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The PERYTON-trial, a phase III RCT, investigates the role of hypofractionation in salvage radiotherapy (SRT) for patients with a biochemical recurrence after prostatectomy. In hypofractionation, accurate dose delivery is crucial. We aim to analyze the inter-fractional displacement (IFD) of the CTV in SRT. 

The first 12 patients treated in the PERYTON-trial were retrospectively analyzed, six patients received the conventional schedule (35x2Gy) and six patients received the hypofractionated schedule (20x3Gy). The PTV margin used was 8 mm. Each patient underwent a planning-CT and MRI. Patients were instructed to show with a comfortably full bladder, no rectal preparation was applied. Prior to each fraction a CBCT was obtained. CBCTs were matched with the planning-CT using a bony verification mask, translations only. Rectum and bladder were contoured for each CBCT. The anterior rectal wall represents the posterior border of the CTV and the bladder wall represents the anterior border of the CTV. To analyze anterior-posterior (AP) IFD of the CTV, five reference points of interest were placed at the anterior rectal wall and three at the posterior bladder wall (Figure 1). These craniocaudal levels were chosen in accordance with the guideline of Wiltshire et al. Positive values represent posterior IFD, negative values anterior IFD. Volume changes and IFD were calculated to evaluate the coverage within the used PTV margin.

A total of 324 CBCTs were analyzed. Both treatment arms showed identical changes in (rectum and bladder) volume and IFD. Treatment time had no influence on volume changes or IFD. Inter-fractional rectal and bladder volume varied widely, with a median of +0.7% (IQR -31.7% to +32.1%) and -25.6% (IQR -46.0% to +10.9%), respectively. The mean IFD, mean population systematic and random errors of all reference points are summarized in Figure 1. IFD >8 mm was correlated with change in rectal and bladder volume during treatment (Mann-Whitney U: p<0.001 and p=0.008, respectively). In 9 patients (75%), rectal wall IFD was <8 mm in >90% of fractions. In 5 patients (41%), bladder wall IFD was <8 mm in >90% of fractions. Patients with IFD of >8 mm showed large rectal or bladder volume during planning-CT, with a median of 185.4 cm³ (IQR 154.8 to 236.5 cm³) and 350.5 cm³ (IQR 225.9 to 402.1 cm³), respectively. The largest IFD was seen at level 5, the most superior level (rectal wall IFD > 8mm in 22% and bladder in 22%) (Figure 2). At the three most inferior levels, the IFD was <8 mm in 98% of fractions.

In post-prostatectomy salvage radiotherapy, inter-fractional AP displacement of the inferior CTV was within the PTV margin of 8 mm in 98% of fractions. However, a wide variation in rectal and bladder volumes during treatment was observed. With a stricter rectum and bladder preparation and image-guided SRT protocol, CTV under- and OAR overdosing is expected to be avoided.