Variation in Androgen Deprivation Therapy Use Among Men With Intermediate-Risk Prostate Cancer: Results From a Statewide Radiation Oncology Quality Consortium.

PURPOSE: For men with intermediate-risk prostate cancer treated with definitive therapy, the addition of androgen deprivation therapy (ADT) reduces the risk of distant metastasis and cancer-related mortality. However, the absolute benefit of ADT varies by baseline cancer risk. Estimates of prognosis have improved over time, and little is known about ADT decision making in the modern era. We sought to characterize variability and identify factors associated with intended ADT use within the Michigan Radiation Oncology Quality Consoritum (MROQC). MATERIALS AND METHODS: Patients with localized prostate cancer undergoing definitive radiation therapy were enrolled from June 9, 2020, to June 26, 2023 (n = 815). Prospective data were collected using standardized patient, physician, and physicist forms. Intended ADT use was prospectively defined and was the primary outcome. Associations with patient, tumor, and practice-related factors were tested with multivariable analyses. Random intercept modeling was used to estimate facility-level variability. RESULTS: Five hundred seventy patients across 26 facilities were enrolled with intermediate-risk disease. ADT was intended for 46% of men (n = 262/570), which differed by National Comprehensive Cancer Network favorable intermediate-risk (23.5%, n = 38/172) versus unfavorable intermediate-risk disease (56.3%, n = 224/398; P < .001). After adjusting for the statewide case mix, the predicted probability of intended ADT use varied significantly across facilities, ranging from 15.4% (95% CI, 5.4%-37.0%) to 71.7% (95% CI, 57.0%-82.9%), with P < .01. Multivariable analyses showed that grade group 3 (OR, 4.60 [3.20-6.67]), ≥50% positive cores (OR, 2.15 [1.43-3.25]), and prostate-specific antigen 10 to 20 (OR, 1.87 [1.24-2.84]) were associated with ADT use. Area under the curve was improved when incorporating MRI adverse features (0.76) or radiation treatment variables (0.76), but there remained significant facility-level heterogeneity in all models evaluated (P < .05). CONCLUSIONS: Within a state-wide consortium, there is substantial facility-level heterogeneity in intended ADT use for men with intermediate-risk prostate cancer. Future efforts are necessary to identify patients who will benefit most from ADT and to develop strategies to standardize appropriate use.

A prototype scintillator real-time beam monitor for ultra-high dose rate radiotherapy.

BACKGROUND: FLASH Radiotherapy (RT) is an emergent cancer RT modality where an entire therapeutic dose is delivered at more than 1000 times higher dose rate than conventional RT. For clinical trials to be conducted safely, a precise and fast beam monitor that can generate out-of-tolerance beam interrupts is required. This paper describes the overall concept and provides results from a prototype ultra-fast, scintillator-based beam monitor for both proton and electron beam FLASH applications. PURPOSE: A FLASH Beam Scintillator Monitor (FBSM) is being developed that employs a novel proprietary scintillator material. The FBSM has capabilities that conventional RT detector technologies are unable to simultaneously provide: (1) large area coverage; (2) a low mass profile; (3) a linear response over a broad dynamic range; (4) radiation hardness; (5) real-time analysis to provide an IEC-compliant fast beam-interrupt signal based on true two-dimensional beam imaging, radiation dosimetry and excellent spatial resolution. METHODS: The FBSM uses a proprietary low mass, less than 0.5 mm water equivalent, non-hygroscopic, radiation tolerant scintillator material (designated HM: hybrid material) that is viewed by high frame rate CMOS cameras. Folded optics using mirrors enable a thin monitor profile of ∼10 cm. A field programmable gate array (FPGA) data acquisition system generates real-time analysis on a time scale appropriate to the FLASH RT beam modality: 100-1000 Hz for pulsed electrons and 10-20 kHz for quasi-continuous scanning proton pencil beams. An ion beam monitor served as the initial development platform for this work and was tested in low energy heavy-ion beams (86Kr+26 and protons). A prototype FBSM was fabricated and then tested in various radiation beams that included FLASH level dose per pulse electron beams, and a hospital RT clinic with electron beams. RESULTS: Results presented in this report include image quality, response linearity, radiation hardness, spatial resolution, and real-time data processing. The HM scintillator was found to be highly radiation damage resistant. It exhibited a small 0.025%/kGy signal decrease from a 216 kGy cumulative dose resulting from continuous exposure for 15 min at a FLASH compatible dose rate of 237 Gy/s. Measurements of the signal amplitude versus beam fluence demonstrate linear response of the FBSM at FLASH compatible dose rates of >40 Gy/s. Comparison with commercial Gafchromic film indicates that the FBSM produces a high resolution 2D beam image and can reproduce a nearly identical beam profile, including primary beam tails. The spatial resolution was measured at 35-40 µm. Tests of the firmware beta version show successful operation at 20 000 Hz frame rate or 50 µs/frame, where the real-time analysis of the beam parameters is achieved in less than 1 µs. CONCLUSIONS: The FBSM is designed to provide real-time beam profile monitoring over a large active area without significantly degrading the beam quality. A prototype device has been staged in particle beams at currents of single particles up to FLASH level dose rates, using both continuous ion beams and pulsed electron beams. Using a novel scintillator, beam profiling has been demonstrated for currents extending from single particles to 10 nA currents. Radiation damage is minimal and even under FLASH conditions would require ≥50 kGy of accumulated exposure in a single spot to result in a 1% decrease in signal output. Beam imaging is comparable to radiochromic films, and provides immediate images without hours of processing. Real-time data processing, taking less than 50 µs (combined data transfer and analysis times), has been implemented in firmware for 20 kHz frame rates for continuous proton beams.

A Prototype Scintillator Real-Time Beam Monitor for Ultra-high Dose Rate Radiotherapy.

Background: FLASH Radiotherapy (RT) is an emergent cancer radiotherapy modality where an entire therapeutic dose is delivered at more than 1000 times higher dose rate than conventional RT. For clinical trials to be conducted safely, a precise and fast beam monitor that can generate out-of-tolerance beam interrupts is required. This paper describes the overall concept and provides results from a prototype ultra-fast, scintillator-based beam monitor for both proton and electron beam FLASH applications. Purpose: A FLASH Beam Scintillator Monitor (FBSM) is being developed that employs a novel proprietary scintillator material. The FBSM has capabilities that conventional RT detector technologies are unable to simultaneously provide: 1) large area coverage; 2) a low mass profile; 3) a linear response over a broad dynamic range; 4) radiation hardness; 5) real-time analysis to provide an IEC-compliant fast beam-interrupt signal based on true two-dimensional beam imaging, radiation do-simetry and excellent spatial resolution. Methods: The FBSM uses a proprietary low mass, less than 0.5 mm water equivalent, non-hygroscopic, radiation tolerant scintillator material (designated HM: hybrid material) that is viewed by high frame rate CMOS cameras. Folded optics using mirrors enable a thin monitor profile of ~10 cm. A field programmable gate array (FPGA) data acquisition system (DAQ) generates real-time analysis on a time scale appropriate to the FLASH RT beam modality: 100-1000 Hz for pulsed electrons and 10-20 kHz for quasi-continuous scanning proton pencil beams. An ion beam monitor served as the initial development platform for this work and was tested in low energy heavy-ion beams (86Kr+26 and protons). A prototype FBSM was fabricated and then tested in various radiation beams that included FLASH level dose per pulse electron beams, and a hospital radiotherapy clinic with electron beams. Results: Results presented in this report include image quality, response linearity, radiation hardness, spatial resolution, and real-time data processing. The HM scintillator was found to be highly radiation damage resistant. It exhibited a small 0.025%/kGy signal decrease from a 216 kGy cumulative dose resulting from continuous exposure for 15 minutes at a FLASH compatible dose rate of 237 Gy/s. Measurements of the signal amplitude vs beam fluence demonstrate linear response of the FBSM at FLASH compatible dose rates of > 40 Gy/s. Comparison with commercial Gafchromic film indicates that the FBSM produces a high resolution 2D beam image and can reproduce a nearly identical beam profile, including primary beam tails. The spatial resolution was measured at 35-40 µm. Tests of the firmware beta version show successful operation at 20,000 Hz frame rate or 50 µs/frame, where the real-time analysis of the beam parameters is achieved in less than 1 µs. Conclusions: The FBSM is designed to provide real-time beam profile monitoring over a large active area without significantly degrading the beam quality. A prototype device has been staged in particle beams at currents of single particles up to FLASH level dose rates, using both continuous ion beams and pulsed electron beams. Using a novel scintillator, beam profiling has been demonstrated for currents extending from single particles to 10 nA currents. Radiation damage is minimal and even under FLASH conditions would require ≥ 50 kGy of accumulated exposure in a single spot to result in a 1% decrease in signal output. Beam imaging is comparable to radiochromic films, and provides immediate images without hours of processing. Real-time data processing, taking less than 50 µs (combined data transfer and analysis times), has been implemented in firmware for 20 kHz frame rates for continuous proton beams.

A Safe and Practical Cycle for Team-Based Development and Implementation of In-House Clinical Software.

PURPOSE: Due to a gap in published guidance, we describe our robust cycle of in-house clinical software development and implementation, which has been used for years to facilitate the safe treatment of all patients in our clinics. METHODS AND MATERIALS: Our software development and implementation cycle requires clarity in communication, clearly defined roles, thorough commissioning, and regular feedback. Cycle phases include design requirements and use cases, development, physics evaluation testing, clinical evaluation testing, and full clinical release. Software requirements, release notes, test suites, and a commissioning report are created and independently reviewed before clinical use. Software deemed to be high-risk, such as those that are writable to a database, incorporate the use of a formal, team-based hazard analysis. Incident learning is used to both guide initial development and improvements as well as to monitor the safe use of the software. RESULTS: Our standard process builds in transparency and establishes high expectations in the development and use of custom software to support patient care. Since moving to a commercial planning system platform in 2013, we have applied our team-based software release process to 16 programs related to scripting in the treatment planning system for the clinic. CONCLUSIONS: The principles and methodology described here can be implemented in a range of practice settings regardless of whether or not dedicated resources are available for software development. In addition to teamwork with defined roles, documentation, and use of incident learning, we strongly recommend having a written policy on the process, using phased testing, and incorporating independent oversight and approval before use for patient care. This rigorous process ensures continuous monitoring for and mitigatation of any high risk hazards.

A simulation study of ionizing radiation acoustic imaging (iRAI) as a real-time dosimetric technique for ultra-high dose rate radiotherapy (UHDR-RT).

PURPOSE: Electron-based ultra-high dose rate radiation therapy (UHDR-RT), also known as Flash-RT, has shown the ability to improve the therapeutic index in comparison to conventional radiotherapy (CONV-RT) through increased sparing of normal tissue. However, the extremely high dose rates in UHDR-RT have raised the need for accurate real-time dosimetry tools. This work aims to demonstrate the potential of the emerging technology of Ionized Radiation Acoustic Imaging (iRAI) through simulation studies and investigate its characteristics as a promising relative in vivo dosimetric tool for UHDR-RT. METHODS: The detection of induced acoustic waves following a single UHDR pulse of a modified 6 MeV 21EX Varian Clinac in a uniform porcine gelatin phantom that is brain-tissue equivalent was simulated for an ideal ultrasound transducer. The full 3D dose distributions in the phantom for a 1 × 1 cm2 field were simulated using EGSnrc (BEAMnrc∖DOSXYZnrc) Monte Carlo (MC) codes. The relative dosimetry simulations were verified with dose experimental measurements using Gafchromic films. The spatial dose distribution was converted into an initial pressure source spatial distribution using the medium-dependent dose-pressure relation. The MATLAB-based toolbox k-Wave was then used to model the propagation of acoustic waves through the phantom and perform time-reversal (TR)-based imaging reconstruction. The effect of the various linear accelerator (linac) operating parameters, including linac pulse duration and pulse repetition rate (frequency), were investigated as well. RESULTS: The MC dose simulation results agreed with the film measurement results, specifically at the central beam region up to 80% dose within approximately 5% relative error for the central profile region and a local relative error of <6% for percentage dose depth. IRAI-based FWHM of the radiation beam was within approximately 3 mm relative to the MC-simulated beam FWHM at the beam entrance. The real-time pressure signal change agreed with the dose changes proving the capability of the iRAI for predicting the beam position. IRAI was tested through 3D simulations of its response to be based on the temporal changes in the linac operating parameters on a dose per pulse basis as expected theoretically from the pressure-dose proportionality. The pressure signal amplitude obtained through 2D simulations was proportional to the dose per pulse. The instantaneous pressure signal amplitude decreases as the linac pulse duration increases, as predicted from the pressure wave generation equations, such that the shorter the linac pulse the higher the signal and the better the temporal (spatial) resolutions of iRAI. The effect of the longer linac pulse duration on the spatial resolution of the 3D constructed iRAI images was corrected for linac pulse deconvolution. This correction has improved the passing rate of the 1%/1 mm gamma test criteria, between the pressure-constructed and dosimetric beam characteristics, to as high as 98%. CONCLUSIONS: A full simulation workflow was developed for testing the effectiveness of iRAI as a promising relative dosimetry tool for UHDR-RT radiation therapy. IRAI has shown the advantage of 3D dose mapping through the dose signal linearity and, hence, has the potential to be a useful dosimeter at depth dose measurement and beam localization and, hence, potentially for in vivo dosimetry in UHDR-RT.

Changes in prostate orientation due to removal of a Foley catheter.

PURPOSE: Investigate the impact on prostate orientation caused by use and removal of a Foley catheter, and the dosimetric impact on men prospectively treated with prostate stereotactic body radiotherapy (SBRT). METHODS: Twenty-two men underwent a CT simulation with a Foley in place (FCT), followed immediately by a second treatment planning simulation without the Foley (TPCT). The change in prostate orientation was determined by rigid registration of three implanted transponders between FCT and TPCT and compared to measured orientation changes during treatment. The impact on treatment planning and delivery was investigated by analyzing the measured rotations during treatment relative to both CT scans, and introducing rotations of ±15° in the treatment plan to determine the maximum impact of allowed rotations. RESULTS: Removing the Foley caused a statistically significant prostate rotation (P < 0.0028) compared to normal biological motion in 60% of patients. The largest change in rotation due to removing a Foley occurs about the left-right axis (tilt) which has a standard deviation two to five times larger than changes in rotation about the Sup-Inf (roll) and Ant-Post (yaw) axes. The change in tilt due to removing a Foley for prone and supine patients was -1.1° ± 6.0° and 0.3° ± 7.4°, showing no strong directional bias. The average tilt during treatment was -1.6° ± 7.1° compared to the TPCT and would have been -2.0° ± 7.1° had the FCT been used as the reference. The TPCT was a better or equivalent representation of prostate tilt in 82% of patients, vs 50% had the FCT been used for treatment planning. However, 92.7% of fractions would still have been within the ±15° rotation limit if only the FCT were used for treatment planning. When rotated ±15°, urethra V105% = 38.85Gy  < 20% was exceeded in 27% of the instances, and prostate (CTV) coverage was maintained above D95%  > 37 Gy in all but one instance. CONCLUSIONS: Removing a Foley catheter can cause large prostate rotations. There does not appear to be a clear dosimetric benefit to obtaining the CT scan with a Foley catheter to define the urethra given the changes in urethral position from removing the Foley catheter. If urethral sparing is desired without the use of a Foley, utilization of an MRI to define the urethra may be necessary, or a pseudo-urethral planning organ at risk volume (PRV) may be used to limit dosimetric hot spots.

A multi-institutional phase 2 trial of prostate stereotactic body radiation therapy (SBRT) using continuous real-time evaluation of prostate motion with patient-reported quality of life.

PURPOSE: The use of stereotactic body radiation therapy (SBRT) for prostate cancer has been reported predominantly from single institutional studies, although concerns for broader adoption exist. METHODS AND MATERIALS: From 2011 through 2013, 66 men were accrued to a phase 2 trial at 5 centers. SBRT consisted of 5 fractions of 7.4 Gy to a total dose of 37 Gy using conventional linear accelerators. Electromagnetic transponders were used for motion management. Health-related quality of life (HRQOL) was evaluated via the Expanded Prostate Cancer Index Composite 26 questionnaire. Acute and late toxicities were collected according to Common Terminology Criteria for Adverse Events, version 4.0. Linear mixed modeling was performed to assess changes in HRQOL over time. RESULTS: Median follow-up was 36 months. All men had low- or intermediate-risk disease. There have been 0 biochemical recurrences. No grade 3 urinary or bowel toxicity was reported. Twenty-three percent of patients had acute grade 2 urinary toxicity, with 9% late grade 2 urinary toxicity. Four percent and 5% experienced acute or late grade 2+ bowel toxicity, respectively. Urinary bother and bowel HRQOL transiently decreased during the first 6 to 12 months post-SBRT, and then returned to baseline. In men with good erectile function at baseline, sexual HRQOL declined during the first 6 months and stabilized thereafter. On linear mixed modeling, the strongest predictor of sustained bowel and sexual HRQOL was baseline HRQOL. CONCLUSIONS: In this multi-institutional phase 2 clinical trial using continuous real-time evaluation of prostate motion, prostate SBRT has excellent intermediate-term tumor control with mild and expected treatment-related side effects.

Incorporating big data into treatment plan evaluation: Development of statistical DVH metrics and visualization dashboards.

PURPOSE: To develop statistical dose-volume histogram (DVH)-based metrics and a visualization method to quantify the comparison of treatment plans with historical experience and among different institutions. METHODS AND MATERIALS: The descriptive statistical summary (ie, median, first and third quartiles, and 95% confidence intervals) of volume-normalized DVH curve sets of past experiences was visualized through the creation of statistical DVH plots. Detailed distribution parameters were calculated and stored in JavaScript Object Notation files to facilitate management, including transfer and potential multi-institutional comparisons. In the treatment plan evaluation, structure DVH curves were scored against computed statistical DVHs and weighted experience scores (WESs). Individual, clinically used, DVH-based metrics were integrated into a generalized evaluation metric (GEM) as a priority-weighted sum of normalized incomplete gamma functions. Historical treatment plans for 351 patients with head and neck cancer, 104 with prostate cancer who were treated with conventional fractionation, and 94 with liver cancer who were treated with stereotactic body radiation therapy were analyzed to demonstrate the usage of statistical DVH, WES, and GEM in a plan evaluation. A shareable dashboard plugin was created to display statistical DVHs and integrate GEM and WES scores into a clinical plan evaluation within the treatment planning system. Benchmarking with normal tissue complication probability scores was carried out to compare the behavior of GEM and WES scores. RESULTS: DVH curves from historical treatment plans were characterized and presented, with difficult-to-spare structures (ie, frequently compromised organs at risk) identified. Quantitative evaluations by GEM and/or WES compared favorably with the normal tissue complication probability Lyman-Kutcher-Burman model, transforming a set of discrete threshold-priority limits into a continuous model reflecting physician objectives and historical experience. CONCLUSIONS: Statistical DVH offers an easy-to-read, detailed, and comprehensive way to visualize the quantitative comparison with historical experiences and among institutions. WES and GEM metrics offer a flexible means of incorporating discrete threshold-prioritizations and historic context into a set of standardized scoring metrics. Together, they provide a practical approach for incorporating big data into clinical practice for treatment plan evaluations.

SafetyNet: Streamlining and Automating QA in radiotherapy.

Proper quality assurance (QA) of the radiotherapy process can be time-consuming and expensive. Many QA efforts, such as data export and import, are inefficient when done by humans. Additionally, humans can be unreliable, lose attention, and fail to complete critical steps that are required for smooth operations. In our group we have sought to break down the QA tasks into separate steps and to automate those steps that are better done by software running autonomously or at the instigation of a human. A team of medical physicists and software engineers worked together to identify opportunities to streamline and automate QA. Development efforts follow a formal cycle of writing software requirements, developing software, testing and commissioning. The clinical release process is separated into clinical evaluation testing, training, and finally clinical release. We have improved six processes related to QA and safety. Steps that were previously performed by humans have been automated or streamlined to increase first-time quality, reduce time spent by humans doing low-level tasks, and expedite QA tests. Much of the gains were had by automating data transfer, implementing computer-based checking and automation of systems with an event-driven framework. These coordinated efforts by software engineers and clinical physicists have resulted in speed improvements in expediting patient-sensitive QA tests.

A measurement technique to determine the calibration accuracy of an electromagnetic tracking system to radiation isocenter.

PURPOSE: To present and characterize a measurement technique to quantify the calibration accuracy of an electromagnetic tracking system to radiation isocenter. METHODS: This technique was developed as a quality assurance method for electromagnetic tracking systems used in a multi-institutional clinical hypofractionated prostate study. In this technique, the electromagnetic tracking system is calibrated to isocenter with the manufacturers recommended technique, using laser-based alignment. A test patient is created with a transponder at isocenter whose position is measured electromagnetically. Four portal images of the transponder are taken with collimator rotations of 45° 135°, 225°, and 315°, at each of four gantry angles (0°, 90°, 180°, 270°) using a 3×6 cm2 radiation field. In each image, the center of the copper-wrapped iron core of the transponder is determined. All measurements are made relative to this transponder position to remove gantry and imager sag effects. For each of the 16 images, the 50% collimation edges are identified and used to find a ray representing the rotational axis of each collimation edge. The 16 collimator rotation rays from four gantry angles pass through and bound the radiation isocenter volume. The center of the bounded region, relative to the transponder, is calculated and then transformed to tracking system coordinates using the transponder position, allowing the tracking system's calibration offset from radiation isocenter to be found. All image analysis and calculations are automated with inhouse software for user-independent accuracy. Three different tracking systems at two different sites were evaluated for this study. RESULTS: The magnitude of the calibration offset was always less than the manufacturer's stated accuracy of 0.2 cm using their standard clinical calibration procedure, and ranged from 0.014 to 0.175 cm. On three systems in clinical use, the magnitude of the offset was found to be 0.053±0.036, 0.121±0.023, and 0.093±0.013 cm. CONCLUSIONS: The method presented here provides an independent technique to verify the calibration of an electromagnetic tracking system to radiation isocenter. The calibration accuracy of the system was better than the 0.2 cm accuracy stated by the manufacturer. However, it should not be assumed to be zero, especially for stereotactic radiation therapy treatments where planning target volume margins are very small.

Randomized phase II trial of urethral sparing intensity modulated radiation therapy in low-risk prostate cancer: implications for focal therapy.

BACKGROUND: Low-risk prostate cancer (PCa) patients have excellent outcomes, with treatment modality often selected by perceived effects on quality of life. Acute urinary symptoms are common during external beam radiotherapy (EBRT), while chronic symptoms have been linked to urethral dose. Since most low-risk PCa occurs in the peripheral zone (PZ), we hypothesized that EBRT using urethral sparing intensity modulated radiation therapy (US-IMRT) could improve urinary health-related quality of life (HRQOL) while maintaining high rates of PCa control. METHODS: Patients with National Comprehensive Cancer Network (NCCN) defined low-risk PCa with no visible lesion within 5 mm of the prostatic urethra on MRI were randomized to US-IMRT or standard (S-) IMRT. Prescription dose was 75.6 Gy in 41 fractions to the PZ + 3-5 mm for US-IMRT and to the prostate + 3 mm for S-IMRT. For US-IMRT, mean proximal and distal urethral doses were limited to 65 Gy and 74 Gy, respectively. HRQOL was assessed using the Expanded Prostate Cancer Index (EPIC) Quality of Life questionnaire. The primary endpoint was change in urinary HRQOL at 3 months. RESULTS: From June 2004 to November 2006, 16 patients were randomized, after which a futility analysis concluded that continued accrual was unlikely to demonstrate a difference in the primary endpoint. Mean change in EPIC urinary HRQOL at 3 months was -0.5 ± 11.2 in the US-IMRT arm and +3.9 ± 15.3 in the S-IMRT arm (p = 0.52). Median PSA nadir was higher in the US-IMRT arm (1.46 vs. 0.78, p = 0.05). At 4.7 years median follow-up, three US-IMRT and no S-IMRT patients experienced PSA failure (p = 0.06; HR 8.8, 95% CI 0.9-86). Two out of 3 patients with PSA failure had biopsy-proven local failure, both located contralateral to the original site of disease. CONCLUSIONS: Compared with S-IMRT, US-IMRT failed to improve urinary HRQOL and resulted in higher PSA nadir and inferior biochemical control. The high rate of PSA failure and contralateral local failures in US-IMRT patients, despite careful selection of MRI-screened low-risk patients, serve as a cautionary tale for focal PCa treatments.

Prostate intrafraction translation margins for real-time monitoring and correction strategies.

The purpose of this work is to determine appropriate radiation therapy beam margins to account for intrafraction prostate translations for use with real-time electromagnetic position monitoring and correction strategies. Motion was measured continuously in 35 patients over 1157 fractions at 5 institutions. This data was studied using van Herk's formula of (αΣ + γσ') for situations ranging from no electromagnetic guidance to automated real-time corrections. Without electromagnetic guidance, margins of over 10 mm are necessary to ensure 95% dosimetric coverage while automated electromagnetic guidance allows the margins necessary for intrafraction translations to be reduced to submillimeter levels. Factors such as prostate deformation and rotation, which are not included in this analysis, will become the dominant concerns as margins are reduced. Continuous electromagnetic monitoring and automated correction have the potential to reduce prostate margins to 2-3 mm, while ensuring that a higher percentage of patients (99% versus 90%) receive a greater percentage (99% versus 95%) of the prescription dose.

Dosimetric impact of density variations in Solid Water 457 water-equivalent slabs.

The purpose of this study was to determine the dosimetric impact of density variations observed in water-equivalent solid slabs. Measurements were performed using two 30 cm × 30 cm water-equivalent slabs, one being 4 cm think and the other 5 cm thick. The location and extent of density variations were determined by computed tomography (CT) scans. Additional imaging measurements were made with an amorphous silicon megavoltage portal imaging device and an ultrasound unit. Dosimetric measurements were conducted with a 2D ion chamber array, and a scanned diode in water. Additional measurements and calculations were made of small rectilinear void inhomogeneities formed with water-equivalent slabs, using a 2D ion chamber array and the convolution superposition algorithm. Two general types of density variation features were observed on CT images: 1) regions of many centimeters across, but typically only a few millimeters thick, with electron densities a few percent lower than the bulk material, and 2) cylindrical regions roughly 0.2 cm in diameter and up to 20 cm long with electron densities up to 5% lower than the surrounding material. The density variations were not visible on kilovoltage, megavoltage or ultrasound images. The dosimetric impact of the density variations were not detectable to within 0.1% using the 2D ion chamber array or the scanning photon diode at distances 0.4 cm to 2 cm beyond the features. High-resolution dosimetric calculations using the convolution-superposition algorithm with density corrections enabled on CT-based datasets showed no discernable dosimetric impact. Calculations and measurements on simulated voids place the upper limit on possible dosimetric variations from observed density variations at much less than 0.6%. CT imaging of water-equivalent slabs may reveal density variations which are otherwise unobserved with kV, MV, or ultrasound imaging. No dosimetric impact from these features was measureable with an ion chamber array or scanned photon diode. Consequently, they were determined to be acceptable for all clinical use.

Relativistic plasma shutter for ultraintense laser pulses.

A relativistic plasma shutter technique is proposed and tested to remove the sub-100 ps pedestal of a high-intensity laser pulse. The shutter is an ultrathin foil placed before the target of interest. As the leading edge of the laser ionizes the shutter material it will expand into a relativistically underdense plasma allowing for the peak pulse to propagate through while rejecting the low intensity pedestal. An increase in the laser temporal contrast is demonstrated by measuring characteristic signatures in the accelerated proton spectra and directionality from the interaction of 30 TW pulses with ultrathin foils along with supporting hydrodynamic and particle-in-cell simulations.

A precision translation stage for reproducing measured target volume motions.

The development of 4D imaging, treatment planning and treatment delivery methods for radiation therapy require the use of a high-precision translation stage for testing and validation. These technologies may require spatial resolutions of 1 mm, and temporal resolutions of 2-30 Hz for CT imaging, electromagnetic tracking, and fluoroscopic imaging. A 1D programmable translation stage capable of reproducing idealized and measured anatomic motions common to the thorax has been design and built to meet these spatial and temporal resolution requirement with phantoms weighing up to 27 kg. The stage consists of a polycarbonate base and table, driven by an AC servo motor with encoder feedback by means of a belt-coupled precision screw. Complex motions are possible through a programmable motion controller that is capable of running multiple independent control and monitoring programs concurrently. Programmable input and output ports allow motion to be synchronized with beam delivery and other imaging and treatment delivery devices to within 2.0 ms. Average deviations from the programmed positions are typically 0.2 mm or less, while the average typical maximum positional errors are typically 0.5 mm for an indefinite number of idealized breathing motion cycles and while reproducing measured target volume motions for several minutes.

Positional stability of electromagnetic transponders used for prostate localization and continuous, real-time tracking.

PURPOSE: To determine the relative positional stability of implanted glass-encapsulated circuits (transponders) used in continuous electromagnetic localization and tracking of target volumes during radiation therapy. Ideally, the distances between transponders remains constant over the course of treatment. In this work, we evaluate the accuracy of these conditions. METHODS AND MATERIALS: Three transponders were implanted in each of 20 patients. Images (CT scan or X-ray pair) were acquired at 13 time points. These images occurred from the day of implant (2 weeks before simulation) to 4 weeks posttreatment. The distance between transponders was determined from each dataset. The average and standard deviation of each distance were determined, and changes were evaluated over several time periods, including pretreatment and during therapy. RESULTS: Of 60 transponders implanted, 58 showed no significant migration from their intended positions. Of the two transponders that did migrate, one appears to have been implanted in the venous plexus, and the other in the urethra, with no clinical consequences to the patients. An analysis that included the planning CT scan and all subsequent distance measurements showed that the standard deviation of intertransponder distances was < or =1.2 mm for up to 1 month after the completion of therapy. CONCLUSIONS: Implanted transponders demonstrate the same long-term stability characteristics as implanted gold markers, within statistical uncertainties. As with gold markers, and using the same implant procedure, basic guidelines for the placement of transponders within the prostate help ensure minimal migration.

Experimental verification of a Monte Carlo-based MLC simulation model for IMRT dose calculation.

Inter- and intra-leaf transmission and head scatter can play significant roles in intensity modulated radiation therapy (IMRT)-based treatment deliveries. In order to accurately calculate the dose in the IMRT planning process, it is therefore important that the detailed geometry of the multi-leaf collimator (MLC), in addition to other components in the accelerator treatment head, be accurately modeled. In this paper, we have used the Monte Carlo method (MC) to develop a comprehensive model of the Varian 120 leaf MLC and have compared it against measurements in homogeneous phantom geometries under different IMRT delivery circumstances. We have developed a geometry module within the DPM MC code to simulate the detailed MLC design and the collimating jaws. Tests consisting of leakage, leaf positioning and static MLC shapes were performed to verify the accuracy of transport within the MLC model. The calculations show agreement within 2% in the high dose region for both film and ion-chamber measurements for these static shapes. Clinical IMRT treatment plans for the breast [both segmental MLC (SMLC) and dynamic MLC (DMLC)], prostate (SMLC) and head and neck split fields (SMLC) were also calculated and compared with film measurements. Such a range of cases were chosen to investigate the accuracy of the model as a function of modulation in the beamlet pattern, beamlet width, and field size. The overall agreement is within 2% /2 mm of the film data for all IMRT beams except the head and neck split field, which showed differences up to 5% in the high dose regions. Various sources of uncertainties in these comparisons are discussed.

Synchronized dynamic dose reconstruction.

Variations in target volume position between and during treatment fractions can lead to measurable differences in the dose distribution delivered to each patient. Current methods to estimate the ongoing cumulative delivered dose distribution make idealized assumptions about individual patient motion based on average motions observed in a population of patients. In the delivery of intensity modulated radiation therapy (IMRT) with a multi-leaf collimator (MLC), errors are introduced in both the implementation and delivery processes. In addition, target motion and MLC motion can lead to dosimetric errors from interplay effects. All of these effects may be of clinical importance. Here we present a method to compute delivered dose distributions for each treatment beam and fraction, which explicitly incorporates synchronized real-time patient motion data and real-time fluence and machine configuration data. This synchronized dynamic dose reconstruction method properly accounts for the two primary classes of errors that arise from delivering IMRT with an MLC: (a) Interplay errors between target volume motion and MLC motion, and (b) Implementation errors, such as dropped segments, dose over/under shoot, faulty leaf motors, tongue-and-groove effect, rounded leaf ends, and communications delays. These reconstructed dose fractions can then be combined to produce high-quality determinations of the dose distribution actually received to date, from which individualized adaptive treatment strategies can be determined.

Target localization and real-time tracking using the Calypso 4D localization system in patients with localized prostate cancer.

PURPOSE: The Calypso 4D Localization System is being developed to provide accurate, precise, objective, and continuous target localization during radiotherapy. This study involves the first human use of the system, to evaluate the localization accuracy of this technique compared with radiographic localization and to assess its ability to obtain real-time prostate-motion information. METHODS AND MATERIALS: Three transponders were implanted in each of 20 patients. Eleven eligible patients of the 20 patients participated in a study arm that compared radiographic triangulated transponder locations to electromagnetically recorded transponder locations. Transponders were tracked for 8-min periods. RESULTS: The implantations were all successful, with no major complications. Intertransponder distances were largely stable. Comparison of the patient localization on the basis of transponder locations as per the Calypso system with the radiographic transponder localization showed an average (+/-SD) 3D difference of 1.5 +/- 0.9 mm. Upon tracking during 8 min, 2 of the 11 patients showed significant organ motion (>1 cm), with some motion lasting longer that 1 min. CONCLUSION: Calypso transponders can be used as magnetic intraprostatic fiducials. Clinical evaluation of this novel 4D nonionizing electromagnetic localization system with transponders indicates a comparable localization accuracy to isocenter, (within 2 mm) compared with X-ray localization.

Influence of intrafraction motion on margins for prostate radiotherapy.

PURPOSE: To assess the impact of intrafraction intervention on margins for prostate radiotherapy. METHODS AND MATERIALS: Eleven supine prostate patients with three implanted transponders were studied. The relative transponder positions were monitored for 8 min and combined with previously measured data on prostate position relative to skin marks. Margins were determined for situations of (1) skin-based positioning, and (2) pretreatment transponder positioning. Intratreatment intervention was simulated assuming conditions of (1) continuous tracking, and (2) a 3-mm threshold for position correction. RESULTS: For skin-based setup without and with inclusion of intrafraction motion, prostate treatments would have required average margins of 8.0, 7.3, and 10.0 mm and 8.2, 10.2, and 12.5 mm, about the left-right, anterior-posterior, and cranial-caudal directions, respectively. Positioning by prostate markers at the start of the treatment fraction reduced these values to 1.8, 5.8, and 7.1 mm, respectively. Interbeam adjustment further reduced margins to an average of 1.4, 2.3, and 1.8 mm. Intrabeam adjustment yielded margins of 1.3, 1.5, and 1.5 mm, respectively. CONCLUSION: Significant reductions in margins might be achieved by repositioning the patient before each beam, either radiographically or electromagnetically. However, 2 of the 11 patients would have benefited from continuous target tracking and threshold-based intervention.