14.1 Radiotherapy modalities and dose fractionation
5 min read•july 31, 2024
Radiotherapy modalities and dose fractionation are key aspects of cancer treatment. External beam radiotherapy and offer different approaches to delivering radiation, each with unique advantages for specific tumor types and locations.
Dose fractionation exploits biological differences between tumor and normal cells. By understanding the "4 Rs" of radiobiology and using models like the linear-quadratic equation, oncologists can optimize treatment schedules to maximize tumor control while minimizing side effects.
External Beam vs Brachytherapy
Delivery Methods and Applications
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External beam radiotherapy (EBRT) delivers radiation from outside the body using linear accelerators or other radiation-producing machines
Brachytherapy involves placing radioactive sources directly in or near the tumor
EBRT treats larger areas and deeper-seated tumors
Brachytherapy typically used for more localized treatments and delivers higher doses to smaller volumes
Common EBRT techniques include , intensity-modulated radiotherapy (IMRT), and
Brachytherapy classified as temporary (removable sources) or permanent (seeds left in place)
Brachytherapy also categorized as or based on dose delivery rate
Treatment Planning and Delivery
EBRT requires careful patient positioning and immobilization for accurate dose delivery (thermoplastic masks, vacuum cushions)
Brachytherapy often involves surgical procedures for source placement (catheters, applicators)
Image-guidance plays a crucial role in both EBRT and brachytherapy for precise target localization and treatment delivery
EBRT uses on-board imaging systems (cone-beam CT, MV/kV imaging)
Brachytherapy employs ultrasound, CT, or MRI for applicator placement and dose planning
EBRT planning utilizes complex algorithms to optimize (inverse planning, Monte Carlo simulations)
Brachytherapy planning focuses on source positioning and dwell times to achieve desired dose coverage
Rationale for Dose Fractionation
Biological Principles
Dose fractionation in radiotherapy exploits the differential response to radiation between tumor cells and normal tissues
Maximizes tumor control while minimizing normal tissue toxicity
The "4 Rs" of radiobiology form the biological basis for fractionation
Repair allows normal tissues to recover between fractions
Repopulation of surviving cells occurs during treatment course
Redistribution of tumor cells into more radiosensitive cell cycle phases
Reoxygenation of hypoxic tumor regions increases radiosensitivity
Normal tissues generally have a greater capacity to repair sublethal damage between fractions compared to tumor cells
Fractionation allows for redistribution of surviving tumor cells into more radiosensitive phases of the cell cycle (G2/M phase)
Reoxygenation of hypoxic tumor regions occurs between fractions, increasing radiosensitivity of previously resistant hypoxic cells
Quantitative Models and Applications
quantifies and compares biological effects of different fractionation schedules
Uses α/β ratio to characterize tissue-specific radiation sensitivity
Standard fractionation typically delivers 1.8-2 Gy per fraction, 5 days a week
calculation helps compare different fractionation schemes
BED=nd(1+d/(α/β))
n number of fractions, d dose per fraction, α/β tissue-specific ratio
allows for standardized comparison
EQD2=D×(d+α/β)/(2+α/β)
D total dose, d dose per fraction, α/β tissue-specific ratio
Biological Basis of Hypofractionation vs Hyperfractionation
Hypofractionation Principles
delivers larger doses per fraction over a shorter overall treatment time
Exploits lower α/β ratio of certain tumors compared to surrounding normal tissues
Potentially improves for tumors with low α/β ratios (prostate cancer, α/β ≈ 1.5 Gy)
Capitalizes on greater sensitivity of low α/β tumors to larger fraction sizes
Reduces overall treatment time, potentially mitigating accelerated repopulation in fast-growing tumors
Examples of hypofractionated regimens
for early-stage lung cancer (54 Gy in 3 fractions)
Moderate hypofractionation for prostate cancer (60 Gy in 20 fractions)
Hyperfractionation Principles
Hyperfractionation uses smaller doses per fraction delivered multiple times per day
Takes advantage of faster repair kinetics of normal tissues compared to tumors
Aims to reduce late normal tissue toxicity while maintaining or improving tumor control
Particularly beneficial for rapidly proliferating tumors with high α/β ratios (head and neck cancers, α/β ≈ 10 Gy)
Allows for dose escalation without significantly increasing
Examples of hyperfractionated regimens
Head and neck cancer treatment (81.6 Gy in 68 fractions, 1.2 Gy twice daily)
Limited-stage small cell lung cancer (45 Gy in 30 fractions, 1.5 Gy twice daily)
Comparative Analysis
α/β ratio derived from linear-quadratic model key factor in determining appropriateness of altered fractionation schedules
Both approaches consider time factor in radiobiology
Hypofractionation potentially reduces impact of accelerated repopulation in fast-growing tumors
Hyperfractionation exploits differential repair rates between tumors and normal tissues
Choice between hypo- and hyperfractionation depends on tumor type, location, and surrounding normal tissue constraints
Clinical trials comparing altered fractionation to standard fractionation crucial for establishing optimal treatment protocols
Advantages and Limitations of Stereotactic Radiotherapy
Advantages and Clinical Applications
Stereotactic radiotherapy (SRT) delivers highly conformal, high-dose radiation to small target volumes with extreme precision
Often administered in single or few fractions (1-5 treatments)
Ability to treat inoperable tumors (brain metastases, early-stage lung cancer)
Reduced overall treatment time improves patient convenience and resource utilization
Potentially improved rates for certain tumor types
Achieves higher biological effective dose (BED) compared to
Potentially overcomes radioresistance in some tumors due to high fractional doses