Defining the optimal radiation-induced lymphopenia metric to discern its survival impact in esophageal cancer.

Background: A detrimental association between radiation-induced lymphopenia (RIL) and oncologic outcomes in esophageal cancer patients has been established. However, an optimal metric for RIL remains undefined, but is important for application of this knowledge in clinical decision-making and trial designs. The aim of this study was to find the optimal RIL metric discerning survival.

Discordance in acute gastrointestinal toxicity between synchrotron-based proton and linac-based electron ultra-high dose rate irradiation.

Purpose: Proton FLASH has been investigated using cyclotron and synchrocyclotron beamlines but not synchrotron beamlines. We evaluated the impact of dose rate (ultra-high [UHDR] vs. conventional [CONV]) and beam configuration (shoot-through [ST] vs.

The first probe of a FLASH proton beam by PET.

The recently observed FLASH effect related to high doses delivered with high rates has the potential to revolutionize radiation cancer therapy if promising results are confirmed and an underlying mechanism understood. Comprehensive measurements are essential to elucidate the phenomenon. We report the first-ever demonstration of measurements of successive in-spill and post-spill emissions of gammas arising from irradiations by a FLASH proton beam.

The first PET glimpse of a proton FLASH beam.

We demonstrate the first ever recorded positron-emission tomography (PET) imaging and dosimetry of a FLASH proton beam at the Proton Center of the MD Anderson Cancer Center. Two scintillating LYSO crystal arrays, read out by silicon photomultipliers, were configured with a partial field of view of a cylindrical poly-methyl methacrylate (PMMA) phantom irradiated by a FLASH proton beam. The proton beam had a kinetic energy of 75.

Optimization of FLASH proton beams using a track-repeating algorithm.

Background: Radiation with high dose rate (FLASH) has shown to reduce toxicities to normal tissues around the target and maintain tumor control with the same amount of dose compared to conventional radiation. This phenomenon has been widely studied in electron therapy, which is often used for shallow tumor treatment. Proton therapy is considered a more suitable treatment modality for deep-seated tumors.

Adaptation and dosimetric commissioning of a synchrotron-based proton beamline for FLASH experiments.

. Irradiation with ultra-high dose rates (>40 Gy s), also known as FLASH irradiation, has the potential to shift the paradigm of radiation therapy because of its reduced toxicity to normal tissues compared to that of conventional irradiations. The goal of this study was to (1) achieve FLASH irradiation conditions suitable for pre-clinicalandbiology experiments using our synchrotron-based proton beamline and (2) commission the FLASH irradiation conditions achieved.

Effect of boron compounds on the biological effectiveness of proton therapy.

Purpose: We assessed whether adding sodium borocaptate (BSH) or 4-borono-l-phenylalanine (BPA) to cells irradiated with proton beams influenced the biological effectiveness of those beams against prostate cancer cells to investigate if the alpha particles generated through proton-boron nuclear reactions would be sufficient to enhance the biological effectiveness of the proton beams.

Methods: We measured clonogenic survival in DU145 cells treated with 80.4-ppm BSH or 86.

Roadmap: helium ion therapy.

Helium ion beam therapy for the treatment of cancer was one of several developed and studied particle treatments in the 1950s, leading to clinical trials beginning in 1975 at the Lawrence Berkeley National Laboratory. The trial shutdown was followed by decades of research and clinical silence on the topic while proton and carbon ion therapy made debuts at research facilities and academic hospitals worldwide. The lack of progression in understanding the principle facets of helium ion beam therapy in terms of physics, biological and clinical findings persists today, mainly attributable to its highly limited availability.

Technical note: Monte Carlo study of the mechanism of proton-boron fusion therapy.

Purpose: Proton beam therapy has been found to have enhanced biological effectiveness in targets that contain the boron isotope B, with the alpha particles resulting from the p + B → 3α reaction being hypothesized as the mechanism; in this study, we aimed to elucidate the causes of the enhanced biological effectiveness of proton-boron fusion therapy by performing a detailed Monte Carlo study of the p + B → 3α reaction in a phantom geometry.

Methods: We utilized the Geant4 toolkit to create Monte Carlo particle physics simulations. These simulations consisted of a proton beam with a range 30 mm, creating a Spread-Out Bragg Peak with a modulation width of 10 mm, directed into a water phantom containing a region of boron material.

Design and validation of a synchrotron proton beam line for FLASH radiotherapy preclinical research experiments.

Purpose: The main purpose of this work was to generate and validate the dosimetric accuracy of proton beams of dimensions that are appropriate for in vivo small animal and in vitro ultrahigh dose rate (FLASH) radiotherapy experiments using a synchrotron-based treatment delivery system. This study was performed to enable future investigations of the relevance of a spread-out Bragg peak (SOBP) under FLASH conditions.

Methods: The spill characteristics of the small field fixed horizontal beam line were modified to deliver accelerated protons in times as short as 2 ms and to control the dose delivered.

Mapping the Relative Biological Effectiveness of Proton, Helium and Carbon Ions with High-Throughput Techniques.

Large amounts of high quality biophysical data are needed to improve current biological effects models but such data are lacking and difficult to obtain. The present study aimed to more efficiently measure the spatial distribution of relative biological effectiveness (RBE) of charged particle beams using a novel high-accuracy and high-throughput experimental platform. Clonogenic survival was selected as the biological endpoint for two lung cancer cell lines, H460 and H1437, irradiated with protons, carbon, and helium ions.

Monte Carlo Simulations of Neutron Ambient Dose Equivalent in a Novel Proton Therapy Facility Design.

Purpose: The neutron shielding properties of the concrete structures of a proposed proton therapy facility were evaluated with help of the Monte Carlo technique. The planned facility's design omits the typical maze-structured entrances to the treatment rooms to facilitate more efficient access and, instead, proposes the use of massive concrete/steel doors. Furthermore, straight conduits in the treatment room walls were used in the design of the facility, necessitating a detailed investigation of the neutron radiation outside the rooms to determine if the design can be applied without violating existing radiation protection regulations.

Comparing 2 Monte Carlo Systems in Use for Proton Therapy Research.

Purpose: Several Monte Carlo transport codes are available for medical physics users. To ensure confidence in the accuracy of the codes, they must be continually cross-validated. This study provides comparisons between MC and Tool for Particle Simulation (TOPAS) simulations, that is, between medical physics applications for Monte Carlo N-Particle Transport Code (MCNPX) and Geant4.

Nonhomologous End Joining Is More Important Than Proton Linear Energy Transfer in Dictating Cell Death.

Purpose: This study seeks to identify biological factors that may yield a therapeutic advantage of proton therapy versus photon therapy. Specifically, we address the role of nonhomologous end-joining (NHEJ) and homologous recombination (HR) in the survival of cells in response to clinical photon and proton beams.

Methods And Materials: We irradiated HT1080, M059K (DNA-PKcs), and HCC1937 human cancer cell lines and their isogenic counterparts HT1080-shDNA-PKcs, HT1080-shRAD51, M059J (DNA-PKcs), and HCC1937-BRCA1 (BRCA1 complemented) to assess cell clonogenic survival and γ-H2AX radiation-induced foci.

Fixed- versus Variable-RBE Computations for Intensity Modulated Proton Therapy.

Purpose: To evaluate how using models of proton therapy that incorporate variable relative biological effectiveness (RBE) versus the current practice of using a fixed RBE of 1.1 affects dosimetric indices on treatment plans for large cohorts of patients treated with intensity modulated proton therapy (IMPT).

Methods And Materials: Treatment plans for 4 groups of patients who received IMPT for brain, head-and-neck, thoracic, or prostate cancer were selected.

RBE Model-Based Biological Dose Optimization for Proton Radiobiology Studies.

Purpose: The purpose of the current study was (1) to develop a straightforward and rapid method to incorporate a dose-averaged linear energy transfer (LET )-based biological effect model into a dose optimization algorithm for scanned protons; and (2) to apply a novel beam delivery strategy with increased LET within the target, thereby enhancing the biological effect predicted using the selected relative biological effectiveness (RBE) model.

Materials And Methods: We first generated pristine dose Bragg curves in water and their corresponding LET distributions for 94 groups of proton beams, using experimentally validated Geant4 Monte Carlo simulations. Next, we developed 1-dimensional dose optimization algorithms by using the Python programming language.

Comparison of Monte Carlo and analytical dose computations for intensity modulated proton therapy.

To evaluate the effect of approximations in clinical analytical calculations performed by a treatment planning system (TPS) on dosimetric indices in intensity modulated proton therapy. TPS calculated dose distributions were compared with dose distributions as estimated by Monte Carlo (MC) simulations, calculated with the fast dose calculator (FDC) a system previously benchmarked to full MC. This study analyzed a total of 525 patients for four treatment sites (brain, head-and-neck, thorax and prostate).

Differences in Normal Tissue Response in the Esophagus Between Proton and Photon Radiation Therapy for Non-Small Cell Lung Cancer Using In Vivo Imaging Biomarkers.

Purpose: To determine whether there exists any significant difference in normal tissue toxicity between intensity modulated radiation therapy (IMRT) or proton therapy for the treatment of non-small cell lung cancer.

Methods And Materials: A total of 134 study patients (n=49 treated with proton therapy, n=85 with IMRT) treated in a randomized trial had a previously validated esophageal toxicity imaging biomarker, esophageal expansion, quantified during radiation therapy, as well as esophagitis grade (Common Terminology Criteria for Adverse Events version 3.0), on a weekly basis during treatment.

Technical Note: Dosimetric characteristics of the ocular beam line and commissioning data for an ocular proton therapy planning system at the Proton Therapy Center Houston.

Purpose: To systematically analyze and present the properties of a small-field, double-scattering proton beam line intended to be used for the treatment of ocular cancer, and to provide configuration data for commission of the Eclipse Ocular Proton Planning System.

Methods: Measurements were made using ionization chambers, diodes, and films to determine dose profiles and output factors of the proton beams of the beam line at the Proton Therapy Center Houston. In parallel, Monte Carlo simulations were performed to validate the measured data and to provide additional insight into detailed beam parameters that are hard to measure, such as field size factors and a comparison of output factors as a function of circular and rectangular fields.

Intensity-Modulated Proton Therapy Adaptive Planning for Patients with Oropharyngeal Cancer.

Purpose: The authors aimed to illustrate the potential dose differences to clinical target volumes (CTVs) and organs-at-risk (OARs) volumes after proton adaptive treatment planning was used.

Patients And Methods: The records of 10 patients with oropharyngeal cancer were retrospectively reviewed. Each patient's treatment plan was generated by using the Eclipse treatment planning system.

Optimization of Monte Carlo particle transport parameters and validation of a novel high throughput experimental setup to measure the biological effects of particle beams.

Purpose: Accurate modeling of the relative biological effectiveness (RBE) of particle beams requires increased systematic in vitro studies with human cell lines with care towards minimizing uncertainties in biologic assays as well as physical parameters. In this study, we describe a novel high-throughput experimental setup and an optimized parameterization of the Monte Carlo (MC) simulation technique that is universally applicable for accurate determination of RBE of clinical ion beams. Clonogenic cell-survival measurements on a human lung cancer cell line (H460) are presented using proton irradiation.

Clinical evidence of variable proton biological effectiveness in pediatric patients treated for ependymoma.

Background And Purpose: A constant relative biological effectiveness (RBE) is used for clinical proton therapy; however, experimental evidence indicates that RBE can vary. We analyzed pediatric ependymoma patients who received proton therapy to determine if areas of normal tissue damage indicated by post-treatment image changes were associated with increased biological dose effectiveness.

Material And Methods: Fourteen of 34 children showed T2-FLAIR hyperintensity on post-treatment magnetic resonance (MR) images.

Evaluation of a deterministic grid-based Boltzmann solver (GBBS) for voxel-level absorbed dose calculations in nuclear medicine.

To evaluate the 3D Grid-based Boltzmann Solver (GBBS) code ATTILA (®) for coupled electron and photon transport in the nuclear medicine energy regime for electron (beta, Auger and internal conversion electrons) and photon (gamma, x-ray) sources. Codes rewritten based on ATTILA are used clinically for both high-energy photon teletherapy and (192)Ir sealed source brachytherapy; little information exists for using the GBBS to calculate voxel-level absorbed doses in nuclear medicine. We compared DOSXYZnrc Monte Carlo (MC) with published voxel-S-values to establish MC as truth.