Emphasis on Repair, Not Just Avoidance of Injury, Facilitates Prudent Stereotactic Ablative Radiotherapy

Stereotactic ablative radiotherapy (SAbR) is a potent, hypofractionated treatment against cancer which puts adjacent normal tissue in potential peril. Accurate delineation of normal tissue injury risks from SAbR has been challenging, and lack of clear understanding of SAbR tolerance continues to limit its potential. In this review, we contend that SAbR effects on normal tissue could be akin to a surgical "wound," and that adequate wound repair of organs at risk is an essential component of effective SAbR therapy. To mitigate risks of clinical relevance from an SAbR wound, in addition to the traditional views on architectural organization and functional organization of an organ at risk, one should also consider the organ's predominant wound healing tendencies. We also propose that avoidance of SAbR injury to organs at risk must involve careful thought to minimize risk factors that could further impair wound healing. It is imperative that efforts aimed at determining appropriate dose constraints based on predicted SAbR wound injury repair mechanisms for a particular organ to be studied as a critically important step to furthering our understanding of SAbR-related normal tissue tolerances. This can be best achieved through thoughtful design of prospective phase I dose-escalation studies.