Monte Carlo (MC) codes are increasingly spreading in the hadrontherapy community due to their detailed description of radiation transport and interaction with matter. The suitability of a MC code for ...application to hadrontherapy demands accurate and reliable physical models capable of handling all components of the expected radiation field. This becomes extremely important for correctly performing not only physical but also biologically based dose calculations, especially in cases where ions heavier than protons are involved. In addition, accurate prediction of emerging secondary radiation is of utmost importance in innovative areas of research aiming at in vivo treatment verification. This contribution will address the recent developments of the FLUKA MC code and its practical applications in this field. Refinements of the FLUKA nuclear models in the therapeutic energy interval lead to an improved description of the mixed radiation field as shown in the presented benchmarks against experimental data with both (4)He and (12)C ion beams. Accurate description of ionization energy losses and of particle scattering and interactions lead to the excellent agreement of calculated depth-dose profiles with those measured at leading European hadron therapy centers, both with proton and ion beams. In order to support the application of FLUKA in hospital-based environments, Flair, the FLUKA graphical interface, has been enhanced with the capability of translating CT DICOM images into voxel-based computational phantoms in a fast and well-structured way. The interface is capable of importing also radiotherapy treatment data described in DICOM RT standard. In addition, the interface is equipped with an intuitive PET scanner geometry generator and automatic recording of coincidence events. Clinically, similar cases will be presented both in terms of absorbed dose and biological dose calculations describing the various available features.
Overview of the FLUKA code Battistoni, Giuseppe; Boehlen, Till; Cerutti, Francesco ...
Annals of nuclear energy,
08/2015, Volume:
82, Issue:
C
Journal Article
Peer reviewed
Open access
The capabilities and physics models implemented inside the FLUKA code are briefly described, with emphasis on hadronic interaction. Examples of the performances of the code are presented including ...basic (thin target) and complex benchmarks, and radiation detector specific applications. In particular the ability of FLUKA in describing existing calorimeter performances and in predicting those of future ones, as well as the use of the code for neutron and mixed field radiation detectors will be demonstrated with several examples.
The FLUKAS code 1–3 is used in research laboratories all around the world for challenging applications spanning a very wide range of energies, projectiles and targets. FLUKAS is also extensively used ...for in hadrontherapy research studies and clinical planning systems. In this paper some of the recent developments in the FLUKAS nuclear physics models of relevance for very different application fields including medical physics are presented. A few examples are shown demonstrating the effectiveness of the upgraded code.
FLUKA is a general purpose Monte Carlo code capable of handling all radiation components from thermal energies (for neutrons) or 1
keV (for all other particles) to cosmic ray energies and can be ...applied in many different fields. Presently the code is maintained on Linux. The validity of the physical models implemented in FLUKA has been benchmarked against a variety of experimental data over a wide energy range, from accelerator data to cosmic ray showers in the Earth atmosphere. FLUKA is widely used for studies related both to basic research and to applications in particle accelerators, radiation protection and dosimetry, including the specific issue of radiation damage in space missions, radiobiology (including radiotherapy) and cosmic ray calculations.
After a short description of the main features that make FLUKA valuable for these topics, the present paper summarizes some of the recent applications of the FLUKA Monte Carlo code in the nuclear as well high energy physics. In particular it addresses such topics as accelerator related applications.
4He ions are considered an attractive modality supplementary to protons and 12C ions for use in cancer radiation therapy. The accelerator and beam application system at the Heidelberg ion-beam ...therapy center (HIT) are currently commissioned for clinical application of 4He ions, which involves the calculation of basic data for the treatment planning system (laterally integrated depth dose profiles, lateral dose profiles and fragment distributions in water). For the commissioning of protons and 12C ions at HIT the FLUKA code 1,2 has been used 3. The models for light ion interactions in FLUKA are undergoing several improvements and enhancements 4 particularly for 4He and their performances have already been investigated for calculation of 4He dosimetric data 5. While the shape of the Bragg peak curve is mostly dominated by the Landau fluctuations in the projectile energy losses, its height is mainly determined by the nuclear interactions undergone by the primary ions. Furthermore, the fragments generated in nuclear interactions can give rise to a fragmentation tail after the Bragg peak and contribute to the quality of the mixed radiation field. Therefore, experimental data about the total nuclear cross-section and fragment distributions for 4He beams are needed to develop and validate the models available for 4He-induced nuclear reactions with the same level of reliability achieved for other ion species (e.g. 12C).
The aim of this work is to present novel fragmentation data 6, in particular mass-changing cross-sections for 4He+12C collisions over the entire energy range relevant for therapy, and to compare them with the 4He-nucleus reaction models currently under development for FLUKA. The presented work will have the potential to improve significantly the dose calculation for helium ion therapy and ensure that future basic data will be as reliable as possible.
The Monte Carlo method was invented by John von Neumann, Stanislaw Ulam, and Nicholas Metropolis (who gave it its name) and independently by Enrico Fermi. Originally, it was not a simulation method ...but a mathematical approach aimed at solving a multidimensional integro-differential equation by means of a stochastic process. The equation itself did not necessarily refer to a stochastic process.
Non-alcoholic fatty liver is the most common liver disease worldwide. Here, we show that the mitochondrial protein mitofusin 2 (Mfn2) protects against liver disease. Reduced Mfn2 expression was ...detected in liver biopsies from patients with non-alcoholic steatohepatitis (NASH). Moreover, reduced Mfn2 levels were detected in mouse models of steatosis or NASH, and its re-expression in a NASH mouse model ameliorated the disease. Liver-specific ablation of Mfn2 in mice provoked inflammation, triglyceride accumulation, fibrosis, and liver cancer. We demonstrate that Mfn2 binds phosphatidylserine (PS) and can specifically extract PS into membrane domains, favoring PS transfer to mitochondria and mitochondrial phosphatidylethanolamine (PE) synthesis. Consequently, hepatic Mfn2 deficiency reduces PS transfer and phospholipid synthesis, leading to endoplasmic reticulum (ER) stress and the development of a NASH-like phenotype and liver cancer. Ablation of Mfn2 in liver reveals that disruption of ER-mitochondrial PS transfer is a new mechanism involved in the development of liver disease.
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•Mfn2 binds directly and specifically to phosphatidylserine (PS)•Hepatic Mfn2 deficiency causes a reduced transfer of PS from ER to mitochondria•Mfn2 ablation in liver causes a NASH-like phenotype and liver cancer•A defective transfer of PS from ER to mitochondria causes liver disease
The mitochondrial protein mitofusin 2 binds and transfers phosphatidylserine across mitochondria-ER contacts, and perturbation of this process leads to aberrant lipid metabolism and liver diseases like NASH, NAFLD, and cancer.
Estimates of cancer risk and the effects of surveillance in Lynch syndrome have been subject to bias, partly through reliance on retrospective studies. We sought to establish more robust estimates in ...patients undergoing prospective cancer surveillance.
We undertook a multicentre study of patients carrying Lynch syndrome-associated mutations affecting
,
,
or
. Standardised information on surveillance, cancers and outcomes were collated in an Oracle relational database and analysed by age, sex and mutated gene.
1942 mutation carriers without previous cancer had follow-up including colonoscopic surveillance for 13 782 observation years. 314 patients developed cancer, mostly colorectal (n=151), endometrial (n=72) and ovarian (n=19). Cancers were detected from 25 years onwards in
and
mutation carriers, and from about 40 years in
and
carriers. Among first cancer detected in each patient the colorectal cancer cumulative incidences at 70 years by gene were 46%, 35%, 20% and 10% for
and
mutation carriers, respectively. The equivalent cumulative incidences for endometrial cancer were 34%, 51%, 49% and 24%; and for ovarian cancer 11%, 15%, 0% and 0%. Ten-year crude survival was 87% after any cancer, 91% if the first cancer was colorectal, 98% if endometrial and 89% if ovarian.
The four Lynch syndrome-associated genes had different penetrance and expression. Colorectal cancer occurred frequently despite colonoscopic surveillance but resulted in few deaths. Using our data, a website has been established at http://LScarisk.org enabling calculation of cumulative cancer risks as an aid to genetic counselling in Lynch syndrome.
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