Investigating Setup Error Differences between Conventional and Ultra-Hypofractionated Whole Pelvis Radiation Therapy:...

The multi-institutional HOPE trial (NCT04197141) compared conventional (25 fractions over 5 weeks) to ultra-hypofractionated (5 fractions over 1.5 weeks) whole pelvis radiotherapy for unfavorable intermediate and high/very high-risk prostate cancer patients treated with brachytherapy boost. Within this randomized controlled trial, we investigated setup errors for clinical target volumes corresponding to the prostate (CTVp) and nodes (CTVn).

Fifty-four patients treated within a single institution were analyzed, with 28 treated on the ultra-hypofractionated arm and 26 on the conventional fractionation arm. Prior to treatment, three fiducial markers were implanted into the prostate for daily cone-beam computed tomography (CBCT) matching. All plans were delivered using volumetric modulated arc therapy with a uniform 6-mm PTV margin. For all treatment fractions, average fiducial matching errors were measured for CTVp, while errors to CTVn were determined based on the difference between the treatment position and an automatic match to bone. Asymmetric PTV margins to account for prostatic and nodal setup errors were calculated using the van Herk formalism.

Median (interquartile range [IQR]) 3D errors for CTVp were 1.4 (0.8-2.5) mm for conventional versus 1.2 (0.7-1.9) mm for the ultra-hypofractionatated arms (p = 0.013), while for CTVn they were 2.8 (1.6-4.2) mm and 2.9 (2.2-4.4) mm, respectively (p = 0.07). Between arms, statistically significant differences in setup errors were noted in all directions for CTVp and in the anterior-posterior direction for CTVn (p < 0.05). To account for setup error, the required PTV margins in the anterior-posterior/superior-inferior/lateral directions were 2.8/3.8/0.8 and 2.7/3.0/1.0 mm for conventional and ultra-hypofractionated treatments, respectively; for elective nodes, margins were 5.4/4.4/0.7 and 5.7/4.9/1.0 mm, respectively.

The 6-mm PTV margin around the CTVn is appropriate to account for residual setup error while the margin around the CTVp could be reduced, assuming other sources of error are controlled. The residual 3D errors for the prostate were statistically significantly smaller in the ultra-fractionated regimen, which was potentially due to longer image matching times and/or the higher percentage of patients treated with a 6-DOF couch in that arm. However, this came at the expense of slightly larger nodal PTV margins in the ultra-hypofractionated arm. These findings highlight the need for individual centers to independently quantify their treatment uncertainties, as measurable differences were observed between treatment arms despite identical image guidance protocols.