A simulation study on the effect of penetration of gold nanoparticles in the cytoplasm of healthy eye organs on dose enhancement of brachytherapy.

PURPOSE: Special properties and recent advances in the synthesis and biomolecular functionalization of gold nanoparticles (GNPs) have led to the evolution of their use in biomedical applications such as photon radiotherapy. Simulation-based studies on the effect of various parameters that govern the dose enhancement due to utilizing GNPs have facilitated the progress of knowledge in this field. Due to their flexibility and easier accessibility compared with experimental works, simulations have the potential to be considered for pre-clinical tests and, therefore, should be close to the realistic conditions as much as possible. MATERIALS AND METHODS: To this aim, the present work investigates the effect of the presence of GNPs that are accumulated in the cytoplasm of the constituent cells in healthy tissues of a human eye phantom, inspired by the published experimental results which report that non-target tissues also receive the drugs containing GNPs. The GNPs' concentrations are assumed to decrease by moving from the tumor toward the depth of the phantom through a suggested pattern. The MCNPX Monte Carlo code is used for the simulations. RESULTS: The results show that for four concentrations tested, the dose enhancement factor in the shallower layer reaches 6, and decreases to 1.2 in the last layer. The dose enhancements are also examined for critical structures of the iris, cornea, sclera, and lens, showing maximum deviations of about 3 to 200% compared with the absence of GNPs in the healthy tissue. Considering the reported doses to the lens by clinical institutions, the effect of penetration of GNPs to deep layers on treatment time is also investigated. CONCLUSIONS: The results show that the penetration of GNPs from the tumor toward healthy tissues strongly controls the dose enhancement over the various eye structures and emphasizes the importance of modeling the GNPs' distribution in the medium on the overall dose enhancement. Considering the current challenges in the clinical use of GNPs, more effort needs to be made to reach an effective endpoint in treatment.

Monte Carlo-based dosimetry of proposed bi-radionuclide (125I and 106Ru/106Rh) eye plaque: A feasibility study.

BACKGROUND: Combining the sharp dose fall off feature of beta-emitting 106Ru/106Rh radionuclide with larger penetration depth feature of photon-emitting125I radionuclide in a bi-radionuclide plaque, prescribed dose to the tumor apex can be delivered while maintaining the tumor dose uniformity and sparing the organs at risk. The potential advantages of bi-radionuclide plaque could be of interest in context of ocular brachytherapy. PURPOSE: The aim of the study is to evaluate the dosimetric advantages of a proposed bi-radionuclide plaque for two different designs, consisting of indigenous 125I seeds and 106Ru/106Rh plaque, using Monte Carlo technique. The study also explores the influence of other commercial 125I seed models and presence or absence of silastic/acrylic seed carrier on the calculated dose distributions. The study further included the calculation of depth dose distributions for the bi-radionuclide eye plaque for which experimental data are available. METHODS: The proposed bi-radionuclide plaque consists of a 1.2-mm-thick silver (Ag) spherical shell with radius of curvature of 12.5 mm, 20 µm-thick-106Ru/106Rh encapsulated between 0.2 mm Ag disk, and a 0.1-mm-thick Ag window, and water-equivalent gel containing 12 symmetrically arranged 125I seeds. Two bi-radionuclide plaque models investigated in the present study are designated as Design I and Design II. In Design I, 125I seeds are placed on the top of the plaque, while in Design II 106Ru/106Rh source is positioned on the top of the plaque. In Monte Carlo calculations, the plaque is positioned in a spherical water phantom of 30 cm diameter. RESULTS: The proposed bi-radionuclide eye plaque demonstrated superior dose distributions as compared to 125I or 106Ru plaque for tumor thicknesses ranges from 5 to 10 mm. Amongst the designs, dose at a given voxel for Design I is higher as compared to the corresponding voxel dose for Design II. This difference is attributed to the higher degree of attenuation of 125I photons in Ag as compared to beta particles. Influence of different 125I seed models on the normalized lateral dose profiles of Design I (in the absence of carrier) is negligible and within 5% on the central axis depth dose distribution as compared to the corresponding values of the plaque that has indigenous 125I seeds. In the presence of a silastic/acrylic seed carrier, the normalized central axis dose distributions of Design I are smaller by 3%-12% as compared to the corresponding values in the absence of a seed carrier. For the published bi-radionuclide plaque model, good agreement is observed between the Monte Carlo-calculated and published measured depth dose distributions for clinically relevant depths. CONCLUSION: Regardless of the type of 125I seed model utilized and whether silastic/acrylic seed carrier is present or not, Design I bi-radionuclide plaque offers superior dose distributions in terms of tumor dose uniformity, rapid dose fall off and lesser dose to nearby critical organs at risk over the Design II plaque. This shows that Design I bi-radionuclide plaque could be a promising alternative to 125I plaque for treatment of tumor sizes in the range 5 to 10 mm.

Novel 3D printed universal conical holder for eye plaque quality assurance.

PURPOSE: For the custom-built construction of eye plaques, the iodine (I-125) seeds of different source strengths are recycled in our eye plaque program. To return I-125 seeds to the correct lot, we developed a novel 3D-printed conical plaque QA holder for relative assay for eye plaques. MATERIALS AND METHODS: A universal 3D-printed conical plaque holder was designed to accommodate six plaque sizes and fit reproducibly in a well-type dose calibrator. A reproducibility test was used to compare the plaque placement consistency in the holder versus without the holder. Plaque assays were performed for assembled plaques both before implant and after explant. The explant reading was compared with the implant reading adjusted for decay, and the relative error was calculated. The plaque response fraction (PRF) is defined as the fraction of well chamber implant reading over the total seed strength for a plaque. The PRF was aggregated for each individual plaque to confirm the seed lot before implant. RESULTS: The reproducibility test showed the chamber reading's relative standard deviation of 0.40% with the QA holder compared to 0.68% without it. The batch relative assay was performed for 251 plaques. The absolute value of measurement deviation between explant and decay-corrected implant readings is 0.89% ± 0.86% (mean ± standard deviation). The PRFs for individual plaques range from 36.49% to 49.87%, with a maximum standard deviation of 2%. CONCLUSIONS: This novel 3D-printed QA holder provides reproducible setup for assaying assembled eye plaques in a well chamber. Batch relative assay can validate the seed batch used and plaque integrity during the implant without assaying individual seeds, saving valuable physicist time and radiation exposure from seed handling.

I-125 eye-plaque seed economics: To re-use or to not re-use? A single institutional cost savings analysis of re-using I-125 radioactive seeds for eye-Plaque brachytherapy.

INTRODUCTION: Iodine-125 (I-125) seeds, commonly used in low-dose rate brachytherapy for ocular malignancies, are often discarded after a single use. This study examines the potential cost savings at an institution with high ocular melanoma referrals, by re-using I-125 seeds for eye-plaque brachytherapy. METHODS: In this single-institutional retrospective analysis, data was collected from I-125 seed orders from 8/2019 through 10/2022. Information including number of seeds ordered per lot, number of plaques built per lot, and number of seeds used per lot were collected. Cost per lot of seed was assumed to be the current cost from the most recent lot of 35 seeds. RESULTS: During the study, 72 I-125 seed lots were ordered bi-weekly, with a median of 35 seeds per lot (Range: 15-35). Each seed was used on average 2.26 times prior to being discarded. The average duration of each seed lot used was 62.2 days (Range: 21-126). Each seed lot contributed to the construction of an average of 8.4 eye plaques (Range: 2-20). With seed recycling, 2,475 seeds were used to construct 608 eye-plaques. Without re-using practice this would require 5,694 seeds. This resulted in a percentage cost savings of 56.5%, with a total seed cost reduction of $344,884, or $559 per eye-plaque on average. CONCLUSION: This is the first study to evaluate cost savings relative to re-using I-125 seeds for eye plaques. The data demonstrates how an institution can decrease costs associated with I-125 radiation seeds used for eye-plaque brachytherapy by re-using them.

Eye Plaque Brachytherapy for Choroidal Malignant Melanoma: A Case Report on the Use of Innovative Technology to Expand Access, Improve Practice, and Enhance Outcomes.

Our institute established an eye plaque interstitial brachytherapy (EPIBT) program in 2007 using the Collaborative Ocular Melanoma Study (COMS) eye plaque. In this case report, we demonstrated an eye plaque treatment planned and executed using Eye Physics Plaque (Los Alamitos, CA) for a 72-year-old male patient with an extra-large tumor with a maximum width of 18.6 mm and height of 13.7 mm. The use of a customized eye plaque, manufactured through three-dimensional (3D) printing, has empowered us to plan and administer treatment for this patient with uveal melanoma. Without this option, enucleation, an option declined by the patient, or proton beam therapy (PBT), which the patient was unwilling to pursue in another state, would have been the alternative course of action. We were able to use more than one activity of the I-125 seeds, which enabled us to shape and reduce the dose to normal surrounding structures at risk within the orbit and in the vicinity of the orbital cavity. Using the dose evaluation tools available with the modern treatment planning system, we reduced the prescription dose from 85 to 70 Gy, with D90 of 140 Gy, thereby providing effective treatment and limiting risk organ doses. In summary, we were able to dose-deescalate without compromising the chances of controlling retinal/scleral tumors. The patient is doing well from a recent follow-up visit 12 months after the eye plaque brachytherapy treatment. The tumor was 4.80 mm high, 1/3 of the original height, and vision is back to 20/60, demonstrating a successful treatment.

Equivalent uniform RBE-weighted dose in eye plaque brachytherapy.

BACKGROUND: Brachytherapy for ocular melanoma is based on the application of eye plaques with different spatial dose nonuniformity, time-dependent dose rates and relative biological effectiveness (RBE). PURPOSE: We propose a parameter called the equivalent uniform RBE-weighted dose (EUDRBE) that can be used for quantitative characterization of integrated cell survival in radiotherapy modalities with the variable RBE, dose nonuniformity and dose rate. The EUDRBE is applied to brachytherapy with 125I eye plaques designed by the Collaborative Ocular Melanoma Study (COMS). METHODS: The EUDRBE is defined as the uniform dose distribution with RBE = 1 that causes equal cell survival for a given nonuniform dose distribution with the variable RBE > 1. The EUDRBE can be used for comparison of cell survival for nonuniform dose distributions with different RBE, because they are compared to the reference dose with RBE = 1. The EUDRBE is applied to brachytherapy with 125I COMS eye plaques that are characterized by a steep dose gradient in tumor base-apex direction, protracted irradiation during time intervals of 3-8 days, and variable dose-rate dependent RBE with a maximum of about 1.4. The simulations are based on dose of 85 Gy prescribed to the farthest intraocular extent of the tumor (tumor apex). To compute the EUDRBE in eye plaque brachytherapy and correct for protracted irradiation, the distributions of physical dose have been converted to non-uniform distributions of biologically effective dose (BED) to include the biological effects of sublethal cellular repair, Our radiobiological analysis considers the combined effects of different time-dependent dose rates, spatial dose non-uniformity, dose fractionation and different RBE and can be used to derive optimized dose regimens brachytherapy. RESULTS: Our simulations show that the EUDRBE increases with the prescription depths and the maximum increase may achieve 6% for the tumor height of 12 mm. This effect stems from a steep dose gradient within the tumor that increases with the prescription depth. The simulations also show that the EUDRBE increase may achieve 12% with increasing the dose rate when implant duration decreases. The combined effect of dose nonuniformity and dose rate may change the EUDRBE up to 18% for the same dose prescription of 85 Gy to tumor apex. The absolute dose range of 48-61 Gy (RBE) for the EUDRBE computed using 4 or 5 fractions is comparable to the dose prescriptions used in stereotactic body radiation therapy (SBRT) with megavoltage X-rays (RBE = 1) for different cancers. The tumor control probabilities in SBRT and eye plaque brachytherapy are very similar at the level of 80% or higher that support the hypothesis that the selected approximations for the EUDRBE are valid. CONCLUSIONS: The computed range of the EUDRBE in 125I COMS eye plaque brachytherapy suggests that the selected models and hypotheses are acceptable. The EUDRBE can be useful for analysis of treatment outcomes and comparison of different dose regimens in eye plaque brachytherapy.

GEC-ESTRO survey of 106Ru eye applicator practice for ocular melanoma - Physicist survey.

AIM: 106Ru eye plaque brachytherapy (BT, interventional radiotherapy) is an eye-preserving treatment for uveal melanoma performed in about 100 clinics worldwide. Despite this relatively low number, there is a considerable variation in clinical practice. In 2022, the BRAPHYQS and Head & Neck and Skin GEC-ESTRO working groups conducted a survey to map the current clinical practice. The survey consisted of a physicist and a physician part. This paper describes the physicist results. However, three physician questions with overlapping interest are included here as well. MATERIALS AND METHODS: The survey questions pertained to commissioning and quality control (QC) of the plaques, treatment planning, radiobiological correction, as well as more general questions on practice improvement. The questions overlapping with the physician survey were related to dose prescription and margins. RESULTS: Sixty-five physicist responses were included. A majority of the centres do not perform an independent measurement of the absorbed dose at reference depth, percentage depth dose (PDD) and off-axis data. A lack of calibration services and suitable equipment are the main reasons. About one third of the centres indicated that they do image based treatment planning. The use of margins and dose prescription showed a large variability, despite the availability of guidelines [1]. Many respondents expressed a strong wish for improvement in a wide range of aspects of clinical practice. CONCLUSION: The physics survey showed a wide variability regarding quality control of the 106Ru sources and treatment planning practice.

Novel intraocular shielding device for eye plaque brachytherapy using magnetite nanoparticles: A proof-of-concept study using radiochromic film and Monte Carlo simulations.

PURPOSE: Eye plaque brachytherapy is a mainstay treatment for uveal melanomas despite potential toxicities to normal tissues. This work proposes a nanoparticle ferrofluid as a novel intraocular shielding device. With a modified magnetic plaque, the shielding particles are drawn to the tumor surface, attenuating dose beyond the tumor while maintaining prescription dose to the target. METHODS AND MATERIALS: Ferromagnetic nanoparticles suspended in a silicone polymer were synthesized to provide a high-density shielding medium. The ferrofluid's half-value layer (HVL) was quantified for 125I photons using radiochromic film and Monte Carlo methods. A magnetic COMS plaque was created and evaluated in its ability to attract ferrofluid over the tumor. Two ferrofluid shielding mediums were evaluated in their ability to attenuate dose at adjacent structures with in vitro measurements using radiochromic film, in addition to Monte Carlo studies. RESULTS: The shielding medium's HVL measured approximately 1.3 mm for an 125I photon spectrum, using film and Monte Carlo methods. With 0.8 mL of shielding medium added to the vitreous humor, it proved to be effective at reducing dose to normal tissues of the eye. Monte Carlo-calculated dose reductions of 65%, 80%, and 78% at lateral distances 5, 10, and 18 mm from a tumor (5-mm apical height) in a modeled 20-mm COMS plaque. CONCLUSIONS: The magnitude of dose reduction could reduce the likelihood of normal tissue side effects for plaque brachytherapy patients, including patients with normal tissues close to the plaque or tumor. Additional studies, safety considerations, and preclinical work must supplement these findings before use.

Monte Carlo investigation of dose distribution of uniformly and non-uniformly loaded standard and notched eye plaques.

To investigate the effect of using non-uniform loading and notched plaques on dose distribution for eye plaques. Using EGSnrc Monte Carlo (MC) simulations, we investigate eye plaque dose distributions in water and in an anatomically representative eye phantom. Simulations were performed in accordance with TG43 formalism and compared against full MC simulations which account for inter-seed and inhomogeneity effects. For standard plaque configurations, uniformly and non-uniformly loaded plaque dose distributions in water showed virtually no difference between each other. For standard plaque, the MC calculated dose distribution in planes parallel to the plaque is narrower than the TG43 calculation due to attenuation at the periphery of the plaque by the modulay. MC calculated the dose behind the plaque is fully attenuated. Similar results were found for the notched plaque, with asymmetric attenuation along the plane of the notch. Cumulative dose volume histograms showed significant reductions in the calculated MC doses for both tumor and eye structures, compared to TG43 calculations. The effect was most pronounced for the notch plaque where the MC dose to the optic nerve was greatly attenuated by the modulay surrounding the optic nerve compared to the TG43. Thus, a reduction of optic nerve D95% from 14 to 0.2 Gy was observed, when comparing the TG43 calculation to the MC result. The tumor D95% reduced from 89.2 to 79.95 Gy for TG43 and MC calculations, respectively. TG43 calculations overestimate the absolute dose and the lateral dose distribution of both standard and notched eye plaques, leading to the dose overestimation for the target and organs at risk. The dose matching along the central axis for the non-uniformly loaded plaques to that of uniformly loaded ones was found to be sufficient for providing comparable coverage and can be clinically used in eye-cancer-busy centers.

Radio-luminescent imaging for rapid, high-resolution eye plaque loading verification.

BACKGROUND: Eye plaque brachytherapy is currently an optimal therapy for intraocular cancers. Due to the lack of an effective and practical technique to measure the seed radioactivity distribution, current quality assurance (QA) practice according to the American Association of Physicists in Medicine TG129 only stipulates that the plaque assembly be visually inspected. Consequently, uniform seed activity is routinely adopted to avoid possible loading mistakes of differential seed loading. However, modulated dose delivery, which represents a general trend in radiotherapy to provide more personalized treatment for a given tumor and patient, requires differential activities in the loaded seeds. PURPOSE: In this study, a fast and low-cost radio-luminescent imaging and dose calculating system to verify the seed activity distribution for differential loading was developed. METHODS: A proof-of-concept system consisting of a thin scintillator sheet coupled to a camera/lens system was constructed. A seed-loaded plaque can be placed directly on the scintillator surface with the radioactive seeds facing the scintillator. The camera system collects the radioluminescent signal generated by the scintillator on its opposite side. The predicted dose distribution in the scintillator's sensitive layer was calculated using a Monte Carlo simulation with the planned plaque loading pattern of I-125 seeds. Quantitative comparisons of the distribution of relative measured signal intensity and that of the relative predicted dose in the sensitive layer were performed by gamma analysis, similar to intensity-modulated radiation therapy QA. RESULTS: Data analyses showed high gamma (3%/0.3 mm, global, 20% threshold) passing rates for correct seed loadings and low passing rates with distinguished high gamma value area for incorrect loadings, indicating that possible errors may be detected. The measurement and analysis only required a few extra minutes, significantly shorter than the time to assay the extra verification seeds the physicist already must perform as recommended by TG129. CONCLUSIONS: Radio-luminescent QA can be used to facilitate and assure the implementation of intensity-modulated, customized plaque loading.

Contemporary trends in management of uveal melanoma.

Purpose: In the management of uveal melanoma, eye plaque brachytherapy (EPBT) has replaced enucleation as the standard of care for small size tumors that require treatment, and for medium size tumors. In the modern era, EPBT is being utilized more frequently for certain large tumors as well. While there is prospective randomized evidence to support utilization of EPBT for tumors of appropriate dimensions, it is unclear what the actual practice patterns are across the United States. The purpose of this publication was to look at contemporary trends in the management of uveal melanoma across the United States to determine whether practices are appropriately adopting EPBT, and to investigate demographic and socio-economic factors that might be associated with deviations from this standard of care. Material and methods: The National Cancer Database was queried (2004-2015) for patients with uveal melanoma. Data regarding tumor characteristics and treatment were collected. Two-sided Pearson χ2 test was used to compare categorical frequencies between patients who received globe preserving treatments vs. those who received enucleation. Multivariable logistic regression modeling was used to determine characteristics predictive for receiving enucleation. Results: The enucleation rate for small/medium tumors (≤ 10 mm apical height and ≤ 16 mm basal diameter) decreased from 20% in 2004 to 10% in 2015. The EPBT rate for large tumors increased from 30% in 2004 to 45% in 2015. Numerous demographic and socio-economic factors were found to be associated with higher rates of enucleation. Conclusions: The overall trend across the nation is a decreased enucleation rate for small/medium tumors, and an increased EPBT rate for large tumors. A fraction of patients who should be candidates for EPBT are instead receiving enucleation, and in this study, we have shown that certain adverse demographic factors are associated with this.

Comparison between dose distribution from 103Pd, 131Cs, and 125I plaques in a real human eye model with different tumor size.

Knowledge of the energy deposition in different eye components is a critical decision-making to the overall effectivity of ocular melanoma treatment with plaques loaded with low-energy sources. The aim of this study is using the GATE 8.2 Monte Carlo code to calculate the 3D dose distribution in a realistic eye model. At first, we validated the GATE simulation for 125I, 103Pd, and 131Cs seeds by calculating the dose rate constant, radial dose function, and anisotropy function of the three radioactive sources. Then, a 12-mm Collaborative Ocular Melanoma Study (COMS) eye plaque was simulated in the eye phantoms to evaluate dose distribution due to low-energy gamma emitters on the three simulated medium-sized tumors. The findings of this study indicate that the estimated doses received by different eye substructures strongly depend on the source type. The results show that the type of seeds used in the plaque, as well as the size of the eye tumor, have significant effects on the dose deposition in the different structures of the eye and dose deposition uniformity. Moreover, comparing different radionuclides showed that the COMS plaque fully loaded with 103Pd presents a higher dose delivery to the tumor and a lower one to the critical structures for medium-sized tumors, while the plaque fully loaded with 131Cs produces the most uniform dose distribution in the tumor.

Dual-source strength seed loading for eye plaque brachytherapy using eye physics eye plaques: A feasibility study.

Purpose: This study quantifies the dosimetric impact of incorporating two iodine-125 (125I) seed source strengths in Eye Physics eye plaques for treatment of uveal melanoma. Material and methods: Plaque Simulator was used to retrospectively plan 15 clinical cases of three types: (1) Shallow tumors (< 5.5 mm) with large base dimensions (range, 16-19 mm); (2) Tumors near the optic nerve planned with notched plaques; and (3) Very shallow (< 3.0 mm) tumors with moderate base dimensions (range, 13.5-15.5 mm) planned with larger plaques than requested by the ocular oncologist. Circular plaques were planned with outer ring sources twice the source strength of inner sources, and notched plaques with the six seeds closest to the notch at twice the source strength. Results: In cases of type (1), the dual-source strength plan decreased prescription depth, and doses to critical structures were lower: inner sclera -25% ±2%, optic disc -7% ±3%, and fovea -6% ±3%. In four out of five cases of type (2), the dual-source strength plan decreased prescription depth, and dose to inner sclera was lower (-22% ±5%), while dose to optic disc (17% ±7%) and fovea (20% ±12%) increased. In cases of type (3), a smaller dual-source strength plaque was used, and scleral dose was lower (-45% ±3%), whereas dose to optic disc (1% ±14%) and fovea (5% ±5%) increased. Conclusions: Dual-source strength loading as described in this study can be used to cover tumor margins and decrease dose to sclera, and therefore the adjacent retina, but can either decrease or increase radiation dose to optic disc and fovea depending on location and size of the tumor. This technique may allow the use of a smaller plaque, if requested by the ocular oncologist. Clinical determination to use this technique should be performed on an individual basis, and additional QA steps are required. Integrating the use of volumetric imaging may be warranted.

Local tumor control and treatment related toxicity after plaque brachytherapy for uveal melanoma: A systematic review and a data pooled analysis.

Uveal melanoma (UM) represents the most common primary intraocular tumor, and nowadays eye plaque brachytherapy (EPB) is the most frequently used visual acuity preservation treatment option for small to medium sized UMs. The excellent local tumor control (LTC) rate achieved by EPB may be associated with severe complications and adverse events. Several dosimetric and clinical risk factors for the development of EPB-related ocular morbidity can be identified. However, morbidity predictive models specifically developed for EPB are still scarce. PRISMA methodology was used for the present systematic review of articles indexed in PubMed in the last sixteen years on EPB treatment of UM which aims at determining the major factors affecting local tumor control and ocular morbidities. To our knowledge, for the first time in EPB field, local tumor control probability (TCP) and normal tissue complication probability (NTCP) modelling on pooled clinical outcomes were performed. The analyzed literature (103 studies including 21,263 UM patients) pointed out that Ru-106 EPB provided high local control outcomes while minimizing radiation induced complications. The use of treatment planning systems (TPS) was the most influencing factor for EPB outcomes such as metastasis occurrence, enucleation, and disease specific survival, irrespective of radioactive implant type. TCP and NTCP parameters were successfully extracted for 5-year LTC, cataract and optic neuropathy. In future studies, more consistent recordings of ocular morbidities along with accurate estimation of doses through routine use of TPS are needed to expand and improve the robustness of toxicity risk prediction in EPB.

Intensity modulated high dose rate ocular brachytherapy using Se-75.

PURPOSE: We propose an alternative to LDR brachytherapy for the treatment of ocular melanomas by coupling intensity modulation, through the use of a gold shielded ring applicator, with a middle energy HDR brachytherapy source, Se-75. In this study, we computationally test this proposed design using MCNP6. METHODS AND MATERIALS: An array of discrete Se-75 sources is formed into a ring configuration within a gold shielded applicator, which collimates the beam to a conical shape. Varying this angle of collimation allows for the prescription dose to be delivered to the apex of various sized targets. Simulations in MCNP6 were performed to calculate the dosimetric output of the Se-75 ring source for various sized applicators, collimators, and target sizes. RESULTS: The prescription dose was delivered to a range of target apex depths 3.5-8 mm in the eye covering targets 10-15 mm in diameter by using various sized applicators and collimators. For a 16 mm applicator with a collimator opening that delivers the prescription dose to a depth of 5 mm in the eye, the maximum percent dose rate to critical structures was 30.5% to the cornea, 35.7% to the posterior lens, 33.3% to the iris, 20.1% to the optic nerve, 278.0% to the sclera, and 267.3% to the tumor. CONCLUSIONS: When using Se-75 in combination with the proposed gold shielded ring applicator, dose distributions are appropriate for ocular brachytherapy. The use of a collimator allows for the dose to more easily conform to the tumor volume. This method also reduces treatment time and cost, and it eliminates hand dose to the surgeon through the use of a remote afterloader device.

How to design, fabricate, and validate a customized COMS-style eye plaque: Illustrated with a narrow-slotted plaque example.

PURPOSE: A customized Collaborative Ocular Melanoma Study (COMS)-style eye plaque may provide superior dosimetric coverage compared with standard models for certain intraocular tumor locations and shapes. This work provides a recipe for developing and validating such customized plaques. METHODS AND MATERIALS: The concept-into-clinical treatment process for a customized COMS-style eye plaque begins with a CAD model design that meets the specifications of the radiation oncologist and surgeon based on magnetic resonance, ultrasound, and clinical measurements, as well as a TG-43 hybrid heterogeneity-corrected dose prediction to model the dose distribution. Next, a 3D printed plastic prototype is created and reviewed. After design approval, a Modulay plaque is commercially fabricated. Quality assurance (QA) is subsequently performed to verify the physical measurements of the Modulay and Silastic and also includes dosimetric measurement of the calibration, depth dose, and dose profiles. Sterilization instructions are provided by the commercial fabricator. This customization procedure and QA methodology is demonstrated with a narrow-slotted plaque that was recently constructed for the treatment of a circumpapillary (e.g., surrounding the optic disk) ocular tumor. RESULTS: The production of a customized COMS-style eye plaque is a multistep process. Dosimetric modeling is recommended to ensure that the design will meet the patient's needs, and QA is essential to confirm that the plaque has the proper dimensions and dose distribution. The customized narrow-slotted plaque presented herein was successfully implemented in the clinic, and provided superior dose coverage of juxtapapillary and circumpapillary tumors compared with standard or notched COMS-style plaques. Plaque development required approximately 30 h of physicist time and a fabrication cost of $1500. CONCLUSION: Customized eye plaques may be used to treat intraocular tumors that cannot be adequately managed with standard models. The procedure by which a customized COMS-style plaque may be designed, fabricated, and validated was presented along with a clinical example.

On the importance of quality assurance (QA) for COMS eye plaque Silastic inserts: A guide to measurement methods, typical variations, and an example of how QA intercepted a manufacturing aberration.

PURPOSE: Eye plaques are widely used for ocular melanoma and provide an effective alternative to enucleation with adequate tumor control. A COMS plaque utilizes a Silastic insert for precise positioning of the radioactive seeds with respect to the scleral surface of the eye; however, due to manufacturing variability, the insert may unintentionally increase or decrease the distance between the sources and tumor. The purpose of this work is to provide guidance in measuring and identifying outliers in Silastic inserts. The importance of regular quality assurance (QA) is illustrated in an experience where a systematic problem was detected and the manufacturer's 22-mm mold was corrected. METHODS: A detailed description of the molds and manufacturing process used to produce Silastic inserts is provided, including photographs of the process steps. The variability in Silastic insert production was evaluated by measuring the thickness of 124 Silastic inserts. An estimate of how the observed Silastic thickness discrepancies impact the dose to the tumor and critical eye structures was performed using homogeneous dose calculations. A standard QA protocol was developed to guide the clinical user. RESULTS: Thickness of the measured Silastic inserts ranged from 1.22 to 2.67 mm, demonstrating variation from the 2.25 mm standard. Six of the 22-mm inserts were outliers (Δthickness >3 standard deviations) and were excluded from the statistics. The outliers were investigated with the help of the manufacturer, who discovered that a systematic error was accidentally introduced into the 22-mm mold. CONCLUSIONS: Due to manufacturing errors or variability, the Silastic inserts used in COMS eye plaques may be thicker or thinner than the design standard. Such variations may impact tumor control or increase the risk of normal tissue side effects. A standardized QA program is recommended to detect variations and communicate unusual findings to the manufacturer.

Comprehensive assessment of the effect of eye plaque tilt on tumor dosimetry.

PURPOSE: Tilting of the posterior plaque margin during eye plaque brachytherapy can lead to tumor underdosing and increased risk of local recurrence. We performed a quantitative analysis of the dosimetric effects of plaque tilt as a function of tumor position, basal dimension, height and plaque type using 3D treatment planning software. MATERIALS AND METHODS: Posterior and anterior tumors with largest basal dimensions of 6, 12 and 18 mm and heights of 4, 7 and 10 mm were modeled. Both Eye Physics and COMS plaques were simulated and uniformly loaded. Plans were normalized to 85 Gy at the tumor apex. Posterior plaque tilts of 1, 2, 3 and 4 mm were simulated. RESULTS: Volumetric coverage is more sensitive to tilt than the area coverage. Wide, flat tumors are more susceptible to tilt. Apical dose changed significantly as a function of tumor height and diameter. No other parameter exhibited significant differences. Posterior tumors are slightly more susceptible to tilt due to the use of notched plaques. Plaque type does not significantly alter the effect of plaque tilt. CONCLUSIONS: Wide, flat tumors are the most susceptible to plaque tilt. Tumor location or plaque type does not have a significant effect on dosimetry changes from plaque tilt. Robust clinical procedures such as the use of mattress sutures, pre- and post-implant ultrasound and post-implant dosimetry can all mitigate the risk associated with plaque tilt.

Shielded high dose rate ocular brachytherapy using Yb-169.

Purpose.We propose an approach for treating ocular melanoma using a new type of brachytherapy treatment device. This device couples Yb-169, a middle-energy high dose rate (HDR) brachytherapy source, with a gold shielded ring applicator to better conform radiation exposures to the tumor. In this study, we computationally test the dosimetric output of our proposed shielded ring applicator design using MCNP6 and validate it against an I-125 COMS plaque.Methods.The proposed Yb-169 ring applicator consists of an assembly of discrete sources delivered into an applicator with a conical collimated opening; this opening is tangent to the outside of the source tube. Using MCNP6, we simulated the dosimetric output of a ring of Yb-169 pellets placed within the collimator at various conical diameters and angles to demonstrate the dosimetric distribution for various prescription dose depths and target sizes using static intensity modulation.Results.Using various angles of collimation, the prescription dose was delivered to target apex depths of 3.5-8.0 mm into the eye covering target sizes ranging from 10 to 15 mm in diameter. This proposed device reduced the maximum absorbed dose to critical structures relative to I-125 by 5.2% to the posterior lens, 9.3% to the iris, 13.8% to the optic nerve, and 1.3% to the sclera.Conclusions.This proposed eye plaque design provides a more conformal dose distribution to the ocular tumor while minimizes dose to healthy ocular structures. In addition, the use of a middle-energy HDR brachytherapy source allows the use of a remote afterloader to expose the tumor after the plaque is sutured in place. This system is inherently safer and eliminates dose to the surgeon's hands.

Update of the CLRP eye plaque brachytherapy database for photon-emitting sources.

PURPOSE: To update and extend the Carleton Laboratory for Radiotherapy Physics (CLRP) Eye Plaque (EP) dosimetry database for low-energy photon-emitting brachytherapy sources using egs_brachy, an open-source EGSnrc application. The previous database, CLRP_EPv1, contained datasets for the Collaborative Ocular Melanoma Study (COMS) plaques (10-22 mm diameter) with 103 Pd or 125 I seeds (BrachyDose-computed, 2008). The new database, CLRP_EPv2, consists of newly calculated three-dimensional (3D) dose distributions for 17 plaques [eight COMS, five Eckert & Ziegler BEBIG, and four others representative of models used worldwide] for 103 Pd, 125 I, and 131 Cs seeds. ACQUISITION AND VALIDATION METHODS: Plaque models are developed with egs_brachy, based on published/manufacturer dimensions and material data. The BEBIG plaques (modeled for the first time) are identical in dimensions to COMS plaques but differ in elemental composition and/or density. Previously benchmarked seed models are used. Eye plaques and seeds are simulated at the center of full-scatter water phantoms, scoring in (0.05 cm)3 voxels spanning the eye for scenarios: (a) "HOMO": simulated TG43 conditions; (b) "HETERO": eye plaques and seeds fully modeled; (c) "HETsi" (BEBIG only): one seed is active at a time with other seed geometries present but not emitting photons (inactive); summation over all i seeds in a plaque then yields "HETsum" (includes interseed effects). For validation, doses are compared to those from CLRP_EPv1 and published data. DATA FORMAT AND ACCESS: Data are available at https://physics.carleton.ca/clrp/eye_plaque_v2, http://doi.org/10.22215/clrp/EPv2. The data consist of 3D dose distributions (text-based EGSnrc "3ddose" file format) and graphical presentations of the comparisons to previously published data. POTENTIAL APPLICATIONS: The CLRP_EPv2 database provides accurate reference 3D dose distributions to advance ocular brachytherapy dose evaluations. The fully-benchmarked eye plaque models will be freely distributed with egs_brachy, supporting adoption of model-based dose evaluations as recommended by TG-129, TG-186, and TG-221.