Charles A. Wemple

Modification of the University of Washington Neutron Radiotherapy Facility for optimization of neutron capture enhanced fast-neutron therapy

A modified neutron production target assembly has been developed to provide improved performance of the proton-cyclotron-based neutron radiotherapy facility at the University of Washington for applications involving neutron capture enhanced fast-neutron therapy. The new target produces a neutron beam that yields essentially the same fast-neutron physical depth-dose distribution as is produced by the current UW clinical system, but that also has an increased fraction of BNCT enhancement relative to the total therapeutic dose. The modified target is composed of a 5-millimeter layer of beryllium, followed by a 2.5-millimeter layer of tungsten, with a water-cooled copper backing. Measurements of the free-field neutron spectrum of the beam produced by the new target were performed using activation foils with a direct spectral unfolding technique. Water phantom measurements were performed using a tissue-equivalent ion chamber to characterize the fast-neutron depth-dose curve and sodium activation in soda-lime glass beads to characterize the thermal-neutron flux (and thus the expected neutron capture dose enhancement) as a function of depth. The results of the various measurements were quite consistent with expectations based on the design calculations for the modified target. The spectrum of the neutron beam produced by the new target features an enhanced low-energy flux component relative to the spectrum of the beam produced by the standard UW target. However, it has essentially the same high-energy neutron flux, with a reduced flux component in the mid-range of the energy spectrum. As a result, the measured physical depth-dose curve in a large water phantom has the same shape compared to the case of the standard UW clinical beam, but approximately twice the level of BNCT enhancement per unit background neutron dose at depths of clinical interest. In-vivo clinical testing of BNCT-enhanced fast-neutron therapy for canine lung tumors using the new beam was recently initiated.

Monte Carlo Treatment Planning for Molecular Targeted Radiotherapy within the MINERVA System

The aim of this project is to extend accurate and patient-specific treatment planning to new treatment modalities, such as molecular targeted radiation therapy, incorporating previously crafted and proven Monte Carlo and deterministic computation methods. A flexible software environment is being created that allows planning radiation treatment for these new modalities and combining different forms of radiation treatment with consideration of biological effects. The system uses common input interfaces, medical image sets for definition of patient geometry and dose reporting protocols. Previously, the Idaho National Engineering and Environmental Laboratory (INEEL), Montana State University (MSU) and Lawrence Livermore National Laboratory (LLNL) had accrued experience in the development and application of Monte Carlo based, three-dimensional, computational dosimetry and treatment planning tools for radiotherapy in several specialized areas. In particular, INEEL and MSU have developed computational dosimetry systems for neutron radiotherapy and neutron capture therapy, while LLNL has developed the PEREGRINE computational system for external beam photon-electron therapy. Building on that experience, the INEEL and MSU are developing the MINERVA (modality inclusive environment for radiotherapeutic variable analysis) software system as a general framework for computational dosimetry and treatment planning for a variety of emerging forms of radiotherapy. In collaboration with this development, LLNL has extended its PEREGRINE code to accommodate internal sources for molecular targeted radiotherapy (MTR), and has interfaced it with the plugin architecture of MINERVA. Results from the extended PEREGRINE code have been compared to published data from other codes, and found to be in general agreement (EGS4-2%, MCNP-10%) (Descalle et al 2003 Cancer Biother. Radiopharm. 18 71-9). The code is currently being benchmarked against experimental data. The interpatient variability of the drug pharmacokinetics in MTR can only be properly accounted for by image-based, patient-specific treatment planning, as has been common in external beam radiation therapy for many years. MINERVA offers 3D Monte Carlo-based MTR treatment planning as its first integrated operational capability. The new MINERVA system will ultimately incorporate capabilities for a comprehensive list of radiation therapies. In progress are modules for external beam photon-electron therapy and boron neutron capture therapy (BNCT). Brachytherapy and proton therapy are planned. Through the open application programming interface (API), other groups can add their own modules and share them with the community.

Application of MINERVA Monte Carlo Simulations to Targeted Radionuclide Therapy

Recent clinical results have demonstrated the promise of targeted radionuclide therapy for advanced cancer. As the success of this emerging form of radiation therapy grows, accurate treatment planning and radiation dose simulations are likely to become increasingly important. To address this need, we have initiated the development of a new, Monte Carlo transport-based treatment planning system for molecular targeted radiation therapy as part of the MINERVA system. The goal of the MINERVA dose calculation system is to provide 3-D Monte Carlo simulation-based dosimetry for radiation therapy, focusing on experimental and emerging applications. For molecular targeted radionuclide therapy applications, MINERVA calculates patient-specific radiation dose estimates using computed tomography to describe the patient anatomy, combined with a user-defined 3-D radiation source. This paper describes the validation of the 3-D Monte Carlo transport methods to be used in MINERVA for molecular targeted radionuclide dosimetry. It reports comparisons of MINERVA dose simulations with published absorbed fraction data for distributed, monoenergetic photon and electron sources, and for radioisotope photon emission. MINERVA simulations are generally within 2% of EGS4 results and 10% of MCNP results, but differ by up to 40% from the recommendations given in MIRD Pamphlets 3 and 8 for identical medium composition and density. For several representative source and target organs in the abdomen and thorax, specific absorbed fractions calculated with the MINERVA system are generally within 5% of those published in the revised MIRD Pamphlet 5 for 100 keV photons. However, results differ by up to 23% for the adrenal glands, the smallest of our target organs. Finally, we show examples of Monte Carlo simulations in a patient-like geometry for a source of uniform activity located in the kidney.

TH‐C‐230A‐09: Implementation of MINERVA/PEREGRINE as An ATC Review Tool

Purpose: To test the feasibility of a system of software (MINERVA/PEREGRINE) developed by the Idaho National Laboratory (INL) and the Lawrence Livermore National Laboratory (LLNL) for supporting quality assurance (QA) review of cooperative‐group clinical trials treatment planning data within the Advanced Technology QA Consortium (ATC). Method and Materials: MINERVA is an open architecture, open source code system, designed to accommodate any computation engine through a plugin structure. MINERVA supports two types of data storage ‐ relational databases and XML files. Patient data is stored in a relational database. XML‐based import/export tools have been developed to transfer patient information between QA Centers and reviewers. Tools have been implemented as plugins to allow addition of more advanced tools. The research version of the LLNL PEREGRINE Monte Carlo code has been relocated to UC Davis Medical Center. The basis has been created for an integration of PEREGRINE with ITC, and it has been integrated with MINERVA as a calculation engine. Results: MINERVA supports submission of digital treatment planning data using RTOG format. Ability to import DICOM‐RT objects that satisfies the ATC DICOM conformance statement is needed. MINERVA provides display of DVHs and axial patient images with overlaid organ‐at‐risk/target‐volume contours, as well as user‐defined isodose curves. Users can edit contours, recalculate DVHs for these user‐defined structures, and display point doses. Test cases for several body sites have been calculated using PEREGRINE to demonstrate feasibility. We believe that the use of Monte Carlo simulation will become a key tool for credentialing and QA review of clinical trials treatment planning and verification data in the near future. Conclusion: The MINERVA/PEREGRINE software system appears to be well suited to meet the needs regarding QA of data submitted for future ATC‐supported clinical trials. Conflict of Interest: This work was supported by NIH U24 Grant CA81647.

SERA: Simulation Environment for Radiotherapy Applications - Users Manual Version 1CO

This document is the user manual for the Simulation Environment for Radiotherapy Applications (SERA) software program developed for boron-neutron capture therapy (BNCT) patient treatment planning by researchers at the Idaho National Engineering and Environmental Laboratory (INEEL) and students and faculty at Montana State University (MSU) Computer Science Department. This manual corresponds to the final release of the program, Version 1C0, developed to run under the RedHat Linux Operating System (version 7.2 or newer) or the Solaris™ Operating System (version 2.6 or newer). SERA is a suite of command line or interactively launched software modules, including graphical, geometric reconstruction, and execution interface modules for developing BNCT treatment plans. The program allows the user to develop geometric models of the patient as derived from Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) images, perform dose computation for these geometric models, and display the computed doses on overlays of the original images as three dimensional representations. This manual provides a guide to the practical use of SERA, but is not an exhaustive treatment of each feature of the code.