Session Item

IMPORT HIGH is a randomised phase 3 trial testing dose escalated simultaneous integrated boost (SIB) against sequential boost using intensity modulated radiotherapy and image guided radiotherapy (IGRT) for early stage breast cancer with high local relapse risk. We report results of primary efficacy analyses and 5-year adverse effects (AE). 

Women aged ≥18 after breast conservation surgery for pT1-3pN0-pN3aM0 invasive carcinoma were randomised (1:1:1) between 40Gy/15F to whole breast (WB) + 16Gy/8F sequential photon boost to tumour bed (40+16Gy; control), 36Gy/15F to WB, 40Gy to partial breast + 48Gy (48Gy) or + 53Gy (53Gy) in 15F SIB to tumour bed. In all patients, boost planning target volume (PTV) was the clip-defined tumour bed + 5mm. AE were assessed annually by clinicians (all patients) and in a planned sub-set (n=840) by photographs at 3 & 5 years and by patients at 6, 12, 36 and 60 months. Primary endpoint was ipsilateral breast tumour relapse (IBTR). Protocol-specified non-inferiority (α=0.025) for IBTR defined as 3% absolute excess in test groups based on expected 5% 5-year rate for 40+16Gy. 95% confidence intervals (CI) are shown. Primary comparison for AE was between 53Gy and 48Gy.

2617 women consented from 03/2009-09/2015 from 76 UK centres.  Median age 49 (IQR 44-56); 9%, 38% & 53% were tumour grade 1, 2 & 3 respectively; 30% were N+. 66% received chemotherapy and 73% endocrine therapy. Median boost CTV was 13cm³ (IQR 7, 22) 5-year follow-up was available for 2335/2411 (96.8%) expected (not died or withdrawn). After median follow-up of 74.0 months (IQR 73.4, 75.6), 76 IBTR events had occurred (40+16Gy: 20, 48Gy: 21, 53Gy: 35). Estimated 5-year IBTR incidence was 1.9% (95%CI 1.2, 3.1) for 40+16Gy, 2.0% (1.2, 3.2) for 48Gy, 3.2% (2.2, 4.7) for 53Gy. Hazard ratios vs 40+16Gy were 1.04 (0.56, 1.92) for 48Gy, 1.76 (1.02, 3.04) for 53Gy. Estimated absolute differences in 5-year IBTR incidence vs 40+16Gy were 0.1% (-0.8, 1.7) for 48Gy, 1.4% (0.03, 3.8) for 53Gy. Since the upper 95%CI limit for 48Gy versus 40+16Gy was <3%, non-inferiority according to pre-specified absolute difference criteria is shown for the 48Gy treatment group.

5-year AE data were available for 1894 clinician assessments, 513 photographs and 708 patient assessments; prevalence of marked AE was low overall (Table). Rates of 5-year moderate/marked AE were broadly similar between each test group and control with higher risk of clinically-assessed breast induration, breast distortion and patient-assessed breast hardness/firmness for 53Gy versus 48Gy.   

IBTR event incidence is low in this higher risk breast cancer group treated with small boost PTVs and IGRT, whether the boost is delivered sequentially or simultaneously with the 95%CI excluding the 5-year 5% rate originally predicted for the control group. Rates of 5-year moderate/marked AE are low. SIB is a safe treatment with reduced patient visits and further escalation of boost dose does not appear advantageous.