General discussion and future perspectives 217 treatment accuracy. Future research should focus on the expected benefits these innovations may offer (see ‘Towards improved outcomes with MRI-guided radiotherapy’). Besides improvements in optimisation times, delivery times could also be improved on Unity MRLinac systems (component 4). For prostate cancer treatment, delivery of a 7.25 Gy fraction currently takes on average 10 min using an intensity modulated radiation therapy (IMRT) technique.30 As shown by de Muinck Keizer et al.30, significant and increasing intrafraction prostate motion can occur during this period. Similar intrafraction motion results were reported for the seminal vesicles in chapter 4. One could imagine that treatment delivery in e.g. 2 min would allow for much less intrafraction motion to occur. This is mainly applicable to the more gradual motion (drift) away from the iso-centre that happens due to bladder filling and muscle relaxation (chapter 4).31 Unpredictable motion, for example anterior motion of the prostate due to bowel movements, can still occur and could even have much more pronounced effects on the actual delivered dose with faster delivery times and thus higher dose rates.32,33 Currently, MR-Linac systems do not offer volumetric modulated arc therapy (VMAT), but only IMRT. Availability of VMAT on MR-Linac systems will potentially shorten treatment times drastically; VMAT delivery times for a 7.0 Gy fraction on a conventional system are less than 3 min.34,35 For single fraction 19.0 Gy treatment, mean beam-on times of approximately 4.5 min are reported using VMAT delivery.36 However, MR-Linac systems are inherently limited by the relatively low dose-rate and therefore the improvements in treatment delivery time with VMAT compared to IMRT are expected to be smaller compared to conventional systems. Currently, research is focused on employing VMAT delivery on Unity MR-Linac systems and to determine the gain compared to IMRT delivery.37,38 Regardless of the prior technical innovations, intrafraction motion will always occur. To counteract the effect of unpredictable intrafraction motion, fast adaptation techniques are needed. These techniques will not necessarily reduce the on-table time (per fraction), but they will allow for extremely hypofractionated treatment, e.g. one-stop treatment or two-fraction treatment. Furthermore, intrafraction adaptation methods would allow significant margin reduction without sacrificing target coverage. To be able to substantially reduce the dose to OARs, such as the bladder wall and rectum, more accurate dose delivery with reduced error margins is warranted. This applies to current standard fractionated and SBRT treatment schedules, but is even more important for treatments with increased fractional doses such as focal boosting or extreme hypofractionation.39– 41 Mitigation of intrafraction motion is needed to deliver these very high fractional doses with enough precision to reach adequate target coverage while respecting OAR constraints. In chapter 5, we presented the sub-fractionation workflow. In essence, this workflow employs the principle of fractionation on a shorter timescale (i.e. minutes instead of days or weeks). By delivering a fraction in multiple parts (sub-fractions) based on the latest anatomy and with each sub-fraction fulfilling the dose-volume histogram (DVH) criteria, the effect of intrafraction motion can be reduced. In prostate cancer patients treated with SBRT, this workflow showed benefits in terms of reduction of intrafraction drift motion of the prostate (the Clinical Target Volume [CTV]). This resulted in smaller required PTV margins in all directions (2 mm in the left-right and cranial-caudal direction, 3 mm in the anterior-posterior direction). Although the benefits in clinical practice have to be prospectively 11
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