Teacher
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ATTILI Andrea
(syllabus)
General introduction to radiation therapy. ○ Physical and biological rationale of ionizing radiation in cancer treatments. ○ Dose-effect curve, TCP, NTCP and therapeutic index. ○ Dose-volume histograms. Physical and biological selectivity. ● Introductory overview of radiotherapy techniques (from x-rays to ion beams): ○ Photon Radiation Therapy: conventional, conformational, IMRT. Brachytherapy. Radiotherapy with ion beams: hadrontherapy. ■ Notes on Facilities (active and under development) and diffusion in the world. ● Classification of ionizing radiation: the problem of choosing the type of radiation for therapeutic applications ○ Definition of relevant physical and radiobiological quantities. ○ Physical Selectivity: ■ Directly and indirectly ionizing radiation ■ Low-LET and high-LET radiation. Bragg's peak. Examples for indirectly ionizing: photons, neutrons; directly ionizing: electrons, positrons, ions. ○ Biological Selectivity: ■ Poorly ionizing and highly ionizing radiation. The Concept trace and micro/nano-dosimetric aspects. ■ Relationship between LET and "biological efficacy" ● Physical aspects of hadrontherapy: interaction of ion beams with matter. ○ Stopping Power Stopping power classification. ■ Derivation of stopping power equations (Bohr, Bethe approaches and Bloch, corrective factors) ■ The average excitation potential. Mixtures. ○ Energy loss and range straggling. ■ CSDA Approximations ■ Landau-Vavilov theory ○ Lateral beam widening ■ Multiple scattering. Coulomb interactions with target nuclei. Equations by Bothe and Moliere. Nuclear interactions and fragmentation ■ Modelling approaches: INC and QMD models. ■ Target Fragmentation and Projectile Fragmentation ■ The "tail of fragments" and mixtures of ions. ● In-depth analysis: in-beam PET ● Radiobiological aspects. ○ Basics of Radiobiology ■ Spatial and temporal scales of radiobiological processes. ■ Oncogenesis. Cell survival: definition, processes of damage (direct and mechanisms. Hypoxia. Mutations and transformations. ■ Clonogenic experiments and L-Q model. ■ Temporal effects and fractionation. ● In-depth: the FLASH effect ○ Radiobiological effects of ion beams ■ Relative biological efficacy (RBE): definition, systematic, complexity and physical aspects. ■ the Oxygen Enhancement Ratio (OER). Physical and Radiobiological Modeling for Ion Beams in Clinical Applications ○ Recall to the concepts of tracing and clustering of damage. ○ The "Local Effect Model" (LEM) ○ Kinetic equations for cell damage and repair. Radio-chemical aspects. ○ Microdosimetry models ■ Mathematical basis of microdosimetry. Stochastic aspects. ■ The Microdosimetric-Kinetic model (MKM) ● In-Depth: Advanced MKM Approaches: Monte Carlo, Effects temporal (FLASH effect), OER, Mutations. TCP/NTCP Models ■ In-depth analysis: models to assess the risk of secondary cancers. ● "Dose Delivery" and "Dose Shaping" ○ Classification of ion beam acceleration systems and types of facilities ■ Synchrotrons, cyclotrons and Laser-driven. ○ General aspects of dose measurements, in-beam monitoring, and radiation protection. ○ General aspects of dose delivery modulation in 3D. ■ The Spread-Out Bragg Peak (SOBP). The gantry system. ■ Passive dose-shaping systems (3D Range Modulator) ■ Active scanning systems (raster scan and energy modulation) ● Simulation and optimization of treatment plans: the "Treatment Planning System" ○ General description of TPS and planning procedures ■ Image acquisition (CT), segmentation, prescription and definition dose-volume constraints, inverse planning, DVH calculation. ○ Monte Carlo simulations for dose calculation General aspects of particle tracking. ■ Use of CT for patient modeling and identification of the elemental composition of tissues. ■ Variance reduction systems ○ Pencil-beam algorithms and WEPL approximation for fast dose calculation. ○ Inverse planning details ■ Pencil beam decomposition and degrees of freedom ■ Examples of optimization algorithms ○ Radiobiological optimization Methods of integrating radiobiological models into TPS calculations with RBE-weighted dose (RWD). Pre-mixing and post-mixing approaches. ■ Examples: RWD distribution calculations with LEM and MKM. ● Practical activity and Hand-on: exemplary exercises with the use of codes Open-source for radiobiological calculations and treatment simulation. ○ Download and install the codes: Topas, Survival and R-Planit. ○ Monte Carlo simulation exercises (code: Topas/Geant4) Evaluation of the Dose Distribution Released by an Ion Beam in a virtual patient. ■ Evaluation of microdosimetric spectra in a cell nucleus for interaction with ions. ○ Radiobiological simulation exercises (code: Survival) ■ Calculation of the probability of cell survival for a sample of cells irradiated with ion beams with the MKM or LEM model. Exercise in planning a treatment plan (code: R-Planit) ■ Calculation and optimization of a treatment starting from the CT of a virtual patient and the clinical prescription given. ■ Calculation of the DVH of the optimized plan. ○ (Follow-up: Combining the results of the previous exercises for the assessment of the distribution of RWD in the treated patient.
(reference books)
Podgoršak, E. B. (2016). Graduate Texts in Physics: Radiation Physics for Medical Physicists. ● Hobbie, R. K., Roth, B. J. (2007). Intermediate physics for medicine and biology. Germany: Springer New York. ● M. Joiner & A. van der Kogel (eds.) (2009). Basic Clinical Radiobiology. Edward Arnold. ● Paganetti, H. (ed.) (2012). Proton Therapy Physics. CRC Press. ● MA, C.-M. C., & Lomax, T. (eds.) (2013). Proton and Carbon Ion Therapy. CRC Press
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