E Schreiber

A carbon nanotube field emission multipixel x-ray array source for microradiotherapy application

The authors report a carbon nanotube (CNT) field emission multipixel x-ray array source for microradiotherapy for cancer research. The developed multipixel x-ray array source has 50 individually controllable pixels and it has several distinct advantages over other irradiation source including high-temporal resolution (millisecond level), the ability to electronically shape the form, and intensity distribution of the radiation fields. The x-ray array was generated by a CNT cathode array (5×10) chip with electron field emission. A dose rate on the order of >1.2 Gy∕min per x-ray pixel beam is achieved at the center of the irradiated volume. The measured dose rate is in good agreement with the Monte Carlo simulation result.

The volumetric response of brain metastases after stereotactic radiosurgery and its post-treatment implications

BACKGROUND Changes in tumor volume are seen on magnetic resonance imaging within weeks after stereotactic radiosurgery (SRS), but it remains unclear what clinical outcomes early radiological changes portend. OBJECTIVE We hypothesized that rapid, early reduction in tumor volume post-SRS is associated with prolonged local control and favorable clinical outcome. METHODS A retrospective review of patients treated with CyberKnife SRS for brain metastases at the University of North Carolina from 2007 to 2009 was performed. Patients with at least 1 radiological follow-up, minimal initial tumor volume of 0.1 cm, no previous focal radiation, and no recent whole-brain radiation therapy were eligible for inclusion. RESULTS Fifty-two patients with 100 metastatic brain lesions were analyzed and had a median follow-up of 15.6 months (range, 2-33 months) and a median of 2 (range, 1-8) metastatic lesions. In treated metastases in which there was a significant tumor volume reduction by 6 or 12 weeks post-SRS, there was no local progression for the duration of the study. Furthermore, patients with metastases that did not reduce in volume by 6 or 12 weeks post-SRS were more likely to require corticosteroids (P = .01) and to experience progression of neurological symptoms (P = .003). CONCLUSION Significant volume reductions of brain metastases measured at either 6 or 12 weeks post-SRS were strongly associated with prolonged local control. Furthermore, early volume reduction was associated with less corticosteroid use and stable neurological symptoms.

Sensitivity of large-field electron beams to variations in a Monte Carlo accelerator model.

Adjustments made to Monte Carlo models during the commissioning of the simulation should be physically realistic and correspond to actual machine characteristics. Large electron fields, with the jaws fully open and the applicator removed, are sensitive to important source and geometry parameters and may provide the most accurate beam models, including those collimated by an applicator. We report on the results of a comprehensive Monte Carlo sensitivity study documenting the response of these large fields to changes in the configuration of a Siemens Primus linear accelerator. The study was performed for 6, 9 12, 15, 18 and 21 MeV configurations, and included variations of thickness, position and lateral alignment of all treatment head components. Variations of electron beam characteristics were also included in the study. Results were classified by their impact on central-axis depth dose distributions, including the bremsstrahlung tail, and on beam profiles near D(max) and in the bremsstrahlung region. Low-energy results show an increased sensitivity to electron beam properties. High-energy bremsstrahlung profiles are shown to be useful in determining misalignments between the beam axis and mechanical isocentre. For all energies, the alignment of the secondary scattering foil and monitor chamber are shown to be critical for correctly modelling beam asymmetries. The results suggest a methodology for commissioning of electron beams using Monte Carlo treatment head simulation.

Monte Carlo simulation of a compact microbeam radiotherapy system based on carbon nanotube field emission technology.

PURPOSE Microbeam radiation therapy (MRT) is an experimental radiotherapy technique that has shown potent antitumor effects with minimal damage to normal tissue in animal studies. This unique form of radiation is currently only produced in a few large synchrotron accelerator research facilities in the world. To promote widespread translational research on this promising treatment technology we have proposed and are in the initial development stages of a compact MRT system that is based on carbon nanotube field emission x-ray technology. We report on a Monte Carlo based feasibility study of the compact MRT system design. METHODS Monte Carlo calculations were performed using EGSnrc-based codes. The proposed small animal research MRT device design includes carbon nanotube cathodes shaped to match the corresponding MRT collimator apertures, a common reflection anode with filter, and a MRT collimator. Each collimator aperture is sized to deliver a beam width ranging from 30 to 200 μm at 18.6 cm source-to-axis distance. Design parameters studied with Monte Carlo include electron energy, cathode design, anode angle, filtration, and collimator design. Calculations were performed for single and multibeam configurations. RESULTS Increasing the energy from 100 kVp to 160 kVp increased the photon fluence through the collimator by a factor of 1.7. Both energies produced a largely uniform fluence along the long dimension of the microbeam, with 5% decreases in intensity near the edges. The isocentric dose rate for 160 kVp was calculated to be 700 Gy∕min∕A in the center of a 3 cm diameter target. Scatter contributions resulting from collimator size were found to produce only small (<7%) changes in the dose rate for field widths greater than 50 μm. Dose vs depth was weakly dependent on filtration material. The peak-to-valley ratio varied from 10 to 100 as the separation between adjacent microbeams varies from 150 to 1000 μm. CONCLUSIONS Monte Carlo simulations demonstrate that the proposed compact MRT system design is capable of delivering a sufficient dose rate and peak-to-valley ratio for small animal MRT studies.

Pilot study for compact microbeam radiation therapy using a carbon nanotube field emission micro-CT scanner

PURPOSE Microbeam radiation therapy (MRT) is defined as the use of parallel, microplanar x-ray beams with an energy spectrum between 50 and 300 keV for cancer treatment and brain radiosurgery. Up until now, the possibilities of MRT have mainly been studied using synchrotron sources due to their high flux (100s Gy/s) and approximately parallel x-ray paths. The authors have proposed a compact x-ray based MRT system capable of delivering MRT dose distributions at a high dose rate. This system would employ carbon nanotube (CNT) field emission technology to create an x-ray source array that surrounds the target of irradiation. Using such a geometry, multiple collimators would shape the irradiation from this array into multiple microbeams that would then overlap or interlace in the target region. This pilot study demonstrates the feasibility of attaining a high dose rate and parallel microbeam beams using such a system. METHODS The microbeam dose distribution was generated by our CNT micro-CT scanner (100 μm focal spot) and a custom-made microbeam collimator. An alignment assembly was fabricated and attached to the scanner in order to collimate and superimpose beams coming from different gantry positions. The MRT dose distribution was measured using two orthogonal radiochromic films embedded inside a cylindrical phantom. This target was irradiated with microbeams incident from 44 different gantry angles to simulate an array of x-ray sources as in the proposed compact CNT-based MRT system. Finally, phantom translation in a direction perpendicular to the microplanar beams was used to simulate the use of multiple parallel microbeams. RESULTS Microbeams delivered from 44 gantry angles were superimposed to form a single microbeam dose distribution in the phantom with a FWHM of 300 μm (calculated value was 290 μm). Also, during the multiple beam simulation, a peak to valley dose ratio of ~10 was found when the phantom translation distance was roughly 4x the beam width. The first prototype CNT-based x-ray tube dedicated to the development of compact MRT technology development was proposed and planned based on the preliminary experimental results presented here and the previous corresponding Monte Carlo simulations. CONCLUSIONS The authors have demonstrated the feasibility of creating microbeam dose distributions at a high dose rate using a proposed compact MRT system. The flexibility of CNT field emission x-ray sources could possibly bring compact and low cost MRT devices to the larger research community and assist in the translational research of this promising new approach to radiation therapy.

A nanotube based electron microbeam cellular irradiator for radiobiology research

A prototype cellular irradiator utilizing a carbon nanotube (CNT) based field emission electron source has been developed for microscopic image-guided cellular region irradiation. The CNT cellular irradiation system has shown great potential to be a high temporal and spatial resolution research tool to enable researchers to gain a better understanding of the intricate cellular and intercellular microprocesses occurring following radiation deposition, which is essential to improving radiotherapy cancer treatment outcomes. In this paper, initial results of the system development are reported. The relationship between field emission current, the dose rate, and the dose distribution has been investigated. A beam size of 23 mum has been achieved with variable dose rates of 1-100 Gy/s, and the system dosimetry has been measured using a radiochromic film. Cell irradiation has been demonstrated by the visualization of H2AX phosphorylation at DNA double-strand break sites following irradiation in a rat fibroblast cell monolayer. The prototype single beam cellular irradiator is a preliminary step to a multipixel cell irradiator that is under development.

SU-FF-T-362: PLanUNC as An Open-Source Radiotherapy Planning System for Research and Education

Purpose: PLanUNC is a radiotherapy planning software package that has been under development and clinical use at the University of North Carolina for approximately 20 years. Under a joint grant from the NCRR and NCI (R01 RR 018615), PLanUNC has been documented, commented, and prepared for distribution as a freely available open‐source treatment planning tool for use as an adaptable and common platform for radiotherapy research. Method and Materials: The software and source code have been made available to qualifying users through a web portal located at http://planunc.radonc.unc.edu. Licenses for PLanUNC are available without fee to institutions, departments, and other facilities engaged in research and education involving radiation therapy.Results: Recent research milestones demonstrating the extensibility and increasing utility of PLanUNC include tools for 4D planning, interfaces with ITK segmentation and registration tools, daily correction of patient positioning, and interfaces with a variety of Monte Carlo dose engines. PLanUNC is currently supported for Linux and Windows operating systems, but has been successfully compiled on Alpha, Macintosh, Solaris, and other platforms. Conclusion: Licensed users will have access to PLanUNC source code, user and development documentation, annual training workshops, and limited support from UNC and the PLanUNC research community. PLanUNC is distributed as source code, making it customizable and extensible to meet the needs of a diverse range of research applications.

27 – Basics of Radiation Therapy

Abstract Radiation therapy is one of the pillars of cancer treatment and has a rich, 125-year history. Radiation oncology is the medical specialty dealing with the planning and delivery of these radiation treatments, typically given daily over a several week period. Treatment planning and delivery requires both advanced technology and a team of radiation oncologists, medical physicists, medical dosimetrists, and radiation therapists. Radiation therapy practice developed mostly empirically during the field’s first 50 years, although increasingly since, it has been informed by technological advances and by our growing understanding of the molecular biology of tumor and normal tissue responses to irradiation. As such, today’s radiation therapy might consist of one or a few large dose increments given over 3 weeks or less, 20 or more small doses given once daily over 4 to 8 weeks, or 40 or more even smaller dose increments given twice daily over 4 to 8 weeks. In addition to these external radiation therapy options, brachytherapy involves the placement of small radioactive pellets or needles in and around the tumor that are left in place either temporarily or permanently. Depending on the site, type, and extent of the cancer, radiation therapy may be used alone or in combination with surgery, chemotherapy, molecularly-targeted therapy, and/or immunotherapy. Many of these treatment combinations result in radiosensitization of the tumor. Other chemical agents in combination with radiation are protectors or mitigators of normal tissue injury in the hopes that higher radiation doses can be given to the tumor without exceeding normal tissue tolerance.

Sensitivity analysis of an asymmetric Monte Carlo beam model of a Siemens Primus accelerator

The assumption of cylindrical symmetry in radiotherapy accelerator models can pose a challenge for precise Monte Carlo modeling. This assumption makes it difficult to account for measured asymmetries in clinical dose distributions. We have performed a sensitivity study examining the effect of varying symmetric and asymmetric beam and geometric parameters of a Monte Carlo model for a Siemens PRIMUS accelerator. The accelerator and dose output were simulated using modified versions of BEAMnrc and DOSXYZnrc that allow lateral offsets of accelerator components and lateral and angular offsets for the incident electron beam. Dose distributions were studied for 40×40cm2 fields. The resulting dose distributions were analyzed for changes in flatness, symmetry, and off‐axis ratio (OAR). The electron beam parameters having the greatest effect on the resulting dose distributions were found to be electron energy and angle of incidence, as high as 5% for a 0.25° deflection. Electron spot size and lateral offset of the electron beam were found to have a smaller impact. Variations in photon target thickness were found to have a small effect. Small lateral offsets of the flattening filter caused significant variation to the OAR. In general, the greatest sensitivity to accelerator parameters could be observed for higher energies and off‐axis ratios closer to the central axis. Lateral and angular offsets of beam and accelerator components have strong effects on dose distributions, and should be included in any high‐accuracy beam model. PACS numbers: 87.55.K‐, 87.55.Gh

SU‐FF‐T‐436: Tools for Integrating Monte Carlo Dose Engines with a Radiotherapy Planning System

Purpose:Monte Carlo simulations represent the gold standard in radiotherapydose calculation. While numerous tools have been developed to facilitate accelerator and patient modeling within a Monte Carlo simulation, there are few commonly available tools for interfacing a Monte Carlodose engine with a fully‐featured treatment planningsoftware package. We report on the development of tools to integrate a Monte Carlodose engine with clinically useful radiotherapy planning software.Method and Materials: The initial release is configured to operate with PLanUNC, a freely available open‐source radiotherapy planning tool. The Monte Carlo integration package consists of several modular scripts and programs that act as a bridge between the treatment planningsoftware and the Monte Carlodose engine. Results: Using PLanUNC as a front end for the Monte Carlo, the user can develop a treatment plan, export beams and patient information to the Monte Carlo, recover the dose distribution, and analyze the results of the calculation in PLanUNC according to isodose, DVH, or EUD, as well as compare the results of the Monte Carlo simulation with results from other calculations. Conclusion: The Monte Carlo interface package facilitates the clinical use of Monte Carlo by allowing a fully‐featured radiotherapy planning suite to be used as a front end, allowing flexible treatment planning and analysis of the Monte Carlo results. The modular nature of the software makes it straightforward to adapt these tools for use with other treatment planningsoftware packages.