Table_5_Risk Factors Related to Acute Radiation Dermatitis in Breast Cancer Patients After Radiotherapy: A Systematic Review and Meta-Analysis.doc

BackgroundAcute 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.
MethodsPubMed, 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.
ResultsA 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, I2 = 57.1%), large breast volume (RR = 1.02, 95% CI = 1.01–1.03, I2 = 93.2%), smoking habits (RR = 1.70, 95% CI = 1.24–2.34, I2 = 50.7%), and diabetes (RR = 2.24, 95% CI = 1.53–3.27, I2 = 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, I2 = 84.5%). Sequential boost and bolus use was significantly associated with ARD (boost, RR = 1.91, 95% CI = 1.34–2.72, I2 = 92.5%; bolus, RR = 1.94, 95% CI = 1.82–4.76, I2 = 23.8%). However, chemotherapy regimen (RR = 1.17, 95% CI = 0.95–1.45, I2 = 57.2%), hormone therapy (RR = 1.35, 95% CI = 0.94–1.93, I2 = 77.1%), trastuzumab therapy (RR = 1.56, 95% CI = 0.18–1.76, I2 = 91.9%), and nodal irradiation (RR = 1.57, 95% CI = 0.98–2.53, I2 = 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.
ConclusionThe 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.

背景：急性放射性皮炎（Acute radiation dermatitis, ARD）是乳腺癌患者接受辅助放疗后最常见的急性不良反应，会对患者的生活质量产生负面影响。已有多项研究报道了可预测乳腺癌ARD高危人群的若干危险因素。本研究旨在明确与ARD相关的患者自身及治疗相关危险因素。

方法：本研究检索了PubMed、Embase、Cochrane图书馆、中国知网（China National Knowledge Infrastructure, CNKI）及万方数据库中探讨乳腺癌患者ARD危险因素的相关研究。采用随机效应模型计算合并效应量、相对危险度（relative risks, RRs）及95%置信区间（confidence intervals, CIs）。同时依据研究设计、ARD评估量表及研究区域开展潜在异质性分析与敏感性分析。

结果：本研究共纳入38项研究，涉及15623名乳腺癌患者。在7项可获取的患者相关危险因素中，4项与ARD显著相关：体重指数（body mass index, BMI）≥25 kg/m²（RR=1.11，95%CI=1.06~1.16，I²=57.1%）、乳房体积较大（RR=1.02，95%CI=1.01~1.03，I²=93.2%）、吸烟史（RR=1.70，95%CI=1.24~2.34，I²=50.7%）及糖尿病（RR=2.24，95%CI=1.53~3.27，I²=0%）。在7项治疗相关危险因素中，相较于常规分割放疗，大分割放疗可降低乳腺癌患者的ARD发生风险（RR=0.28，95%CI=0.19~0.43，I²=84.5%）。序贯推量照射与组织填充物（bolus）的使用与ARD显著相关（推量照射：RR=1.91，95%CI=1.34~2.72，I²=92.5%；组织填充物：RR=1.94，95%CI=1.82~4.76，I²=23.8%）。然而，化疗方案（RR=1.17，95%CI=0.95~1.45，I²=57.2%）、内分泌治疗（RR=1.35，95%CI=0.94~1.93，I²=77.1%）、曲妥珠单抗（trastuzumab）治疗（RR=1.56，95%CI=0.18~1.76，I²=91.9%）及淋巴结照射（RR=1.57，95%CI=0.98~2.53，I²=72.5%）与ARD无显著相关性。敏感性分析结果显示，BMI与ARD的关联始终稳定存在，而吸烟史、乳房体积及推量照射与ARD的关联则取决于研究设计、研究所在国家及所采用的毒性评估量表。大分割放疗始终表现出保护性作用。研究设计、毒性评估量表及研究区域之间的差异仅能解释少量异质性来源。

结论：本系统评价与荟萃分析结果表明，BMI≥25 kg/m²是ARD的显著预测因素，而大分割放疗始终具有保护性作用。根据研究所在国家、研究设计及所采用的毒性评估量表的不同，乳房体积、吸烟史、糖尿病及序贯推量照射与组织填充物的使用也可作为ARD的预测因素。