Basic Clinical Radiobiology PDF

Presented by: An Introduction to clinical Dr Heather Radiobiology Lawrence. Senior Lecturer: Radiotherap Code: CKQBFU y and Oncology What is radiobiology The study of the sequence of events that follow the absorption of energy from ionising radiations, the efforts of the organi...

Presented by: An Introduction to clinical Dr Heather Radiobiology Lawrence. Senior Lecturer: Radiotherap Code: CKQBFU y and Oncology What is radiobiology The study of the sequence of events that follow the absorption of energy from ionising radiations, the efforts of the organism to compensate and the damage to the organism that may be produced. (Travis, 1989) Image taken from: Joiner & Van Der Kogel, 2009: 4 The clinical significance of radiobiology Provides the conceptual basis for radiotherapy. It helps to explain how normal tissue and tumours respond to radiation. Provides the foundation for the development of new approaches in radiotherapy. Guides the development of new fractionation schedules in radiotherapy Provides the foundation for schedule changes when schedules are interrupted or dose rates change. Plays a leading role in developing individualised radiotherapy protocols. The interaction of radiation with matter Important points to consider Radiation may or may not interact with a cell. If an interaction occurs, damage may or may not be produced in the cell. Energy is deposited in the cell in a random and non- selective way. The initial deposit of energy occurs in less than 1 second. Visible changes are not usually different to those caused by others traumas. Biologic changes that occur after irradiation do so after a latent period which is inversely related to the dose administered. This can range from minutes to years. (Travis, 1989: 26) The interaction of radiation with matter Direct action: Occurs when ionising radiation interacts with a cell. Damage occurs as a result of damage to a critical cell structure e.g the DNA & chromosomes Most likely to occur with electrons and protons (high LET radiations) The radiation has the ability to ionise or to eject electrons from the cell molecules. The interaction of radiation with matter Indirect action As 80% of the cell consists of water, the interaction of radiation with water in the cell is common. Free radicals are formed which are considered to be a major factor in the production of damage to cells, particularly when low LET radiations are used. 1 Gy = 1000 single DNA strand breaks and 40 double strand breaks. LET and RBE LET: the rate at which energy is deposited by charged particles while they travel thru matter. High LET = greater radiotoxicity or RBE E.g RBE of neutrons = 2 (twice as effective at cell kill than photons) RBE Cellular response to radiation The fate of irradiated cells One of 4 main things can happen to a cell after irradiation: Division delay Interphase Death Reproductive failure Apoptosis Image taken from: Travis, 1989: 50 Cell survival curves When a cell population is irradiated, the following can happen: Some cells are lethally damaged. Some cells are sublethally damaged. Some cells are not damaged. Factors that influence cellular response There are 3 groups of factors that can change the response of cells to radiation: Physical factors (LET and dose rate) Chemical: radiosensitisers and radioprotectors (NB: oxygen) Biologic factors (position in the cell cycle and ability to repair sublethal damage) Explaining the shape of the cell survival curve The linear quadratic model. The shape or bendiness if the curve can be explained by the ratio of α/ β α describes the linear component of the curve (initial slop) β describes the quadratic component (the curve) Image taken from: Joiner and Van Der Kogel, 2009:49 Tissue response to radiation From cells to tissues The ratio of α/ β helps us in clinical radiotherapy to predict how tumours and normal tissue will respond to a dose of radiation. Tissues that contain cells that cells that are actively dividing are more sensitive to radiation damage than those that contain cells that normally do not divide. Radioresistant = muscle, liver, brain, spinal cord (smaller α/ β) Radiosensitive = bone marrow, testis (large α/ β) Image taken from: Travis, 1989: 86 Response of tissues Tissue response to radiation is a function of: Dose administered The volume of tissue irradiated and their FSUs The healing ability of the tissue Uncontrollable factors such as patient age, genetics, lifestyle etc Volume and FSU The total dose that tissue can tolerate depends on the volume irradiated and the architecture of the functional sub units (FSU’s). Enough of the tissues cells must remain clonogenic for repair of damage to take place. If the tissue has structurally undefined FSUs, the tissue contains cells that can migrate and repair the damage. This is also known as a Parallel organ design EG = skin Tissues with structurally defined FSU’s cannot do this and can only repair a predetermined area/space. This is also known as a Serial organ design. EG = spinal cord The Volume Effect Serial organ – Small volume of high irradiation can stop organ function e.g. Spinal cord Parallel organ – can withstand high dose to a small volume and maintain overall function e.g. skin Radiation effects on tissue Deterministic as they have a dose threshold with a clear clinical response. Acute changes: seen within 6 months of treatment Chronic changes: seen 6 months + after treatment. References Joiner, M and Van Der Kogel, A (2009) Basic Clinical; Radiobiology. 4th Edition. CRC Press. New York Travis, E.L (1989) Premier of Medical Radiobiology. 2nd edition. Mosby. Houston. Washington, C,M., Leaver, D. and Trad, M. (2021). Washington and Leaver’s Principles and Practice of Radiation Therapy. 5th Edition. Elsevier. St.Louis.