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. The Mann-Whitney U test was used to identify the top 2 clinical and top 20 radiomics features that were significantly different between progression and progression-free patients. Two dimensionality reduction methods were used to define two feature sets (manually filtered or machine-driven). A forward feature selection scheme was conducted on each feature set to build models of increased complexity (number of input features from 1 to 6) and evaluate model robustness and overfitting. The machine-driven features had superior performance and were less prone to overfitting compared to the manually filtered features. The four-variable Gaussian Naïve Bayes model using the 'Radiation Type' clinical feature and three machine-driven features achieved a training accuracy of 79% and testing accuracy of 77%. These results demonstrate that radiomics features can provide risk stratification beyond HPV-status to formulate individualized treatment and follow-up strategies.

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. METHODS: Ten normal and 9 infarcted in situ porcine hearts received proton beam irradiation (40 Gy) delivered to the left ventricular myocardium with follow-up for 8 weeks. High-resolution electroanatomical mapping of the left ventricular was performed at baseline and follow-up. Bipolar voltage amplitude, conduction velocity, and connexin-43 were determined within the irradiated and nonirradiated areas. RESULTS: The irradiated area in normal hearts showed a significant reduction of bipolar voltage amplitude (10.1±4.9 mV versus 5.7±3.2, P<0.0001) and conduction velocity (85±26 versus 55±13 cm/s, P=0.03) beginning at 4 weeks after irradiation. In infarcted myocardium after irradiation, bipolar voltage amplitude of the infarct scar (2.0±2.9 versus 0.8±0.7 mV, P=0.008) was significantly reduced as well as the conduction velocity in the infarcted heart (43.7±15.7 versus 26.3±11.4 cm/s, P=0.02). There were no significant changes in bipolar voltage amplitude and conduction velocity in nonirradiated myocardium. Myocytolysis, capillary hyperplasia, and dilation were seen in the irradiated myocardium 8 weeks after irradiation. Active caspase-3 and reduction of connexin-43 expression began in irradiated myocardium 1 week after irradiation and decreased over 8 weeks. CONCLUSIONS: Irradiation of the myocardium with proton beams reduce connexin-43 expression, conduction velocity, and bipolar conducted electrogram amplitude in a large porcine model. The changes in biomarkers preceded electrophysiological changes after proton beam therapy.

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. Treatment plans were individualized to provide maximal prescription dose delivery to the tumor target volume while sparing organs at risk. The utilized beam angles were grouped, and anatomic sites with at least 10 different beam angles were sorted into histograms. RESULTS: A total of 467 patients with 484 plans and 1196 unique beam angles were evaluated and characterized by anatomic treatment site and the number of beam angles utilized. The most common beam angles used were 0° and 180°. A wide range of beam angles were used in treating almost all anatomic sites. Only esophageal cancers had a predominantly unimodal grouping of beam angles. Pancreas cancers showed a modest grouping of beam angles. CONCLUSIONS: The wide distribution of beam angles used to treat CIRT-eligible patients suggests that a rotating gantry is optimal to provide highly individualized beam arrangements.

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. The development IMS benchmark considered a 5×5-cm2 pixelated charged-particle detector stack positioned downstream from a target phantom and list-mode data acquisition. The abundance and production origins, that is, vertices, of the detected fragments were studied. Fragment trajectories were approximated by straight lines and a beam back-projection algorithm was built to reconstruct the vertices. The spatial distribution of the vertices was then used to determine plan relevant markers. Results: The IMS technique was applied for a simulated CIRT case, a primary brain tumor. Four treatment plan monitoring markers were conclusively recovered: a depth dose distribution correlated profile, ion beam range, treatment target boundaries, and the beam spot position. Promising millimeter-scale (3-mm, ≤10% uncertainty) beam range and submillimeter (≤0.6-mm precision for shifts <3 cm) beam spot position verification accuracies were obtained for typical therapeutic energies between 150 and 290 MeV/u. Conclusions: This work demonstrated a viable online monitoring technique for CIRT treatment delivery. The method's strong advantage is that it requires few signal inputs (position and timing), which can be simultaneously acquired with readily available technology. Future investigations will probe the technique's applicability to motion-sensitive organ sites and patient tissue heterogeneities. In-beam measurements with candidate detector-acquisition systems are ultimately essential to validate the IMS benchmark performance and subsequent deployment in the clinic.

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 >3.0 kPa as representing fibrosis. RILD was defined as an increase in Child-Pugh (CP) score of ≥2 from baseline within 1 year of RT. Univariate and multivariate Cox models were used to assess correlation. RESULTS: One hundred two patients, 51 with primary liver tumors and 51 with liver metastases, were identified with sufficient follow-up. In univariate models, pre-RT LS >3.0 kPa (hazard ratio [HR] 4.9; 95% confidence interval [CI], 1.6-14; P = .004), body mass index (BMI), clinical cirrhosis, CP score, albumin-bilirubin (ALBI) grade 2, primary liver tumor, and mean liver dose were significantly associated with risk of post-RT RILD. In a multivariate analysis, LS >3.0 and mean liver dose both were significantly associated with RILD risk. CONCLUSIONS: Elevated pre-RT LS is associated with an increased risk of RILD in patients receiving liver-directed RT.

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. OS data was obtained from institutional tumor registry. We used multivariate Cox model to determine patient specific covariates predictive for reduced overall survival. We examined age, prescription dose, mean lung dose, lung V20, RT technique, stage, chemotherapy, tumor laterality, tumor volume, and tumor site as candidate covariates. We subsequently used novel statistical techniques within multivariate Cox model to systematically search the whole heart dose-volume histogram (DVH) for dose parameters associated with OS. RESULTS: Patients were followed until death or 2.5 to 81.2 months (median 30.4 months) in those alive at last follow up. On multivariate analysis of whole heart DVH, the dose of 51 Gy was identified as a threshold dose above which the dose volume relationship becomes predictive for OS. We identified V55Gy (percentage of the whole heart volume receiving at least 55 Gy) as the best single DVH index which can be used to set treatment optimization constraints (Hazard Ratio = 1.044 per 1% increase in heart volume exposed to at least 55 Gy, P = 0.03). Additional characteristics correlated with OS on multivariate analysis were age, stage (IIIA/IIIB), and administration of chemotherapy. CONCLUSION: Doses above 51 Gy, applied to small volumes of the heart, are associated with worse OS in stage III NSCLC patients treated with definitive RT. Higher stage, older age and lack of chemotherapy were also associated with reduced OS.

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. A "Gatekeeper" logic allowing therapists to adjust the time of a patient's call-back to the treatment room was developed. It uses a two-pronged approach to minimize overlap of long treatment and the possibility of excessive wait in the queue to receive the proton beam. The goal was to reduce the maximum wait time to less than eight minutes per field for a four-room facility. The effectiveness of this logic was evaluated through simulation, and five scenarios were compared. Four scenarios implementing various levels of gatekeeper logic were compared with the original scenario without the logic. The best performing model provided a reduction of the maximum field wait by 26% and met the predefined goal. Adjusting call-back extended the treatment day length by an average of 6 min and a maximum of 12 min in total. The use of this gatekeeper logic significantly reduces patient field wait with minimal impact on treatment day length for a four-room proton facility. A sample interface that adopts this logic for therapists to make informed decision on patient call-back time is demonstrated.

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. The purpose of this investigation was to create a precise and efficient method of treating the mouse spinal cord with various portions of the proton Bragg curve and to quantify associated uncertainties for the characterization of proton RBE. Mice were restrained in 3D printed acrylic boxes, shaped to their external contour, with a silicone insert extending down to mold around the mouse. Brass collimators were designed for parallel opposed beams to treat the spinal cord while shielding the brain and upper extremities of the animal. Up to six animals may be accommodated for simultaneous treatment within the restraint system. Two plans were generated targeting the cervical spinal cord, with either the entrance (ENT) or the BP portion of the beam. Dosimetric uncertainty was measured using EBT3 radiochromic film with a dose-averaged linear energy transfer (LETd) correction. Positional uncertainty was assessed by collecting a library of live mouse scans (n = 6 mice, two independent scans per mouse) and comparing the following dosimetric statistics from the mouse cervical spinal cord: Volume receiving 90% of the prescription dose (V90); mean dose to the spinal cord; and LETd. Film analysis results showed the dosimetric uncertainty to be ±1.2% and ±5.4% for the ENT and BP plans, respectively. Preliminary results from the mouse library showed the V90 to be 96.3 ± 4.8% for the BP plan. Positional uncertainty of the ENT plan was not measured due to the inherent robustness of that treatment plan. The proposed high-throughput mouse proton irradiation setup resulted in accurate dose delivery to mouse spinal cords positioned along the ENT and BP. Future directions include adapting the setup to account for weight fluctuations in mice undergoing fractionated irradiation.

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. Radiotherapy consisted of 6 MV photons and the entrance beam or Bragg peak of a 76.8 MeV spot scanning proton beam. More complex DNA double-strand breaks (DSB) induced by Bragg peak proton irradiation preferentially underwent resection and engaged homologous recombination (HR) machinery. Unexpectedly, the ataxia-telangiectasia mutated (ATM) inhibitor, AZD0156, but not an inhibitor of ATM and Rad3-related, rendered cells hypersensitive to more densely ionizing proton Bragg peak irradiation. ATM inhibition blocked resection and shunted more DSBs to processing by toxic ligation through nonhomologous end-joining, whereas loss of DNA ligation via XRCC4 or Lig4 knockdown rescued resection and abolished the enhanced Bragg peak cell killing. Proton Bragg peak monotherapy selectively sensitized cell lines and tumor xenografts with inherent HR defects, and the repair defect induced by ATM inhibitor coadministration showed enhanced efficacy in HR-proficient models. In summary, inherent defects in HR or administration of an ATM inhibitor in HR-proficient tumors selectively enhances the relative biological effectiveness of proton Bragg peak irradiation. SIGNIFICANCE: Coadministration of an ATM inhibitor rewires DNA repair machinery to render cancer cells uniquely hypersensitive to DNA damage induced by the proton Bragg peak, which is characterized by higher density ionization.See related commentary by Nickoloff, p. 3156.

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. MATERIALS AND METHODS: The setup included a modified patient-couch top coupled with a high-precision robotic arm for positioning. An acrylic phantom was created to hold 4 6-well cell-culture plates at 2 different positions along the Bragg curve in a reproducible manner. The proton treatment plan consisted of 1 large field encompassing all 4 plates with a monoenergetic 76.8-MeV posterior beam. For robust delivery, a mini pyramid filter was used to broaden the Bragg peak (BP) in the depth direction. Both a Markus ionization chamber and EBT3 radiochromic film measurements were used to verify absolute dose. RESULTS: A treatment plan for the simultaneous irradiation of 2 plates irradiated with high linear energy transfer protons (BP, 7 keV/µm) and 2 plates irradiated with low linear energy transfer protons (entrance, 2.2 keV/µm) was created. Dose uncertainty was larger across the setup for cell plates positioned at the BP because of beam divergence and, subsequently, variable proton-path lengths. Markus chamber measurements resulted in uncertainty values of ±1.8% from the mean dose. Negligible differences were seen in the entrance region (<0.3%). CONCLUSION: The proposed proton irradiation setup allows 4 plates to be simultaneously irradiated with 2 different portions (entrance and BP) of a 76.8-MeV beam. Dosimetric uncertainties across the setup are within ±1.8% of the mean dose.

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. ECG-gated computed tomography scans were acquired at end-expiration breath hold. Structures (atrioventricular junction or left ventricular myocardium) and organs at risk were contoured. Doses of 30, 40, and 55 Gy were delivered during expiration to the atrioventricular junction (n=5) and left ventricular myocardium (n=20) of intact animals. RESULTS: In this study, procedural success was tracked by pacemaker interrogation in the atrioventricular junction group, time-course magnetic resonance imaging in the left ventricular group, and correlation of lesion outcomes displayed in gross and microscopic pathology. Protein extraction (active caspase-3) was performed to investigate tissue apoptosis. Doses of 40 and 55 Gy caused slowing and interruption of cardiac impulse propagation at the atrioventricular junction. In 40 left ventricular irradiated targets, all lesions were identified on magnetic resonance after 12 weeks, being consistent with outcomes from gross pathology. In the majority of cases, lesion size plateaued between 12 and 16 weeks. Active caspase-3 was seen in lesions 12 and 16 weeks after irradiation but not after 20 weeks. CONCLUSIONS: Scanned proton beams can be used as a tool for catheter-free ablation, and time-course of tissue apoptosis was consistent with lesion maturation.

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. OBJECTIVE: The purpose of this study was to investigate the structural effects of cardiac scanned pencil beam proton therapy on infarct scar, the time course of imaging biomarkers, arrhythmias, and cardiac function in a porcine model. METHODS: Fourteen infarcted swine underwent proton beam treatment of the scar (40 or 30 Gy) and were followed for up to 30 weeks. Magnetic resonance imaging was performed every 4 weeks. RESULTS: Treated scar areas showed a significantly lower fraction of surviving myocytes at 30 weeks compared to untreated scar (30.1% ± 18.5% and 59.9% ± 10.1% in treated and untreated infarct, respectively), indicating scar homogenization. Four animals died suddenly during follow-up, all from documented monomorphic ventricular tachycardia. Cardiac function remained stable over the course of the study. Distinct imaging morphologies corresponded to certain tissue dose ranges and time points. CONCLUSION: Radioablation of cardiac infarct scar leads to significant homogenization of the scar, replicating the histologic effects of radiofrequency ablation. These changes correspond to distinct imaging morphologies on delayed contrast-enhanced cardiac magnetic resonance imaging, enabling noninvasive confirmation of tissue ablation effects The present study is the first to thoroughly investigate the structural effects of cardiac proton beam therapy in infarcted myocardium.

Prediction of MGMT Status for Glioblastoma Patients Using Radiomics Feature Extraction From 18F-DOPA-PET Imaging.

PURPOSE: Methylation of the O6-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 18F-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). We performed a radiomics analysis on 18F-DOPA PET images by extracting features from 2 tumor-based contours: a "Gold" contour of all abnormal uptake per expert nuclear medicine physician and a high-grade glioma (HGG) contour based on a tumor-to-normal hemispheric ratio >2.0, representing the most aggressive components. Feature selection was performed by comparing the weighted feature importance and filtering with bivariate analysis. Optimization of model parameters was explored using grid search with selected features. The stability of the model with increasing input features was also investigated for model robustness. The model predictions were then applied by comparing the overall survival probability of the patients with GB and unknown MGMT status versus those with known MGMT status. RESULTS: A radiomics signature was constructed to predict MGMT methylation status. Using features extracted from HGG contour alone with a random forest model, we achieved 80% ± 10% accuracy for 95% confidence level in predicting MGMT status. The prediction accuracy was not improved with the addition of the Gold contour or with more input features. The model was applied to the patients with unknown MGMT methylation status. The prediction results are consistent with what is expected using overall survival as a surrogate. CONCLUSIONS: This study suggests that 3 features from radiomics modeling of 18F-DOPA PET imaging can predict MGMT methylation status with reasonable accuracy. These results could provide valuable therapeutic guidance for patients in whom MGMT testing is inconclusive or nondiagnostic.

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. Ion particles were transported in TOPAS MC. The microdosimetric-kinetic model (MKM) parameter, saturation corrected specific energy ([Formula: see text]), was calculated with a customized MKM implementation in TOPAS MC. Intensity modulated ion therapy robust optimization was performed by a quasi-Newton iterative method based on dose-volume objective function. The robust optimization took setup and range uncertainties into account. In the present work, the biological dose for each individual spot was calculated, and then summed together to calculate total biological dose. In other published works, radiosensitive parameters, such as [Formula: see text], were first averaged over all beam spots within a mixed-beam field, after which biological dose was calculated using the averaged radiosensitive parameters. The difference between the two mixed-beam biological dose calculations was quantified. Robust plans were achieved with the three particle types. The effect of averaging [Formula: see text] depended on particle type. The difference between biological doses calculated with individual [Formula: see text] and averaged [Formula: see text] may be greater than 3% for a carbon beam. MC based radiobiological and robust optimization was made flexible to incorporate dose-volume histogram constraints and to be independent of RBE models. Iterative optimization with RBE models was feasible. Evaluation of the RBE calculation for mixed beam could be necessary if better accuracy was demanded.

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. A library of treatment plans was created to span the Pareto surfaces over a 30% range of doses in each of five DVH metrics. The PNaV method, which uses a nonnegative least-squares model to interpolate the library plans, was compared against pure optimization for 11,250 navigated plans using data envelopment analysis. The visualization of the metric trade-offs was accomplished using numerically estimated partial derivatives to plot the local curvature of the Pareto surface. PNaV enables the user to control both the magnitude and direction of the trade-off during navigation. RESULTS: Proof of principle of PNaV was demonstrated using a graphical user interface with visualization tools to enabled rapid plan selection and a quantitative review of metric trade-offs. PNaV produced deliverable plans with DVH metrics within < 0.4%, 0.6%, and 1.1% (95% confidence interval) of the Pareto surface using plan libraries with nominal plan spacing of 10%, 15%, and 30% in each metric dimension, respectively. The interpolation used for the navigation executed in 0.1 s. The fast interpolation allows for quick and efficient exploration of trade-off options by the physician, after an initial preprocessing step to generate the library. CONCLUSIONS: Generation, visualization, and navigation of the Pareto surface were validated for brachytherapy treatment planning. The PNaV method enables efficient and informed decision-making for radiotherapy.

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. We describe a process and methodology successfully used in our practice with the hope that it saves time and effort for others when implementing RCF in their clinics. Two RCF analysis software programs which differ in cost and complexity, the commercially available FilmQA Pro package and the freely available ImageJ software, were used to show the accuracy, consistency and limitations of each. The process described resulted in a majority of the measurements across a wide dose range to be accurate within ± 2% of the intended dose using either FilmQA Pro or ImageJ.

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. Existing medical physics practice guidelines will be reviewed for the purpose of revision or renewal, as appropriate, on their fifth anniversary or sooner. Each medical physics practice guideline represents a policy statement by the AAPM, has undergone a thorough consensus process in which it has been subjected to extensive review, and requires the approval of the Professional Council. The medical physics practice guidelines recognize that the safe and effective use of diagnostic and therapeutic radiology requires specific training, skills, and techniques, as described in each document. Reproduction or modification of the published practice guidelines and technical standards by those entities not providing these services is not authorized. The following terms are used in the AAPM practice guidelines: Must and Must Not: Used to indicate that adherence to the recommendation is considered necessary to conform to this practice guideline. Should and Should Not: Used to indicate a prudent practice to which exceptions may occasionally be made in appropriate circumstances. Approved by AAPM's Executive Committee May 28, 2019.

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. The interplay effect was studied by modeling proton delivery from a clinical synchrotron-based spot scanning system and respiratory target motion, patterned from surrogate patient breathing traces. Motion both parallel and orthogonal to the beam scanning direction was investigated. Repainting was modeled using a layer-based technique. For each of 13 patient breathing traces, the dose from 20 distinct delivery schemes (combinations of four gate window amplitudes and five repainting techniques) was computed. Delivery strategies were inter-compared based on target coverage, dose homogeneity, high dose spillage, and delivery time. RESULTS: Notable degradation and variability in plan quality were observed for ungated delivery. Decreasing the gate window reduced this variability and improved plan quality at the expense of longer delivery times. Dose deviations were substantially greater for motion orthogonal to the scan direction when compared with parallel motion. Repainting coupled with gating was effective at partially restoring dosimetric coverage at only a fraction of the delivery time increase associated with very small gate windows alone. Trends for orthogonal motion were similar, but more complicated, due to the increased severity of the interplay. CONCLUSIONS: Layer-based repainting helps suppress the interplay effect from intra-gate motion, with only a modest penalty in delivery time. The magnitude of the improvement in target coverage is strongly influenced by individual patient breathing patterns and the tumor motion trajectory.

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. METHODS: Twenty domestic swine underwent proton beam treatment of LV sites in a dose-finding design and were followed for up to 40 weeks by cardiac magnetic resonance imaging at 4-week intervals. Doses investigated were either 40 Gy at 1 site (n = 8) or 30 Gy at 2 sites (n = 4) in the low-dose group and 40 Gy at 3 sites (n = 8) in the high-dose group. RESULTS: LV mean dose (13.2 ± 1.8 Gy vs 4.6 ± 1.8 Gy) and the volume receiving at least 20 Gy (V20Gy) (24.7% ± 4.8% vs 6.4% ± 3.0%) differed significantly between groups. Dose-dependent effects on left ventricular ejection fraction (LVEF) and LV end-diastolic volume became manifest about 3 months after treatment. LVEF decline was correlated to mean dose (correlation coefficient ρ = -0.69; P = .008) and V20Gy (ρ = -0.66; P = .01), as was LV dilation (ρ = 0.72; P = .005; and ρ = 0.75, P = .003 respectively). CONCLUSION: Possible adverse effects on LV function, seen about 3 months after treatment, are dose dependent. Therefore, precise target definition and focused energy delivery are paramount in catheter-free ablation.