Part II | Chapter 9 190 Also, especially in this patient group with recurrent prostate cancer, radioresistance can play a role in oncologic outcomes of the treatment. Overall BPFS ranges between 47% and 54% at 5-year follow-up and a recent update by Van Son et al.19,20 showed that 73% of the intraprostatic recurrences after FS-HDR-BT occurred in-field. Accordingly, this may imply that treatment of these tumours might benefit from an increased dose. Dose escalation and/or fractionation could improve oncologic outcomes, but may go hand-in-hand with increased acute toxicity as suggested by Murgic et al.21 If future study results demonstrate improved oncologic outcomes by applying e.g. two or three fractions, the MR-Linac is a more attractive treatment modality due to both the noninvasiveness and easier logistics. Stratifying the target dose by tumour location showed areas with higher and lower median D95%. However, the low numbers complicate drawing conclusions about these observations. Obviously, reaching target coverage strongly depends on the anatomy and therefore a decision should be made for each patient individually. This study has several strengths. We included 30 patients with various tumour locations and sizes, thereby showing the feasibility in a non-selected patient group comparable to the target population. Secondly, froma FS-HDR-BT perspective, we used clinically delivered plans, which reflect the real capabilities of the FS-HDR-BT treatment modality. Conversely, a limitation of this study is the fact that the MR-Linac plans are optimal plans based on several assumptions. Firstly, we have used a 1 mm PTV margin. As discussed in the materials and methods section, this 1 mm margin has to account for additional uncertainty due to intrafraction prostatic motion and geometrical (in)accuracy that are introduced with the use of an MR-Linac system compared to FS-HDR-BT. Based on the mentioned prostate tracking algorithm and adaptive treatment planning systems that have been developed at our department, this 1 mmmargin seems to be achievable.9,11,13,14 Since interobserver contouring variability of the target is present in FS-HDRBT as well, we do not expect this to lead to additional inaccuracy with MR-Linac treatments. Also, we believe that the full potential of MR-Linac systems lies in achieving these very small PTV margins that are not possible with conventional systems. Based on our prostate motion analyses, 3 to 4 mm margins are sufficient for current prostate cancer treatment without intrafraction adaptation.12 Enlarging the PTV margin in our study to e.g. 3 or 5 mm would thus not make full use of MR-Linac system capabilities that distinguish it from conventional cone-beam CT linear accelerators. Still, this will remain hypothetical until it is technically possible to combine all the aforementioned developments into a clinically released system. Another limitation is the fact that we only had full field-of-view CT scans available for MR-Linac treatment planning. The registration between the intraoperative MRI and the CT scan and the contour propagation could lead to differences in the exact dose distributions. However, these potential differences were assumed to be minor and have no impact on the planning comparison study. Thirdly, we used FS-HDR-BT OAR constraints for our evaluation. We assessed the highest dose to small volumes (1.0 cm3) for both the rectum and bladder. Contrary to FS-HDR-BT, mean dose to OAR is generally higher with external beam radiotherapy due to the more gradual dose fall-off. However, delivery of a single 19.0 Gy dose to a
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