Radiobiological Principles Underlying Stereotactic Radiation Therapy

Abstract

We review the radiobiological principles underlying stereotactic radiation therapy (SRT) and their clinical applications to single- and multi-fraction radiotherapy—both for malignant tumors, benign tumors, and vascular disorders. The classic radiobiological phenomena of repair, reoxygenation, and repopulation (the three Rs) are discussed, as well as their relationship to cell death, a clearly important mechanism by which radiotherapy produces both tumor control and normal tissue complications. Mechanistic models of radiotherapeutic response are useful for calculating isoeffect relationships for alternate fractionation schemes and for understanding the underlying biophysical mechanisms of radiation response. The linear–quadratic (LQ) formalism, which models the three Rs, is now almost universally used for isoeffect calculations of different fractionation and protraction schemes. While other radiobiological mechanisms at high doses per fraction have been shown in the laboratory, there is to date no clinical evidence of their relevance to SRT response, and the LQ model appears to be appropriate for use at all the doses and fractionation schemes of relevance to SRT. Rather than new biological mechanisms, recent analyses of clinical data suggest that the great success of SRT is primarily related to its improved conformal dose delivery that permits significant escalation of the biologically effective doses.