Fractionation versus Adaptation for Compensation of Target Volume Changes during Online Adaptive Radiotherapy for Bladder Cancer: Answers from a Prospective Registry.

Online adaptive radiotherapy (ART) allows adaptation of the dose distribution to the anatomy captured by with pre-adaptation imaging. ART is time-consuming, and thus intra-fractional deformations can occur. This prospective registry study analyzed the effects of intra-fraction deformations of clinical target volume (CTV) on the equivalent uniform dose (EUD CTV ) of focal bladder cancer radiotherapy. Using margins of 5-10 mm around CTV on pre-adaptation imaging, intra-fraction CTV-deformations found in a second imaging study reduced the 10th percentile of EUD CTV values per fraction from 101.1% to 63.2% of the prescribed dose. Dose accumulation across fractions of a series was determined with deformable-image registration and worst-case dose accumulation that maximizes the correlation of cold spots. A strong fractionation effect was demonstrated-the EUD CTV was above 95% and 92.5% as determined by the two abovementioned accumulation methods, respectively, for all series of dose fractions. A comparison of both methods showed that the fractionation effect caused the EUD CTV of a series to be insensitive to EUD CTV -declines per dose fraction, and this could be explained by the small size and spatial variations of cold spots. Therefore, ART for each dose fraction is unnecessary, and selective ART for fractions with large inter-fractional deformations alone is sufficient for maintaining a high EUD CTV for a radiotherapy series.