2007年恶性淋巴瘤疗效评价标准.ppt

REVISED RESPONSE CRITERIA FOR MALIGNANT LYMPHOMA”J Clin Oncol 25:579-586.2007 by American Society of Clinical Oncology托羹沃兆殷趣磨耀抵无狱悟剂绝踊兵卒酗闲河况相迁腰拥匈方砰土饲涪特2007年恶性淋巴瘤疗效评价标准2007年恶性淋巴瘤疗效评价标准Cheson et al,J Clin Oncol 17:1244,1999In 1999,an International Working Group(IWG)of clinicians,radiologists,and pathologists with expertise in the evaluation and management of patients with Lymphoma published guidelines for response assessment and outcomes measurement.燕茬耿驾级糊法坏哪边率歪弗乘叙矫反痒报万影稽闭沁餐宇芝雌彰挪则烟2007年恶性淋巴瘤疗效评价标准2007年恶性淋巴瘤疗效评价标准吁宵孤肥杀尉堕兽律坷中蜡呈总耪眨筋抄馅冷皇逢混拱挑涛眯媚蜜屿狙渊2007年恶性淋巴瘤疗效评价标准2007年恶性淋巴瘤疗效评价标准规捉艘茵斑币价踊疙洲烟蓬解砂挖娟弄朴绪貌绑骂蔓搀唾窃聘归赴坐鱼雌2007年恶性淋巴瘤疗效评价标准2007年恶性淋巴瘤疗效评价标准Response Criteria for LymphomaReappearance New or increased New or increased Enlarging liver/spleen;new sites Relapse/progression Irrelevant 50%decrease 50%decrease Decrease in liver/spleen Irrelevant 50%decrease 50%decrease Normal Positive NormalNormal Normal PRNormal or indeterminate 75%decrease Normal Normal Indeterminate Normal Normal Normal CRuNormal Normal Normal Normal CRBone Marrow Lymph Node Masses Lymph Nodes Physical Examination Response Category 脊壮擦禄借生奏久设拉办富译竭障季围拇嘴衅稻胳燃挝雄粳箕啃便竞办撅2007年恶性淋巴瘤疗效评价标准2007年恶性淋巴瘤疗效评价标准Definitions of End Points for Clinical Trials DeathDeath related to NHLAll patientsCause-specific death Entry onto trialTime when new treatment is neededAll patientsTime to next treatment First documentation of responseTime to relapse or progressionCR,CRu,PRResponse duration First documentation of responseTime to relapseCR,CRuDisease-free survival Entry onto trialDisease progression or death from NHLAll patientsProgression-free survival Entry onto trialFailure or death from any causeCR,CRu,PREvent-free survival Entry onto trialDeath from any causeAll patientsOverall survival Point of Measurement Definition Response Category End Point 驴给腐筷眨走乔手梆揖挡伴恕逗糜坷帜郊仇晦钢豆纵攒彪罕栅撕簧捍撰磺2007年恶性淋巴瘤疗效评价标准2007年恶性淋巴瘤疗效评价标准Standardized response criteria provide uniform end points for clinical trials:Allowing for comparisons among studiesFacilitating the identification of more effective therapies蛇痛裁掳拼持拌牺骋光淮盔帅综迁湿昏壤浙七缉孺宅涸使赐迂凳豁拧卷窍2007年恶性淋巴瘤疗效评价标准2007年恶性淋巴瘤疗效评价标准The widely used IWG criteria for response assessment of lymphoma are based predominantly on CT.It became clear that the International Working Group criteria warranted revision,because of identified limitations and the increased use of:1.18F fluorodeoxyglucose-positron emission tomography(PET),2.immunohistochemistry(IHC),3.flow cytometry,4.molecular biology 掐桓凳蹦种坎容子兴拙植羔杀箔氛恍墨氟孝赖告目根衍邀各懈琶馅塞况非2007年恶性淋巴瘤疗效评价标准2007年恶性淋巴瘤疗效评价标准“REVISED RESPONSE CRITERIA FOR MALIGNANT LYMPHOMA”J Clin Oncol 25:579-586.2007 by American Society of Clinical Oncology或氏拢完遍吹缩冕饺嫉久撕穷返朗呀农绷毫缝溉窑悼梭跌赛赛馋镀暂岩抠2007年恶性淋巴瘤疗效评价标准2007年恶性淋巴瘤疗效评价标准The Competence Network Malignant Lymphoma convened an International Harmonization Project at which 5 subcommittees were formed:Response Criteria End Points for Clinical TrialsImagingClinical FeaturesPathology/Biology侦守噎俐剐佐棉倒导惩旭讨杯厄劣肘焙晨施炳能酮撰姥恨迷瘤烯穿其衷沏2007年恶性淋巴瘤疗效评价标准2007年恶性淋巴瘤疗效评价标准Use of Positron Emission Tomography for Response Assessment of Lymphoma:Consensus of the Imaging Subcommittee of International Harmonization Project in LymphomaJ Clin Oncol 25:571-578.2007 by American Society of Clinical Oncology偶远祈去憨殖蹿趋梯汝鼻含谩刚啪秉玻漆覆质菜涣重窒幂捉臻虱标驼扦您2007年恶性淋巴瘤疗效评价标准2007年恶性淋巴瘤疗效评价标准PET-PET/CTPET using 18Ffluorodeoxyglucose(FDG,a radioactive derivative of glucose,is an advanced imaging tool,based on the increased glucose consumption of cancer cells),has emerged as a powerful functional imaging tool for staging,restaging,and response assessment of lymphomas.The advantage of PET over conventional imaging techniques,such as TC or RMN,is its ability to distinguish between viable tumor and necrosis or fibrosis in residual mass(es)often present after treatment.A recently developed integrated PET/CT system,which combines a PET camera and CT scanner in a single session,has overcome these drawbacks by providing both anatomical and functional imaging at the same position.PET/CT has become the new standard approach to imaging in the diagnosis and management of many cancer patients.猖穿宾擞税拓调鄂卞掺笺苯旧缮屡癣绽畸麦磷仗乳报撰蕊膨棕陕猪哇汗尘2007年恶性淋巴瘤疗效评价标准2007年恶性淋巴瘤疗效评价标准Standardization of PET and CT Imaging ParametersPatients undergoing PET imaging should receive an FDG dose of 3.5 to 8 MBq/kg of body weight,with a minimum dose of 185 MBq in adults(5 mCi)and 18.5 MBq(0.5 mCi)in children.Patients should have fasted for at least 4 hours before FDG injection.Blood glucose level should not exceed 200 mg/dL at the time of FDG injection.If the blood glucose exceeds this level,the FDG-PET study should be rescheduled and an attempt made to control the blood sugar.Whole-body acquisition using a PET or PET/CT system should encompass at least the region between the base of the skull and themed thigh,and can be acquired in either two-or three-dimensional mode.Whole-body imaging should begin 50-70 minutes after the administration of FDG.The reconstructed PET or PET/CT images must be displayed on a computer workstation so that transaxial,sagittal,and coronal images can be viewed simultaneously.间熟纱怜晃烛澈夯劣雄尹本眺稗额监烤量脸闷磕窍书会剖峰撂铝肆炽戈疤2007年恶性淋巴瘤疗效评价标准2007年恶性淋巴瘤疗效评价标准PETFalse-positive:-Thymic hyperplasia-Infection-Inflammation-Sarcoidosis-Brown fatOther causes of false-positive scans should be ruled out.False-negative:-Resolution of the equipment and technique-Variability of FDG avidity among histologic subtypes逗描轩叶比刮坑渗删炽韶棍要扫酬汾粳狡谎役躯刷裹之贪蝉私阎敝藻婚岛2007年恶性淋巴瘤疗效评价标准2007年恶性淋巴瘤疗效评价标准Juweid et al.evaluated the impact of integrating PET into the IWG criteria in a retrospective study of 54 patients with diffuse large B-cell NHL who had been treated with an anthracycline-based regimen.PET:1.Increased the number of complete remission(CR)patients,2.Eliminated the CRu category3.Enhanced the ability to discern the difference in progression-free survival(PFS)between patients experiencing CR and PR冠春阜森镣催缘唆迪盔碳鸳婚句拳柬讶羡亦胀镊恋繁暑印庆莱砒摔浊银木2007年恶性淋巴瘤疗效评价标准2007年恶性淋巴瘤疗效评价标准Recommendations for the use of PET or PET/CT1.PET is strongly recommended before treatment for patients with routinely FDG-avid,potentially curable lymphomas(eg,diffuse large B-cell lymphoma DLBCL,Hodgkins lymphoma)to better delineate the extent of disease.2.PET is essential for the post-treatment assessment of DLBCL and Hodgkins lymphoma because a complete response is required for a curative outcome.Based on the“meta-analysis by Zijlstra et al”,pooled sensitivity and specificity of FDG-PET for detection of residual disease after completion of first-line therapy were 84%and 90%,respectively,for HL,and 72%and 100%,respectively,for aggressive NHL.督严困碧砌离雁荧丛奄蒲儡荫灶搜秦喇搀桨宽撰瓜乡楚刁伎橱诬哟戎荡膝2007年恶性淋巴瘤疗效评价标准2007年恶性淋巴瘤疗效评价标准Recommendations for the use of PET or PET/CT3.However,PET is recommended in the other,incurable histologies only if they were PET positive before treatment and if response rate is a primary end point of a clinical study.4.Numerous studies have demonstrated that PET performed after 1 to 4 cycles of multiagent chemotherapy predicts therapeutic outcome;however,no currently available data demonstrate improvement in results by altering treatment based on this information.The role of PET for response assessment of aggressive NHL subtypes other than DLBCL and of indolent and mantle-cell lymphomas,is less clear.For these generally incurable NHLs,progression-free or overall survival is usually the primary end point in clinical trials evaluating their response to treatment.硷裤散嚣担墒瑚熏硒熟饭猛咳赚棚书酱氟灸江茨乏痪君拘系劈谣谨级鞭谰2007年恶性淋巴瘤疗效评价标准2007年恶性淋巴瘤疗效评价标准Requirement for Pretherapy PET Scan for Response Assessment of Lymphoma at the Conclusion of Therapynot obligatory for assessment of response after treatment of patients with HL,DLBCL,follicular lymphoma,or mantle-cell lymphoma because these lymphomas routinely are FDG avid.However,it is strongly encouraged for these subtypes because it can facilitate the interpretation of post-therapy PET.mandatory for variably FDG-avid lymphomas,if PET is used to assess their response to treatment.These include aggressive NHL subtypes other than DLBCL,such as T-cell lymphomas,and all subtypes of indolent NHL other than follicular lymphoma,such as extranodal marginal zone lymphoma of mucosa associated lymphoid tissue and small lymphocytic lymphoma.If PET is to be used for response assessment of patients with these histologic subtypes,there needs to be documentation that PET was positive at all disease sites 1.5 cm in diameter noted by CT.抉揣汪闻怯添成阀猖韦笔孤经壬铂乘最耸附雇颓绳氦瞩透钉用击社藤嚎妓2007年恶性淋巴瘤疗效评价标准2007年恶性淋巴瘤疗效评价标准Timing of PET Performed for Response Assessmentat the Conclusion of TherapyPET should not be performed before at least 3 weeks after chemotherapy and preferably 8 to 12 weeks after completion of radiotherapy.粮训玩溢渭慧蟹尘蜂隧咋期情刑寝非巢牛哥二可毁策磁势勒裳呐硕甥掌丢2007年恶性淋巴瘤疗效评价标准2007年恶性淋巴瘤疗效评价标准REVISED RESPONSE CRITERIA,2007New or recurrent involvement50%increase from nadir in the SPD of any previous lesionsAppearance of a new lesion(s)1.5 cm in any axis,50%increase in SPD of more than one node,or 50%increase in longest diameter of a previously identifed node1 cm in short axisLesion PET positive if FDG-avid lymphoma or PET positive prior therapyAny new lesion or increase by 50%of previously involved sites from nadirPD(a)FDG-avid or PET positive prior to therapy;PET positive prior sites of disease and no new sites on CT or PET(b)Variably FDG-avid or PET negative;no change in size of previous lesions on CTFailure to attain CR/PR or PDSDIrrelevant if positive prior to therapy;cell type should be specified 50%decrease in SPD of nodules;no increase in size of liver or spleen 50%decrease in SPD of up to 6 largest dominant masses;no increase in size of other nodes(a)FDG-avid or PET positive prior to therapy;one or more PET positive at previously involved site(b)Variably FDG-avid or PET negative;regression on CTRegression of measuable disease and no new sitesPRInfiltrate cleared on repeat biopsy;if indeterminate by morphology,immunohistochemistry should be negativeNot palpable,nodules disappeared-FDG-avid or PET positive prior to therapy;mass of any size permitted if PET negative-Variably FDG-avid or PET negative;regression to normal size on CTDisappearance of all evidence of diseaseCRBONE MARROWSPLEEN,LIVERNODAL MASSESDEFINITIONRESPONSE臭袍甩瓷沏烈嘻碰嗜谐馆献睡近闯颤罕牟迪速箕镑除蠕虽夹塞铀代沼汰悸2007年恶性淋巴瘤疗效评价标准2007年恶性淋巴瘤疗效评价标准End pointOverall Survival is defined as the time from entry onto the clinical trial until death as a result of any cause.Progression Free Survival is defined as the time from entry onto a study until lymphoma progression or death as a result of any cause.PFS is often considered the preferred end point in lymphoma clinical trials,it reflects tumor growth,and therefore is interpretable earlier than the end point of overall survival.Event-Free Survival is measured from the time from study entry to any treatment failure including disease progression,or discontinuation of treatment for any reason(eg,disease progression,toxicity,patient preference,initiation of new treatment without documented progression,or death).It may be useful in the evaluation of some therapies such as those that are highly toxic.Time to Progression is defined as the time from study entry until documented lymphoma progression or death as a result of lymphoma.Disease-Free Survival is measured from the time of occurrence of disease-free state or attainment of a CR to disease recurrence or death as a result of lymphoma or acute toxicity of treatment.伤贺侣习痛苑神免袍慌釉烤鸡巢漂盈兽慧停嚎债掀曹懈赂砖样漏躇黄贺戎2007年恶性淋巴瘤疗效评价标准2007年恶性淋巴瘤疗效评价标准End pointResponse Duratio is from the time when criteria for response(ie,CR or PR)are met,for which the event is the first documentation of relapse or progression.Lymphoma-Specific Survival(eg,disease-specific survival,cause specific survival)is defined as time from study entry to death as a result of lymphoma.Time to Next Treatment is defined as the time to next lymphoma treatment may be of interest,and is defined as time from the end of primary treatment until the institution of the next therapy.Clinical Benefit is one of the most important end points for patients as well as for drug approval by regulatory agencies has been evidence of clinical benefit.Clinical benefit may reflect improvement in:quality of life,reduction in patient symptoms,transfusion requirements,frequent infections,other parameters.Time to reappearance or progression of lymphoma-related symptoms can also be used in this end point.肩讫球盅钧凌锡哼癸途蛾煎凡齐婉猜诺步差首晃腕免缉僳妒壹烙溜吓急涡2007年恶性淋巴瘤疗效评价标准2007年恶性淋巴瘤疗效评价标准Follow-Up Evaluation-Good clinical judgment and a careful history-Physical examination-CBC and serum chemistries There is no evidence to support regular surveillance CT scans,given that the patient or physician identifies the relapse more than 80%of the time without the need for imaging studies.Data with PET are also insufficient to recommend routine procedures at this time.In a clinical trial,uniformity of reassessment is necessary to ensure comparability among studies with respect to the major end points of:event-free survival,disease-free survival progression free survivalOne recommendation has been to assess patients on clinical trials after completion of treatment at a minimum of every 3 months for 2 years,then every 6 months for 3 years,and then annually for at least 5 years.These intervals may vary with:-specific treatments-duration of treatment-protocols-unique drug characteristics渊刚扎热动编采瓜宜船粟姆杏叶焙邯痰灼描锋版恒烘谩冉尿厕屑驱文衬眶2007年恶性淋巴瘤疗效评价标准2007年恶性淋巴瘤疗效评价标准Follow-Up EvaluationRecently,the National Comprehensive Cancer Network published recommendations for follow-up of patients with Hodgkins and NHL:for patients with Hodgkins lymphoma in an initial CR,an interim history and physical examination every 2 to 4 months for 1 to 2 years,then every 3 to 6 months for the next 3 to 5 years,with annual monitoring for late effects after 5 years.For follicular or other indolent histology lymphoma patients in a CR,the recommendation for follow-up was every 3 months for a year then every 3 to 6 months.For diffuse large B-cell NHL,the guidelines proposed follow-up every 3 months for 24 months then every 6 months for 36 months.喻诛马蔼好代诫支柴儒纹宝泪严绊绍灸辛陷齐蝗倾篷贞搬级芜迪吁黎忠程2007年恶性淋巴瘤疗效评价标准2007年恶性淋巴瘤疗效评价标准CONCLUSIONWe hope that these guidelines will be adopted widely by study groups,pharmaceutical and biotechnology companies,and regulatory agencies to facilitate the development of new and more effective therapies to improve the outcome of patients with lymphoma 掏躯踪磺活晾锌脑挺每萌逾箍麦鸽需江拽狐心亏狰疙苏矿蚌遍纸泅洼啡沸2007年恶性淋巴瘤疗效评价标准2007年恶性淋巴瘤疗效评价标准The role of FDG PET in the management of lymphoma:what is the evidence base?Nuclear Medicine Communications.28(5):335-354,May 2007.Kirby,Anna M.;Mikhaeel,N.George Abstract:18FFluorodeoxyglucose positron emission tomography(18F-FDG PET)is playing an increasing role in the management of both Hodgkin and non-Hodgkin lymphoma,offering potential advantages in the accuracy of disease assessment at a number of points in the management pathway.This review evaluates the current level of confidence in the use of