TARGIT-B: An international randomised controlled trial to compare targeted intra-operative radiotherapy boost with conventional external beam radiotherapy boost after lumpectomy for breast cancer in women with a high risk of local recurrence.
Despite advances in breast cancer treatments, a subgroup of patients, especially young women, remain at a significant risk of cancer returning in the breast (recurrence) after receiving the standard breast conserving surgery and post operative course of radiotherapy. In this group of patients, standard radiotherapy would have been given several months after surgery and would normally consist of a 3-5 week course of daily radiotherapy to the whole breast, as well as a shorter 5-8 day course to the tumour bed (the normal breast tissue immediately around the tumour); it is difficult to accurately aim the boost at the tumour bed.
We developed a new radiotherapy technique- TARGeted Intraoperative radioTherapy (TARGIT), in 1998 and have accumulated considerable experience through worldwide collaboration in over 30 centres. With TARGIT, radiotherapy is delivered accurately to the tissues at highest risk of recurrence- the tumour bed- at the time of surgery in a single session. The long-term analysis of the first 300 patients treated with this technique found a remarkably low recurrence rate (1.73%, SE 0.77) - less than half of the expected rate. We have also found laboratory evidence that could provide a biological explanation. Normally body fluid collects in the surgical wound and we found that this fluid stimulates cancers cells- but not when the patient had received TARGIT, suggesting that radiotherapy immediately after surgery is probably very important. Hence we have designed a randomised trial of 1796 patients to compare TARGIT boost with conventional boost to test its superiority. The research will be a global collaborative effort of over 30 centres co-ordinated from London.
The primary outcome will be local recurrence of cancer at 5 years. We shall also be looking at breast appearance, patient satisfaction and quality of life, the effects of radiation on cardio-pulmonary function and health economics (separate protocols).
The only ethical issue is the necessity of an additional procedure that might be required in a small proportion of patients who are found to be suitable for the trial after their primary operation is already performed, and who would otherwise not need a second operation. We expect that these will constitute about less than 10% of cases.
The team running the study has pioneered the new approach, developed the technology and successfully administered multi-centre trials for over 20 years. The planned steering committee will bring together expertise in surgical oncology, radiation oncology, innovation, medical physics, patient advocacy and trial administration.
Participating centres are self-financing and the equipment is already in place. Our team has also recently successfully analysed, presented and fast-tracked and published on-line, in The Lancet, the TARGIT-A study in low-risk women over the age of 45 years. In this trial our results show that giving a single dose of radiation with the TARGIT technique at the time of operation gives similar results as the usual several weeks' course of radiotherapy. We now wish to test whether in high risk women, TARGIT given accurately and immediately after surgery, as a boost to the tumour bed can improve the local control of breast cancer.
Our vision is to tailor radiation treatment (risk-adjusted radiotherapy, rather than one-size-fits-all) for every women undergoing a lumpectomy for cancer so that it is focussed and minimised for low risk women and enhanced for high risk women so that the outcomes are ultimately better.