Increasing the Therapeutic Ratio of Stereotactic Ablative Radiotherapy by Individualized Isotoxic Dose Prescription

To obtain a favorable tradeoff between treatment benefits and morbidity ("therapeutic ratio"), radiotherapy (RT) dose is prescribed according to the tumor volume, with the goal of controlling the disease while respecting normal tissue tolerance levels. We propose a new paradigm for tumor dose prescription in stereotactic ablative radiotherapy (SABR) based on organ-at-risk (OAR) tolerance levels called isotoxic dose prescription (IDP), which is derived from experiences and limitations of conventionally fractionated radiotherapy. With IDP, the radiation dose is prescribed based on the predefined level of normal tissue complication probability of a nearby dose-limiting OAR at a prespecified dose-volume constraint. Simultaneously, the prescribed total tumor dose (TTD) is maximized to the technically highest achievable level in order to increase the local tumor control probability (TCP). IDP is especially relevant for tumors located at eloquent locations or for large tumors in which severe toxicity has been described. IDP will result in a lower RT dose or a treatment scheduled with more fractions if the OAR tolerance level is exceeded, and potential dose escalation occurs when the OAR tolerance level allows it and when it is expected to be beneficial (if TCP < 90%). For patients with small tumors at noneloquent sites, the current SABR dose prescription already results in high rates of local control at low toxicity rates. In this review, the concept of IDP is described in the context of SABR.