Modeling the acute mucosal toxicity to fractionated radiotherapy combined with the ATM inhibitor WSD0628.

ATM inhibitors are being developed as radiosensitizers to improve the antitumor effects of radiotherapy, but ATM inhibition can also radiosensitize normal tissues. Therefore, understanding the elevated risk for normal tissue toxicities is critical for radiosensitizer development. This study focused on modeling the relationship between acute mucosal toxicity, radiation dose, fractionation schedule, and radiosensitizer exposure.

A Radiomics-Based Classifier for the Progression of Oropharyngeal Cancer Treated with Definitive Radiotherapy.

In this study, we investigated whether radiomics features from pre-treatment positron emission tomography (PET) images could be used to predict disease progression in patients with HPV-positive oropharyngeal cancer treated with definitive proton or x-ray radiotherapy. Machine learning models were built using a dataset from Mayo Clinic, Rochester, Minnesota (n = 72) and tested on a dataset from Mayo Clinic, Phoenix, Arizona (n = 22). A total of 71 clinical and radiomics features were considered.

Early Impact of Proton Beam Therapy on Electrophysiological Characteristics in a Porcine Model.

Background: Particle therapy is a noninvasive, catheter-free modality for cardiac ablation. We previously demonstrated the efficacy for creating ablation lesions in the porcine heart. Despite several earlier studies, the exact mechanism of early biophysical effects of proton and photon beam delivery on the myocardium remain incompletely resolved.

Rotating Gantries Provide Individualized Beam Arrangements for Charged Particle Therapy.

Purpose: This study evaluates beam angles used to generate highly individualized proton therapy treatment plans for patients eligible for carbon ion radiotherapy (CIRT).

Methods And Materials: We retrospectively evaluated patients treated with pencil beam scanning intensity modulated proton therapy from 2015 to 2020 who had indications for CIRT. Patients were treated with a 190° rotating gantry with a robotic patient positioning system.

Nuclear Fragmentation Imaging for Carbon-Ion Radiation Therapy Monitoring: an In Silico Study.

Purpose: This article presents an in vivo imaging technique based on nuclear fragmentation of carbon ions in irradiated tissues for potential real-time monitoring of carbon-ion radiation therapy (CIRT) treatment delivery and quality assurance purposes in clinical settings.

Materials And Methods: A proof-of-concept imaging and monitoring system (IMS) was devised to implement the technique. Monte Carlo simulations were performed for a prospective pencil-beam scanning CIRT nozzle.

Evaluation of Pretreatment Magnetic Resonance Elastography for the Prediction of Radiation-Induced Liver Disease.

Purpose: Magnetic resonance (MR) elastography (E) is a noninvasive technique for quantifying liver stiffness (LS) for fibrosis. This study evaluates whether LS is associated with risk of developing radiation-induced liver disease (RILD) in patients receiving liver-directed radiation therapy (RT).

Methods And Materials: Based on prior studies, LS ≤3 kPa was considered normal and LS >3.

Using Novel Statistical Techniques to Accurately Determine the Predictive Dose Range in a Study of Overall Survival after Definitive Radiotherapy for Stage III Non-Small Cell Lung Cancer in Association with Heart Dose.

Purpose: Recent studies of radiotherapy (RT) for stage III non-small-cell lung cancer (NSCLC) have associated high dose to the heart with cardiac toxicity and decreased overall survival (OS). We used advanced statistical techniques to account for correlations between dosimetric variables and more accurately determine the range of heart doses which are associated with reduced OS in patients receiving RT for stage III NSCLC.

Methods: From 2006 to 2013, 119 patients with stage III NSCLC received definitive RT at our institution.

Reduce Patient Treatment wait time in a Proton Beam Facility - A Gatekeeper Approach.

Patient wait time can negatively impact treatment quality in a proton therapy center, where multiple treatment rooms share one proton beam. Wait time increases patient discomfort that can lead to patient motion, dissatisfaction, and longer treatment delay. This study was to develop a patient call-back model that reduced patient wait while efficiently utilizing the proton beam.

Dosimetric Assessment of a High Precision System for Mouse Proton Irradiation to Assess Spinal Cord Toxicity.

The uncertainty associated with the relative biological effectiveness (RBE) in proton therapy, particularly near the Bragg peak (BP), has led to the shift towards biological-based treatment planning. Proton RBE uncertainty has recently been reported as a possible cause for brainstem necrosis in pediatric patients treated with proton therapy. Despite this, in vivo studies have been limited due to the complexity of accurate delivery and absolute dosimetry.

Inhibition of ATM Induces Hypersensitivity to Proton Irradiation by Upregulating Toxic End Joining.

Proton Bragg peak irradiation has a higher ionizing density than conventional photon irradiation or the entrance of the proton beam profile. Whether targeting the DNA damage response (DDR) could enhance vulnerability to the distinct pattern of damage induced by proton Bragg peak irradiation is currently unknown. Here, we performed genetic or pharmacologic manipulation of key DDR elements and evaluated DNA damage signaling, DNA repair, and tumor control in cell lines and xenografts treated with the same physical dose across a radiotherapy linear energy transfer spectrum.

A High-Precision Method for In Vitro Proton Irradiation.

Purpose: Although proton therapy has become a well-established radiation modality, continued efforts are needed to improve our understanding of the molecular and cellular mechanisms occurring during treatment. Such studies are challenging, requiring many resources. The purpose of this study was to create a phantom that would allow multiple in vitro experiments to be irradiated simultaneously with a spot-scanning proton beam.

Catheter-Free Arrhythmia Ablation Using Scanned Proton Beams: Electrophysiologic Outcomes, Biophysics, and Characterization of Lesion Formation in a Porcine Model.

Background: Proton beam therapy offers radiophysical properties that are appealing for noninvasive arrhythmia elimination. This study was conducted to use scanned proton beams for ablation of cardiac tissue, investigate electrophysiological outcomes, and characterize the process of lesion formation in a porcine model using particle therapy.

Methods: Twenty-five animals received scanned proton beam irradiation.

Catheter-free ablation of infarct scar through proton beam therapy: Tissue effects in a porcine model.

Background: Scar-related ventricular arrhythmias are common after myocardial infarction. Catheter ablation can improve prognosis, but the procedure is invasive and results are not always satisfactory. Noninvasive, catheter-free ablation using ionizing radiation has recently gained interest among electrophysiologists, but the tissue effects and physiological outcome have not been fully characterized.

Prediction of MGMT Status for Glioblastoma Patients Using Radiomics Feature Extraction From F-DOPA-PET Imaging.

Purpose: Methylation of the O-methylguanine methyltransferase (MGMT) gene promoter is associated with improved treatment response and survival in patients with glioblastoma (GB), but the necessary pathologic specimen can be nondiagnostic. In this study, we assessed whether radiomics features from pretreatment F-DOPA positron emission tomography (PET) imaging could be used to predict pathologic MGMT status.

Methods And Materials: This study included 86 patients with newly diagnosed GB, split into 3 groups (training, validating, and predicting).

Robust radiobiological optimization of ion beam therapy utilizing Monte Carlo and microdosimetric kinetic model.

To develop a Monte Carlo (MC)-based and robust ion beam therapy optimization system that separates the optimization algorithm from the relative biological effectiveness (RBE) modeling. Robustly optimized dose distributions were calculated and compared across three ion therapy beams (proton, helium, carbon). The effect of different averaging techniques in calculating RBE in mixed beams was also investigated.

Methodology for radiochromic film analysis using FilmQA Pro and ImageJ.

Radiochromic film (RCF) has several advantageous characteristics which make it an attractive dosimeter for many clinical tasks in radiation oncology. However, knowledge of and strict adherence to complicated protocols in order to produce accurate measurements can prohibit RCF from being widely adopted in the clinic. The purpose of this study was to outline some simple and straightforward RCF fundamentals in order to help clinical medical physicists perform accurate RCF measurements.

PNaV: A tool for generating a high-dose-rate brachytherapy treatment plan by navigating the Pareto surface guided by the visualization of multidimensional trade-offs.

Purpose: A Pareto Navigation and Visualization (PNaV) tool is presented for interactively constructing a high-dose-rate (HDR) brachytherapy treatment plan by navigating and visualizing the multidimensional Pareto surface. PNaV aims to improve treatment planning time and quality and is generalizable to any number of dose-volume histogram (DVH) and convex dose metrics.

Methods And Materials: Pareto surface visualization and navigation were demonstrated for prostate, breast, and cervix HDR brachytherapy sites.

AAPM medical physics practice guideline 7.a.: Supervision of medical physicist assistants.

The American Association of Physicists in Medicine (AAPM) is a nonprofit professional society whose primary purposes are to advance the science, education and professional practice of medical physics. The AAPM has more than 8,000 members and is the principal organization of medical physicists in the United States. The AAPM will periodically define new practice guidelines for medical physics practice to help advance the science of medical physics and to improve the quality of service to patients throughout the United States.

Optimization of motion management parameters in a synchrotron-based spot scanning system.

Purpose: To quantify the effects of combining layer-based repainting and respiratory gating as a strategy to mitigate the dosimetric degradation caused by the interplay effect between a moving target and dynamic spot-scanning proton delivery.

Methods: An analytic routine modeled three-dimensional dose distributions of pencil-beam proton plans delivered to a moving target. Spot positions and weights were established for a single field to deliver 100 cGy to a static, 15-cm deep, 3-cm radius spherical clinical target volume with a 1-cm isotropic internal target volume expansion.

Left ventricular function after noninvasive cardiac ablation using proton beam therapy in a porcine model.

Background: Noninvasive cardiac ablation of ventricular tachycardia (VT) using radiotherapy has recently gained interest among electrophysiologists. The effects of left ventricular (LV) ablative radiation treatment on global LV function and volumes are unknown.

Objective: The purpose of this study was to investigate the effects of noninvasive ablation on LV function over time.

Clinical implementation of respiratory-gated spot-scanning proton therapy: An efficiency analysis of active motion management.

Purpose: The aim of this work is to describe the clinical implementation of respiratory-gated spot-scanning proton therapy (SSPT) for the treatment of thoracic and abdominal moving targets. The experience of our institution is summarized, from initial acceptance and commissioning tests to the development of standard clinical operating procedures for simulation, motion assessment, motion mitigation, treatment planning, and gated SSPT treatment delivery.

Materials And Methods: A custom respiratory gating interface incorporating the Real-Time Position Management System (RPM, Varian Medical Systems, Inc.

A Monte-Carlo-based and GPU-accelerated 4D-dose calculator for a pencil beam scanning proton therapy system.

Purpose: The presence of respiratory motion during radiation treatment leads to degradation of the expected dose distribution, both for target coverage and healthy tissue sparing, particularly for techniques like pencil beam scanning proton therapy which have dynamic delivery systems. While tools exist to estimate this degraded four-dimensional (4D) dose, they typically have one or more deficiencies such as not including the particular effects from a dynamic delivery, using analytical dose calculations, and/or using nonphysical dose-accumulation methods. This work presents a clinically useful 4D-dose calculator that addresses each of these shortcomings.

Investigating Dependencies of Relative Biological Effectiveness for Proton Therapy in Cancer Cells.

Purpose: Relative biological effectiveness (RBE) accounts for the differences in biological effect from different radiation types. The RBE for proton therapy remains uncertain, as it has been shown to vary from the clinically used value of 1.1.

A robust intensity modulated proton therapy optimizer based on Monte Carlo dose calculation.

Purpose: Accuracy of dose calculation models and robustness under various uncertainties are key factors influencing the quality of intensity modulated proton therapy (IMPT) plans. To mitigate the effects of uncertainties and to improve the dose calculation accuracy, an all-scenario robust IMPT optimization based on accurate Monte Carlo (MC) dose calculation was developed.

Methods: In the all-scenario robust IMPT optimization, dose volume histograms (DVHs) were computed for the nominal case and for each uncertainty scenario.