Very APBI in 1 or 2 Days: Late Toxicity and Early Oncological Outcomes of the GEC-ESTRO Cohort

Abstract

To analyze late toxicity after very accelerated partial breast irradiation (VAPBI) for low-risk breast cancer. In this retrospective observational international multicenter study (HDH F20220713143949) from 7 European centers, patients with low-risk breast cancer underwent lumpectomy + adjuvant VAPBI based on high-dose rate (HDR) multicatheter interstitial brachytherapy (MIB). VAPBI was performed with 4 (4 × 6.2 Gy/2 d), 3 (3 × 7.45 Gy/2 d) or 1 fraction (1 × 16 Gy or 1 × 18 Gy/1 d). Primary endpoint was late toxicity. Secondary endpoints were oncological outcome based on cumulative incidence of breast cancer local relapse (LR) and distant metastasis disease (DMD) and cause-specific (CSS) and overall (OS) survival. Prognostic factors for late toxicity were analyzed. From 01/2012 to 06/2022, the GEC-ESTRO VAPBI cohort included 516 pts with an early breast cancer. Median follow-up was 42 months [95% CI = 39 - 44]. Median age was 71 years [40 - 100]. Median tumor size was 12 mm [1 - 46]. Tumor was mainly invasive ductal carcinoma (78%), pN0 (88.5%), with positive hormonal receptors (98.5%) and negative HER2 overexpression (96%). Patients underwent hormonal and chemo-therapy in 93.8% and 2.3% respectively. Catheter placement was performed peri or post-operatively in 50.2% and 49.8% respectively. Median time interval between surgery and VABPI was 10 days [6 - 65]. VAPBI delivered 1, 3 and 4 fractions for 205 pts (39.7%), 167 pts (32.4%) and 144 pts (28%) respectively. Median CTV was 40.7 cc [95% CI = 26.6 - 72], median V100%, V150%, D90% and Dose non-uniformity ratio (DNR) were 90.2% [95% CI = 84.1 - 97.2], 24.2% [95% CI = 18.9 - 31.6], 103.8% [95% CI = 100.1 - 107.4] and 0.28 [95% CI = 0.23 - 0.33] respectively, 211 late toxicity events were observed in 168 pts (32.6%). Fibrosis, dyschromia, pain and telangiectasia were observed in 26.7%, 7.9%, 7.2% and 0.4 respectively. Grade 2 and 3 late toxicities were observed in 7.2 and 0.6% respectively (no G4). Grade ≥2 late toxicity was observed in 8.1%, 16.7% and 3.7% after 1, 3 and 4 fractions, respectively (p = 0.004). CTV > 50 cc (p = 0.007) and V150 > 40% (p = 0.027) were prognostic factors for G≥2 late toxicity. Regarding oncological outcome, 4-year cumulative incidence of LR, RR and DMD were 2% [95% CI = 0 - 3], 1% [95% CI = 0 - 2] and 1% [95% CI = 0 - 2] respectively. CSS and OS were 98% [95% CI = 96 - 100] and 93% [95% CI = 90 - 96] respectively. No significant difference was observed in terms of oncological outcome between the 3-fractionation groups. VAPBI based on 1 or 2 days of HDR MIB represents an attractive de-escalation irradiation approach for low-risk breast cancer. Late toxicity profile appears acceptable while early oncological outcome shows excellent local control. Brachytherapy technique remains a key component of clinical outcome. Longer follow-up is warranted in order to confirm these encouraging preliminary results.