APBI with 50 kV Photons: Targeted Intraoperative Radiotherapy (TARGIT)

Abstract

Whole-organ analysis of mastectomy specimens vis-a-vis the results of breast-conserving surgery trials suggests that clinically important breast cancer is a regional disease. A geographical miss of the tumor bed boost can occur in 50-79% of cases and could contribute considerably to local recurrence. A temporal miss (a crucial delay in delivering radiotherapy) is most likely to occur in the few hours/days immediately after surgery when the tumor bed bathes in wound fluid. Translational research has shown that TARGIT abrogates the potentially harmful effects of wound fluid. The results of the START trials corroborate with our mathematical models of TARGIT and suggest that single high doses delivered accurately might be superior to multiple fractions of smaller doses. Targeting radiotherapy to the tumor bed means that it can be delivered accurately at the time of surgery, does not delay adjuvant chemotherapy, and could allow breast-conserving surgery (rather than mastectomy) when a long postoperative course of radiotherapy is not desirable or practical. With our TARGIT approach (pioneered in 1998), a single fraction of 20 Gy is delivered to the surface of the tumor bed, in the cavity produced by the excision of tumor tissue, using a spherical applicator (the Intrabeam system; Carl Zeiss Meditec, Germany), while the patient is anesthetized for primary surgery. TARGIT can also be delivered as a second procedure and even under local anesthetic because, unlike the Novac7 system being used in the Italian ELIOT trial, TARGIT does not require extensive dissection of skin flaps and the chest wall away from the breast disc. The TARGIT technique uses low-energy X-rays (50 kV); hence, unlike other methods of PBI, the volume of tissue that receives very high doses of radiation is small, which means that external-beam whole breast radiotherapy (EBRT) can be added without causing acute or long-term toxicity. The heart and the lungs do not receive any significant irradiation during TARGIT application. In addition, unlike MammoSite (Cytyc Corp., Marlborough, MA, USA), TARGIT does not require complicated CT planning, and patients do not become ineligible on the basis of having particular tumor locations. The cost of delivering TARGIT, the most economical method of PBI, is considerably less than that associated with the use of a linear accelerator, which it could potentially replace for a significant proportion of patients. The technique itself has FDA approval and the CE mark for clinical use in any part of the body. The use of TARGIT as the sole treatment in low-risk patients over 45 years, instead of the usual 3-6 week postoperative EBRT course, is being tested in the TARGIT-A trial launched in March 2000 and which is currently recruiting in 22 centers worldwide. TARGIT is already being used as a standard boost technique in many centers and is included in the German national guidelines. Updated results (ASCO2008) for the 300 unselected patients treated in five international centers using TARGIT as a boost treatment followed by EBRT demonstrated a very low five-year actuarial recurrence rate of 1.52%, despite having a relatively high-risk patient population (29% were node positive, and a third were younger than 51 and grade 3). The TARGIT-B trial, which has just started recruitment, will test whether the TARGIT boost is indeed superior in high-risk patients. The results of the TARGIT trials could usher in a novel individualized local treatment for breast cancer. © 2009 Springer Berlin Heidelberg.