Principles of Radiation Therapy

Radiobiology - Cell Kill Chronicles

• Primary Target: DNA; DSBs most lethal.
• Mechanisms:
  • Direct: Direct DNA ionization.
  • Indirect: H₂O ionization → free radicals ($OH·$) → DNA damage (X/gamma rays).
• Cell Cycle Sensitivity:
  • Most Sensitive: M & G2.
  • Most Resistant: Late S.
• 📌 4 Rs of Radiobiology:
  • Repair (sublethal damage)
  • Redistribution (to sensitive phases)
  • Repopulation (growth)
  • Reoxygenation (hypoxia ↓, O₂ ↑)
• Oxygen Effect: O₂ ↑ radiosensitivity. OER: 2.5-3.5. Hypoxia → resistance.
• LET & RBE:
  • Low LET (X-rays): Sparse ions, ↑repair, ↓RBE.
  • High LET (particles): Dense ions, ↓repair, ↑RBE (to ~100 keV/µm).

⭐ Most radiosensitive phases of the cell cycle are M and G2; most resistant is the late S phase.

Radiation Physics - Beam Me Up!

• Key Units:
  • Absorbed Dose: Gray (Gy). $1 Gy = 1 J/kg$ (energy absorbed per unit mass).
  • Equivalent Dose (Sv): Accounts for radiation type ($W_R$).
  • Effective Dose (Sv): Accounts for tissue sensitivity ($W_T$).
• Radiation Production & Types:
  • Photons (X-rays/Gamma rays):
    • LINACs: X-rays (Bremsstrahlung from electron-target interaction). For deep tumors.
    • Cobalt-60: Gamma rays (radioactive decay).
  • Electrons: From LINACs; treat superficial tumors (e.g., skin, nodes). Rapid dose fall-off.
• Photon Beam Properties:
  • Interactions: Compton scattering (dominant at MV energies), Photoelectric effect, Pair production (at >1.02 MeV).
  • Depth Dose: Build-up region, then exponential fall-off. Skin sparing.
• Inverse Square Law (ISL): Dose rate $\propto 1/d^2$. Critical for distance calculations.

⭐ Linear Accelerators (LINACs) are the workhorses of modern radiotherapy, capable of producing both photon (X-ray) and electron beams of various energies for treating a wide range of cancers.

Treatment Delivery - Zap Attack Tech

• Goal: Maximize tumor dose, minimize normal tissue toxicity.
• Main Modalities:
  • External Beam RT (EBRT): Source outside body.
    • Linac (Linear Accelerator): X-rays, electrons; most common.
    • Cobalt-60: Gamma rays; simpler, older.
  • Brachytherapy: Source inside/near tumor.
• Key EBRT Techniques:
  • 3D Conformal RT (3D-CRT): Beams conform to tumor shape.
  • Intensity-Modulated RT (IMRT): Modulates beam intensity; ↑ conformity, spares Organs at Risk (OARs).
  • Volumetric Modulated Arc Therapy (VMAT): Rapid IMRT via rotating gantry.
  • Stereotactic Radiosurgery (SRS): Single high dose fraction (typically brain).
  • Stereotactic Body RT (SBRT): 1-5 high dose fractions (extracranial).
• Precision Tools:
  • Image-Guided RT (IGRT): Verifies target position daily (e.g., Cone Beam CT - CBCT).
  • Particle Therapy (e.g., Protons): Bragg peak reduces exit dose. 📌 Minimizes damage beyond target.

⭐ IMRT enables dose escalation to the target while better sparing adjacent normal tissues, improving therapeutic ratio.

Radiation Effects & Safety - Damage Control Duty

• Radiation Effects:
  • Deterministic: Threshold dose; severity ↑ with dose (e.g., mucositis, fibrosis).
  • Stochastic: No threshold; probability ↑ with dose (e.g., cancer, genetic effects).
  • Acute: Occur during/soon after RT (e.g., skin erythema, mucositis).
  • Late: Occur months/years after RT (e.g., fibrosis, necrosis, secondary malignancy).
• Key Radiobiology (4 R's): Repair, Repopulation, Redistribution, Reoxygenation.
• TD 5/5 (Tolerance Dose): Dose for 5% severe complication risk in 5 years.
  • Spinal Cord: 45-50 $Gy$
  • Lens (Cataract): 10 $Gy$
  • Lung (Pneumonitis): 17.5 $Gy$
• Radiation Safety: 📌 ALARA & TDS
  • ALARA: As Low As Reasonably Achievable.
  • TDS: Time, Distance, Shielding.

⭐ Radiation protection principles are Time, Distance, and Shielding (TDS).

High‑Yield Points - ⚡ Biggest Takeaways

• DNA damage: Primarily indirect action (free radicals) for photons.
• Radiosensitivity: Peak in M & G2 phases, nadir in late S. Bergonie & Tribondeau.
• Fractionation: Spares normal tissue (4 R's: Repair, Reoxygenation, Repopulation, Redistribution), ↑tumor kill.
• Therapeutic Ratio: Maximize TCP / NTCP.
• Oxygen Effect: OER ~3 for photons; hypoxic tumors are radioresistant.
• Units: Gray (Gy) (absorbed dose); Sievert (Sv) (equivalent dose).
• Delivery: Teletherapy (external), Brachytherapy (internal).