TARGIT-A trial summary
TARGIT-A trial, an international randomised clinical trial, was designed to test the hypothesis that a risk-adapted strategy using a single dose of targeted intraoperative radiotherapy (IORT) given using the INTRABEAM device in breast cancer patients suitable for breast conserving therapy (with the addition of whole breast radiotherapy in those patients at high risk of recurrence elsewhere in the breast [e.g. lobular carcinomas and extensive intraductal component]) is non-inferior to a conventional course of post-operative external beam radiotherapy (EBRT) delivered over several weeks. The primary endpoint was local recurrence in the conserved breast. The secondary endpoints included breast cancer and non-breast cancer mortality and local toxicity.
Eligible patients were those 45 years or older with breast cancer (invasive ductal carcinoma) that is up to 3.5cm in diameter and suitable for breast conserving surgery. After giving consent patients are randomised to either TARGIT group or to EBRT group. They may receive any other adjuvant treatments as deemed necessary. The protocol requires that patients be followed at six monthly intervals for five years and then annually.
In the randomised TARGIT-A trial, two policies of local radiation treatment are compared:
Eligible patients were recruited at two stages of their treatment in the pragmatic Targit trial:
Before the primary surgery (Prepathology randomisation)
This is the original method of entry into the TARGIT-A trial for a breast cancer patient. Once the decision to do a wide local excision (lumpectomy) is taken, and informed consent obtained, the randomisation takes place before surgery and if randomised to TARGIT, it is delivered to the fresh tumour bed immediately after lumpectomy for breast cancer. If at the postoperative pathology review, it is felt that they have a particularly high risk of local recurrence especially in other quadrants ( EIC, invasive lobular carcinoma or positive excision margins) then external beam radiotherapy can be added- all as part of the experimental arm of the trial. Centres could pre-specify additional such factors such as extensive lymphovascular invasion, multiple positive nodes, etc.
After the primary surgery (Postpathology randomisation)
This mode of entry into the trial was added to enable patients in whom the excision of the cancer had already been performed. This was logistically easier in some centres and theoretically allowed better case selection - although it required a second procedure to be performed. Randomisation in the Targit-A trial is performed after the the primary cancer is removed and if allocated to receive TARGIT, single session intraoperative radiotherapy is given as a day-case operation .