Design of a modulated orthovoltage stereotactic radiosurgery system.

PURPOSE: To achieve stereotactic radiosurgery (SRS) dose distributions with sharp gradients using orthovoltage energy fluence modulation with inverse planning optimization techniques. METHODS: A pencil beam model was used to calculate dose distributions from an orthovoltage unit at 250 kVp. Kernels for the model were derived using Monte Carlo methods. A Genetic Algorithm search heuristic was used to optimize the spatial distribution of added tungsten filtration to achieve dose distributions with sharp dose gradients. Optimizations were performed for depths of 2.5, 5.0, and 7.5 cm, with cone sizes of 5, 6, 8, and 10 mm. In addition to the beam profiles, 4π isocentric irradiation geometries were modeled to examine dose at 0.07 mm depth, a representative skin depth, for the low energy beams. Profiles from 4π irradiations of a constant target volume, assuming maximally conformal coverage, were compared. Finally, dose deposition in bone compared to tissue in this energy range was examined. RESULTS: Based on the results of the optimization, circularly symmetric tungsten filters were designed to modulate the orthovoltage beam across the apertures of SRS cone collimators. For each depth and cone size combination examined, the beam flatness and 80-20% and 90-10% penumbrae were calculated for both standard, open cone-collimated beams as well as for optimized, filtered beams. For all configurations tested, the modulated beam profiles had decreased penumbra widths and flatness statistics at depth. Profiles for the optimized, filtered orthovoltage beams also offered decreases in these metrics compared to measured linear accelerator cone-based SRS profiles. The dose at 0.07 mm depth in the 4π isocentric irradiation geometries was higher for the modulated beams compared to unmodulated beams; however, the modulated dose at 0.07 mm depth remained <0.025% of the central, maximum dose. The 4π profiles irradiating a constant target volume showed improved statistics for the modulated, filtered distribution compared to the standard, open cone-collimated distribution. Simulations of tissue and bone confirmed previously published results that a higher energy beam (≥ 200 keV) would be preferable, but the 250 kVp beam was chosen for this work because it is available for future measurements. CONCLUSIONS: A methodology has been described that may be used to optimize the spatial distribution of added filtration material in an orthovoltage SRS beam to result in dose distributions with decreased flatness and penumbra statistics compared to standard open cones. This work provides the mathematical foundation for a novel, orthovoltage energy fluence-modulated SRS system.

Technical Note: Dose gradients and prescription isodose in orthovoltage stereotactic radiosurgery.

PURPOSE: The purpose of this work is to examine the trade-off between prescription isodose and dose gradients in orthovoltage stereotactic radiosurgery. METHODS: Point energy deposition kernels (EDKs) describing photon and electron transport were calculated using Monte Carlo methods. EDKs were generated from 10 to 250 keV, in 10 keV increments. The EDKs were converted to pencil beam kernels and used to calculate dose profiles through isocenter from a 4π isotropic delivery from all angles of circularly collimated beams. Monoenergetic beams and an orthovoltage polyenergetic spectrum were analyzed. The dose gradient index (DGI) is the ratio of the 50% prescription isodose volume to the 100% prescription isodose volume and represents a metric by which dose gradients in stereotactic radiosurgery (SRS) may be evaluated. RESULTS: Using the 4π dose profiles calculated using pencil beam kernels, the relationship between DGI and prescription isodose was examined for circular cones ranging from 4 to 18 mm in diameter and monoenergetic photon beams with energies ranging from 20 to 250 keV. Values were found to exist for prescription isodose that optimize DGI. CONCLUSIONS: The relationship between DGI and prescription isodose was found to be dependent on both field size and energy. Examining this trade-off is an important consideration for designing optimal SRS systems.

Selective omission of level V nodal coverage for patients with oropharyngeal cancer: Clinical validation of intensity-modulated radiotherapy experience and dosimetric significance.

BACKGROUND: We sought to validate the consensus recommendation and assess dosimetric significance of selective omission of nodal level V from intensity-modulated radiotherapy (IMRT) clinical target volume (CTV) for oropharyngeal cancer. METHODS: IMRT plans and clinical outcomes for 112 patients with oropharyngeal cancer (nodal classification N0-N2b) were analyzed for coverage of ipsilateral and contralateral nodal level V. Additionally, new IMRT plans were generated in 6 randomly selected patients to assess its dosimetric impact. RESULTS: With median follow-up of 3.4 years, there were no failures identified in nodal level V with or without nodal level V omission. Upon dosimetric evaluation, significant reduction in integral dose, V10 Gy , V20 Gy , V30 Gy , V40 Gy , and V50 Gy was observed by excluding unilateral and bilateral level V from the CTV. CONCLUSION: We clinically validate the consensus recommendation for selective omission of level V nodal coverage in IMRT planning of patients with oropharyngeal cancer and demonstrate significant dosimetric advantages.

Development of Compton lens design for increased dose rate in linear accelerator based SRS.

PURPOSE: To develop a fundamentally new stereotactic radiosurgery (SRS) collimator design which utilizes initially off-axis Compton scattered photons to increase the dose rate at isocenter for small field treatments. MATERIALS AND METHODS: The proposed design added a set of conical slits to a standard cylindrical collimator to allow for scattered photons within the collimator to still contribute to the overall target dose. The design optimization was broken down into two regions: a solid interaction plate and a Compton slit region. The interaction plate geometry was developed to facilitate Compton scattering towards the target, and the Compton slit geometry was optimized to allow for Compton scattered photons to travel unattenuated towards the target. A series of sensitivity studies were performed using Monte Carlo N-Particle (MCNP6) Transport Code to optimize the geometry of the collimator focusing on the material, thickness, cone size, number of slits and slit width. RESULTS: An optimized collimator design incorporating 6 slits for a 4 mm target allowed for an increase in the dose rate of 3.5% while limiting off axis increases between 1 and 5 cm to an average of less than 1% relative to standard collimator designs. CONCLUSION: Preliminary designs present a proof of concept and suggest the potential for increases in dose rate for linac-based SRS systems. These designs have been able to achieve increases while maintaining a relatively low dose rate outside of the target. Further exploration into non-linear optimization of the slits and interaction plate geometry may lead to further increases than presently demonstrated.This concept warrants further study with actual measurement and to be tested for its practicality in clinical use.

On voxel-by-voxel accumulated dose for prostate radiation therapy using deformable image registration.

Since delivered dose is rarely the same with planned, we calculated the delivered total dose to ten prostate radiotherapy patients treated with rectal balloons using deformable dose accumulation (DDA) and compared it with the planned dose. The patients were treated with TomoTherapy using two rectal balloon designs: five patients had the Radiadyne balloon (balloon A), and five patients had the EZ-EM balloon (balloon B). Prostate and rectal wall contours were outlined on each pre-treatment MVCT for all patients. Delivered fractional doses were calculated using the MVCT taken immediately prior to delivery. Dose grids were accumulated to the last MVCT using DDA tools in Pinnacle3 TM (v9.100, Philips Radiation Oncology Systems, Fitchburg, USA). Delivered total doses were compared with planned doses using prostate and rectal wall DVHs. The rectal NTCP was calculated based on total delivered and planned doses for all patients using the Lyman model. For 8/10 patients, the rectal wall NTCP calculated using the delivered total dose was less than planned, with seven patients showing a decrease of more than 5% in NTCP. For 2/10 patients studied, the rectal wall NTCP calculated using total delivered dose was 2% higher than planned. This study indicates that for patients receiving hypofractionated radiotherapy for prostate cancer with a rectal balloon, total delivered doses to prostate is similar with planned while delivered dose to rectal walls may be significantly different from planned doses. 8/10 patients show significant correlation between rectal balloon anterior-posterior positions and some VD values.

Increasing dose gradient and uniformity in small fields using modulation: theory and prototypes for cone-based stereotactic radiosurgery.

PURPOSE: To investigate the theoretical limits to the tradeoff between dose gradient and uniformity when modulation is used in the context of cone based SRS, and to design a prototype collimation device that allows for steeper dose gradients and/or higher target uniformity as compared to a standard circular collimator. METHODS: An inverse planning optimization is performed in the context of idealized phantom geometry to determine the ideal fluence pattern that best approximates a "rect function" dose distribution. Ideal fluence patterns were approximated in a prototype device and radiochromic film dosimetry was utilized to compare the prototype device to a standard circular collimator. RESULTS: For choices of prescription isodose lines above approximately 50%, utilizing modulation allows for an improved tradeoff between dose gradient index and dose heterogeneity index. Compensators placed within the circular collimator can achieve the necessary modulation. CONCLUSIONS: Using modulation with features on a submillimeter distance scale, it is possible to increase the dose gradient and/or uniformity in small fields.

The effect on dose accumulation accuracy of inverse-consistency and transitivity error reduced deformation maps.

It has previously been shown that deformable image registrations (DIRs) often result in deformation maps that are neither inverse-consistent nor transitive, and that the dose accumulation based on these deformation maps can be inconsistent if different image pathways are used for dose accumulation. A method presented to reduce inverse consistency and transitivity errors has been shown to result in more consistent dose accumulation, regardless of the image pathway selected for dose accumulation. The present study investigates the effect on the dose accumulation accuracy of deformation maps processed to reduce inverse consistency and transitivity errors. A set of lung 4DCT phases were analysed, consisting of four images on which a dose grid was created. Dose to 75 corresponding anatomical locations was manually tracked. Dose accumulation was performed between all image sets with Demons derived deformation maps as well as deformation maps processed to reduce inverse consistency and transitivity errors. The ground truth accumulated dose was then compared with the accumulated dose derived from DIR. Two dose accumulation image pathways were considered. The post-processing method to reduce inverse consistency and transitivity errors had minimal effect on the dose accumulation accuracy. There was a statistically significant improvement in dose accumulation accuracy for one pathway, but for the other pathway there was no statistically significant difference. A post-processing technique to reduce inverse consistency and transitivity errors has a positive, yet minimal effect on the dose accumulation accuracy. Thus the post-processing technique improves consistency of dose accumulation with minimal effect on dose accumulation accuracy.

Brain necrosis after fractionated radiation therapy: is the halftime for repair longer than we thought?

PURPOSE: To derive a radiobiological model that enables the estimation of brain necrosis and spinal cord myelopathy rates for a variety of fractionation schemes, and to compare repair effects between brain and spinal cord. METHODS: Sigmoidal dose response relationships for brain radiation necrosis and spinal cord myelopathy are derived from clinical data using nonlinear regression. Three different repair models are considered and the repair halftimes are included as regression parameters. RESULTS: For radiation necrosis, a repair halftime of 38.1 (range 6.9-76) h is found with monoexponential repair, while for spinal cord myelopathy, a repair halftime of 4.1 (range 0-8) h is found. The best-fit alpha beta ratio is 0.96 (range 0.24-1.73). CONCLUSIONS: A radiobiological model that includes repair corrections can describe the clinical data for a variety of fraction sizes, fractionation schedules, and total doses. Modeling suggests a relatively long repair halftime for brain necrosis. This study suggests that the repair halftime for late radiation effects in the brain may be longer than is currently thought. If confirmed in future studies, this may lead to a re-evaluation of radiation fractionation schedules for some CNS diseases, particularly for those diseases where fractionated stereotactic radiation therapy is used.

Using spatial information about recurrence risk for robust optimization of dose-painting prescription functions.

PURPOSE: To develop a robust method for deriving dose-painting prescription functions using spatial information about the risk for disease recurrence. METHODS: Spatial distributions of radiobiological model parameters are derived from distributions of recurrence risk after uniform irradiation. These model parameters are then used to derive optimal dose-painting prescription functions given a constant mean biologically effective dose. RESULTS: An estimate for the optimal dose distribution can be derived based on spatial information about recurrence risk. Dose painting based on imaging markers that are moderately or poorly correlated with recurrence risk are predicted to potentially result in inferior disease control when compared the same mean biologically effective dose delivered uniformly. A robust optimization approach may partially mitigate this issue. CONCLUSIONS: The methods described here can be used to derive an estimate for a robust, patient-specific prescription function for use in dose painting. Two approximate scaling relationships were observed: First, the optimal choice for the maximum dose differential when using either a linear or two-compartment prescription function is proportional to R, where R is the Pearson correlation coefficient between a given imaging marker and recurrence risk after uniform irradiation. Second, the predicted maximum possible gain in tumor control probability for any robust optimization technique is nearly proportional to the square of R.

On the dosimetric effect and reduction of inverse consistency and transitivity errors in deformable image registration for dose accumulation.

PURPOSE: Deformable image registration (DIR) is necessary for accurate dose accumulation between multiple radiotherapy image sets. DIR algorithms can suffer from inverse and transitivity inconsistencies. When using deformation vector fields (DVFs) that exhibit inverse-inconsistency and are nontransitive, dose accumulation on a given image set via different image pathways will lead to different accumulated doses. The purpose of this study was to investigate the dosimetric effect of and propose a postprocessing solution to reduce inverse consistency and transitivity errors. METHODS: Four MVCT images and four phases of a lung 4DCT, each with an associated calculated dose, were selected for analysis. DVFs between all four images in each data set were created using the Fast Symmetric Demons algorithm. Dose was accumulated on the fourth image in each set using DIR via two different image pathways. The two accumulated doses on the fourth image were compared. The inverse consistency and transitivity errors in the DVFs were then reduced. The dose accumulation was repeated using the processed DVFs, the results of which were compared with the accumulated dose from the original DVFs. To evaluate the influence of the postprocessing technique on DVF accuracy, the original and processed DVF accuracy was evaluated on the lung 4DCT data on which anatomical landmarks had been identified by an expert. RESULTS: Dose accumulation to the same image via different image pathways resulted in two different accumulated dose results. After the inverse consistency errors were reduced, the difference between the accumulated doses diminished. The difference was further reduced after reducing the transitivity errors. The postprocessing technique had minimal effect on the accuracy of the DVF for the lung 4DCT images. CONCLUSIONS: This study shows that inverse consistency and transitivity errors in DIR have a significant dosimetric effect in dose accumulation; Depending on the image pathway taken to accumulate the dose, different results may be obtained. A postprocessing technique that reduces inverse consistency and transitivity error is presented, which allows for consistent dose accumulation regardless of the image pathway followed.

On the estimation of the location of the hippocampus in the context of hippocampal avoidance whole brain radiotherapy treatment planning.

We demonstrate a technique for estimating the location of the hippocampus in MRI and CT images for use in radiotherapy treatment planning, using both rigid and contour based deformable image registration. The automatically generated contours can be subsequently modified for a given patient. By mapping the hippocampi from several patients into a template image set, a population-based average hippocampal atlas was generated. Approximate hippocampal contours can be automatically generated in a given image set by mapping this atlas onto it. The performance and accuracy of several atlases generated in different ways was tested on 10 MRI images and 7 CT images. Auto-contouring based on deformable registration significantly outperformed that based on rigid registration alone, with an average Dice similarity score of 0.62 (range .40-.76) for methods utilizing deformation. Comparable results were achieved in auto-contouring CT images when deformable registration was used, demonstrating that the methodology is robust with respect to imaging modality.

The utilization of consistency metrics for error analysis in deformable image registration.

The aim of this study was to investigate the utility of consistency metrics, such as inverse consistency, in contour-based deformable registration error analysis. Four images were acquired of the same phantom that has experienced varying levels of deformation. The deformations were simulated with deformable image registration. Using calculated deformation maps, the inconsistencies within the algorithm were investigated. This can be done, for example, by calculating deformation maps both in forward and reverse directions and applying them subsequently to an image. If the algorithm is not inverse consistent, then this final image will not be the same as the original, as it should be. Other consistency tests were done, for example by comparing different algorithms or by applying the deformation maps to a circular set of multiple deformations, whereby the original and final images are in fact the same. The resulting composite deformation map in this case contains a combination of the errors within those maps, because if error free, the resulting deformation map should be zero everywhere. We have termed this the generalized inverse consistency error map (Sigma(Chi)). The correlation between the consistency metrics and registration error varied considerably depending on the registration algorithm and type of consistency metric. There was also a trend for the actual registration error to be larger than the consistency metrics. A disadvantage of these techniques is that good performance in these consistency checks is a necessary but not sufficient condition for an accurate deformation method.