The role of acupoint stimulation as an adjunct - BioMed Central PDF
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Chenetal.BMCComplementaryandAlternativeMedicine2013,13:362 http://www.biomedcentral.com/1472-6882/13/362 RESEARCH ARTICLE Open Access The role of acupoint stimulation as an adjunct therapy for lung cancer: a systematic review and meta-analysis Hai-Yong Chen1†, Shi-Guang Li2†, William CS Cho3* and Zhang-Jin Zhang1* Abstract Background: Lung cancer is theleading cause of death in cancer patients. Clinical studies showed that a variety of acupoint stimulationshave been extensivelyused for lung cancer patients, including needle insertion, injection with herbal extraction, plaster application, and moxibustion. However, therole of acupoint stimulation in lung cancer treatment was not fully reviewed. Methods: In the present study, we conducted a systematic review and meta-analysis onthe roleof acupoint stimulation in lung cancer treatment by electronic and manual searching in seven databases, including Ovid (Ovid MEDLINE, AMED, CAB Abstracts, EMBASE), EBSCOhost research databases (Academic Search premier, MEDLINE, CIHAHL Plus), PreQuest (British Nursing Index, ProQuest MedicalLibrary, ProQuest Dissertations&ThesesA&I, PsycINFO), and ISI web ofknowledge(Webof Science, BIOSIS Citation Index, Biological Abstracts,ChineseScience Citation Database), CNKI, Wanfang Data, and CQVIP. Results: Our study showed that acupoint stimulation has strong immunomodulatory effect for lung cancer patients as demonstratedby the significant increase of IL-2, T cell subtypes (CD3+ and CD4+, but not CD8+ cells), and natural killer cells. Further analysis revealed that acupointstimulation remarkably alleviates the conventional therapy-induced bone marrow suppression (hemoglobin, platelet, and WBC reduction) in lung cancer patients, as well as decreases nausea and vomiting. The pooled studies also showed thatacupoint stimulation can improve Karnofsky performance status,immediate tumor response, quality oflife (EORCT-QLQ-C30), and pain control of cancer patients. Conclusions: Acupoint stimulation is found to be effective in lung cancer treatment, further confirmatory evaluation via large scale randomizedtrials is warranted. Keywords: Acupuncture, Chinesemedicine, Lung cancer, Systematic review, Meta-analysis Background imbalance is the basis of diseases and stimulation of Acupuncture has been widely used for more than three certain acupoints along the collaterals can nurture the thousand years in China. It is one of the key treatment qi (or vital energy) and rebalance Yin-Yang in the body. modalities in traditional Chinese medicine (TCM), which Recently, acupuncture has been widely developed into a is also based on the Yin-Yang, Channel and Collateral variety form of acupoint stimulation, including needle Theories. Accordingly to TCM theories, Yin-Yang insertion, injection with herbal extract, plaster appli- cation, and moxibustion, etc. [1]. Previous studies have shown that acupoint stimulation can be used to treat a *Correspondence:[email protected];[email protected] †Equalcontributors variety of diseases and symptoms, e.g. insomnia [2], de- 3DepartmentofClinicalOncology,QueenElizabethHospital,30Gascoigne pression [3], and pain [4]. In recent decades, TCM is Road,Kowloon,HongKongSpecialAdministrativeRegion,China regarded as a complementary therapy to cancer patients 1SchoolofChineseMedicine,LiKaShingFacultyofMedicine,TheUniversity worldwide [5-7]. A number of literatures have reported ofHongKong,G/F,10SassoonRoad,Pokfulam,HongKongSpecial AdministrativeRegion,China that acupoint stimulation may be effective on symptom Fulllistofauthorinformationisavailableattheendofthearticle ©2013Chenetal.;licenseeBioMedCentralLtd.ThisisanopenaccessarticledistributedunderthetermsoftheCreative CommonsAttributionLicense(http://creativecommons.org/licenses/by/2.0),whichpermitsunrestricteduse,distribution,and reproductioninanymedium,providedtheoriginalworkisproperlycited. Chenetal.BMCComplementaryandAlternativeMedicine2013,13:362 Page2of14 http://www.biomedcentral.com/1472-6882/13/362 management [8,9], reduction of chemotherapy-induced iv)Immediatetumorresponse:numberofpatients side effects [10-12], and quality of life improvement with complete response(CR)orpartial response [13] in cancer patients. (PR)evaluatedwith theWHO scale. Lung cancer is a leading cause of cancer mortality with v) Performancestatus:the changesofKarnofsky 1.37 million deaths in 2008 worldwide. It is the most performancestatus(KPS)scores. prevalent cancer in male and the fourth prevalent cancer vi)Other quality of life assessments, in female. Conventional therapies for lung cancer include e.g. EORTC-QLQ-C30. surgery, radiotherapy, chemotherapy, and targeted thera- pies (e.g. erlotinib and bevacizumab). Recently, the use of Databases alternative and complementary therapies is increasingly Fourmajorsearch engines were retrieved,including: widespread[14,15].WehavepreviouslyfoundthatChinese herbal medicine, as an adjunct therapy, has advantage in 1. OVID® (Ovid MEDLINE 1946to January 2013, the reduction of side effects and improvement of symp- AMED1985to2013,CAB Abstracts1910to toms in patients with non-small cell lung carcinoma [16]. January2013,EMBASE1996to February2013). Some clinical studies have also reported the use of acu- 2. EBSCOhostresearch databases(Academic Search point stimulation as a treatment for lung cancer [17,18]. premier,MEDLINE,CIHAHLPlus,all to However,theroleofacupoint stimulationintreatinglung January2013). cancer is not thoroughly evaluated. Thus, we conducted 3. PreQuest(BritishNursingIndex1994to January a systematic review and meta-analysis on the efficacy 2013, ProQuestMedicalLibraryfromstartsto of acupoint stimulation for lung cancer patients in the January2013,ProQuestDissertations&Theses A&I presentstudy. from startstoJanuary2013, PsycINFO1806to January2013). Methods 4. ISIwebofknowledge(WebofScience®1956to Selectioncriteria January2013,BIOSISCitationIndex2006to January Included studies have to meet all of the following 2013, BiologicalAbstracts®1980to2012, Chinese criteria: ScienceCitationDatabase1989toJanuary2013). 1. Studies claimed as random allocation or showed TheChinese electronicdatabaseswereasthefollows: the baseline data without significant difference (age, gender, and severity) among the intervention 1. CNKI(ChinaAcademicJournalsFull-text Database and control groups. 1979toJanuary2013,ChinaDoctoralDissertations 2. Studieshad touseacupoint stimulationasthe Full-textDatabase1984toJanuary2013,China adjunctintervention,orhad touseacupoint Masters’ Theses Full-text Database1984to January stimulationasthe primary studying objective or 2013, China Proceedings ofConference Full-text evaluatingpurpose. Database1953toJanuary 2013). 3. Studieshad atleastone control groupwith 2. WanfangData(1990to January 2013). conventionaltherapies,placebo,orother appropriate 3. CQVIP(1989toJanuary2013). controls. 4. Studiesinvestigated atleastoneoftheoutcomes of Searchstrategy interestlistedbelow: Electronic databases were searched using the following i) Immunomodulation:changesinCD3,CD4,CD8 strategy: levelsofTcell, natural killer (NK)cells,andIL-2 Searching terms: (acupuncture OR acupressure OR levels. acupoint OR massage OR meridian OR moxibustion OR ii) Bone marrow suppression:changesin moxa)AND(pulmonarycancerORpulmonarycarcinoma hemoglobin,platelets,and whitebloodcells ORpulmonaryadenocarcinomaORpulmonarysquamous (WBCs). cell carcinomasORpulmonaryneoplasmsORpulmonary iii)Conventionaltherapy-inducedsideeffect:nausea nodules OR pulmonary tumor OR lung cancer OR lung and vomiting. Judgmentof vomiting grade was carcinoma OR lung adenocarcinoma OR lung squamous basedonWHO toxicityreaction:grade0:no cell carcinoma OR lung neoplasms OR lung nodules OR nausea andvomiting;grade I:nausea;grade II: lung tumor OR non-small-cell lung carcinoma OR non- casualvomiting,notrequiring medication;grade small-cell-lung carcinoma OR NSCLCOR small-cell lung III:frequentvomiting,requiringmedication; carcinoma OR small-cell-lung carcinoma OR SCLC). grade IV:seriousvomiting,uncontrolledwith Chinese language database was retrieved with similar medication. searchstrategy.“AND”and“OR”areBooleanoperators. Chenetal.BMCComplementaryandAlternativeMedicine2013,13:362 Page3of14 http://www.biomedcentral.com/1472-6882/13/362 Riskbiasassessment Z-testwasusedtocomparetheoveralleffectsofthetreat- Risk bias of studies was assessed using the Cochrane Risk ment groups and the control groups, differences were of Bias Assessment Tool (http://handbook.cochrane.org/, consideredtobestatisticallysignificantwhenP<0.05. part 2, chapter 8). All trials were reviewed by at least two reviewers (HYC and SGL) and any disagreement was re- Results and discussion solvedthroughtheinvolvementofathirdreviewerincon- 993 abstracts were retrieved with 155 duplications. 154 sensusconferences. studies in full text were further examined. A total of 31 studiessatisfiedtheselectioncriteriaandwereanalyzedin Datasynthesis the present study (Figure 1) and their characteristics are All analyses were performed with RevMan version 5.2 to listed in Table 1. Acupoint stimulation varies from needle quantify and compare the efficacy outcomes of the treat- insertion, pressure, plaster application, and moxibustion ment versus the control groups. Dichotomous data were to herbal extraction injection on the acupoints. The most reported as relative ratio (RR) whereas continuous data commonlyusedacupointswerelistedinTable2.Therisk were reported as standardized mean difference (SMD)± of bias in the included studies was assessed as shown in standard deviation (SD). The random-effect model was Figure 2. The risk of bias in each study was shown in employed when the study of heterogeneity (I2) was large (Additionalfile1:TableS1). than50%,otherwiseafix-effectmodelwasusedwhenthe I2 was less than 50%. To test the heterogeneity, subgroup Immunomodulation analysiswasperformedaccordingtothetypesofacupoint A remarkable increase in CD3+ Tcell level was reported stimulation (needle insertion, acupuncture injection with in patients treated with acupoint stimulation (SMD, 0.41 herbs,acupointplasterapplication,andmoxibustion).The [95% CI, 0.20 to 0.62], P=1E-4, 9 studies, 370 patients) Figure1Flowchartofstudyselection. Table1Characteristicsofincludedstudies hC ttphe Studies pNaot.ieonfts Acupuncturegroup Controlgroupintervention Assessmentofoutcomes Duration ://wnet Acupoints Intervention w a w l. CaiandWu[19] 80 Fixedpoints:ST36 ADceuxpamunectthuarseon+eGPandOndansetrontdn GDPexaanmdeOthnadsoannseetron Nauseaandvomiting 8weeks .biom BMC Chen[20] 32 Fixedpoints:ST36andBL23 Astragalusinjectioninacupuncture NP/CEandHuangqilifei Tumorresponse;immunomodulation 8weeks edc Com pdoecinotcsti+onNP/CEandHuangqilifei decoction (sCuDrv3iv+a,lCraDt4e+;c,hCeDm4/oCtoDx8i)c;itKyPS; entra plem l.c en CChheenn[[2212]] 6600 SFFTiixx3ee6dd,PppCoo6iinn,ttesst::cBR.LN143,LU1,LU9, AhGecinrubgpseurbnmyctosuyxrneibd+urosTtmiPoe/nGd+PifafgenerdenneCtrihaalitninoeunsresing TsGyPen/nGderProamalnnedudrCsifihnfeignreecnsaetrieahteiorbnsby TiSmulemperpoorvqeruemaslpeitonynta;sniemd;mcWliunBnicCoasmlsoydmuplattoiomn 810wdeaeykss om/1472 taryand Chenetal.[23] 50 FBiLx2e3d,DpoUi1n4ts:LU9,PC6,ST36, cAacruepuncture+CAP/EP CAP/EP NKandleukocytecells 8weeks -6882/13/3 Alternative Ding[24]a 86 Fixedpoints:LU9,BL13,ST36, Acupuncture+Fuzhenganfei FuzhenganfeiDecoction Clinicalsymptomimprovement; 8weeks 62 M e ST40,SP3,BL20,BL43(bilateral) decoction WBCs;Hb;Plt;KPS dic in Ding[25]b 32 Fixedpoints:ST36,PC6 Acupuncture+cis-platinumbased Cis-platinumbased Nauseaandvomiting 4weeks e 2 chemotherapyandondansetron chemotherapyand 0 1 ondansetron 3 , 1 Fan&Wei[26] 80 Fixedpoints:ST36 VitaminB6acupointinjection+NP/TP NP/TPchemotherapy Nauseaandvomiting;KPS Notreported 3:3 chemotherapycombinedwith combinedwithondansetron 62 ondansetron Guetal.[27] 40 Fixedpoints:ST36,RN4,BL23, Acupointplasterapplication+Chinese Chineseherbs(unclear Immunomodulation(CD3+,CD4+, 8weeks DU4 herbs(unclearingredient) ingredient) CD4/CD8),IL-2 He&Lou[28] 49 PC6,LI10,SP46,SP4(bilateral); Acupointstimulation+EPwith EPwithondansetron Nauseaandvomiting;chemotoxicity 3days RN12(unilateral);auricularpoint: ondansetron liver,spleen,shenmen,jiaogan Huang[29] 40 LU9,BL13,BL17,ST36(bilateral) Crudeherbmoxibustion(Semen Cis-platinumbased Chemotoxicity;livingquality;body 6weeks Brassicae,ManchurianWildginger, chemotherapy weight;clinicalsymptoms;tumor EphedrasinicaStapf)+cis-platinum size;immunomodulation(CD3+,CD4 basedchemotherapy +,CD4/CD8) Huangetal.[30] 80 PC6,ST21,ST36(bilateral) Acupointplasterapplication+NP/GP NP/GPwithondansetron Survival;KPS;clinicalsymptom 3weeks withondansetron improvement;chemotoxicity Jiangetal.[31] 43 BL23,ST36(bilateral);DU4,RN4 Acupointplasterapplicationdecoction Gemcitabine/pemetrexed/ Timetoprogression(TTP);qualityof 8weeks (unilateral) (ofherbalmedicine)+gemcitabine/ docetaxel life pemetrexed/docetaxel Li[32] 60 BL13,BL15,BL17(bilateral) Acupointplasterapplicationwith Diprophylline Dyspneavaluatedbynumericscale 7days decoction(ofSemenBrassicae, ManchurianWildginger,Ephedrasinica Stapf)+Diprophylline P Linetal.[33] 83 BL17(bilateral) Acupuncture+NP/EP NP/EP Chemotoxicity(reductionofWBCs, 10days a g Hb,Plt);KPS e 4 Linetal.[34] 80 fourflowersacupoints:BL17, Moxibustion+NPwithGranisetron NPwithGranisetron Chemotoxicity(reductionofWBCs, 10days o f BL19(bilateral) hydrochloride Hydrochloride Hb,Plt) 1 4 Table1Characteristicsofincludedstudies(Continued) hC ttphe Lin[34] 60 ST36,BL13(bilateral) AAmcuipnooipnhtyinllijneectiinojnec(Ctiohnuankezhi)+ Aminophyllineinjection K+P);Sc;liimnicmaulnsyommpotdoumlastiiomnp(rCoDve3m+,eCnDt4 2weeks ://wwneta w l. Liu&Wang[35] 60 RN12 mAceudpicoiinnetp(PlainsetellriaapTupbliceartaionndwSyitzhyghieurmbal Cchise-pmlaottihneurmapbya+seGdranisetron KPS;appetitescore 3days .biom BMC achroemmaottichuemra,peytc+.)G+racnisis-petlarotinnuhmydbroacsehdlor- Hydrochlorideinjection edc Com e p ideinjection ntra lem Lou[36] 51 bilateral:ST36,RN4,LU5 Acupointmagnet+GP GP Immunomodulation(CD3+,CD4+, 2weeks l.c en OuYangetal.[37] 69 RN8 Moxibustionwithsalt+NP/GP NP/GP CCiCmlDDinm41i/1cuCa+nDl)o;s8myn)maoupdstueolaamtaionimndp(vCrooDmv3ei+tmi,neCgnDt4;+, 4~8weeks om/1472-6882 taryandAltern Qiaoetal.[38] 56 Ashiacupoints,ST36,KI1 Mgriallnimuleetserwavetreatment+Gusefang Gusefanggranules Clinicalsymptomimprovement;KPS 4weeks /13/3 ative 6 M 2 Shietal.[39] 32 ST36,BL23,BL20,RN6,RN4,LU10, Acupuncture+generalanesthesia Generalanesthesia Immunomodulation(CD3+,CD4+, Notreported e d LI10,LI4,SI3,PC4,PC6,SJ6 CD4/CD8) ic in (bilateral) e 2 0 Taoetal.[40] 100 ST36,PC6(bilateral);RN4 Acupointplasterapplication+ Chemotherapywith Nauseaandvomiting 7days 1 3 chemotherapywithmetoclopramideor metoclopramideor , 1 ondansetron ondansetron 3 :3 6 Wang[41] 60 Fourflowersacupoints:BL17, Moxibustion+NP NP TNF-α,IL-2,WBCs;nauseaandvomit- 7days 2 BL19(bilateral) ing;KPS Xu[42] 60 Fourflowersacupoints:BL17, Fireneedletherapy+GP/DPcombined GP/DPcombinedwith Immunomodulation(CD3+,CD4+, 7days BL19(bilateral) withondansetron ondansetron CD4/CD8);TNF-α,IL-2;KPS Xuetal.[43] 45 ST36,DU14 Acupointinjection(RadixSophorae Anti-tumorChineseherbs KPS;bloodcells;chemotoxicity 4weeks Flavescentisextraction)+anti-tumor (WBCs,Hb,Plt) Chineseherbs Xuanetal.[44] 60 BL13(bilateral);DU14 Acupointplasterapplication+traditional TraditionalChinesemedicine Immunomodulation(CD3+,CD4+, 4weeks Chinesemedicine CD4/CD8);KPS Zhang[45] 60 Fourflowersacupoints:BL17, Moxibustion+GP/DPcombinedwith GP/DPcombinedwith Immunomodulation(CD3+,CD4+, 7days BL19(bilateral) ondansetron ondansetron CD4/CD8),TNF-α,IL-2,CSF;KPS Zhang&Cheng. 40 ST36,BL13 Chuankezhiinjectioncombinedwith Routinetreatmentfor Lungfunction,clinicalsymptoms; 2weeks [46] Aminophyllineinjectiontoacupoint+ symptoms immunomodulation(CD3+,CD4+, routinetreatmentforsymptoms CD4/CD8) Zhouetal.[47] 15 ST36,BL23,BL20,RN6,RN4,LU10, Acupuncture+generalanesthesia Generalanesthesia Immunomodulation(CD3+,CD4+, Notreported LI10,LI4,SI3,PC4,PC6,SJ6 CD4/CD8) (bilateral) Zhouetal.[48] 35 Acupointselectiontreatment Abdominalacupuncture+routine Routinetreatmentfor KPS,EORTC-QLQ-C30 4weeks basedonsyndrome treatmentforsymptoms symptoms differentiation P a g CAP,cyclophosphamide+adriamycin+cisplatinum;CE,carboplatinandetoposide;CSF,colonystimulatingfactors;DP,docetaxel+cisplatinum;EP,VP-16+cisplatinum;GP,gemcitabine+cisplatinum;Hb,hemoglobin; e KPS,Karnofskyperformancescore;NP,vinorelbine+cisplatinum;Plt,platelet;TP,paclitaxel+cisplatinum;WBCs,whitebloodcells. 5 o f 1 4 Chenetal.BMCComplementaryandAlternativeMedicine2013,13:362 Page6of14 http://www.biomedcentral.com/1472-6882/13/362 Table2Commonlyusedacupoints acupoint needle insertion (SMD, 0.0 [95% CI, -0.31 to Acupoints Counts Frequency(%) 0.31], P=0.99, 4 studies) had no significant advantage. Heterogeneity test indicated a significant difference ST36(ZuSanLi) 19 64.5 among the acupoint needle insertion subgroup. After PC6(NeiGuan) 8 25.8 further removing any study among them, the acupoint BL17(GeShu) 8 25.8 needle insertion group still showed no significant alter- BL13(FeiShu) 7 22.6 nationcomparedwiththecontrolgroups. RN4(GuanYuan) 7 22.6 As shown in Additional file 2: Figure S1B, the pooled BL23(ShenShu) 6 19.4 studies indicated that acupoint stimulation can increase chemotherapy-inducedNKcellreductioncomparedtothe (Figure 3A), and the heterogeneity test indicated no sig- controlgroup(SMD,0.59[95%CI,0.21to0.97],P=0.002, nificant difference among those studies [20,21,27,29, 3 studies, 114 patients) [20,23,47]. Among them, two stu- 36,39,42,46,47]. Subgroup analysis showed that acupoint diesusedneedleinsertionandtheleftusedacupointinjec- needle insertion (SMD, 0.35 [95% CI, 0.04 to 0.66], tionwithherbextraction. P=0.03, 4 studies) and acupoint injection with herbs Four studies used IL-2 as the outcome measurement (SMD, 0.59 [95% CI, 0.12 to 1.07], P=0.01, 2 studies) to assess the efficacy of acupoint stimulation as an ad- had advantage in improving CD3+ while acupoint juncttherapyforlungcancer[27,41,42,45].Theacupoint plaster application (SMD, 0.22 [95% CI, -0.19 to 0.64], stimulation group showed a slightly better outcome than P=0.29, 2 studies) had no significant advantage in the control (SMD, 0.28 [95% CI,0.01 to 0.55],P=0.04, 4 CD3+improvement. studies,220patients)(Additionalfile2:Figure S1C). We also observed an improvement in the CD4+ Tcell There was no significant difference in the baseline of level (SMD, 0.61 [95% CI, 0.42 to 0.80], P<1E-5, 10 CD3+, CD4+, CD8+ Tcells, NK cells, and IL-2 between studies, 459 patients) (Figure 3B) [20,21,27,36,37,39,42, the acupoint stimulation and control groups as shownin 44,46,47]. Subgroup analysisshowed thatacupointneedle Table3. insertion (SMD, 0.50 [95% CI, 0.19 to 0.82], P=0.002, 4 studies) and acupoint injection with herbs (SMD, 0.72 Bonemarrowsuppression [95%CI, 0.17to0.83],P=0.003,2studies)had advantage The pooled study showed that the prevention against in improving CD4+ while acupoint plaster application hemoglobin reduction was significantly in favor of the (SMD, 0.50 [95% CI, 0.17 to 0.83], P=0.003, 3 studies) acupoint stimulation group (SMD, 0.40 [95% CI, 0.17 to hadnosignificantadvantageinCD4+improvement. 0.63], P=7E-4, 5 studies, 296patients) (Additional file 2: The CD8+ T cell level in patients treated with acu- Figure S2A) [24,42,43,45,49]. There was no significant puncture has shown no significant difference compared heterogeneity amongthesestudies(P=0.64). with the control group (SMD, 0.0 [95% CI, -0.19 to The number of patients with decreased platelets was 0.19],P=1.0,10studies,459patients)(Additionalfile2: significantly reduced in the acupoint stimulation group Figure S1A) [20,21,27,36,37,39,42,44,46,47]. Subgroup (SMD, 0.28[95%CI, 0.05to0.51],P=0.02, 5 studies, 296 analysis showed that acupoint injection with herbs patients)(Additionalfile2:FigureS2B)[24,42,43,45,49]. (SMD=−0.67, 95% CI=-1.15 to -0.20, p=0.006, 2 stu- The inhibition of WBCs in lung cancer patients with dies) had advantage in lowing CD8+, acupoint plaster acupoint stimulation was significant reduced (SMD, 0.93 application (SMD, 0.21 [95% CI, -0.18 to 0.61], P=0.29, [95% CI, 0.44 to 1.42], P<2E-4, 8 studies, 519 patients) 2 studies) had advantage in upregulating CD8+, and [22,24,33,34,42,43,45,49], but there was a prominent Figure2Riskofbiasassessmentamongincludedstudies. Chenetal.BMCComplementaryandAlternativeMedicine2013,13:362 Page7of14 http://www.biomedcentral.com/1472-6882/13/362 Figure3Immunomodulationofacupunctureinlungcancerpatients.(A)CD3+Tcells;(B)CD4+Tcells. Chenetal.BMCComplementaryandAlternativeMedicine2013,13:362 Page8of14 http://www.biomedcentral.com/1472-6882/13/362 Table3Baselineofincludedstudies Index Standardmeandifference95%CI Heterogeneity Overalleffect(Pvalue) Immunomodulation CD3+Tcells 0.07[−0.30,0.44] I2=67% Z=0.35(P=0.72) CD4+Tcells −0.04[−0.31,0.24] I2=52% Z=0.27(P=0.79) CD8+Tcells −0.01[−0.19,0.18] I2=0% Z=0.08(P=0.94) Naturalkillercells −0.38[−1.39,0.62] I2=79% Z=0.75(P=0.45) IL-2 0.05[−0.21,0.32] I2=0% Z=0.39(P=0.70) Bonemarrowsuppression Hemoglobin 0.04[−0.19,0.27] I2=0% Z=0.37(P=0.71) Platelets 0.06[−0.17,0.29] I2=0% Z=0.53(P=0.60) Whitebloodcells 0.07[−0.11,0.24] I2=0% Z=0.75(P=0.45) Clinicalefficacy Karnofskyperformancescore −0.08[−0.25,0.09] I2=0% Z=0.93(P=0.35) heterogeneity among these studies (P=1E-5) (Additional significant advantage in KPS without heterogeneity in file 2: Figure S2C). Sensitivity test showed that removing studies (P=0.0002, P=0.001, and P<0.0001 respec- anyofthestudiesdidnotalterthepatterns,however,there tively).Acupoint needle insertion alsohadno advantage isstillheterogeneityamongthestudies(datanotshown). in KPS, but Zhou et al.’s study in the needle insertion As shown in Table 3, there was no significant differ- group showed a high heterogeneity (P=0.51, I2=79%) ence in the baseline of hemoglobin, platelets, and WBCs compared to the other two studies [48]. The baseline of betweentheacupoint stimulation andcontrol groups. KPS showed no significant difference between the acu- pointstimulationgroupandthecontrolgroup(Table3). Nauseaandvomiting EORTC-QLQ-C30 also showed a total favorable score As shown in Figure 4, the occurrence of chemotherapy- in the acupoint stimulation group compared to the con- induced nausea and vomiting at Grade II-IV was re- trol group (SMD, 0.47 [95% CI, 0.04 to 0.90], P=0.03, 2 markably reduced in the acupoint stimulation group studies, 85 patients) as shown in Figure 6A [31,48]. In comparedtothecontrolgroup(RR,0.46[95%CI,0.37-0.51], addition, the Visual Analog Scale had a significant im- P=1E-5, 8 studies, 501 patients) [19,20,25,26,28,41,42,45]. provement in the acupoint stimulation group compared Subgroup analysis showed that acupoint needle insertion, tothecontrolgroup(SMD,-1.13[95%CI,-1.58to−0.69], acupoint injection with herbs, and moxibustion sig- P<1E-5,2studies,92patients)[20,32](Figure6). nificantly attenuated the grade of nausea and vomiting (P=0.02,P=0.005,andP=0.01,respectively). Discussion In the present study, we systematically reviewed the role Clinicalefficacy of acupoint stimulation in lung cancer management. Our The immediate tumor response indicated that acupoint results showed that acupoint stimulation has immuno- stimulation had a significant advantage compared to the modulatory effect for lung cancer patients, which was controlgroup(RR,1.54[95%CI,1.15to2.07],P=0.004,3 demonstrated by a significant increase of IL-2, CD3+ and studies, 148 patients) (Figure 5A) [20,38,49]. Two studies CD4+Tcells,NKcells,butnotCD8+Tcells.Furtherana- usedacupointinjectionwithherbextractionandoneused lysis also revealed that acupoint stimulation remarkably microwavetreatmentintheassessedstudies. reduces the conventional therapy-induced bone marrow The pooled KPS Scale showed a significant increase of suppression, enhances hemoglobin and platelets in lung clinical performance in the acupoint stimulation group cancer patients, and decreases the chemotherapy-induced compared to the control group (SMD, 0.76 [95% CI, 0.42 nausea and vomiting. In addition, the pooled studies also to 1.10], P<1E-4, 9 studies, 508 patients) as shown in showedthatacupoint stimulation hasanadvantageinthe Figure 5B [25,33,38,41,42,44,45,48,49]. However, the hete- improvement of performance status, immediate tumor rogeneity study showed a significant difference among response,andqualityoflife(EORCT-QLQ-C30). these studies. Sensitivity test indicated a significant in- We found that acupoint stimulation enhances T cell crease of KPS in the acupoint stimulation group with re- subtype CD3+ and CD4+ cells, but not CD8+ cells. Sub- moval of anyone study in the nine studies. Subgroup groupanalysisindicatedthatacupointinsertionandinjec- analysis showed that acupoint injection with herb tion with herb extraction are able to elevate the total extraction, plaster application, and moxibustion had Tcells (CD3+) and T helper cells (CD4+) in lung cancer Chenetal.BMCComplementaryandAlternativeMedicine2013,13:362 Page9of14 http://www.biomedcentral.com/1472-6882/13/362 Figure4Effectiveresponsesofnauseaandvomiting(vomitinggradeIItoIV). patients.Acupoint plaster application enhances CD4+ T increaseofCD8+Tcellscomparedtothecontrolgroup. cells, but not CD3+ T cells. CD8+ is cytotoxic T cells Subgroup analysis showed that acupoint needle inser- which are one of the most effective immune cells to kill tion has no significant effect, while acupoint injection tumor cells [50]. Interestingly, our study showed that with herbs decreases CD8+ Tcells and plaster applica- acupoint stimulation has no significant effect on the tion increases CD8+ T cells in lung cancer patients. Chenetal.BMCComplementaryandAlternativeMedicine2013,13:362 Page10of14 http://www.biomedcentral.com/1472-6882/13/362 Figure5Clinicalefficacy.(A)Tumorresponse;(B)KPS.
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