Dosimetric validation of the couch and coil model for high-field MR-linac treatment planning.

Purpose: The precision of the dose delivery in radiation therapy with high-field MR-linacs is challenging due to the substantial variation in the beam attenuation of the patient positioning system (PPS) (the couch and coils) as a function of the gantry angle. This work aimed to compare the attenuation of two PPSs located at two different MR-linac sites through measurements and calculations in the treatment planning system (TPS).

Methods: Attenuation measurements were performed at every 1° gantry angle at the two sites with a cylindrical water phantom with a Farmer chamber inserted along the rotational axis of the phantom.

Modelling tissue specific RBE for different radiation qualities based on a multiscale characterization of energy deposition.

Purpose: We present the nanoCluE model, which uses nano- and microdosimetric quantities to model RBE for protons and carbon ions. Under the hypothesis that nano- and microdosimetric quantities correlates with the generation of complex DNA double strand breakes, we wish to investigate whether an improved accuracy in predicting LQ parameters may be achieved, compared to some of the published RBE models.

Methods: The model is based on experimental LQ data for protons and carbon ions.

Patterns of practice for adaptive and real-time radiation therapy (POP-ART RT) part I: Intra-fraction breathing motion management.

Purpose: The POP-ART RT study aims to determine to what extent and how intra-fractional real-time respiratory motion management (RRMM) and plan adaptation for inter-fractional anatomical changes (ART), are used in clinical practice and to understand barriers to implementation. Here we report on part I: RRMM.

Material And Methods: A questionnaire was distributed worldwide to assess current clinical practice, wishes for expansion or new implementation and barriers to implementation.

Patterns of practice for adaptive and real-time radiation therapy (POP-ART RT) part II: Offline and online plan adaption for interfractional changes.

Purpose: The POP-ART RT study aims to determine to what extent and how intrafractional real-time respiratory motion management (RRMM), and plan adaptation for interfractional anatomical changes (ART) are used in clinical practice and to understand barriers to implementation. Here we report on part II: ART using more than one plan per target per treatment course.

Materials And Methods: A questionnaire on the current practice of ART, wishes for expansion or implementation, and barriers to implementation was distributed worldwide.

Target Size Variation in Microdosimetric Distributions and its Impact on the Linear-Quadratic Parameterization of Cell Survival.

The linear-quadratic (LQ) parameterization of survival fraction [SF( D)] inherently assumes that all cells in a population receive the same dose ( D), albeit the distribution of specific energy z over the individual cells f( z, D) can be very wide. From these microdosimetric distributions, which are target size dependent, we estimate the size of the cellular sensitive volume by analyzing its influence on the LQ parameterization of cell survival. A Monte Carlo track structure code was used to simulate detailed tracks from a Co source as well as proton and carbon ions of various energies.

Quantification of proteins by data independent acquisition: Performance assessment of the Hi3 methodology.

Proteomics greatly benefited from the development of mass spectrometry. Over the last years, data-independent acquisitions increased in popularity in an effort to provide routine label free quantitative information. In this report, the performance of the Hi3 label free method was assessed based on the analysis of a plasma-derived protein mixture.

Biochemical characterization of LR769, a new recombinant factor VIIa bypassing agent produced in the milk of transgenic rabbits.

Background: The bypassing agent factor VII (FVIIa) is a first-line therapy for the treatment of acute bleeding episodes in patients with haemophilia and high-titre inhibitors. FVIIa is a highly post-translationally modified protein that requires eukaryotic expression systems to produce a fully active molecule. A recombinant FVIIa was produced in the milk of transgenic rabbits to increase expression and provide an efficient, safe and affordable product after purification to homogeneity (LR769).

Energy deposition clustering as a functional radiation quality descriptor for modeling relative biological effectiveness.

Purpose: To explore the use of the frequency of the energy deposition (ED) clusters of different sizes (cluster order, CO) as a surrogate (instead of, e.g., LET) classification of the physical characteristics of ionizing radiation at a nanometer scale, to construct a framework for the calculation of relative biological effectiveness (RBE) with cell survival as endpoint.

Mass spectrometry based analysis of human plasma-derived factor X revealed novel post-translational modifications.

Human coagulation factor X is a central component of the blood coagulation cascade that converts, under its activated form, prothrombin into thrombin. Generation of thrombin is the final step of the clotting cascade that leads to the clot by polymerization of fibrinogen molecules into a fibrin network. Today, research of new by-passing agents of the coagulation may contribute to an increased interest for human factor X, which may, in consequence, lead to the need of a more exhaustive picture of its structural features.

Microdosimetric spread for cell-sized targets exposed to ⁶⁰Co, ¹⁹²Ir and ¹²⁵I sources.

The magnitude of the spread in specific energy deposition per cell may be a confounding factor in dose-response analysis motivating derivation of explicit data for the most common brachytherapy isotopes (125)I and (192)Ir, and for (60)Co radiation frequently used as reference in RBE studies. The aim of this study is to analyse the microdosimetric spread as given by the frequency distribution of specific energy for a range of doses imparted by (125)I, (192)Ir and (60)Co sources. An upgraded version of the Monte Carlo code PENELOPE was used for scoring energy deposition distributions in liquid water for each of the radiation qualities.

Cluster pattern analysis of energy deposition sites for the brachytherapy sources 103Pd, 125I, 192Ir, 137Cs, and 60Co.

Analysing the pattern of energy depositions may help elucidate differences in the severity of radiation-induced DNA strand breakage for different radiation qualities. It is often claimed that energy deposition (ED) sites from photon radiation form a uniform random pattern, but there is indication of differences in RBE values among different photon sources used in brachytherapy. The aim of this work is to analyse the spatial patterns of EDs from 103Pd, 125I, 192Ir, 137Cs sources commonly used in brachytherapy and a 60Co source as a reference radiation.

Monte Carlo calculated microdosimetric spread for cell nucleus-sized targets exposed to brachytherapy 125I and 192Ir sources and 60Co cell irradiation.

The stochastic nature of ionizing radiation interactions causes a microdosimetric spread in energy depositions for cell or cell nucleus-sized volumes. The magnitude of the spread may be a confounding factor in dose response analysis. The aim of this work is to give values for the microdosimetric spread for a range of doses imparted by (125)I and (192)Ir brachytherapy radionuclides, and for a (60)Co source.

Dose mapping sensitivity to deformable registration uncertainties in fractionated radiotherapy - applied to prostate proton treatments.

Background: Calculation of accumulated dose in fractionated radiotherapy based on spatial mapping of the dose points generally requires deformable image registration (DIR). The accuracy of the accumulated dose thus depends heavily on the DIR quality. This motivates investigations of how the registration uncertainty influences dose planning objectives and treatment outcome predictions.

Track structure of protons and other light ions in liquid water: applications of the LIonTrack code at the nanometer scale.

Purpose: The LIonTrack (Light Ion Track) Monte Carlo (MC) code for the simulation of H(+), He(2+), and other light ions in liquid water is presented together with the results of a novel investigation of energy-deposition site properties from single ion tracks.

Methods: The continuum distorted-wave formalism with the eikonal initial state approximation (CDW-EIS) is employed to generate the initial energy and angle of the electrons emitted in ionizing collisions of the ions with H2O molecules. The model of Dingfelder et al.

Limitations (and merits) of PENELOPE as a track-structure code.

Purpose: To outline the limitations of PENELOPE (acronym of PENetration and Energy LOss of Positrons and Electrons) as a track-structure code, and to comment on modifications that enable its fruitful use in certain microdosimetry and nanodosimetry applications.

Methods: Attention is paid to the way in which inelastic collisions of electrons are modelled and to the ensuing implications for microdosimetry analysis.

Results: Inelastic mean free paths and collision stopping powers calculated with PENELOPE and two well-known optical-data models are compared.

Fast analysis of recombinant monoclonal antibodies using IdeS proteolytic digestion and electrospray mass spectrometry.

We describe a fast and informative method to investigate the posttranslational modifications of monoclonal antibodies (MAbs). The MAb is first digested by a specific enzyme that cleaves heavy chains under the hinge domain. After reduction of disulfide bridges, three polypeptide chains of approximately 25 kDa are released and analyzed by liquid chromatography-mass spectrometry (LC-MS).

Reference dosimetry in a scanned pulsed proton beam using ionisation chambers and a Faraday cup.

In order to give the correct dose to a patient, the monitor chamber for a proton scanning system has to be calibrated. As recombination of ion pairs occurs in the monitor chamber, the relation between the number of particles traversing it per time unit and the ionization chamber signal is not linear. A method developed for a scanned pulsed proton beam taking the nonlinear monitor signal into account is described.

Parametrization and application of scatter kernels for modelling scanned proton beam collimator scatter dose.

Collimators are routinely used in proton radiotherapy to laterally confine the field and improve the penumbra. Collimator scatter contributes up to 15% of the local dose and is therefore important to include in treatment planning dose calculation. We present a method for reconstruction of the collimator scatter phase space based on the parametrization of pre-calculated scatter kernels.

Monte Carlo simulation and analysis of proton energy-deposition patterns in the Bragg peak.

The spatial pattern of energy depositions is crucial for understanding the mechanisms that modify the relative biological effectiveness of different radiation qualities. In this paper, we present data on energy-deposition properties of mono-energetic protons (1-20 MeV) and their secondary electrons in liquid water. Proton-impact ionization was described by means of the Hansen-Kocbach-Stolterfoht doubly differential cross section (DDCS), thus modelling both the initial energy and angle of the emitted electron.

Experimental test of Monte Carlo proton transport at grazing incidence in GEANT4, FLUKA and MCNPX.

The ability of the Monte Carlo (MC) particle transport codes GEANT4.8.1 and GEANT4.

A beam source model for scanned proton beams.

A beam source model, i.e. a model for the initial phase space of the beam, for scanned proton beams has been developed.

Development and verification of the pulsed scanned proton beam at The Svedberg Laboratory in Uppsala.

In this paper we present the recent developments made for the scanning system for proton beams at TSL in Uppsala, showing that this system is now fully functional being able to produce conformal intensity modulated scan patterns with sufficient accuracy. A new control and supervising system handling the beam delivery including the control of the synchrocyclotron and the scanning system is developed and described in detail. A complete dosimetry system with transmission ionization chambers and a multi-wire ionization chamber for monitoring of the beam during scanning has been constructed.

Endothelin-1 levels in patients with Paget's disease of bone.

A locally accelerated bone turnover is the pathophysiological basis of Paget's disease of bone (PD) and may result in severe bone deformations and pain. Affected bone sites are hypervascularized. Secreted endothelial products such as endothelin-1 (ET-1), influence bone metabolism.

Dose and time dependent apoptotic response in a human melanoma cell line exposed to accelerated boron ions at four different LET.

The aim was to investigate and compare the influence of linear energy transfer (LET), dose and time on the induction of apoptosis in a human melanoma cell line exposed to accelerated light boron ((10)B) ions and photons. Cells were exposed in vitro to doses up to 6 Gy accelerated boron ions (40, 80, 125 and 160 eV nm(-1)) and up to 12 Gy photons (0.2 eV nm(-1)).

The influence of RBE variations in a clinical proton treatment plan for a hypopharynx cancer.

Currently, most clinical range-modulated proton beams are assumed to have a fixed overall relative biological effectiveness (RBE) of 1.1. However, it is well known that the RBE increases with depth in the spread-out Bragg peak (SOBP) and becomes about 10% higher than mid-SOBP RBE at 2 mm from the distal edge (Paganetti 2003 Technol.