Università Roma Tre

● General introduction to radiotherapy.
○ 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 radiotherapy: conventional, conformational, IMRT. Brachytherapy.
○ Ion beam radiotherapy: hadrontherapy.
■ Notes on Facility (active and under development) and dissemination 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
■ Classification of stopping power.
■ 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.
● Insight: in-beam PET
● Radiobiological aspects.
○ Basics of radiobiology
■ Spatial and temporal scales of radiobiological processes.
■ Oncogenesis.
■ Cell survival: definition, damage processes (direct and
indirect), repair mechanisms. Hypoxia. Mutations and transformations.
■ Clonogenic experiments and the L-Q model.
■ Temporal effects and fractionation.
● Insight: the FLASH effect
○ Radiobiological effects of ion beams
■ Relative biological efficacy (RBE): definition, systematics, complexity
and physical aspects.
■ The Oxygen Enhancement Ratio (OER).
● Physical and radiobiological modelling for ion beams in clinical applications
○ Reference to the concepts of trace and clustering of damage.
○ The "Local Effect Model" (LEM)
○ Kinetic equations for cell damage and repair. Radio-chemical aspects.
○ Microdosimetric models
■ Mathematical basis of microdosimetry. Stochastic aspects.
■ The Microdosimetry-Kinetic model (MKM)
● In-depth: advanced MKM approaches: Monte Carlo, effects
Temporal (FLASH effect), OER, Mutations.
○ TCP/NTCP models
■ Deepening: 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 3D dose release modulation.
■ 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 tracing.
■ Use of CT for patient modelling and identification of
elemental composition of tissues.
■ Variance reduction systems
○ Pencil-beam algorithms and WEPL approximation for fast dose calculation.
○ Details on "reverse planning"
■ Decomposition in pencil beam and degrees of freedom
■ Examples of optimization algorithms
○ Radiobiological optimization
■ Methods of integration of radiobiological models in 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: sample exercises with the use of codes
Open-source for radiobiological calculations and treatment simulation.
○ Download and install codes: Topas, Survival and R-Planit.
○ Monte Carlo simulation exercises (code: Topas/Geant4)
■ Evaluation of dose distribution dose 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.
○ Planning exercise of a treatment plan (code: R-Planit)
■ Calculation and optimization of a treatment starting from the CT of a
virtual patient and clinical prescription given.
■ Calculation of DVH of the optimized plan.
○ (Deepening: combination of the results of previous years for the
evaluation of RWD distribution in the treated patient.

● 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