Integrating chromosome conformation and DNA repair in a computational framework to assess cell radiosensitivity.

The arrangement of chromosomes in the cell nucleus has implications for cell radiosensitivity. The development of new tools to utilize Hi-C chromosome conformation data in nanoscale radiation track structure simulations allows forinvestigation of this phenomenon. We have developed a framework employing Hi-C-based cell nucleus models in Monte Carlo radiation simulations, in conjunction with mechanistic models of DNA repair, to predict not only the initial radiation-induced DNA damage, but also the repair outcomes resulting from this damage, allowing us to investigate the role chromosome conformation plays in the biological outcome of radiation exposure.

Optimization of hexagonal-pattern minibeams for spatially fractionated radiotherapy using proton beam scanning.

Purpose: In this study, we investigated computationally and experimentally a hexagonal-pattern array of spatially fractionated proton minibeams produced by proton pencil beam scanning (PBS) technique. Spatial fractionation of dose delivery with millimeter or submillimeter beam size has proven to be a promising approach to significantly increase the normal tissue tolerance. Our goals are to obtain an optimized minibeam design and to show that it is feasible to implement the optimized minibeams at the existing proton clinics.

ASSESSMENT OF AMBIENT NEUTRON DOSE EQUIVALENT IN SPATIALLY FRACTIONATED RADIOTHERAPY WITH PROTONS USING PHYSICAL COLLIMATORS.

New technique is trending in spatially fractionated radiotherapy with protons to utilize the spot scanning together with a physical collimator to obtain minibeams. The primary goal of this study is to quantify ambient neutron dose equivalent (${H}^{\ast }(10)$) due to the secondary neutrons when physical collimator is used to achieve desired minibeams. The ${H}^{\ast }(10)$ per treatment proton dose (D) was assessed using Monte Carlo code TOPAS and measured using WENDI-II detector at different angles (135, 180, 225 and 270 degrees) and distances (11 cm, 58 and 105 cm) from the phantom for two cases: with and without physical collimation.

A cell-by-cell Monte Carlo simulation for assessing radiation-induced DNA double strand breaks.

This paper presents a cell-by-cell Monte Carlo simulation study that combines charged particle track structure data with an interphase cell nucleus model to quantify DNA double strand breaks (DSBs), spatial distribution of DSBs in a cell nucleus, and resulting potentially lethal or mutagenic events (PLMEs) between DSBs in close proximity. Cell nucleus is simulated according to the chromosome territory-interchromatin compartment (CT-IC) model in that chromatin content is unevenly distributed in chromatin domains (CDs) and IC with a chromatin compaction ratio of 22:1. A particle track structure coordinate (PTSC) library was first generated for each particle type, energy, and dose based on a large number of particle track data obtained by running the Monte Carlo track structure code Geant4-DNA.

A retrospective study of californium-252 neutron brachytherapy combined with EBRT versus 3D-CRT in the treatment of esophageal squamous cell cancer.

Background: We conducted a retrospective analysis on 884 patients who were diagnosed with esophageal squamous cell carcinoma (ESCC) and treated with either the neutron brachytherapy in combination with external beam radiotherapy (NBT + EBRT) or 3-dimensional conformal radiation therapy (3D-CRT) to determine the differences in efficacy and morbidity between the two treatment groups.

Methods: The 884 ESCC patients treated with either NBT + EBRT or 3D-CRT between 2002 and 2012 were retrospectively reviewed and analyzed. Multivariable Cox regression was used to compare oncologic outcomes of the two groups of patients in the context of other clinically relevant variables.

Californium-252 neutron brachytherapy combined with external beam radiotherapy for esophageal cancer: long-term treatment results.

Purpose: The aim of this study was to retrospectively observe and analyze the long-term treatment outcomes for a total of 952 esophageal cancer patients who were treated with (252)Cf neutron brachytherapy (NBT) in combination with external beam radiotherapy (EBRT).

Methods And Materials: From November 2001 to March 2012, 952 patients with esophageal cancer underwent NBT in combination with EBRT. The patient numbers distributed over various cancer Stages I, IIA, IIB, III, and IVA were 9, 290, 51, 579, and 23, respectively.

Liposome-based delivery of a boron-containing cholesteryl ester for high-LET particle-induced damage of prostate cancer cells: a boron neutron capture therapy study.

Purpose: The efficacy of a boron-containing cholesteryl ester compound (BCH) as a boron neutron capture therapy (BNCT) agent for the targeted irradiation of PC-3 human prostate cancer cells was examined.

Materials And Methods: Liposome-based delivery of BCH was quantified with inductively coupled plasma-mass spectrometry (ICP-MS) and high-performance liquid chromatography (HPLC). Cytotoxicity of the BCH-containing liposomes was evaluated with neutral red, 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS), and lactate dehydrogenase assays.

Early-stage esophageal squamous cell carcinoma treated with californium-252 neutron brachytherapy: clinical report on 16 cases.

Aims And Background: Californium-252 (²⁵²Cf) neutron brachytherapy is a form of high linear energy transfer radiotherapy, which has proven effective when used in combination with external beam radiotherapy to treat intracavitary cancers of the cervix, colon/rectum and esophagus. No study has been reported for treatment of intracavitary cancers with neutron brachytherapy alone. The aim of the study was to observe and analyze the long-term curative effects and complications for early stage thoracic esophageal cancer patients treated with neutron brachytherapy alone.

The progress of radiobiological models in modern radiotherapy with emphasis on the uncertainty issue.

Radiobiological models are used in modern radiotherapy to evaluate the biological effects of different treatment plans or modalities. A radiobiological model typically converts a physical quantity (e.g.

Development and test of a GEM-based TEPC for neutron protection dosimetry.

A novel tissue-equivalent proportional counter (TEPC) based on a gas electron multiplier (GEM) for measuring H*(10) for neutrons was designed and constructed. The pulse height spectra (PHS) of two different neutron sources (a 252Cf source and a AmBe source) were measured using the new TEPC. The measurements were made with the TEPC filled with two different gases (10P gas and a propane-based tissue-equivalent gas) at various pressures.

Experimental validation of the new nanodosimetry-based cell survival model for mixed neutron and gamma-ray irradiation.

The new nanodosimetry-based linear-quadratic (LQ) formula has been reviewed for mixed-LET irradiation. V-79 Chinese hamster cells have been irradiated with a mixed-LET field of fission neutrons and gamma rays at the University of Maryland Training Reactor (MUTR). The results show that the experimental survival curve agrees well with that predicted by the new nanodosimetry-based LQ model.