Interventions for Radiation-Induced Fibrosis in Patients With Breast Cancer: Systematic Review and Meta-analyses

Abstract

Purpose: Radiation therapy can affect normal tissues in patients with breast cancer, causing adverse effects such as fibrosis. Although there are several interventions for radiation-induced fibrosis, the efficacy of these procedures is still unclear. The purpose of this review is to evaluate the efficacy of interventions for radiation-induced fibrosis in patients with breast cancer.

Methods and materials: This is a systematic review of randomized clinical trials. Studies that compared any intervention for fibrosis to another intervention, placebo, or no intervention were included. Outcomes assessed were fibrosis, adverse events, quality of life, treatment adherence, pain, and functionality.

Results: A total of 2501 publications were found, and 7 studies were selected because they met the inclusion criteria. The interventions for fibrosis were pentoxifylline and vitamin E, grape seed extract, kinesiotherapy, and endermotherapy. The results showed great heterogeneity in the treatment protocols for radiation-induced fibrosis in patients with breast cancer and in their evaluation metrics. The meta-analyses showed no benefit in using pentoxifylline and vitamin E compared with placebo or no intervention (standardized mean difference: -0.30; 95% confidence interval, -0.79 to 0.20; P = .24 [very low evidence]) compared with placebo and vitamin E (standardized mean difference: -0.09; 95% confidence interval, -0.66 to 0.49; P = .77 [moderate evidence]), respectively, assessed by the Late Effects Normal Tissue Task Force-Subjective, Objective, Management, and Analytic (LENT-SOMA) scoring scale.

Conclusions: The effectiveness of these interventions for the treatment of radiation-induced fibrosis in patients with breast cancer could not be determined. Although isolated studies show significant results favorable to the experimental groups, caution should be exercised in these findings because of the small number, small sample size, and high risk of bias presented by some of the included studies, which makes the recommendation for clinical practice still weak.

© 2022 The Authors.

Figures

Fig. 1

Graph and summary of the risk of bias judgment for each domain. (A) Graph of judgment of risk of bias for each domain in percentages. (B) Summary of the risk of bias judgment for each included study. Abbreviations: + = low risk of bias; ? = some concerns; - = high risk of bias.

Fig. 2

Forest plots of the meta-analyses. (A) Forest plot of comparison: pentoxifylline and vitamin E versus placebo or no intervention. Outcome: fibrosis measured by the LENT-SOMA scoring scale. (B) Forest plot of comparison: pentoxifylline and vitamin E versus placebo and vitamin E. Outcome: fibrosis measured by the LENT-SOMA scale. Abbreviations: + = low risk of bias; ? = some concerns; - = high risk of bias; CI = confidence interval; IV = inverse variance; LENT-SOMA = Late Effects Normal Tissue Task Force–Subjective, Objective, Management, and Analytic; SD = standard deviation; Std. = standardized.