S Price

Three-dimensional dose accumulation in pseudo-split-field IMRT and brachytherapy for locally advanced cervical cancer

PURPOSE Dose accumulation of split-field external beam radiotherapy (EBRT) and brachytherapy (BT) is challenging because of significant EBRT and BT dose gradients in the central pelvic region. We developed a method to determine biologically effective dose parameters for combined split-field intensity-modulated radiation therapy (IMRT) and image-guided BT in locally advanced cervical cancer. METHODS AND MATERIALS Thirty-three patients treated with split-field-IMRT to 45.0-51.2 Gy in 1.6-1.8 Gy per fraction to the elective pelvic lymph nodes and to 20 Gy to the central pelvis region were included in this study. Patients received six weekly fractions of high-dose rate BT to 6.5-7.3 Gy per fraction. A dose tracker software was developed to compute the equivalent dose in 2-Gy fractions (EQD2) to gross tumor volume (GTV), organs-at-risk and point A. Total dose-volume histogram parameters were computed on the 3D combined EQD2 dose based on rigid image registration. The dose accumulation uncertainty introduced by organ deformations between IMRT and BT was evaluated. RESULTS According to International Commission on Radiation Unit and Measurement and GEC European Society for Therapeutic Radiology and Oncology recommendations, D98, D90, D50, and D2cm3 EQD2 dose-volume histogram parameters were computed. GTV D98 was 84.0 ± 26.5 Gy and D2cc was 99.6 ± 13.9 Gy, 67.4 ± 12.2 Gy, 75.0 ± 10.1 Gy, for bladder, rectum, and sigmoid, respectively. The uncertainties induced by organ deformation were estimated to be -1 ± 4 Gy, -3 ± 5 Gy, 2 ± 3 Gy, and -3 ± 5 Gy for bladder, rectum, sigmoid, and GTV, respectively. CONCLUSIONS It is feasible to perform 3D EQD2 dose accumulation to assess high and intermediate dose regions for combined split-field IMRT and BT.

TH‐C‐204B‐10: Implementation of a Small Animal Image Guided Microirradiator: The MicroIGRT

Purpose: Implementation of a conformal small animal image guided microirradiation therapy instrument (microIGRT) consisting of a cone beam microCT subsystem for submillimeter low dose structural imagingimage guided radiotherapy and orthovoltage conformal microirradiation with high dose rate and high throughput. Method and Materials: The microCT subsystem is based on an 80kVp micro‐focus x‐ray source with 75×75 μm2 focal spot and a flat panel amorphous silicondetector with 1024×1024 pixels. The irradiator consists of a high power commercially available 320 kVp orthovoltage source with a 0.4×0.4 mm2 focal spot that can be operated at a nominal power of 800W. The beam characteristics are controlled with two variable jaws used to pre‐collimate the radiation beam along each orthogonal direction. An aperture exchange mechanism is used to conform the beam cross section by using computer generated apertures. The microCT radiationdose the orthovoltage source spectral output and dose rate are under evaluation using a mouse digital phantom and a pencil beam algorithm. Results:CTimaging with micrometric resolution is achievable using 128 projections and a maximum radiationdose of 2cGy. Automatic animal positioning and handling is performed within sub‐millimeter precision. The treatment beam can be aimed at different latitude and longitude angles and translated with 500 μm steps. The source was tested to deliver a radiationdose rate of 20 Gy/min when is filtered to a half‐value layer of 4.6 mm Cu. Conclusion: We present our progress and initial tests of a highly conformal image guided small animal microirradiator.

SU-E-J-213: Imaging and Treatment Isocenter Verification of a Gantry Mounted Proton Therapy System

PURPOSE The Mevion proton therapy machine is the first to feature a gantry mounted sychro-cyclotron. In addition, the system utilizes a 6D motion couch and kV imaging for precise proton therapy. To quantify coincidence between these systems, isocentricity tests were performed based on kV imaging alignment using radiochromic film. METHODS The 100 ton gantry and 6D robotic couch can rotate 190° around isocenter to provide necessary beam angles for treatment. The kV sources and detector panels are deployed as needed to acquire orthogonal portals. Gantry and couch mechanical isocenter were tested using star-shots and radiochromic-film (RCF). Using kV imaging, the star-shot phantom was aligned to an embedded fiducial and the isocenter was marked on RCF with a pinprick. The couch and gantry stars were performed by irradiating films at every 45° and 30°, respectively. A proton beam with a range and modulation-width of 18 cm was used. A Winston-Lutz test was also performed at the same gantry and couch rotations using a custom jig holding RCF and a tungsten ball placed at isocenter. A 2 cm diameter circular aperture was used for the irradiation. RESULTS The couch star-shot indicated a minimum tangent circle of 0.6 mm, with a 0.9 mm offset from the manually marked isocenter. The gantry star-shot showed a 0.6 mm minimum tangent circle with a 0.5 mm offset from the pinprick. The Winston Lutz test performed for gantry rotation showed a maximum deviation from center of 0.5 mm. CONCLUSION Based on star-shots and Winston-Lutz tests, the proton gantry and 6D couch isocentricity are within 1 mm. In this study, we have shown that the methods commonly utilized for Linac characterization can be applied to proton therapy. This revolutionary proton therapy system possesses excellent agreement between the mechanical and radiation isocenter, providing highly precise treatment.

SU‐C‐BRE‐01: 3D Conformal Micro Irradiation Results of Four Treatment Sites for Preclinical Small Animal and Clinical Treatment Plans

PURPOSE Small animal irradiation can provide preclinical insights necessary for clinical advancement. In order to provide clinically relevant data, these small animal irradiations must be designed such that the treatment methods and results are comparable to clinical protocols, regardless of variations in treatment size and modality. METHODS Small animal treatments for four treatment sites (brain, liver, lung and spine) were investigated, accounting for change in treatment energy and target size. Up to five orthovoltage (300kVp) beams were used in the preclinical treatments, using circular, square, and conformal tungsten apertures, based on the treatment site. Treatments were delivered using the image guided micro irradiator (microIGRT). The plans were delivered to a mouse sized phantom and dose measurements in axial and coronal planes were performed using radiochromic film. The results of the clinical and preclinical protocols were characterized in terms of conformality number, CTV coverage, dose nonuniformity ratio, and organ at risk sparing. RESULTS Preclinical small animal treatment conformality was within 1-16% of clinical results for all treatment sites. The volume of the CTV receiving 100% of the prescription dose was typically within 10% of clinical values. The dose non-uniformity was consistently higher for preclinical treatments compared to clinical treatments, indicating hot spots in the target. The ratios of the mean dose in the target to the mean dose in an organ at risk were comparable if not better for preclinical versus clinical treatments. Finally, QUANTEC dose constraints were applied and the recommended morbidity limits were satisfied in each small animal treatment site. CONCLUSION We have shown that for four treatment sites, preclinical 3D conformal small animal treatments can be clinically comparable if clinical protocols are followed. Using clinical protocols as the standard, preclinical irradiation methods can be altered and iteratively improved to achieve a clinically relevant irradiation model.

TU‐C‐BRB‐01: Commissioning and Characterization of a Dual Gantry Image Guided Orthovoltage Micro Irradiator for Preclinical Small Animal Radiobiological Experiments

Purpose: The purpose of this study was to accurately commission and characterize our small animalimage guided micro irradiator, the microIGRT, for preclinical translational radiobiological research. The microIGRT has a dual gantry architecture with a microCT subsystem gantry for low dose high resolution anatomical imaging and treatment planning, and a second coaxial microRT subsystem gantry for conformal image guided orthovoltage irradiation. Methods: The microCT image resolution, contrast, and dose were evaluated with specialized phantoms and animal models. The micro RT subsystem percent depth dose, beam profile, multibeam irradiation precision and conformality, animal repositioning accuracy, mechanical resolution, and dosimetric accuracy were measured using specialized phantoms equipped with radiochromic film. For each measurement, results were compared with standards adapted from external beam Linac and patient quality assurance protocols scaled to animal dimensions and orthovoltage energies. Results: The microCT dose is 4.15 cGy/scan for 100 um imaging resolution, up to 33.2 cGy/scan for 800 um imaging resolution. The percent depth dose for a 300 kVp beam with 3.8 mm of Cu HVL is 2.7 cGy/mm with a buildup of 2.8 mm. A 1 cm2 standard square field has a 265 um penumbra, 7% homogeneity, and 9% symmetry. Anatomical positioning is within 500 um for fractionated treatments and multibeam isocentric irradiation central axis uncertainty is within a 150 um radius for three, four, and five coplanar beam treatments. Conclusions: We characterized the small animal microIGRT developed by our group to provide complete parameterization of the instruments imaging and treatment capabilities. Anatomical imaging, irradiation distributions, and beam dosimetry indicate that our system satisfies requirements established by scaling clinical imaging and radiotherapy protocols to animal models to perform clinically relevant translational radiobiological experiments.

TU-F-BRE-01: A High Resolution Micro Fiber Scintillator Detector Optimized for SRS and SBRT in Vivo Real Time Treatment Verification

PURPOSE We have built a high resolution real time scintillating fiber detector prototype to determine in real time the accuracy of stereotactic radiosurgery (SRS) and stereotactic body radiotherapy (SBRT) treatments when only a fraction of the planned dose was delivered. The motivation of this work is to enhance dose delivery accuracy and to achieve error free radiosurgery. METHODS A high density array of scintillating fibers and a high speed photo detectors array were integrated to implement a high resolution real time dosimeter that can sample with high resolution pulsed SRS and SBRT beams cross sections. The high efficiency of the developed system allows to read each linac pulse in real time and to compute the accumulated dose and dose errors when only a fraction of the beam was delivered. The fibers are highly packed in a substrate that is directly coupled to two 128 pixel arrays with a pitch matching the fiber spacing to achieve accurate spatial localization. The small cross section of the fiber array allows stacking multiple fiber arrays to measure independent angular profiles that are digitally processed in parallel for real time dosimetry. RESULTS We implemented a high density array detector prototype with a pitch of 0.5 mm, readout speed of 1.2 msec, and a response time of 0.5 usec. The fast reading speed has the capability to determining the dose in flattening free filter beams. The detector can be installed in transmission mode at the output port of a micro-MLC. Treatment deviations smaller than 3% are detected when less than 1/100 of the planned dose was delivered. CONCLUSIONS We built a prototype of a high resolution fiber scintillator array detector for SRS and SBRT in vivo dosimetry. Results show that the developed detector has the potential to assure error free SRS and SBRT treatments.

A microelectronic portal imaging device for image guided conformal microirradiation of murine cancer models.

Image guided conformal small animal orthovoltage microirradiators are currently under development to perform radiobiological experiments with preclinical cancer models. An important component of these instruments is the treatment delivery image guidance system, a microelectronic portal imaging device (μEPID). Here, we present the design and implementation of a μEPID, specifically designed and constructed for small animal orthovoltage microirradiators. The μEPID can acquire images in the range of 60 kVp to 320 kVp x-ray photon energies and can endure high doses from orthovoltage beams without radiation damage. The μEPID can acquire 200 μm resolution images at a rate of 17 frames per second for online in vivo co-registration between irradiation beams and small animal anatomy. An exposure with less than 1% of a 2 Gy treatment field is required for imaging, which is an adequate ratio between imaging dose and treatment dose to avoid undesired irradiation of healthy tissue or alteration of the preclinical cancer model. The μEPID was calibrated for microdosimetry with a precision of 4.1% with respect to an ion chamber, used as a gold standard. To validate the in vivo device performance, irradiations of lung, brain, and xenograft breast cancer preclinical models were performed and analyzed.

TU‐C‐108‐05: High Density Organic Scintillator Arrays for High Resolution Stereotactic Body Radiation Therapy Dosimetry

Purpose: Radiation oncology patients receiving stereotactic body radiation therapy (SBRT) are treated with high dose and high dose rate treatment procedures in which delivered dose should be recorded, and verified for quality assurance and patient safety. We implemented a high resolution scintillating fiber detector array to perform high resolution dosimetry of SBRT fields. Materials: Scintillating fibers have a water equivalent attenuation coefficient, excellent reproducibility, stability and a linear response versus dose, do not require any polarizing voltage, and are water impermeable. We constructed a high resolution dosimeter based on an array of sub‐millimeter organic fiber sensors mounted on a supporting frame that provides support, alignment, and buildup material. The fiber detector interface consists of a high density linear array of high speed linear photodetectors. The analog output is transmitted to a high throughput parallel data acquisition system integrated with a dedicated computer for signal processing, analysis, and recording. The detector was specially designed to perform high resolution dosimetric verification of small SBRT fields delivered with conventional dose rates (600 MU/min) to high dose rate flattening filter free beams (up to 2400 MU/min). Results: We determined fiber sensor sensitivity and linearity response with respect to beam intensity field size and dose. Detector spatial resolution is 0.5 mm and linearity response with respect to beam intensity and field size was within 2% for photon beams from 6MV to 18 MV and electron beams from 6 MeV to 20 MeV. Spatial beam profiles were compared with film dosimetry showing excellent agreement within 3% in the penumbra region. Conclusions: The development of this technology addresses the need for high resolution dosimeters for SBRT. The developed detector provides accurate dose, beam localization, and beam profile verification and will be a valuable tool for quality assurance of SBRT treatments.

TU‐C‐BRB‐09: In Silico Model of Glioblastoma Tumor Microenvironment to Predict Radiotherapy Outcome

Purpose: We developed a tumor model for glioblastomas with the aim to study tumor growth, transition from avascular to vascular, oxygenation effects, cell repair, and to predict glioma control or recurrence when the malignancy is treated with ionizing radiation.Methods: Anatomical structures imaged using MRI were contoured and compartmentalized to simulate white matter, grey matter, and vasculature structures proximal to a simulated glioblastoma tumor. The gliomas were modeled using micro compartments to represent groups of tumor cells of the same structure and functionality. The model incorporates the interactions between healthy and tumor tissue using a mechanistic approach based on forces and link strengths between cells and the extra cellular matrix. The evolution and response of the cells to biomolecules, nutrients, and oxygen distribution were modeled through discrete transport and diffusion equations. Cell biology was simulated using parameters that represent nutrient consumption, cell cycle, cell history, and cell oxygenation. The delivered dose was modeled using a probabilistic approach to compute the likelihood of DNA damage and repair. Results: We successfully simulated tumor growth, invasion, and disruption of the local anatomy and tumorcontrol or recurrence under ionizing radiation stress. We modeled tumorradiotherapy under hypoxic and oxic conditions. Results of these numerical experiments show qualitative agreement with observed tumor evolution and response to ionizing radiationtreatment. Transition from an avascular to a vascular tumor and recruitment of blood vessels was also successfully modeled. Spatial resolution of compartments is higher than current imaging devices, making our model a valuable tool to link simulations with anatomical and functional imaging.Conclusions: We developed a micro compartmental model of glioblastoma tumors to evaluate the role of the local anatomy and the microenvironment oxygenation when the malignancy is treated with ionizing radiation. The model can be used to predict glioblastoma growth and response to radiotherapy.

TU‐C‐BRB‐07: Comparison of Preclinical and Clinical Conformal Radiation Therapy Techniques and Protocols to Establish a Translational Pathway

Purpose: The purpose of this study was to compare the techniques and protocols used in clinical radiation therapy and recently developed preclinical image guided micro irradiation to establish a link between small animal conformal irradiation and clinical treatment protocols. This work will establish protocols that, according to treatment site, will facilitate the translation of conclusions from radiobiological experiments to clinical applications, fostering the advancement of radiotherapy.Methods: Data was gathered using our small animal image guided micro irradiation device, the microIGRT, as an example of preclinical techniques which mimic equivalent clinical treatment protocols. The microIGRT utilizes fractionated treatments, multibeam irradiations, modulated beams, image guided treatment verification, and doses to emulate clinical protocols. Consequently, it is well suited to establish parametric comparisons between clinical and preclinical techniques. In this study, we concentrated on two treatment sites, brain and lung, to define treatment conformality index, homogeneity, penumbra, PDD, and fractionated doses to establish a link to guide radiobiological experiments using clinical protocols as a gold standard. Results: Three and five beam irradiations were delivered to a small animal body and head phantom with radiochromic film to simulate lung and braintreatment. A three beam irradiation to the lung yielded a 625 um penumbra. Compare this value with a human treatment penumbra of 1 cm, and penumbra scales as the ratio between body sizes. The homogeneity of our system is similar to the 10% typically used in clinical treatment planning.Conclusions: By comparing preclinical and clinical treatment metrics, the extent of translation can be determined and improved, leading to better understanding of preclinical results and improved correlation with clinical procedures. This will lead to more clinically based preclinical experiments and improve translation efficiency between the two testing environments, thus providing new clinical treatment strategies and improved human cancer treatment.