Title: Trial of Intraoperative Cell salvage vs Transfusion in Ovarian Cancer (TIC TOC) - a feasibility study
Funder: Department of Health and Social Care

Abstract: Background With 5,917 new cases of ovarian cancer registered in England in 2011, ovarian cancer is the second most common gynaecological cancer but it is the leading cause of death from gynaecological cancer. 65% of women with ovarian cancer die within 5 years of their diagnosis, over three-quarters of them because of their cancer. NICE guidance for treatment of women with ovarian cancer comprises surgical resection of all macroscopic tumour, in those patients suitable for surgery, followed by chemotherapy. The surgery can be an extensive procedure associated with substantial blood loss. Blood lost during surgery is conventionally replaced with the transfusion of donor blood (allogeneic transfusion). Whilst often necessary and life-saving, the use of donor blood is associated with increased risks of a range of complications and adverse surgical outcomes including mortality, wound infection, pulmonary and renal complications, systemic sepsis, and prolonged hospital stay. Recognising this, patient blood management programmes focus on minimising the use of donor blood. Intraoperative cell salvage (IOCS) is an approach used in a wide range of surgical procedures which avoids the use of donor blood. IOCS is the practice of recovering red cells from blood lost in operative field and returning them to the patient. Despite evidence that there is no additional risk, IOCS has not been widely used in cancer surgery because of fears of reintroducing cancerous cells. Aims We intend to conduct a multi-centre randomised trial of IOCS against allogenic transfusion in women undergoing surgery for ovarian cancer. Before such a study can be planned with confidence we need this feasibility study to test our methods and procedures and establish the extent to which the use of IOCS would be acceptable to patients and clinicians during surgery. Population The study population comprises 60 patients undergoing primary or interval debulking surgery for ovarian cancer (Appendix 1). Exclusion criteria have been kept to a minimum, mostly factors which affect the patients fitness for surgery. Plan This two year feasibility study will be conducted in three gynaecological oncology services in England. Patients will be randomised to either IOCS or allogeneic transfusion to replace blood lost during surgery. Potentially eligible patients will be identified from referrals to the gynaecological oncology services and, once their management has been confirmed, asked if they would like to participate in the study. The study will allow us to assess our ability to collect a range of outcomes (e.g. survival, recurrence, length of stay, post-operative complications, return to theatre, infection rates, etc.) but also, importantly, the willingness of both surgeons and patients to participate. This will be assessed not only by recording recruitment and retention rates but also by an integrated qualitative study, including both participants and non-participants. Potential Benefits This feasibility study will enable the successful planning and delivery of a large trial to assess the clinical and cost-effectiveness of IOCS in surgery for ovarian cancer. We hypothesise that IOCS, by avoiding the hazards of allogeneic transfusion and the risk of transfusion-induced immunomodulation, will result in fewer complications without compromising rates of recurrence. Accordingly we expect it potentially to improve survival and quality of life following surgery. If those expected results materialise, IOCS could very quickly be adopted as routine practice across the country, as the technology exists in hospitals. Moreover, if such benefits are demonstrated for ovarian cancer, it is likely that IOCS will be used for other cancers, with far-reaching benefits for patients and for the health service as a whole. Conversely, if disbenefits are shown, then further adoption of an ineffective intervention can be pre-empted.

Lay abstract: Ovarian cancer is diagnosed in about 6000 women in England each year. Surgery for ovarian cancer is often extensive and can result in substantial blood loss. Currently, donated blood is used to replace blood lost during surgery (usual care). An alternative method of replacing blood is to retrieve the blood lost, clean it and return it to the patient. This process is known as &ldquo;intraoperative cell salvage&rdquo; (IOCS). Research has shown that patients who have had their own blood back do better than patients who have donor blood in non-cancer related surgery. The use of IOCS in ovarian cancer surgery has been held back by concerns of reintroducing cancer cells although, reportedly, 80-100% of these cells have been removed. We intend to conduct a large trial comparing outcomes following IOCS or donor blood in women undergoing surgery for ovarian cancer. We first need to assess the feasibility of conducting this study. We shall test the methods to be used in the later trial and the way it will be organised. We will recruit those women with ovarian cancer listed for surgery and who consent to take part. Participants will be assessed by a research nurse and then randomly allocated to receive either IOCS or usual care. The assessments will be carried out within the normal clinical pathway. A researcher will interview some of the women about their personal experience in order to understand how well the research process worked. This includes: acceptability of randomisation, experience of being in a control group, and appropriateness of the measures used. We also aim to interview the surgeons about their experience and views on IOCS. Interviews will be audio-recorded, transcribed, and analysed. The results will be widely distributed among the medical profession and patient population through the PANTS cancer charity and patient representatives.

Research activity codes: 6.4 SURGERY
Health categories: CANCER AND NEOPLASMS