Introduction to Clinical Radiobiology Part 2

Introduction to Clinical Radiobiology, Part 2

• Clinical radiobiology introduces the principles of clinical radiation treatment.
• The presentation covers cell survival, tumour response, radiosensitivity, and radiocurability.
• Fractionation, hyperfractionation, hypofractionation, and biologically effective dose (BED) are discussed.

Cell Survival and Tumour Response

• Most radiation damage to cells repairs within a few hours after radiation.
• Repair is the process of restoring the function of cellular macromolecules.
• Recovery is an increase in cell survival or a reduction in radiation damage with time.
• Tolerance is the amount of radiation that tissues can absorb without functional impairment.
• Tumour tolerance is not the limiting factor for prescribed radiation doses. Normal tissue tolerance is the limiting factor.
• Therapeutic radio/window is the range of doses that effectively target tumours while minimizing harm to surrounding healthy tissue.

Tumour Radiobiology Basics

• Tumours have both parenchymal (tumour cells) and stromal (blood vessels, connective tissue) components.
• Parenchymal components consist of four cell types.
  • Group 1: Well-oxygenated, viable, and actively proliferating
  • Group 2: Well-oxygenated, viable, but not proliferating
  • Group 3: Hypoxic but viable
  • Group 4: Anoxic and necrotic
• Tumour growth is unorganised compared to normal tissue.
• Tumours often outgrow their vascular supply.
• A gradient of oxygen can vary across a tumour.
• Hypoxic regions of tumours are often the most radioresistant.

Radiosensitivity and Radiocurability

• Tumours and normal tissues exhibit varying sensitivities to radiation.
• Curative doses for different tumours vary. (e.g., 30Gy for seminoma vs. >80Gy for glioblastoma)
• Repair capability differences in various tumours, affect their response to radiation.
• Tolerance dose (TD5/5 or TD50/5) represents the dose causing a specific rate of complications within a set time.

Time-Dose Fractionation

• Radiation therapy divides high doses into smaller, repeated doses (fractions) over time.
• Treatment is fractionated based on tumour sensitivity and normal tissue tolerance.
• Fractionated doses are less effective for causing cell death compared to single high doses biologically.

The 5 R's of Radiotherapy

• These five factors influence the effectiveness of radiation treatment.
• Repair: the ability of cells to repair sub-lethal damage.
• Reassortment/redistribution: cells may relocate to more or less sensitive phases of the cell cycle after radiation.
• Repopulation: surviving cells can multiply, increasing the total number needing eradication.
• Reoxygenation: hypoxic cells may become reoxygenated, becoming more sensitive to radiation.
• Radiosensitivity: variation in the sensitivity to radiation among different tissues and cells.

Repair

• Repair refers to the repair of sub-lethal damage.
• Cells in a tumour have varying repair capacity for sub-lethal damage.

Reassortment / Redisrbution

• Surviving cells may move to more sensitive phases of the cell cycle.

Repopulation

• Surviving tumour cells can repopulate, increasing their number.
• Repopulation is faster in tissues with quick cell turnover, requiring more radiation exposure.

Reoxygenation

• Hypoxic cells (low oxygen) can become reoxygenated.
• Reoxygenation occurs during fractionated radiotherapy.
• Little effect on normal tissues since they are already well oxygenated.

Radiosensitivity

• Repair and repopulation will cause a tumour response to successive treatments.
• Reassortment and reoxygenation make a tumour more sensitive to successive radiation.
• The factors combined affect the tumour response to fractionated radiotherapy.
• The steepness and curvature of isoeffect curves are related to the a/β ratio.

The α/β Ratio and Fractionation

• The α/β ratio is a critical factor in determining the best dose fractionation regimen.
• Different types of tissue and tumours have diverse a/β ratios.
• Lower α/β values are beneficial for normal tissue sparing and preserving tolerance.
• Higher α/β values are beneficial for maximizing tumour cell killing within a limited treatment duration.

Fractionation Schedules in Clinical Radiotherapy

• Conventional fractionation schedules employ doses of 1.8-2 Gy 5 times per week.
• Hyperfractionation gives fractions smaller than 1.8 Gy, increasing the number of fractions daily.
• Hypofractionation reduces normal tissue complications by employing doses above 2 Gy per fraction but reducing treatment duration
• Accelerated radiotherapy reduces the overall treatment time by increasing the dose and frequency of fractions.

Biologically Effective Dose (BED)

• BED helps estimate the observed biological effect of diverse fractionation schedules.
• BED is beneficial for calculating effective equivalent doses for different fractionation schedules.

Fractionation and Tolerance Dose

• Tolerance tables for standard fractionation regimens are useful but require the calculation of corresponding equivalent dose.
• Example: Prescribing 4 Gy x 5 fractions, for bone mets to assess safety.

Calculations

• Radiobiologists often calculate changes resulting from unplanned treatment gaps, incorrect fractionation, or radiation variations.
• The choice of α/β ratio greatly affects these calculations.

Caution

• Cautious calculation is advisable due to the significant impact of α/β ratio.

Self-Directed Reading

• Explore the FAST and CHHiP trials.
• Investigate treatment options for missed radiotherapy treatments.

This quiz explores key concepts in clinical radiobiology, focusing on cell survival, tumor response, and radiation treatment principles. Topics include radiosensitivity, recovery processes, and treatment fractionation. Strengthen your understanding of how radiobiology applies to effective cancer therapies.