A simplified and effective off-axis Winston-Lutz for single-isocenter multi-target SRS.

PURPOSE: To safely perform single-iso multi-target (SIMT) stereotactic radiosurgery (SRS), clinics must demonstrate SRS delivery accuracy for off-axis targets. The traditional Winston-Lutz (W-L) was widely adopted because it provides a simple and accurate solution for testing radiation-isocenter coincidence that uses a static target, enables testing arbitrary treatment angles, and does not require expensive commercial phantoms. The current noncommercial tests are cumbersome and insufficiently accurate. For an off-axis Winston-Lutz (OAWL) test, one must design MLC fields centered on off-axis targets. Unfortunately, because MLC leaf-interfaces are often misaligned with the target center, accomplishing this presents a nontrivial geometry problem that has not been previously solved in the literature. We present a solution for evaluating SIMT SRS accuracy that provides a straightforward method for creating OAWL test fields and offers all the benefits of the standard W-L test. METHODS: We have developed a method to use any gantry, table, and initial collimator angles to create OAWL fields. This method calculates a series of nested coordinate transformations that produce a small collimator angle adjustment to align the MLC and create a symmetric field around an off-axis target. RESULTS: For an 8 cm off-axis target, the described method yields OAWL results within 0.07 mm of standard isocentric W-L results. Our six most recent isocentric W-L tests show max and mean errors of 0.59 and 0.37 mm, respectively. For six runs of our proposed OAWL test, the average max and mean errors are 0.66 and 0.40 mm, respectively. CONCLUSION: This method accurately evaluates SRS delivery accuracy for off-axis distances that span the majority of a typical human brain for a centered SIMT arc. We have made this method publicly available, so that physicists can employ it within their clinics, foregoing the need for expensive phantoms and improving access to the state-of-the-art SIMT SRS technique.

A system for equitable workload distribution in clinical medical physics.

BACKGROUND: Clinical medical physics duties include routine tasks, special procedures, and development projects. It can be challenging to distribute the effort equitably across all team members, especially in large clinics or systems where physicists cover multiple sites. The purpose of this work is to study an equitable workload distribution system in radiotherapy physics that addresses the complex and dynamic nature of effort assignment. METHODS: We formed a working group that defined all relevant clinical tasks and estimated the total time spent per task. Estimates used data from the oncology information system, a survey of physicists, and group consensus. We introduced a quantitative workload unit, "equivalent workday" (eWD), as a common unit for effort. The sum of all eWD values adjusted for each physicist's clinical full-time equivalent yields a "normalized total effort" (nTE) metric for each physicist, that is, the fraction of the total effort assigned to that physicist. We implemented this system in clinical operation. During a trial period of 9 months, we made adjustments to include tasks previously unaccounted for and refined the system. The workload distribution of eight physicists over 12 months was compared before and after implementation of the nTE system. RESULTS: Prior to implementation, differences in workload of up to 50% existed between individual physicists (nTE range of 10.0%-15.0%). During the trial period, additional categories were added to account for leave and clinical projects that had previously been assigned informally. In the 1-year period after implementation, the individual workload differences were within 5% (nTE range of 12.3%-12.8%). CONCLUSION: We developed a system to equitably distribute workload and demonstrated improvements in the equity of workload. A quantitative approach to workload distribution improves both transparency and accountability. While the system was motivated by the complexities within an academic medical center, it may be generally applicable for other clinics.

Impact of the MLC leaf-tip model in a commercial TPS: Dose calculation limitations and IROC-H phantom failures.

PURPOSE: Treatment planning system (TPS) dose calculation is sensitive to multileaf collimator (MLC) modeling, especially when treating with intensity-modulated radiation therapy (IMRT) or VMAT. This study investigates the dosimetric impact of the MLC leaf-tip model in a commercial TPS (RayStation v.6.1). The detectability of modeling errors was assessed through both measurements with an anthropomorphic head-and-neck phantom and patient-specific IMRT QA using a 3D diode array. METHODS AND MATERIALS: An Agility MLC (Elekta Inc.) was commissioned in RayStation. Nine IMRT and VMAT plans were optimized to treat the head-and-neck phantom from the Imaging and Radiation Oncology Core Houston branch (IROC-H). Dose distributions for each plan were re-calculated on 27 beam models, varying leaf-tip width (2.0, 4.5, and 6.5 mm) and leaf-tip offset (-2.0 to +2.0 mm) values. Doses were compared to phantom TLD measurements. Patient-specific IMRT QA was performed, and receiver-operating characteristic (ROC) analysis was performed to determine the detectability of modeling errors. RESULTS: Dose calculations were very sensitive to leaf-tip offset values. Offsets of ±1.0 mm resulted in dose differences up to 10% and 15% in the PTV and spinal cord TLDs respectively. Offsets of ±2.0 mm caused dose deviations up to 50% in the spinal cord TLD. Patient-specific IMRT QA could not reliably detect these deviations, with an ROC area under the curve (AUC) value of 0.537 for a ±1.0 mm change in leaf-tip offset, corresponding to >7% dose deviation. Leaf-tip width had a modest dosimetric impact with <2% and 5.6% differences in the PTV and spinal cord TLDs respectively. CONCLUSIONS: Small changes in the MLC leaf-tip offset in this TPS model can cause large changes in the calculated dose for IMRT and VMAT plans that are difficult to identify through either dose curves or standard patient-specific IMRT QA. These results may, in part, explain the reported high failure rate of IROC-H phantom tests.

Inverse planning for IMRT with nonuniform beam profiles using total-variation regularization (TVR).

PURPOSE: Radiation therapy with high dose rate and flattening filter-free (FFF) beams has the potential advantage of greatly reduced treatment time and out-of-field dose. Current inverse planning algorithms are, however, not customized for beams with nonuniform incident profiles and the resultant IMRT plans are often inefficient in delivery. The authors propose a total-variation regularization (TVR)-based formalism by taking the inherent shapes of incident beam profiles into account. METHODS: A novel TVR-based inverse planning formalism is established for IMRT with nonuniform beam profiles. The authors introduce a TVR term into the objective function, which encourages piecewise constant fluence in the nonuniform FFF fluence domain. The proposed algorithm is applied to lung and prostate and head and neck cases and its performance is evaluated by comparing the resulting plans to those obtained using a conventional beamlet-based optimization (BBO). RESULTS: For the prostate case, the authors' algorithm produces acceptable dose distributions with only 21 segments, while the conventional BBO requires 114 segments. For the lung case and the head and neck case, the proposed method generates similar coverage of target volume and sparing of the organs-at-risk as compared to BBO, but with a markedly reduced segment number. CONCLUSIONS: TVR-based optimization in nonflat beam domain provides an effective way to maximally leverage the technical capacity of radiation therapy with FFF fields. The technique can generate effective IMRT plans with improved dose delivery efficiency without significant deterioration of the dose distribution.

Characterizing a deformable registration algorithm for surface-guided breast radiotherapy.

PURPOSE: Surface-guided radiation therapy (SGRT) is a nonionizing imaging approach for patient setup guidance, intra-fraction monitoring, and automated breath-hold gating of radiation treatments. SGRT employs the premise that the external patient surface correlates to the internal anatomy, to infer the treatment isocenter position at time of treatment delivery. Deformations and posture variations are known to impact the correlation between external and internal anatomy. However, the degree, magnitude, and algorithm dependence of this impact are not intuitive and currently no methods exist to assess this relationship. The primary aim of this work was to develop a framework to investigate and understand how a commercial optical surface imaging system (C-RAD, Uppsala, Sweden), which uses a nonrigid registration algorithm, handles rotations and surface deformations. METHODS: A workflow consisting of a female torso phantom and software-introduced transformations to the corresponding digital reference surface was developed. To benchmark and validate the approach, known rigid translations and rotations were first applied. Relevant breast radiotherapy deformations related to breast size, hunching/arching back, distended/deflated abdomen, and an irregular surface to mimic a cover sheet over the lower part of the torso were investigated. The difference between rigid and deformed surfaces was evaluated as a function of isocenter location. RESULTS: For all introduced rigid body transformations, C-RAD computed isocenter shifts were determined within 1 mm and 1˚. Additional translational shifts to correct for rotations as a function of isocenter location were determined with the same accuracy. For yaw setup errors, the difference in shift corrections between a plan with an isocenter placed in the center of the breast (BrstIso) and one located 12 cm superiorly (SCFIso) was 2.3 mm/1˚ in lateral direction. Pitch setup errors resulted in a difference of 2.1 mm/1˚ in vertical direction. For some of the deformation scenarios, much larger differences up to 16 mm and 7˚ in the calculated shifts between BrstIso and SCFIso were observed that could lead to large unintended gaps or overlap between adjacent matched fields if uncorrected. CONCLUSIONS: The methodology developed lends itself well for quality assurance (QA) of SGRT systems. The deformable C-RAD algorithm determined accurate shifts for rigid transformations, and this was independent of isocenter location. For surface deformations, the position of the isocenter had considerable impact on the registration result. It is recommended to avoid off-axis isocenters during treatment planning to optimally utilize the capabilities of the deformable image registration algorithm, especially when multiple isocenters are used with fields that share a field edge.

Application of stochastic finite element methods to study the sensitivity of ECG forward modeling to organ conductivity.

Because numerical simulation parameters may significantly influence the accuracy of the results, evaluating the sensitivity of simulation results to variations in parameters is essential. Although the field of sensitivity analysis is well developed, systematic application of such methods to complex biological models is limited due to the associated high computational costs and the substantial technical challenges for implementation. In the specific case of the forward problem in electrocardiography, the lack of robust, feasible, and comprehensive sensitivity analysis has left many aspects of the problem unresolved and subject to empirical and intuitive evaluation rather than sound, quantitative investigation. In this study, we have developed a systematic, stochastic approach to the analysis of sensitivity of the forward problem of electrocardiography to the parameter of inhomogeneous tissue conductivity. We apply this approach to a two-dimensional, inhomogeneous, geometric model of a slice through the human thorax. We assigned probability density functions for various organ conductivities and applied stochastic finite elements based on the generalized polynomial chaos-stochastic Galerkin (gPC-SG) method to obtain the standard deviation of the resulting stochastic torso potentials. This method utilizes a spectral representation of the stochastic process to obtain numerically accurate stochastic solutions in a fraction of the time required when employing classic Monte Carlo methods. We have shown that a systematic study of sensitivity is not only easily feasible with the gPC-SG approach but can also provide valuable insight into characteristics of the specific simulation.

Resection and brain brachytherapy with permanent iodine-125 sources for brain metastasis.

OBJECTIVE Stereotactic radiosurgery (SRS) with or without whole-brain radiotherapy can be used to achieve local control (> 90%) for small brain metastases after resection. However, many brain metastases are unsuitable for SRS because of their size or previous treatment, and whole-brain radiotherapy is associated with significant neurocognitive morbidity. The purpose of this study was to investigate the efficacy and toxicity of surgery and iodine-125 (125I) brachytherapy for brain metastases. METHODS A total of 95 consecutive patients treated for 105 brain metastases at a single institution between September 1997 and July 2013 were identified for this analysis retrospectively. Each patient underwent MRI followed by craniotomy with resection of metastasis and placement of 125I sources as permanent implants. The patients were followed with serial surveillance MRIs. The relationships among local control, overall survival, and necrosis were estimated by using the Kaplan-Meier method and compared with results of log-rank tests and multivariate regression models. RESULTS The median age at surgery was 59 years (range 29.9-81.6 years), 53% of the lesions had been treated previously, and the median preoperative metastasis volume was 13.5 cm3 (range 0.21-76.2 cm3). Gross-total resection was achieved in 81% of the cases. The median number of 125I sources implanted per cavity was 28 (range 4-93), and the median activity was 0.73 mCi (range 0.34-1.3 mCi) per source. A total of 476 brain MRIs were analyzed (median MRIs per patient 3; range 0-22). Metastasis size was the strongest predictor of cavity volume and shrinkage (p < 0.0001). Multivariable regression modeling failed to predict the likelihood of local progression or necrosis according to metastasis volume, cavity volume, or the rate of cavity remodeling regardless of source activity or previous SRS. The median clinical follow-up time in living patients was 14.4 months (range 0.02-13.6 years), and crude local control was 90%. Median overall survival extended from 2.1 months in the shortest quartile to 62.3 months in the longest quartile (p < 0.0001). The overall risk of necrosis was 15% and increased significantly for lesions with a history of previous SRS (p < 0.05). CONCLUSIONS Therapeutic options for patients with large or recurrent brain metastases are limited. Data from this study suggest that resection with permanent 125I brachytherapy is an effective strategy for achieving local control of brain metastasis. Although metastasis volume significantly influences resection cavity size and remodeling, volumetric parameters do not seem to influence local control or necrosis. With careful patient selection, this treatment regimen is associated with minimal toxicity and can result in long-term survival for some patients. ▪ CLASSIFICATION OF EVIDENCE Type of question: therapeutic; study design: retrospective case series; evidence: Class IV.

Dual-Gated Volumetric Modulated Arc Therapy.

BACKGROUND: Gated Volumetric Modulated Arc Therapy (VMAT) is an emerging radiation therapy modality for treatment of tumors affected by respiratory motion. However, gating significantly prolongs the treatment time, as delivery is only activated during a single respiratory phase. To enhance the efficiency of gated VMAT delivery, a novel dual-gated VMAT (DG-VMAT) technique, in which delivery is executed at both exhale and inhale phases in a given arc rotation, is developed and experimentally evaluated. METHODS: Arc delivery at two phases is realized by sequentially interleaving control points consisting of MUs, MLC sequences, and angles of VMAT plans generated at the exhale and inhale phases. Dual-gated delivery is initiated when a respiration gating signal enters the exhale window; when the exhale delivery concludes, the beam turns off and the gantry rolls back to the starting position for the inhale window. The process is then repeated until both inhale and exhale arcs are fully delivered. DG-VMAT plan delivery accuracy was assessed using a pinpoint chamber and diode array phantom undergoing programmed motion. RESULTS: DG-VMAT delivery was experimentally implemented through custom XML scripting in Varian's TrueBeam™ STx Developer Mode. Relative to single gated delivery at exhale, the treatment time was improved by 95.5% for a sinusoidal breathing pattern. The pinpoint chamber dose measurement agreed with the calculated dose within 0.7%. For the DG-VMAT delivery, 97.5% of the diode array measurements passed the 3%/3 mm gamma criterion. CONCLUSIONS: The feasibility of DG-VMAT delivery scheme has been experimentally demonstrated for the first time. By leveraging the stability and natural pauses that occur at end-inspiration and end-exhalation, DG-VMAT provides a practical method for enhancing gated delivery efficiency by up to a factor of two.

Cardiac position sensitivity study in the electrocardiographic forward problem using stochastic collocation and boundary element methods.

The electrocardiogram (ECG) is ubiquitously employed as a diagnostic and monitoring tool for patients experiencing cardiac distress and/or disease. It is widely known that changes in heart position resulting from, for example, posture of the patient (sitting, standing, lying) and respiration significantly affect the body-surface potentials; however, few studies have quantitatively and systematically evaluated the effects of heart displacement on the ECG. The goal of this study was to evaluate the impact of positional changes of the heart on the ECG in the specific clinical setting of myocardial ischemia. To carry out the necessary comprehensive sensitivity analysis, we applied a relatively novel and highly efficient statistical approach, the generalized polynomial chaos-stochastic collocation method, to a boundary element formulation of the electrocardiographic forward problem, and we drove these simulations with measured epicardial potentials from whole-heart experiments. Results of the analysis identified regions on the body-surface where the potentials were especially sensitive to realistic heart motion. The standard deviation (STD) of ST-segment voltage changes caused by the apex of a normal heart, swinging forward and backward or side-to-side was approximately 0.2 mV. Variations were even larger, 0.3 mV, for a heart exhibiting elevated ischemic potentials. These variations could be large enough to mask or to mimic signs of ischemia in the ECG. Our results suggest possible modifications to ECG protocols that could reduce the diagnostic error related to postural changes in patients possibly suffering from myocardial ischemia.

Incorporating patient breathing variability into a stochastic model of dose deposition for stereotactic body radiation therapy.

Hypo-fractionated stereotactic body radiation therapy (SBRT) employs precisely-conforming high-level radiation dose delivery to improve tumor control probabilities and sparing of healthy tissue. However, the delivery precision and conformity of SBRT renders dose accumulation particularly susceptible to organ motion, and respiratory-induced motion in the abdomen may result in significant displacement of lesion targets during the breathing cycle. Given the maturity of the technology, sensitivity of dose deposition to respiratory-induced organ motion represents a significant factor in observed discrepancies between predictive treatment plan indicators and clinical patient outcome statistics and one of the major outstanding unsolved problems in SBRT. Techniques intended to compensate for respiratory-induced organ motion have been investigated, but very few have yet reached clinical practice. To improve SBRT, it is necessary to overcome the challenge that uncertainties in dose deposition due to organ motion present. This requires incorporating an accurate prediction of the effects of the random nature of the respiratory process on SBRT dose deposition for improved treatment planning and delivery of SBRT. We introduce a means of characterizing the underlying day-to-day variability of patient breathing and calculate the resulting stochasticity in dose accumulation.

Stochastic Markovian modeling of electrophysiology of ion channels: reconstruction of standard deviations in macroscopic currents.

Markovian models of ion channels have proven useful in the reconstruction of experimental data and prediction of cellular electrophysiology. We present the stochastic Galerkin method as an alternative to Monte Carlo and other stochastic methods for assessing the impact of uncertain rate coefficients on the predictions of Markovian ion channel models. We extend and study two different ion channel models: a simple model with only a single open and a closed state and a detailed model of the cardiac rapidly activating delayed rectifier potassium current. We demonstrate the efficacy of stochastic Galerkin methods for computing solutions to systems with random model parameters. Our studies illustrate the characteristic changes in distributions of state transitions and electrical currents through ion channels due to random rate coefficients. Furthermore, the studies indicate the applicability of the stochastic Galerkin technique for uncertainty and sensitivity analysis of bio-mathematical models.

Sensitivity analysis of cardiac electrophysiological models using polynomial chaos.

Mathematical models of biophysical phenomena have proven useful in the reconstruction of experimental data and prediction of biological behavior. By quantifying the sensitivity of a model to certain parameters, one can place an appropriate amount of emphasis in the accuracy with which those parameters are determined. In addition, investigation of stochastic parameters can lead to a greater understanding of the behavior captured by the model. This can lead to possible model reductions, or point out shortcomings to be addressed. We present polynomial chaos as a computationally efficient alternative to Monte Carlo for assessing the impact of stochastically distributed parameters on the model predictions of several cardiac electrophysiological models.

The Influence of Stochastic Organ Conductivity in 2D ECG Forward Modeling: A Stochastic Finite Element Study.

Quantification of the sensitivity of the electro-cardiographic forward problem to various parameters can effectively direct the generalization of patient specific models without significant loss in accuracy. To this purpose we applied polynomial chaos based stochastic finite elements to assess the effect of variations in the distributions of tissue conductivity in a two-dimensional torso geometry generated from MRI scans and epicardial boundary conditions specified by intra-operatively recorded heart potentials. The polynomial chaos methodology allows sensitivity analysis of this type to be done in a fraction of the time required for a Monte Carlo analysis.