Thermally boosted interstitial high-dose-rate brachytherapy in high-risk early-stage breast cancer conserving therapy - large cohort long-term results.

Abstract

Early-stage high-risk breast cancer (BC) is standardly treated with breast-conserving therapy (BCT), combined with systemic therapy and radiotherapy (RT) ± tumor bed boost, e.g., with interstitial high-dose-rate brachytherapy (HDR-BT). To improve local recurrence rate (LRR), BT radiosensitization (thermal boost, TB) with interstitial microwave hyperthermia (MWHT) may be an option. The paper aims to report a retrospective single-institutional study on 5- and 10-year local control (LC), distant metastasis-free survival (DMFS), disease-free survival (DFS), overall survival (OS), cosmetic outcome (CO), and late toxicity (fibrosis, fat necrosis) after thermally enhanced HDR-BT boost to the BC tumor bed. In 2006-2018, 557 early-stage (I-IIIA) high-risk BC patients were treated with BCT. If indicated, they were administered systemic therapy, then referred for 40.0-50.0 Gy whole breast irradiation (WBI) and 10 Gy interstitial HDR-BT boost (group A). Eligible patients had a single MWHT session preceding BT (group B). Based on present risk factors (RF), medium-risk (1-2 RF) and high-risk subgroups (≥ 3 RF) were formed. Patients were standardly checked, and control mammography (MMG) was performed yearly. Breast cosmesis (Harvard scale) and fibrosis were recorded. LC, DMFS, DFS, and OS were statistically analyzed. Out of 557 patients aged 57 years (26-84), 364 (63.4%) had interstitial HDR-BT boost (group A), and 193 (34.6%) were preheated with MWHT (group B). Patients in group B had a higher clinical stage and had more RFs. The median follow-up was 65.9. Estimated 5-year and 10-year LC resulted in 98.5% and 97.5%, respectively. There was no difference in LC, DMFS, DFS, and OS between groups A and B and between extracted high-risk subgroups A and B. Five- and ten-year OS probability was 95.4% and 88.0%, respectively, with no difference between groups A and B. Harvard criteria-based CO assessment revealed good/excellent cosmesis in 74.9-79.1%. Tumor bed hardening was present in 40.1-42.2%. Asymptomatic fat necrosis-related macrocalcifications were detected in 15.6%, more frequently in group B (p = 0.016). Thermally boosted or not, HDR-BT was locally highly effective as part of combined treatment. Five- and ten-year LC, DMFS, DFS, and OS were high and equally distributed between the groups, although TB was prescribed in more advanced one with more RFs. TB did not influence CO and fibrosis. TB added to late toxicity regarding asymptomatic fat necrosis detected on MMG.