The randomized phase III trial TARGIT A showed non-inferiority regarding local control after intraoperative radiotherapy (IORT 20 Gy which was followed by whole breast radiotherapy (WBRT) in patients with risk factors only) in comparison to standard WBRT (50–56 Gy) after breast-conserving surgery in selected patients. This is the first analysis of long-term toxicities in the setting of TARGIT. Between 02/2002 and 12/2008, 305 patients were treated within TARGIT A (Arm A: n = 34 IORT, n = 20 IORT + WBRT for risk factors; Arm B WBRT: n = 55) or received IORT as a planned boost (control group: n = 196) at a single center. Toxicity was assessed according to the LENT SOMA scales. No significant differences were seen between Arm A and Arm B regarding fibrosis, breast edema, retraction, ulceration, lymphedema, hyperpigmentation, and pain. Arm A had significantly less telangiectases compared to Arm B (p = 0.049). In the subanalysis (Arm A IORT vs. Arm A IORT + WBRT vs. Arm B), fibrosis had a cumulative rate of 5.9 versus 37.5 versus 18.4 %, respectively (38.2 % IORT boost control group), at 3 years. No telangiectases were seen after IORT alone (0 % Arm A IORT vs. 17.5 % Arm A IORT + WBRT vs. 17.7 % Arm B). The hazard ratio of higher grade toxicity as first event was 0.46 (95 % CI, 0.26–0.83) for Arm A IORT as compared to Arm B (p = 0.010). No recurrences were seen after a median follow-up of 40 months (Arm A) and 42 months (Arm B). With its very low chronic skin toxicity rates and outstanding long-term results regarding toxicity and local control, IORT with 50 kV X-rays is a safe and effective method for treatment of selected breast cancer patients.
Breast cancer Intraoperative radiotherapy (IORT) Toxicity LENT SOMA TARGIT Fibrosis
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The authors want to thank Markus Bohrer MD, Brigitte Hermann MD, Yasser Abou-Madyan MD, Anette Kipke, Sven Clausen, Frank Schneider PhD, Anika Klabes, Volker Steil, and Carsten Herskind PhD for their work within the IORT Group in Mannheim and the German Federal Ministry of Education and Research (BMBF) and the Dietmar Hopp foundation for funding.
Conflict of interest
Frederik Wenz has received a research grant from Carl Zeiss for supporting radiobiological research. Carl Zeiss sponsors most of the travel and accommodation for meetings of the International Steering Committee and when necessary for conferences where a presentation about targeted intraoperative radiotherapy is being made for all authors. The TARGIT A trial is supported by grant FKZ01ZP0508 from the German Ministry for Education and.Research (BMBF). Grit Welzel received funding for neuropsychological research (Dietmar Hopp foundation).
The authors of the manuscript declare that the trial comply with the current laws of the country and was proven by the local ethics committee (Ethikkommission II, Mannheim, Universität Heidelberg).
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