Intraoperative irradiation for early breast cancer (ELIOT): long-term recurrence and survival outcomes from a single-centre, randomised, phase 3 equivalence trial

background

In the Phase 3 Randomized Electron Intraoperative Radiation Therapy (ELIOT) equivalence study, accelerated partial breast irradiation (APBI) using intraoperative radiation therapy was associated with a higher rate of ipsilateral breast tumor recurrence (IBTR) than whole breast irradiation (WBI) in patients with breast cancer in the early stages. Here we wanted to examine the planned long-term relapse and survival results from the ELIOT study.

Methods

This phase 3 randomized single center equivalence study was conducted at the European Institute of Oncology (Milan, Italy). Eligible women aged 48 to 75 years with a clinical diagnosis of unicentric breast cancer with an ultrasound diameter of no more than 25 mm, clinically negative axillary lymph nodes suitable for breast-conserving surgery were selected at random (1: 1). via a web-based system with a randomly permuted block design (block size 16) and stratified according to clinical tumor size to get postoperative WBI with conventional fractionation (50 Gy as 25 fractions of 2 Gy plus 10 Gy boost) or 21 Gy intraoperative radiation therapy with electrons (ELIOT) in a single dose to the tumor bed during surgery. The study was open-ended and no one was masked for assigning treatment groups. The primary endpoint was the occurrence of IBTR. The study was designed assuming a 5-year IBTR rate of 3% in the WBI group and the equivalence of the two groups when the 5-year IBTR rate in the ELIOT group was 2.5 times Excess did not exceed, which corresponds to 7 ·. 5%. Overall survival was the secondary endpoint. The main analysis was carried out with the intention of treating. The cumulative incidence of IBTR events and overall survival were assessed at 5, 10, and 15 years of follow-up. This study is registered with ClinicalTrials.gov, NCT01849133.

Results

Between November 20, 2000 and December 27, 2007, 1305 women were enrolled and randomly assigned: 654 to the WBI group and 651 to the ELIOT group. After a median follow-up of 12.4 years (IQR 9.7–14.7), 86 (7%) patients developed an IBTR, with 70 (11%) cases in the ELIOT group and 16 (2%) in the ELIOT -Group occurred in the WBI group, corresponding to an absolute excess of 54 IBTRs in the ELIOT group (HR 4 · 62, 95% CI 2 · 68-7 · 95, p <0 · 0001). In the ELIOT group, the 5-year IBTR rate was 4 · 2% (95% CI 2 · 8–5 · 9), the 10-year rate 8 · 1% (6 · 1–10 · 3) and the 15-year rate was 12.6% (9.8-15.9). In the WBI group, the 5-year IBTR rate was 0.5% (95% CI 0.1–1.3), the 10-year rate 0.1% (0.5–2.2) and the 15 year rate was 2.4% (1.4-4.0). At the last follow-up visit on March 11, 2019, 193 (15%) women had died for any reason, with no difference between the two groups (98 deaths in the ELIOT group versus 95 in the WBI group; HR 1 03, 95) % CI 0x77-1x36, p = 0x85). In the ELIOT group, the overall survival rate after 5 years was 96.8% (95% CI 95 · 1–97 · 9), after 10 years 90.7% (88 · 2–92 · 7) and after 83 years 83 · . 4% (79 x 7-86 x 4) after 15 years; and in the WBI group the overall survival rate was 96.8% (95-1.97.9) after 5 years, 92.7% (90.4-94.4) after 10 years and 82.4% (78 5–85 · 6) after 15 years. We did not collect long-term data on adverse events.

interpretation

The long-term results of this study confirmed the higher IBTR rate in the ELIOT group than in the WBI group, with no differences in overall survival. ELIOT should be offered to select patients with a low risk of IBTR.

financing

Italian Association for Cancer Research, Jacqueline Seroussi Memorial Foundation for Cancer Research, Umberto Veronesi Foundation, American Italian Cancer Foundation, Lombardy Region and Italian Ministry of Health.