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The radiobiology of hypofractionation
1Clatterbridge Cancer Centre, Bebington, UK.
Clinical Oncology (Royal College of Radiologists (Great Britain))
|March 24, 2015
Summary
Conventional radiotherapy uses many small doses, but hypofractionation with fewer large doses is proving effective for some cancers. This approach is supported by radiobiology, especially with advanced techniques like proton therapy, allowing personalized treatment plans.
Area of Science:
- Radiation oncology
- Medical physics
- Cancer biology
Background:
- The linear-quadratic model traditionally guides radiotherapy fractionation, favoring numerous small doses for optimal therapeutic ratio.
- Stereotactic radiotherapy regimens challenge this by successfully using extreme hypofractionation (fewer, larger doses) for cancers like non-small cell lung cancer.
- Tumor and normal tissue alpha/beta (α/β) ratios are critical for determining optimal fractionation, with some tumors exhibiting lower ratios than previously assumed.
Purpose of the Study:
- To re-evaluate the principles of radiotherapy fractionation in light of emerging hypofractionation evidence.
- To explore the radiobiological basis for the success of stereotactic ablative radiotherapy (SABR).
- To investigate how normal tissue behavior and dose delivery conformality influence hypofractionation efficacy and safety.
Main Methods:
- Analysis of clinical outcomes from various radiotherapy fractionation schedules, including conventional, hyper-, and extreme hypofractionation.
- Application of the linear-quadratic model and the effective alpha/beta ((α/β)eff) concept to predict normal tissue responses.
- Consideration of factors like re-oxygenation, hypoxic cell radiosensitivity, and vascular damage in large-dose fraction scenarios.
Main Results:
- Clinical data for non-small cell lung cancer radiotherapy align with linear-quadratic radiobiology, even with large fraction sizes.
- Highly conformal dose delivery and quasi-parallel normal tissue behavior enable safe hypofractionation, predictable by (α/β)eff.
- The (α/β)eff concept highlights normal tissue sparing in quasi-parallel tissues, favoring hypofractionation, particularly relevant for proton therapy.
Conclusions:
- Hypofractionation, including SABR, is a viable and effective radiotherapy strategy, supported by radiobiological principles.
- Improved dose conformality allows for individualized treatment planning, optimizing dose and fraction number based on normal tissue complication probability (iso-NTCP).
- Understanding (α/β)eff and normal tissue behavior is crucial for advancing personalized radiotherapy, including techniques like proton therapy.
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