Oraya Therapeutics Research Articles

SU‐E‐T‐207: Comparison of Integrated Tissue Air Ratio (ITAR) to Traditional TAR for Kilovoltage Pencil‐Beams

Purpose:Clinically viable depth dose determination in kilovoltage pencil‐beams is a great challenge that resulted in a published dosimetry method called ITAR, which involves measurement of air kerma and attenuation with a detector in a low scatter environment coupled with MCNP scatter calculations. The objective of this work is to compare ITAR to traditional TAR using inherently water‐proof microchambers that have only recently become commercially available.Methods:An Exradin A26 microchamber was centered 150 mm from a 100 kVp x‐ray source with 2 mm aluminum HVL. Depth dose in water from 16 to 24 mm in 2 mm increments was determined by: (1) placing blocks of Plastic Water LR near the source to minimize scatter and using previously published conversion coefficients [ITAR method] and (2) submerging the detector in a water tank with 2 mm thick Plastic Water LR walls and jogging the tank with motor controllers while keeping the detector position fixed [traditional TAR method]. Each method was repeated four to five times. For each repetition, dose was measured free in‐air to normalize the data for exponential regression.Results:Traditional TAR indicated higher depth dose than ITAR; differences ranged from 2.1% at 24 mm depth to 2.5% at 16 mm depth. However, the results of traditional TAR did not include a correction for Pq,cham because it is unknown for this detector type in these conditions. It is estimated that the component of Pq,cham due to the effect of water displacement alone is ∼0.94, but Pq,cham is likely several percent larger than 0.94 due to the energy dependency of the microchamber in the presence of low energy scatter that is not present during in‐air calibration.Conclusion:The ITAR method remains preferable for clinical depth dose determination in kilovoltage pencil‐beams due to Pq,cham being unknown for suitable detectors in relevant conditions.All four of the authors are either current full time employees, which include stock option grants, or consultants of Oraya Therapeutics Inc.

Brachytherapy in Neovascular AMD

Neovascular age-related macular degeneration (AMD) has a complex pathophysiology, and although anti-VEGF therapy has been one of the most significant and successful advances, it is not effective for all patients with neovascular AMD. The potential role of radiation in the management of neovascular AMD has been suggested for several years. While previous work focused on the role of radiation alone, recent trials have evaluated the role of ionizing radiation as a synergistic treatment with anti-VEGF drugs, with endpoints being to reduce choroidal neovascular lesions faster, preserve visual acuity, and extend the treatment interval between injections. We review the current evidence available for the safety and efficacy of radiation in conjunction with anti-VEGF treatment for neovascular AMD delivered using three approaches—epimacular brachytherapy involving a pars plana vitrectomy (Vidion Neovista, Inc., Newark, CA, USA), episcleral brachytherapy without a pars plana vitrectomy (Salutaris Medical Devices, Tucson, AZ), and low-voltage stereotactic radiotherapy (IRay, Oraya Therapeutics, Inc., Newark, CA, USA).

SU-E-T-477: Influence of Eye Size on Radiation Absorbed Dose Delivered to Non- Targeted Tissues during Stereotactic Radiosurgery for Age-Related Macular Degeneration.

This work determines how variations in eye size will influence the radiation absorbed dose delivered to non-targeted tissues within the eye during stereotactic radiosurgery of age-related macular degeneration (AMD) using the IRay™ treatment. Stylized models of the eye were created with axial lengths of 20, 22, 24, 26, and 28mm. Each model was based upon the reference eye model from NCRP Report 130 and then scaled appropriately for each axial length. Models were incorporated with MCNPX radiation transport code in order to simulate the three beam IRay™ delivery system. Simulation results were assessed for both the mean absorbed dose and dose-volume histograms (DVH) for both target (macula) and non- targeted eye tissues, including the lens, retina, central retinal artery, and optic nerve. For each of the three beams, an average dose of 8Gy was delivered to the macula resulting in a total average dose of 24Gy for each eye model. The lens of the eye received a total average dose ranging from 146 to 189mGy, with the larger doses occurring in the smaller eye models since the beams traverse through the sciera closer to the limbus. The distal tip (1.5mm) of the central retinal artery received a total average dose ranging from 499 to 567mGy, with the larger doses occurring in the larger eye models due to increased scatter resulting from longer tissue path length to the nominal target. The optic nerve received a total average dose ranging from 207 to 225mGy, with the larger doses occurring in the smaller eye models. The small variation in dose to the lens, central retinal artery, and optic nerve suggests that eye size does not significantly affect radiation dose to non-targeted eye tissues. This work was sponsored by Oraya Therapeutics.

SU-E-T-408: Enhancing Stereotactic Radiosurgery for Neovascular Age-Related Macular Degeneration, Using Gold Nanoparticles.

Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss for people over the age of 60 in the United States. In this study the dosimetric feasibility of using gold nanoparticles (AuNP) as radiosensitizers to enhance stereotactic radiosurgery for neovascular AMD is investigated. Analytic calculations were carried out to estimate the nucleus dose enhancement factor (nDEF) due to photon-induced photo- /Auger electrons from AuNP targeting neovascular AMD endothelial cells (EC). The nDEF represents the ratio of the dose to the nucleus with and without the presence of AuNP. As in previous studies, the EC is modeled as a slab of 2 μm (thickness) × 10 μm (length) × 10 μm (width) containing a nucleus of 5 μm diameter and thickness of 0.5 - 1 μm. The targeted AuNP are attached to the exterior of the EC. The nDEF was calculated for a range of feasible AuNP local concentrations (1-7 mg/g) using the clinically applicable 100 kVp x-rays employed by the IRayTM system (Oraya Therapeutics Inc. Newark, CA), with total filtration of 0.75 mm Al and 0.8 mm Be. For comparison the nDEF for other energies: 80 kVp, 90 kVp, 110 kVp, and 120 kVp was also investigated. For 100 kVp x-rays, the results revealed nDEF values of 1.30 - 3.26 for the investigated concentration range of 1 - 7 mg/g, respectively. In comparison, for the same concentration range, nDEF values of 1.32 - 3.40, 1.31-3.33, 1.29 - 3.19, 1.28 - 3.12 were calculated for 80 kVp, 90 kVp, 110 kVp, and 120 kVp x-rays, respectively. The results predict substantial dose enhancement to the sensitive nucleus of neovascular endothelial cells, targeted by AuNP during kilovoltage stereotactic radiosurgery. This suggests that AuNP may be employed as radiosensitizers to enhance therapeutic efficacy during radiosurgery for neovascular AMD.

SU‐E‐T‐204: Real‐Time Monitoring of Age‐Related Macular Degeneration Radiosurgery Using Plastic Scintillation Dosimetry

Purpose: Age‐related macular degeneration (AMD) is the leading cause of vision loss and blindness among those over age 65. In its wet form, blood vessels grow from the choroid, causing macular tension and sometimes retinal displacement. As an alternative to monthly direct‐injection methods, Oraya Therapeutics has developed the IRayTM stereotactic radiosurgery device. This table‐top system has been validated in Monte Carlo simulations, human cadaver eye studies, pre‐clinical animal studies, and a phase 1 clinical trial. A plastic scintillation dosimetry (PSD) system was developed to monitor dose delivery in real‐time and provide measurement of total dose delivered. Methods: The IRayTM uses 100 keV x‐rays to deliver 24 Gy of macular dose, divided into three positions along the inferior pars plana. The PSDˈs small volume (0.5 mm diameter and 2 mm height), allows placement within the machine head. The PSD is fiber‐optically coupled to a photomultiplier tube via a plastic waveguide. Before direct characterization of the IRayTM, the preliminary PSD performance was tested using a portable x‐ray unit, mobile c‐arm fluoroscopy unit, and an ion chamber. Results: In order to avoid buffering issues, real‐time measurements used 250 ms bins, but can be adjustable to 10 ms. A calibration factor (CF) from PSD percent‐depth‐dose to ion chamber percent‐depth‐dose was 1.06 at a depth of 1.5 cm in solid water, the typical macular target depth. Counts‐to‐exposure CF varied less than 1% from 0.862 to 15.26R. Counts‐to‐exposure CF remained linear with R2 of 0.999 up to 16R even with varying dose rate (.002 R/s to 1.0 R/s). Conclusions: The PSD demonstrated linear dose measurements even at high dose and high dose rates. This study demonstrates the feasibility, accuracy, and precision of a PSD for clinical implantation in the IRayTM, a device for treatment of AMD.This research was supported by a grant from Oraya Therapeutics, Inc.

SU‐E‐T‐684: Simple Integrated Tissue‐Air Ratio (SITAR)

Purpose: Performing direct depth‐dose measurements on the IRay ophthalmological SRS device (designed to treat wet age‐related macular degeneration), with its narrow (4mm), low energy (100kVp) photon beam is not feasible using currently available equipment. The constant SAD indicates use of Tissue‐Air Ratio (TAR). The imperfect water‐equivalency of available tissue‐equivalent plastics at these energies and the absence of small water‐proof, energy‐independent detectors make it impossible to measure TAR directly. The Simple Integrated Tissue‐Air Ratio (SITAR) is a novel method of determining depth‐dose for this novel device. SITAR is Simple in that it is measured simply using a tissue‐equivalent plastic, and applied simply as if to water. It is Integrated because it integrates all appreciable effects: inverse R‐squared divergence, attenuation in water and in tissue‐equivalent plastic, and scatter. SITAR is used to characterize the depth dose of individual IRay devices. Methods: The attenuation properties of three tissue‐equivalent plastics are compared to those of water by direct measurement. The scatter properties of these plastics are compared to scatter in water using Monte‐Carlo simulation. The most water‐like plastic in attenuation and scatter is selected for use in SITAR. Comparing the properties of plastic to water, determinations are made of the SITAR Correction: values that correct measurements taken through the plastic to measurements in water. The SITAR Correction enables a simple series of measurements through plastic to be corrected to a TAR in water. Results: Plastic Water LR (CIRS, Norfolk, VA) is found to be the most water‐like plastic for the IRay treatment beam. Kerma measurements made through varying thicknesses of Plastic Water LR and converted with the SITAR Correction yield a very good estimate of measurements in water. Conclusions: SITAR allows each IRay device to be characterized for depth dose in water simply by taking measurements through plastic.Research sponsored by Oraya Therapeutics.This work is funded by Oraya Therapeutics Inc., Newark, CA

SU-E-T-713: Kilovoltage Stereotactic Radiosurgery for AMD: A More Complete Evaluation of Effective Dose

Purpose: Age‐related Macular Degeneration is a leading cause of blindness for the elderly population in industrialized nations. Monthly injections of ranibizumab stabilize the progression of the disease, and a novel non‐invasive stereotactic radiosurgery is being explored as an adjunct to injections. An estimation of effective dose for a 3 beam × 8 Gy therapeuticdose to the macula had been reported previously by the authors of this paper using head and neck phantoms. Several improvements have been made: expansion of the geometric models to include tissues in the torso, an estimation of leakage contribution, and effect of lead vest usage.Methods: Male and female hybrid voxel torso phantoms were derived from CT slice segmentation and scaled to ICRP Publication 89 reference values. A MATLAB code was developed to “wrap” a single layer of voxels around the torsos, representative of a 0.5 mm lead vest equivalent. A three‐beam photontreatment (100 kVp) was modeled using the MCNPXradiation transport code to evaluate effective dose as per the ICRP Publication 103 schema. A similar calculation was made for leakage, but using a “hard” mono‐energetic (100 keV) point source as an approximation. Results: The calculations yielded an effective dose of 0.389 mSv for the control group, and 0.369 and 0.376 mSv for the use of a lead vest with and without a neck cover, respectively. Comparatively, 0.281 mSv was reported previously for the head and neck phantoms (19% versus 99% wT's). Leakage contribution was estimated to be approximately 0.009 mSv Conclusions: The expanded geometric models and inclusion of leakage contribution provide a more complete estimation of the effective dose than previously reported. The use of lead vests with and without a neck cover result in a 5% and 3% reduction of effective dose, respectively. This work was sponsored by Oraya Therapeutics.

WE‐D‐BRB‐03: Automated Self‐Test Provides Routine QA for a Narrow‐Field, Low‐Energy X‐Ray, Ophthalmic SRS System

Purpose: A narrow‐field, low energy, stereotactic radiosurgery (SRS) device (the “IRay”) designed specifically for the treatment of wet age‐related macular degeneration is being evaluated in a European clinical trial. Because of precise targeting requirements for ophthalmological SRS, a new QA method has been designed to automate the evaluation of system alignment, targeting, and kerma consistency. This poster describes that method. Method and Materials: The IRay delivers up to 24 Gy in three lOOkVp, 4mm‐diameter beams that converge on the retina with a source‐axis distance of 150mm. The beams are delivered inferiorly in a fashion that avoids the patients lens and optic nerve, requiring submillimeter targeting precision. The eye is stabilized with a suction‐enabled lens assembly (the “I‐Guide”) that has retroreflective fiducials used by the imaging system for targeting and eye motion assessment. A self‐test fixture has been designed that incorporates similar fiducials for automatic alignment, a scintillant strip for direct imaging of the X‐ray beam, and an ion chamber for kerma measurements. Results and Discussion Using the retroreflective fiducials, the IRay is able to repeatably and accurately target the fixture. This is critical not only for targeting assessment, but also for accurate kerma measurements which are difficult in a narrow field with a finite‐sized detector. Once targeted, software automatically evaluates and enforces several critical parameters including X‐ray to targeting laser coaxiality (< 100 microns), robotic motion, imaging system alignment (better than 100 microns), X‐ray targeting (within 300 microns), and air kerma consistency (within 3%). Other system tests are performed, including lighting, communication, and dose‐timer checks. Conclusion: Performing comprehensive QA on a narrow‐field, low‐energy SRS unit requiring submillimeter precision is non‐trivial. An automated method of evaluating alignment, targeting, and kerma consistency allows regular (even daily) assessment to provide confidence that all systems are performing within specification. Research sponsored by Oraya Therapeutics.

SU‐GG‐T‐548: Energy and Spatial Distribution of Photon Fluence Emanating from the Head during Stereotactic Radiosurgery for Age‐Related Macular Degeneration

Purpose: Kilovoltage stereotactic radiosurgery (SRS) is currently being explored as a treatment option for wet age‐related macular degeneration (AMD), a leading cause of vision loss in the United States. An evaluation of the distribution of photons exiting the head during treatment will be useful in determining safety parameters regarding clinical staff present. Method and Materials: A male reference head phantom was computationally modeled with Rhinoceros 4.0 using CT slice segmentation scaled to ICRP Publication 89 reference values. The head phantom was voxelized and a three‐beam photon treatment (100 kVp) was modeled using the MCNPX radiation transport code. The beams enter through the sciera at a 30° polar angle relative to the geometric axis of the eye, and deliver a cumulative therapeutic dose of 24 Gy to the macula (8 Gy per beam). An F1 tally sphere, with its origin at the macula target and normal vector aligned with the geometric axis, was used to evaluate the energy and angular distributions of photon fluence at a radius of 0.5 meters. Two‐dimensional matrices were implemented using type 1 mesh tallies, flush with the head tissue, which were used to characterize the spatial distribution of photons emanating from each side of the model. Results: Photon fluence was mostly forward directed with respect to the patient's gaze (backscattered in reference to beam entry) with maxima in the 50–60° and 44.4–50 keV bins. A portion of the beam traverses through the head unattenuated, resulting in a smaller peak around 150°. Color coded contour fluence maps will be created from the mesh tallies to supply a visual representation of fluence. Conclusion: The results of this study will contribute towards the design development of safety parameters related to the treatment device. This work was sponsored by Oraya Therapeutics.

WE-C-BRA-09: A Monte Carlo Method for Assessing Targeting Error in an Ophthalmological Stereotactic Radiosurgical Device

Purpose: To propose and demonstrate a Monte Carlo‐based method of assessing the targeting uncertainty of an ophthalmologic‐specific stereotactic radiosurgerydevice that provides a physically realistic assessment of end‐to‐end uncertainty in targeting accuracy. Using this method, the minimum acceptable an ongoing European clinical trial in the treatment of macular degeneration, separation between optic disc (organ at risk) and fovea (target) was calculated for Method and Materials: All sources of uncertainty in targeting were estimated in categories that include mechanical precision, machine alignment, calibration error, patient motion, and biometric uncertainty. These sources were characterized in terms of their magnitude of error as well as the resulting two‐dimensional shape of their uncertainty distribution on the retina, such as Gaussian, constant, or random. Once uncertainties were characterized, sample “treatments” were simulated by choosing a random magnitudes and directions for each source of error. After statistical noise was adequately reduced, an uncertainty distribution resulted that described the probabilistic position of the beam on the retina. Armed with this distribution, the probability that the proximal portion of the optic disc could receive a dose greater than a threshold could be calculated and a patient eligibility criterion defined. Results: Using this technique, a minimum acceptable fovea to optic disc edge distance was calculated for patients eligible for the radiation treatment of macular degeneration using this SRSdevice.Conclusion: For complex, multi‐dimensional systems this method is more straightforward than the traditional Taylor's expansion method of uncertainty propagation. It explicitly takes into account the non‐normal distribution of most input uncertainties and, as the result itself is a multi‐dimensional probability distribution, provides more insight than a single number like a standard deviation. It allows the user to explicitly select an acceptable risk and tailor the operational parameters to achieve that. Conflict of Interest: Research sponsored by Oraya Therapeutics

Kilovoltage stereotactic radiosurgery for age-related macular degeneration: Assessment of optic nerve dose and patient effective dose

Age-related macular degeneration (AMD) is a leading cause for vision loss for people over the age of 65 in the United States and a major health problem worldwide. Research for new treatments of the wet form of the disease using kilovoltage stereotactic radiosurgery is currently underway at Oraya Therapeutics, Inc. In the present study, the authors extend their previous computational stylized model of a single treated eye [Med. Phys. 35, 5151-5160 (2008)] to include full NURBS-based reference head phantoms of the adult male and female using anatomical data from ICRP Publication 89. The treatment was subsequently modeled in MCNPX 2.5 using a 1 x 1 x 1 mm3 voxelized version of the NURBS models. These models incorporated several organs of interest including the brain, thyroid, salivary glands, cranium, mandible, and cervical vertebrae. A higher resolution eye section at 0.5 x 0.5 x 0.5 mm3 voxel resolution was extracted from the head phantoms to model smaller eye structures including the macula target, cornea, lens, vitreous humor, sclera/retina layer, and optic nerve. Due to lack of literature data on optic nerve pathways, a CT imaging study was undertaken to quantify the anatomical position of the optic nerve. The average absorbed doses to the organs of interest were below generally accepted thresholds for radiation safety. The estimated effective dose was 0.28 mSv which is comparable to diagnostic procedures such as a head radiograph and a factor of 10 lower than a head CT scan.

MO‐FF‐A2‐05: A Novel Stereotactic Radiosurgical Device for the Treatment of Age‐Related Macular Degeneration (AMD)

Purpose: Age‐related Macular Degeneration (AMD) is the leading cause of blindness in people over 65 in the U.S. It is caused by a proliferation of capillaries in the retina and can result in profound and rapid loss of central vision. As a neovascular disease, it has been shown to be susceptible to radiotherapy. Recently, a 100kVp tabletop stereotactic radiosurgical (SRS) device has been developed to deliver highly‐collimated beams of X‐rays to the fovea to treat AMD. This study is an evaluation of that system. Method and Materials: The device delivers a three‐port, 16Gy single fraction dose to the macula. Using a suction‐enabled contact lens assembly (“the I‐Guide”) to stabilize the eye, three 4mm diameter beams of 100kVp x‐rays are delivered to the fovea, directed by a positioning robot. The beams enter the eye through the sclera and avoid the radio‐sensitive lens. The I‐Guide includes reflective fiducials that are monitored by cameras, and the real‐time position of the beam on the retina is calculated from the fiducial positions. Because of uniformity across adult eye populations, a class‐solution treatment plan was implemented using a single parameter (eye length). Software manages treatment time and automatic gating of beam in case of excessive eye motion. A clinical trial is underway. Results: 100kVp proves an optimal energy for ophthalmic radiotherapy. A therapeutic dose to the retina can be delivered with negligible impact to the brain and the scleral entry dose is well‐tolerated. The scatter from the narrow beam is minimal to sensitive structures in the eye. Submillimeter targeting precision was demonstrated in the lab and in the clinic. Submillimeter motion‐management was also demonstrated. Conclusion: The eye‐specific SRS device shows great promise for providing a precise and non‐invasive method of treating AMD.Research sponsored by Oraya Therapeutics.

SU‐FF‐T‐374: Dynamic Anthropomorphic Eye Phantoms for Targeting and Dose Verification of a Novel Ophthalmic Radiosurgical Device

Purpose: Age‐related Macular Degeneration (AMD) is the leading cause of blindness in people over 65 in the U.S. It is a neovascular disease that can result in profound and rapid loss of central vision and has been shown to be susceptible to radiotherapy. A 100kVp tabletop stereotactic radiosurgical (SRS) device has recently been developed to treat AMD. Here we evaluate a new set of anthropomorphic eye phantoms for verifying the targeting and dosimetric accuracy of the device. Method and Materials: A series of eye phantoms were developed to match human eyes in size and shape. The phantoms are made of Solid Water, have a post at the cornea to attach to the clinical fixation assembly, and at the retina have a cutout with fiducial posts that support the precise mounting of laser‐cut pieces of radiochromic film. After irradiation of the phantom, a flatbed scanner and image analysis software are used to assess the accuracy of beam targeting using the fiducial holes in the film. Multiple “treatments” were repeated on stationary phantoms to assess system precision and accuracy. A dynamic eye was also created by attaching set of stepper motors to a phantom. While irradiating the phantom, the motors were driven with clinically‐measured human eye motions to simulate actual treatment and test the automatic beam shut‐off of the system when motion exceeded an established threshold. Results: Phantom measurement precision of 0.1mm was achieved. Static repeated delivery of the therapy showed a system precision of 0.2mm and an accuracy of 0.4mm. Analysis of films irradiated while the eye phantom was being driven with clinically‐measured human motion verified the gating algorithm was capable of protecting radiosensitive structures. Conclusion: The eye phantoms demonstrate that a specialized ophthalmic SRS device can accurately target the back of the eye.Research Supported by Oraya Therapeutics

WE‐C‐BRB‐09: Sensitivity of a Novel External X‐Ray Treatment for Age‐Related Macular Degeneration to Variations in the Position of the Eye

Purpose: Age‐related macular degeneration (AMD) is the leading cause of blindness of the elderly in the United States. A novel external beam treatment has been developed for the treatment of AMD that delivers a 16‐Gy prescribed dose to the fovea (clinical target volume, CTV) using three overlapping low‐energy x‐ray fields while adequately sparing normal tissues in the eye and brain. The purpose of this study was to test the sensitivity of the successful delivery of the prescribed dose to the CTV and of the sparing of normal tissues to plausible variations in the position of the eye. Method and Materials: In the standard case, the axial length of the eye is 24 mm and the gaze is straight ahead. Using Monte Carlo simulations, we examined the overlap of the three beams on the posterior surface of concentric spheres with radii from 10 mm to 14 mm. In addition, we calculated absorbed dose in the CTV and structures at risk while varying varied the gaze angle by ±5° vertically and laterally and the displacement of the eye ±1 mm in all orthogonal directions. Results: The three fields did not diverge for all radii tested. For variations in the position of the eye, the dose to the CTV was stable (<6% fluctuation), the maximum dose to the sclera was <20 Gy, the maximum dose to the optic disc was <0.7 Gy, and the mean doses to the optic nerve, lens, and cornea were <0.3 Gy. Conclusion: The results of this study provide strong evidence that variations in the position of the eye will not hinder the successful delivery of the prescribed dose to the CTV and the sparing of critical structures for this stereotactic radiosurgical treatment of AMD. Conflict of Interest: Research sponsored in part by Oraya Therapeutics, Inc.

TU-D-BRB-05: Dosimetry of a Novel Ophthalmic Stereotactic Radiosurgical Device

Purpose: To propose a method for verifying the dosimetry of a low-energy narrow-beam stereotactic radiosurgical (SRS) device with constant source-axis distance (SAD) for ophthalmic indications. Method and Materials: An SRS under development delivers narrow, overlapping beams to the fovea through the sclera, avoiding the lens. The fovea is always placed at 150mm SAD, so the dose rate at the target can be determined from the air kerma rate at 150mm and the tissue air ratio (TAR) as long as the distance the X-rays travel through eye tissue is known. The TG61 “in-air” protocol is followed to calculate surface dose rate to water at 150mm, though extra precautions must be taken because of the difficulty of working with a 4mm-diameter 100kVp beam. To account for tissue attenuation, predetermined Tissue-Air Ratios (TARs) are applied based on measurements of the eye's axial length. Beam shape, overlap, and system targeting are evaluated by irradiating and analyzing radiochromic film coupons in anthropomorphic eye phantoms. Results: Of the TG61 corrections, end effect is most substantial, requiring explicit compensation to account for the finite ramp-up time of the source. Typical air kerma rate at 150mm for the 100kVp, 18mA treatment is 10.17Gy/min. For a nominal eye (24mm AL), the TAR at the fovea is 0.429. Film coupons show the full-power portion of the beam to have a 2mm radius at 150mm with a geometrical penumbra of 1mm. Scatter at 100kVp is minimal. Conclusion: The combination of the ion chamber and film provide a consistent dosimetric picture, and allow full characterization of low-energy, narrow-beam dosimetry. It is possible to collimate a narrow X-ray beam precisely enough to accurately target the macula and miss the optic nerve and the lens. Research sponsored by Oraya Therapeutics

TH-C-BRD-03: Kilovoltage Stereotactic Radiosurgery for Age Related Macula Degeneration: Assessment of Patient Effective Dose and Patient Specific Tissue Doses

Purpose: Age-related macula degeneration (AMD) is a leading cause of vision loss in the United States. Radiation therapy was initially explored as a treatment option in the 1990's, but has since been abandoned in favor of intraocular drug injections. Interest continues for stereotactic radiosurgery (SRS), an option that provides a noninvasive treatment for the wet form of AMD. Method and Materials: Two adult heads, male and female, were computationally modeled with Rhinoceros 4.0 using CT slice segmentation scaled to ICRP Publication 89 reference values. The head phantoms were voxelized and a three-beam photon treatment (100 kVp) was modeled using the MCNPX radiation transport code to evaluate tissue dose and effective dose. Treatment was also simulated using the reference heads with changeable optic nerve positions based on individual patient variability seen in a head CT scan review. Results: A cumulative dose of 24 Gy to the macula (8 Gy per beam) yielded an effective dose of 0.28 mSv. The maximum doses to the most extreme patient specific optic nerve positions were evaluated using Dose Volume Histograms and found to be below the thresholds for serious complications, as were other reference tissues. Conclusion: The results of this study show that SRS is a safe option considering effective dose and tissue toxicity for a reference individual. Patient specific models will be created from the CT review and treatment will be modeled using MCNPX to establish certainty that this is a safe treatment option for all individuals considering other patient specific variations in anatomy. This work was sponsored by Oraya Therapeutics.

MO‐EE‐A3‐04: Motion Management for a Novel Ophthalmic Stereotactic Radiosurgical Device

Purpose: Teletherapy of an unconstrained eye poses risks because of the likelihood of substantial eye motion. A new 100kVp tabletop stereotactic radiosurgical unit has recently been developed to deliver highly‐collimated beams of x‐rays to the retina. Here we evaluate the efficacy of a hardware and software motion‐management solution designed for that system. Method and Materials: To minimize the effects of motion during therapy, an eye fixation device (the “I‐Guide”) was developed. It consists of a contact‐lens, a central post, and a fixed, horizontal stabilizer bar. The contact lens is held to the eye with suction and attached to the central post. The post is mounted to stabilizer bar via a ball‐joint. The I‐Guide steadies the eye and incorporates reflective fiducials that are used by an imaging system to monitor the position and gaze‐angle of the eye. During treatment, software continuously evaluates the deviation of the eye from nominal position. When necessary, the beam is automatically gated off by an algorithm that incorporates time as well as displacement, allowing brief excursions while still maintaining effective targeting. Results: The motion‐management system was evaluated in a clinical trial of 40 patients. With the I‐Guide in place, rapid eye motion was damped considerably. Because of the time component, the gating algorithm permitted brief, random excursions while stopping the beam when excess drift was apparent. With a 3‐second x‐ray source ramp‐up, this flexibility was important for efficient treatment flow. Although patients' heads were immobilized, head mobility was found to be the dominant source of motion. However, the automatic gating‐off of the beam followed by repositioning kept the average motion error under 0.4mm in all cases. Conclusion: The combination of I‐Guide fixation, fiducial tracking, and automated beam gating enables precise targeting and dose conformality for ophthalmic radiotherapy.Research sponsored by Oraya Therapeutics

Dosimetry characterization of a multibeam radiotherapy treatment for age‐related macular degeneration

Age-related macular degeneration (ARMD) is a major health problem worldwide. Advanced ARMD, which ultimately leads to profound vision loss, has dry and wet forms, which account for 20% and 80% of cases involving severe vision loss, respectively. A new device and approach for radiation treatment of ARMD has been recently developed by Oraya Therapeutics, Inc. (Newark, CA). The goal of the present study is to provide a initial dosimetry characterization of the proposed radiotherapy treatment via Monte Carlo radiation transport simulation. A 3D eye model including cornea, anterior chamber, lens, orbit, fat, sclera, choroid, retina, vitreous, macula, and optic nerve was carefully designed. The eye model was imported into the MCNPX2.5 Monte Carlo code and radiation transport simulations were undertaken to obtain absorbed doses and dose volume histograms (DVH) to targeted and nontargeted structures within the eye. Three different studies were undertaken to investigate (1) available beam angles that maximized the dose to the macula target tissue, simultaneously minimizing dose to normal tissues, (2) the energy dependency of the DVH for different x-ray energies (80, 100, and 120 kVp), and (3) the optimal focal spot size among options of 0.0, 0.4, 1.0, and 5.5 mm. All results were scaled to give 8 Gy to the macula volume, which is the current treatment requirement. Eight beam treatment angles are currently under investigation. In all eight beam angles, the source-to-target distance is 13 cm, and the polar angle of entry is 300 from the geometric axis of the eye. The azimuthal angle changes in eight increments of 45 degrees in a clockwise fashion, such that an azimuthal angle of 0 degreee corresponds to the 12 o'clock position when viewing the treated eye. Based on considerations of nontarget tissue avoidance, as well as facial-anatomical restrictions on beam delivery, treatment azimuthal angles between 135 degrees and 225 degrees would be available for this treatment system (i.e., directly upward and entering the eye from below). At beam directions approaching 225 degrees and higher, some dose contribution to the optic nerve would result under the assumption that the optic nerve is tilted cranially above the geometric axis in a given patient, a feature not typically seen in past studies. A total treatment dose of 24 Gy would be delivered in three 8 Gy treatments at these selected azimuthal angles. Dose coefficients, defined as the macula radiation absorbed dose per unit air kerma in units of Gy/Gy, were 16% higher for 120 kVp x-ray beams in comparison to those at 80 kVp, thus requiring only 86% of the integrated tube current (mAs) for equivalent dose delivery. When 0.0, 0.4, and 1.0 mm focal spot sizes were used, the dose profiles in the macula are very similar and relatively uniform, whereas a 5.5 mm focal spot size produced a more nonuniform dose profile. The results of this study dem onstrate the therapeutic promise of this device and provide important information for further design and clinical implementation for radiotherapy treatments for ARMD.