PETCT在淋巴瘤中的应用

PET/CT在淋巴瘤中的应用,复旦大学附属肿瘤医院肿瘤内科 郭 晔,指南更新,JCO 2007;25:579-586,JCO 2014;32:3048-3058,新的淋巴瘤分期,JCO 2014;32:3059-3067,内容,背景介绍PET/CT用于淋巴瘤的分期评估PET/CT用于淋巴瘤治疗后评估PET/CT用于淋巴瘤治疗中期评估,背景知识,PET：正电子发射型计算机断层显象，是以人体解剖结构为基础，利用正电子核素标记药物的示踪作用，显示人体内物质代谢，细胞增殖，血流灌注及脏器功能状态。缺点是不能准确测量肿瘤大小CT：显示人体解剖结构及形态学改变，有较强的空间分辨率PET/CT：PET和CT图像同机融合，一次成象获得全身PET和CT的图象，将功能影象与解剖形态学优化组合，两者结合取长补短,18FDG在肿瘤细胞中的摄取,FDG在常见淋巴瘤中的摄取,进行FDG-PET的要求,Juweid ME, et al. J Clin Oncol 2007; 25:571-578.,PET图像的解读标准 (视觉判断法),Juweid ME, et al. J Clin Oncol 2007; 25:571-578.,5分类法 (Deauville 标准),Barrington S, et al. J Clin Oncol 2014;32:3048,举例：治疗前,治疗后：1分,Example of score 1: complete metabolic response with no uptake in normal-size lymph nodes at site of initial disease in left neck (arrow).,举例：治疗前,治疗后：2分,Example of score 2: residual uptake of intensity mediastinal blood pool but liver in residual mediastinal mass (arrow). Maximum standardized uptake value (SUVmax) in mass was 4.5; SUVmax in liver was 3.2.,举例：治疗前,治疗后：5分,Example of score 5: residual uptake in mediastinum with intensity markedly higher than normal liver. Maximum standardized uptake value (SUVmax) in mass was 13.0; SUVmax in liver was 2.3.,新的指南推荐级别,Experts in nuclear medicine and radiology applied to lymphoma undertook a literature review and shared knowledge about research in progress. Recommendations were formulated as follows:Based on established current knowledge (type 1)To identify emerging applications (type 2)To highlight key areas requiring further research (type 3),Barrington S, et al. J Clin Oncol 2014;32:3048,肿瘤缓解术语,CTCR：complete responseCRu：complete response unconfirmedPR：partial responseSD：stable diseasePD：progressive disease,PET/CTCMR：complete metabolic responsePMR：partial metabolic responseNMR： no metabolic responsePMR： progressive metabolic disease,Cheson BD, et al. J Clin Oncol 1999; 17:1244.,Cheson BD, et al. J Clin Oncol 2014;32:3059,Interpretation of PET-CT scans,Staging of FDG-avid lymphomas is recommended using visual assessment, with PET-CT images scaled to fixed SUV display and color table; focal uptakein HL and aggressive NHL is sensitive for bone marrow involvement and may obviate need for biopsy; MRI is modality of choice for suspected CNS lymphoma (type 1)Five-point scale is recommended for reporting PET-CT; results should be interpreted in context of anticipated prognosis, clinical findings, and othermarkers of response; scores 1 and 2 represent CMR; score 3 also probably represents CMR in patients receiving standard treatment (type 1)Score 4 or 5 with reduced uptake from baseline likely represents partial metabolic response, but at end of treatment represents residual metabolicdisease; increase in FDG uptake to score 5, score 5 with no decrease in uptake, and new FDG-avid foci consistent with lymphoma represent treatment failure and/or progression (type 2),Barrington S, et al. J Clin Oncol 2014;32:3048,PET结果假阳性产生的原因,化疗/放疗后的坏死/炎症反应化疗间隔：至少3周（最佳6-8周）放疗间隔：8-12周造血因子的骨髓刺激增生的胸腺组织某些摄取FDG的良性疾病免疫细胞的影响不规范的操作和图像的解读,内容,背景介绍PET/CT用于淋巴瘤的分期评估PET/CT用于淋巴瘤治疗后评估PET/CT用于淋巴瘤治疗中期评估,传统CT分期评估的缺点,仅根据病变/淋巴结的形态和大小决定临床意义对于结外病变的判断能力不足评估能力受扫描区域或部位的限制需要增强扫描，无法用于碘过敏的患者,PET与CT用于分期评估的比较,PET分期评估的结果,Role of PET-CT for staging,PET-CT should be used for staging in clinical practice and clinical trials but is not routinely recommended in lymphomas with low FDG avidity; PET-CT may be used to select best site to biopsy (type 1)Contrast-enhanced CT when used at staging or restaging should ideally occur during single visit combined with PET-CT, if not already performed; baseline findings will determine whether contrast-enhanced PET-CT or lower-dose unenhanced PET-CT will suffice for additional imaging examinations (type 2)Bulk remains an important prognostic factor in some lymphomas; volumetric measurement of tumor bulk and total tumor burden, including methods combining metabolic activity and anatomical size or volume, should be explored as potential prognosticators (type 3),Barrington S, et al. J Clin Oncol 2014;32:3048,内容,背景介绍PET/CT用于淋巴瘤的分期评估PET/CT用于淋巴瘤治疗后评估PET/CT用于淋巴瘤治疗中期评估,基于CT的IWG标准,1999年IWG制定了淋巴瘤疗效评价和预后评估指南IWG指南统一了原本各异的疗效评估标准该指南得到了临床医生和监管机构的广泛认可，并用于大量新药的审批程序,Cheson BD, et al. J Clin Oncol 1999; 17:1244.,疗效评估标准,1999年，IWG国际工作小组发布了NHL疗效评估标准,Cheson BD, et al. J Clin Oncol 1999; 17:1244.,IWG标准的缺点,无法区分肿瘤残留抑或纤维化CRu的解读容易发生歧义没有针对骨髓以外结外病变的评价,PET疗效评估的阳性和阴性预测值,基于PET的IHP标准,Cheson BD, et al. J Clin Oncol 2007; 25:579,2007年IHP制定了新的淋巴瘤疗效评价标准IHP标准是对于IWG标准的改进和补充IHP标准适用于以治愈为目的的淋巴瘤类型，特别是DLBCL和HL,IHP标准的淋巴瘤类型推荐,Cheson BD, et al. J Clin Oncol 2007; 25:579,临床试验中的疗效定义,Cheson BD, et al. J Clin Oncol 2007; 25:579,新的PET疗效定义,CMR: complete metabolic responseScore 1, 2, or 3 with or without a residual mass on 5PSPMR: partial metabolic responseScore 4 or 5 with reduced uptake compared with baseline and residual mass(es) of any sizeAt interim, these findings suggest responding diseaseAt end of treatment, these findings indicate residual diseaseNMR: no metabolic responseScore 4 or 5 with no significant change in FDG uptake from baseline at interim or end of treatmentPMR: progressive metabolic diseaseScore 4 or 5 with an increase in intensity of uptake from baseline and/orNew FDG-avid foci consistent with lymphoma at interim or end-of-treatment assessment,Cheson BD, et al. J Clin Oncol 2014;32:3059,Role of PET at end of treatment,PET-CT is standard of care for remission assessment in FDG-avid lymphoma; in presence of residual metabolically active tissue, where salvage treatment is being considered, biopsy is recommended (type 1)Investigation of significance of PET-negative residual masses should be collected prospectively in clinical trials; residual mass size and location should be recorded on end-of-treatment PET-CT reports where possible (type 3)Emerging data support use of PET-CT after rituximab-containing chemotherapy in hightumor burden FL; studies are warranted to confirm this finding in patients receiving maintenance therapy (type 2)Assessment with PET-CT could be used to guide decisions before high-dose chemotherapy and ASCT, but additional studies are warranted (type 3),Barrington S, et al. J Clin Oncol 2014;32:3048,内容,背景介绍PET/CT用于淋巴瘤的分期评估PET/CT用于淋巴瘤治疗后评估PET/CT用于淋巴瘤治疗中期评估,背景,淋巴瘤包括DLBCL是一个异质性很大的疾病现有的预后因素有助于判断总体预后，但往往难以据此作出个体化的治疗方案选择如何早期筛选出难治性或容易复发的患者，有助于尽早实施解救方案，如化疗、移植或新的靶向药物等，从而改善预后如何早期筛选出预后良好的患者，有助于调整治疗强度，从而减少远期毒性或第二原发肿瘤,重要的预后因素-治疗敏感性,治疗的敏感性即肿瘤缓解情况往往与预后具有相关性治疗后的缓解状态有助于早期调整治疗方案对于肿瘤缓解状态的判断，PET/CT优于普通增强CTPET/CT可以判断肿瘤内部的代谢情况，从而有助于早期明确治疗的敏感性,PET图像的解读方法,视觉判断法 (IHP标准)5分类法 (Deauville标准) 半定量法 (SUVmax),视觉判断法,103例DLBCL接受CHOP利妥昔单抗的治疗2-4个周期后行CT和PET评价疗效,Dupuis J, et al. Ann Oncol 2009; 20(3):503-507.,系统性综述,Terasawa T, et al. J Clin Oncol 2009;27(11):1906-1914,视觉判断法存在的重要问题,过低的结果判断一致率,一致率：68%,一致率：71%,Horning SJ, et al. Blood 2010;115(4):775-777,过高的假阳性率,(假阳性：87%),MSKCC 研究,Moskowitz CH, et al. J Clin Oncol 2010;28(11):1896-1903,扫描时间的重要性,Httmann A, et al. J Clin Oncol 2010;28(27):e488-e489,5分类法 (Deauville 标准),Meignan M, et al. Leuk Lymphoma 2010;51(12):21712180,采用纵隔血池和肝脏作为参照的比较,Itti E, et al. J Nucl Med 2010;51(12):1857-1862,半定量法 (SUVmax),优点：SUVmax的变化反映了肿瘤的动态代谢半定量标准有助于个体化判断疗效与视觉判断法/五分类法相比减少了假阳性的几率解读的一致性和重复性较高缺点：需要强制性的基线PET检查对于PET操作标准化的要求提高对于基线SUVmax较小的病灶，有可能带来假阳性