Risk Factors Related to Acute Radiation Dermatitis in Breast Cancer Patients After Radiotherapy: A Systematic Review and Meta-Analysis

Abstract

Background: Acute radiation dermatitis (ARD) is the most common acute response after adjuvant radiotherapy in breast cancer patients and negatively affects patients' quality of life. Some studies have reported several risk factors that can predict breast cancer patients who are at a high risk of ARD. This study aimed to identify patient- and treatment-related risk factors associated with ARD.

Methods: PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, and WanFang literature databases were searched for studies exploring the risk factors in breast cancer patients. The pooled effect sizes, relative risks (RRs), and 95% CIs were calculated using the random-effects model. Potential heterogeneity and sensitivity analyses by study design, ARD evaluation scale, and regions were also performed.

Results: A total of 38 studies composed of 15,623 breast cancer patients were included in the analysis. Of the seven available patient-related risk factors, four factors were significantly associated with ARD: body mass index (BMI) ≥25 kg/m² (RR = 1.11, 95% CI = 1.06-1.16, I ² = 57.1%), large breast volume (RR = 1.02, 95% CI = 1.01-1.03, I ² = 93.2%), smoking habits (RR = 1.70, 95% CI = 1.24-2.34, I ² = 50.7%), and diabetes (RR = 2.24, 95% CI = 1.53-3.27, I ² = 0%). Of the seven treatment-related risk factors, we found that hypofractionated radiotherapy reduced the risk of ARD in patients with breast cancer compared with that in conventional fractionated radiotherapy (RR = 0.28, 95% CI = 0.19-0.43, I ² = 84.5%). Sequential boost and bolus use was significantly associated with ARD (boost, RR = 1.91, 95% CI = 1.34-2.72, I ² = 92.5%; bolus, RR = 1.94, 95% CI = 1.82-4.76, I ² = 23.8%). However, chemotherapy regimen (RR = 1.17, 95% CI = 0.95-1.45, I ² = 57.2%), hormone therapy (RR = 1.35, 95% CI = 0.94-1.93, I ² = 77.1%), trastuzumab therapy (RR = 1.56, 95% CI = 0.18-1.76, I ² = 91.9%), and nodal irradiation (RR = 1.57, 95% CI = 0.98-2.53, I ² = 72.5%) were not correlated with ARD. Sensitivity analysis results showed that BMI was consistently associated with ARD, while smoking, breast volume, and boost administration were associated with ARD depending on study design, country of study, and toxicity evaluation scale used. Hypofractionation was consistently shown as protective. The differences between study design, toxicity evaluation scale, and regions might explain a little of the sources of heterogeneity.

Conclusion: The results of this systematic review and meta-analysis indicated that BMI ≥ 25 kg/m² was a significant predictor of ARD and that hypofractionation was consistently protective. Depending on country of study, study design, and toxicity scale used, breast volume, smoking habit, diabetes, and sequential boost and bolus use were also predictive of ARD.

Keywords: acute radiation dermatitis; breast cancer; meta-analysis; radiotherapy; risk factor.

Figure 1

The flowchart of the literature search.

Figure 2

Forest plot of studies among patient-related risk factors associated with acute radiation dermatitis. (A) Age. (B) Body mass index (BMI). (C) Breast volume. (D) Smoking. (E) Chronic disease (hypertension/diabetes). (F) Race.

Figure 3

Forest plot of studies among treatment-related risk factors associated with acute radiation dermatitis. (A) Boost. (B) Hypofractionated radiotherapy (HFRT) vs. conventional fractionated radiotherapy (CFRT). (C) Chemotherapy regimen. (D) Trastuzumab therapy. (E) Hormone therapy. (F) Nodal irradiation. (G) Bolus.