recist1.1中英文校準(zhǔn)完整版

1.Background1背景HistoryofRECISTcriteriaRECIST標(biāo)準(zhǔn)的歷史Assessmentofthechangeintumourburdenisanimportantfeatureoftheclinicalevaluationofcancertherapeutics.Bothtumourshrinkage(objectiveresponse)andtimetothedevelopmentofdiseaseprogressionareimportantendpointsincancerclinicaltrials.TheuseoftumourregressionastheendpointforphaseIItrialsscreeningnewagentsforevidenceofanti-tumoureffectissupportedbyyearsofevidencesuggestingthat,formanysolidtumours,agentswhichproducetumourshrinkageinaproportionofpatientshaveareasonable(albeitimperfect)chanceofsubsequentlydemonstratinganimprovementinoverallsurvivalorothertimetoeventmeasuresinrandomisedphaseIIIstudies(reviewedin[1],[2],[3]and[4]).AtthecurrenttimeobjectiveresponsecarrieswithitabodyofevidencegreaterthanforanyotherbiomarkersupportingitsutilityasameasureofpromisingtreatmenteffectinphaseIIscreeningtrials.Furthermore,atboththephaseIIandphaseIIIstageofdrugdevelopment,clinicaltrialsinadvanceddiseasesettingsareincreasinglyutilisingtimetoprogression(orprogression-freesurvival)asanendpointuponwhichefficacyconclusionsaredrawn,whichisalsobasedonanatomicalmeasurementoftumoursize.評(píng)價(jià)腫瘤負(fù)荷的改變是癌癥治療的臨床評(píng)價(jià)的一個(gè)重要特征。腫瘤縮?。陀^緩解）和疾病進(jìn)展時(shí)間都是癌癥臨床試驗(yàn)中的重要終點(diǎn)。為了篩查新的抗腫瘤藥物，腫瘤縮小作為II期試驗(yàn)重點(diǎn)被多年研究的證據(jù)所支持。這些研究提示對(duì)于多種實(shí)體腫瘤來(lái)說(shuō)，促使部分病人腫瘤縮小的藥物以后都有可能（盡管不完美）被證實(shí)可提高在隨機(jī)Ⅲ期試驗(yàn)中病人的總體生存期或進(jìn)入其他事件評(píng)價(jià)的可能。目前在Ⅱ期篩查試驗(yàn)中評(píng)價(jià)治療效果的指標(biāo)中，客觀緩解比任何其他生物標(biāo)記更可靠。而且，在Ⅱ和Ⅲ期藥物試驗(yàn)中，進(jìn)展期疾病中的臨床試驗(yàn)正越來(lái)越利用疾病進(jìn)展的時(shí)間（無(wú)進(jìn)展生存）作為得出有治療效果結(jié)論的終點(diǎn)，而這些也是建立在腫瘤大小的解剖學(xué)測(cè)量基礎(chǔ)上。However,bothofthesetumourendpoints,objectiveresponseandtimetodiseaseprogression,areusefulonlyifbasedonwidelyacceptedandreadilyappliedstandardcriteriabasedonanatomicaltumourburden.In1981theWorldHealthOrganisation(WHO)firstpublishedtumourresponsecriteria,mainlyforuseintrialswheretumourresponsewastheprimaryendpoint.TheWHOcriteriaintroducedtheconceptofanoverallassessmentoftumourburdenbysummingtheproductsofbidimensionallesionmeasurementsanddeterminedresponsetotherapybyevaluationofchangefrombaselinewhileontreatment.5However,inthedecadesthatfollowedtheirpublication,cooperativegroupsandpharmaceuticalcompaniesthatusedtheWHOcriteriaoften‘modified‘themtoaccommodatenewtechnologiesortoaddressareasthatwereunclearintheoriginaldocument.Thisledtoconfusionininterpretationoftrialresults6andinfact,theapplicationofvaryingresponsecriteriawasshowntoleadtoverydifferentconclusionsabouttheefficacyofthesameregimen.7Inresponsetotheseproblems,anInternationalWorkingPartywasformedinthemid1990stostandardiseandsimplifyresponsecriteria.Newcriteria,knownasRECIST(ResponseEvaluationCriteriainSolidTumours),werepublishedin2000.8KeyfeaturesoftheoriginalRECISTincludedefinitionsofminimumsizeofmeasurablelesions,instructionsonhowmanylesionstofollow(upto10;amaximumfiveperorgansite),andtheuseofunidimensional,ratherthanbidimensional,measuresforoverallevaluationoftumourburden.Thesecriteriahavesubsequentlybeenwidelyadoptedbyacademicinstitutions,cooperativegroups,andindustryfortrialswheretheprimaryendpointsareobjectiveresponseorprogression.Inaddition,regulatoryauthoritiesacceptRECISTasanappropriateguidelinefortheseassessments.然而這些腫瘤終點(diǎn)、客觀緩解和疾病進(jìn)展時(shí)間，只有建立在以腫瘤負(fù)荷解剖學(xué)基礎(chǔ)上的廣泛接受和容易使用的標(biāo)準(zhǔn)準(zhǔn)則上才有價(jià)值。1981年世界衛(wèi)生組織（WHO）首次出版了腫瘤評(píng)價(jià)標(biāo)準(zhǔn)，主要用于腫瘤WHO通過(guò)評(píng)價(jià)治療期間基線(xiàn)的改變而判斷治療的反應(yīng)。然而，在該標(biāo)準(zhǔn)出版后的十幾年中，使用該標(biāo)準(zhǔn)的協(xié)作組和制藥公司通常對(duì)其進(jìn)行修改以適應(yīng)新的技術(shù)或在原始文獻(xiàn)中提出了不清楚的地方，這就導(dǎo)致了試驗(yàn)結(jié)果解釋的混亂。事實(shí)上，各種評(píng)價(jià)標(biāo)準(zhǔn)的應(yīng)用導(dǎo)致同一種治療方法的治療效果大相徑庭。對(duì)這些問(wèn)題的反19實(shí)體腫瘤的反應(yīng)評(píng)價(jià)標(biāo)準(zhǔn)）2000RECIST關(guān)鍵特征包括病變最小大小的確定、對(duì)隨訪病變數(shù)目的建議（105個(gè)）、一維而不是二維的使用、腫瘤負(fù)荷的總體評(píng)價(jià)。這些標(biāo)RECIST作為這些評(píng)價(jià)的合適的標(biāo)準(zhǔn)。WhyupdateRECIST?SinceRECISTwaspublishedin2000,manyinvestigatorshaveconfirmedinprospectiveanalysesthevalidityofsubstitutingunidimensionalforbidimensional(andeventhree-dimensional)-basedcriteria(reviewedin[9]).Withrareexceptions(e.g.mesothelioma),theuseofunidimensionalcriteriaseemstoperformwellinsolidtumourphaseIIstudies.RECIST？2000RECIST后，許多研究者在前瞻性研究中證實(shí)了將二維測(cè)量為基礎(chǔ)的標(biāo)準(zhǔn)（甚至是三維測(cè)量）替換為一維測(cè)量的有效性。除了少數(shù)例外（如間皮瘤），一維測(cè)量標(biāo)準(zhǔn)似乎在實(shí)體腫瘤Ⅱ期試驗(yàn)中更好。However,anumberofquestionsandissueshavearisenwhichmeritanswersandfurtherclarity.Amongstthesearewhetherfewerthan10lesionscanbeassessedwithoutaffectingtheoverallassignedresponseforpatients(ortheconclusionaboutactivityintrials);howtoapplyRECISTinrandomisedphaseIIItrialswhereprogression,notresponse,istheprimaryendpointparticularlyifnotallpatientshavemeasurabledisease;whetherorhowtoutilisenewerimagingtechnologiessuchasFDG-PETandMRI;howtohandleassessmentoflymphnodes;whetherresponseconfirmationistrulyneeded;and,notleast,theapplicabilityofRECISTintrialsoftargetednon-cytotoxicdrugs.ThisrevisionoftheRECISTguidelinesincludesupdatesthattouchonallthesepoints.然而大量問(wèn)題開(kāi)始出現(xiàn)需要回答和進(jìn)一步闡明。如在不影響病人總體預(yù)定評(píng)價(jià)（或試驗(yàn)活動(dòng)的結(jié)論）10RECISTFDG-PET和MRI？如何評(píng)價(jià)淋巴結(jié)？是否確實(shí)需要確認(rèn)緩解？RECIST在靶向非細(xì)胞毒性藥物試驗(yàn)中適用性等等。而RECIST標(biāo)準(zhǔn)的修改包括所有這些問(wèn)題的更新。ProcessofRECIST1.1developmentTheRECISTWorkingGroup,consistingofclinicianswithexpertiseinearlydrugdevelopmentfromacademicresearchorganisations,governmentandindustry,togetherwithimagingspecialistsandstatisticians,hasmetregularlytosettheagendaforanupdatetoRECIST,determinetheevidenceneededtojustifythevariouschangesmade,andtoreviewemergingevidence.Acriticalaspectoftherevisionprocesswastocreateadatabaseofprospectivelydocumentedsolidtumourmeasurementdataobtainedfromindustryandacademicgrouptrials.Thisdatabase,assembledattheEORTCDataCentreundertheleadershipofJanBogaertsandPatrickTherasse(co-authorsofthisguideline),consistsof>6500patientswith>18,000targetlesionsandwasutilisedtoinvestigatetheimpactofavarietyofquestions(e.g.numberoftargetlesionsrequired,theneedforresponseconfirmation,andlymphnodemeasurementrules)onresponseandprogression-freesurvivaloutcomes.Theresultsofthiswork,whichafterevaluationbytheRECISTWorkingGroupledtomostofthechangesinthisrevisedguideline,arereportedindetailinaseparatepaperinthisspecialissue.10LarrySchwartzandRobertFord(alsoco-authorsofthisguideline)alsoprovidedkeydatabasesfromwhichinferenceshavebeenmadethatinformtheserevisions1.1RECIST1.1形成過(guò)程RECISTRECIST更新定期舉行會(huì)議，確定所需的證據(jù)，以證明所做的各種更改是合理的，并審查新出現(xiàn)的證據(jù)。修訂過(guò)程中一個(gè)最重要的方面是建立一個(gè)回顧性的數(shù)據(jù)庫(kù)，該數(shù)據(jù)庫(kù)JanBogaertsPatrickTherasseEORTC資料中心完成的。該數(shù)據(jù)庫(kù)有>6500病人，病變器官>18000個(gè)，被用來(lái)調(diào)查各種問(wèn)題（如需靶病灶的數(shù)量、緩解確認(rèn)的需要性，淋巴結(jié)測(cè)量規(guī)則）對(duì)緩解和無(wú)疾病進(jìn)展生存期的影RECIST工作組做出評(píng)價(jià)后，這項(xiàng)工作的結(jié)果是本版指南中發(fā)生了較大變動(dòng)，并且在這個(gè)專(zhuān)期中做出了具體報(bào)道。LarrySchwartzandRobertFord（該指南的共同作者）也提供了來(lái)用于推斷的關(guān)鍵的數(shù)據(jù)1.1版本。Thepublicationofthisrevisedguidelineisbelievedtobetimelysinceitincorporateschangestosimplify,optimiseandstandardisetheassessmentoftumourburdeninclinicaltrials.AsummaryofkeychangesisfoundinAppendixI.Becausethefundamentalapproachtoassessmentremainsgroundedintheanatomical,ratherthanfunctional,assessmentofdisease,wehaveelectedtonamethisversionRECIST1.1,ratherthan2.0.這個(gè)修改指南的出版被認(rèn)為是及時(shí)的，因?yàn)樗鼘⒏鞣N變化進(jìn)行了簡(jiǎn)化、優(yōu)化，使臨床試驗(yàn)的腫瘤負(fù)荷的評(píng)價(jià)標(biāo)準(zhǔn)化。關(guān)鍵的變動(dòng)鑒于附錄Ⅰ。由于基本的評(píng)價(jià)方法仍然是解剖上，而不是功能上的，因此我們將這個(gè)版本命名為RECIST1.1而不是2.0.Whataboutvolumetricorfunctionalassessment?Thisraisesthequestion,frequentlyposed,aboutwhetheritis‘time‘tomovefromanatomicunidimensionalassessmentoftumourburdentoeithervolumetricanatomicalassessmentortofunctionalassessment(e.g.dynamiccontrastenhancedMRIorCTor(18)F-fluorodeoxyglucosepositronemissiontomographic(FDG-PET)techniquesassessingtumourmetabolism).Ascanbeseen,theWorkingGroupandparticularlythoseinvolvedinimagingresearch,didnotbelievethatthereisatpresentsufficientstandardisationandwidespreadavailabilitytorecommendadoptionofthesealternativeassessmentmethods.TheonlyexceptiontothisisintheuseofFDG-PETimagingasanadjuncttodeterminationofprogression,asdescribedlaterinthisguideline.Asdetailedpaperinthisspecialissue12,webelievethattheuseofthesepromisingnewerapproaches(whichcouldeitheraddtoorsubstituteforanatomicalassessmentasdescribedinRECIST)requiresappropriateandrigorousclinicalvalidationstudies.ThispaperbySargentetal.illustratesthetypeofdatathatwillbeneededtobeabletodefine“endpoints”forthesemodalitiesandhowtodeterminewhereandwhensuchcriteria/modalitiescanbeusedtoimprovethereliabilitywithwhichtrulyactivenewagentsareidentifiedandtrulyinactivenewagentsarediscardedincomparisontoRECISTcriteriainphaseIIscreeningtrials.TheRECISTWorkingGrouplooksforwardtosuchdataemerginginthenextfewyearstoallowtheappropriatechangestothenextiterationoftheRECISTcriteria.體積或功能評(píng)價(jià)怎么樣？（如動(dòng)態(tài)造MRICTFDG-PET評(píng)價(jià)腫瘤代謝）。正如大家看到的，工作組特別是那些從事影像學(xué)研究者，相信目前沒(méi)有足夠的標(biāo)準(zhǔn)和廣泛的可用性來(lái)建議采用這些替代的評(píng)估方法。正如指南后面描述的，唯FDG-PET12，我們相信這些有希望的新的方法（RECIST描述中的增加或替代解剖評(píng)價(jià)）Sargent等的文章表明那些/形式何時(shí)何地能夠用來(lái)提高其可靠性，以至于在Ⅱ期篩查試驗(yàn)中通過(guò)與RECIST標(biāo)準(zhǔn)比較，確定哪些為有活性的新的藥物，而哪些不是。RECIST工作組期望未來(lái)幾年出現(xiàn)這樣的資料，允許在下一版的RECIST標(biāo)準(zhǔn)中做出適當(dāng)?shù)淖儎?dòng)。2.Purposeofthisguideline該指南的目的Thisguidelinedescribesastandardapproachtosolidtumourmeasurementanddefinitionsforobjectiveassessmentofchangeintumoursizeforuseinadultandpaediatriccancerclinicaltrials.Itisexpectedthesecriteriawillbeusefulinalltrialswhereobjectiveresponseistheprimarystudyendpoint,aswellasintrialswhereassessmentofstabledisease,tumourprogressionortimetoprogressionanalysesareundertaken,sincealloftheseoutcomemeasuresarebasedonanassessmentofanatomicaltumourburdenanditschangeonstudy.Therearenoassumptionsinthispaperabouttheproportionofpatientsmeetingthecriteriaforanyoftheseendpointswhichwillsignalthatanagentortreatmentregimenisactive:thosedefinitionsaredependentontypeofcancerinwhichatrialisbeingundertakenandthespecificagentunderstudy.Protocolsmustincludeappropriatestatisticalsectionswhichdefinetheefficacyparametersuponwhichthetrialsamplesizeanddecisioncriteriaarebased.Inadditiontoprovidingdefinitionsandcriteriaforassessmentoftumourresponse,thisguidelinealsomakesrecommendationsregardingstandardreportingoftheresultsoftrialsthatutilisetumourresponseasanendpoint.本指南描述了用于成人和兒童癌癥臨床試驗(yàn)的實(shí)體腫瘤測(cè)量的標(biāo)準(zhǔn)方法和腫瘤大小變化客觀評(píng)估的定義。預(yù)計(jì)這些標(biāo)準(zhǔn)將有效用于所有以客觀緩解為主要的研究終點(diǎn)的試驗(yàn)，以及承擔(dān)疾病穩(wěn)定、腫瘤進(jìn)展或進(jìn)展時(shí)間分析的試驗(yàn)，因?yàn)樗兄委熜Ч暮饬慷际腔谘芯恐薪馄蕦W(xué)腫瘤負(fù)荷及其變化的評(píng)估。本文沒(méi)有任何關(guān)于滿(mǎn)足這些終點(diǎn)標(biāo)準(zhǔn)的病人比例的假設(shè)，這些終點(diǎn)將表明一種藥物或治療方案是有效的：這些定義取決于于試驗(yàn)中癌癥的類(lèi)型以及正在研究中的特殊試劑。方案必須包括適當(dāng)?shù)慕y(tǒng)計(jì)學(xué)章節(jié)，介紹如何以實(shí)驗(yàn)樣本大小和決策標(biāo)準(zhǔn)為基礎(chǔ)來(lái)界定療效參數(shù)。除了為腫瘤評(píng)估提供定義和標(biāo)準(zhǔn)外，這一指南也為以腫瘤緩解為終點(diǎn)的試驗(yàn)推薦了標(biāo)準(zhǔn)的研究結(jié)果報(bào)告。Whiletheseguidelinesmaybeappliedinmalignantbraintumourstudies,therearealsoseparatecriteriapublishedforresponseassessmentinthatsetting.13Thisguidelineisnotintendedforuseforstudiesofmalignantlymphomasinceinternationalguidelinesforresponseassessmentinlymphomaarepublishedseparately.14盡管這些指南可用于惡性腦腫瘤的研究，在這一領(lǐng)域關(guān)于緩解評(píng)估已有單獨(dú)的標(biāo)準(zhǔn)出版[13]。由于淋巴瘤緩解評(píng)估的國(guó)際準(zhǔn)則也已單獨(dú)出版[14]，這一指南不用于惡性淋巴瘤的研究。Finally,manyoncologistsintheirdailyclinicalpracticefollowtheirpatients‘malignantdiseasebymeansofrepeatedimagingstudiesandmakedecisionsaboutcontinuedtherapyonthebasisofbothobjectiveandsymptomaticcriteria.ItisnotintendedthattheseRECISTguidelinesplayaroleinthatdecisionmaking,exceptifdeterminedappropriatebythetreatingoncologist.RECIST指南才會(huì)在決策中起到重要作用。Measurabilityoftumouratbaseline3.基線(xiàn)腫瘤檢測(cè)Definitions定義Atbaseline,tumourlesions/lymphnodeswillbecategorisedmeasurableornon-measurableasfollows:基線(xiàn)，腫瘤病灶/淋巴結(jié)將如下分為可測(cè)量與不可測(cè)量?jī)深?lèi)：Measurable可測(cè)量腫瘤Tumourlesions:Mustbeaccuratelymeasuredinatleastonedimension(longestdiameterintheplaneofmeasurementistoberecorded)withaminimumsizeof:腫瘤性病變：至少有一個(gè)能被準(zhǔn)確測(cè)量的尺寸（儀器檢測(cè)）低限的尺寸（測(cè)量平面上最長(zhǎng)的直徑將被記錄下來(lái)）最小滿(mǎn)足：10mmbyCTscan(CTscanslicethicknessnogreaterthan5mm;seeAppendixIIonimagingguidance).10CT掃描（CT5II）。10mmcalipermeasurementbyclinicalexam(lesionswhichcannotbeaccuratelymeasuredwithcalipersshouldberecordedasnon-measurable).10毫米用卡尺測(cè)量（不能用卡尺準(zhǔn)確測(cè)量的病變，應(yīng)記錄為不可測(cè)量的）。20mmbychestX-ray.20X光檢查。Malignantlymphnodes:Tobeconsideredpathologicallyenlargedandmeasurable,alymphnodemustbe15mminshortaxiswhenassessedbyCTscan(CTscanslicethicknessrecommendedtobenogreaterthan5mm).Atbaselineandinfollow-up,onlytheshortaxiswillbemeasuredandfollowed(seeShisSpecialIssue15).Seealsonotesbelowon‘Baselinedocumentationoftargetandnon-targetlesions‘forinformationonlymphnodemeasurement.CT（CT5毫米15mm（15中施瓦茨等有關(guān)淋巴結(jié)測(cè)量的信息，同樣請(qǐng)參閱以下“靶區(qū)和非靶區(qū)病變的基線(xiàn)記錄”。Non-measurable不可測(cè)量的（腫瘤）Allotherlesions,includingsmalllesions(longestdiameter<10mmorpathologicallymphnodeswith10to<15mmshortaxis)aswellastrulynon-measurablelesions.Lesionsconsideredtrulynon-measurableinclude:leptomeningealdisease,ascites,pleuralorpericardialeffusion,inflammatorybreastdisease,lymphangiticinvolvementofskinorlung,abdominalmasses/abdominalorganomegalyidentifiedbyphysicalexamthatisnotmeasurablebyreproducibleimagingtechniques.其他所有病變，包括小病灶（最長(zhǎng)直徑小于10毫米或病理淋巴結(jié)短軸為10毫米到小于15毫米的）以及真正的不可測(cè)病變。視為真正不可測(cè)的病變包括：理學(xué)檢查確定的腦膜疾病、腹水、胸膜或心包積液、炎癥乳腺疾病、皮膚或肺的淋巴管受累，經(jīng)體格檢查發(fā)現(xiàn)的腹部腫塊/腹部器官腫大，但無(wú)法用可復(fù)制的成像技術(shù)測(cè)量。Specialconsiderationsregardinglesionmeasurability病變可測(cè)量性的特例Bonelesions,cysticlesions,andlesionspreviouslytreatedwithlocaltherapyrequireparticularcomment:需要特別注意骨病變、囊性病變和之前進(jìn)行了局部治療的病變：Bonelesions:骨病變Bonescan,PETscanorplainfilmsarenotconsideredadequateimagingtechniquestomeasurebonelesions.However,thesetechniquescanbeusedtoconfirmthepresenceordisappearanceofbonelesions.PET確認(rèn)骨病變的存在或消失。Lyticbonelesionsormixedlytic-blasticlesions,withidentifiablesofttissuecomponents,thatcanbeevaluatedbycrosssectionalimagingtechniquessuchasCTorMRIcanbeconsideredasmeasurablelesionsifthesofttissuecomponentmeetsthedefinitionofmeasurabilitydescribedabove./CTMRI等橫斷面成像技術(shù)進(jìn)行評(píng)估時(shí)，它們可被視為可測(cè)性病變。Blasticbonelesionsarenon-measurable.成骨性骨病變是不可測(cè)量的。Cysticlesions:囊性病變：Lesionsthatmeetthecriteriaforradiographicallydefinedsimplecystsshouldnotbeconsideredasmalignantlesions(neithermeasurablenornon-measurable)sincetheyare,bydefinition,simplecysts.符合X線(xiàn)定義的簡(jiǎn)單囊腫標(biāo)準(zhǔn)的病變不應(yīng)視為惡性病變（既非可測(cè)量的，也非不可測(cè)量的），其定義，它們是簡(jiǎn)單的囊腫?！瓹ysticlesions‘thoughttorepresentcysticmetastasescanbeconsideredasmeasurablelesions,iftheymeetthedefinitionofmeasurabilitydescribedabove.However,ifnon-cysticlesionsarepresentinthesamepatient,thesearepreferredforselectionastargetlesions.者體內(nèi)存在非囊性病變，這些就會(huì)被選定為目標(biāo)病灶。Lesionswithpriorlocaltreatment:已經(jīng)受到局部治療的病變：Tumourlesionssituatedinapreviouslyirradiatedarea,orinanareasubjectedtootherloco-regionaltherapy,areusuallynotconsideredmeasurableunlesstherehasbeendemonstratedprogressioninthelesion.Studyprotocolsshoulddetailtheconditionsunderwhichsuchlesionswouldbeconsideredmeasurable.實(shí)了病變的進(jìn)展。研究方案應(yīng)詳細(xì)說(shuō)明在何種條件下這種病變將被視為可測(cè)量的。Specificationsbymethodsofmeasurements測(cè)量方法說(shuō)明Measurementoflesions病灶的測(cè)量Allmeasurementsshouldberecordedinmetricnotation,usingcalipersifclinicallyassessed.臨床評(píng)估用測(cè)徑器（卡尺）測(cè)量，所有測(cè)量用米制為單位記錄。Allbaselineevaluationsshouldbeperformedascloseaspossibletothetreatmentstartandnevermorethan4weeksbeforethebeginningofthetreatment.所有基線(xiàn)評(píng)估必須盡可能在接近治療開(kāi)始前進(jìn)行，在治療前四周內(nèi)完成。Methodofassessment測(cè)量方法Thesamemethodofassessmentandthesametechniqueshouldbeusedtocharacteriseeachidentifiedandreportedlesionatbaselineandduringfollow-up.在評(píng)價(jià)同一個(gè)病灶時(shí)，基線(xiàn)和隨診應(yīng)使用同樣的技術(shù)和評(píng)估方法。Imagingbasedevaluationshouldalwaysbedoneratherthanclinicalexaminationunlessthelesionbeingfollowedcannotbeimagedbutareassessablebyclinicalexam.除只能用臨床檢查評(píng)估不適用影像檢測(cè)外，病灶必須采用影像檢測(cè)評(píng)價(jià)，不要單純采用臨床檢查。Clinicallesions:Clinicallesionswillonlybeconsideredmeasurablewhentheyaresuperficialand10mmdiameterasassessedusingcalipers(e.g.skinnodules).臨床檢查病灶：只有在達(dá)到10mm的表淺病灶（如皮下小結(jié)）考慮使用測(cè)徑器來(lái)進(jìn)行臨床檢測(cè)。Forthecaseofskinlesions,documentationbycolourphotographyincludingarulertoestimatethesizeofthelesionissuggested.皮膚表淺病灶建議使用彩色照片記錄，照片附上測(cè)量病灶大小的比例尺。Asnotedabove,whenlesionscanbeevaluatedbybothclinicalexamandimaging,imagingevaluationshouldbeundertakensinceitismoreobjectiveandmayalsobereviewedattheendofthestudy.如前所述，當(dāng)病灶既可用臨床檢測(cè)也可用影像學(xué)檢查時(shí)，由于影像學(xué)更客觀并可用于治療后研究終點(diǎn)的回顧，應(yīng)該進(jìn)行影像學(xué)檢查。ChestX-ray:ChestCTispreferredoverchestX-ray,particularlywhenprogressionisanimportantendpoint,sinceCTismoresensitivethanX-ray,particularlyinidentifyingnewlesions.胸部X片：胸片和胸部CT測(cè)量病灶，因?yàn)镃T在發(fā)現(xiàn)新病灶等方面比較X片更敏感，優(yōu)先選用CT掃描，特別在進(jìn)展作為治療終點(diǎn)時(shí)。However,lesionsonchestX-raymaybeconsideredmeasurableiftheyareclearlydefinedandsurroundedbyaeratedlung.SeeAppendixIIformoredetails.然而，肺通氣正常，實(shí)質(zhì)中邊界清楚的病灶也可使用胸片檢測(cè)。詳見(jiàn)附錄二。CT,MRI:CTisthebestcurrentlyavailableandreproduciblemethodtomeasurelesionsselectedforresponseassessment.CT，MRI：CT是目前用來(lái)評(píng)估病灶療效最有效和重復(fù)性最好的檢測(cè)方法。ThisCTscanbasedontheassumptionmmorless.指南定義可測(cè)量病灶用CT掃描基于層厚不超過(guò)5mm。AsisdescribedinAppendixCTscanshave5mm,theminimumsizeforameasurablelesionshouldbetwicetheCT5mmMRIisalsoacceptableincertaisituation(e.gfobodyscans).MRI在某也情況下也可使用（如全身掃描）。MoretheuseofbothCTandMRIforassessmentofobjectivetumourresponseprovidedinAppendixII.CTMRII。Ultrasound:Ultrasoundisnotusefulinassessmentoflesionsizeandshouldnotbeusedasamethodofmeasurement.超聲檢查：超聲檢查不適用于評(píng)估病灶大小，不應(yīng)用于測(cè)量方法。Ultrasoundexaminationscannotbereproducedintheientiretfoindependentreviewatalaterdateand,becausetheyareoperatordependent,beguaranteedthatthesametechniqueandmeasurementstakenfromoneassessmenttothenext(describedingreaterdetailinAppendix超聲檢查不能完全重復(fù)，以便日后進(jìn)行獨(dú)立審查，而且由于它們依賴(lài)于操作者，不能保證從一次評(píng)估到下一次評(píng)估采用相同的技術(shù)和測(cè)量方法（詳見(jiàn)附錄二）。ultrasoundinthecourseoftheCTorMRIisadvised.IfthereisconcernaboutatCT,MRImaybeusedinsteadofCTinselectedinstances.如果在研究過(guò)程中通過(guò)超聲發(fā)現(xiàn)新的病灶，建議用CT或MRI驗(yàn)證。如果顧慮CT的射線(xiàn)照射，可用MRI代替來(lái)檢測(cè)待檢病灶。Endoscopy,laparoscopyTheutilisatonthesetechniquesfoobjectivtumouradvised.內(nèi)鏡、腹腔鏡：不建議用這些技術(shù)評(píng)估實(shí)體瘤。However,theycanbeusefutoconfirmcompletepathologicaresponsewhenbiopsieareortodeterminerelapseintriahererecurrencefollowincompleteresponseorsurgicaresectioianendpoint.然而，它們可以在活檢時(shí)確認(rèn)病理上的CR，或在CR或手術(shù)切除后以復(fù)發(fā)為終點(diǎn)的試驗(yàn)中確定復(fù)發(fā)情況。Tumourmarkers:Tumourmarkersalonecannotbeusedtoassessresponse.腫瘤標(biāo)志物：腫瘤標(biāo)記物不能單獨(dú)用于評(píng)估實(shí)體瘤療效。aretheuppernormaltheymustnormaliseforaconsideredincompleteresponse.然而，腫瘤標(biāo)志物開(kāi)始高于正常上限時(shí)，如果用來(lái)判斷病人CR，標(biāo)志物必須恢復(fù)正常。Becausetumourmarkersarediseasespecific,instructionsfortheirmeasurementshouldbeincorporatedintoprotocolsonadiseasespecificbasis.因?yàn)槟[瘤標(biāo)志物具有疾病特異性，測(cè)量技術(shù)應(yīng)該在方案中體現(xiàn)對(duì)于某一特殊疾病基線(xiàn)檢測(cè)。SpecificguidelinesforbothCA-125response(inrecurrentovariancancer)andPSAresponse(inrecurrentprostatecancer),havebeenpublished.[16],[17]and[18]Inaddition,theGynecologicCancerIntergrouphasdevelopedCA125progressioncriteriawhicharetobeintegratedwithobjectivetumourassessmentforuseinfirst-linetrialsinovariancancer.19CA-125變化（在卵巢癌復(fù)發(fā)）PSA變化（在前列腺癌復(fù)發(fā)）的特別指南已經(jīng)出版，見(jiàn)[16]、[17]、[18]CA125進(jìn)展用于實(shí)體瘤評(píng)估的標(biāo)準(zhǔn)，將與客觀腫瘤評(píng)估相結(jié)合，用于卵巢癌的一線(xiàn)試驗(yàn)。[19]。Cytology,histology:ThesetechniquescanbeusedtodifferentiatebetweenPRandCRinrarecasesifrequiredbyprotocol(forexample,residuallesionsintumourtypessuchasgermcelltumours,whereknownresidualbenigntumourscanremain).細(xì)胞學(xué)、組織學(xué)：如果方案需要，必要時(shí)這些技術(shù)可用于個(gè)別病例來(lái)區(qū)分部分緩解和完全緩解，（比如在鑒定殘存病灶的腫瘤類(lèi)型時(shí)，實(shí)例如生殖細(xì)胞腫瘤能顧殘存良性瘤病灶）。Wheneffusionsareknowntobeapotentialadverseeffectoftreatment(e.g.withcertaintaxanecompoundsorangiogenesisinhibitors),thecytologicalconfirmationoftheneoplasticoriginofanyeffusionthatappearsorworsensduringtreatmentcanbeconsideredifthemeasurabletumourhasmetcriteriaforresponseorstablediseaseinordertodifferentiatebetweenresponse(orstabledisease)andprogressivedisease.當(dāng)已知治療中滲出是潛在的不良反應(yīng)（如某些紫杉醇類(lèi)化療藥或血管生成抑制劑），即使可測(cè)量腫瘤符合緩解或穩(wěn)定的標(biāo)準(zhǔn)，在治療過(guò)程中出現(xiàn)的以及惡化的任何滲出液都要考慮用細(xì)胞學(xué)證實(shí)其腫瘤性質(zhì)，以區(qū)分可評(píng)價(jià)腫瘤的療效是有效、穩(wěn)定（無(wú)效）還是進(jìn)展。Tumourresponseevaluation腫瘤緩解評(píng)估Assessmentofoveralltumourburdenandmeasurabledisease評(píng)估所有腫瘤負(fù)擔(dān)與可測(cè)量病灶Toassessobjectiveresponseorfutureprogression,itisnecessarytoestimatetheoveralltumourburdenatbaselineandusethisasacomparatorforsubsequentmeasurements.Onlypatientswithmeasurablediseaseatbaselineshouldbeincludedinprotocolswhereobjectivetumourresponseistheprimaryendpoint.Measurablediseaseisdefinedbythepresenceofatleastonemeasurablelesion(asdetailedaboveinSection3).Instudieswheretheprimaryendpointistumourprogression(eithertimetoprogressionorproportionwithprogressionatafixeddate),theprotocolmustspecifyifentryisrestrictedtothosewithmeasurablediseaseorwhetherpatientshavingnon-measurablediseaseonlyarealsoeligible.為評(píng)價(jià)客觀緩解或未來(lái)可能的進(jìn)展，有必要對(duì)所有腫瘤病灶腫瘤的總負(fù)荷進(jìn)行基線(xiàn)評(píng)估，為后面的測(cè)量結(jié)果作參照。在以客觀緩解作為主要治療終點(diǎn)的臨床方案中，只有在基線(xiàn)時(shí)具有可測(cè)量病灶的患者才能入選。可測(cè)量病灶定義為存在至少一處可測(cè)量的病灶。而對(duì)于那些以疾病進(jìn)展（疾病進(jìn)展時(shí)間或固定日期進(jìn)展比例）為主要治療終點(diǎn)的試驗(yàn)，方案入選標(biāo)準(zhǔn)中必須明確是僅限于有可測(cè)量病灶的患者，還是沒(méi)有可測(cè)量病灶也可以入選Baselinedocumentationof‘target’and‘non-target’lesions靶病灶和非靶病灶的基線(xiàn)記錄Whenmorethanonemeasurablelesionispresentatbaselinealllesionsuptoamaximumoffivelesionstotal(andamaximumoftwolesionsperorgan)representativeofallinvolvedorgansshouldbeidentifiedastargetlesionsandwillberecordedandmeasuredatbaseline(thismeansininstanceswherepatientshaveonlyoneortwoorgansitesinvolvedamaximumoftwoandfourlesionsrespectivelywillberecorded).Forevidencetosupporttheselectionofonlyfivetargetlesions,seeanalysesonalargeprospectivedatabaseinthearticlebyBogaertsetal.10.基線(xiàn)評(píng)估時(shí)有超過(guò)一個(gè)以上可測(cè)量病灶時(shí)，應(yīng)記錄并測(cè)量所有病灶，總數(shù)不超過(guò)5個(gè)（2個(gè)），作為靶病灶代表所有累及器官（也就是說(shuō)只有一個(gè)或兩個(gè)累計(jì)器官的患者最多選擇兩個(gè)或四個(gè)靶病灶作為基線(xiàn)測(cè)量病灶）。Targetlesionsshouldbeselectedonthebasisoftheirsize(lesionswiththelongestdiameter),berepresentativeofallinvolvedorgans,butinadditionshouldbethosethatlendthemselvestoreproduciblerepeatedmeasurements.Itmaybethecasethat,onoccasion,thelargestlesiondoesnotlenditselftoreproduciblemeasurementinwhichcircumstancethenextlargestlesionwhichcanbemeasuredreproduciblyshouldbeselected.ToillustratethispointseetheexampleinFig.3ofAppendixII.靶病灶必須基于尺寸進(jìn)行選擇（最長(zhǎng)直徑），能代表所有累及器官，且測(cè)量必須具有良好的重復(fù)性。有時(shí)候當(dāng)最大的病灶不能重復(fù)測(cè)量時(shí)可重新選擇一個(gè)可重復(fù)測(cè)量的最大病灶。Lymphnodesmeritspecialmentionsincetheyarenormalanatomicalstructureswhichmaybevisiblebyimagingevenifnotinvolvedbytumour.AsnotedinSection3,pathologicalnodeswhicharedefifinedasmeasurableandmaybeidentififiedastargetlesionsmustmeetthecriterionofashortaxisofP15mmbyCTscan.Onlytheshortaxisofthesenodeswillcontributetothebaselinesum.Theshortaxisofthenodeisthediameternormallyusedbyradiologiststojudgeifanodeisinvolvedbysolidtumour.Nodalsizeisnormallyreportedastwodimensionsintheplaneinwhichtheimageisobtained(forCTscanthisisalmostalwaystheaxialplane;forMRItheplaneofacquisitionmaybeaxial,saggitalorcoronal).Thesmallerofthesemeasuresistheshortaxis.Forexample,anabdominalnodewhichisreportedasbeing20mm·30mmhasashortaxisof20mmandqualififiesasamalignant,measurablenode.Inthisexample,20mmshouldberecordedasthenodemeasurement(SeealsotheexampleinFig.4inAppendixII).Allotherpathologicalnodes(thosewithshortaxisP10mmbut<15mm)shouldbeconsiderednon-targetlesions.Nodesthathaveashortaxis<10mmareconsiderednon-pathologicalandshouldnotberecordedorfollowed.測(cè)量短直徑≥15mm通常借助結(jié)節(jié)的短直徑來(lái)判斷該結(jié)節(jié)是否已有腫瘤轉(zhuǎn)移。結(jié)節(jié)尺寸一般用影像檢測(cè)的兩維數(shù)據(jù)來(lái)表示2030mm20mmmm即是結(jié)節(jié)10mm但<15mm<10mm的結(jié)節(jié)則不屬于病理結(jié)節(jié)范疇，不必予以記錄和進(jìn)一步觀察。Asumofthediameters(longestfornon-nodallesions,shortaxisfornodallesions)foralltargetlesionswillbecalculatedandreportedasthebaselinesumdiameters.Iflymphnodesaretobeincludedinthesum,thenasnotedabove,onlytheshortaxisisaddedintothesum.Thebaselinesumdiameterswillbeusedasreferencetofurthercharacteriseanyobjectivetumourregressioninthemeasurabledimensionofthedisease.所有靶病灶的直徑經(jīng)過(guò)計(jì)算所求之和（包括非結(jié)節(jié)病灶的最長(zhǎng)直徑和結(jié)節(jié)病灶的短直徑）將作為基線(xiàn)直徑總和上報(bào)。如含有淋巴結(jié)直徑，如上面提到的，只將短直徑計(jì)算在內(nèi)?；€(xiàn)直徑總和將作為疾病基線(xiàn)水平的參考數(shù)值。Allotherlesions(orsitesofdisease)includingpathologicallymphnodesshouldbeidentififiedasnon-targetlesionsandshouldalsoberecordedatbaseline.Measurementsarenotrequiredandtheselesionsshouldbefollowedorinrarecases‘unequivocalprogression’(moredetailstofollow).Inaddition,itispossibletorecordmultiplenon-targetlesionsinvolvingthesameorganasasingleitemonthecaserecordform(e.g.‘multipleenlargedpelviclymphnodes’or‘multiplelivermetastases’).其余所有的病灶（或病灶點(diǎn)）包括病理淋巴結(jié)可視為非靶病灶，無(wú)需進(jìn)行測(cè)量，但應(yīng)在基線(xiàn)評(píng)估時(shí)進(jìn)行記錄。如記錄為“存在”，“缺失”或極少數(shù)情況下“明確進(jìn)展”。廣泛存在的靶病灶可與靶器官記錄在一起(如大量擴(kuò)增骨盆淋巴結(jié)或大規(guī)模肝轉(zhuǎn)移)。Responsecriteria緩解標(biāo)準(zhǔn)Thissectionprovidesthedefinitionsofthecriteriausedtodetermineobjectivetumourresponsefortargetlesions.本節(jié)為目標(biāo)病灶定義用來(lái)確定實(shí)體瘤緩解的標(biāo)準(zhǔn)。Evaluationoftargetlesions目標(biāo)病灶的療效評(píng)價(jià)CompleteResponse(CR):完全緩解Disappearanceofalltargetlesions.Anypathologicallymphnodes(whethertargetornon-target)musthavereductioninshortaxisto<10mm.所有目標(biāo)病灶消失，任何病理性淋巴結(jié)（無(wú)論是否為目標(biāo)病灶）的短軸值必須<10mmPartialResponse(PR):部分緩解Atleasta30%decreaseinthesumofdiametersoftargetlesions,takingasreferencethebaselinesumdiameters.以基線(xiàn)直徑總和為參照，所有目標(biāo)病灶半徑的總和至少減小30%，ProgressiveDisease(PD):疾病進(jìn)展Atleasta20%increaseinthesumofdiametersoftargetlesions,takingasreferencethesmallestsumonstudy(thisincludesthebaselinesumifthatisthesmallestonstudy).Inadditiontotherelativeincreaseof20%,thesummustalsodemonstrateanabsoluteincreaseofatleast5mm.(Note:theappearanceofoneormorenewlesionsisalsoconsideredprogression).以所研究（目標(biāo)病灶半徑）的總和最小值為參照（包括最小值等于臨界值的情況），所有目標(biāo)病灶半徑的總和至少增加20%，另外，半徑總和增加的絕對(duì)值還至少達(dá)到5mm（注：出現(xiàn)新的病灶也可認(rèn)為是惡化）StableDisease(SD):疾病穩(wěn)定NeithersufficientshrinkagetoqualifyforPRnorsufficientincreasetoqualifyforPD,takingasreferencethesmallestsumdiameterswhileonstudy.達(dá)不到緩減標(biāo)準(zhǔn)，參考研究（目標(biāo)病灶半徑）的總和最小值，也達(dá)不到惡化標(biāo)準(zhǔn)者。Specialnotesontheassessmentoftargetlesions目標(biāo)病灶療效評(píng)價(jià)的注意事項(xiàng)Lymphnodes淋巴結(jié)Lymphnodesidentifiedastargetlesionsshouldalwayshavetheactualshortaxismeasurementrecorded(measuredinthesameanatomicalplaneasthebaselineexamination),evenifthenodesregresstobelow10mmonstudy.Thismeansthatwhenlymphnodesareincludedastargetlesions,the‘sum‘oflesionsmaynotbezeroevenifcompleteresponsecriteriaaremet,sinceanormallymphnodeisdefinedashavingashortaxisof<10mm.Casereportformsorothe