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An Overview of the Radiobiology of Hypofractionation and Stereotactic Radiotherapy
February 2, 2021 from 2:00pm EST to 2:30pm EST
As the field of Radiation Oncology continues to shift towards hypofractionation, made possible through advances in imaging and treatment delivery technology, there remains a need to better understand the underlying biological mechanisms in an effort to improve clinical outcomes. While vital data from clinical trials of high-dose stereotactic radiation therapy continues to emerge, further optimization of treatment planning, fractionation, and delivery have the potential to improve patient care. An overview of biological mechanisms, alternate biophysical models, and recent clinical data for stereotactic radiotherapy will be presented. Our conceptual understanding and mathematical models of biological dose response are often based on in vitro or animal data leading to the question: do the classical 5 R’s of radiobiology still apply in the clinical paradigm of SRS and SBRT? The possibility of unique radiobiological mechanisms and secondary targets in addition to tumor cell DNA will be discussed, including tumor vasculature, immune system activation, and the impact of tumor hypoxia. Molecular imaging of inter-patient variation in radiosensitivy and treatment response may also provide opportunities for treatment individualization. Mathematical models can be used to evaluate the biological effectiveness of altered dose fractionations and to facilitate the design and comparison of treatments. The applicability of the linear-quadratic (LQ) model at high doses per fraction has been critically examined by many investigators. A brief overview will be given of several extensions to the LQ model that have been proposed in an attempt to overcome this potential high-dose limitation. However, while the LQ model is known to be an approximation to more sophisticated kinetic reaction rate models, some clinical outcome data suggest the LQ is still a reasonable approximation at stereotactic doses.