EP-1232: Will extreme hypofractionation always improve outcome in prostate radiotherapy?

Abstract

Purpose/Objective: This study aimed to investigate the impact of increasing radiation delivery time on the outcome of hypofractionated radiation therapy for prostate cancer. Intrafraction repair is seldom discussed in relation to external beam radiation therapy as most fractional doses are delivered in the course of a few minutes and the beam-on time is not very much different from the time to deliver all individual fields. Advanced techniques aimed at delivering high fractional dose, employing multiple fields, scanning the target volume or requiring multiple imaging sessions may however take considerably longer, increasing the importance of intrafraction repair. Materials and Methods: Mono-exponential and bi-exponential repair models have been used in prostate patients to study the loss of biologically effective dose for several clinicallyrelevant irradiation times between 5 and 60 minutes. These were then converted into loss of biochemical control at 5 years using clinically-relevant dose response curves derived from 10688 prostate patients treated with conventional fractionation. The theoretical predictions were subsequently compared with clinical results from 14 newly reported studies totalling 4363 patients undergoing conventionallyfractionated and hypofractionated prostate radiotherapy. Results: For low-risk patients the equivalent doses delivered were quite high and consequently the reported results were very good and in agreement with theoretical predictions. For intermediateand high-risk patients however, the results from hypofractionated schedules delivered with timeconsuming techniques appear to be compatible with predictions accounting for intrafraction repair taking place during longer irradiations, while results from moderately hypofractionated or conventionally-fractionated schedules are in agreement with short irradiation times. Treatment sessions lasting more than about 20 minutes could lead to significant loss of biochemical control even when relatively slow repair is relevant for prostate tumours. Large effect losses could therefore be expected from extremely hypofractionated schedules with long irradiation sessions as might be the case of scanned beams and/or with multiple intrafraction imaging sessions to check the positioning of the patient. The loss of effect might also be reflected into an apparent reduced sensitivity to fractionation for the tumours. Conclusions: Intrafraction repair plays an important role for prostate radiation therapy and may lead to loss of biological effect in the case of extremely hypofractionated techniques requiring increased irradiation times Neglecting intrafraction could also interfere with the derivation of the fractionation sensitivity for prostate tumours.