Citation: Cancer Research. 2019, 79(4)
Author: Coles C.E.; Griffin C.L.; Kirby A.M.; Haviland J.S.; Titley J.C.; Benstead K.; Brunt A.M.; Chan C.; Ciurlionis L.; Din O.S.; Donovan E.M.; Eaton D.J.; Harnett A.N.; Hopwood P.; Jefford M.L.; Jenkins P.J.; Lee C.E.; McCormack M.; Sherwin L.; Syndikus I.; Tsang Y.; Twyman N.I.; Ventikaraman R.; Wickers S.; Wilcox M.H.; Bliss J.M.; Yarnold J.R
Abstract: Background IMPORT HIGH is a randomised, multi-centre phase III trial testing dose escalated simultaneous integrated boost (SIB) against sequential boost each delivered by intensity modulated radiotherapy (IMRT) for early stage breast cancer with higher risk of local relapse. The primary endpoint was initially breast induration at 3 years, requiring 840 patients? accrual was extended (target 2568) with the new primary endpoint of local relapse. We report adverse effects (AE) at 3 years. Methods Women age >=18 after breast conservation surgery for pT1-3 pN0-pN3a M0 invasive carcinoma were eligible. Randomisation was 1:1:1 between 40Gy/15F to whole breast (WB) + 16Gy/8F sequential photon boost to tumour bed (40+16Gy), 36Gy/15F to WB, 40Gy to partial breast + 48Gy (48Gy) or + 53Gy (53Gy) in 15F SIB to tumour bed. AEs were assessed annually by clinicians in all patients and in a planned sub-set (840) of patients by photographs at 3 years and by patients at 6 months, 1 and 3 years. AE scores were dichotomised as none/mild vs marked for photographs and none/mild vs moderate/marked for patients and clinicians. Fisher's exact tests compared groups? principal comparison (protocol-specified) between 53Gy and 48Gy (p<0.01 defined as statistical significance).
Results 2617 women consented between 03/2009 and 09/2015 from 39 UK radiotherapy centres. Median follow-up was 49.1 (IQR 36.8-63.2) months. Median age was 49 (IQR 44-56)? 9%, 38% & 53% were tumour grade 1, 2 & 3 respectively? 30% were node positive. 66% received chemotherapy and 73% endocrine therapy. 3-year AE data were available for 2017 clinician assessments, 641 photographs and 842 patient assessments. Proportions of patients with marked AEs were low overall. Rates of moderate/marked AEs at 3 years were broadly similar between the randomised groups? with a suggestion of a slightly increased risk for breast induration in 53Gy compared with control (borderline significance). AE at 3 years <sup>View inline</sup> Conclusions These results represent the largest and most mature reported AE outcomes of breast SIB within a clinical trial. At 3 years, rates of moderate/marked AEs were similar between SIB IMRT and WB + sequential boost IMRT delivered over 3 and 4.5 weeks respectively.
