Title: Magnetic Resonance Guided High Intensity Focused Ultrasound: An Adjunctive Cancer Therapy For Improved Tumour Control
Funder: Department of Health and Social Care

Abstract: Primary Aim: To establish the safety and potential efficacy of High Intensity Focused Ultrasound delivered under Magnetic Resonance Imaging guidance (MRgHIFU) for treating patients with recurrent gynaecological tumours who are ineligible for further conventional treatment. To achieve this in a pilot study we will undertake 2 workpackages: Objective 1: Perform a planning study assessing the feasibility of access of recurrent gynaecological tumours to MRgHIFU, and the risk of damage to soft-tissues in the beam path. Objective 2: Perform a pilot treatment study using MRgHIFU for treating symptomatic (pain, bleeding) recurrent gynaecological malignancy when conventional treatment options are not suitable and establish the safety profile of the technique as well as change in symptoms and MRI volume at 3 months. Study Design: Pilot study assessing safety of a new image-guided thermal therapy for treating recurrent gynaecological malignancy when conventional treatments have been exhausted in a planning (cohort 1) and a treatment (cohort 2) phase. In cohort 1 n=20 we will determine anatomical locations that are feasible to treat, the best patient set-up and optimal MR parameters for planning, delivering and monitoring treatments. In cohort 2 (n=15) we will implement MRgHIFU treatments, evaluate complications (procedural, immediate post-procedural, acute and at 3 months), symptom control (quality of life and standardised blood loss assessment questionnaires) and tumour volume (on MRI) at 3 months. Setting: Radiology department at a specialist oncology centre (The Royal Marsden Hospital); infrastructure support from Philips Medical Systems and The Focussed Ultrasound Foundation. Primary endpoint: Feasibility and safety of performing MRgHIFU in patients with recurrent gynaecological malignancy, in whom other treatment options are not available Secondary endpoints: Improvement in pain control at 30 and 90 days from baseline, measured by changes in numerical rating scale (NRS) pain score and decrease in medication use. Changes in bleeding up to 90 days from baseline, measured by patient reported estimated blood loss and questionnaires Changes in lesion volume at 30 and 90 days post-treatment Effect of MRgHIFU on patients quality-of-life (measured by the EORTC-C15-PAL and EQ-5D-5L questionnaires) and reported pain Pain management drugs pre- and post-procedure Target Population: Women with recurrent gynaecological cancer, who have exhausted conventional therapy Inclusion Criteria Patients with recurrent pelvic gynaecological malignancy For Cohort 2: painful lesion (NRS>4) or causing troublesome bleeding, not suitable for alternative treatments Intended target volume accessible for MRgHIFU treatment Intended target volume visible on non-contrast MR imaging Distance between target and skin &ge;1cm Exclusion Criteria MRI contra-indicated (metal implants or claustrophobia) Pregnancy For Cohort 2: Sedation contra-indicated MRI contrast agent contra-indicated Critical anatomical structure, radiation fibrosis/ scar along the beam path or at target Sample size: This is a pilot study. Sample size has been estimated from the number of patients we envisage will be eligible for the treatment in our centre for cohort 1 in the first year. For cohort 2 we estimate that 50% of patients in the next 18 months will agree to participate, and we may have a few patients who cross-over from cohort 1 to cohort 2 Project timetables and Recruitment rate: Project length=30 months; 12 months for the planning study, although, if the first 4 patients appear feasible to treat, we would have achieved our aim of 20% of lesions potentially treatable and would commence cohort 2 alongside completion of cohort 1.

Lay abstract: In treating cancer, patients undergo surgery, radiation and/or drug treatment. Because of their side-effects, repeating these treatments is not always possible when tumours return. In gynaecological cancers, which mainly affect young or middle years women, tumour recurrence has considerable negative impact on patients, and on families, employers and society. High Intensity Focused Ultrasound (HIFU) offers an alternative, complementary treatment. It delivers a tight focus of heat at a distance from its source. This kills tissue solely at the focal point; the margin between the treated (dead) and normal tissue is a few cells wide (10). HIFU does not use X-rays, so can be delivered to tissue that has previously received radiation without risking additional side-effects and, as it is very tightly focused on the target tissue, it avoids side-effects to the patient as a whole. To take full advantage of this tightly focused, non-invasive technique, it is essential to use imaging both to view and outline the target and to monitor changes in the target that occur during treatment. Magnetic Resonance Imaging (MRI) is able to clearly show tumour and its margins, monitor tissue temperature increases and and changes due to tissue damage during treatment. It can be used to guide the ultrasound beam to ensure that only targeted tissues experience a significant temperature rise. In this feasibility study we will determine eligibility for MRguidedHIFU and establish its safety in women with gynaecological tumours that have returned who are not eligible for standard treatments. We will assess control of symptoms (pain, bleeding) and of tumour growth. The research will be performed in conjunction with patients; they will form part of the research management team, help develop patient resources, contribute to study reports and dissemination of findings. This work will inform the design and development of a further trial (Phase2, NIHR-PGfAR).

Research activity codes: 6.5 RADIOTHERAPY AND OTHER NON-INVASIVE THERAPIES
Health categories: CANCER AND NEOPLASMS