CT-less electron radiotherapy simulation and planning with a consumer 3D camera.

PURPOSE: Electron radiation therapy dose distributions are affected by irregular body surface contours. This study investigates the feasibility of three-dimensional (3D) cameras to substitute for the treatment planning computerized tomography (CT) scan by capturing the body surfaces to be treated for accurate electron beam dosimetry. METHODS: Dosimetry was compared for six electron beam treatments to the nose, toe, eye, and scalp using full CT scan, CT scan with Hounsfield Unit (HU) overridden to water (mimic 3D camera cases), and flat-phantom techniques. Radiation dose was prescribed to a depth on the central axis per physician's order, and the monitor units (MUs) were calculated. The 3D camera spatial accuracy was evaluated by comparing the 3D surface of a head phantom captured by a 3D camera and that generated with the CT scan in the treatment planning system. A clinical case is presented, and MUs were calculated using the 3D camera body contour with HU overridden to water. RESULTS: Across six cases the average change in MUs between the full CT and the 3Dwater (CT scan with HU overridden to water) calculations was 1.3% with a standard deviation of 1.0%. The corresponding hotspots had a mean difference of 0.4% and a standard deviation of 1.9%. The 3D camera captured surface of a head phantom was found to have a 0.59 mm standard deviation from the surface derived from the CT scan. In-vivo dose measurements (213 ± 8 cGy) agreed with the 3D-camera planned dose of 209 ± 6 cGy, compared to 192 ± 6 cGy for the flat-phantom calculation (same MUs). CONCLUSIONS: Electron beam dosimetry is affected by irregular body surfaces. 3D cameras can capture irregular body contours which allow accurate dosimetry of electron beam treatment as an alternative to costly CT scans with no extra exposure to radiation. Tools and workflow for clinical implementation are provided.

Optimizing efficiency and safety in external beam radiotherapy using automated plan check (APC) tool and six sigma methodology.

PURPOSE: To develop and implement an automated plan check (APC) tool using a Six Sigma methodology with the aim of improving safety and efficiency in external beam radiotherapy. METHODS: The Six Sigma define-measure-analyze-improve-control (DMAIC) framework was used by measuring defects stemming from treatment planning that were reported to the departmental incidence learning system (ILS). The common error pathways observed in the reported data were combined with our departmental physics plan check list, and AAPM TG-275 identified items. Prioritized by risk priority number (RPN) and severity values, the check items were added to the APC tool developed using Varian Eclipse Scripting Application Programming Interface (ESAPI). At 9 months post-APC implementation, the tool encompassed 89 check items, and its effectiveness was evaluated by comparing RPN values and rates of reported errors. To test the efficiency gains, physics plan check time and reported error rate were prospectively compared for 20 treatment plans. RESULTS: The APC tool was successfully implemented for external beam plan checking. FMEA RPN ranking re-evaluation at 9 months post-APC demonstrated a statistically significant average decrease in RPN values from 129.2 to 83.7 (P < .05). After the introduction of APC, the average frequency of reported treatment-planning errors was reduced from 16.1% to 4.1%. For high-severity errors, the reduction was 82.7% for prescription/plan mismatches and 84.4% for incorrect shift note. The process shifted from 4σ to 5σ quality for isocenter-shift errors. The efficiency study showed a statistically significant decrease in plan check time (10.1 ± 7.3 min, P = .005) and decrease in errors propagating to physics plan check (80%). CONCLUSIONS: Incorporation of APC tool has significantly reduced the error rate. The DMAIC framework can provide an iterative and robust workflow to improve the efficiency and quality of treatment planning procedure enabling a safer radiotherapy process.

Chemoradiation impairs normal developmental cortical thinning in medulloblastoma.

Medulloblastoma patients are treated with surgery, radiation and chemotherapy. Radiation dose to the temporal lobe may be associated with neurocognitive sequelae. Longitudinal changes of temporal lobe cortical thickness may result from neurodevelopmental processes such as synaptic pruning. This study applies longitudinal image analysis to compare developmental change in cortical thickness in medulloblastoma (MB) patients who were treated by combined modality therapy to that of cerebellar juvenile pilocytic astrocytoma (JPA) patients who were treated by surgery alone. We hypothesized that the rates of developmental change in cortical thickness would differ between these two groups. This retrospective cohort study assessed changes in cortical thickness over time between MB and JPA patients. High-resolution magnetic resonance (MR) images of 14 MB and 7 JPA subjects were processed to measure cortical thickness of bilateral temporal lobe substructures. A linear mixed effects model was used to identify differences in substructure longitudinal changes in cortical thickness. The left temporal lobe exhibited overall increased cortical thickness in MB patients relative to JPA patients who showed overall cortical thinning (mean annual cortical thickness change: MB 0.14 mm/year versus JPA -0.018 mm/year across all substructures), particularly in the inferior temporal lobe substructures (p < 0.0001). The cortical thickness change of the right temporal lobe substructures exhibited similar, though attenuated trends (p = 0.002). MB patients exhibit overall increased cortical thickness rather than cortical thinning as seen in JPA patients and as expected in normal cortical development. These observations are possibly due to chemoradiation induced-disruption of normal neuronal mechanisms. Longitudinal image analysis may identify early biomarkers for neurocognitive function with routine imaging.

AVATAR 2.0: next level communication systems for radiotherapy through face-to-face video, biofeedback, translation, and audiovisual immersion.

Purpose: This paper discusses an advanced version of our audiovisual-assisted therapeutic ambience in radiotherapy (AVATAR) radiolucent display systems designed for pediatric radiotherapy, enabling anesthesia-free treatments, video communication, and biofeedback. The scope of the AVATAR system is expanded here in two major ways: (i) through alternative mounting systems to accommodate a broader range of radiotherapy machines (specifically to fit robotic-arm and toroidal geometry photon radiotherapy and proton radiotherapy systems) and (ii) through additional hardware to provide video-calling, optimized audio for clear communication, and combined video inputs for biofeedback, translation, and other advanced functionalities. Methods and materials: Because robustness requires strong parts and radio-transparency requires thin, light parts, three-dimensional printing was used to rapidly prototype hollow structures and to iteratively improve robustness. Two system designs were made: one that mounts superior and another that mounts inferior to the patient's head. Radiation dose measurements and calculations were conducted to assess dose perturbations at surface and depth due to the screen. Results: For 6-MV volumetric modulated arc therapy (VMAT) plans, with and without the screen, the mean and maximum dose differences inside the planning target volume were 0.2% and 2.6% of the 200 cGy prescription, respectively. For a single static beam through the screen, the maximum measured excess surface dose was 13.4 ± 0.5%, and the largest measured dose attenuation at 5-cm water-equivalent depth was 2.1 ± 0.2%. These percentages are relative to the dose without the screen at those locations. Conclusions: The radiolucent screen systems provided here are shown to give minimal dosimetric effects on megavoltage VMAT photon treatments. For static beams, however, surface dose effects should be considered when these beams pass through the thickest components of the screen. Design files are also provided.

Dosimetric calibration of anatomy-specific ultra-high dose rate electron irradiation platform for preclinical FLASH radiobiology experiments.

BACKGROUND: FLASH radiation therapy (RT) offers a promising avenue for the broadening of the therapeutic index. However, to leverage the full potential of FLASH in the clinical setting, an improved understanding of the biological principles involved is critical. This requires the availability of specialized equipment optimized for the delivery of conventional (CONV) and ultra-high dose rate (UHDR) irradiation for preclinical studies. One method to conduct such preclinical radiobiological research involves adapting a clinical linear accelerator configured to deliver both CONV and UHDR irradiation. PURPOSE: We characterized the dosimetric properties of a clinical linear accelerator configured to deliver ultra-high dose rate irradiation to two anatomic sites in mice and for cell-culture FLASH radiobiology experiments. METHODS: Delivered doses of UHDR electron beams were controlled by a microcontroller and relay interfaced with the respiratory gating system. We also produced beam collimators with indexed stereotactic mouse positioning devices to provide anatomically specific preclinical treatments. Treatment delivery was monitored directly with an ionization chamber, and charge measurements were correlated with radiochromic film measurements at the entry surface of the mice. The setup for conventional dose rate irradiation utilized the same collimation system but at increased source-to-surface distance. Monte Carlo simulations and film dosimetry were used to characterize beam properties and dose distributions. RESULTS: The mean electron beam energies before the flattening filter were 18.8 MeV (UHDR) and 17.7 MeV (CONV), with corresponding values at the mouse surface of 17.2 and 16.2 MeV. The charges measured with an external ion chamber were linearly correlated with the mouse entrance dose. The use of relay gating for pulse control initially led to a delivery failure rate of 20% (± 1 pulse); adjustments to account for the linac latency improved this rate to < 1/20. Beam field sizes for two anatomically specific mouse collimators (4 × 4 cm2 for whole-abdomen and 1.5 × 1.5 cm2 for unilateral lung irradiation) were accurate within < 5% and had low radiation leakage (< 4%). Normalizing the dose at the center of the mouse (∼0.75 cm depth) produced UHDR and CONV doses to the irradiated volumes with > 95% agreement. CONCLUSION: We successfully configured a clinical linear accelerator for increased output and developed a robust preclinical platform for anatomically specific irradiation, with highly accurate and precise temporal and spatial dose delivery, for both CONV and UHDR irradiation applications.

Integrating Audiovisual Immersion Into Pediatric Radiation Therapy Across Multiple Centers: Methodology, Timeliness, and Cost of the Audiovisual-Assisted Therapeutic Ambience in Radiation Therapy Prospective Multi-Institutional Trial.

Purpose: The Audiovisual-Assisted Therapeutic Ambience in Radiotherapy (AVATAR) trial was a prospective multicenter study (NCT03991156) examining the combination of video immersion with radiation therapy and was successfully conducted through the collaboration of pediatric radiation oncology teams at 10 institutions independent of any pre-existing consortium. We sought to analyze and report the methodology of trial conception and development, process map, and cost. Methods and Materials: The study enrolled patients aged 3 to 10 years preparing to undergo radiation therapy, integrated the combination of AVATAR-based video immersion with radiation therapy at each institution, and offered AVATAR use as an alternative to anesthesia, with rates of anesthesia use and outcomes of serial standardized anxiety and quality-of-life assessments assessed among the 81 children enrolled. A process map was created based on the trial timeline with the following components: study development time (time from conception of the trial to the accrual of the first patient, including design phase, agreement and approval phase, and site preparation phase), and accrual duration time (time from the first to last accrual). Costs and institutional success rates were calculated. Results: Time from inception of study to last accrual was 3.6 years (1313 days). The study development time was 417 days (31.7%), and accrual duration time was 896 days (68.3%), with the final 50% of accrual occurring in <6 months. Equipment cost was approximately $550 per institution and was covered by funding from the lead study institution. All 10 centers were successful with AVATAR implementation, defined as ≥50% of patients able to avoid anesthesia with the use of AVATAR, including centers with both photon and proton therapy. Conclusions: This report elaborates on the methodology and timeline of trial conception and development using data from a previously published supportive care study combining video immersion with radiation therapy among 10 cooperating pediatric oncology institutions. It highlights the potential for multicenter collaborations on prospective trials integrating supportive care therapies with radiation therapy.

FLASH-RT does not affect chromosome translocations and junction structures beyond that of CONV-RT dose-rates.

BACKGROUND AND PURPOSE: The impact of radiotherapy (RT) at ultra high vs conventional dose rate (FLASH vs CONV) on the generation and repair of DNA double strand breaks (DSBs) is an important question that remains to be investigated. Here, we tested the hypothesis as to whether FLASH-RT generates decreased chromosomal translocations compared to CONV-RT. MATERIALS AND METHODS: We used two FLASH validated electron beams and high-throughput rejoin and genome-wide translocation sequencing (HTGTS-JoinT-seq), employing S. aureus and S. pyogenes Cas9 "bait" DNA double strand breaks (DSBs) in HEK239T cells, to measure differences in bait-proximal repair and their genome-wide translocations to "prey" DSBs generated after various irradiation doses, dose rates and oxygen tensions (normoxic, 21% O2; physiological, 4% O2; hypoxic, 2% and 0.5% O2). Electron irradiation was delivered using a FLASH capable Varian Trilogy and the eRT6/Oriatron at CONV (0.08-0.13 Gy/s) and FLASH (1x102-5x106 Gy/s) dose rates. Related experiments using clonogenic survival and γH2AX foci in the 293T and the U87 glioblastoma lines were also performed to discern FLASH-RT vs CONV-RT DSB effects. RESULTS: Normoxic and physioxic irradiation of HEK293T cells increased translocations at the cost of decreasing bait-proximal repair but were indistinguishable between CONV-RT and FLASH-RT. Although no apparent increase in chromosome translocations was observed with hypoxia-induced apoptosis, the combined decrease in oxygen tension with IR dose-rate modulation did not reveal significant differences in the level of translocations nor in their junction structures. Furthermore, RT dose rate modality on U87 cells did not change γH2AX foci numbers at 1- and 24-hours post-irradiation nor did this affect 293T clonogenic survival. CONCLUSION: Irrespective of oxygen tension, FLASH-RT produces translocations and junction structures at levels and proportions that are indistinguishable from CONV-RT.

FLASH-RT does not affect chromosome translocations and junction structures beyond that of CONV-RT dose-rates.

The molecular and cellular mechanisms driving the enhanced therapeutic ratio of ultra-high dose-rate radiotherapy (FLASH-RT) over slower conventional (CONV-RT) radiotherapy dose-rate remain to be elucidated. However, attenuated DNA damage and transient oxygen depletion are among several proposed models. Here, we tested whether FLASH-RT under physioxic (4% O 2 ) and hypoxic conditions (≤2% O 2 ) reduces genome-wide translocations relative to CONV-RT and whether any differences identified revert under normoxic (21% O 2 ) conditions. We employed high-throughput rejoin and genome-wide translocation sequencing ( HTGTS-JoinT-seq ), using S. aureus and S. pyogenes Cas9 "bait" DNA double strand breaks (DSBs), to measure differences in bait-proximal repair and their genome-wide translocations to "prey" DSBs generated by electron beam CONV-RT (0.08-0.13Gy/s) and FLASH-RT (1×10 2 -5×10 6 Gy/s), under varying ionizing radiation (IR) doses and oxygen tensions. Normoxic and physioxic irradiation of HEK293T cells increased translocations at the cost of decreasing bait-proximal repair but were indistinguishable between CONV-RT and FLASH-RT. Although no apparent increase in chromosome translocations was observed with hypoxia-induced apoptosis, the combined decrease in oxygen tension with IR dose-rate modulation did not reveal significant differences in the level of translocations nor in their junction structures. Thus, Irrespective of oxygen tension, FLASH-RT produces translocations and junction structures at levels and proportions that are indistinguishable from CONV-RT.

Feasibility of the Audio-Visual Assisted Therapeutic Ambience in Radiotherapy (AVATAR) System for Anesthesia Avoidance in Pediatric Patients: A Multicenter Trial.

PURPOSE: The Audio-Visual Assisted Therapeutic Ambience in Radiotherapy (AVATAR) system was the first published radiation therapy (RT)-compatible system to reduce the need for pediatric anesthesia through video-based distraction. We evaluated the feasibility of AVATAR implementation and effects on anesthesia use, quality of life, and anxiety in a multicenter pediatric trial. METHODS AND MATERIALS: Pediatric patients 3 to 10 years of age preparing to undergo RT at 10 institutions were prospectively enrolled. Children able to undergo at least 1 fraction of RT using AVATAR without anesthesia were considered successful (S). Patients requiring anesthesia for their entire treatment course were nonsuccessful (NS). The PedsQL3.0 Cancer Module (PedsQL) survey assessed quality of life and was administered to the patient and guardian at RT simulation, midway through RT, and at final treatment. The modified Yale Preoperative Anxiety Scale (mYPAS) assessed anxiety and was performed at the same 3 time points. Success was evaluated using the χ2 test. PedsQL and mYPAS scores were assessed using mixed effects models with time points evaluated as fixed effects and a random intercept on the subject. RESULTS: Eighty-one children were included; median age was 7 years. AVATAR was successful at all 10 institutions and with photon and proton RT. There were 63 (78%) S patients; anesthesia was avoided for a median of 20 fractions per patient. Success differed by age (P = .04) and private versus public insurance (P < .001). Both patient (P = .008) and parent (P = .006) PedsQL scores significantly improved over the course of RT for patients aged 5 to 7. Anxiety in the treatment room decreased for both S and NS patients over RT course (P < .001), by age (P < .001), and by S versus NS patients (P < .001). CONCLUSIONS: In this 10-center prospective trial, anesthesia avoidance with AVATAR was 78% in children aged 3 to 10 years, higher than among age-matched historical controls (49%; P < .001). AVATAR implementation is feasible across multiple institutions and should be further studied and made available to patients who may benefit from video-based distraction.

Acute and Late Esophageal Toxicity After SABR to Thoracic Tumors Near or Abutting the Esophagus.

PURPOSE: Our purpose was to evaluate the incidence of acute and late esophageal toxicity in patients with thoracic tumors near or abutting the esophagus treated with SABR. METHODS AND MATERIALS: Among patients with thoracic tumors treated with SABR, we identified those with tumors near or abutting the esophagus. Using the linear-quadratic model with an α/ß ratio of 10, we determined the correlation between dosimetric parameters and esophageal toxicity graded using the Common Terminology Criteria for Adverse Events, version 5.0. RESULTS: Out of 2200 patients treated with thoracic SABR, 767 patients were analyzable for esophageal dosimetry. We identified 55 patients with tumors near the esophagus (52 evaluable for esophagitis grade) and 28 with planning target volume (PTV) overlapping the esophagus. Dose gradients across the esophagus were consistently sharp. Median follow-up and overall survival were 16 and 23 months, respectively. Thirteen patients (25%) developed temporary grade 2 acute esophageal toxicity, 11 (85%) of whom had PTV overlapping the esophagus. Symptoms resolved within 1 to 3 months in 12 patients and 6 months in all patients. No grade 3 to 5 toxicity was observed. Only 3 patients (6%) developed late or persistent grade 2 dysphagia or dyspepsia of uncertain relationship to SABR. The cumulative incidence of acute esophagitis was 15% and 25% at 14 and 60 days, respectively. Acute toxicity correlated on univariate analysis with esophageal Dmax, D1cc, D2cc, Dmax/Dprescription, and whether the PTV was overlapping the esophagus. Esophageal Dmax (BED10) <62 Gy, D1cc (BED10) <48 Gy, D2cc (BED10) <43 Gy, and Dmax/Dprescription <85% were associated with <20% risk of grade 2 acute esophagitis. Only 2 local recurrences occurred. CONCLUSIONS: Although 25% of patients with tumors near the esophagus developed acute esophagitis (39% of those with PTV overlapping the esophagus), these toxicities were all grade 2 and all temporary. This suggests the safety and efficacy of thoracic SABR for tumors near or abutting the esophagus when treating with high conformity and sharp dose gradients.

Design and validation of a dosimetric comparison scheme tailored for ultra-high dose-rate electron beams to support multicenter FLASH preclinical studies.

BACKGROUND AND PURPOSE: We describe a multicenter cross validation of ultra-high dose rate (UHDR) (>= 40 Gy/s) irradiation in order to bring a dosimetric consensus in absorbed dose to water. UHDR refers to dose rates over 100-1000 times those of conventional clinical beams. UHDR irradiations have been a topic of intense investigation as they have been reported to induce the FLASH effect in which normal tissues exhibit reduced toxicity relative to conventional dose rates. The need to establish optimal beam parameters capable of achieving the in vivo FLASH effect has become paramount. It is therefore necessary to validate and replicate dosimetry across multiple sites conducting UHDR studies with distinct beam configurations and experimental set-ups. MATERIALS AND METHODS: Using a custom cuboid phantom with a cylindrical cavity (5 mm diameter by 10.4 mm length) designed to contain three type of dosimeters (thermoluminescent dosimeters (TLDs), alanine pellets, and Gafchromic films), irradiations were conducted at expected doses of 7.5 to 16 Gy delivered at UHDR or conventional dose rates using various electron beams at the Radiation Oncology Departments of the CHUV in Lausanne, Switzerland and Stanford University, CA. RESULTS: Data obtained between replicate experiments for all dosimeters were in excellent agreement (±3%). In general, films and TLDs were in closer agreement with each other, while alanine provided the closest match between the expected and measured dose, with certain caveats related to absolute reference dose. CONCLUSION: In conclusion, successful cross-validation of different electron beams operating under different energies and configurations lays the foundation for establishing dosimetric consensus for UHDR irradiation studies, and, if widely implemented, decrease uncertainty between different sites investigating the mechanistic basis of the FLASH effect.

Understanding the impact of RapidArc therapy delivery errors for prostate cancer.

The purpose of this study is to simulate random and systematic RapidArc delivery errors for external beam prostate radiotherapy plans in order to determine the dose sensitivity for each error type. Ten prostate plans were created with a single 360° arc. The DICOM files for these treatment plans were then imported into an in-house computer program that introduced delivery errors. Random and systematic gantry position (0.25°, 0.5°, 1°), monitor unit (MU) (1.25%, 2.5%, 5%), and multileaf collimator (MLC) position (0.5, 1, 2 mm) errors were introduced. The MLC errors were either random or one of three types of systematic errors, where the MLC banks moved in the same (MLC gaps remain unchanged) or opposing directions (increasing or decreasing the MLC gaps). The generalized equivalent uniform dose (gEUD) was calculated for the original plan and all treatment plans with errors introduced. The dose sensitivity for the cohort was calculated using linear regression for the gantry position, MU, and MLC position errors. Because there was a large amount of variability for systematic MLC position errors, the dose sensitivity of each plan was calculated and correlated with plan MU, mean MLC gap, and the percentage of MLC leaf gaps less than 1 and 2 cm for each individual plan. We found that random and systematic gantry position errors were relatively insignificant (< 0.1% gEUD change) for gantry errors up to 1°. Random MU errors were also insignificant, and systematic MU increases caused a systematic increase in gEUD. For MLC position errors, random MLC errors were relatively insignificant up to 2 mm as had been determined in previous IMRT studies. Systematic MLC shift errors caused a decrease of approximately -1% in the gEUD per mm. For systematic MLC gap open errors, the dose sensitivity was 8.2%/mm and for MLC gap close errors the dose sensitivity was -7.2%/mm. There was a large variability for MLC gap open/close errors for the ten RapidArc plans which correlated strongly with MU, mean gap width, and percentage of MLC gaps less than 1 or 2cm. This study evaluates the magnitude of various simulated RapidArc delivery errors by calculating gEUED on various prostate plans.

Small-field measurement and Monte Carlo model validation of a novel image-guided radiotherapy system.

PURPOSE: The RefleXion™ X1 is a novel radiotherapy system that is designed for image-guided radiotherapy, and eventually, biology-guided radiotherapy (BgRT). BgRT is a treatment paradigm that tracks tumor motion using real-time positron emission signals. This study reports the small-field measurement results and the validation of a Monte Carlo (MC) model of the first clinical RefleXion unit. METHODS: The RefleXion linear accelerator (linac) produces a 6 MV flattening filter free (FFF) photon beam and consists of a binary multileaf collimator (MLC) system with 64 leaves and two pairs of y-jaws. The maximum clinical field size achievable is 400 × 20 mm2 . The y-jaws provide either a 10 or 20 mm opening at source-to-axis distance (SAD) of 850 mm. The width of each MLC leaf at SAD is 6.25 mm. Percentage depth doses (PDDs) and relative beam profiles were acquired using an Edge diode detector in a water tank for field sizes from 12.5 × 10 to 100 × 20 mm2 . Beam profiles were also measured using films. Output factors of fields ranging from 6.25 × 10 to 100 × 20 mm2 were measured using W2 scintillator detector, Edge detector, and films. Output correction factors k of the Edge detector for RefleXion were calculated. An MC model of the linac including pre-MLC beam sources and detailed structures of MLC and lower y-jaws was validated against the measurements. Simulation codes BEAMnrc and GATE were utilized. RESULTS: The diode measured PDD at 10 cm depth (PDD10) increases from 53.6% to 56.9% as the field opens from 12.5 × 10 to 100 × 20 mm2 . The W2-measured output factor increases from 0.706 to 1 as the field opens from 6.25 × 10 to 100 × 20 mm2 (reference field size). The output factors acquired by diode and film differ from the W2 results by 1.65% (std = 1.49%) and 2.09% (std = 1.41%) on average, respectively. The profile penumbra and full-width half-maximum (FWHM) measured by diode agree well with the film results with a deviation of 0.60 mm and 0.73% on average, respectively. The averaged beam profile consistency calculated between the diode- and film-measured profiles among different depths is within 1.72%. By taking the W2 measurements as the ground truth, the output correction factors k for Edge detector ranging from 0.958 to 1 were reported. For the MC model validation, the simulated PDD10 agreed within 0.6% to the diode measurement. The MC-simulated output factor differed from the W2 results by 2.3% on average (std = 3.7%), while the MC simulated beam penumbra differed from the diode results by 0.67 mm on average (std = 0.42 mm). The MC FWHM agreed with the diode results to within 1.40% on average. The averaged beam profile consistency calculated between the diode and MC profiles among different depths is less than 1.29%. CONCLUSIONS: This study represents the first small-field dosimetry of a clinical RefleXion system. A complete and accurate MC model of the RefleXion linac has been validated.

Precision radiotherapy using monochromatic inverse Compton x-ray sources.

PURPOSE: The dosimetric properties of inverse Compton (IC) x-ray sources were investigated to determine their utility for stereotactic radiation therapy. METHODS: Monte Carlo simulations were performed using the egs brachy user code of EGSnrc. Nominal IC source x-ray energies of 80 and 150 keV were considered in this work. Depth-dose and lateral dose profiles in water were calculated, as was dose enhancement in the bone. Further simulations were performed for brain and spine treatment sites. The impact of gold nanoparticle doping was also investigated for the brain treatment site. Analogous dose calculations were performed in a clinical treatment planning system using a clinical 6 MV photon beam model and were compared to the Monte Carlo simulations. RESULTS: Both 80 and 150 keV IC beams were observed to have sharp 80-20 penumbra (i.e., < 0.1 mm) with broad low-dose tails in water. For reference, the calculated penumbra for the 6 MV clinical beam was 3 mm. Maximum dose enhancement factors in bone of 3.1, 1.4, and 1.1 were observed for the 80, 150 keV, and clinical 6 MV beams, respectively. The plan quality for the single brain metastasis case was similar between the IC beams and the 6 MV beam without gold nanoparticles. As the concentration of gold within the target increased, the V12 Gy to the normal brain tissue and D max within the target volume significantly decreased and the conformity significantly improved, which resulted in superior plan quality over the clinical 6 MV beam plan. In the spine cases, the sharp penumbra and enhanced dose to bone of the IC beams produced superior plan quality (i.e., better conformity, normal tissue sparing, and spinal cord sparing) as compared to the clinical 6 MV beam plans. CONCLUSIONS: The findings from this work indicate that inverse Compton x-ray sources are well suited for stereotactic radiotherapy treatments due to their sharp penumbra and dose enhancement around high atomic number materials. Future work includes investigating the properties of intensity-modulated inverse Compton x-ray sources to improve the homogeneity within the target tissue.

A robotically assisted 3D printed quality assurance lung phantom for Calypso.

Purpose. Radiation dose delivered to targets located near the upper-abdomen or in the thorax are significantly affected by respiratory-motion. Relatively large-margins are commonly added to compensate for this motion, limiting radiation-dose-escalation. Internal-surrogates of target motion, such as a radiofrequency (RF) tracking system, i.e. Calypso®System, are used to overcome this challenge and improve normal-tissue sparing. RF tracking systems consist of implanting transponders in the vicinity of the tumor to be tracked using radiofrequency-waves. Unfortunately, although the manufacture provides a universal quality-assurance (QA) phantom, QA-phantoms specifically for lung-applications are limited, warranting the development of alternative solutions to fulfil the tests mandated by AAPM's TG142. Accordingly, our objective was to design and develop a motion-phantom to evaluate Calypso for lung-applications that allows the Calypso®Beacons to move in different directions to better simulate truelung-motion.Methods and Materials.A Calypso lung QA-phantom was designed, and 3D-printed. The design consists of three independent arms where the transponders were attached. A pinpoint-chamber with a buildup-cap was also incorporated. A 4-axis robotic arm was programmed to drive the motion-phantom to mimic breathing. After acquiring a four-dimensional-computed-tomography (4DCT) scan of the motion-phantom, treatment-plans were generated and delivered on a Varian TrueBeam®with Calypso capabilities. Stationary and gated-treatment plans were generated and delivered to determine the dosimetric difference between gated and non-gated treatments. Portal cine-images were acquired to determine the temporal-accuracy of delivery by calculating the difference between the observed versus expected transponders locations with the known speed of the transponders' motion.Results.Dosimetric accuracy is better than the TG142 tolerance of 2%. Temporal accuracy is greater than, TG142 tolerance of 100 ms for beam-on, but less than 100 ms for beam-hold.Conclusions.The robotic QA-phantom designed and developed in this study provides an independent phantom for performing Calypso lung-QA for commissioning and acceptance testing of Calypso for lung treatments.

Local Recurrence Outcomes of Colorectal Cancer Oligometastases Treated With Stereotactic Ablative Radiotherapy.

PURPOSE: The aim of this study was to report local failure (LF) outcomes and associated predictors in patients with oligometastatic colorectal cancer (CRC) treated with stereotactic ablative radiotherapy (SABR). MATERIALS AND METHODS: We retrospectively reviewed patients with CRC metastases to the brain, liver, spine, or lung treated with SABR between 2001 and 2016. Time to LF was summarized using cumulative incidence of LF curves with death as a competing risk. RESULTS: The analysis included a total of 130 patients and 256 lesions. Of the metastases treated, 129 (50%) were brain, 50 (20%) liver, 49 (19%) spine, and 28 (11%) lung. Median gross tumor volume was 24 mL for liver metastases, 2 mL for brain metastases, 4 mL for spine metastases, and 1 mL for lung metastases. The overall 1, 2, and 3-year cumulative incidence of LF rates were 21.6% (16.5, 27.1), 28.2% (22.3, 34.4), and 31.5% (25.2, 38.0), respectively. LF was highest among the liver metastases (1 y: 26.0%, 2 y: 38.5%), followed by spine (1 y: 25.1%, 2 y: 31.1%), brain (1 y: 20%, 2 y: 25.2%), and lung (1 y: 13.7%, 2 y: insufficient data). Metastases from right-sided primary CRC were significantly more likely to have LF (P=0.0146, HR=2.23). Biologically effective dose>70 Gy, defined using a standard linear quadratic model using α/ß ratio of 10 on the individual lesion level, and pre-SABR chemotherapy were also significant predictors of LF (P= 0.0009 and 0.018, respectively). CONCLUSIONS: CRC metastases treated with SABR had significantly higher rates of LF if they originated from right-sided primary CRC, compared with left-sided. Liver metastases had the highest rates of LF compared with other metastatic sites. Thus, CRC liver metastases and metastases from right-sided CRC may benefit from more aggressive radiotherapy.

IEC accelerator beam coordinate transformations for clinical Monte Carlo simulation from a phase space or full BEAMnrc particle source.

Monte Carlo simulation of clinical treatment plans require, in general, a coordinate transformation to describe the incident radiation field orientation on a patient phantom coordinate system. The International Electrotechnical Commission (IEC) has defined an accelerator coordinate system along with positive directions for gantry, couch and collimator rotations. In order to describe the incident beam's orientation with respect to the patient's coordinate system, DOSXYZnrc simulations often require transformation of the accelerator's gantry, couch and collimator angles to describe the incident beam. Similarly, versions of the voxelized Monte Carlo code (VMC(++)) require non-trivial transformation of the accelerator's gantry, couch and collimator angles to standard Euler angles α, ß, γ, to describe an incident phase space source orientation with respect to the patient's coordinate system. The transformations, required by each of these Monte Carlo codes to transport phase spaces through a phantom, have been derived with a rotation operator approach. The transformations have been tested and verified against the Eclipse treatment planning system.

Initial Steps Towards a Clinical FLASH Radiotherapy System: Pediatric Whole Brain Irradiation with 40 MeV Electrons at FLASH Dose Rates.

In this work, we investigated the delivery of a clinically acceptable pediatric whole brain radiotherapy plan at FLASH dose rates using two lateral opposing 40-MeV electron beams produced by a practically realizable linear accelerator system. The EGSnrc Monte Carlo software modules, BEAMnrc and DOSXYZnrc, were used to generate whole brain radiotherapy plans for a pediatric patient using two lateral opposing 40-MeV electron beams. Electron beam phase space files were simulated using a model of a diverging beam with a diameter of 10 cm at 50 cm SAD (defined at brain midline). The electron beams were collimated using a 10-cm-thick block composed of 5 cm of aluminum oxide and 5 cm of tungsten. For comparison, a 6-MV photon plan was calculated with the Varian AAA algorithm. Electron beam parameters were based on a novel linear accelerator designed for the PHASER system and powered by a commercial 6-MW klystron. Calculations of the linear accelerator's performance indicated an average beam current of at least 6.25 µA, providing a dose rate of 115 Gy/s at isocenter, high enough for cognition-sparing FLASH effects. The electron plan was less homogenous with a homogeneity index of 0.133 compared to the photon plan's index of 0.087. Overall, the dosimetric characteristics of the 40-MeV electron plan were suitable for treatment. In conclusion, Monte Carlo simulations performed in this work indicate that two lateral opposing 40-MeV electron beams can be used for pediatric whole brain irradiation at FLASH dose rates of >115 Gy/s and serve as motivation for a practical clinical FLASH radiotherapy system, which can be implemented in the near future.

Cost Analysis of Audiovisual-Assisted Therapeutic Ambiance in Radiation Therapy (AVATAR)-Aided Omission of Anesthesia in Radiation for Pediatric Malignancies.

PURPOSE: Because children cannot reliably remain immobile during radiation therapy (RT) for cancer anatomy targeting requiring millimeter precision, daily anesthesia plays a large role in each RT session. Unfortunately, anesthesia is a source of financial burden for patients' families and is invasive and traumatic. This study attempts to assess the cost-savings benefit of audiovisual-assisted therapeutic ambiance in radiation therapy (AVATAR)-aided omission of pediatric anesthesia in RT. METHODS AND MATERIALS: The baseline time of anesthesia during RT was derived from documented anesthesia billing time during RT simulation at our institution and from the published literature. Current Procedural Terminology and relative value unit codes encompassing anesthesia-related charges from radiation oncology and anesthesia were analyzed in concert with this value to calculate the total cost of pediatric anesthesia per RT session. RESULTS: The mean number of RT fractions administered per patient with AVATAR-directed anesthesia omission at our institution was 19.0, similar to the 17.6 previously reported. At a mean anesthesia time exceeding 30 minutes (with mean RT duration of 4 weeks), the cost of pediatric anesthesia per RT fraction in non-AVATAR sessions was $1,904.35, yielding a total RT treatment anesthesia cost of $38,087.00 per patient (including simulation). Patients at our institution were not billed for AVATAR-assisted RT. CONCLUSIONS: The ability of AVATAR to obviate the need for daily anesthesia in pediatric RT provides substantial cost-savings. These findings argue for increased utilization of AVATAR and for analyses of RT targeting the accuracy of AVATAR versus conventional anesthesia-guided treatment of pediatric malignancies.

Impact of Audiovisual-Assisted Therapeutic Ambience in Radiation Therapy (AVATAR) on Anesthesia Use, Payer Charges, and Treatment Time in Pediatric Patients.

PURPOSE: Pediatric radiation therapy (RT) requires optimal immobilization that often necessitates daily anesthesia. To decrease anesthesia use, we implemented a novel audiovisual-assisted therapeutic ambience in RT (AVATAR) system that projects video onto a radiolucent screen within the child's line of vision to provide attentional diversion. We investigated its reduction on anesthesia use, payer charges, and treatment time, in addition to its impact on radiation delivery. METHODS AND MATERIALS: A 6-year retrospective analysis was performed among children undergoing RT (n = 224) 3 years before and 3 years after the introduction of AVATAR. The frequency of anesthesia use before and after AVATAR implementation, in addition to RT treatment times, were compared. The number of spared anesthesia treatments allowed for a charge to payer analysis. To document the lack of surface dose perturbation by AVATAR, a phantom craniospinal treatment course was delivered both with and without AVATAR. Additionally, an ion chamber course was delivered to document changes to the dose at depth. RESULTS: More children were able to avoid anesthesia use entirely in the post-AVATAR cohort compared with the pre-AVATAR cohort (73.2% vs 63.4%; P = .03), and fewer required anesthesia for each treatment (18.8% vs 33%; P = .03). AVATAR introduction reduced anesthesia use for all ages studied. Treatment time per session was reduced by 38% using AVATAR compared with anesthesia. There were 326 fewer anesthesia sessions delivered over 3 years after AVATAR was introduced, with an estimated savings of >$500,000. Optically stimulated luminescent dosimeters revealed a small increase in dose of 0.8% to 9.5% with AVATAR, whereas the use of a thermomolded face mask increased skin dose by as much as 58%. CONCLUSIONS: AVATAR introduction decreased anesthesia use in children undergoing RT. More children avoided anesthesia entirely, and fewer needed anesthesia for every treatment, resulting in a reduction in treatment time and savings of nearly $550,000 in approximately 3 years, with minimal perturbation of RT dose delivery.