Intensity-modulated radiotherapy (IMRT) with simultaneously integrated boost shortens treatment time and is non-inferior to conventional radiotherapy followed by sequential boost in adjuvant breast cancer treatment: results of a large randomized phase III trial (IMRT-MC2 trial)

Abstract Purpose In the modern era, improvements in radiotherapy techniques have paved the way for simultaneous integrated boost irradiation in adjuvant breast radiotherapy following breast conservation surgery (BCS). Nevertheless, randomized trials supporting the non-inferiority of this treatment to historical standards of care approach are lacking. Methods and Materials A prospective, multicenter, randomized phase-III-trial (XXX) was performed to analyze non-inferiority of conventional fractionated intensity-modulated radiotherapy with simultaneous integrated boost (IMRT-SIB) to 3-D-conformal radiotherapy with sequential boost (3-D-CRT-seqB) for breast cancer patients. Primary outcomes were local control (LC) rates at 2 and 5 years (non-inferiority margin at hazard ratio of 3.5) as well as cosmetic results 6 weeks and 2 years post radiotherapy (evaluated via photo documentation calculating the relative breast retraction assessment (pBRA) score (non-inferiority margin of 1.25)). Results A total of 502 patients were randomly assigned from 2011 to 2015. After a median follow-up of 5.1 years, the 2-year LC for the IMRT-SIB arm was non-inferior to the 3-D-CRT-seqB arm (99.6% vs. 99.6%, respectively; HR 0.602, 95%-CI: [0.123-2.452], p=0.487). In addition, non-inferiority was also demonstrated for cosmesis following IMRT-SIB and 3-D-CR-seqB at both 6 weeks (median pBRA 9.1% versus 9.1%) and 2 years (median pBRA 10.4% versus 9.8%) post radiotherapy (95%-CI [-0.317; 0.107] %/year, p=0.332). Cosmetic assessment according to the Harvard scale by both the patient and the treating physician as well as late toxicity evaluation with the LENT-SOMA criteria revealed no significant differences between treatment arms. Finally, there was no difference in overall survival rates (99.6% versus 99.6%; HR 3.281, 95%-CI: [-0.748-22.585], p=0.148) for IMRT-SIB and 3-D-CRT-seqB, respectively. Conclusion This is the first prospective trial reporting the non-inferiority of IMRT-SIB versus 3-D-CRT-seqB with respect to cosmesis and LC at 2 years of follow up. This treatment regimen considerably shortens adjuvant radiotherapy times without compromising clinical outcomes.