胸腔化療聯(lián)合熱療治療癌性胸腔積液有效性和安全性的Meta分析

胡 月,李 征,曲 雁,丁俊琴,祖淑文,李海濱,楊志慧,李燕紅,謝俊芳

·論著· ·醫(yī)學(xué)循證·

胸腔化療聯(lián)合熱療治療癌性胸腔積液有效性和安全性的Meta分析

胡 月1,李 征2*,曲 雁3*,丁俊琴4,祖淑文5,李海濱1,楊志慧1,李燕紅1,謝俊芳1

目的系統(tǒng)評價(jià)胸腔化療聯(lián)合熱療治療癌性胸腔積液的有效性及安全性。方法2015年8月—2016年1月，計(jì)算機(jī)檢索Cochrane Library、PubMed、EMBase、Web of Science等外文數(shù)據(jù)庫以及中國生物醫(yī)學(xué)文獻(xiàn)數(shù)據(jù)庫、中國知網(wǎng)、維普網(wǎng)和萬方數(shù)據(jù)知識服務(wù)平臺等中文數(shù)據(jù)庫，并輔以補(bǔ)充檢索手段，收集比較胸腔化療聯(lián)合熱療(聯(lián)合組)與單純胸腔化療(對照組)治療癌性胸腔積液有效性及安全性的隨機(jī)對照試驗(yàn)。提取納入文獻(xiàn)資料，包括第一作者、發(fā)表時(shí)間、樣本量、年齡、卡氏評分、化療方案及結(jié)局指標(biāo)，并進(jìn)行方法學(xué)質(zhì)量評價(jià)。結(jié)果共納入23篇文獻(xiàn)，包括1 647例患者，其中聯(lián)合組819例，對照組828例。5篇文獻(xiàn)報(bào)道了隨機(jī)方法，各納入文獻(xiàn)均未說明分配隱藏和盲法實(shí)施情況，各文獻(xiàn)兩組患者基本特征具有可比性,1篇文獻(xiàn)有患者失訪，各文獻(xiàn)均無選擇性報(bào)告結(jié)果偏倚。聯(lián)合組治療癌性胸腔積液總有效率〔OR=3.72,95%CI(2.92,4.74)〕、完全緩解率〔OR=2.24,95%CI(1.18,2.78)〕、生活質(zhì)量改善率〔OR=3.66,95%CI(2.64,5.07)〕均高于對照組(P<0.05)。聯(lián)合組與對照組惡心嘔吐〔OR=0.80,95%CI(0.60,1.06)〕、白細(xì)胞計(jì)數(shù)下降〔OR=0.81,95%CI(0.60,1.10)〕、發(fā)熱〔OR=0.98,95%CI(0.69,1.40)〕、肝臟損害〔OR=0.45,95%CI(0.11,1.81)〕、氣胸〔OR=0.41,95%CI(0.06,2.91)〕、皮膚燙傷〔OR=5.33,95%CI(0.91,31.14)〕發(fā)生率比較，差異均無統(tǒng)計(jì)學(xué)意義(P>0.05)；聯(lián)合組胸痛〔OR=0.34,95%CI(0.16,0.74)〕發(fā)生率低于對照組，皮下脂肪硬結(jié)〔OR=6.27,95%CI(1.08,36.27)〕發(fā)生率高于對照組(P<0.05)。結(jié)論與單純胸腔化療相比，胸腔化療聯(lián)合熱療可提高癌性胸腔積液患者近期療效，顯著改善患者生活質(zhì)量，并且臨床安全性較好，但其長期療效和安全性評價(jià)尚需大樣本高質(zhì)量的研究進(jìn)一步驗(yàn)證。

胸腔積液，惡性；化學(xué)療法，腫瘤；熱療；療效；Meta分析

本文文獻(xiàn)檢索策略(以PubMed數(shù)據(jù)庫為例)

#1 randomized controlled trial[pt]

#2 randomized controlled trials as topic[sh]

#3 controlled clinical trial[pt]

#4 controlled clinical trials as topic[sh]

#5 random*[tiab]

#6 trial[tiab]

#7 groups[tiab]

#8 #1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7

#9 pleural effusion,malignant[sh]

#10 malignant pleural effusion OR malignant pleural effusions OR pleural effusion,malignant OR pleural effusions,malignant OR effusion,malignant pleural OR effusions,malignant pleural[tiab]

#11 #9 OR #10

#12 hyperthermia,induced[sh]

#13 hyperthermia OR thermotherapy OR fever therapy[tiab]

#14 #12 OR #13

#15 drug therapy[sh]

#16 chemotherapy OR chemotherapies OR pharmacotherapy OR pharmacotherapies OR drug therapy OR drug therapies OR therapy,drug OR therapies,drug[tiab]

#17 #15 OR #16

#18 #8 AND #11 AND #14 AND #17

統(tǒng)計(jì)顯示，2012年全球新發(fā)癌癥患者約1 410萬例，同時(shí)約820萬例患者死于癌癥[1]。鼻咽癌、肺癌及消化系腫瘤晚期患者常伴有胸腔積液，嚴(yán)重影響患者的生活質(zhì)量和生存時(shí)間，如不及時(shí)治療可造成患者呼吸循環(huán)功能障礙、低蛋白血癥等并發(fā)癥，嚴(yán)重者甚至危及生命。胸腔化療是治療惡性胸腔積液的首選，但其臨床療效有限。腫瘤熱療作為一種特色療法，近年來發(fā)展迅速，The Lancet Onclolgy發(fā)表的一篇研究顯示，熱療能有效殺傷癌細(xì)胞，并有助于增強(qiáng)化療敏感性[2]。相關(guān)臨床試驗(yàn)初步顯示胸腔化療聯(lián)合熱療可有效地控制惡性胸腔積液并改善患者生活質(zhì)量，但前期研究多為散在小樣本試驗(yàn)，偏倚風(fēng)險(xiǎn)各異且統(tǒng)計(jì)學(xué)檢驗(yàn)效能不足。本研究采用Meta分析方法系統(tǒng)評價(jià)胸腔化療聯(lián)合熱療治療癌性胸腔積液的有效性及安全性，為臨床實(shí)踐決策和循證指南的制定提供依據(jù)。

1 資料與方法

1.1 文獻(xiàn)納入及排除標(biāo)準(zhǔn) 納入標(biāo)準(zhǔn)：(1)確診為伴有癌性胸腔積液的腫瘤患者，腫瘤類型不限；(2)聯(lián)合組采用胸腔化療聯(lián)合熱療，對照組僅單純采用胸腔化療，胸腔熱療實(shí)施方式為應(yīng)用體外熱療儀進(jìn)行的胸腔局部熱療；(3)結(jié)局指標(biāo)包括總有效率、完全緩解率、生活質(zhì)量改善率及毒副作用發(fā)生率；(4)研究類型為隨機(jī)對照試驗(yàn)，分配隱藏或盲法不作要求；(5)文獻(xiàn)來源期刊收錄在2015年SCI、PubMed、中國科學(xué)引文數(shù)據(jù)庫(CSCD)、北京大學(xué)中文核心數(shù)據(jù)庫、中國科技核心(CSTPCD)數(shù)據(jù)庫。排除標(biāo)準(zhǔn)：會議摘要、重復(fù)發(fā)表文獻(xiàn)及總體質(zhì)量明顯較差文獻(xiàn)。

1.2 文獻(xiàn)檢索及篩選 2015年8月—2016年1月，計(jì)算機(jī)檢索Cochrane Library、PubMed、EMBase、Web of Science等外文數(shù)據(jù)庫以及中國生物醫(yī)學(xué)文獻(xiàn)數(shù)據(jù)庫(CBM)、中國知網(wǎng)(CNKI)、維普網(wǎng)(VIP)和萬方數(shù)據(jù)知識服務(wù)平臺(Wanfang)等中文數(shù)據(jù)庫，時(shí)間限制為建庫至2016-01-06，語種不限。追溯納入文獻(xiàn)的參考文獻(xiàn)以補(bǔ)充檢索，同時(shí)應(yīng)用Google Scholar、Medical Matrix等搜索引擎實(shí)施擴(kuò)展檢索。將數(shù)據(jù)庫導(dǎo)出的檢索結(jié)果統(tǒng)一導(dǎo)入EndNote X5文獻(xiàn)管理軟件，在對不同數(shù)據(jù)庫可能重復(fù)收錄的文獻(xiàn)進(jìn)行去重工作后，根據(jù)納入、排除標(biāo)準(zhǔn)進(jìn)行文獻(xiàn)篩選，對文獻(xiàn)題目和摘要全面審查，淘汰明顯背離納入標(biāo)準(zhǔn)的文獻(xiàn)，對初步選定的文獻(xiàn)全部查閱全文，進(jìn)一步淘汰不合格文獻(xiàn)，從而確定最終的納入文獻(xiàn)。兩位研究員(胡月、曲雁)對文獻(xiàn)檢索及篩選獨(dú)立操作并交叉核對，有意見分歧通過討論深入研究并由第3位研究員(李征)裁定。

1.3 資料提取及偏倚風(fēng)險(xiǎn)評估 精讀最終納入的文獻(xiàn)并進(jìn)行資料提取，包括第一作者、發(fā)表時(shí)間、樣本量、年齡、卡氏評分、化療方案及結(jié)局指標(biāo)。對文獻(xiàn)中缺乏的重要資料嘗試通過電話或郵件等方式與作者聯(lián)系進(jìn)行補(bǔ)充，對無法直接獲得而僅存在于圖表中的數(shù)據(jù)嘗試通過AutoCAD 18.2或DraftSight 11.3軟件進(jìn)行提取[3-4]。參考Cochrane標(biāo)準(zhǔn)進(jìn)行文獻(xiàn)偏倚風(fēng)險(xiǎn)評估，重點(diǎn)評估條目如下：(1)隨機(jī)分配方法，即產(chǎn)生隨機(jī)序列所用的具體方法；(2)分配隱藏及其實(shí)施的具體方法；(3)各組基線情況可比性；(4)盲法，包括是否對結(jié)果測量者和統(tǒng)計(jì)分析人員施盲；(5)對失訪情況的報(bào)道及結(jié)果數(shù)據(jù)的完整性；(6)是否選擇性報(bào)告結(jié)果；(7)其他偏倚來源。兩位研究員(胡月、丁俊琴)對資料提取及偏倚風(fēng)險(xiǎn)評估獨(dú)立操作并交叉核對，有意見分歧通過討論深入研究并由第3位研究員(李征)裁定。

1.4 統(tǒng)計(jì)學(xué)方法 采用Cochrane協(xié)作網(wǎng)提供的RevMan 5.3軟件進(jìn)行統(tǒng)計(jì)學(xué)分析。采用Q檢驗(yàn)(P值)和I2值評價(jià)文獻(xiàn)的異質(zhì)性，如P>0.1，I2<50%表明同質(zhì)性較好，以固定效應(yīng)模型實(shí)施合并分析；否則，采用Meta回歸分析或亞組分析，或適當(dāng)選用隨機(jī)效應(yīng)模型；部分不宜進(jìn)行Meta合并或無充分?jǐn)?shù)據(jù)的指標(biāo)則采用定性分析。以P<0.05為差異有統(tǒng)計(jì)學(xué)意義。

2 結(jié)果

2.1 文獻(xiàn)檢索及篩選結(jié)果 初篩獲得文獻(xiàn)473篇，排除重復(fù)文獻(xiàn)124篇，閱讀文題及摘要排除251篇，查閱全文后排除75篇(其中來源于日本的一項(xiàng)研究因采用的熱療方式及對照組的設(shè)置不符合納入標(biāo)準(zhǔn)而排除[5])，最終納入23篇文獻(xiàn)[6-28]，其中英文文獻(xiàn)1篇[8]。文獻(xiàn)篩選流程見圖1。

2.2 納入文獻(xiàn)的基本特征和質(zhì)量評價(jià) 23篇文獻(xiàn)[6-28]共納入1 647例患者，其中聯(lián)合組819例，對照組828例。多數(shù)文獻(xiàn)納入患者卡氏評分>50分，預(yù)計(jì)生存時(shí)間超過3個月。5篇文獻(xiàn)[9,13,18,22-23]報(bào)道了隨機(jī)方法，各納入文獻(xiàn)均未說明分配隱藏和盲法實(shí)施情況，各文獻(xiàn)兩組患者基本特征(如性別、年齡、臨床分期等)具有可比性，1篇文獻(xiàn)[8]有患者失訪，各文獻(xiàn)均無選擇性報(bào)告的偏倚。納入文獻(xiàn)基本特征及質(zhì)量評價(jià)見表1、2。

表1 納入文獻(xiàn)基本特征Table 1 Basic characteristics of the included studies

注：T=聯(lián)合組，C=對照組；①=總有效率，②=完全緩解率，③=生活質(zhì)量改善率，④=毒副作用

表2 納入文獻(xiàn)質(zhì)量評價(jià)Table 2 Methodological quality assessment results of the included studies

圖1 文獻(xiàn)篩選流程Figure 1 Flow chart of included literatures

2.3 Meta分析

2.3.1 有效性 23篇文獻(xiàn)[6-28]均報(bào)道了聯(lián)合組和對照組治療癌性胸腔積液總有效率，各文獻(xiàn)間無統(tǒng)計(jì)學(xué)異質(zhì)性(P=0.99，I2=0)，采用固定效應(yīng)模型進(jìn)行Meta分析。結(jié)果顯示，聯(lián)合組治療癌性胸腔積液總有效率高于對照組，差異有統(tǒng)計(jì)學(xué)意義〔OR=3.72,95%CI(2.92,4.74)，P<0.000 01，見圖2〕。

23篇文獻(xiàn)[6-28]均報(bào)道了聯(lián)合組和對照組治療癌性胸腔積液完全緩解率，各文獻(xiàn)間無統(tǒng)計(jì)學(xué)異質(zhì)性(P=0.71，I2=0)，采用固定效應(yīng)模型進(jìn)行Meta分析。結(jié)果顯示，聯(lián)合組治療癌性胸腔積液完全緩解率高于對照組，差異有統(tǒng)計(jì)學(xué)意義〔OR=2.24,95%CI(1.18,2.78)，P<0.000 01，見表3〕。13篇文獻(xiàn)[6-7,10-11,13-16,19-23]報(bào)道了聯(lián)合組和對照組治療癌性胸腔積液生活質(zhì)量改善率，各文獻(xiàn)間無統(tǒng)計(jì)學(xué)異質(zhì)性(P=0.99，I2=0)，采用固定效應(yīng)模型進(jìn)行Meta分析。結(jié)果顯示，聯(lián)合組治療癌性胸腔積液生活質(zhì)量改善率高于對照組，差異有統(tǒng)計(jì)學(xué)意義〔OR=3.66,95%CI(2.64,5.07)，P<0.000 01，見表3〕。CHEN等[8]研究觀察了兩組遠(yuǎn)期療效，聯(lián)合組中位生存時(shí)間為8.9個月，優(yōu)于對照組中位生存時(shí)間的6.2個月。

2.3.2 安全性 Meta分析結(jié)果顯示，聯(lián)合組與對照組惡心嘔吐、白細(xì)胞計(jì)數(shù)下降、發(fā)熱、肝臟損害、氣胸、皮膚燙傷發(fā)生率比較，差異均無統(tǒng)計(jì)學(xué)意義(P>0.05)；聯(lián)合組胸痛發(fā)生率低于對照組，皮下脂肪硬結(jié)發(fā)生率高于對照組，差異均有統(tǒng)計(jì)學(xué)意義(P<0.05，見表3)。

2.4 發(fā)表偏倚 對納入文獻(xiàn)總有效率的發(fā)表偏倚評價(jià)顯示，漏斗圖對稱性較好，受發(fā)表偏倚影響的可能性較小(見圖3)。

表3 聯(lián)合組與對照組治療癌性胸腔積液完全緩解率、生活質(zhì)量改善率及安全性比較的Meta分析Table 3 Meta-analysis of the complete remission rate,improving rate of life quality and adverse reactions between ITCT and ITC for MPE

圖2 聯(lián)合組與對照組治療癌性胸腔積液總有效率比較的森林圖Figure 2 Forest plot of the overall response rate between ITCT and ITC for MPE

圖3 總有效率的漏斗圖Figure 3 Funnel plot for assessing the publication bias based on the total effective rate

3 討論

癌性胸腔積液是晚期癌癥患者常見并發(fā)癥，其來源常為鼻咽癌、肺癌及消化系腫瘤等。癌細(xì)胞侵犯胸膜使其毛細(xì)血管通透性增加，侵犯淋巴系統(tǒng)阻塞淋巴管道，導(dǎo)致滲出增多而回吸收減少，從而使胸腔積液病理性聚積。癌性胸腔積液使大量的體液、清蛋白和血細(xì)胞丟失，同時(shí)大量癌性胸腔積液影響肺活動度，壓迫心臟和縱隔，嚴(yán)重影響患者的心肺功能，導(dǎo)致胸悶、心悸和呼吸困難等癥狀，更甚者發(fā)生呼吸、循環(huán)衰竭，患者生活質(zhì)量下降并嚴(yán)重影響預(yù)后。因此，迅速而高效地控制癌性胸腔積液是整個癌癥治療過程中的重要環(huán)節(jié)。

單純的胸腔穿刺抽液或胸腔閉式引流不能有效控制癌性胸腔積液的增長，且因胸腔積液大量丟失易造成低蛋白血癥及電解質(zhì)紊亂等癥狀。全身化療控制胸腔積液的效果較差，常以局部治療為主，胸腔化療是治療癌性胸腔積液最常見的方法之一[29-30]，藥動學(xué)優(yōu)勢明顯，效果優(yōu)于靜脈化療，且全身毒副作用較小。胸腔化療的作用機(jī)制主要是化療藥物刺激胸膜，導(dǎo)致化學(xué)性胸膜炎并產(chǎn)生粘連從而控制積液生成；此外化療藥物滲透到腫瘤組織直接殺滅癌細(xì)胞，同時(shí)胸腔內(nèi)的藥物在吸收入體循環(huán)后可再次到達(dá)腫瘤組織進(jìn)行殺傷。

熱療于1985年被美國食品藥品監(jiān)督管理局認(rèn)證為繼手術(shù)、放療、化療、生物治療之后的第5大腫瘤治療手段。熱療是運(yùn)用熱效應(yīng)及其繼發(fā)效應(yīng)選擇性地殺死癌細(xì)胞并抑制癌細(xì)胞轉(zhuǎn)移的一種特色療法。相關(guān)研究已經(jīng)證實(shí)化療與熱療治療腫瘤有互補(bǔ)增效的作用[5,31-35]?；熍c熱療協(xié)同抗癌機(jī)制主要有：熱療能促進(jìn)化療藥物攻入癌細(xì)胞；熱因子使化療藥物與癌細(xì)胞DNA交聯(lián)增強(qiáng)；熱因子通過對癌細(xì)胞DNA修復(fù)及合成等的抑制能加強(qiáng)癌細(xì)胞對化療藥物的敏感性，從而逆轉(zhuǎn)其耐藥性；化療聯(lián)合熱療能促進(jìn)癌細(xì)胞凋亡發(fā)生；乏氧和富氧細(xì)胞對熱療及化療不同的敏感性決定了熱化療互補(bǔ)增效的抗癌作用。

本研究系統(tǒng)評價(jià)結(jié)果顯示，胸腔化療聯(lián)合熱療綜合療法治療癌性胸腔積液可提高近期療效，有效控制胸腔積液，改善患者生活質(zhì)量，并且臨床安全性較好。此外應(yīng)特殊注意的是，熱療有利于改善患者的抗腫瘤免疫功能[36-38]，熱療對抗腫瘤免疫能力的正向調(diào)節(jié)作用可能是聯(lián)合療法提高療效的關(guān)鍵因素之一。

本研究納入文獻(xiàn)均采用了體外熱療儀的熱療方式，雖然具體實(shí)施方案可能各有不同，但其作用本質(zhì)同為熱量，所以并無臨床異質(zhì)性。聯(lián)合組胸痛發(fā)生率低于對照組，可能為熱療緩解疼痛所致，但同時(shí)聯(lián)合組熱療所致脂肪硬結(jié)的發(fā)生風(fēng)險(xiǎn)增加。胸痛及脂肪硬結(jié)癥狀輕微，一般可自然消失或?qū)ΠY處理后好轉(zhuǎn)，對患者生活質(zhì)量影響較小。KIMURA等[5]研究設(shè)置了胸腔熱灌注化療組(A組)、單純胸腔熱灌注組(B組)及空白對照組(C組)，通過B組與C組的比較發(fā)現(xiàn)，熱療除輔助化療增效外，其本身也有獨(dú)立的治療效果，該研究更加確定了熱療在癌性胸腔積液治療中的應(yīng)用價(jià)值。

伴隨著循證醫(yī)學(xué)的發(fā)展，腫瘤熱療被不斷證實(shí)其獨(dú)特的抗癌作用。然而熱療的效果受到各種臨床因素的影響，其臨床實(shí)施如無嚴(yán)格的質(zhì)量保證，可能會收效甚微[39]，臨床實(shí)施標(biāo)準(zhǔn)有待進(jìn)一步加強(qiáng)和改進(jìn)[40]。精確靶向熱療和無創(chuàng)實(shí)時(shí)測溫是關(guān)鍵突破點(diǎn)，為進(jìn)一步提高療效和安全性，尚需精準(zhǔn)控制熱劑量，有效降低熱耐受，科學(xué)調(diào)控?zé)峄熉?lián)合的時(shí)間順序，熟練把握熱化療的實(shí)施方式和組配劑量。熱療技術(shù)的成熟，有待于熱療生物學(xué)和熱療工程學(xué)的不斷突破。

綜上所述，相比于單純胸腔化療，胸腔化療聯(lián)合熱療的綜合療法治療癌性胸腔積液能提高近期療效，有效改善患者的生活質(zhì)量，并且臨床安全性較好。在臨床實(shí)踐中可根據(jù)患者的具體情況選擇適當(dāng)?shù)臒岑煼桨?，選用合適的化療藥物配伍和劑量。同時(shí)尚需在實(shí)踐中不斷改進(jìn)熱療的臨床技術(shù)，不斷提高熱療的療效和臨床安全性。為保證納入文獻(xiàn)的質(zhì)量，本研究對納入文獻(xiàn)的來源期刊進(jìn)行了篩選，Meta分析結(jié)果的證據(jù)級別較高，結(jié)論可靠，但仍存在一定的局限性：(1)部分文獻(xiàn)對隨機(jī)和盲法的實(shí)施不清楚；(2)遠(yuǎn)期療效數(shù)據(jù)不足，且未見有文獻(xiàn)報(bào)道經(jīng)濟(jì)學(xué)指標(biāo)數(shù)據(jù)，建議后期的臨床試驗(yàn)注意保證隨訪長度并積極開展經(jīng)濟(jì)學(xué)數(shù)據(jù)的收集分析，以實(shí)現(xiàn)對胸腔化療聯(lián)合熱療治療癌性胸腔積液有效性、安全性及臨床經(jīng)濟(jì)學(xué)的全面評價(jià)。

作者貢獻(xiàn)：胡月進(jìn)行課題設(shè)計(jì)與實(shí)施、文獻(xiàn)檢索及篩選、資料收集整理、撰寫論文并對文章負(fù)責(zé)；丁俊琴、祖淑文負(fù)責(zé)資料收集和評估；李海濱、楊志慧、李燕紅、謝俊芳負(fù)責(zé)數(shù)據(jù)處理及核對；李征進(jìn)行數(shù)據(jù)分析及論文修改；李征、曲雁進(jìn)行質(zhì)量控制及審校。

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2016-12-15；

2017-07-07)

(本文編輯：吳立波)

EfficacyandSafetyofIntrathoracicChemotherapyCombinedwithThermotherapyforMalignantPleuralEffusion:aMeta-analysis

HUYue1,LIZheng2*,QUYan3*,DINGJun-qin4,ZUShu-wen5,LIHai-bin1,YANGZhi-hui1,LIYan-hong1,XIEJun-fang1

1.DepartmentofGeneralPractice,WestCampusoftheThirdHospitalofHebeiMedicalUniversity,Shijiazhuang050051,China2.DepartmentofGeneralSurgery,theFirstAffiliatedHospitalofLanzhouUniversity,Lanzhou730000,China3.DepartmentofScientificResearch,theThirdHospitalofHebeiMedicalUniversity,Shijiazhuang050051,China4.DepartmentofNursing,theThirdHospitalofHebeiMedicalUniversity,Shijiazhuang050051,China5.DepartmentofTeaching,theThirdHospitalofHebeiMedicalUniversity,Shijiazhuang050051,China

* Corresponding authors: LI Zheng，Attending physician; E-mail: lizhenglys@126.com

Objective To systematically review the efficacy and safety of intrathoracic chemotherapy combined with thermotherapy(ITCT) for malignant pleural effusion(MPE) .Methods From August 2015 to January 2016，a computer-based retrieval was performed in foreign databases such as Cochrane Library，PubMed，EMBase，Web of Science and Chineseones such as CBM，CNKI，VIP and Wanfang，and supplementary retrieval was also performed with other sources.All relevantrandomized controlled trials(RCTs) were collected to compare ITCT(ITCT group) and monotherapy of intrathoracicchemotherapy(ITC group) .We extracted the relevant information from the literatures，including the first author，publishedtime，sample size，age，Karnofsky performance status，chemotherapy regimens and outcome indicators.Then we assessed themethodologic quality of included studies.Results A total of 23 literatures were included，comprising 1 647 patients，including819 in the ITCT group and 828 in the ITC group.Five studies reported random methods，yet none of the included studiesmentioned the concealment of allocation and blinding.The baseline comparability of the two groups had fine balance.One studyhad loss of follow-up.There was no selective outcome reporting in any of the included studies.Total effective rate (OR=3.72，95%CI(2.92，4.74))，complete remission rate (OR=2.24，95% CI(1.81，2.78))and improving rate of lifequality (OR=3.66，95%CI(2.64，5.07))of ITCT group were superior to those of ITC group and there were all significantdifference(P<0.05) .There were no significant difference between the two groups on the incidence of nausea and vomiting(OR=0.80，95% CI(0.60，1.06))，leukocytopenia(OR=0.81，95% CI(0.60，1.10))，fever(OR=0.98，95% CI(0.69，1.40))，hepatic lesion (OR=0.45，95% CI(0.11，1.81))，pneumothorax (OR=0.41，95% CI(0.06，2.91))and skin scald(OR=5.33，95%CI(0.91，31.14)).The incidence of stethalgia in ITCT group was lower than ITCgroup(OR=0.34，95%CI(0.16，0.74))，the incidence of subcutaneous fat scleroma in ITCT group was higher than ITCgroup(OR=6.27，95%CI(1.08，36.27))，and there were all significant difference(P<0.05) .Conclusion Comparedwith ITC，ITCT can significant improve short-term curative effect and life quality of patients with MPE; additionally，it is safeand feasible.But its long-term survival rate and security still needs to be further verified by more large sample and high qualitystudies.

Pleural effusion,malignant；Chemotherapy,cancer；Thermotherapy;Effectiveness；Meta-analysis

1.050051河北省石家莊市，河北醫(yī)科大學(xué)第三醫(yī)院西院全科醫(yī)學(xué)科

2.730000甘肅省蘭州市，蘭州大學(xué)第一附屬醫(yī)院普外科

3.050051河北省石家莊市，河北醫(yī)科大學(xué)第三醫(yī)院科研處

4.050051河北省石家莊市，河北醫(yī)科大學(xué)第三醫(yī)院護(hù)理部

5.050051河北省石家莊市，河北醫(yī)科大學(xué)第三醫(yī)院教務(wù)處

*通信作者：李征，主治醫(yī)師；E-mail:lizhenglys@126.com

曲雁，主任醫(yī)師；E-mail:quyanebm@163.com

R 734.3

A

10.3969/j.issn.1007-9572.2017.00.047

胡月,李征,曲雁，等.胸腔化療聯(lián)合熱療治療癌性胸腔積液有效性和安全性的Meta分析[J].中國全科醫(yī)學(xué)，2017，20(32)：4034-4041.[www.chinagp.net]

HU Y,LI Z,QU Y,et al.Efficacy and safety of intrathoracic chemotherapy combined with thermotherapy for malignant pleural effusion:a meta-analysis[J].Chinese General Practice，2017，20(32)：4034-4041.

QU Yan，Chief physician; E-mail: quyanebm@163.com