Biomedical Physics in Radiotherapy for Cancer

Chapter 1. Radiation interaction with matter. The first chapter introduces the main types of radiation (photons, electrons, neutrons, protons) and their interaction with matter. All these interactions are described and illustrated. From a radiobiology perspective, the effect of the above interactions with the basic target inside the cell (DNA) are presented. Chapter 2. Elements of radiobiology. This chapter presents the fundamental quantities and processes radiobiology works with. LET (linear energy transfer), RBE (relative biological effectiveness), OER (oxygen enhancement ratio) will be defined and explained in details, and the cell cycle will be also presented from a radiobiology perspective. Biological effects of radiation like types of cell damage and repair, and cell survival curves with their elements are described here. Chapter 3. Elements of radiotherapy physics. Chapter 3 deals with measurements of radiation, calculation of absorbed dose, radiotherapy treatment machines and ancillary equipment used in diagnosis/treatment of tumours. Current dosimetry protocols and relevant measuring equipment will be discussed. Chapter 4. Tumour characteristics, development and response to radiation. The aim of this chapter is to present tumour development and behaviour during radiotherapy. Therefore, the parameters dictating the growth of tumours, the differences between normal tissue and cancerous tissues, and also tumour hypoxia and the process of angiogenesis are described. The 5 R's of radiobiology (Repair, Repopulation, Redistribution of cells along the mitotic cycle, Reoxygenation and Radioresistance) are explained as the rationale behind fractionation. The next chapter then follows automatically, since it deals with fractionation in radiotherapy. Chapter 5. Fractionation and altered fractionation in radiotherapy. Fractionation in radiotherapy is crucial for both tumour control and normal tissue sparing. Since different tumours respond differently to radiation, due to variations in cell kinetics and not only, conventional fractionation does not suit all tumours. Altered fractionation methods, and the rationale behind them are presented in this chapter. Also, the possibility to assess one treatment regimen relative to another is presented through the linear quadratic model and the calculation of biologically effective doses. Chapter 6. Treatment planning techniques. Planning or dose distribution calculation of treatment plays a crucial role in the process of radiation therapy. Modern radiotherapy cannot be performed without careful imaging of a patient anatomy and radiation target volumes. The position of radiation beams as well as various blocking devices to shield surrounding healthy structures can be them identified and delivered radiation dose calculated. Manual, three-dimensional, inverse-planning techniques are presented here with optimization methods. Chapter 7. Three-dimensional conformal radiotherapy: radiobiology and physics aspects of treatment. Therapeutic ratio is defined in radiotherapy as the ratio between TCP (tumour control probability) and NTCP (normal tissue complication probability). One way to achieve a high therapeutic ratio is to decrease NTCP by keeping TCP constant. Sparing of normal tissue can be increased through treatment conformality, so a better target delineation. In order to achieve a good therapeutic ratio, both tumour imaging and treatment should be performed in 3D so that the conformality of the dose to the tumour volume can be guaranteed. Technology, apparatus and physics rationale behind conformal radiotherapy will be provided. Chapter 8. IMRT: radiobiology and physics aspects of treatment. With IMRT, treatment is conformal to the tumour, however more normal tissue is exposed to radiation, though very small doses. It is under investigation whether such small doses could possibly lead to secondary malignancies. Also, due to treatment prolongation (2-3 times higher monitor units than in conventional treatment), there is a possibility for the tumour to repair the damage created by radiation during treatment. Though theoretical, these radiobiological assumptions are valid, unless otherwise proven. There are several IMRT delivery options: step-and-shoot IMRT, sliding window IMRT, tomotherapy and dynamic arc therapy. Special technology is required for IMRT that includes multileaf collimators, electronic portal imaging devices, inverse planning systems and advanced patient immobilization and record-and-verify systems. Chapter 9. Brachytherapy: radiobiology and physics aspects of treatment. Nowadays, brachytherapy gains more space within radiotherapy due to its localized aspect. Since LDR is the brachy-equivalent of hyperfractionated radiotherapy and HDR -- the brachy equivalent of hypofractionation, several tumours, which allow for intracavitary (head and neck) or interstitial (prostate) insertion gain from brachytherapy. The treatment being highly localized, tumour control is high, and, at the same time, normal tissue toxicity is reduced. The physics and technique of brachytherapy depends on the properties and activities of the radioactive sources used for the treatment. Whether a particular radioactive source can be used for brachytherapy depends on its physical characteristics but also on the practicality and ease of use. Several source delivery methods have been developed over the years from manual loading to remote after-loaders based on mechanical, hydraulic and pneumatic principles. Chapter 10. SRS/SRT: radiobiology and physics aspects of treatment. Stereotactic radiosurgery is another example of localized treatment. Though used mainly for brain lesions, it still covers a vast area of treatment sites. A major radiobiological aspect of SRS is sparing of late responding tissues, since, unavoidably, the critical organs would receive doses that could be of severe consequences unless accounted for when planning the treatment. The radiobiological aspects of the brain and CNS are also presented. Delivery techniques for SRS can vary from using simple circular collimators to specialized equipment like gamma knife and cyberknife. In addition, micromultileaf collimators are becoming a wide-spread option. While the delivery radiation delivery technique is very sophisticated, the calculation of dose distribution is surprisingly simple and many planning algorithms assume head to be a spherical and homogenous object. Chapter 11. Whole-body irradiation: radiobiology and physics aspects of treatment. After total body irradiation the hematopoietic system is, obviously, affected, as lymphocytes are one of the most sensitive cells in the body. The effect of TBI on blood cells and the consequences are presented here together with the radiobiological properties of the hematopoietic system. A description of biological dosimetry is also presented, as a valuable tool in assessing the incidental/accidental unknown dose an individual has been exposed to. The technical and physical details of this treatment, eg how to achieve whole body dose uniformity, how to protect lungs, how to calculate and measure the dose distribution will be discussed. These parameters need to be known before anyone can implement TBI in their clinic. Chapter 12. Electron therapy: radiobiology and physics aspects of treatment. Electrons are low LET particles, therefore they cause the same type of damage to the tissue as photons. As a consequence, cells have the same ability to repair the damage as they do for photons. Because of these properties, the sparing of normal tissue is easier achieved than for high LET particles. Physics of electrons is quite different to that of x-rays and this has considerable implications on the shape of dose distributions and clinical applications as well as on the production of clinically useful electron beams and their measurement. Both technical and physical details will be provided. Chapter 13. Proton therapy: radiobiology and physics aspects of treatment. Protons are used in radiotherapy due to their dose distribution, which is superior to x-rays. Due to the Bragg peak they present with, protons are highly conformal to small tumours, offering a good sparing of the normal tissue. While interactions of protons with matter is discussed in chapter 1, this chapter will concentrate not specific aspects of proton treatment delivery, eg use of synchrotrons, production of useful proton beams in order to produce a Spread-Out-Bragg peak, scanning beam techniques versus scattering foils, etc. Chapter 14. Neutron therapy: radiobiology and physics aspects of treatment. Depending on their initial energy neutrons have radiation weighting factors ranging from 5 to 20. This illustrates the range of RBE neutrons present with. The rationale for using neutrons in cancer treatment is their advantage over low LET particles in controlling hypoxic tumours (oxygen enhancement ratio close to one) and also slowly proliferating tumours which have high percentage of cells situated in the G0 phase of the cell cycle, conferring them resistance to low LET radiation. Specific description of neutron production, neutron dose delivery and monitoring will be provided. Chapter 15. High Let (Linear Energy Transfer) targeted radiotherapy for cancer This chapter will cover some of the latest, currently investigated, and perhaps less-known radiotherapy modalities involving external and internal high LET radiations. Topics will include: Boron Neutron Capture Therapy (BNCT) - covering radiobiology, neutron sources, compounds and clinical trials, Targeted Alpha Therapy (TAT) - covering alpha sources, in vitro and in vivo studies and clinical trials. Also discussed will be Photodymanic Therapy (radiation sources, in vitro and in vivo studies and clinical trials) and Photoactivation Therapy (X-ray sources, in vitro and in vivo studies and clinical trials), followed by External High LET radiotherapy (radiobiology specific to high LET radiation, heavy ions and clinical trials). Chapter 16. Predictive assays and treatment delivery verification. The ultimate aim of radiotherapy is to cure cancers. Ideally, this can be achieved by knowing the radiobiological properties of tumours and the surrounding normal tissue, to understand the radiation beam's physical properties and also to have the technology to deliver the radiation. Since tumours have different properties, and because even tumours with the same histopathological type depend on their host, ideally, treatments should be individually designed for each patient. Predictive assays are a step towards individualized treatment planning: tumour oxygenation status, proliferative potential, and intrinsic radioresistance are three major parameters that dictate tumour response to radiotherapy. Although there are some obstacles in implementing these assays into clinics (presented here), the near future will, hopefully, bring the answers to these problems. In addition to this, the last step in the radiotherapy process is the verification of the dose delivered to patient. In-vivo as well as in-vitro techniques will be discussed using point, 2D and 3D detectors, for example ionization chambers, electronic portal imagining devices and polymer gels. Chapter 17. Health Physics Issues This chapter will deal with the opposite end of radiation doses, ie low level irradiation and its effect on the concept of radiation hormesis and radiation health physics as relevant to radiation protection and legislation. Effects of low level radiation doses on cell repair, adaptive protective response or bystander effect will be discussed. Relevant radiation incidents and accidents, both the historical Atomic bombing and Chernobyl - as a base for epidemiological data - and accidents in radiotherapy departments will be presented as well as consequences of living in the areas of high natural background radiation.