恶性淋巴瘤疗效评价标准

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1、“REVISED RESPONSE CRITERIA FOR MALIGNANT LYMPHOMA”J Clin Oncol 25:579-586.2007 by American Society of Clinical OncologyCheson 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 patie

2、nts with Lymphoma published guidelines for response assessment and outcomes measurement.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

3、 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 Definitions of End Points for Clinical Trials Deat

4、hDeath 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

5、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 Standard

6、ized response criteria provide uniform end points for clinical trials:Allowing for comparisons among studies Facilitating the identification of more effective therapiesThe widely used IWG criteria for response assessment of lymphoma are based predominantly on CT.It became clear that the Internationa

7、l Working Group criteria warranted revision,because of identified limitations and the increased use of:18F fluorodeoxyglucose-positron emission tomography(PET),immunohistochemistry(IHC),flow cytometry,molecular biology“REVISED RESPONSE CRITERIA FOR MALIGNANT LYMPHOMA”J Clin Oncol 25:579-586.2007 by

8、American Society of Clinical OncologyThe Competence Network Malignant Lymphoma convened an International Harmonization Project at which 5 subcommittees were formed:Response Criteria End Points for Clinical Trials Imaging Clinical Features Pathology/BiologyUse of Positron Emission Tomography for Resp

9、onse 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 OncologyPET-PET/CT PET using 18Ffluorodeoxyglucose(FDG,a radioactive derivative of glucose,is an advanced imaging tool,base

10、d 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 necr

11、osis 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

12、new standard approach to imaging in the diagnosis and management of many cancer patients.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

13、 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 acqui

14、sition 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 mus

15、t be displayed on a computer workstation so that transaxial,sagittal,and coronal images can be viewed simultaneously.PET False-positive:-Thymic hyperplasia-Infection-Inflammation-Sarcoidosis-Brown fatOther causes of false-positive scans should be ruled out.False-negative:-Resolution of the equipment

16、 and technique-Variability of FDG avidity among histologic subtypesJuweid 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:Increased the number of com

17、plete remission(CR)patients,Eliminated the CRu category1.Enhanced the ability to discern the difference in progression-free survival(PFS)between patients experiencing CR and PRRecommendations for the use of PET or PET/CTPET is strongly recommended before treatment for patients with routinely FDG-avi

18、d,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-anal

19、ysis 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.Recommendations for the use of PET or PET/CT3.However,PET is recommended

20、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

21、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

22、 survival is usually the primary end point in clinical trials evaluating their response to treatment.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 lymp

23、homa,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 inclu

24、de 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

25、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.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

26、to 12 weeks after completion of radiotherapy.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

27、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 FD

28、G-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 increas

29、e 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,immunohis

30、tochemistry 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 MASSESDEFINITION

31、RESPONSEEnd 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

32、 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

33、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 lymphom

34、a 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.End pointResponse Duratio is from the time when criteria for

35、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

36、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 benefi

37、t.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.Follow-Up Evaluation-Good clinical judgment an

38、d 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 r

39、outine 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 trial

40、s 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 characteristicsFollow-Up EvaluationRecently,the National Co

41、mprehensive 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 mo

42、nitoring 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

43、6 months for 36 months.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 The role of FDG

44、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 l

45、ymphoma,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 PET technology in:(1)initial staging,(2)the assessment of early response to chemotherapy,(3)the assessment of residual masses at completion of initial treatment,(4)follow-up,and(5)radiotherapy planning.