value of 1.1 is used for the relative biological effectiveness (RBE) of protons, whereas in reality, the RBE is known to vary with the physical dose level, tissue type and biological endpoint. In order to investigate the heterogeneity of biological doses to structures associated with cognition in pediatric brain tumor patients, we included a wide selection of published models accounting for variable RBE. We also aimed to identify the most suitable RBE models for this endpoint and patient group through a criteria-based approach, and further use the identified models to estimate risk of cognitive impairment.
 +
 +
The thesis is available in pdf format [http://bora.uib.no/handle/1956/21312 here].
 +
 +
==== Dosimetric comparison and complication risk of estimation for photon and proton therapy of Pediatric tumors - Master thesis by Kemal Hussen Tahier ====
 +
 +
The aim of this study is to compare photon and proton therapy by estimating late radiation lung damage and cardiac toxicity using Dose volumehistogram, DVH metrices for both lungs and heart in terms of relative cardiac mortality and NTCP values for the heart and lungs respectively. The comparison has also been made based on the value of mean and maximum doses received by organs at risk (OARs).
 +
 +
The thesis is available in pdf format [http://bora.uib.no/handle/1956/21111 here].
 +
 +
==== Monte Carlo simulations of neutron based in-vivo range verification in proton therapy – characterstics of proton-induced secondary particles - Master thesis by Eidi Helland ====
 +
 +
Despite the beneficial qualities of proton radiation, uncertainties in the proton beam range prevents full exploitation of proton therapy’s potential to reduce dose to healthy tissues compared to photon therapy. Detection of secondary neutrons created in the patient through nuclear interactions, has been proposed as a method for monitoring the proton beam range during treatment, as there has been shown a correlation between the spatial neutron production distribution and the beam range. However, other generated secondaries may interfere with the secondary neutron detection. The amount and distribution of different secondaries which may reach the proposed neutron detector has not yet been investigated. The overall objective of this thesis was therefore to use Monte Carlo (MC) simulations to quantify the production of secondary radiation, including protons, prompt gamma-rays, neutrons and alpha particles. This knowledge is essential for estimating interference from the different secondary particle species on the measurements of secondary neutrons for the purposes of range monitoring.
 +
 +
The thesis will be available in pdf format [http://bora.uib.no/handle/1956/21138 here].
 +
 +
==== Monte Carlo simulations of neutron based in-vivo range verification in proton therapy – optimization of detector dimensions and positioning - Master thesis by Janne Therese Syltøy ====
 +
 +
Due to the finite range of a monoenergetic proton beam, it is possible to spare more of the healthy tissue surrounding the tumour compared with using traditional radiation therapy with photons. However, this finite range will also make the treatment plan more susceptible to density changes, which will affect the dose delivered to the tumour. To reduce the need for large safety margins in particle therapy and enable proton therapy treatments of patient groups where motion is an issue, there is a substantial ongoing research effort in so-called range verification techniques. Range estimates can be performed in-vivo through the detection of secondary radiation species emitted in nuclear interactions between the incident protons and the nuclei in the patient, such as β+ emitters, prompt gamma-rays, charged fragments and secondary fast neutrons. The objective of this project was to optimize detector dimensions and positioning of an existing detector concept for neutron-based range verifications using Monte Carlo simulations.
 +
 +
The thesis is available in pdf format [http://bora.uib.no/handle/1956/21062 here].
 +
 +
==== Analysis and Development of Phenomenological Models for the Relative Biological Effectiveness in Proton Therapy - PhD thesis by Eivind Rørvik ====
 +
Irradiation experiments on cells and animal models have shown that protons are slightly more effective in producing biological damage than photons. This difference in biological response is quantified by the relative biological effectiveness (RBE). A conservative and constant RBE of 1.1 is used in proton therapy clinics, even though experiments have shown that the RBE can be both higher and lower, varying with different biological and physical quantities, including the linear energy transfer (LET). Phenomenological RBE models try to determine the various RBE dependencies from large experimental databases of cell irradiation experiments. In this work, existing phenomenological models were analysed and explored in a coherent manner: All models were parameterised and described by functions of the maximum RBE (RBEmax) and minimum RBE (RBEmin), the two model functions that make every model unique. A new phenomenological RBE model was proposed, introducing the full LET spectrum as an input parameter for phenomenological models. Statistical methods were used to test whether a non-linear LET dependency of RBEmax would give a superior description of the experimental data compared to using the established linear dependency of the dose-averaged LET (LETd). Further, we analysed the LETd dependency of RBEmin in a two-step regression analysis, as the RBEmin function is most commonly assumed to be constant for all LETd values.
 +
 +
The thesis is available in pdf format [http://bora.uib.no/handle/1956/20923 here].
 +
 +
==== The experimental dose ranges influence the LET<sub>d</sub> dependency of the proton minimum RBE (RBE<sub>min</sub>) ====
 +
<small>''Rørvik, Eivind et al. Physics in Medicine and Biology (2019)''</small>
 +
 +
Cell experiments have shown the proton RBE to vary with dose and LET, which has led to development of variable RBE models. The RBE is normally estimated from two independent functions, the RBE<sub>max</sub> and RBE<sub>min</sub>, describing the extreme RBE at low and high doses. While there is consensus that RBE<sub>max</sub> increases with increasing LET, the RBE<sub>min</sub> is not uniformly defined and its dependency on LET is deviating. In this work, we analysed this dependency and its sensitivity to variations of the experimental dose range.
 +
 +
The article is available in pdf format [https://iopscience.iop.org/article/10.1088/1361-6560/ab369a/meta here].
 +
 +
==== A Predictive Model for Biological Range Shift in Proton Therapy - Master thesis by Vegard Aas Mjelde ====
 +
The biological effects on cells due to proton irradiation are different than for photons. The protons cause more damage for the same deposited physical dose, because of their increased Linear Energy Transfer (LET). This increase in biological effectiveness is quantified by the Relative Biological Effectiveness (RBE). Clinically a constant RBE factor of 1.1 (RBE1.1) is used, but multiple studies on RBE indicate that it increases with depth due to the increase in LET with depth. This leads to a potential underestimation of the biological effects when using RBE1.1,
 +
especially in the distal part of the treatment fields, towards the end of the particles’ range. The increase in dose due to variable RBE increases the depth of the distal 80% dose fall-off, which is often used to quantify the beam range. This range shift between the RBE1.1 and the variable RBE models may cause unexpected radiation damage to healthy tissue and organs at risk. Modelling or predicting the biological range shift in different scenarios is therefore of importance, and the it was the goal for this project.
 +
 +
The thesis is available in pdf format [https://pdfs.semanticscholar.org/fa11/1346bbeee1091b9579f7234961bc34e50ab6.pdf?_ga=2.214184720.603770558.1566806831-1181862505.1566806831 here].
  
 
===2018:===
 
===2018:===
 +
 +
==== Impact of variable proton relative biological effectiveness on estimates of secondary cancer risk in paediatric cancer patients - Master thesis by Vilde Grandemo ====
 +
 +
Proton therapy has an increased dose-conformity compared to conventional radiotherapy with photons, and paediatric cancer patients receiving cranio-spinal irradiation (CSI) are routinely referred to this treatment modality. With long life-expectancy and enhanced radiosensitivity, children are at a significant risk of developing radiation-induced secondary cancers, emphasising the importance of secondary cancer risk estimations following proton therapy for these patients. Previous comparative studies on secondary cancer risk following proton and photon CSI treatment plans for paediatric cancer patients have based the proton risk estimates on a constant proton relative biological effectiveness (RBE) of 1.1. In this study, proton CSI treatment plans for ten paediatric medulloblastoma patients were analysed with respect to the risk of radiation-induced secondary cancer of the lungs and thyroid by comparing risks predicted by the clinical proton RBE of 1.1 to the risk predictions of four variable RBE models (LET-weighted dose, the McNamara model, the Rørvik model, and the Wilkens model). By applying the organ equivalent dose (OED) concept to different dose-response scenarios, the lifetime attributable risk (LAR) and the excess absolute risk (EAR) were estimated based on age-, sex-, and site-specific risk coefficients gathered from epidemiological data on the Japanese A-bomb survivors.
 +
 +
The thesis is available in pdf format [http://bora.uib.no/handle/1956/18763 here].
 +
 +
==== Sensitivity study of the microdosimetric kinetic model parameters for carbon ion radiotherapy ====
 +
<small>''Dahle, Tordis et al. Physics in Medicine and Biology (2018)''</small>
 +
 +
The relative biological effectiveness (RBE) calculation methods currently applied clinically in carbon ion therapy are derived from the microdosimetric kinetic model (MKM) in Japan and the local effect model (LEM) in Europe. The input parameters of these models are based on fit to experimental data subjected to uncertainties. We therefore performed a sensitivity study of the MKM input parameters, i.e. the domain radius (rd), the nucleus radius (Rn) and the parameters of the linear quadratic model (αx and β).
 +
 +
The article is available in pdf format [http://iopscience.iop.org/article/10.1088/1361-6560/aae8b4/meta here].
  
 
==== Exploration and application of phenomenological RBE models for proton therapy ====
 
==== Exploration and application of phenomenological RBE models for proton therapy ====

Latest revision as of 15:55, 30 October 2020

Information and examples on FLUKA Monte Carlo simulations

FLUKA wiki page for UoB Medphysmc. The purpose of this wiki is to provide information for students and employees at the University of Bergen interested in the field of particle therapy, i.e., radiation therapy with protons and heavier ions. This page contains information on ongoing and previous projects on particle therapy at IFT.

For the majority of our projects on particle therapy we use the Monte Carlo simulation code FLUKA, either as the main tool, or to support the project. Several projects are based on clinical treatment plans which we recalculate in FLUKA to enable more accurate estimates of dose, and to apply various models for biological dose/response based on physical quantities such as absorbed dose and Linear Energy Transfer.

Contents

Introduction to FLUKA

FLUKA is a general purpose Monte Carlo code and is used for a number of applications in experimental physics, dosimetry, detector design, medical physics and radio-biology.

Flair and Flair-Geoeditor

Flair is the Graphical user interface for FLUKA and is used for preparing the simulation as well as running the simulations, process and plot the data (through Gnuplot). Flair also contain a geometry viewer/editor named flair-geoviewer, which is used for visualization and editing of the simulation geometry.


The Flair-Geoeditor

The Flair-Geoeditor (previously geoviewer) can be used for visualization and edition of the geometry. Several tutorials are available on youtube. See e.g. this tutorial on selection of regions and zones.

Installation and running

Installation

In order to install FLUKA you must, as a registered user, download the necessary software from the FLUKA web-page. At the University of Bergen we use Ubuntu and the 64bit Gfortran version of FLUKA, and this is what we recommend for new users at the university. If you wish to use a Windows-pc you can download FLUPIX. FLUPIX is Linux Live CD, with pre-installed FLUKA, flair and all the necessary tools in for performing fluka runs. In the packages.txt you will find a complete list of the packages currently included in the ISO image. To save disk space, FLUPIX is only able to run through the VirtualBox machine (www.virtualbox.org) a free and open source Virtual machine supported by Sun. More information on FLUPIX can be found here.


If you wish to install FLUKA, Flair and Flair-Geoviewer yourself, you can find a detailed installation guide here

Lectures, presentations and exercises

The best way to learn FLUKA is to attend one of the courses held by the FLUKA-team. If this is not an immediate option you can find a large number of lectures and exercises from both basic courses and advanced courses on the FLUKA web-page. Lectures and exercises from one of the beginners courses are available here.

Available Master's Thesis projects and topics

A broad range of topics within particle therapy are available for Master's studies at IFT. You may find some of them (but far from a complete list)

Oxygen effect - Oxygen enhancement ratio - in proton therapy

Difference in Relative biological effectiveness of passive scattering - and intensity modulated proton therapy

Phenomenological models for the Relative biological effectiveness in proton therapy - on the impact of cell-irradiation design

Monte Carlo simulations of neutron based in vivo range verification in proton/particle therapy

This aim of this project (which is available for new students) is to exploit secondary particles produced during particle therapy to verify the correctness of the treatment, i.e. that the dose to the patient was delivered as planning. This will be done by detecting secondary neutrons (using Monte Carlo simulations) and from the distribution of these, try to calculate the range and dose from the primary beam. A more detailed project description can be found here.

Local FLUKA projects

2020:

Implementation of a double scattering nozzle for Monte Carlo recalculation of proton plans with variable relative biological effectiveness

Fjæra, Lars Fredrik et al. Physics in Medicine and Biology (2020)

A constant relative biological effectiveness (RBE) of 1.1 is currently used in clinical proton therapy. However, the RBE varies with factors such as dose level, linear energy transfer (LET) and tissue type. Multiple RBE models have been developed to account for this biological variation. To enable recalculation of patients treated with double scattering (DS) proton therapy, including LET and variable RBE, we implemented and commissioned a Monte Carlo (MC) model of a DS treatment nozzle.

The article is available in pdf format here.

Spatial agreement of brainstem dose distributions depending on biological model in proton therapy of pediatric brain tumors

Fjæra, Lars Fredrik et al. Advances in Radiation Oncology (2020)

During radiotherapy of paediatric brain tumours, the brainstem is a critical organ at risk, possibly with different radio-sensitivity across its substructures. In proton therapy, treatment planning is currently performed using a constant relative biological effectiveness (RBE) of 1.1, whereas preclinical studies point toward spatial variability of this factor. To shed light on this biological uncertainty, we investigated the spatial agreement between isodose maps produced by different RBE models, with emphasis on (smaller) substructures of the brainstem.

The article is available in pdf format here.

The FLUKA Monte Carlo code coupled with an OER model for biologically weighted dose calculations in proton therapy of hypoxic tumors

Dahle, Tordis J. et al. Physica Medica (2020)

The increased radioresistance of hypoxic cells compared to well-oxygenated cells is quantified by the oxygen enhancement ratio (OER). In this study we created a FLUKA Monte Carlo based tool for inclusion of both OER and relative biological effectiveness (RBE) in biologically weighted dose (ROWD) calculations in proton therapy and applied this to explore the impact of hypoxia.

The article is available in pdf format here.

Models for the relative biological effectiveness in proton therapy: on the impact of cell-irradiation design - Master thesis by Odin Nødset Alvestad

In clinical practice, a constant Relative Biological Effectiveness (RBE) of 1.1 is used in treatment planning for protons, to account for the difference in biological effects between photon and proton irradiation. The RBE is, however, known to vary with variables such as physical dose levels, tissue type and Linear Energy Transfer (LET). RBE models are generally based on data derived from in vitro experiments. The aim of this study was to investigate how the restrictions of input data affect the estimates of RBE for protons predicted by such models.

The thesis is available in pdf format here.

Comparison of relative biological effectiveness in passive scattering- and pencil beam scanning proton therapy of pediatric cancer - Master thesis by Lars Sandnes

In proton radiation therapy, the vast majority of patients have been treated using the passive scattering (PS) beam delivery technique. Increasingly, new proton therapy centers apply the pencil beam scanning (PBS) delivery technique instead of PS. PBS is generally considered to provide an increased sparing of surrounding healthy tissue and organs at risk (OARs). While a lot of clinical data is available for the PS modality, the original treatment plans does not take the linear energy transfer (LET) into account when calculating the relative biological effectiveness (RBE). Although the physical dose distributions for PBS and PS proton plans may be similar, the LET and RBE distributions could differ leading to potential different outcome from PBS compared to predictions based on clinical data from PS. The aim of this project was therefore to investigate whether or not a variable RBE negates the dosimetric benefits of PBS over PS.

The thesis is available in pdf format here.

Studies of the Relative Biological Effectiveness and Biological Dose in Proton and Carbon Ion Therapy - PhD thesis by Tordis J. Dahle

Protons and heavier ions have an increased relative biological effectiveness (RBE) compared to photons. While variable RBE models are applied clinically in carbon ion therapy, the RBE in proton therapy is accounted for clinically by applying a constant RBE of 1.1. However, an increasing amount of experimental and clinical data show that also the proton RBE varies spatially within the patient. In addition, the existing carbon ion RBE models give substantially different RBE-weighted dose (often referred to as biological dose) distributions for the same irradiation scenarios. In this thesis, variables affecting the RBE and biological dose models were studied using the FLUKA Monte Carlo code. Overall, this thesis has contributed to knowledge on the RBE and biological dose calculations in proton and carbon ion therapy. Monte Carlo studies of an experimental or clinical proton or carbon ion beam may help reducing the uncertainties in the RBE and biological dose.

The thesis is available in pdf format here.

Inter-patient variations in relative biological effectiveness for cranio-spinal irradiation with protons

Ytre-Hauge, Kristian S. et al. Scientific Reports (2020)

Cranio-spinal irradiation (CSI) using protons has dosimetric advantages compared to photons and is expected to reduce risk of adverse effects. The proton relative biological effectiveness (RBE) varies with linear energy transfer (LET), tissue type and dose, but a variable RBE has not replaced the constant RBE of 1.1 in clinical treatment planning. We examined inter-patient variations in RBE for ten proton CSI patients.

The article is available in pdf format here.

2019:

Variations in biological doses to cognitive brain structures following pediatric proton therapy by using different models for the relative biological effectiveness - Master thesis by Ole Marius Otterlei

In clinical practice, a constant value of 1.1 is used for the relative biological effectiveness (RBE) of protons, whereas in reality, the RBE is known to vary with the physical dose level, tissue type and biological endpoint. In order to investigate the heterogeneity of biological doses to structures associated with cognition in pediatric brain tumor patients, we included a wide selection of published models accounting for variable RBE. We also aimed to identify the most suitable RBE models for this endpoint and patient group through a criteria-based approach, and further use the identified models to estimate risk of cognitive impairment.

The thesis is available in pdf format here.

Dosimetric comparison and complication risk of estimation for photon and proton therapy of Pediatric tumors - Master thesis by Kemal Hussen Tahier

The aim of this study is to compare photon and proton therapy by estimating late radiation lung damage and cardiac toxicity using Dose volumehistogram, DVH metrices for both lungs and heart in terms of relative cardiac mortality and NTCP values for the heart and lungs respectively. The comparison has also been made based on the value of mean and maximum doses received by organs at risk (OARs).

The thesis is available in pdf format here.

Monte Carlo simulations of neutron based in-vivo range verification in proton therapy – characterstics of proton-induced secondary particles - Master thesis by Eidi Helland

Despite the beneficial qualities of proton radiation, uncertainties in the proton beam range prevents full exploitation of proton therapy’s potential to reduce dose to healthy tissues compared to photon therapy. Detection of secondary neutrons created in the patient through nuclear interactions, has been proposed as a method for monitoring the proton beam range during treatment, as there has been shown a correlation between the spatial neutron production distribution and the beam range. However, other generated secondaries may interfere with the secondary neutron detection. The amount and distribution of different secondaries which may reach the proposed neutron detector has not yet been investigated. The overall objective of this thesis was therefore to use Monte Carlo (MC) simulations to quantify the production of secondary radiation, including protons, prompt gamma-rays, neutrons and alpha particles. This knowledge is essential for estimating interference from the different secondary particle species on the measurements of secondary neutrons for the purposes of range monitoring.

The thesis will be available in pdf format here.

Monte Carlo simulations of neutron based in-vivo range verification in proton therapy – optimization of detector dimensions and positioning - Master thesis by Janne Therese Syltøy

Due to the finite range of a monoenergetic proton beam, it is possible to spare more of the healthy tissue surrounding the tumour compared with using traditional radiation therapy with photons. However, this finite range will also make the treatment plan more susceptible to density changes, which will affect the dose delivered to the tumour. To reduce the need for large safety margins in particle therapy and enable proton therapy treatments of patient groups where motion is an issue, there is a substantial ongoing research effort in so-called range verification techniques. Range estimates can be performed in-vivo through the detection of secondary radiation species emitted in nuclear interactions between the incident protons and the nuclei in the patient, such as β+ emitters, prompt gamma-rays, charged fragments and secondary fast neutrons. The objective of this project was to optimize detector dimensions and positioning of an existing detector concept for neutron-based range verifications using Monte Carlo simulations.

The thesis is available in pdf format here.

Analysis and Development of Phenomenological Models for the Relative Biological Effectiveness in Proton Therapy - PhD thesis by Eivind Rørvik

Irradiation experiments on cells and animal models have shown that protons are slightly more effective in producing biological damage than photons. This difference in biological response is quantified by the relative biological effectiveness (RBE). A conservative and constant RBE of 1.1 is used in proton therapy clinics, even though experiments have shown that the RBE can be both higher and lower, varying with different biological and physical quantities, including the linear energy transfer (LET). Phenomenological RBE models try to determine the various RBE dependencies from large experimental databases of cell irradiation experiments. In this work, existing phenomenological models were analysed and explored in a coherent manner: All models were parameterised and described by functions of the maximum RBE (RBEmax) and minimum RBE (RBEmin), the two model functions that make every model unique. A new phenomenological RBE model was proposed, introducing the full LET spectrum as an input parameter for phenomenological models. Statistical methods were used to test whether a non-linear LET dependency of RBEmax would give a superior description of the experimental data compared to using the established linear dependency of the dose-averaged LET (LETd). Further, we analysed the LETd dependency of RBEmin in a two-step regression analysis, as the RBEmin function is most commonly assumed to be constant for all LETd values.

The thesis is available in pdf format here.

The experimental dose ranges influence the LETd dependency of the proton minimum RBE (RBEmin)

Rørvik, Eivind et al. Physics in Medicine and Biology (2019)

Cell experiments have shown the proton RBE to vary with dose and LET, which has led to development of variable RBE models. The RBE is normally estimated from two independent functions, the RBEmax and RBEmin, describing the extreme RBE at low and high doses. While there is consensus that RBEmax increases with increasing LET, the RBEmin is not uniformly defined and its dependency on LET is deviating. In this work, we analysed this dependency and its sensitivity to variations of the experimental dose range.

The article is available in pdf format here.

A Predictive Model for Biological Range Shift in Proton Therapy - Master thesis by Vegard Aas Mjelde

The biological effects on cells due to proton irradiation are different than for photons. The protons cause more damage for the same deposited physical dose, because of their increased Linear Energy Transfer (LET). This increase in biological effectiveness is quantified by the Relative Biological Effectiveness (RBE). Clinically a constant RBE factor of 1.1 (RBE1.1) is used, but multiple studies on RBE indicate that it increases with depth due to the increase in LET with depth. This leads to a potential underestimation of the biological effects when using RBE1.1, especially in the distal part of the treatment fields, towards the end of the particles’ range. The increase in dose due to variable RBE increases the depth of the distal 80% dose fall-off, which is often used to quantify the beam range. This range shift between the RBE1.1 and the variable RBE models may cause unexpected radiation damage to healthy tissue and organs at risk. Modelling or predicting the biological range shift in different scenarios is therefore of importance, and the it was the goal for this project.

The thesis is available in pdf format here.

2018:

Impact of variable proton relative biological effectiveness on estimates of secondary cancer risk in paediatric cancer patients - Master thesis by Vilde Grandemo

Proton therapy has an increased dose-conformity compared to conventional radiotherapy with photons, and paediatric cancer patients receiving cranio-spinal irradiation (CSI) are routinely referred to this treatment modality. With long life-expectancy and enhanced radiosensitivity, children are at a significant risk of developing radiation-induced secondary cancers, emphasising the importance of secondary cancer risk estimations following proton therapy for these patients. Previous comparative studies on secondary cancer risk following proton and photon CSI treatment plans for paediatric cancer patients have based the proton risk estimates on a constant proton relative biological effectiveness (RBE) of 1.1. In this study, proton CSI treatment plans for ten paediatric medulloblastoma patients were analysed with respect to the risk of radiation-induced secondary cancer of the lungs and thyroid by comparing risks predicted by the clinical proton RBE of 1.1 to the risk predictions of four variable RBE models (LET-weighted dose, the McNamara model, the Rørvik model, and the Wilkens model). By applying the organ equivalent dose (OED) concept to different dose-response scenarios, the lifetime attributable risk (LAR) and the excess absolute risk (EAR) were estimated based on age-, sex-, and site-specific risk coefficients gathered from epidemiological data on the Japanese A-bomb survivors.

The thesis is available in pdf format here.

Sensitivity study of the microdosimetric kinetic model parameters for carbon ion radiotherapy

Dahle, Tordis et al. Physics in Medicine and Biology (2018)

The relative biological effectiveness (RBE) calculation methods currently applied clinically in carbon ion therapy are derived from the microdosimetric kinetic model (MKM) in Japan and the local effect model (LEM) in Europe. The input parameters of these models are based on fit to experimental data subjected to uncertainties. We therefore performed a sensitivity study of the MKM input parameters, i.e. the domain radius (rd), the nucleus radius (Rn) and the parameters of the linear quadratic model (αx and β).

The article is available in pdf format here.

Exploration and application of phenomenological RBE models for proton therapy

Rørvik, Eivind et al. Physics in Medicine and Biology (2018)

The relative biological effectiveness (RBE) of protons varies with multiple physical and biological factors. Phenomenological RBE models have been developed to include such factors in the estimation of a variable RBE, in contrast to the clinically applied constant RBE of 1.1. In this study, eleven published phenomenological RBE models and two plan-based models were explored and applied to simulated patient cases.

The article is available in pdf format here.

Optmization of proton therapy plans with respect to biological and physical dose distributions - Master thesis by Helge Henjum

Proton therapy is a radiation treatment method growing around the world. This is mainly due to the protons ability to deposit dose more conformal compared to conventional photon therapy. Protons also differ in terms of biological effect compared to photons for the same physical dose. To account for this increased relative biological effectiveness (RBE), a constant RBE of 1.1 is applied in clinical proton therapy treatment planning, i.e. approximately 10% lower physical dose is given to the tumor if proton therapy is used. It is however known that the RBE is not constant, and is dependent on e.g. the linear energy transfer (LET), physical dose and tissue type. By using biological optimization the tumor may get a homogeneous biological dose distribution, and prevent over- and under dosage to healthy tissue and the tumor volume. Variable RBE models can be used to optimize a treatment plan with respect to RBE-weighted dose, but these are not yet available in commercial treatment planning systems.

The aim of this study was to implement a method for optimization of treatment plans with respect to both biological and physical dose, and further use this to analyze the differences in physical and biological dose distributions depending on the optimization strategies applied.

The thesis is available in pdf format here.

2017:

A phenomenological biological dose model for proton therapy based on linear energy transfer spectra

Rørvik, Eivind et al. Medical Physics (2017)

The relative biological effectiveness (RBE) of protons varies with the radiation quality, quantified by the linear energy transfer (LET). Most phenomenological models employ a linear dependency of the dose-averaged LET (LETd) to calculate the biological dose. However, several experiments have indicated a possible non-linear trend. Our aim was to investigate if biological dose models including non-linear LET dependencies should be considered, by introducing a LET spectrum based dose model.

The article is available in pdf format here.

Monte Carlo based comparison of constant vs. variable RBE for proton therapy patients - Master thesis by Johan Martin Søbstad

The primary objective of this project was to calculate and compare the dose-to-patient results of constant RBE versus variable RBE calculated by different models for protons. The calculations were done by a combination of FLUKA Monte Carlo (MC) simulations and post-processing using custom scrips written in Python. CT images and treatment plan information for a medulloblastoma patient was imported into FLUKA, where the dose and linear energy transfer (LET) was calculated. The RBE values were subsequently calculated for four different models, assuming constant tissue parameters. An in-depth investigation of the different model properties was performed by systematically varying the model parameters. RBE calculations with a simple treatment plan on a water phantom were also performed.

The thesis is available in pdf format here.

Monte Carlo simulations of neutron doses from pencil beam scanning proton therapy - Master thesis by Yannick Alexander Broese van Groenou

A side effect of proton therapy is the production of secondary neutrons generated by the beam particles through nuclear interactions. Neutrons contribute with an unwanted, additional dose, and because neutrons are highly penetrating, they can reach organs and tissue far outside the treatment field. As these particles can have a very strong biological impact, a small dose can lead to a high risk of radiation-induced cancer and other secondary malignancies. In this thesis, a cranio-spinal irradiation treatment using intensity-modulated proton therapy for a pediatric medulloblastoma patient was simulated by using the Monte Carlo simulation code FLUKA. Two obliquely opposed proton beams with energies 175 – 190 MeV were used for the cranial fields, and 135 – 150 MeV proton beams for the spinal fields. The therapeutic biological proton dose was 23.4 Gy(RBE). The neutron absorbed dose and ambient dose equivalent were scored for organs at risk and the PTVs. In the treatment, organs at risk were thyroid, liver, colon, stomach, lung, kidneys, bone and bladder. The dose distributions were plotted in a dose-volume histogram, visualized in two-dimensional plots and one-dimensional graphs of dose as a function of depth inside the patient.

The thesis is available in pdf format here.

Linear energy transfer distributions in the brainstem depending on tumour location in intensity-modulated proton therapy of paediatric cancer

Fjæra, Lars Fredrik, et al. Acta Oncologica (2017)

For tumours near organs at risk, there is concern about unintended increase in biological dose from elevated linear energy transfer (LET) at the distal end of treatment fields. The objective of this study was therefore to investigate how different paediatric posterior fossa tumour locations impact LET and biological dose to the brainstem during intensity-modulated proton therapy (IMPT).

The article is available in pdf format here.

The FLUKA Monte Carlo code coupled with the NIRS approach for clinical dose calculations in carbon ion therapy

Magro, Giuseppe et al. Physics in Medicine and Biology (2017)

In this paper, we describe the coupling of the NIRS (National Institute for Radiological Sciences, Japan) clinical dose to the FLUKA MC code. We moved from the implementation of the model itself to its application in clinical cases, according to the NIRS approach, where a scaling factor is introduced to rescale the (carbon-equivalent) biological dose to a clinical dose level. A high level of agreement was found with published data by exploring a range of values for the MKM input parameters, while some differences were registered in forward recalculations of NIRS patient plans, mainly attributable to differences with the analytical TPS dose engine (taken as reference) in describing the mixed radiation field (lateral spread and fragmentation). We presented a tool which is being used at the Italian National Center for Oncological Hadrontherapy to support the comparison study between the NIRS clinical dose level and the LEM dose specification.

The article is available in pdf format here.

Monte Carlo simulations of a low energy proton beamline for radiobiological experiments

Dahle, Tordis J., et al. Acta Oncologica (2017)

In this study, we characterized and explored a novel low energy proton beam cell irradiation setup through dosimetry and dedicated MC simulations. Such low energy proton beams are ideal for radiobiological experiments, since low energy proton beams can produce high LETd values and narrow LET spectra. The objective of this study was to determine the initial beam parameters for MC simulations of the novel cell irradiation setup, and further use MC simulations to determine spatial variations in LET in positions intended for cell irradiation. We further compared LET values from our proton beam to LET values from an 80 MeV proton beam, representing a typical minimum energy, and thus maximum LETd, available at clinical facilities.

The article is available in pdf format here.

The workflow for dose verification with FLUKA. The custom made scripts (green boxes) enable dose recalculation in FLUKA and comparison to the original dose distribution. Treatment plans (DICOM format) from the TPS are run through the scripts which obtain relevant parameters and information required by FLUKA. Figure: Lars Fredrik Fjæra

2016:

Development of a Monte Carlo Based Treatment Planning Verification Tool for Particle Therapy - Master thesis by Lars Fredrik Fjæra 

In this project, a tool that translates treatment plan information into data readable for the FLUKA code was developed. The tool includes several routines based on Python scripts. It enables reading of relevant treatment plan settings required to automatically generate a FLUKA simulation file for dose recalculation. Functions for data analysis and visualization, as well as comparison between the TPS and FLUKA results were also created. In addition, scripts for converting a FLUKA calculated dose distribution into DICOM format were created.

The thesis is available in pdf format here.

2015:

A Comparative Study of Radiation Environment and Secondary Dose Production in a Particle Therapy Treatment Room Applying Proton, Helium and Carbon Ion Beams - Master thesis by Jarle Rambo Sølie

The purpose of this master thesis has been to perform a comparative study of the induced radiation environment inside a typical treatment room during irradiation of a water phantom with proton, helium and carbon beams, and introduce various entrance structures and shielding materials to the treatment room in order to compare and illuminate their effects and study the differential fluence spectra of neutrons and photons entering and exiting these featured structures. Water equivalent worker phantoms representing hospital personnel were placed inside and outside the vicinity of the entrance structures and effective dose to each of them were scored. A total of 24 simulations covering eight different treatment room layouts were performed in FLUKA and the final results illuminated the many considerations and deliberations that must be taken into account during the planning, building and shielding fitting of a treatment room for use in particle therapy.

The thesis is available in pdf format here.

The Influence of the Energy Degrader Material for a Therapeutical Proton Beam - Master thesis work by John Alfred Brennseter

In cyclotron based proton therapy an energy degrader is needed to modulate the proton beam energy. The proton beamenergy decides the range of the particles and thereby where the dose is imparted. The influence of the material of the energy degrader for a 250 MeV therapeutic proton beam has been evaluated with FLUKA, a Monte Carlo based particle transport software. A geometry of a double wedge degrader of beryllium, carbon or lexan and a collimator of copper and carbon has been used. The momentum spread, angular spread, transmission fraction neutron yield and photon yield have been measured.

The thesis is available in pdf format here.

A Comparison of Biological Dose Estimates in Proton and Carbon Ion Therapy Based on Averaged and Full Linear Energy Transfer Spectra - Master thesis work by Eivind Rørvik

Radiotherapy with ions, also known as particle therapy, is increasing rapidly. To adapt from the higher biological effectiveness of particles compared to photons, the concept of relative biological effectiveness (RBE) is used. Protons are slightly more effective than photons, and the RBE is set to be constant 1.1. The constant RBE value is not a physical property of the beam, it is simply assigned to be 1.1 by a consensus in the scientifc community. Experiments indicate that the RBE in reality is marginally increasing along with the treatment depth. For carbon ions the variations in RBE are signifcantly higher and typically range between 1 and 3. The variation is taken into account in treatment planning, however, relatively large uncertainties are present in the radiobiological models applied. Many of these models are based on correlations between the calculated linear energy transfer (LET) and experimentally measured RBE. Most phenomenological models are based on the dose averaged LET, LETd. However, it should also be possible to correlate the biological effect to the full dose weighted LET spectrum, d(L). By using a biological weighting function (BWF), it is possible to estimate the RBE from either LETd or d(L). In this work, several proton and carbon ion beams were simulated with the FLUKA Monte Carlo code. The physical absorbed dose and the LET spectrum d(L) were estimated at different depths in a water phantom. A BWF was created upon existing cell experiments databases and applied to quantify the effect of the averaging.

The thesis is available in pdf format here.

2014:

Dosimetric Consequences of Dropping the Momentum Analysis System in a Compact Proton Therapy System - Project thesis by Eivind Rørvik

The high investment cost of proton therapy centers could be lowered by building just one single room systems. When a accelerator serves a single treatment room, the beam line could be minimized to cut the cost further. One of the systems available on the market today is cutting the Momentum Analysis system (MAS, Momentum analyser), and degrading the beam directely in front of the patient. The momentum of the beam is then larger compared to other systems, which further enlarges the distal dose falloff, a common dosimetric parameter used in clinics. A higher distal dose falloff will create a higher dose to organs at risk behind the tumor volume, which enlarges the NTCP, as shown in the figure.

In this thesis a simplified 250 MEV proton beam is degraded through PMMA and dropped into a water phantom. The thickness of PMMA is varied to get different clinical relevant ranges. Other proton beams were dropped directly into the water phantom, with realistic ESS/Synchrotron parameters. The bragg curves of the beams were recorded by a usrbin-card in FLUKA, and the range (90%) and distal dose falloff (80%-20%) were analysed by a matlab script. The plot shows the 5 different beams.

As seen, the systems without a momentum analyser have a constant distal dose falloff for all ranges, compared to the ESS/synchrotron systems, which have an almost proportional ratio between the parameters.

At deep treatment depths (prostate etc.), the clinically differences between the systems nearly negligible. But for shallow treatment depths (Breast, spine etc), the should be accounted for. For some conditions, as left sided breast cancer, treatment with such a system MIGHT not be favoured over high precision photon therapy. Multiple dose plans should be made and compared for these potential cancer type, to either confirm or rule out the possible dosimetric consequence of dropping the MAS.

The thesis was written in a project course at NTNU under supervision of Pål Erik Goa, in collaboration with Kristian Smeland Ytre-Hauge.

Files:

Fluka input file (change from .txt to .inp)

Flair file

Project report

Simulations of Neutron Fluence Through Concrete Wall in Proton Therapy - Project thesis by John Alfred Brennsæter

In proton therapy secondary particles are generated when the protons interact with matter. As the protons have larger energy than photons in conventional radiation therapy, there are generated neutrons with higher energy. This leads to that thick walls are needed to keep the neutron radiation from the treatment room away from the surroundings.

In this thesis proton beams with varying energy from 70 - 250 MeV have been dumped in a water phantom of (100x30x40)cm3 . The neutron fluence was recorded by the usrbin-card, and the energy spectrum was recorded by the usrbdx-card.

This simulations show that the penetration depths of neutrons are increasing with increasing proton beam energy.

The thesis was written in a project course at NTNU under supervision of Pål Erik Goa, in collaboration with Kristian Smeland Ytre-Hauge.

Files:

Fluka input file (change from .txt to .inp )

Flair file

Project report

Extremely high-granularity digital tracking calorimeter for the detection of scattered protons in proton computed tomography - Master thesis by Daniel Aadnevik

The ability to accurately position the Bragg peak at a planned location is a major advantage of protons and light ions, but incomplete knowledge about the tissue properties and their relative position limits the treatment precision, and range uncertainties of several millimeters may arise. This occurs when photon attenuation maps from computed tomography (CT) scans are converted into relative stopping power. The principles of a proton CT scanner as an alternative to X-ray CT will be outlined in this thesis. Imaging with protons allows direct information about the stopping power to be obtained, and has the potential to reduce range uncertainties from current values of 3-10 mm to 1-3 mm.

A simplified model of the FoCal detector has been implemented in the Monte Carlo simulation package FLUKA, and the detector response to a 180 MeV - 280 MeV proton beam has been studied. Results on the tracking precision was found to be comparable to existing prototypes, but the thickness of the absorbers was found to limit the ability to accurately determine the Bragg peak position. The result of replacing the absorbers with a lighter material resulted in an improved tracking resolution, and an alternative detector construction optimized for proton CT will be presented. The ultimate goal is to measure the calorimeter response to a therapeutic proton beam. The aim of this thesis has been to prepare the beam tests, both through Monte Carlo simulations and systematic detector studies.

The thesis is available in pdf format here.

2013:

Simulations of a Therapeutic Proton Beam with FLUKA Monte Carlo Code and Varian Eclipse Proton Planning Software - Master thesis work by Kine Johnsen

The purpose of this project has been to apply Monte Carlo software to simulate a proton beam resembling a therapeutic beam, and to study the interactions of this beam in phantoms of various design.

The Monte Carlo simulations were compared to results from Eclipse (a clinical dose planning system). The overall agreement between the two calculation methods were adequate, especially with respect to dose coverage within the defined target volume. However, when introducing different materials such as bone, air and aluminium into the geometry, the differences between the two methods became apparent and it illustrates the tentative limitations of a fast, clinical optimized, dose planning tool compared with a more accurate and detailed, hence tentatively slower, Monte Carlo simulation tool.

Kine looked into the source.f user routine in FLUKA in order to be able to define more complex beams than a simple pencil beam. Some example files for creating Spread-Out-Bragg-Peaks for protons and Fluka input files are available here: source_kine.f

The thesis is available in pdf format here.

Measurements and Monte Carlo Simulations of Neutron Doses from Radiation Therapy with Photons, Protons and Carbon Ions - Ph.D. thesis by Kristian Smeland Ytre-Hauge

The overall objective of this thesis has been to investigate the magnitude and distribution of neutron dose from radiation therapy with photons, protons and carbon ions. The pursuit of this ambition has also required an extensive study of the applied neutron detectors’ properties. Measurements in proton and carbon ion beams were performed with a novel neutron detector based on radiation effects in Static Random Access Memory (SRAM) chips. For measurements of neutron dose in photon therapy, bubble detectors and thermoluminescence detectors (TLDs) were applied. Monte Carlo simulations with the FLUKA Monte Carlo simulation package were conducted for comparison with the experimental data.

The thesis is available in pdf format here.

Biasing exercise from Workshop