recist1.1中英文校准完整版

1.Background1背景1.1.HistoryofRECISTcriteria1.1RECIST标准的历史Assessmentofthechangeintumourburdenisanimportantfeatureoftheclinicalevaluationofcancertherapeutics.Bothtumourshrinkage(objectiveresponse)andtimetothedevelopmentofdiseaseprogressionareimportantendpointsincancerclinicaltrials.TheuseoftumourregressionastheendpointforphaseIItrialsscreeningnewagentsforevidenceofanti-tumoureffectissupportedbyyearsofevidencesuggestingthat,formanysolidtumours,agentswhichproducetumourshrinkageinaproportionofpatientshaveareasonable(albeitimperfect)chanceofsubsequentlydemonstratinganimprovementinoverallsurvivalorothertimetoeventmeasuresinrandomisedphaseIIIstudies(reviewedin[1],[2],[3]and[4]).AtthecurrenttimeobjectiveresponsecarrieswithitabodyofevidencegreaterthanforanyotherbiomarkersupportingitsutilityasameasureofpromisingtreatmenteffectinphaseIIscreeningtrials.Furthermore,atboththephaseIIandphaseIIIstageofdrugdevelopment,clinicaltrialsinadvanceddiseasesettingsareincreasinglyutilisingtimetoprogression(orprogression-freesurvival)asanendpointuponwhichefficacyconclusionsaredrawn,whichisalsobasedonanatomicalmeasurementoftumoursize.评价肿瘤负荷的改变是癌症治疗的临床评价的一个重要特征。肿瘤缩小（客观缓解）和疾病进展时间都是癌症临床试验中的重要终点。为了筛查新的抗肿瘤药物，肿瘤缩小作为II期试验重点被多年研究的证据所支持。这些研究提示对于多种实体肿瘤来说，促使部分病人肿瘤缩小的药物以后都有可能（尽管不完美）被证实可提高在随机Ⅲ期试验中病人的总体生存期或进入其他事件评价的可能。目前在Ⅱ期筛查试验中评价治疗效果的指标中，客观缓解比任何其他生物标记更可靠。而且，在Ⅱ和Ⅲ期药物试验中，进展期疾病中的临床试验正越来越利用疾病进展的时间（无进展生存）作为得出有治疗效果结论的终点，而这些也是建立在肿瘤大小的解剖学测量基础上。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.然而这些肿瘤终点、客观缓解和疾病进展时间，只有建立在以肿瘤负荷解剖学基础上的广泛接受和容易使用的标准准则上才有价值。1981年世界卫生组织（WHO）首次出版了肿瘤评价标准，主要用于肿瘤缓解是主要终点的试验中。WHO标准通过测量病变二维大小并进行合计介绍了肿瘤负荷总体评价的概念，通过评价治疗期间基线的改变而判断治疗的反应。然而，在该标准出版后的十几年中，使用该标准的协作组和制药公司通常对其进行修改以适应新的技术或在原始文献中提出了不清楚的地方，这就导致了试验结果解释的混乱。事实上，各种评价标准的应用导致同一种治疗方法的治疗效果大相径庭。对这些问题的反应是国际工作组于19世纪中期形成，并对评价标准进行了标准化和简化。新的标准，也称为RECIST（实体肿瘤的反应评价标准）于2000年出版。最初的RECIST关键特征包括病变最小大小的确定、对随访病变数目的建议（最多10个；每个器官最多5个）、一维而不是二维的使用、肿瘤负荷的总体评价。这些标准后来被学术团体、协作组和制药工业广泛采用，而该标准的主要终点就是客观缓解或疾病进展。另外，当局接受RECIST作为这些评价的合适的标准。1.2.WhyupdateRECIST?SinceRECISTwaspublishedin2000,manyinvestigatorshaveconfirmedinprospectiveanalysesthevalidityofsubstitutingunidimensionalforbidimensional(andeventhree-dimensional)-basedcriteria(reviewedin[9]).Withrareexceptions(e.g.mesothelioma),theuseofunidimensionalcriteriaseemstoperformwellinsolidtumourphaseIIstudies.1.2为什么要更新RECIST？自从2000年出版RECIST后，许多研究者在前瞻性研究中证实了将二维测量为基础的标准（甚至是三维测量）替换为一维测量的有效性。除了少数例外（如间皮瘤），一维测量标准似乎在实体肿瘤Ⅱ期试验中更好。However,anumberofquestionsandissueshavearisenwhichmeritanswersandfurtherclarity.Amongstthesearewhetherfewerthan10lesionscanbeassessedwithoutaffectingtheoverallassignedresponseforpatients(ortheconclusionaboutactivityintrials);howtoapplyRECISTinrandomisedphaseIIItrialswhereprogression,notresponse,istheprimaryendpointparticularlyifnotallpatientshavemeasurabledisease;whetherorhowtoutilisenewerimagingtechnologiessuchasFDG-PETandMRI;howtohandleassessmentoflymphnodes;whetherresponseconfirmationistrulyneeded;and,notleast,theapplicabilityofRECISTintrialsoftargetednon-cytotoxicdrugs.ThisrevisionoftheRECISTguidelinesincludesupdatesthattouchonallthesepoints.然而大量问题开始出现需要回答和进一步阐明。如在不影响病人总体预定评价（或试验活动的结论）情况下是否可以少于10病灶进行评估？在随机Ⅲ期试验中，特别当病人没有可测量的病变，不是应用缓解，而是把疾病进展作为主要的终点时，如何应用RECIST？是否或怎样利用新的影像学技术如FDG-PET和MRI？如何评价淋巴结？是否确实需要确认缓解？RECIST在靶向非细胞毒性药物试验中适用性等等。而RECIST标准的修改包括所有这些问题的更新。1.3.ProcessofRECIST1.1developmentTheRECISTWorkingGroup,consistingofclinicianswithexpertiseinearlydrugdevelopmentfromacademicresearchorganisations,governmentandindustry,togetherwithim