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. 2022 Jun 9;20(1):191.
doi: 10.1186/s12957-022-02653-8.

The impact of intraoperative radiotherapy on breast cancer: focus on the levels of angiogenic factors

Nahid Nafissi  1 , Maryam Mohammadlou  2   3 , Mohammad Esmaeil Akbari  4 , Seyed Rabie Mahdavi  5 , Maryam Sheikh  2 , Mohammad Borji  6 , Ebrahim Babaee  7 , Rasoul Baharlou  8   9
Affiliations

The impact of intraoperative radiotherapy on breast cancer: focus on the levels of angiogenic factors

Nahid Nafissi et al. World J Surg Oncol. .

Abstract

Objective: Angiogenesis is one of the hallmarks of cancers that is involved in tumor progression. Angiogenic factors induce the formation of new blood vessels and tumor extension, and finally reduce the survival of patients. Intraoperative radiotherapy (IORT), in which radiation is delivered to the tumor bed can kill cells and change tumor microenvironment. Here, we compared the impact of IORT on the levels of angiogenic factors in the blood and surgical wound fluids (SWF) of the breast cancer patients.

Patients and methods: Three hundred sixty patients, who had undergone breast-conserving surgery between 2013 and 2018, were enrolled in IORT and non-IORT groups non-randomly. Blood and drained wound fluid (WF) samples were collected from the patients before and after surgery, followed by quantification of the amounts of TGF-β, EGF, FGF, VEGF, and DLL4 in the patients using ELISA.

Results: Our results were indicative of significant differences between the pre-surgery and post-surgery serum levels of EGF, DLL4, and VEGF. Furthermore, ROC analyses showed that TGF-β and DLL4 can differentiate of the early-stage from late-stage of the disease. Interestingly, the rate of the death and recurrence was reduced in IORT group.

Conclusions: In summary, IORT is a safe and effective treatment that can affect angiogenic factors and improve the overall- and recurrence-free survival of breast cancer patients.

Keywords: Breast cancer; DLL4; EGF; FGF; IORT; TGF-β; VEGF.

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Conflict of interest statement

The authors have no conflicts of interest to declare.

Figures

Fig. 1
Fig. 1
The level of TGF-β, EGF, FGF, DLL4, and VEGF in the peripheral blood and WF of breast cancer patients with and without IORT. Significant difference was found in the serum level of EGF (B), DLL4 (D), and VEGF (E) between before and after IORT. Results were analyzed with non-parametric Wilcoxon matched-pairs rank test and two-tailed Mann-Whitney U test. Values are the mean ± SEM; * = p < 0.05; ** = p < 0.01
Fig. 2
Fig. 2
Receiver operating characteristics (ROC) curve analyses of levels of TGF-β, EGF, FGF, DLL4 and VEGF in the stage, LN involvement and tumor size groups. (A) As diagnostic biomarkers differentiating early from late stage. (B) Diagnostic biomarkers differentiating LN free from > 1 LN involvement. (C) Diagnostic biomarkers differentiating tumor size ≤ 2 from > 2 cm. AUC: area under the curve; LN: lymph node
Fig. 3
Fig. 3
Kaplan–Meier analysis of survival rate (A) and recurrence rate (B) in IORT and non-IORT groups. Significant differences were determined by log-rank (Mantel–Cox) analysis for (A) overall survival (IORT median survival 59.00 and non-IORT median survival 48.70) and (B) recurrence-free survival (IORT median survival 47.03 and non-IORT median survival 32.87). IORT: intraoperative radiotherapy
See this image and copyright information in PMC

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