龍小慶 王繼生 賈霖 陳靜 楚明明 韓建軍 何霞 曹莉莎 趙德華
中圖分類號(hào) R730.55;R818 文獻(xiàn)標(biāo)志碼 A 文章編號(hào) 1001-0408(2019)02-0258-06
DOI 10.6039/j.issn.1001-0408.2019.02.24
摘 要 目的:系統(tǒng)評(píng)價(jià)三乙醇胺防治放射性皮炎(RD)的有效性,并評(píng)價(jià)結(jié)局指標(biāo)的證據(jù)質(zhì)量,為臨床治療提供參考。方法:計(jì)算機(jī)檢索PubMed、Cochrane圖書館、Embase、中國(guó)知網(wǎng)數(shù)據(jù)庫(kù)、萬(wàn)方數(shù)據(jù)庫(kù)、維普數(shù)據(jù)庫(kù),收集三乙醇胺(試驗(yàn)組)對(duì)比常規(guī)護(hù)理(對(duì)照組)用于防治RD的隨機(jī)對(duì)照試驗(yàn)(RCT),提取資料并按Cochrane偏倚風(fēng)險(xiǎn)評(píng)估工具5.0.2評(píng)價(jià)文獻(xiàn)質(zhì)量后,采用Rev Man 5.3統(tǒng)計(jì)軟件對(duì)數(shù)據(jù)進(jìn)行Meta分析。采用GRADE證據(jù)質(zhì)量分級(jí)系統(tǒng)對(duì)結(jié)局指標(biāo)的證據(jù)質(zhì)量進(jìn)行評(píng)價(jià)。結(jié)果:共納入7項(xiàng)RCT,合計(jì)782例患者。Meta分析結(jié)果顯示,兩組患者RD總發(fā)生率[OR=0.50,95%CI(0.23,1.11),P=0.09]、Ⅰ級(jí)RD發(fā)生率[OR=1.32,95%CI(0.96,1.81),P=0.09]、Ⅱ級(jí)RD發(fā)生率[OR=1.07,95%CI(0.80,1.42),P=0.66]、Ⅲ級(jí)RD發(fā)生率[OR=0.69,95%CI(0.45,1.04),P=0.07]、Ⅳ級(jí)RD發(fā)生率[OR=0.43,95%CI(0.17,1.05),P=0.07]比較,差異均無(wú)統(tǒng)計(jì)學(xué)意義。GRADE證據(jù)質(zhì)量評(píng)價(jià)結(jié)果顯示,兩組患者RD總發(fā)生率以及Ⅱ級(jí)、Ⅳ級(jí)RD發(fā)生率為中級(jí)證據(jù)質(zhì)量,Ⅰ級(jí)和Ⅲ級(jí)RD發(fā)生率為低級(jí)證據(jù)質(zhì)量。結(jié)論:三乙醇胺不能用于防治RD,也不能降低RD的發(fā)生率。
關(guān)鍵詞 三乙醇胺;放射性皮炎;防治;有效性;Meta分析;GRADE證據(jù)質(zhì)量評(píng)價(jià)
ABSTRACT OBJECTIVE: To evaluate the effectiveness of trolamine for preventing and treating radiation dermatitis (RD) and evidence quality, and to provide reference for clinical use. METHODS: Retrieved from PubMed, Cochrane library, Embase, CNKI, Wanfang and VIP database, randomized controlled trials (RCTs) about trolamine (trial group) versus usual care (control group) for preventing and treating RD were collected. After data extraction, Cochrane bias risk assessment tool 5.0.2 was used to assess the bias risk, and Rev Man 5.3 statistical software was used to perform the Meta-analysis. GRADE evidence quality grading system was used to evaluate the evidence quality of outcome indexes. RESULTS: Seven RCTs were included, involving 782 patients. Results of Meta-analysis showed that there was no statistical significance in total incidence of RD [OR=0.50, 95%CI (0.23, 1.11), P=0.09], and the incidence of grade Ⅰ RD [OR=1.32, 95%CI(0.96,1.81), P=0.09], grade Ⅱ RD [OR=1.07, 95%CI(0.80,1.42), P=0.66], grade Ⅲ RD [OR=0.69, 95%CI(0.45,1.04), P=0.07] or grade Ⅳ RD [OR=0.43, 95%CI(0.17,1.05), P=0.07] between 2 groups. Results of Grade evidence quality evaluation showed that total incidence of RD, and the incidence of grade Ⅱ RD and grade Ⅳ RD were recommended by moderate-level evidence in 2 groups, while the incidence of grade Ⅰ and grade Ⅲ RD were recommended by low-level evidence. CONCLUSIONS: Trolamine is not effective in preventing and treating RD, and can not reduce the incidence of RD.
KEYWORDS Trolamine; Radiation dermatitis; Preventing and treating; Effectiveness; Meta-analysis; GRADE evidence quality evaluation
放射治療及外科手術(shù)、化學(xué)治療、靶向治療、生物治療是目前治療腫瘤的主要手段,尤其在直腸、乳腺以及頭頸部腫瘤中,放射治療具有重要的地位[1-2]。隨著放療方法、放療設(shè)備的不斷改進(jìn),放射治療致不良反應(yīng)雖明顯減少,但仍有一些不良反應(yīng)存在,如放射性皮炎(Radiation dermatitis,RD)。RD是放射治療最常見(jiàn)的不良反應(yīng),發(fā)生率約為95%,嚴(yán)重影響患者的生存質(zhì)量,也是患者治療中斷的主要原因之一[3-4]。
RD的臨床表現(xiàn)主要為皮膚紅斑、色素沉著、脫屑、潰瘍、出血、壞死及皮膚萎縮等,其發(fā)生機(jī)制主要為電離輻射產(chǎn)生的自由基和活性氧導(dǎo)致皮膚基底層細(xì)胞損傷[5]。目前,RD尚未有標(biāo)準(zhǔn)的防治方法,臨床多采用三乙醇胺預(yù)防RD,但其有效性存在爭(zhēng)議[6-12]。有部分研究認(rèn)為,三乙醇胺對(duì)RD無(wú)預(yù)防作用[6-8];也有部分研究認(rèn)為,三乙醇胺可降低RD的發(fā)生率和嚴(yán)重程度[9-12]。為此,本研究采用Meta分析系統(tǒng)評(píng)價(jià)了三乙醇胺防治RD的有效性,并評(píng)價(jià)了結(jié)局指標(biāo)的證據(jù)質(zhì)量,旨在為臨床治療提供參考。
1 資料與方法
1.1 納入與排除標(biāo)準(zhǔn)
1.1.1 研究類型 國(guó)內(nèi)外公開(kāi)發(fā)表的隨機(jī)對(duì)照試驗(yàn)(RCT)。語(yǔ)種限定為中文和英文。
1.1.2 研究對(duì)象 接受放射治療的腫瘤患者。
1.1.3 干預(yù)措施 試驗(yàn)組患者給予常規(guī)護(hù)理+三乙醇胺軟膏;對(duì)照組患者給予常規(guī)護(hù)理。
1.1.4 結(jié)局指標(biāo) ①RD總發(fā)生率;②Ⅰ級(jí)RD發(fā)生率;③Ⅱ級(jí)RD發(fā)生率;④Ⅲ級(jí)RD發(fā)生率;⑤Ⅳ級(jí)RD發(fā)生率。
1.1.5 排除標(biāo)準(zhǔn) ①重復(fù)檢出或發(fā)表的文獻(xiàn);②非放射治療的文獻(xiàn);③未預(yù)防性使用三乙醇胺的文獻(xiàn);④研究結(jié)果不完整的文獻(xiàn);⑤非RCT。
1.2 文獻(xiàn)檢索策略
計(jì)算機(jī)檢索PubMed、Cochrane圖書館、Embase、中國(guó)知網(wǎng)數(shù)據(jù)庫(kù)、萬(wàn)方數(shù)據(jù)庫(kù)和維普數(shù)據(jù)庫(kù)。中文檢索詞為“三乙醇胺”“比亞芬”“放射性皮炎”;英文檢索詞為“Trolamine”“Biafine”“Radiation dermatitis”。同時(shí)以“隨機(jī)對(duì)照試驗(yàn)”為關(guān)鍵詞對(duì)引用文獻(xiàn)的相關(guān)文獻(xiàn)進(jìn)行二次檢索。檢索時(shí)限均為各數(shù)據(jù)庫(kù)建庫(kù)起至2018年7月。
1.3 文獻(xiàn)篩選與數(shù)據(jù)提取
由2位研究者按照納入與排除標(biāo)準(zhǔn)進(jìn)行篩選,若文獻(xiàn)提供的信息不全,可通過(guò)與作者聯(lián)系獲得相關(guān)信息,經(jīng)閱讀后再?zèng)Q定是否納入該文獻(xiàn)。若遇分歧,由第3位研究者協(xié)助解決。資料提取包括第一作者、發(fā)表年份、例數(shù)、性別、年齡、腫瘤類型、干預(yù)措施、結(jié)局指標(biāo)等。采用美國(guó)國(guó)家癌癥研究所常見(jiàn)毒性判定標(biāo)準(zhǔn)(NCI-CTC)[13]或放射治療腫瘤學(xué)協(xié)作組(RTOG)放療毒性標(biāo)準(zhǔn)[14]對(duì)RD嚴(yán)重程度進(jìn)行分級(jí),詳見(jiàn)表1。
1.4 文獻(xiàn)質(zhì)量評(píng)價(jià)
采用Cochrane偏倚風(fēng)險(xiǎn)評(píng)估工具5.0.2對(duì)納入研究的質(zhì)量進(jìn)行評(píng)價(jià),主要包括:隨機(jī)分配方法是否正確;是否分配隱藏;是否采用盲法;結(jié)果數(shù)據(jù)是否完整;是否無(wú)選擇性報(bào)告研究結(jié)果;有無(wú)其他偏倚來(lái)源。每項(xiàng)情況按“是”“否”“不清楚”進(jìn)行劃分,分別表示“低偏倚風(fēng)險(xiǎn)”“高偏倚風(fēng)險(xiǎn)”“偏倚風(fēng)險(xiǎn)不確定”。
1.5 GRADE證據(jù)質(zhì)量評(píng)價(jià)
采用GRADE證據(jù)質(zhì)量分級(jí)系統(tǒng)對(duì)結(jié)局指標(biāo)的證據(jù)質(zhì)量進(jìn)行評(píng)價(jià)[15]。GRADE證據(jù)質(zhì)量分級(jí)系統(tǒng)中,RCT被設(shè)定為最高等級(jí)證據(jù),以5個(gè)降級(jí)條件和3個(gè)升級(jí)條件評(píng)估證據(jù)質(zhì)量等級(jí)的高低,詳見(jiàn)表 2。
1.6 統(tǒng)計(jì)學(xué)方法
采用Rev Man 5.3軟件對(duì)數(shù)據(jù)進(jìn)行Meta分析。計(jì)數(shù)資料采用比值比(OR)及其95%置信區(qū)間(CI)表示。納入研究間的異質(zhì)性采用χ2檢驗(yàn),檢驗(yàn)水準(zhǔn)α=0.05。若各研究間無(wú)統(tǒng)計(jì)學(xué)異質(zhì)性(P≥0.05,I 2≤50%),采用固定效應(yīng)模型進(jìn)行分析;反之,則采用隨機(jī)效應(yīng)模型進(jìn)行分析。采用倒漏斗圖分析潛在的發(fā)表偏倚。P<0.05為差異有統(tǒng)計(jì)學(xué)意義。
2 結(jié)果
2.1 文獻(xiàn)檢索結(jié)果與納入研究基本信息
初檢得到相關(guān)文獻(xiàn)1 070篇,按照納入與排除標(biāo)準(zhǔn)對(duì)文獻(xiàn)進(jìn)行篩選,排除非RCT、結(jié)果不完整的文獻(xiàn)及綜述,最終納入7篇文獻(xiàn)[6-12],共計(jì)782例患者,其中試驗(yàn)組395例、對(duì)照組387例。文獻(xiàn)篩選流程見(jiàn)圖1;納入研究基本信息見(jiàn)表3。
2.2 納入研究質(zhì)量評(píng)價(jià)結(jié)果
7項(xiàng)研究[6-12]均為RCT,2項(xiàng)研究[10,12]描述了具體的隨機(jī)方法,1項(xiàng)研究[7]為非盲法;所有研究均未描述分配隱藏、選擇性報(bào)告研究結(jié)果、其他偏倚;所有研究均描述了結(jié)局?jǐn)?shù)據(jù)是否完整,詳見(jiàn)表4。
2.3 Meta分析結(jié)果
2.3.1 RD總發(fā)生率 7項(xiàng)研究[6-12]均報(bào)道了RD總發(fā)生率,各研究間無(wú)統(tǒng)計(jì)學(xué)異質(zhì)性(P=0.89,I 2=0),采用固定效應(yīng)模型進(jìn)行分析,詳見(jiàn)圖2。Meta分析結(jié)果顯示,兩組患者RD總發(fā)生率比較,差異無(wú)統(tǒng)計(jì)學(xué)意義[OR=0.50,95%CI(0.23,1.11),P=0.09]。
2.3.2 Ⅰ級(jí)RD發(fā)生率 7項(xiàng)研究[6-12]均報(bào)道了Ⅰ級(jí)RD發(fā)生率,各研究間無(wú)統(tǒng)計(jì)學(xué)異質(zhì)性(P=0.07,I 2=49%),采用固定效應(yīng)模型進(jìn)行分析,詳見(jiàn)圖3。Meta分析結(jié)果顯示,兩組患者Ⅰ級(jí)RD發(fā)生率比較,差異無(wú)統(tǒng)計(jì)學(xué)意義[OR=1.32,95%CI(0.96,1.81),P=0.09]。
2.3.3 Ⅱ級(jí)RD發(fā)生率 7項(xiàng)研究[6-12]均報(bào)道了Ⅱ級(jí)RD發(fā)生率,各研究間無(wú)統(tǒng)計(jì)學(xué)異質(zhì)性(P=0.56,I 2=0),采用固定效應(yīng)模型進(jìn)行分析,詳見(jiàn)圖4。Meta分析結(jié)果顯示,兩組患者Ⅱ級(jí)RD發(fā)生率比較,差異無(wú)統(tǒng)計(jì)學(xué)意義[OR=1.07,95%CI(0.80,1.42),P=0.66]。
2.3.4 Ⅲ級(jí)RD發(fā)生率 6項(xiàng)研究[6-10,12]報(bào)道了Ⅲ級(jí)RD發(fā)生率,各研究間無(wú)統(tǒng)計(jì)學(xué)異質(zhì)性(P=0.11,I 2=45%),采用固定效應(yīng)模型進(jìn)行分析,詳見(jiàn)圖5。Meta分析結(jié)果顯示,兩組患者Ⅲ級(jí)RD發(fā)生率比較,差異無(wú)統(tǒng)計(jì)學(xué)意義[OR=0.69,95%CI(0.45,1.04),P=0.07]。
2.3.5 Ⅳ級(jí)RD發(fā)生率 7項(xiàng)研究[6-12]均報(bào)道了Ⅳ級(jí)RD發(fā)生率,各研究間無(wú)統(tǒng)計(jì)學(xué)異質(zhì)性(P=0.25,I 2=27%),采用固定效應(yīng)模型進(jìn)行分析,詳見(jiàn)圖6。Meta分析結(jié)果顯示,兩組患者Ⅳ級(jí)RD發(fā)生率比較,差異無(wú)統(tǒng)計(jì)學(xué)意義[OR=0.43,95%CI(0.17,1.05),P=0.07]。
2.4 GRADE證據(jù)質(zhì)量評(píng)價(jià)
兩組患者RD總發(fā)生率以及Ⅱ級(jí)、Ⅳ級(jí)RD發(fā)生率為中級(jí)證據(jù)質(zhì)量,Ⅰ級(jí)和Ⅲ級(jí)RD發(fā)生率為低級(jí)證據(jù)質(zhì)量,提示該結(jié)果仍需更大規(guī)模、多中心RCT進(jìn)一步證實(shí),詳見(jiàn)表5。
2.5 發(fā)表偏倚分析
以RD總發(fā)生率及各級(jí)RD發(fā)生率為指標(biāo),繪制倒漏斗圖,詳見(jiàn)圖7~圖11。由圖可知,各研究散點(diǎn)均分布在倒漏斗圖內(nèi),圖形基本對(duì)稱,提示本研究存在發(fā)表偏倚的可能性較小。
3 討論
放射治療引起的RD可分為急性RD和遲發(fā)性RD。急性RD通常在放療開(kāi)始后2~3周出現(xiàn),主要表現(xiàn)為輕度紅斑、干性或濕性脫屑及潰瘍[4];遲發(fā)性RD通常在放療開(kāi)始后90 d出現(xiàn),主要表現(xiàn)為毛細(xì)血管擴(kuò)張、皮膚萎縮、水腫和潰瘍[3]。嚴(yán)重的RD不僅會(huì)影響患者的生存質(zhì)量,還會(huì)導(dǎo)致治療劑量減少或治療中斷,從而降低治療效果[16]。因此,如何降低RD的發(fā)生率和嚴(yán)重程度,已成為一項(xiàng)重要的研究課題。
目前,臨床多使用三乙醇胺軟膏[6-12]、局部糖皮質(zhì)激素[17]、金盞菊制劑[18]、止汗劑[19]、蘆薈凝膠[20]、燒傷膏[21]、透明質(zhì)酸[22-25]、磺胺嘧啶銀乳膏[26]以及銀敷料[27]來(lái)預(yù)防或治療RD。其中,以三乙醇胺軟膏的使用最為廣泛,但其有效性尚不確定。為此,本研究對(duì)三乙醇胺預(yù)防RD的有效性進(jìn)行了Meta分析,并對(duì)結(jié)局指標(biāo)的證據(jù)質(zhì)量等級(jí)進(jìn)行GRADE評(píng)價(jià)。本次Meta分析結(jié)果顯示,兩組患者RD總發(fā)生率以及Ⅰ級(jí)、Ⅱ級(jí)、Ⅲ級(jí)、Ⅳ級(jí)RD發(fā)生率比較,差異均無(wú)統(tǒng)計(jì)學(xué)意義。GRADE證據(jù)質(zhì)量評(píng)價(jià)結(jié)果顯示,兩組患者RD總發(fā)生率以及Ⅱ級(jí)、Ⅳ級(jí)RD發(fā)生率為中級(jí)證據(jù)質(zhì)量,Ⅰ級(jí)和Ⅲ級(jí)RD發(fā)生率為低級(jí)證據(jù)質(zhì)量。這提示三乙醇胺不能有效預(yù)防RD的發(fā)生,納入研究的結(jié)局指標(biāo)等級(jí)較低。
相關(guān)研究表明,蘆薈凝膠[20]、燒傷膏[21]、銀敷料[27]對(duì)RD均無(wú)預(yù)防作用。Kirova YM等[22]和Leonardi MC等[25]研究表明,透明質(zhì)酸對(duì)RD無(wú)預(yù)防作用。但Liguori V等[23]和Primavera G等[24]研究表明,透明質(zhì)酸可降低RD的嚴(yán)重程度。也有研究認(rèn)為,局部糖皮質(zhì)激素[17]、金盞菊制劑[18]、止汗劑[19]以及磺胺嘧啶銀乳膏[26]對(duì)RD具有一定的預(yù)防作用,提示臨床可考慮使用上述藥物來(lái)降低RD的發(fā)生和嚴(yán)重程度。
綜上所述,三乙醇胺不能用于預(yù)防RD,也不能降低RD的發(fā)生率。本研究的局限性:(1)本研究?jī)H納入了中文和英文文獻(xiàn),且納入研究的樣本量較小,可能影響結(jié)論的可靠性。(2)納入評(píng)價(jià)的文獻(xiàn)質(zhì)量較低,雖然7項(xiàng)研究均為RCT,但只有2項(xiàng)研究提及了具體的隨機(jī)方法,1項(xiàng)研究為非盲法,可能影響結(jié)局指標(biāo)的證據(jù)質(zhì)量。故此結(jié)論有待高質(zhì)量、大樣本、多中心RCT進(jìn)一步驗(yàn)證。
參考文獻(xiàn)
[ 1 ] KUMAR R,AMOLS HI,LOVELOCK M,et al. Quick,efficient and effective patient-specific intensity-modulated radiation therapy quality assurance using log file and electronic portal imaging device[J]. J Cancer Res Ther,2017,13(2):297-303.
[ 2 ] HU ZI,MCARTHUR HL,HO AY. The abscopal effect of radiation therapy:what is it and how can we use it in breast cancer[J]. Curr Breast Cancer Rep,2017,9(1):45- 51.
[ 3 ] HEGEDUS F,MATHEW LM,SCHWARTZ RA. Radiation dermatitis:an overview[J]. Int J Dermatol,2017,56(9):909-914.
[ 4 ] CHAN RJ,LARSEN E,CHAN P. Re-examining the evidence in radiation dermatitis management literature:an overview and a critical appraisal of systematic reviews[J].Int J Radiat Oncol Biol Phys,2012,84(3):e357-e362.
[ 5 ] H?FNER MF,F(xiàn)ETZNER L,HASSEL JC,et al. Prophylaxis of acute radiation dermatitis with an innovative fda- approved two-step skin care system in a patient with head and neck cancer undergoing a platin-based radiochemotherapy:a case report and review of the literature[J]. Dermatology,2013,227(2):171-174.
[ 6 ] ELLIOTT EA,WRIGHT JR,SWANN RS,et al. Phase Ⅲ trial of an emulsion containing trolamine for the prevention of radiation dermatitis in patients with advanced squamous cell carcinoma of the head and neck:results of radiation therapy oncology group trial 99-13[J]. J Clin Oncol,2006,24(13):2092-2097.
[ 7 ] FISHER J,SCOTT C,STEVENS R,et al. Randomized phase Ⅲ study comparing Best Supportive Care to Biafine as a prophylactic agent for radiation-induced skin toxicity for women undergoing breast irradiation:radiation therapy oncology group (RTOG) 97-13[J]. Int J Radiat Oncol Biol Phys,2000,48(5):1307-1310.
[ 8 ] ABBAS H,BENSADOUN RJ. Trolamine emulsion for the prevention of radiation dermatitis in patients with squamous cell carcinoma of the head and neck[J]. Support Care Cancer,2012,20(1):185-190.
[ 9 ] 陳琴,謝淑萍.三乙醇胺乳膏對(duì)直腸癌放射性皮膚損傷預(yù)防及治療效果觀察[J].中國(guó)現(xiàn)代醫(yī)生,2011,49(32):120-121.
[10] 俞斐,童金龍,魯世慧.三乙醇胺乳膏防治頭頸部腫瘤放射性皮炎的臨床觀察[J].中國(guó)藥房,2015,26(14):1962- 1964.
[11] 張建清,張侖,張莉.三乙醇胺(比亞芬)防治頭頸部腫瘤放射性皮膚損傷的療效觀察[J].實(shí)用腫瘤雜志,2011,26(3):269-271.
[12] 張明,陳琳,吳琦.三乙醇胺乳膏預(yù)防乳腺癌放療皮膚損傷的臨床研究[J].實(shí)用醫(yī)院臨床雜志,2010,7(1):65-66.
[13] TROTTI A,BYHARDT R,STETZ J,et al. Common Toxicity Criteria:version 2.0. an improved reference for grading the acute effects of cancer treatment:impact on radiotherapy[J]. Int J Radiat Oncol Biol Phys,2000,47(1):13-47.
[14] COX JD,STETZ J,PAJAK TF. Toxicity criteria of the Radiation therapy oncology group (RTOG) and the European organization for research and treatment of cancer (EORTC)[J]. Int J Radiat Oncol Biol Phys,1995,31(5):1341-1346.
[15] AGUAYO-ALBASINI JL,F(xiàn)LORES-PASTOR B,SORIA-ALEDO V. GRADE system:classification of quality of evidence and strength of recommendation[J]. Cir Esp,2014,92(2):82-88.
[16] WONG RK,BENSADOUN RJ,BOERS-DOETS CB,et al. Clinical practice guidelines for the prevention and treatment of acute and late radiation reactions from the MASCC skin toxicity study group[J]. Support Care Cancer,2013,21(10):2933-2948.
[17] MILLER RC,SCHWARTZ DJ,SLOAN JA,et al. Mometasone furoate effect on acute skin toxicity in breast cancer patients receiving radiotherapy:a phase Ⅲ double-blind,randomized trial from the north central cancer treatment group N06C4[J]. Int J Radiat Oncol Biol Phys,2011,79(5):1460-1466.
[18] POMMIER P,GOMEZ F,SUNYACH MP,et al. Phase Ⅲ randomized trial of Calendula officinalis compared with trolamine for the prevention of acute dermatitis during irradiation for breast cancer[J]. J Clin Oncol,2004,22(8):1447-1453.
[19] THéBERGE V,HAREL F,DAGNAULT A. Use of axillary deodorant and effect on acute skin toxicity during radiotherapy for breast cancer:a prospective randomized noninferiority trial[J]. Int J Radiat Oncol Biol Phys,2009,75(4):1048-1052.
[20] AHMADLOO N,KADKHODAEI B,OMIDVARI SH,et al. Lack of prophylactic effects of aloe vera gel on radiation induced dermatitis in breast cancer patients[J]. Asian Pac J Cancer Prev,2017,18(4):1139-1143.
[21] GEARA FB,EID T,ZOUAIN N,et al. Randomized,prospective,open-label phase Ⅲ trial comparing mebo ointment with biafine cream for the management of acute dermatitis during radiotherapy for breast cancer[J]. Am J Clin Oncol,2018. DOI:10.1097/COC.0000000000000460.
[22] KIROVA YM,F(xiàn)ROMANTIN I,DE RYCKE Y,et al. Can we decrease the skin reaction in breast cancer patients using hyaluronic acid during radiation therapy? Results of phase Ⅲ randomised trial[J]. Radiother Oncol,2011,100(2):205-209.
[23] LIGUORI V,GUILLEMIN C,PESCE GF,et al. Double-blind,randomized clinical study comparing hyaluronic acid cream to placebo in patients treated with radiotherapy[J]. Radiother Oncol,1997,42(2):155-161.
[24] PRIMAVERA G,CARRERA M,BERARDESCA E,et al.A double-blind,vehicle-controlled clinical study to evaluate the efficacy of MAS065D (XClairTM),a hyaluronic acid-based formulation,in the management of radiation-induced dermatitis[J]. Cutan Ocul Toxicol,2006,25(3):165-171.
[25] LEONARDI MC,GARIBOLDI S,IVALDI GB,et al. A double-blind,randomised,vehicle-controlled clinical study to evaluate the efficacy of MAS065D in limiting the effects of radiation on the skin:interim analysis[J]. Eur J Dermatol,2008,18(3):317-321.
[26] HEMATI S,ASNAASHARI O,SARVIZADEH M,et al.Topical silver sulfadiazine for the prevention of acute dermatitis during irradiation for breast cancer[J]. Support Care Cancer,2012,20(8):1613-1618.
[27] KOLE AJ,KOLE L,MORAN MS. Acute radiation dermatitis in breast cancer patients:challenges and solutions[J].Breast Cancer,2017. DOI:10.2147/BCTT.S109763.
(收稿日期:2018-08-03 修回日期:2018-11-12)
(編輯:陳 宏)