Objective: To assess the feasibility of targeting recurrent gynaecological tumours with MR guided high intensity focused ultrasound (MRgHIFU). Methods: 20 patients with recurrent gynaecological tumours were prospectively scanned on a Philips/Profound 3 T Achieva MR/ Sonalleve HIFU system. Gross tumour volume (GTV) and planning target volume (PTV) were delineated on T 2W and diffusion-weighted imaging (DWI). Achievable treatment volumes that (i) assumed bowel and/or urogenital tract preparation could be used to reduce risk of damage to organs-at-risk (TVoptimal), or (ii) assumed no preparations were possible (TVno-prep) were compared with PTV on virtual treatment plans. Patients were considered treatable if TVoptimal ≥ 50 % PTV. Results: 11/20 patients (55%) were treatable if preparation strategies were used: nine had central pelvic recurrences, two had tumours in metastatic locations. Treatable volume ranged from 3.4 to 90.3 ml, representing 70 ± 17 % of PTVs. Without preparation, 6/20 (30%) patients were treatable (four central recurrences, two metastatic lesions). Limiting factors were disease beyond reach of the HIFU transducer, and bone obstructing tumour access. DWI assisted tumour outlining, but differences from T 2W imaging in GTV size (16.9 ± 23.0%) and PTV location (3.8 ± 2.8 mm in phase-encode direction) limited its use for treatment planning. Conclusions: Despite variation in size and location within the pelvis, ≥ 50 % of tumour volumes were considered targetable in 55 % patients while avoiding adjacent critical structures. A prospective treatment study will assess safety and symptom relief in a second patient cohort. Advances in knowledge: Target size, location and access make MRgHIFU a viable treatment modality for treating symptomatic recurrent gynaecological tumours within the pelvis.

Aims: Target delineation uncertainty is arguably the largest source of geometric uncertainty in radiotherapy. Several factors can affect it, including the imaging modality used for delineation. It is accounted for by applying safety margins to the target to produce a planning target volume (PTV), to which treatments are designed. To determine the margin, the delineation uncertainty is measured as the delineation error, and then a margin recipe used. However, there is no published evidence of such analysis for recurrent gynaecological cancers (RGC). The aims of this study were first to quantify the delineation uncertainty for RGC gross tumour volumes (GTVs) and to calculate the associated PTV margins and then to quantify the difference in GTV, delineation uncertainty and PTV margin, between a computed tomography-magnetic resonance imaging (CT-MRI) and MRI workflow. Materials and methods: Seven clinicians delineated the GTV for 20 RGC tumours on co-registered CT and MRI datasets (CT-MRI) and on MRI alone. The delineation error, the standard deviation of distances from each clinician's outline to a reference, was measured and the required PTV margin determined. Differences between using CT-MRI and MRI alone were assessed. Results: The overall delineation error and the resulting margin were 3.1 mm and 8.5 mm, respectively, for CT-MRI, reducing to 2.5 mm and 7.1 mm, respectively, for MRI alone. Delineation errors and therefore the theoretical margins, varied widely between patients. MRI tumour volumes were on average 15% smaller than CT-MRI tumour volumes. Discussion: This study is the first to quantify delineation error for RGC tumours and to calculate the corresponding PTV margin. The determined margins were larger than those reported in the literature for similar patients, bringing into question both current margins and margin calculation methods. The wide variation in delineation error between these patients suggests that applying a single population-based margin may result in PTVs that are suboptimal for many. Finally, the reduced tumour volumes and safety margins suggest that patients with RGC may benefit from an MRI-only treatment workflow.

Objective: To document longitudinal symptom, quality-of-life and imaging response in patients with recurrent gynecological tumors treated with magnetic resonance guided high intensity focused ultrasound (MRgHIFU), and compare changes in patients with intra-versus extra-pelvic lesions. Methods: Eleven symptomatic patients with painful recurrent gynecological tumors were treated with MRgHIFU (Profound Sonalleve) in a prospective single center study (NCT02714621). Pain scores, analgesic intake and quality-of-life metrics, whole tumor volume, and perfused tumor volume from Gadolinium-enhanced T1W imaging documented before and up to 90 days after treatment were compared between patients with intra-and extra-pelvic tumors. Results: Two of five patients with intra-pelvic and three of six patients with extra-pelvic tumors were classified as responders (>2 point reduction in NRS pain score without analgesia increase or a > 25% reduction in analgesic use). Cohort reductions in worst pain scores were not significant for either group. Emotional functioning for the whole cohort improved, although physical functioning did not. Ablative thermal temperatures were achieved in three patients with extra-pelvic tumors, but in none whose tumors were intra-pelvic. Pain response did not correlate with thermal dose. Tumor volume increased by 18% immediately post-treatment in the extra-pelvic but not in the intra-pelvic group. Ratio of perfused to whole lesion volume decreased by >20% by day 30 in extra-pelvic, but not intrapelvic tumors although at day 30 both extra-pelvic and intra-pelvic tumors increased in volume. Conclusion: MRgHIFU treatments can be delivered safely to patients with recurrent gynecological tumors. Extra-pelvic tumors responded better than intra-pelvic tumors and showed immediate swelling and reduction in perfused volume by day 30.