As proton therapy has joined the mainstream of radiation treatment, Monte Carlo simulation (MC) has been the research engine driving highly accurate dose delivery. The TOPAS Tool for Particle Simulation, developed in the previous funding cycle, makes MC accessible as never before. As radiation therapy pushes to the next challenge, where physics and biology come together, TOPAS will bridge the divide between these two research domains. TOPAS can track any kind of particle through any kind of treatment head, import a patient geometry, score dose, fluence, etc., has advanced graphics and scoring features, and is fully four-dimensional to handle all time-dependent aspects of a simulation. Research physicists use TOPAS to improve proton delivery systems towards safer and more effective treatments, easily setting up and running complex MC simulations that used to take MC specialists months to prepare. Clinical physicists use TOPAS to optimize the therapeutic ratio, simulating patient- specific treatment plans with the full accuracy of MC at the touch of a button. We will bring the same benefits to the radiobiological community. Where radiobiology research has previously suffered from insufficient interdisciplinary collaboration between physicists and biologists, TOPAS will bridge the gap. TOPAS will let biologists study detailed physics aspects of their experiments and let physicists employ the latest radiobiology results in the clinic. TOPAS will provide a common research platform to proton therapy facilities, biology laboratories and universities.
Specific Aim 1 : Expand TOPAS to facilitate research on organ effect biology a. Provide a framework for tumor and normal tissue outcome modeling b. Validate by reproducing published data on proton beam normal tissue complications Specific Aim 2: Expand TOPAS to facilitate research on cellular effect biology a. Provide a framework for cellular effect RBE modeling b. Validate by calculating the relative biological effectiveness f proton beams Specific Aim 3: Expand TOPAS to facilitate research on sub-cellular effect biology a. Provide a framework for sub-cellular effect mechanistic modeling b. Validate by reproducing data on ionization frequencies and DNA damage Specific Aim 4: Support and share TOPAS for all user communities a. Support current TOPAS user communities in proton therapy physics b. Reach out to new user communities in other therapy modalities and imaging c. Continuing software innovation, enhanced graphical user interfaces and beyond

Public Health Relevance

Medical physics is reaching the boundary where further improvements require connecting the physics to the underlying biology. In particular, in proton therapy there are several controversies related to biological effects that need to be studied experimentally and theoretically. This application will extend the TOPAS functionality into the regime of chemical processes and biological modeling. This expansion will make Monte Carlo particle transport techniques as available to the biologist as TOPAS has already made them available to the medical physicist. We envisage that TOPAS will become the preferred platform for both physics and biology research in proton therapy. Our new proposal focus is on all three domains of radiation biology modeling;i.e. organ effects (outcome), cellular effects (RBE) and sub-cellular (mechanistic) effects. Currently there is no single application that covers the whole spectrum from organ to sub-cellular biology.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
5R01CA140735-06
Application #
8690791
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Deye, James
Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02199
Testa, Mauro; Min, Chul Hee; Verburg, Joost M et al. (2014) Range verification of passively scattered proton beams based on prompt gamma time patterns. Phys Med Biol 59:4181-95
Ramos-Mendez, Jose; Perl, Joseph; Faddegon, Bruce et al. (2013) Geometrical splitting technique to improve the computational efficiency in Monte Carlo calculations for proton therapy. Med Phys 40:041718
Dowdell, Stephen J; Clasie, Benjamin; Depauw, Nicolas et al. (2012) Monte Carlo study of the potential reduction in out-of-field dose using a patient-specific aperture in pencil beam scanning proton therapy. Phys Med Biol 57:2829-42
Bednarz, Bryan; Lu, Hsiao-Ming; Engelsman, Martijn et al. (2011) Uncertainties and correction methods when modeling passive scattering proton therapy treatment heads with Monte Carlo. Phys Med Biol 56:2837-54
Bednarz, Bryan; Daartz, Juliane; Paganetti, Harald (2010) Dosimetric accuracy of planning and delivering small proton therapy fields. Phys Med Biol 55:7425-38