Exploring HIFU as a Treatment for Rectal and Other Pelvic Cancers

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.

The second part of the study will involve a cohort of 30 patients with either locally advanced pelvic cancer (rectal, endometrial or cervical) or locally recurrent disease. These patients will be unsuitable for operative intervention or any further chemo-radiotherapy treatment. 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 intracavity HIFU using the Sonatherm™ 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 with HIFU and observed overnight to monitor for any toxicity related to treatment with HIFU. Antibiotic prophylaxis will be given for five days to reduce the risk of abscess formation and sepsis. Patients will be followed up closely to monitor for toxicity and any changes in symptom control/quality of life. Patients will complete the same pre-operative questionnaires at multiple time-points post HIFU treatment. Questionnaires will be completed at seven, thirty, sixty and ninety days post HIFU, and three-monthly thereafter. This will enable us to accurately chart the change in quality of life and symptom control created by the HIFU treatment. Post-treatment imaging will be performed at between 3-4 weeks, as within this time frame the ablative effect (a necrotic area) as seen in prostate cancer treated by HIFU. This will allow comparison with pre-operative imaging to evaluate the effect of HIFU. A video record of the ultrasound and ablation will be reviewed by the team to evaluate the quality of the ablation performed.

Patients will be reviewed at regular intervals after treatment with HIFU to monitor the effect of HIFU on quality of life. Regular blood tests will be taken to monitor tumour markers and markers of systemic inflammation.

Potential patients will be identified during MDT meetings which include surgeons, radiologists, gynaecologists, oncologists and cancer nurse specialists. The team will confirm eligibility and suitability prior to patient recruitment. If felt appropriate by the MDT, patients may be offered a second application of HIFU as necessary.

The trial will run in two stages: the end of the first phase (for regulatory requirements) is defined as 30 days from the date that the last patient has completed trial therapy. The non-interventional follow-up stage will then commence in which patients are followed up for a minimum of 6 months or death.