Intraoperative Radiotherapy as a Tumour-Bed Boost Combined with Whole Breast Irradiation Versus Conventional Radiotherapy in Patients with Early-Stage Breast Cancer: A Systematic Review and Meta-analysis
Authors: He Jiafa , Chen Shengying , Ye Lingling , Sun Yang , Dai Yan , Song Xue , Lin Xiaojie , Xu Rui 
Published: July 2023

Abstract
Background
There is no definitive answer regarding the efficacy of intraoperative radiotherapy (IORT) as a tumour bed boost for patients with early-stage breast cancer. The purpose of this meta-analysis was to summarise the available evidence and explore the efficacy and safety of IORT combined with whole breast irradiation (WBI) versus conventional radiotherapy in women with early-stage breast cancer who underwent breast-conserving surgery.

Methods
The PUBMED, MEDLINE, EMBASE, Web of Science, and Cochrane Library databases were searched from inception to December 31, 2022. We collected studies on the efficacy, cosmetic outcome, and safety of IORT boost combined with WBI compared with those of conventional radiotherapy in patients with early-stage breast cancer after breast-conserving surgery. Two authors independently performed the literature selection and data extraction. The quality of the randomised, controlled trials (RCTs) was assessed according to the PEDro scale. The quality of non-RCTs was assessed according to the Methodological Index for Non-Randomised Studies. Risk ratios (RRs) for the local recurrence rate (LRR), distant metastasis rate (DMR), disease-free survival (DFS), cosmetic outcome, and toxicity were pooled using fixed or random effects models. Meta-analysis of the included studies was performed by using RevMan 5.3 software.

Results
Nine studies, including one RCT and eight non-RCTs, with a total of 3219 patients were included. In terms of LRR, there was no significant benefit of IORT boost+WBI over conventional radiotherapy (with or without the tumour bed boost) (RR = 0.77, 95% confidence interval (CI): 0.54–1.09, P = 0.14), but a trend towards benefit could be identified. There was a significant reduction in DMR in the IORT boost+WBI group (RR = 0.63, 95% CI: 0.46–0.85, P = 0.003) and a significant improvement in DFS (RR = 0.40, 95% CI: 0.25–0.65, P = 0.0002). Exploratory subgroup analysis showed that the DMR and DFS of the electron boost group were significantly better than those of conventional radiotherapy group, and there was a tendency for LRR to improve in the electron boost group. However, the LRR, DMR, and DFS did not effectively improve in the x-ray boost group. In terms of appearance and toxicity, there were no significant differences in cosmetic outcome, fibrosis, and hyperpigmentation between the two groups (RR = 0.99, 95% CI: 0.91–1.07, P = 0.78; RR = 1.02, 95% CI: 0.41–2.56, P = 0.96; RR = 0.42, 95% CI: 0.10–1.72, P = 0.23), but the incidence of oedema was significantly reduced in the IORT boost+WBI group (RR = 0.27, 95% CI: 0.13–0.59, P = 0.0009).

Conclusions
IORT boost+WBI is more effective than conventional radiotherapy after breast-conserving surgery in patients with early-stage breast cancer, and electron boost exhibits better efficacy than x-ray boost. In addition, the cosmetic and safety profiles of IORT boost+WBI are not inferior to those of conventional radiotherapy.