Accumulation of sublethal radiation damage and its effect on cell survival.

Determine the extent of sublethal radiation damage (SRD) in a cell population that received a given dose of radiation and the impact of this damage on cell survival.We developed a novel formalism to account for accumulation of SRD with increasing dose. It is based on a very general formula for cell survival that correctly predicts the basic properties of cell survival curves, such as the transition from the linear-quadratic to a linear dependence at high doses.

Monte Carlo evaluation of target dose coverage in lung stereotactic body radiation therapy with flattening filter-free beams.

Aim: Previous studies showed that replacing conventional flattened beams (FF) with flattening filter-free (FFF) beams improves the therapeutic ratio in lung stereotactic body radiation therapy (SBRT), but these findings could have been impacted by dose calculation uncertainties caused by the heterogeneity of the thoracic anatomy and by respiratory motion, which were particularly high for target coverage. In this study, we minimized such uncertainties by calculating doses using high-spatial-resolution Monte Carlo and four-dimensional computed tomography (4DCT) images. We aimed to evaluate more reliably the benefits of using FFF beams for lung SBRT.

Using FFF Beams to Improve the Therapeutic Ratio of Lung SBRT.

Aim: To investigate the extent to which lung stereotactic body radiotherapy (SBRT) treatment plans can be improved by replacing conventional flattening filter (FF) beams with flattening filter-free (FFF) beams.

Material And Methods: We selected 15 patients who had received SBRT with conventional 6-MV photon beams for early-stage lung cancer. We imported the patients' treatment plans into the Eclipse 13.

Impact of Intra-Fractional Motion on Dose Distributions in Lung IMRT.

Aim: To investigate the impact of intra-fractional motion on dose distribution in patients treated with intensity-modulated radiation therapy (IMRT) for lung cancer.

Materials And Methods: Twenty patients who had undergone IMRT for non-small cell lung cancer were selected for this retrospective study. For each patient, a four-dimensional computed tomography (CT) image set was acquired and clinical treatment plans were developed using the average CT.

On calculation of the average linear energy transfer for radiobiological modelling.

Applying the concept of linear energy transfer (LET) to modeling of biological effects of charged particles usually involves calculation of the average LET. To calculate this, the energy distribution of particles is characterized by either the source spectrum or fluence spectrum. Also, the average can be frequency-or dose-weighted.

A simple model for calculating relative biological effectiveness of X-rays and gamma radiation in cell survival.

Objectives: The relative biological effectiveness (RBE) of X-rays and γ radiation increases substantially with decreasing beam energy. This trend affects the efficacy of medical applications of this type of radiation. This study was designed to develop a model based on a survey of experimental data that can reliably predict this trend.

AAPM Task Group 329: Reference dose specification for dose calculations: Dose-to-water or dose-to-muscle?

Linac calibration is done in water, but patients are comprised primarily of soft tissue. Conceptually, and specified in NRG/RTOG trials, dose should be reported as dose-to-muscle to describe the dose to the patient. Historically, the dose-to-water of the linac calibration was often converted to dose-to-muscle for patient calculations through manual application of a 0.

Systematic microdosimetric data for protons of therapeutic energies calculated with Geant4-DNA.

The purpose of this study was to generate physical data needed for microdosimetry-based models of proton RBE. Our focus was on the frequency and dose average lineal energies, y  and y  . We report data for proton energies from 0.

Analysis of histone ubiquitylation by MSL1/MSL2 proteins in vitro.

Histone posttranslational modifications (PTM) control gene activity by targeting chromatin-regulatory proteins. By altering histone charges PTMs could also modulate inter- and intra-nucleosomal interactions, and thus affect chromatin high-order compaction and nucleosome stochastic folding, respectively. However, recently it has been shown that histone H2BK34- ubiquitylation (which is deposited in vivo by MOF-MSL) can destabilize one of the nucleosomal H2A-H2B dimers in symmetrically and (albeit to a lesser extend) asymmetrically modified nucleosomes, and thus promote formation of a hexasome particle.

Radiotherapy of lung cancers: FFF beams improve dose coverage at tumor periphery compromised by electronic disequilibrium.

The purpose of this work was to investigate radiotherapy underdosing at the periphery of lung tumors, and differences in dose for treatments delivered with flattening filter-free (FFF) beams and with conventional flattened (FF) beams. The true differences between these delivery approaches, as assessed with Monte Carlo simulations, were compared to the apparent differences seen with clinical treatment planning algorithms AAA and Acuros XB. Dose was calculated in a phantom comprised of a chest wall, lung parenchyma, and a spherical tumor (tested diameters: 1, 3, and 5 cm).

Average stopping powers for electron and photon sources for radiobiological modeling and microdosimetric applications.

This study concerns calculation of the average electronic stopping power for photon and electron sources. It addresses two problems that have not yet been fully resolved. The first is defining the electron spectrum used for averaging in a way that is most suitable for radiobiological modeling.

A new formalism for modelling parameters α and β of the linear-quadratic model of cell survival for hadron therapy.

We propose a new formalism for calculating parameters α and β of the linear-quadratic model of cell survival. This formalism, primarily intended for calculating relative biological effectiveness (RBE) for treatment planning in hadron therapy, is based on a recently proposed microdosimetric revision of the single-target multi-hit model. The main advantage of our formalism is that it reliably produces α and β that have correct general properties with respect to their dependence on physical properties of the beam, including the asymptotic behavior for very low and high linear energy transfer (LET) beams.

Radial dose distributions from carbon ions of therapeutic energies calculated with Geant4-DNA.

We report on radial dose distributions [Formula: see text] for carbon ions calculated with Geant4-DNA code. These distributions characterize ion tracks on a nanoscale and are important for understanding the biological effects of ion beams. We present data for carbon ion beams in the energy range from 20 to 400 MeV u.

Reducing the cost of proton radiation therapy: the feasibility of a streamlined treatment technique for prostate cancer.

Proton radiation therapy is an effective modality for cancer treatments, but the cost of proton therapy is much higher compared to conventional radiotherapy and this presents a formidable barrier to most clinical practices that wish to offer proton therapy. Little attention in literature has been paid to the costs associated with collimators, range compensators and hypofractionation. The objective of this study was to evaluate the feasibility of cost-saving modifications to the present standard of care for proton treatments for prostate cancer.

Radial dose distributions from protons of therapeutic energies calculated with Geant4-DNA.

Models based on the amorphous track structure approximation have been successful in predicting the biological effects of heavy charged particles. Development of such models remains an active area of research that includes applications to hadrontherapy. In such models, the radial distribution of the dose deposited by delta electrons and directly by the particle is the main characteristic of track structure.

Remodeling of nucleosome-dimer particles with yIsw2 promotes their association with ALL-1 SET domain in vitro.

Functioning of histone lysine methyltransferases (HKMTs) involves interactions of their catalytic domain "SET" with the N-termini of histone H3. However, these interactions are restricted in canonical nucleosomes due to the limited accessibility of H3 termini. Here we investigated whether nucleosome remodeling with the yeast Isw2 affects nucleosome affinity to the SET domain of ALL-1 HKMT.

Electron slowing-down spectra in water for electron and photon sources calculated with the Geant4-DNA code.

Recently, a very low energy extension was added to the Monte Carlo simulation toolkit Geant4. It is intended for radiobiological modeling and is referred to as Geant4-DNA. Its performance, however, has not been systematically benchmarked in terms of transport characteristics.

Formulation of the multi-hit model with a non-Poisson distribution of hits.

Purpose: We proposed a formulation of the multi-hit single-target model in which the Poisson distribution of hits was replaced by a combination of two distributions: one for the number of particles entering the target and one for the number of hits a particle entering the target produces. Such an approach reflects the fact that radiation damage is a result of two different random processes: particle emission by a radiation source and interaction of particles with matter inside the target.

Methods And Materials: Poisson distribution is well justified for the first of the two processes.

Dosimetric impact of fiducial markers in patients undergoing photon beam radiation therapy.

Fiducial markers are widely used in image-guided radiation therapy to correct for setup error and organ motion. These markers, however, can cause dose perturbations in the target volume for patients undergoing external-beam radiation therapy. The goal of this study was to determine the dosimetric impact of various types of fiducial markers commonly used in patients receiving photon radiation therapy.

Interaction of SET domains with histones and nucleic acid structures in active chromatin.

Changes in the normal program of gene expression are the basis for a number of human diseases. Epigenetic control of gene expression is programmed by chromatin modifications-the inheritable "histone code"-the major component of which is histone methylation. This chromatin methylation code of gene activity is created upon cell differentiation and is further controlled by the "SET" (methyltransferase) domain proteins which maintain this histone methylation pattern and preserve it through rounds of cell division.

Displacement of periurethral stranded seeds and its dosimetric consequences in prostate brachytherapy.

Purpose: The use of stranded seeds for prostate brachytherapy has raised concern that displacement of strands, particularly in the periurethral region, may result in inadequate coverage of the prostate. We sought here to evaluate the displacement of periurethral stranded seeds after a prostate brachytherapy implant (Day 0) and its dosimetric consequences 1 month later (Day 30).

Methods And Materials: Subjects were 10 consecutive patients who underwent implantation with (125)I stranded seeds via a peripheral-loading technique.

The Saccharomyces cerevisiae Swi/Snf complex can catalyze formation of dimeric nucleosome structures in vitro.

The Swi/Snf chromatin-remodeling complexes, human BAF/PBAF and yeast RSC, can catalyze formation of stably altered dimeric forms of nucleosomes. However, the ability to create remodeled dimers has not yet been reported for the Saccharomyces cerevisiae Swi/Snf complex. Despite its similarity with the other Swi/Snf proteins, the yeast Swi/Snf complex features certain structural and functional differences.

Histone acetylation facilitates association of nucleosomes with SET domain of ALL-1 methyltransferase in vitro.

The inheritable methylation pattern of gene activity, created upon cell differentiation, is further maintained by the "SET" (methyltransferase)-domain proteins. However, it is still not clear how SET-proteins can decide on the required gene activity state and the way their chromatin association is maintained. Here we have found that high levels of histone acetylation--the hallmarks of active chromosome regions in vivo--can increase the affinity of reconstituted nucleosomes to the SET domain of ALL-1 histone methyltransferase in a defined system in vitro.

Out-of-field photon dose following removal of the flattening filter from a medical accelerator.

The aim of this paper is to determine the effect of removing the flattening filter from a linear accelerator on the out-of-field photon dose. A Monte Carlo model was used to simulate 6 MV and 18 MV photon beams from a Varian 2100 accelerator with the flattening filter in place and with it removed. The out-of-field photon doses and composition (head leakage, patient scatter and collimator scatter) were calculated from square open fields in a water tank as a function of distance from central axis, field size and depth.

Validation of a new grid-based Boltzmann equation solver for dose calculation in radiotherapy with photon beams.

A new grid-based Boltzmann equation solver, Acuros, was developed specifically for performing accurate and rapid radiotherapy dose calculations. In this study we benchmarked its performance against Monte Carlo for 6 and 18 MV photon beams in heterogeneous media. Acuros solves the coupled Boltzmann transport equations for neutral and charged particles on a locally adaptive Cartesian grid.