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

SIMPLE SUMMARY: Online adaptive radiotherapy (ART) allows adaptation of the dose distribution to the anatomy captured with pre-adaptation imaging. Since ART is time-consuming, intra-fraction deformations can occur, antagonizing the advantages of ART. In this study from a prospective registry, the effects of intra-fraction deformations of the clinical target volume (CTV) on the equivalent uniform dose (EUD(CTV)) of focal radiotherapy of invasive bladder cancer were evaluated. Using margins of 5–10 mm around CTV, intra-fraction CTV-deformations reduced the effect of ART, lowering the 10th percentile of EUD(CTV) values per fraction from 101.1% to 63.2% of the prescribed dose. A strong fractionation effect was demonstrated, making the EUD(CTV) for a series of dose fractions insensitive to EUD(CTV)-declines per fractions. Two dose accumulation methods showed that EUD(CTV) values were >92.5% for all series of dose fractions, which could be explained by the small size and the spatial variations of cold spots. Our data showed that ART for each dose fraction is unnecessary. ABSTRACT: 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.