A Phase I/II Feasibility/Efficacy Study of HIFU in Otherwise Untreatable Pelvic Rectal Cancer

CURRENT TREATMENT OF LOCALLY ADVANCED PELVIC CANCER Colorectal cancer This is a common condition with about 40,000 new cases a year in the United Kingdom. The optimal multimodality management of stage III & IV rectal cancer remains an increasing challenge. There is a high risk of local recurrence and poor survival has been reported for patients treated by surgery alone. About 20% of patients may present with locally advanced tumours, which are partially or totally fixed (T3/T4). Until recently there have been no widely accepted and validated methods of defining preoperatively either locally advanced rectal cancer or unresectable disease. The use of pre-operative pelvic magnetic resonance imaging (MRI) to predict the likelihood of achieving an R0 resection (Beets-Tan et al 2001, Brown et al 2003) has resulted in improved selection. Pre-operative chemoradiotherapy can downstage locally advanced tumours, and result in higher resection rates being achieved with reduced risk of local recurrence (Bosset et al 1993, Rich et al 1995).

Gynaecological cancers Treating other advanced pelvic malignancies including vaginal, ovarian, endometrial and cervical cancers is similarly challenging. Disease recurrence at the site of surgical resection or adjacent lymph nodes can also preclude further curative options, due to chemotherapy resistance, reaching maximum safe radiotherapy limits or unsuitable surgical options.

It is proposed that High Intensity Focused Ultrasound (HIFU) may become another modality of treatment in locally advanced or unresectable pelvic disease.

RATIONALE FOR PERFORMING THE STUDY Colorectal cancer This is the third most common cause of cancer and cancer death in both men and women (40,000 cases and just under 16 000 deaths per year in the UK). Worldwide, there are approximately 1 million cases and 500 000 deaths per annum. Primary treatment is usually surgical with, in appropriate cases, adjuvant or neo-adjuvant therapy currently including radiotherapy, cytotoxic chemotherapy or a combination. Unfortunately, the overall survival of locally advanced disease is at best 50%. Many patients who have residual, refractory or recurrent rectal cancer experience serious morbidity from local tumour invading and destroying adjacent tissues including bone, nerves (sacrum), bladder and the skin. These interfere severely with normal daily activities, especially bowel function and cause great distress in terms of pain, with many patients requiring permanent palliative colostomies.

Gynaecological cancers Other advanced pelvic malignancies can be equally problematic to manage successfully. Annually in the UK, approximately 250 vaginal cancer, 7000 ovarian cancer, 8000 endometrial cancer and 3000 cervical cancer diagnoses are made, with some being incurable at the time of presentation. Treatment options include surgery, hormonal therapy, chemotherapy, radiotherapy or a combination, although palliative patients can often be left with debilitating symptoms including severe pain and fistula formation, compromising their quality of life.