Part I | Chapter 5 98 intrafraction displacements during each fraction were calculated using these translational shifts. For the sub-fractionation workflow, the average 3D displacement was calculated as the average of the intrafraction 3D displacement that occurred between PV2-PV1 (delivery of sub-fraction 1) and INTRA-PV2 (delivery of sub-fraction 2). Furthermore, intrafraction 3D displacements were estimated for two hypothetical clinical scenarios: [1] applying the previous clinical UMC Utrecht workflow (1xATS followed by 1xATP just before beam-on and delivery of 7.25 Gy in one go17) and [2] applying a single ATS procedure without additional ATP step(s). For scenario 1, residual intrafraction displacements were estimated from PV2-PV1 (‘lower’ limit, as PV2 captures the anatomy during the first 3 min of a 10 min 7.25 Gy delivery) and INTRA-PV1 (‘upper’ limit, as the average time between PV1-INTRA is 17.3 min, which is slightly longer than the average 15 min actually involved17). For scenario 2, intrafraction motion was estimated from PV1-PRE. The estimated 3D displacements from these scenarios were compared to those from the applied sub-fractionation workflow. Finally, both the population systematic (Σ) and population random (σ) residue intrafraction motion components were calculated for the sub-fractionation scheme and PTV margins were determined for the anterior-posterior (AP), cranial-caudal (CC), and left-right (LR) direction using the van Herk formula (see Supplementary for full details).19 Results Between December 2021 and May 2022, 15 prostate cancer patients completed their treatment using the sub-fractionation workflow. Of the 75 fractions, 73 (97%) were executed according to plan following the sub-fractionation workflow. Two fractions (two patients) were excluded due to (human) errors leading to delays in treatment. In both cases, the ‘jam’ procedure was executed prematurely and therefore new treatment plans had to be created. In these patients, a second ATS procedure was employed to deliver the second sub-plan and the treatment was completed, delivering the prescribed dose per fraction. The average time from start of PRE imaging to end of beam-on of the second sub-fraction (on-table time) was 42.7 min (Table 1). Except for the two excluded cases (on-table times of 76 and 80 min), on-table time was £ 60 min for all fractions (range: 35-58 min). The intrafraction motion over the course of a fraction (between PRE and INTRA, see Figure 1) was smallest in the left-right direction (0.3 mm, standard deviation [SD] 1.2 mm) and comparable in the cranial-caudal (-1.8 mm, SD 2.7 mm) and anterior-posterior direction (1.7 mm, SD 2.8). Average 1D intrafraction CTV displacement with the sub-fractionation workflow ranged between -2.5 mm and 2.0 mm in all directions (Figure 2). The residual 3D intrafraction CTV displacement was 1.1 mm (SD 0.7 mm) for the sub-fractionation workflow, 1.6 mm (SD 1.1 mm) and 2.3 mm (SD 1.4 mm) for the previous clinical workflow (lower and upper limit, respectively), and 3.5 mm (SD 2.4 mm) for the ATSonly workflow (Figure 3). For the sub-fractionation workflow, the residual 3D intrafraction CTV displacement was £ 2.7 mm in all fractions, whereas this ranged up to 14.9 mm with the ATS-only workflow (Figure 3 and 4).
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