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Adjuvant chemotherapy does not benefit patients with esophageal squamous cell carcinoma treated with definitive chemoradiotherapy

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Title:
Adjuvant chemotherapy does not benefit patients with esophageal squamous cell carcinoma treated with definitive chemoradiotherapy
Creator:
Mingqiu Chen
Minmin Shen
Yu Lin
Pingping Liu
Xiaohong Liu
Xiqing Li
Anchuan Li
Rongqiang Yang
Wei Ni
Xin Zhou
Lurong Zhang
Benhua Xu
Jianhua Lin
Junqiang Chen
Ye Tian1
Publisher:
BMC, Radiation Oncology
Publication Date:
Language:
English

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Subjects / Keywords:
Adjuvant chemotherapy ( fast )
Concurrent chemoradiotherapy ( fast )
Esophageal squamous cell carcinoma ( fast )
Survival ( fast )

Notes

Abstract:
Background: The aim of the present study was to assess the efficacy of adjuvant chemotherapy (AC) in patients with esophageal squamous cell carcinoma (ESCC) treated with definitive chemoradiotherapy (CRT). Methods: The clinical data of patients with ESCC treated with chemoradiotherapy with or without AC were collected and retrospectively reviewed. The overall survival (OS), locoregional failure-free survival (LFFS) and distant failure-free survival (DFFS) rates were analyzed statistically. Results: A total of 187 patients fulfilled the inclusion criteria, 98 of whom were treated with CRT-alone, while 89 were treated with CRT-AC. Patient characteristics did not significantly differ between the CRT-alone and CRT-AC groups, with the exception of sex and the number of cycles of concurrent chemotherapy. Following CRT, 50 patients achieved complete response (CR), 67 had partial response (PR), 63 patients maintained stable disease (SD) and 7 developed progression of disease (PD). The OS, LFFS and DFFS at 1, 2 and 5 years for the entire cohort were 67.5, 41.4 and 27.2%; 68.7, 57.9 and 52.4%; and 78.5, 68.9 and 63.9%, respectively. The clinical N-stage, M-stage, and short-term response to CRT were identified as significant factors that influenced patient prognosis. No significant differences in OS, LFFS or DFFS were observed between the CRT-alone and CRT-AC groups for the entire cohort and for clinical N-stage, clinical M-stage and short-term response subgroups. Conclusions: The short-term response to CRT and the tumor clinical stage were significant prognosis factors for patients with ESCC treated with CRT. With current chemotherapy regimens, AC did not improve survival for patients with ESCC treated with CRT. The retrospective nature of the current study serves as a limitation; thus, further clinical trials are required to evaluate the efficacy of AC in patients with ESCC treated with CRT. Keywords: Adjuvant chemotherapy, Concurrent chemoradiotherapy, Esophageal squamous cell carcinoma, Survival
General Note:
Chen et al. Radiation Oncology (2018) 13:150 https://doi.org/10.1186/s13014-018-1086-y; Pages 1-8

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University of Florida
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University of Florida
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© The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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mods:abstract displayLabel Abstract Background: The aim of the present study was to assess the efficacy of adjuvant chemotherapy (AC) in patients
with esophageal squamous cell carcinoma (ESCC) treated with definitive chemoradiotherapy (CRT).
Methods: The clinical data of patients with ESCC treated with chemoradiotherapy with or without AC were collected
and retrospectively reviewed. The overall survival (OS), locoregional failure-free survival (LFFS) and distant failure-free
survival (DFFS) rates were analyzed statistically.
Results: A total of 187 patients fulfilled the inclusion criteria, 98 of whom were treated with CRT-alone, while 89 were
treated with CRT-AC. Patient characteristics did not significantly differ between the CRT-alone and CRT-AC groups, with
the exception of sex and the number of cycles of concurrent chemotherapy. Following CRT, 50 patients achieved
complete response (CR), 67 had partial response (PR), 63 patients maintained stable disease (SD) and 7 developed
progression of disease (PD). The OS, LFFS and DFFS at 1, 2 and 5 years for the entire cohort were 67.5, 41.4 and 27.2%;
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with ESCC treated with CRT. The retrospective nature of the current study serves as a limitation; thus, further clinical
trials are required to evaluate the efficacy of AC in patients with ESCC treated with CRT.
Keywords: Adjuvant chemotherapy, Concurrent chemoradiotherapy, Esophageal squamous cell carcinoma, Survival
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Minmin Shen
Yu Lin
Pingping Liu
Xiaohong Liu
Xiqing Li
Anchuan Li
Rongqiang Yang
Wei Ni
Xin Zhou
Lurong Zhang
Benhua Xu
Jianhua Lin
Junqiang Chen
Ye Tian1
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https://doi.org/10.1186/s13014-018-1086-y; Pages 1-8
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mods:topic Adjuvant chemotherapy
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Esophageal squamous cell carcinoma
Survival
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RESEARCHOpenAccess AdjuvantchemotherapydoesnotbenefitpatientswithesophagealsquamouscellcarcinomatreatedwithdefinitivechemoradiotherapyMingqiuChen1,2,3†,MinminShen4†,YuLin5,PingpingLiu4,XiaohongLiu4,XiqingLi4,AnchuanLi3,RongqiangYang6,WeiNi6,XinZhou6,LurongZhang7,8,BenhuaXu3,JianhuaLin7,JunqiangChen5*andYeTian1,2*AbstractBackground:Theaimofthepresentstudywastoassesstheefficacyofadjuvantchemotherapy(AC)inpatientswithesophagealsquamouscellcarcinoma(ESCC)treatedwithdefinitivechemoradiotherapy(CRT).Methods:TheclinicaldataofpatientswithESCCtreatedwithchemoradiotherapywithorwithoutACwerecollectedandretrospectivelyreviewed.Theoverallsurvival(OS),locoregionalfailure-freesurvival(LFFS)anddistantfailure-freesurvival(DFFS)rateswereanalyzedstatistically.Results:Atotalof187patientsfulfilledtheinclusioncriteria,98ofwhomweretreatedwithCRT-alone,while89weretreatedwithCRT-AC.PatientcharacteristicsdidnotsignificantlydifferbetweentheCRT-aloneandCRT-ACgroups,withtheexceptionofsexandthenumberofcyclesofconcurrentchemotherapy.FollowingCRT,50patientsachievedcompleteresponse(CR),67hadpartialresponse(PR),63patientsmaintainedstabledisease(SD)and7developedprogressionofdisease(PD).TheOS,LFFSandDFFSat1,2and5yearsfortheentirecohortwere67.5,41.4and27.2%;68.7,57.9and52.4%;and78.5,68.9and63.9%,respectively.TheclinicalN-stage,M-stage,andshort-termresponsetoCRTwereidentifiedassignificantfactorsthatinfluencedpatientprognosis.NosignificantdifferencesinOS,LFFSorDFFSwereobservedbetweentheCRT-aloneandCRT-ACgroupsfortheentirecohortandforclinicalN-stage,clinicalM-stageandshort-termresponsesubgroups.Conclusions:Theshort-termresponsetoCRTandthetumorclinicalstageweresignificantprognosisfactorsforpatientswithESCCtreatedwithCRT.Withcurrentchemotherapyregimens,ACdidnotimprovesurvivalforpatientswithESCCtreatedwithCRT.Theretrospectivenatureofthecurrentstudyservesasalimitation;thus,furtherclinicaltrialsarerequiredtoevaluatetheefficacyofACinpatientswithESCCtreatedwithCRT.Keywords:Adjuvantchemotherapy,Concurrentchemoradiotherapy,Esophagealsquamouscellcarcinoma,SurvivalBackgroundEsophagealcancerisafrequentlyoccurringtypeofcancerindevelopinganddevelopedcountries[1].Concurrentchemoradiotherapy(CRT)isconsideredtobethestandardtreatmentforpatientswithunresectableesopha-gealcancer[2].Severalchemotherapeuticdrugsandad-vancedradiotherapytechniqueshavebeenappliedtotreatpatientswithesophagealcancerinthepastdecades.The5-yearsurvivalrateofpatientswithesophagealcancertreatedwithCRTremains10–30%[2,3],althoughthesideeffectsoftreatmentweredecreased[4].Uncontrolledtumorgrowthandlocalrecurrenceremaintheprimarydifficultiesassociatedwithradiationtherapy[5].Forpatientswhoencounterthesedifficulties,particularlythosewithuncontrolledtumorgrowthfollowingCRT, *Correspondence:junqiangc@163.com;dryetian@126.com†MingqiuChenandMinminShencontributedequallytothiswork.5DepartmentofRadiationOncology,FujianCancerHospital&FujianMedicalUniversityCancerHospital,No.420,FumaluRoad,JinAnDistrict,FuZhouCity350014,FuJianProvince,People’sRepublicofChina1DepartmentofRadiationOncology,theSecondAffiliatedHospitalofSoochowUniversity,Jiangsu,ChinaFulllistofauthorinformationisavailableattheendofthearticle TheAuthor(s).2018OpenAccessThisarticleisdistributedunderthetermsoftheCreativeCommonsAttribution4.0InternationalLicense(http://creativecommons.org/licenses/by/4.0/),whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedyougiveappropriatecredittotheoriginalauthor(s)andthesource,providealinktotheCreativeCommonslicense,andindicateifchangesweremade.TheCreativeCommonsPublicDomainDedicationwaiver(http://creativecommons.org/publicdomain/zero/1.0/)appliestothedatamadeavailableinthisarticle,unlessotherwisestated.Chenetal.RadiationOncology (2018) 13:150 https://doi.org/10.1186/s13014-018-1086-y

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salvagesurgeryisusedandhasbeendeclaredtoimprovethesurvivalrate[6].Forpatientswhocannotundergoorrefusesalvagesurgery,adjuvantchemotherapy(AC)isoftenthealternative.However,todate,nolargescaleclinicaltrialshavebeenperformedtoconfirmtheefficacyofACfollowingCRTinpatientswithesophagealcancer,thusnoexplicitACguidelinesorconsensushavebeenprovidedinthelatestNationalComprehensiveCancerNetworkguidelines[7].Inthecurrentstudy,theclinicaldataofpatientstreatedwithCRTfollowedwithorwithoutACatthetwoeminentspecialistcancerhospitalsinFujianProv-ince,China,werecollectedretrospectively.PatientdatawereretrospectivelyanalyzedtoexplorethestatusofACinpatientswithesophagealsquamouscellcarcinoma(ESCC)treatedwithCRT.MethodsPatientselectioncriteriaThisretrospectivestudywasapprovedbyFujianMedicalUniversityUnionHospital(No.2016KY001)andFujianProvinceCancerHospital(No.K201427)InstitutionalReviewBoard.Allpatientsprovidedwritteninformedconsentpriortotreatment,andallinformationwasanonymizedpriortoanalysis.Theeligibilityandexclusioncriteriaforthepresentretrospectivestudyweresimilartothatreportedinourpreviousstudy[8].Inbrief,theinclusioncriteriawereasfollows:PatientsdiagnosedwithESCCusinghistologyviaesophagogastroduodenoscopy;70yearsold;EasternCooperativeOncologyGroupscoring(ECOG)2;clinicalstageofTanyNanyM0orM1withsupraclavicularlymphnodemetastasis;sufficientpretreatmentassessmentavail-abletodefinetheclinicalstageandtoassesstheadapta-tionfortreatment(includingsurgery,chemotherapyandradiotherapy);treatedinitiallywithCRTfollowedwithorwithoutAC;nopriorsalvagesurgeryperformed;andsuffi-cientfollow-updataavailableforshort-termtreatmentre-sponseandsurvivalassessment.TheclinicalTNMstagewasdeterminedaccordingtothe8thAmericanJointCommitteeonCancer(AJCC)TNMstagingsystem[9]basedoncomputedtomography(CT)scanfindingsanalyzedbyatleasttworadiologists.CRTconsistedofconcurrentchemotherapy(CC)andradi-ationwiththree-dimensionalconformalradiationtherapy(3D-CRT)orintensitymodulatedradiationtherapy(IMRT).CCwasdefinedaschemotherapywhichstartedlessthan2weeksbeforeor1weekaftertheinitiationofradiotherapy(RT)[10].ACwasdefinedaschemotherapyinitiatedatleast2,butlessthan6weeksafterthecomple-tionofCRT.WhethertheACusedwasthesamedrugasCC,oradifferentdrug,wasdependentontheshort-termresponsetoCRT.AdjustmentstotheACandCCtimeintervalsanddoseintensitieshavebeenreportedinourpreviousstudy[8].Thetargets,includinggrosstumorvolume(GTV),clinicaltargetvolume(CTV)andorgansatrisk(OARs)ofradiotherapy,thetargetsdoseandthedoselimitationsofOARsweredefinedandadjustedasdescribedinourpreviousstudy[8].CriteriafortoxicityandtreatmentresponseThechemotherapyandacuteradiationtoxicityweregradedusingtheNationalCancerInstitutecommontox-icitycriteria(NCICTCv3.0)[11]andtheRadiationTherapyOncologyGroup(RTOG)criteria[12],respectively.Theshort-termresponsetoCRTwasfirstevaluatedonthecompletiondateofCRTandwasreassessedafter4–6weeks.Thetumorshort-termresponsetoCRTwasdefinedastheclinicallycompleteresponse(CR),partialresponse(PR),stabledisease(SD)andprogressionofdisease(PD)usingtheJapaneseClassificationofEsopha-gealCancerguidelines[13].TheseresponseindicatorswerebasedonfindingsfromCTscanningandbariumesophagography,whichwereanalyzedbytworadiolo-gistsandconfirmedbyendoscopicbiopsy.SurveillanceandstatisticalanalysisThefollow-upscheduleforpatientswasaspreviouslyre-ported[8].Inbrief,patientswereevaluatedevery3monthsforthefirst2yearsafterCRT,every6monthsforthenext3years,andthenonceannually.AllpatientoutcomeswereevaluatedinMarch2018.Theprimaryendpointwasoverallsurvival(OS).Thesecondaryendpointswerelocoregional(primarytumorandregionalnode,includingthesupracla-vicularlymphnode)failure-freesurvival(LFFS)anddistantfailure-freesurvival(DFFS).TheOSwascalculatedfromthedateofdiagnosistothedateofmortalityorlastfollow-up.TheLFFSandDFFSweredefinedasthedur-ationbetweenthedateofdiagnosistolocoregionalprogres-sion,anddistantprogression,respectively.DatawereanalyzedusingSPSSversion18.0(SPSS,Inc.,Chicago,IL,USA).SurvivalcurveswereproducedusingtheKaplan-Meierestimatormethodandcomparedwiththelog-ranktest.Multivariableanalysisofclinicalcharacteristics(includinggender,age,ECOGscore,tumorlocation,clinicalTNMstages,theradiotherapydoseofGTVandCTV,regimensandcyclesofCC,andshort-termtumorresponsetoCRT)wasperformedusingtheCoxpro-portionalhazardsmodel.Confidenceintervals(CI)repre-sented95%lowerandupperbounds.P0.05wasconsideredtoindicateastatisticallysignificantdifference.ResultsPatientcharacteristicsBetweenSeptember1,2004andDecember31,2015,atotalof577patientstreatedwithdefinitiveCRTwereChenetal.RadiationOncology (2018) 13:150 Page2of8

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reviewed.Atotalof193patientsfulfilledtheinclusioncriteria,ofwhom3patientswereadministeredwithsingle-agentCCand3patientssuccumbedtoacuteradiation-inducedpneumonitisfollowingCRT.Thesepatientswereexcluded.Datafromtheremaining187pa-tientswerecollectedforanalysis.98patientsweredealtwithCRT-aloneand89weretreatedwithCRT-AC.Nosignificantdifferencesinclinicalcharacteristicswereidentifiedbetweenthetwogroups,withtheexceptionofsexandcyclenumberofCC(Table1),whichdidnotin-fluencepatientsurvivalintheunivariateandmultivari-ateanalyses.Amediannumberof2(range,1–3)cyclesofCCwereadministratedtoallenrolledpatients.TheregimensofCCincludedadual-agentplatinumcompound(cisplatin,lobaplatin,nidaplatinumoroxaliplatin)plusfluoropyri-midine(5-fluorouracilorcapecitabine;PF)oraplatinumcompoundplustaxane(paclitaxelordocetaxel;TP)[14,15].ThedifferencesinCCregimenswerenotsignificantbetweentheCRT-aloneandCRT-ACgroups(Table1).Tumorresponse,failurepatternandsurvivalFollowingCRT,50(26.7%)patientsachievedCR(26inCRT-aloneand24inCRT-AC),67(35.8%)hadPR(37and30,respectively),63(33.7%)maintainedSD(31and32,respectively)and7(3.7%)developedPD(4and3,re-spectively)(Table2).ThetreatmentfailurepatternsarepresentedinTable2.Atthelastfollow-up,54patientsremainedalive,133patientssuccumbed.Ofthese,114patientssuccumbedtothedisease(61forlocoregionalrecurrence,46fordis-tantmetastasis,7forbothlocoregionalanddistant)and19patientssuccumbedforunknownreasons.Theme-dianfollow-uptimeinthecurrentstudywas20months(range,3–124months).TheOS,LFFSandDFFSat1,2and5yearsfortheentirecohortwere67.5,41.4and27.2%;68.7,57.9and52.4%;and78.5,68.9and63.9%,respectively.NosignificantdifferencesinOS,LFFSorDFFSwereobservedbetweentheCRT-aloneandCRT-ACgroups(Table2;Figs.1and2).UnivariateandmultivariateanalysesindicatedthatclinicalN-stage,clinicalM-stageandshort-termre-sponsetoCRTweresignificantfactorsthatinfluencedOS(Table3andFig.3).ClinicalN-stageandshort-termresponsetoCRTwerethefactorstosignificantlyinflu-enceLFFS,whereasclinicalN-stageandM-stagewerethefactorstosignificantlyinfluenceDFFS(Table3).PatientswhoachievedCRhadimprovedsurvivalratescomparedwithnon-CR(PR,SDandPD)intermsofOS,LFFSandDFFS.Furthermore,thesurvivalrateswerenotsignificantlydifferentamongnon-CRpatients.Notably,PRpatientsexhibitedworseOScomparedwithSDpatients;however,thisdifferencewasnotstatisticallysignificant(Fig.3C).Thisobservationmaybeexplained Table1ClinicalcharacteristicsofpatientsCharacteristicsCRTaloneCRT-ACX2pGender4.9040.027Male7277Female2612Medianage(y,range)59(40–70)58(43–70)0.0820.265ECOGscoring4.3420.1160202617663220Tumorlocation0.1740.982Cervical1212Upper4034Middle3836Lower87ClinicalTstage0,4230.809T21112T34638T44139ClinicalNstage3.7610.153N01821N17065N2103ClinicalMstage00.997M07669M12220Clinicalstage2.5020.475II1720III2918IVA3031IVB2220Dose(Gy,range)GTV61.5(50–66)61.5(50–66)0.0230.755CTV50(45–54)50(45–50.4)0.0810.282CyclesofCC8.2940.0161341926261329RegimenofCC0.2960.586PF1612TP8277CCconcurrentchemotherapy;CRT-ACchemoradiotherapyfollowedwithadjuvantchemotherapy;CRTconcurrentchemoradiotherapy;ECOGEasternCooperativeOncologyGroupscoring;GTVgrosstumorvolume;CTVclinicaltargetvolume;PFplatinumplusfluorouracil;TPplatinumplustaxane;M1supraclavicularlymphnodemetastasisChenetal.RadiationOncology (2018) 13:150 Page3of8

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byPRpatientsexhibitingworseclinicalNandMstagescomparedwithSDpatients,whichwerebothidentifiedassignificantprognosticfactors.AdjuvantchemotherapyandsurvivalAmediannumberof2(range,1–4)cyclesofACwereperformedinpatientswhoreceivedAC.TheregimensofACandCCwerethesameinCRandPRpatients.Only5SDpatientshadtheirtreatmentregimenchangedfromCCtoAC,whereasall3PDpatientsintheACgrouphadtheirtreatmentregimenchanged.AstherearesofeweffectivechemotherapydrugsforESCC,ifadifferentdrugwasrequiredforAC,thedrugwouldbechangedfromPFtoTPorviceversa,withdifferentcompoundsforT,ForP.ToidentifypatientswhomaybenefitfromAC,weconductedfurtheranalysisamongvarioussubgroupsofpatientsbasedondifferentsignificantprognosticfactors,includingclinicalN-stage(N0,1and2),clinicalM-stage(M0andM1)andshort-termresponsetoCRT(CR,PR,SDandPD).Nosignificantdifferencesinsurvival(OS,LFFSandDFFS)betweenpatientstreatedwithCRT-ACorCRT-alonewereobservedforanysubgroups(Table4).DiscussionHishikawaetal.[16]hadfirstlyconductedarandomizedclinicaltrialtoevaluatethebenefitsofACinpatientswithESCCtreatedwithRTinJapanin1991.Inthisstudy,patientswithunresectableesophagealcancerwererandomizedandtreatedwithRTfollowedwithorwith-outAC.Theresultsindicatedthat,comparedwithRT-alone,ACdidnotimprovethesurvivalofpatientstreatedwithRT-AC.However,thebiggestlimitationofthisresearchwasthatpatientsweretreatedwithRT-alone,whichhadbeenverifiedtohavepoorereffi-cacycomparedwithCRTinnumerousclinicaltrialsandmightimpactthebenefitsofAC[17].Tothebestofourknowledge,nostudieshavebeenperformedtospecificallyinvestigatetheeffectsofACfollowingCRTwithoutpriorsalvagesurgery,andthecurrentstudytooktheleadindiscussingtheefficacyofACinpatientswithESCCtreatedwithCRT.Unfortu-nately,similarlytoHishikawa’sresultsasmanifestedinthisstudy,comparedwithCRT-alone,ACfollowingCRThadnotdemonstratedsignificantsurvivalbenefits Table2Tumorresponse,failurePatternandsurvivalCRT-aloneCRT-ACTotalp*Tumorresponse,n(%)0.91CR26(26.5)24(27.0)50(26.7)PR37(37.8)30(33.7)67(35.8)SD31(31.6)32(36.0)63(33.7)PD4(4.1)3(3.3)7(3.7)Patternoffailure,n(%)0.399Locoregionalalone30(16.1)35(18.7)65(34.8)Locoregionalanddistant6(3.2)2(1.1)8(4.3)Distantalone26(13.9)21(11.2)47(25.1)1,2,5ysurvivalrates(%)OS66.7,39.1,27.675.3,47.1,26.967.5,41.4,27.20.732LFFS70.4,57.2,55.169.7,58.6,49.868.7,57.9,52.40.876DFFS74.1,65.3,6383.3,73,65.478.5,68.9,63.90.200*:pvaluebetweenCRT-aloneandCRT-AC Fig.1TheOS,LFFS,DFFSintheentirecohortofpatientsChenetal.RadiationOncology (2018) 13:150 Page4of8

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Fig.2TheOS(a),LFFS(b),DFFS(c)betweenCRTaloneandCRT-ACintheentirecohortofpatients Table3PrognosticfactorsbyunivariateandmultivariateanalysesOSLFFSDFFSOSLFFSDFFSPrognosticfactorspHR(95.0%CI)pHR(95.0%CI)pHR(95.0%CI)pHR(95.0%CI)pHR(95.0%CI)pHR(95.0%CI)Gender0.380.817(0.521–1.281)0.370.75(0.406–1.402)0.960.984(0.508–1.907)Age0.701.005(0.980–1.031)0.030.97(0.934–0.997)0.031.049(1.005–1.094)ECOG0.600.904(0.622–1.313)0.510.85(0.521–1.385)0.681.133(0.627–2.050)Tumorlocation0.050.814(0.661–1.001)0.010.69(0.518–0.905)0.640.927(0.671–1.279)ClinicalTstage0.191.191(0.919–1.543)0.981.00(0.714–1.414)0.471.158(0.775–1.730)ClinicalNstage<0.012.996(2.037–4.408)0.002.68(1.671–4.289)<0.012.495(1.440–4.324)<0.012.465(1.612–3.769)<0.012.293(1.384–3.798)<0.012.418(1.345–4.346)ClinicalMstage<0.012.142(1.463–3.136)0.021.83(1.094–3.046)<0.012.463(1.391–4.362)<0.011.856(1.268–2.716)<0.012.424(1.358–4.238)ClinicalTNMstage<0.011.402(1.181–1.665)0.031.29(1.023–1.616)<0.011.487(1.133–1.953)CyclesofCC0.950.990(0.719–1.365)0.831.05(0.682–1.608)0.200.725(0.442–1.187)RegimenofCC0.070.646(0.405–1.030)0.870.94(0.485–1.481)0.631.235(0.529–2.884)DoseofGTV0.511.000(0.999–1.000)0.061.00(0.999–1.000)0.811.000(0.999–1.001)DoseofCTV0.181.001(0.999–1.003)0.781.00(0.999–1.002)0.701.000(0.998–1.002)TumorresponsetoCRT<0.011.691(1.389–2.060)<0.011.71(1.315–2.228)0.441.127(0.834–1.524)<0.011.548(1.262–1.899)<0.011.532(1.162–2.021)AC0.740.971(0.819–1.152)0.881.02(0.809–1.281)0.210.841(0.643–1.100)CCconcurrentchemotherapy;GTVgrosstumorvolume;CTVclinicaltargetvolume;CRTconcurrentchemoradiotherapy;ACadjuvantchemotherapyChenetal.RadiationOncology (2018) 13:150 Page5of8

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inpatientswithESCC.InsufficientsurvivalbenefitsofACwereusuallyownedtopatientintolerancetointensiveACresultingfromtheacutetoxicityofCRT[18].Therefore,combinationsofnewerandmoretolerablechemothera-peuticagentsbefore,ratherthanafter,CRTtoimprovetheefficacyofradiotherapyshouldbeconsidered[19].Itiswellestablishedthattheinitialstageofcanceristhemostimportantindeterminingtheprognosisandtreatmentplan.Thelaterthestaging,theworsetheprognosisofpatients,andthisoftenmeansthatpatientsrequiremoreintensetreatments,suchaschemotherapy,inordertoimprovesurvival.ToidentifywhetherintensetreatmentssuchasACmayimprovethesurvivalofpa-tientsatdifferenttumorstages,weperformedastratifiedanalysisofdifferentstagingfactors,includingclinicalNandMstages,thatwererecognizedasindependentprognosisfactorsinthepresentstudy.However,ourre-sultsrevealednosignificantdifferencesinsurvivalforsubgroupsstratifiedbyN-stage(N0–2)orM-stage(M0andM1)treatedwithorwithoutAC.Noteworthy,pa-tientswithN2orM1(supraclavicularlymphnodeme-tastasis)stagewhowereregardedaspronetodevelopdistantorganmetastasesandinitiallyexpectedtobenefitfromAC,failedtodemonstrateasurvivaladvantagewiththeuseofACinthecurrentstudy.Thisindicatedthatmoreintensivechemotherapyregimenstoeradicateoccultmetastaseswereurgentlyneededtoimprovepa-tientoutcomes[20]. Fig.3TheOSinvarioussubgroupsofindependentsignificantfactorsN-stage(a),M-stage(b)andshort-termresponse(c) Table4EfficacyofACindifferentsubgroups1,2,5-yOS1,2,5-yLFFS1,2,5-yDFFSCRT-aloneCRT-ACpCRT-aloneCRT-ACpCRT-aloneCRT-ACpClinicalNstageN076.5,58.8,52.395.0,81.0,66.70.29769.3,69.3,69.395.2,95.2,89.60.10594.4,87.2,87.295.2,89.6,89.60.777N168.2,37.9,23.579.0,33.6,14.40.32469.7,58.8,55.362.6,45.7,31.30.13168.9,60.7,57.378.5,68.3,53.40.377N240.0,26.7,0.033.0,0.0,0.00.78551.9,0.0,.0.033.3,33.3,33.30.87780.0,53.3,53.30.0,0.0,0.00.942ClinicalMstageM071.7,45.8,35.579.7,57.0,31.00.88070.0,61.0,61.070.6,63.5,57.10.86079.5,70.3,67.589.6,79.4,79.40.191M150.0,18.2,4.550.0,18.7,12.50.93660.6,44.2,29.567.3,26.9,0.00.69252.6,46.1,46.159.2,47.4,47.40.792ClinicalTNMstageII75.3,43.9,43.995.0,80.0,55.00.20872.7,58.2,58.290.0,90.0,84.40.07981.6,74.2,74.295.0,95.0,87.10.195III71.7,37.9,33.261.1,38.9,16.70.37868.8,51.6,51.659.3,37.6,37.60.54961.4,62.2,62.287.7,68.2,56.80.598IVA69.7,54.9,33.867.7,38.7,23.50.65177.8,72.9,72.964.2,59.9,47.20.12086.7,76.6,69.786.6,71.9,63.90.878short-termresponseCR88.5,76.5,58.4100,87.5,78.00.27488.0,79.4,74.195.8,91.3,84.20.27684.4,76.2,71.195.8,83.3,74.80.590PR46.1,17.1,1260.0,20.0,0.00.99855.4,50.8,50.868.2,52.8,33.00.95460.6,48.6,48.667.9,55.7,55.70.470SD77.4,36.1,2456.3,37.2,22.30.61665.7,48.3,48.350.8,36.9,31.60.27780.3,72.3,72.392.8,86.2,77.60.117PD25.0,0.0,0.033.3,0.0,0.00.70433.3,33.3,33.366.7,66.7,66.70.64275.0,75.0,75.00.0,0.0,0.00.247M1:supraclavicularlymphnodemetastasisChenetal.RadiationOncology (2018) 13:150 Page6of8

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Asdemonstratedhereandinpreviousstudies[8,21],theshort-termresponsetoCRTisapowerfulpredictorofsurvivalinpatientswithESCCtreatedwithCRT.PatientswhoachieveCRexhibitimprovedsurvivalratescomparedwithnon-CRpatientsintermsofOS,LFFSandDFFS.However,nosignificantdifferencesinsurvivalrateswereobservedamongnon-CRpatients(PRvs.SD).Theseresultsareconsistentwiththedatafromourpre-vioussingle-centerstudy[8],suggestingthataggressivetreatmentsuchasescalatingirradiation-doseoftumorbymodernradiationtechniquestoobtainbettershort-termresponseshouldbeexecuted[22].Inprecedingstudies,thebenefitsofACinESCCpa-tientstreatedwithtrimodaltherapy(neoadjuvantCRT,surgeryandAC,TMT)havevarieddependingontheshort-termresponsetoCRT,andevenwithinshort-termresponsesubgroups,theresultshavebeeninconsistent.Tametal.....reportedthatACinTMTimprovedtheOSinpatientswithPRtoneoadjuvantCRT,butnotincompleterespondersandnon-responders[23].While,Kimetal[24]foundthatAConlyimprovedtheOSinpatientswithgrossresidualdisease,butnotpatientswithCRormacroscopicresidualdisease.Incontrast,anovelstudyfromSaeedetalindicatedthatACdidnotimprovesurvivalinpatientstreatedwithTMTregardlessoftheresponsetoneoadjuvantCRT[25].However,nostudieshadbeenperformedtoidentifywhichshort-termresponsesubgroupsofpatientswithESCCwouldbenefitfromACfollowingCRTwithoutsurgery.Disappoint-ingly,comparedwithCRT-alone,AChadnotdemon-stratedprolongationofsurvivalinvariousresponsesubgroupsofpatientsinthecurrentstudy.Thediscrep-ancybetweenourresultsandotherstudiesindicatestheneedforfurtherprospectiverandomizedclinicaltrialstodeterminewhethercertainsubgroupsofpatientswhomightpotentiallybenefitfromACcanbeidentifiedbasedonshort-termresponsetoCRT.Therewerecertainlimitationstothepresentstudy,suchastheretrospectivedesign,theinadequateintensityofchemotherapyandunifiedchemotherapyregimens,thelackofchangewithadjuvantCCinpatientswithSDre-sponsetoCRT,thelowernumberofACcycles,andthesuboptimalassessmentofshort-termresponsebyCTscan.Duetotheselimitations,theresultsofourinvestiga-tionmustbeinterpretedwithcaution.Inaddition,theroleofACasapossiblepalliativetherapytorelievedysphagia,whichisthemostcommonsymptomofesophagealcancerseriouslyaffectingthequalityoflifeofthepatients[14],hasnotbeendiscussedinthecurrentstudy.ConclusionsTheshort-termresponsetoCRTandthetumorclinicalstagewereidentifiedassignificantprognosisfactorsforpatientswithESCC.Withthecurrentchemotherapyregimens,ACdidnotprovideanysignificantimprove-mentsinpatientsurvivalfollowingCRT.Theretrospect-ivenatureofthecurrentstudyisalimitation;thus,furtherclinicaltrialsarerequiredtoevaluatetheefficacyofACinpatientswithESCCtreatedwithCRT.Abbreviations3D-CRT:three-dimensionalconformalradiationtherapy;AC:adjuvantchemotherapy;AJCC:AmericanJointCommitteeonCancer;CC:concurrentchemotherapy;CI:Confidenceintervals;CR:completeresponse;CRT:Concurrentchemoradiotherapy;CT:computedtomography;CTV:clinicaltargetvolume;DFFS:distantfailure-freesurvival;ECOG:EasternCooperativeOncologyGroup;ESCC:esophagealsquamouscellcarcinoma;GTV:grosstumorvolume;IMRT:intensitymodulatedradiationtherapy;LFFS:Locoregionalfailure-freesurvival;NCICTC:NationalCancerInstitutecommontoxicitycriteria;OAR:organatrisk;OS:overallsurvival;PD:progressionofdisease;PF:platinumcompoundplusfluoropyrimidine;PR:partialresponse;RT:radiotherapy;RTOG:RadiationTherapyOncologyGroup;SD:stabledisease;TP:platinumcompoundplustaxaneFundingThisstudywassupportedinpartbygrantsfromtheFujianProvincialHealth&FamilyPlanningCommission(ProjectNumber:2016-ZQN-32);theFujianProvincialDepartmentofScience&Technology(ProjectNumber:2018J01306);theFujianProvincialJointFundsfortheInnovationofScienceandTechnology(Projectnumber:2017Y9079);theFujianPlatformforMedicalResearchatFirstAffiliatedHospitalandtheFujianKeyLabofIndividualizedActiveImmunotherapy&KeyLabofRadiationBiology(ProjectNumber:FYKFKT-2017015).AvailabilityofdataandmaterialsThedatasetgeneratedandanalyzedduringthecurrentstudyareavailablefromthecorrespondingauthoronreasonablerequest.AuthorsÂ’contributionsMingqiuChen,MinminShen,YeTianandJunqiangChenconceivedthestudy,manuscript,andstasticsanalysis;YuLin,PingpingLiu,XiaohongLiu,XiqingLi,JianyuanSongandAnchuanLiassistancewithcollectingclinicaldata;RongqiangYang,WeiNi,XinZhou,YeTian,BenhuaXu,LurongZhangandJianhuaLinprovidedassistancewithstudydesignandrevisionsofthemanuscript;Allauthorsreadandapprovedthefinalmanuscript.EthicsapprovalandconsenttoparticipateThestudywasapprovedbyFujianMedicalUniversityUnionHospital(No.2016KY001)andFujianProvinceCancerHospital(No.K201427)InstitutionalReviewBoard.Writteninformedconsentforscientificusageofclinicaldatawasobtainedfromallpatients.ConsentforpublicationConsentforscientificusageofclinicaldatawasobtainedfromallpatientsincludedinthestudy.CompetinginterestsTheauthorsdeclarethattheyhavenocompetinginterests.PublisherÂ’sNoteSpringerNatureremainsneutralwithregardtojurisdictionalclaimsinpublishedmapsandinstitutionalaffiliations.Authordetails1DepartmentofRadiationOncology,theSecondAffiliatedHospitalofSoochowUniversity,Jiangsu,China.2InstituteofRadiotherapy&Oncology,SoochowUniversity,Jiangsu,China.3DepartmentofRadiationOncology,FujianMedicalUniversityUnionHospital,No.29,XinQuanRoad,GuLouDistric,FuZhouCity,FuJianProvince,China.4FujianMedicalUniversity,Fuzhou,China.5DepartmentofRadiationOncology,FujianCancerHospital&FujianMedicalUniversityCancerHospital,No.420,FumaluRoad,JinAnDistrict,FuZhouCity350014,FuJianProvince,PeopleÂ’sRepublicofChina.6CancerandGeneticsResearchComplex,DepartmentMolecularGeneticsandMicrobiology,CollegeMedicine,UniversityofFlorida,Gainesville,USA.7FujianKeyLabofIndividualizedActiveChenetal.RadiationOncology 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ImmunotherapyandKeyLabofRadiationBiologyofFujianProvinceUniversities,Fuzhou,China.8FujianPlatformforMedicalResearchatFirstAffiliatedHospital,Fuzhou,China.Received:27April2018Accepted:25July2018 References1.TorreLA,BrayF,SiegelRL,FerlayJ,Lortet-TieulentJ,JemalA.Globalcancerstatistics,2012.CACancerJClin.2015;65(2):87–108.2.CooperJS,GuoMD,HerskovicA,MacdonaldJS,MartensonJAJr,Al-SarrafM,ByhardtR,RussellAH,BeitlerJJ,SpencerS,etal.Chemoradiotherapyoflocallyadvancedesophagealcancer:long-termfollow-upofaprospectiverandomizedtrial(RTOG85-01).Radiationtherapyoncologygroup.JAMAjAmMedAssoc.1999;281(17):1623–7.3.GwynneS,HurtC,EvansM,HoldenC,VoutL,CrosbyT.Definitivechemoradiationforoesophagealcancer--astandardofcareinpatientswithnon-metastaticoesophagealcancer.ClinOncol.2011;23(3):182–8.4.WangH,MuX,HeH,ZhangXD.CancerRadiosensitizers.TrendsPharmacolSci.2018;39(1):24–48.5.VersteijneE,vanLaarhovenH,vanHooftJ,vanOsR,GeijsenE,vanBergeHM,HulshofM.Definitivechemoradiationforpatientswithinoperableand/orunresectableesophagealcancer:locoregionalrecurrencepattern.DisEsophagus.2015;28(5):453–9.6.SudoK,XiaoL,WadhwaR,ShiozakiH,ElimovaE,TaketaT,BlumMA,LeeJH,BhutaniMS,WestonB.Importanceofsurveillanceandsuccessofsalvagestrategiesafterdefinitivechemoradiationinpatientswithesophagealcancer.JClinOncol.2014;32(30):3400.7.AjaniJEA,D’AmicoTA,BaggstromM,BentremDJ,ChaoJ,DasP,DenlingerCS,EnzingerPC,FantaP,FarjahFetal:EsophagealandEsophagogastricJunctionCancers.2018https://www.nccnorg/professionals/physician_gls/pdf/esophagealpdf.8.ChenMQ,LinQL,ChenYG,GuoJH,XuBH,TianY.Neoadjuvantchemotherapymaynotbenefitesophagealsquamouscellcarcinomapatientstreatedwithdefinitivechemoradiotherapy.JChineseMedAssocJCMA.2017;80(10):636–43.9.RiceTW,GressDM,PatilDT,HofstetterWL,KelsenDP,BlackstoneEH.Canceroftheesophagusandesophagogastricjunction—majorchangesintheAmericanjointcommitteeonCancereightheditioncancerstagingmanual.CACancerJClin.2017;67(4):304–17.10.WalravenI,DamhuisR,TenBergeM,RosskampM,vanEyckenL,deRuysscherD,BelderbosJ.TreatmentvariationofsequentialversusconcurrentChemoradiotherapyinstageIIInon-smallcelllungCancerpatientsintheNetherlandsandBelgium.ClinOncol.2017;29(11):e177–85.11.TrottiA,ColevasAD,SetserA,RuschV,JaquesD,BudachV,LangerC,MurphyB,CumberlinR,ColemanCN,etal.CTCAEv3.0:developmentofacomprehensivegradingsystemfortheadverseeffectsofcancertreatment.SeminRadiatOncol.2003;13(3):176–81.12.CoxJD,StetzJ,PajakTF.Toxicitycriteriaoftheradiationtherapyoncologygroup(RTOG)andtheEuropeanOrganizationforResearchandTreatmentofCancer(EORTC).IntJRadiatOncolBiolPhys.1995;31(5):1341–6.13.JapanEsophagealS.JapaneseClassificationofEsophagealCancer,11thEdition:partIIandIII.Esophagus.2017;14(1):37–65.14.ChenMQ,ChenC,LuHJ,XuBH.Theefficacyandtoxicitiesofcombinedlobaplatinwithpaclitaxelasafirst-linechemotherapyforadvancedesophagealsquamouscellcarcinoma.Jthoracdis.2015;7(10):1749–55.15.ChenJ,SuT,LinY,WangB,LiJ,PanJ,ChenC.Intensity-modulatedradiotherapycombinedwithpaclitaxelandplatinumtreatmentregimensinlocallyadvancedesophagealsquamouscellcarcinoma.ClintransoncoloffipublicFederationSpanishOncolSocNationalCanInsMexico.2018;20(3):411–9.16.HishikawaY,MiuraT,OshitaniT,YoshimuraH,OnoK,TakahashiM,NakajimaT,MurakamiM,IkedaH,ImanakaK.Arandomizedprospectivestudyofadjuvantchemotherapyafterradiotherapyinunresectableesophagealcarcinoma.DisEsophagus.1991;4(2):85–90.17.Al-SarrafM,MartzK,HerskovicA,LeichmanL,BrindleJS,VaitkeviciusVK,CooperJ,ByhardtR,DavisL,EmamiB.Progressreportofcombinedchemoradiotherapyversusradiotherapyaloneinpatientswithesophagealcancer:anintergroupstudy.JClinOncol.1997;15(1):277–84.18.ChenL,HuC-S,ChenX-Z,HuG-Q,ChengZ-B,SunY,LiW-X,ChenY-Y,XieF-Y,LiangS-B.Concurrentchemoradiotherapyplusadjuvantchemotherapyversusconcurrentchemoradiotherapyaloneinpatientswithlocoregionallyadvancednasopharyngealcarcinoma:aphase3multicentrerandomisedcontrolledtrial.lancetoncol.2012;13(2):163–71.19.MaN-Y,CaiX-W,FuX-L,LiY,ZhouX-Y,WuX-H,HuX-C,FanM,XiangJ-Q,ZhangY-W.Safetyandefficacyofnimotuzumabincombinationwithradiotherapyforpatientswithsquamouscellcarcinomaoftheesophagus.IntJClinOncol.2014;19(2):297–302.20.OhnumaH,SatoY,HirakawaM,OkagawaY,OsugaT,HayashiT,SatoT,MiyanishiK,KobuneM,TakimotoR.APhase1/2StudyofDefinitiveChemoradiationTherapyUsingDocetaxel,Nedaplatin,and5-Fluorouracil(DNF-R)forEsophagealCancer.IntJRadiatOncolBiolPhysics.2015;93(2):382–90.21.AdenisA,TreschE,DewasS,RomanoO,MessagerM,AmelaE,ClisantS,KramarA,MarietteC,MirabelX.Clinicalcompleteresponderstodefinitechemoradiationorradiationtherapyforoesophagealcancer:predictorsofoutcome.BMCCancer.2013;13(1):413.22.ChangCL,TsaiHC,LinWC,ChangJH,HsuHL,ChowJM,YuanKS,WuATH,WuSY.Doseescalationintensity-modulatedradiotherapy-basedconcurrentchemoradiotherapyiseffectiveforadvanced-stagethoracicesophagealsquamouscellcarcinoma.RadiotherapyoncoljEuropSocTherapRadiolOncol.2017;125(1):73–9.23.TamV,HookerCM,MolenaD,HulbertA,LeeB,KleinbergL,YangSC,ForastiereAA,BrockM.Clinicalresponsetoneoadjuvanttherapytopredictsuccessofadjuvantchemotherapyforesophagealadenocarcinoma.In:AmericansocietyofClinicalOncology;2014.24.KimGJ,KoshyM,HanlonAL,HoribaMN,EdelmanMJ,BurrowsWM,BattafaranoRJ,SuntharalingamM.ThebenefitofchemotherapyinesophagealCancerpatientswithresidualdiseaseafterTrimodalitytherapy.AmJClinOncol.2016;39(2):136–41.25.SaeedNA,MellonEA,MeredithKL,HoffeSE,ShridharR,FrakesJ,FontaineJP,PimientoJM,KothariN,AlmhannaK.Adjuvantchemotherapyandoutcomesinesophagealcarcinoma.JGastrointestOncol.2017;8(5):816–24. 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