High Intensity Focused Ultrasound as a Treatment for Rectal and Pelvic Cancers - Laboratory and Clinical Feasibility Studies

The hypothesis of this study is that high intensity focused ultrasound (HIFU) can be safely and effectively used to treat rectal and advanced pelvic cancers. This study is composed of two feasibility trials to evaluate the safety and efficacy of use in HIFU in early rectal cancer and late pelvic cancer.

The first trial will involve a cohort of 30 patients with early rectal cancer. They will have full work up as per normal care including history, examination, bloods, endoscopy and imaging (CT and MRI scan). Once eligibility has been confirmed, patients will be approached and offered to be enrolled in the study. Once successfully recruited, they will be admitted transrectal HIFU using the Sonatherm (Sonacare Medical, Charlotte, North Carolina, USA) device under general anaesthetic with monitoring for toxicity. Baseline quality of life questionnaires will be filled in by patients prior to HIFU to establish their symptoms prior to treatment. Patients will be admitted for treatment and observed overnight. They will then complete the same questionnaires at two and seven days post HIFU. Blood tests will be taken one week after HIFU administration to monitor levels of tumour markers and inflammatory markers. One week after their HIFU treatment, the patients will undergo their total mesorectal excision (TME) to remove their cancer as per normal treatment protocol. The specimen will be examined to evaluate the histological changes in the tumour and surrounding tissues created by the HIFU. We will be able to quantify the effect of HIFU on the rectal cancer and evaluate for possible thermal damage to surrounding tissues.

Potential patients will be identified during multidisciplinary team (MDT) meetings which include surgeons, radiologists, oncologists and cancer nurse specialists. The team will confirm eligibility and suitability prior to patient recruitment to ensure there is no negative effect on overall patient care due to their involvement in the trial.

The Sonatherm™ systems used ultrasound visualisation to monitor and regulate the HIFU delivery. This allows tissue response to HIFU to be monitored via echogenic changes seen during coagulative necrosis. The strong correlation between echogenic changes and tissue destruction will allow us to alter the power settings if needed to achieve suitable ablation of the target area. A video record of the ultrasound and ablation will be reviewed by the team to evaluate the quality of the ablation performed.

The trial will run for approximately 1 month for each patient: from recruitment into the study to the resection of the cancer. The HIFU dose will cover the entire tumour, the rectal wall, and a 5 mm margin of tissue surrounding the tumour. It is anticipated that all tissue exposed to HIFU, including the rectal wall, will be part of the coagulative necrosis. Antibiotic prophylaxis will be given for five days to reduce the risk of abscess formation and sepsis. Patients will be followed up on day 2 post HIFU and the day of their TME to assess their response to treatment and any complications that develop. Post resection the patients will be followed up as per the normal local guidelines following surgical excision of rectal cancer. They will have their quality of life post resection assessed by completing questionnaires 30 days post resection.