Recommendations for using analytical anisotropic algorithm and AcurosXB for epidermal dose calculations in breast radiotherapy from an in vivo Gafchromic film study.

BACKGROUND AND PURPOSE: This study recommends clinical epidermal dose calculation methods based on in-vivo film measurements and registered skin dose distributions with the Eclipse (Varian Medical Systems) treatment planning system's Analytical Anisotropic Algorithm (AAA) and Acuros XB (AXB) dose calculation algorithms. MATERIALS AND METHODS: Eighteen AAA V13.6 breast plans were recalculated using AXB (dose to medium) V13.5 with the same beam parameters and monitor units as in the original plans. These are compared against in-vivo Gafchromic film measurements from the lateral and inferior breast regions. Three skin structures in the treatment planning system are evaluated: a surface layer of voxels of the body contour, a 0.2 cm internal skin rind, and a 0.5 cm internal skin rind. RESULTS: Systematic shifts are demonstrated between the film measurements of skin dose and the Eclipse dose calculations. On average, the dose to the surface layer of pixels is underestimated by AAA by 8% and overestimated by AXB by 3%. A 5 mm skin rind extended into the body can increase epidermal dose calculations on average by 8% for AAA and 4% for AXB. CONCLUSION: This is the first study to register in-vivo skin dose distributions in the breast to the treatment planning system for comparison. Based on the results from this study it is recommended that epidermal dose is calculated with a 0.5 cm skin rind for the AAA algorithm and with rind thickness up to 0.2 cm for the AXB algorithm.

Linear accelerator maintenance cost analysis.

PURPOSE: Medical linear accelerators are the most costly standard equipment used in radiation oncology, however the service costs for these machines are not well understood. With an increasing demand for linear accelerators due to a global increase in cancer incidence, it is important to understand the expected maintenance costs of a larger global installed base so that these costs can be incorporated into budgeting. The purpose of this investigation is to analyze the costs for medical linear accelerator service and maintenance at our institution, in order to estimate the service cost ratio. METHODS: We collected the costs of parts used for all service work done on 32 medical linear accelerators over a two year period. The data was segregated by center, machine, linear accelerator type, and failure area in the machine. RESULTS: We found the service cost ratio (excluding software support expenses) to be 3.13% [2.74%, 3.52%,]. We observed a variability of parts costs, and overall variability of the service cost ratio to be between 2.14% and 5.25%. This result is lower than other estimates for service costs for medical equipment in general and medical linear accelerators specifically. Two-thirds of the service costs were due to labor costs, which indicate the importance of a well-trained service technician workforce. CONCLUSIONS: We estimated the service cost ratio for medical linear accelerators to be 3.13% [3.52%, 2.74%] of the initial capital cost. This result was lower than other estimates of the service cost ratio.

A novel carbon-fibre adjustable reusable accessory (CARA) for supine breast positioning to reduce toxicity in breast adjuvant radiotherapy: a study protocol for a multicentre phase III randomized controlled trial.

BACKGROUND: A novel device for supine positioning in breast radiotherapy for patients with large or pendulous breasts has been developed and tested in phase II studies. This trial is designed to assess the efficacy of the device to reduce skin toxicity and unwanted normal tissue dose in comparison to the current clinical standard for supine breast support during breast radiotherapy. METHODS: Patients at high risk for moist desquamation, having infra-mammary fold or lateral ptosis, will be randomized into two arms. Patients in the control arm will receive breast radiotherapy with supine positioning using current standard of care. Patients in the experimental arm will be positioned supine with the novel device. The primary endpoint is the incidence of moist desquamation in the infra-mammary fold. We hypothesize a 20% reduction (from 50 to 30%) in the rate of moist desquamation in the study arm versus the control arm. For 80% power, two-tailed α = 0.05 and 10% loss to follow up, 110 patients will be assigned to each arm. The proportion of patients experiencing moist desquamation in the two arms will be compared using logistic regression adjusting for brassiere cup size, skin fold size, body mass index, smoking status, and dose fractionation schedule. An unadjusted comparison will also be made using the chi-square test, or Fisher's exact test, if appropriate. Secondary endpoints include dose-volume statistics for the lung and heart, skin dose and clinical parameters including setup time, reproducibility, and staff experience with setup procedures. Patient-reported pain, skin condition interference with sleep and daily activities, and comfort during treatment are also secondary endpoints. DISCUSSION: Based on results from earlier phase II studies, it is expected that the device-enabled elimination of infra-mammary fold should reduce toxicity and improve quality of life for this patient population. Earlier studies showed reduction in dose to organs at risk including lung and heart, indicating potential for other long-term benefits for patients using the device. This study is limited to acute skin toxicity, patient-reported outcomes, and clinical factors to inform integration of the device into standard breast radiotherapy procedures. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT04257396 . Registered February 6 2020.

Amplitude gating for a coached breathing approach in respiratory gated 10 MV flattening filter-free VMAT delivery.

The purpose of this study was to investigate amplitude gating combined with a coached breathing strategy for 10 MV flattening filter-free (FFF) volumetric-modulated arc therapy (VMAT) on the Varian TrueBeam linac. Ten patient plans for VMAT SABR liver were created using the Eclipse treatment planning system (TPS). The verification plans were then transferred to a CT-scanned Quasar phantom and delivered on a TrueBeam linac using a 10 MV FFF beam and Varian's real-time position management (RPM) system for respiratory gating based on breathing amplitude. Breathing traces were acquired from ten patients using two kinds of breathing patterns: free breathing and an interrupted (~ 5 s pause) end of exhale coached breathing pattern. Ion chamber and Gafchromic film measurements were acquired for a gated delivery while the phantom moved under the described breathing patterns, as well as for a nongated stationary phantom delivery. The gate window was set to obtain a range of residual target motion from 2-5 mm. All gated deliveries on a moving phantom have been shown to be dosimetrically equivalent to the nongated deliveries on a static phantom, with differences in point dose measurements under 1% and average gamma 2%/2 mm agreement above 98.7%. Comparison with the treatment planning system also resulted in good agreement, with differences in point-dose measurements under 2.5% and average gamma 3%/3 mm agreement of 97%. The use of a coached breathing pattern significantly increases the duty cycle, compared with free breathing, and allows for shorter treatment times. Patients' free-breathing patterns contain considerable variability and, although dosimetric results for gated delivery may be acceptable, it is difficult to achieve efficient treatment delivery. A coached breathing pattern combined with a 5 mm amplitude gate, resulted in both high-quality dose distributions and overall shortest gated beam delivery times.

Monte Carlo modeling of HD120 multileaf collimator on Varian TrueBeam linear accelerator for verification of 6X and 6X FFF VMAT SABR treatment plans.

A Monte Carlo (MC) validation of the vendor-supplied Varian TrueBeam 6 MV flattened (6X) phase-space file and the first implementation of the Siebers-Keall MC MLC model as applied to the HD120 MLC (for 6X flat and 6X flattening filter-free (6X FFF) beams) are described. The MC model is validated in the context of VMAT patient-specific quality assurance. The Monte Carlo commissioning process involves: 1) validating the calculated open-field percentage depth doses (PDDs), profiles, and output factors (OF), 2) adapting the Siebers-Keall MLC model to match the new HD120-MLC geometry and material composition, 3) determining the absolute dose conversion factor for the MC calculation, and 4) validating this entire linac/MLC in the context of dose calculation verification for clinical VMAT plans. MC PDDs for the 6X beams agree with the measured data to within 2.0% for field sizes ranging from 2 × 2 to 40 × 40 cm2. Measured and MC profiles show agreement in the 50% field width and the 80%-20% penumbra region to within 1.3 mm for all square field sizes. MC OFs for the 2 to 40 cm2 square fields agree with measurement to within 1.6%. Verification of VMAT SABR lung, liver, and vertebra plans demonstrate that measured and MC ion chamber doses agree within 0.6% for the 6X beam and within 2.0% for the 6X FFF beam. A 3D gamma factor analysis demonstrates that for the 6X beam, > 99% of voxels meet the pass criteria (3%/3 mm). For the 6X FFF beam, > 94% of voxels meet this criteria. The TrueBeam accelerator delivering 6X and 6X FFF beams with the HD120 MLC can be modeled in Monte Carlo to provide an independent 3D dose calculation for clinical VMAT plans. This quality assurance tool has been used clinically to verify over 140 6X and 16 6X FFF TrueBeam treatment plans.

Toward a Skin Dose-Area Metric Predictive of Moist Desquamation Using In Vivo Skin Dosimetry and Skin Assessments.

Purpose: Moist desquamation (MD) is a concerning acute side effect of radiation therapy for breast cancer, often seen in skin folds for patients having large or pendulous breasts. In vivo skin dosimetry, clinical assessments, and patient-reported skin reactions were used to determine a relationship between dose-area metrics and the development of MD, to lend insight into skin tolerances and possibly guide future treatment planning dose constraints. Methods and Materials: Skin dose was measured using GafChromic film on the inner surface of an early prototype carbon-fiber accessory for breast support to remove the inframammary fold in 20 patients at high risk of developing MD undergoing adjuvant whole breast radiation therapy. Prescribed doses were 42.5 Gray (Gy) in 16 fractions or 50 Gy in 25 fractions using 6 to 15 MV x-rays. To account for fraction size differences, analysis was performed using the equivalent dose in 2 Gy fractions using α/ß = 11 (EQD211). MD was assessed out to 2 weeks post radiation therapy by trained therapists and by a patient-reported outcome questionnaire. Results: Statistically significant differences in areas receiving 30 to 48 Gy (EQD211) were observed between patients who did and did not develop MD in the inframammary area. Patients receiving EQD211 maximum dose ≤ 46 Gy and ≥ 38 Gy to ≤ 50 cm2 of their breast skin did not develop MD. Conclusions: The findings of this study offer insight into the relationship between skin toxicity and areas of skin irradiated to doses up to 50 Gy. Potential skin dose constraints to test in future studies to prevent MD are suggested.

In Vitro and In Vivo Synergetic Radiotherapy with Gold Nanoparticles and Docetaxel for Pancreatic Cancer.

This research underscores the potential of combining nanotechnology with conventional therapies in cancer treatment, particularly for challenging cases like pancreatic cancer. We aimed to enhance pancreatic cancer treatment by investigating the synergistic effects of gold nanoparticles (GNPs) and docetaxel (DTX) as potential radiosensitizers in radiotherapy (RT) both in vitro and in vivo, utilizing a MIA PaCa-2 monoculture spheroid model and NRG mice subcutaneously implanted with MIA PaCa-2 cells, respectively. Spheroids were treated with GNPs (7.5 µg/mL), DTX (100 nM), and 2 Gy of RT using a 6 MV linear accelerator. In parallel, mice received treatments of GNPs (2 mg/kg), DTX (6 mg/kg), and 5 Gy of RT (6 MV linear accelerator). In vitro results showed that though RT and DTX reduced spheroid size and increased DNA DSBs, the triple combination of DTX/RT/GNPs led to a significant 48% (p = 0.05) decrease in spheroid size and a 45% (p = 0.05) increase in DNA DSBs. In vivo results showed a 20% (p = 0.05) reduction in tumor growth 20 days post-treatment with (GNPs/RT/DTX) and an increase in mice median survival. The triple combination exhibited a synergistic effect, enhancing anticancer efficacy beyond individual treatments, and thus could be employed to improve radiotherapy and potentially reduce adverse effects.

Detection of FLASH-radiotherapy tissue sparing in a 3D-spheroid model using DNA damage response markers.

PURPOSE: The oxygen depletion hypothesis has been proposed as a rationale to explain the observed phenomenon of FLASH-radiotherapy (FLASH-RT) sparing normal tissues while simultaneously maintaining tumor control. In this study we examined the distribution of DNA Damage Response (DDR) markers in irradiated 3D multicellular spheroids to explore the relationship between FLASH-RT protection and radiolytic-oxygen-consumption (ROC) in tissues. METHODS: Studies were performed using a Varian Truebeam linear accelerator delivering 10 MeV electrons with an average dose rate above 50 Gy/s. Irradiations were carried out on 3D spheroids maintained under a range of O2 and temperature conditions to control O2 consumption and create gradients representative of in vivo tissues. RESULTS: Staining for pDNA-PK (Ser2056) produced a linear radiation dose response whereas γH2AX (Ser139) showed saturation with increasing dose. Using the pDNA-PK staining, radiation response was then characterised for FLASH compared to standard-dose-rates as a function of depth into the spheroids. At 4 °C, chosen to minimize the development of metabolic oxygen gradients within the tissues, FLASH protection could be observed at all distances under oxygen conditions of 0.3-1 % O2. Whereas at 37 °C a FLASH-protective effect was limited to the outer cell layers of tissues, an effect only observed at 3 % O2. Modelling of changes in the pDNA-PK-based oxygen enhancement ratio (OER) yielded a tissue ROC g0-value estimate of 0.73 ± 0.25 µM/Gy with a km of 5.4 µM at FLASH dose rates. CONCLUSIONS: DNA damage response markers are sensitive to the effects of transient oxygen depletion during FLASH radiotherapy. Findings support the rationale that well-oxygenated tissues would benefit more from FLASH-dose-rate protection relative to poorly-oxygenated tissues.

Validation of a Patient-Reported Outcome Measure for Moist Desquamation among Breast Radiotherapy Patients.

There has been an increasing interest in patient-reported outcome (PRO) measures in both the clinical and research settings to improve the quality of life among patients and to identify when clinical intervention may be needed. The primary purpose of this prospective study was to validate an acute breast skin toxicity PRO measure across a broad sample of patient body types undergoing radiation therapy. Between August 2018 and September 2019, 134 women undergoing adjuvant breast radiotherapy (RT) consented to completing serial PRO measures both during and post-RT treatment and to having their skin assessed by trained trial radiation therapists. There was high patient compliance, with 124 patients (92.5%) returning to the clinic post-RT for at least one staff skin assessment. Rates of moist desquamation (MD) in the infra-mammary fold (IMF) by PRO were compared with skin assessments completed by trial radiation therapists. There was high sensitivity (86.5%) and good specificity (79.4%) between PRO and staff-reported presence of MD in the IMF, and there was a moderate correlation between the peak severity of the MD reported by PRO and assessed by staff (rho = 0.61, p < 0.001). This prospective study validates a new PRO measure to monitor the presence of MD in the IMF among women receiving breast RT.

Reduction in Doses to Organs at Risk and Normal Tissue During Breast Radiation Therapy With a Carbon-Fiber Adjustable Reusable Accessory.

PURPOSE: This pilot study (ClinicalTrials.gov NCT04543851) investigates a novel breast positioning device using a low density, high tensile carbon-fiber cradle to support the breast, remove the inframammary fold, and reduce dose to organs at risk for whole breast radiation therapy in the supine position. METHODS AND MATERIALS: Thirty patients with inframammary folds ≥1 cm or lateral ptosis in supine treatment position were planned with standard positioning and with a carbon-fiber Adjustable Reusable Accessory (CARA) breast support. Twenty patients received whole breast with or without regional nodal irradiation with 42.5 Gy in 16 fractions or 50 Gy in 25 fractions using CARA. Median body mass index was 32 in this study. RESULTS: CARA removed all inframammary folds and reduced V20Gyipsilateral lung, V105%breast, and V50% body, without compromising target coverage. Median (range) V20Gyipsilateral lung for whole breast radiation therapy was 12.3% (1.4%-28.7%) with standard of care versus 10.9% (1.2%-17.3%) with CARA (Wilcoxon P = .005). Median V105% breast was 8.0% (0.0%-29%) with standard of care versus 4.0% (0.0%-23%) with CARA (P = .006) and median V50% body was 3056 mL (1476-5285 mL) versus 2780 mL (1415-5123 mL) with CARA (P = .001). CARA was compatible with deep inspiration breath hold and achieved median V25Gyheart = 0.1% (range 0%-1.9%) for all patients with left breast cancer. Skin reactions with CARA were consistent with historical data and daily variation in treatment setup was consistent with standard supine positioning. CONCLUSIONS: CARA can reduce V105%breast, lung and normal tissue dose, and remove the inframammary fold for breast patients with large or pendulous breasts and high body mass index treated in the supine position, without compromising target coverage. CARA will undergo further study in a randomized controlled trial.

Monte Carlo based, patient-specific RapidArc QA using Linac log files.

PURPOSE: A Monte Carlo (MC) based QA process to validate the dynamic beam delivery accuracy for Varian RapidArc (Varian Medical Systems, Palo Alto, CA) using Linac delivery log files (DynaLog) is presented. Using DynaLog file analysis and MC simulations, the goal of this article is to (a) confirm that adequate sampling is used in the RapidArc optimization algorithm (177 static gantry angles) and (b) to assess the physical machine performance [gantry angle and monitor unit (MU) delivery accuracy]. METHODS: Ten clinically acceptable RapidArc treatment plans were generated for various tumor sites and delivered to a water-equivalent cylindrical phantom on the treatment unit. Three Monte Carlo simulations were performed to calculate dose to the CT phantom image set: (a) One using a series of static gantry angles defined by 177 control points with treatment planning system (TPS) MLC control files (planning files), (b) one using continuous gantry rotation with TPS generated MLC control files, and (c) one using continuous gantry rotation with actual Linac delivery log files. Monte Carlo simulated dose distributions are compared to both ionization chamber point measurements and with RapidArc TPS calculated doses. The 3D dose distributions were compared using a 3D gamma-factor analysis, employing a 3%/3 mm distance-to-agreement criterion. RESULTS: The dose difference between MC simulations, TPS, and ionization chamber point measurements was less than 2.1%. For all plans, the MC calculated 3D dose distributions agreed well with the TPS calculated doses (gamma-factor values were less than 1 for more than 95% of the points considered). Machine performance QA was supplemented with an extensive DynaLog file analysis. A DynaLog file analysis showed that leaf position errors were less than 1 mm for 94% of the time and there were no leaf errors greater than 2.5 mm. The mean standard deviation in MU and gantry angle were 0.052 MU and 0.355 degrees, respectively, for the ten cases analyzed. CONCLUSIONS: The accuracy and flexibility of the Monte Carlo based RapidArc QA system were demonstrated. Good machine performance and accurate dose distribution delivery of RapidArc plans were observed. The sampling used in the TPS optimization algorithm was found to be adequate.

Technical Note: Development of a phantom for dosimetric comparison of murine micro-CT protocols with optically stimulated luminescent dosimeters.

PURPOSE: This work aims to evaluate the utility and accuracy of a mouse-like phantom and optically stimulated luminescent dosimeters (OSLDs) in measuring dose delivered to the body and lung of mice undergoing micro-CT imaging. METHODS: A phantom with two cavities for NanoDot OSLDs (Landauer, Inc., Greenwood, IL) was designed and constructed using acrylic to model the mouse body and polyurethane foam to obtain an approximate lung tissue dose. The OSLD dose was compared to ion chamber measurements for the same imaging protocols delivered by a Siemens Inveon micro-CT (Siemens Medical Solutions USA, Inc., Hoffman Estates, IL, USA). A whole body scan, using 80 kV, 0.5 mA and 0.5 mm of aluminum filter, was used to compare results to previously published data. Additionally, dose was measured for the whole body scan without the aluminum filter and two chest protocols (full and half rotation). RESULTS: OSLD dose results agree with chamber measurements within 3%. Average OSLD measurements for the whole body scan without filter were 10.7 ± 0.7 cGy in the abdomen and 11.2 ± 0.7 cGy in the lung. For the full rotation chest protocol, the average dose measured in the lung was 65.8 ± 4.3 cGy and 60.2 ± 3.9 cGy in the abdomen. Average doses were 41.1 ± 2.7 cGy in the lung and 38.2 ± 2.5 cGy in the abdomen for the half rotation chest protocol. The OSLD measurements showed a coefficient of variation under 1.4%. A maximum rotational geometry under-response of 0.86% with respect to exposure at normal incidence to the OSLD was measured. CONCLUSIONS: The doses measured were found to be comparable to other studies for the scanner configuration and protocols chosen. The phantom built for this study was found to give reproducible dose measurements with 4% uncertainty. In this way, a robust and convenient method is established for future dose assessment of micro-CT protocols and interinstitutional comparisons.

In vitro study of cell survival following dynamic MLC intensity-modulated radiation therapy dose delivery.

The possibility of reduced cell kill following intensity-modulated radiation therapy (IMRT) compared to conventional radiation therapy has been debated in the literature. This potential reduction in cell kill relates to prolonged treatment times typical of IMRT dose delivery and consequently increased repair of sublethal lesions. While there is some theoretical support to this reduction in cell kill published in the literature, direct experimental evidence specific to IMRT dose delivery patterns is lacking. In this study we present cell survival data for three cell lines: Chinese hamster V79 fibroblasts, human cervical carcinoma, SiHa and colon adenocarcinoma, WiDr. Cell survival was obtained for 2.1 Gy delivered as acute dose with parallel-opposed pair (POP), irradiation time 75 s, which served as a reference; regular seven-field IMRT, irradiation time 5 min; and IMRT with a break for multiple leaf collimator (MLC) re-initialization after three fields were delivered, irradiation time 10 min. An actual seven-field dynamic MLC IMRT plan for a head and neck patient was used. The IMRT plan was generated for a Varian EX or iX linear accelerator with 120 leaf Millenium MLC. Survival data were also collected for doses 1X, 2X, 3X, 4X, and 5x 2.1 Gy to establish parameters of the linear-quadratic equation describing survival following acute dose delivery. Cells were irradiated inside an acrylic cylindrical phantom specifically designed for this study. Doses from both IMRT and POP were validated using ion chamber measurements. A reproducible increase in cell survival was observed following IMRT dose delivery. This increase varied from small for V79, with a surviving fraction of 0.8326 following POP vs 0.8420 following uninterrupted IMRT, to very pronounced for SiHa, with a surviving fraction of 0.3903 following POP vs 0.5330 for uninterrupted IMRT. When compared to IMRT or IMRT with a break for MLC initialization, cell survival following acute dose delivery was significantly different, p < 0.05, in three out of six cases. In contrast, when cell survival following IMRT was compared to that following IMRT with a break for MLC initialization the difference was always statistically insignificant. When projected to a 30 fraction treatment, dose deficit to bring cell survival to the same value as in POP was calculated as 4.1, 24.9, and 31.1 Gy for V79, WiDr, and SiHa cell lines, respectively. The dose deficit did not relate to the alpha/beta ratio obtained in this study for the three cell lines. Clinical data do not show reduction in local control following IMRT. Possible reasons for this are discussed. The obtained data set can serve as a test data set for models designed to explore the effect of dose delivery prolongation/fractionation in IMRT on radiation therapy outcome.

Direct aperture optimization for IMRT using Monte Carlo generated beamlets.

This work introduces an EGSnrc-based Monte Carlo (MC) beamlet does distribution matrix into a direct aperture optimization (DAO) algorithm for IMRT inverse planning. The technique is referred to as Monte Carlo-direct aperture optimization (MC-DAO). The goal is to assess if the combination of accurate Monte Carlo tissue inhomogeneity modeling and DAO inverse planning will improve the dose accuracy and treatment efficiency for treatment planning. Several authors have shown that the presence of small fields and/or inhomogeneous materials in IMRT treatment fields can cause dose calculation errors for algorithms that are unable to accurately model electronic disequilibrium. This issue may also affect the IMRT optimization process because the dose calculation algorithm may not properly model difficult geometries such as targets close to low-density regions (lung, air etc.). A clinical linear accelerator head is simulated using BEAMnrc (NRC, Canada). A novel in-house algorithm subdivides the resulting phase space into 2.5 X 5.0 mm2 beamlets. Each beamlet is projected onto a patient-specific phantom. The beamlet dose contribution to each voxel in a structure-of-interest is calculated using DOSXYZnrc. The multileaf collimator (MLC) leaf positions are linked to the location of the beamlet does distributions. The MLC shapes are optimized using direct aperture optimization (DAO). A final Monte Carlo calculation with MLC modeling is used to compute the final dose distribution. Monte Carlo simulation can generate accurate beamlet dose distributions for traditionally difficult-to-calculate geometries, particularly for small fields crossing regions of tissue inhomogeneity. The introduction of DAO results in an additional improvement by increasing the treatment delivery efficiency. For the examples presented in this paper the reduction in the total number of monitor units to deliver is approximately 33% compared to fluence-based optimization methods.

Practice Patterns Analysis of Ocular Proton Therapy Centers: The International OPTIC Survey.

PURPOSE: To assess the planning, treatment, and follow-up strategies worldwide in dedicated proton therapy ocular programs. METHODS AND MATERIALS: Ten centers from 7 countries completed a questionnaire survey with 109 queries on the eye treatment planning system (TPS), hardware/software equipment, image acquisition/registration, patient positioning, eye surveillance, beam delivery, quality assurance (QA), clinical management, and workflow. RESULTS: Worldwide, 28,891 eye patients were treated with protons at the 10 centers as of the end of 2014. Most centers treated a vast number of ocular patients (1729 to 6369). Three centers treated fewer than 200 ocular patients. Most commonly, the centers treated uveal melanoma (UM) and other primary ocular malignancies, benign ocular tumors, conjunctival lesions, choroidal metastases, and retinoblastomas. The UM dose fractionation was generally within a standard range, whereas dosing for other ocular conditions was not standardized. The majority (80%) of centers used in common a specific ocular TPS. Variability existed in imaging registration, with magnetic resonance imaging (MRI) rarely being used in routine planning (20%). Increased patient to full-time equivalent ratios were observed by higher accruing centers (P=.0161). Generally, ophthalmologists followed up the post-radiation therapy patients, though in 40% of centers radiation oncologists also followed up the patients. Seven centers had a prospective outcomes database. All centers used a cyclotron to accelerate protons with dedicated horizontal beam lines only. QA checks (range, modulation) varied substantially across centers. CONCLUSIONS: The first worldwide multi-institutional ophthalmic proton therapy survey of the clinical and technical approach shows areas of substantial overlap and areas of progress needed to achieve sustainable and systematic management. Future international efforts include research and development for imaging and planning software upgrades, increased use of MRI, development of clinical protocols, systematic patient-centered data acquisition, and publishing guidelines on QA, staffing, treatment, and follow-up parameters by dedicated ocular programs to ensure the highest level of care for ocular patients.

Monte Carlo validation of the TrueBeam 10XFFF phase-space files for applications in lung SABR.

PURPOSE: To establish the clinical acceptability of universal Monte Carlo phase-space data for the 10XFFF (flattening filter free) photon beam on the Varian TrueBeam Linac, including previously unreported data for small fields, output factors, and inhomogeneous media. The study was particularly aimed at confirming the suitability for use in simulations of lung stereotactic ablative radiotherapy treatment plans. METHODS: Monte Carlo calculated percent depth doses (PDDs), transverse profiles, and output factors for the TrueBeam 10 MV FFF beam using generic phase-space data that have been released by the Varian MC research team were compared with in-house measurements and published data from multiple institutions (ten Linacs from eight different institutions). BEAMnrc was used to create field size specific phase-spaces located underneath the jaws. Doses were calculated with DOSXYZnrc in a water phantom for fields ranging from 1 × 1 to 40 × 40 cm(2). Particular attention was paid to small fields (down to 1 × 1 cm(2)) and dose per pulse effects on dosimeter response for high dose rate 10XFFF beams. Ion chamber measurements were corrected for changes in ion collection efficiency (P(ion)) with increasing dose per pulse. MC and ECLIPSE ANISOTROPIC ANALYTICAL ALGORITHM (AAA) calculated PDDs were compared to Gafchromic film measurement in inhomogeneous media (water, bone, lung). RESULTS: Measured data from all machines agreed with Monte Carlo simulations within 1.0% and 1.5% for PDDs and in-field transverse profiles, respectively, for field sizes >1 × 1 cm(2) in a homogeneous water phantom. Agreements in the 80%-20% penumbra widths were better than 2 mm for all the fields that were compared. For all the field sizes considered, the agreement between their measured and calculated output factors was within 1.1%. Monte Carlo results for dose to water at water/bone, bone/lung, and lung/water interfaces as well as within lung agree with film measurements to within 2.8% for 10 × 10 and 3 × 3 cm(2) field sizes. This represents a significant improvement over the performance of the ECLIPSE AAA. CONCLUSIONS: The 10XFFF phase-space data offered by the Varian Monte Carlo research team have been validated for clinical use using measured, interinstitutional beam data in water and with film dosimetry in inhomogeneous media.

Image filtering for improved dose resolution in CT polymer gel dosimetry.

X-ray computed tomography (CT) has been established as a feasible method of performing dosimetry using polyacrylamide gels (PAGs). A small density change occurs in PAG upon irradiation that provides contrast in PAG CT images. However, low dose resolution limits the clinical usefulness of the technique. This work investigates the potential of using image filtering techniques on PAG CT images in order to reduce image noise and improve dose resolution. CT image noise for the scanner and protocol used for the gel images is analyzed and found to be Gaussian distributed and independent of the contrast level in the images. As a result, several filters for reducing spatially invariant noise are investigated: mean, median, midpoint, adaptive mean, alpha-trimmed mean, sigma mean, and a relatively new filter called SUSAN (smallest univalue segment assimilating nucleus). All filters are applied, using 3x3, 5x5, and 7x7 pixel masks, to a CT image of a PAG irradiated with a stereotactic radiosurgery dose distribution. The dose resolution within 95% confidence (D(delta)95%) is calculated and compared for each filtered image, as well the unfiltered image. In addition, the ability of the filters to maintain the spatial integrity of the dose distribution is evaluated and compared. Results clearly indicate that the filters are not equal in their ability to improve D(delta)95% or in their effect on the spatial integrity of the dose distribution. In general, increasing mask size improves D(delta)95% but simultaneously degrades spatial dose information. The mean filter provides the greatest improvement in D(delta)95%, but also the greatest loss of spatial dose information. The SUSAN, mean adaptive, and alpha-trimmed mean filters all provide comparable, but slightly poorer dose resolution. In addition, the SUSAN and adaptive filters both excel at maintaining the spatial distribution of dose and overall are the best performing filters for this application. The midpoint filter, normally useful for Gaussian noise, is poor all-round, dramatically distorting the dose distribution for masks greater than 3x3. The median filter, a common edge preserving noise reduction filter, performs moderately well, but artificially increases high dose gradients. The sigma filter preserves the spatial distribution of dose very well but is least effective at improving dose resolution. In summary, dose resolution can be significantly improved in CT PAG dosimetry through postprocessing of CT images using spatial noise reduction filters. However, such filters are not equal in their ability to improve dose resolution or to maintain the spatial integrity of the dose distribution and an appropriate filter must be chosen depending on clinical demands of the application.

The use of modified single pencil beam dose kernels to improve IMRT dose calculation accuracy.

Intensity modulated radiation therapy (IMRT) is used to deliver highly conformal radiation doses to tumors while sparing nearby sensitive tissues. Discrepancies between calculated and measured dose distributions have been reported for regions of high dose gradients corresponding to complex radiation fluence patterns. For the single pencil beam convolution dose calculation algorithm, the ability to resolve areas of high dose structure is partly related to the shape of the pencil beam dose kernel (similar to how a photon detector's point spread function relates to imaging resolution). Improvements in dose calculation accuracy have been reported when the treatment planning system (TPS) is recommissioned using high-resolution measurement data as input. This study proposes to improve the dose calculation accuracy for IMRT planning by modifying clinical dose kernel shapes already present in the TPS, thus avoiding the need to reacquire higher resolution commissioning data. The in-house optimization program minimizes a cost-function based on a two-dimensional composite dose subtraction/distance-to-agreement (gamma) analysis. The final modified kernel shapes are reintroduced into the treatment planning system and improvements to the dose calcula tion accuracy for complex IMRT dose distributions evaluated. The central kernel value (radius =0 cm) has the largest effect on the dose calculation resolution and is the focus of this study.

Are neutrons responsible for the dose discrepancies between Monte Carlo calculations and measurements in the build-up region for a high-energy photon beam?

This study presents measured neutron dose using a neutron dosimeter in a water phantom and investigates a hypothesis that neutrons in a high-energy photon beam may be responsible for the reported significant dose discrepancies between Monte Carlo calculations and measurements at the build-up region in large fields. Borated polyethylene slabs were inserted between the accelerator head and the phantom in order to remove neutrons generated in the accelerator head. The thickness of the slab ranged from 2.5 cm to 10 cm. A lead slab of 3 mm thickness was also used in the study. The superheated drop neutron dosimeter was used to measure the depth-dose curve of neutrons in a high-energy photon beam and to verify the effectiveness of the slab to remove these neutrons. Total dose measurements were performed in water using a WELLHOFER WP700 beam scanner with an IC-10 ionization chamber. The Monte Carlo code BEAM was used to simulate an 18 MV photon beam from a Varian Clinac-2100EX accelerator. Both EGS4/DOSXYZ and EGSnrc/DOSRZnrc were used in the dose calculations. Measured neutron dose equivalents as a function of depth per unit total dose in water were presented for 10 x 10 and 40 x 40 cm2 fields. The measured results have shown that a 5-10 cm thick borated polyethylene slab can reduce the neutron dose by a factor of 2 when inserted between the accelerator head and the detector. In all cases the measured neutron dose equivalent was less than 0.5% of the photon dose. In order to study if the ion chamber was highly sensitive to the neutron dose, we have investigated the disagreement between the Monte Carlo calculated and measured central-axis depth-dose curves in the build-up region when different shielding materials were used. The result indicated that the IC-10 chamber was not highly sensitive to the neutron dose. Therefore, neutrons present in a high-energy photon beam were unlikely to be responsible for the reported discrepancies in the build-up region for large fields.

A Monte Carlo approach to validation of FFF VMAT treatment plans for the TrueBeam linac.

PURPOSE: To commission and benchmark a vendor-supplied (Varian Medical Systems) Monte Carlo phase-space data for the 6 MV flattening filter free (FFF) energy mode on a TrueBeam linear accelerator for the purpose of quality assurance of clinical volumetric modulated arc therapy (VMAT) treatment plans. A method for rendering the phase-space data compatible with BEAMnrc/DOSXYZnrc simulation software package is presented. METHODS: Monte Carlo (MC) simulations were performed to benchmark the TrueBeam 6 MV FFF phase space data that have been released by the Varian MC Research team. The simulations to benchmark the phase space data were done in three steps. First, the original phase space which was created on a cylindrical surface was converted into a format that was compatible with BEAMnrc. Second, BEAMnrc was used to create field size specific phase spaces located underneath the jaws. Third, doses were calculated with DOSXYZnrc in a water phantom for fields ranging from 1 × 1 to 40 × 40 cm(2). Calculated percent depth doses (PDD), transverse profiles, and output factors were compared with measurements for all the fields simulated. After completing the benchmarking study, three stereotactic body radiotherapy (SBRT) VMAT plans created with the Eclipse treatment planning system (TPS) were calculated with Monte Carlo. Ion chamber and film measurements were also performed on these plans. 3D gamma analysis was used to compare Monte Carlo calculation with TPS calculations and with film measurement. RESULTS: For the benchmarking study, MC calculated and measured values agreed within 1% and 1.5% for PDDs and in-field transverse profiles, respectively, for field sizes >1 × 1 cm(2). Agreements in the 80%-20% penumbra widths were better than 2 mm for all the fields that were compared. With the exception of the 1 × 1 cm(2) field, the agreement between measured and calculated output factors was within 1%. It is of note that excellent agreement in output factors for all field sizes including highly asymmetric fields was achieved without accounting for backscatter into the beam monitor chamber. For the SBRT VMAT plans, the agreement between Monte Carlo and ion chamber point dose measurements was within 1%. Excellent agreement between Monte Carlo, treatment planning system and Gafchromic film dose distribution was observed with over 99% of the points in the high dose volume passing the 3%, 3 mm gamma test. CONCLUSIONS: The authors have presented a method for making the Varian IAEA compliant 6 MV FFF phase space file of the TrueBeam linac compatible with BEAMnrc/DOSXYZnrc. After benchmarking the modified phase space against measurement, they have demonstrated its potential for use in MC based quality assurance of complex delivery techniques.