Radiobiology and Radiotherapy

Types of Radiation Used in Radiotherapy

• Electromagnetic Radiation (Photons):
  • High energy X-rays
  • Gamma rays
• Particle Radiation:
  • Electrons (beta particles)
  • Protons
  • Helium nuclei (alpha particles)
  • Carbon ions
• Characteristics:
  • All forms are ionizing radiation sufficient to dislodge electrons from atoms.

How Ionizing Radiation Damages DNA

• Indirect Action:
  • Interactions with water molecules generating Reactive Oxygen Species (ROS) that damage DNA.
• Direct Action:
  • Interactions directly with DNA or associated molecules may cause strand breaks.

Importance of DNA Damage in Radiotherapy

• Sensitivity:
  • Nuclei are more sensitive to radiation than cytoplasm.
  • Altering DNA structure modifies the biological effects of radiotherapy.
• Correlations:
  • Effectiveness correlates with radiation-induced chromosome abnormalities and density of double-strand breaks (DSBs).
• Defects in DNA Repair:
  • Cells with defective DNA repair mechanisms are more sensitive to radiation.

Cell Cycle and Radiosensitivity

• Variability:
  • Radiosensitivity varies with cell cycle phase.
  • DNA damage checkpoints in the cell cycle play a key role, with mitosis delayed during checkpoint activation to allow repair.

Types of DNA Damage

• Main Lesion:
  • Double Strand Breaks (DSBs) are critical post ionizing radiation exposure.
• Repair Mechanisms:
  • Non-Homologous End Joining (NHEJ): occurs when sister chromatids are unavailable (G0, G1, early S).
  • Homologous Recombination (HR): occurs when sister chromatids are present (late S, G2, early M).

Chromosome Abnormalities due to Radiation

• G1 or G0 Phase:
  • Damage leads to dicentric chromosomes and acentric fragments.
• S or G2 Phase:
  • Chromatid types of structural damage observed (e.g., asymmetric and symmetric exchanges).

Mechanisms Leading to Cell Death from DNA Damage

• Mitotic Catastrophe:
  • Cells with complex chromosome damage fail to survive mitosis, producing multinucleated or abnormal cells.

Clinical Radiotherapy Goals

• Objectives:
  • Control tumor growth, potentially cure (radical) or relieve symptoms (palliative).
• Success Factors:
  • Radiation dose and tumor sensitivity are key; maximizing therapeutic ratio is crucial.

Delivery Methods of Radiotherapy

• Local Radiotherapy:
  • External beam photon radiotherapy
  • Particle radiotherapy
  • Brachytherapy
• Systemic Radiotherapy:
  • Delivers radiation throughout the body, minimizing healthy tissue exposure while maximizing tumor dose.

External Beam Photon Radiotherapy

• Mechanism:
  • Radiation is delivered via a rotating gantry targeting the tumor.
• Equipment:
  • A linear accelerator (LINAC) generates high-energy X-rays.

Fractionation in Radiotherapy

• Concept:
  • Administering discrete, repeated doses improves therapeutic ratios.
• 4 R's:
  • Repair (sublethal damage): Healthy cells better at repairing than cancer cells.
  • Repopulation: Surviving cells proliferate, potentially favouring tumors.
  • Redistribution: Cells may synchronize to more sensitive phases after treatment.
  • Reoxygenation: Improving oxygenation enhances radiosensitivity as tumors shrink.

Adverse Effects of Radiation Therapy

• Acute vs. Late Effects:
  • Acute (short-term) effects can occur during treatment; late (long-term) effects emerge later (months to years).
  • Advantages are dose-dependent and vary based on exposed tissues.
• Normal Tissue Toxicity:
  • Sensitivity to radiation varies; renewing tissues show pronounced acute effects, while late effects appear in less frequently dividing cells.

Radiotherapy Administration Methods

• Electron Beam:
  • Applied directly for superficial tissue cancers like skin lymphomas.
• Particle Therapy:
  • High-energy particle accelerators (e.g., protons) provide precise depth control.
• Brachytherapy:
  • Insertion of radioisotopes into tumors minimizes surrounding tissue exposure.
• Systemic Therapy:
  • Radioisotopes targeted to tumor cells through antibodies, delivering localized effects throughout the body.

Summary of Radiobiology and Radiotherapy

• Understanding the types of ionizing radiation, effects on DNA damage, cell repair mechanisms, radiosensitivity across cell cycles, delivery methods, and the significance of fractionation are essential in optimizing radiotherapy treatments for better patient outcomes.