Introduction to Clinical Radiobiology

Introduction to Clinical Radiobiology

• Presented by Dr Heather Lawrence, Senior Lecturer in Radiotherapy and Oncology
• Course code: CKQBFU

What is Radiobiology?

• Studies the sequence of events following ionizing radiation absorption
• Examines how the body compensates for and is damaged by this energy absorption
• Provides a time-scale of effects from physical to biological, including early and late effects
• Includes ionization, excitation, free-radical reactions, enzyme reactions, repair processes, and cell proliferation.

Clinical Significance of Radiobiology

• Provides a theoretical basis for radiotherapy
• Explains how normal tissues and tumors respond to radiation
• Guides the development of new radiotherapy approaches and fractionation schedules
• Helps adjust schedules when interrupted or dose rates change
• Important in developing personalized radiotherapy protocols

Interaction of Radiation with Matter

• Direct action: Ionizing radiation directly interacts with the cell, damaging critical structures like DNA and chromosomes, often by electrons or protons.
• Indirect action: Radiation interacts with water molecules in the cell, creating free radicals (OH, H•), that cause cellular damage, primarily when low-LET radiation is used.

Important Considerations

• Radiation interaction with a cell may not always result in damage.
• Energy deposition is random and non-selective.
• Initial energy deposition is extremely fast (<1 second).
• Visible changes after irradiation are often similar to other traumas.
• Biologic changes after irradiation follow a latent period inversely proportional to the dose (ranging from minutes to years).

The Linear Quadratic Model

• Explains the shape of cell survival curves (exp(-ad - βd²))
• α represents the linear component (initial slope)
• β represents the quadratic component (curve bending)
• The ratio α/β can be used to evaluate the type of tissue response to radiation.

LET and RBE

• LET (Linear Energy Transfer): Rate at which energy is deposited by charged particles as they travel through matter.
• High LET radiation has greater radiotoxicity (RBE) which means it is more damaging.
• Example: RBE of neutrons is 2, meaning neutrons are twice as effective at killing cells than photons.

Cellular Response to Radiation

• Four primary responses after irradiation include:
• Division delay
• Interphase death
• Reproductive failure
• Apoptosis

Cell Survival Curves

• When cells are irradiated, some are damaged lethally, some are damaged sub-lethally, and some are not damaged.
• Cell survival curves depict the relationship between radiation dose and the fraction of surviving cells.
• Dose curves are influenced by physical, chemical, and biologic factors.

Factors Influencing Cellular Response

• Physical factors: LET and dose rate
• Chemical factors: radiosensitizers (e.g., oxygen) and radioprotectors
• Biological factors: position in the cell cycle and the ability to repair sublethal damage

Tissue Response to Radiation

• The response of tissues is a function of administered dose, the volume of tissue irradiated, and the tissue's healing ability.
• Uncontrollable factors like patient age, genetics, and lifestyle also affect it.

Volume and FSU

• Tissue tolerance depends on the irradiated volume and the architecture of functional units (FSUs).
• Enough clonogenic cells must remain for tissue repair
• Parallel organs have structurally undefined FSUs, while serial organs have defined FSUs.
• Examples: skin-parallel, spinal cord-serial

Radiation Effects on Tissue

• Deterministic effects: clear dose-response relationship with a threshold. Acute changes occur within 6 months, and chronic changes outside that period.

References

• Joiner and Van Der Kogel (2009)
• Travis (1989)
• Washington et al (2021)

This quiz delves into the key concepts of Clinical Radiobiology as presented by Dr. Heather Lawrence. It covers the sequence of events following ionizing radiation absorption, the clinical significance of understanding normal and tumor tissue responses, and how this knowledge informs radiotherapy practices. Test your understanding of these crucial elements in modern cancer treatment.