PETCT在淋巴瘤中的应用ppt课件

1 PET/CT在淋巴瘤中的应用 2 指南更新 JCO 2007;25:579-586 JCO 2014;32:3048-3058 3 新的淋巴瘤分期 JCO 2014;32:3059-3067 4 内容 n 背景介绍 n PET/CT用于淋巴瘤的分期评估 n PET/CT用于淋巴瘤治疗后评估 n PET/CT用于淋巴瘤治疗中期评估 5 背景知识 n 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 n CT： 显示人体解剖结构及形态学改变，有较强的 空间分辨率 n 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 6 18FDG在肿瘤细胞中的摄取 7 FDG在常见淋巴瘤中的摄取 8 进行 FDG-PET的要求 Juweid ME, et al. J Clin Oncol 2007; 25:571-578. 9 PET图像的解读标准 (视觉判断法 ) Juweid ME, et al. J Clin Oncol 2007; 25:571-578. 10 5分类法 (Deauville 标准 ) Barrington S, et al. J Clin Oncol 2014;32:3048 11 举例：治疗前 12 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). 13 举例：治疗前 14 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. 19 举例：治疗前 20 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. 21 新的指南推荐级别 n 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 22 肿瘤缓解术语 n CT CR： complete response CRu： complete response unconfirmed PR： partial response SD： stable disease PD： progressive disease n PET/CT CMR： complete metabolic response PMR： partial metabolic response NMR： no metabolic response PMR： progressive metabolic disease Cheson BD, et al. J Clin Oncol 1999; 17:1244. Cheson BD, et al. J Clin Oncol 2014;32:3059 23 Interpretation of PET-CT scans 1. 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) 2. 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) 3. 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 24 PET结果假阳性产生的原因 n 化疗 /放疗后的坏死 /炎症反应 n 化疗间隔：至少 3周（最佳 6-8周） n 放疗间隔： 8-12周 n 造血因子的骨髓刺激 n 增生的胸腺组织 n 某些摄取 FDG的良性疾病 n 免疫细胞的影响 n 不规范的操作和图像的解读 25 内容 n 背景介绍 n PET/CT用于淋巴瘤的分期评估 n PET/CT用于淋巴瘤治疗后评估 n PET/CT用于淋巴瘤治疗中期评估 26 传统 CT分期评估的缺点 n 仅根据病变 /淋巴结的形态和大小决定临床意义 n 对于结外病变的判断能力不足 n 评估能力受扫描区域或部位的限制 n 需要增强扫描，无法用于碘过敏的患者 27 PET与 CT用于分期评估的比较 28 PET分期评估的结果 29 Role of PET-CT for staging 1. 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) 2. 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) 3. 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 30 内容 n 背景介绍 n PET/CT用于淋巴瘤的分期评估 n PET/CT用于淋巴瘤治疗后评估 n PET/CT用于淋巴瘤治疗中期评估 31 基于 CT的 IWG标准 n 1999年 IWG制定了淋巴瘤疗效评价和预后评估指南 n IWG指南统一了原本各异的疗效评估标准 n 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. 32 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 疗效 体格检查 淋巴结 淋巴结肿块 骨髓 CR 正常 正常 正常 正常 CRu 正常 正常 正常 不确定 正常 正常 缩小 75% 正常或 不确定 PR 正常 正常 正常 阳性 正常 缩小 50% 缩小 50% 无关 肝 /脾缩小 缩小 50% 缩小 50% 无关 Relapse/PD 肝 /脾增大新病变 新病变或增大 新病变或增大 再发 Cheson BD, et al. J Clin Oncol 1999; 17:1244. 33 IWG标准的缺点 n 无法区分肿瘤残留抑或纤维化 n CRu的解读容易发生歧义 n 没有针对骨髓以外结外病变的评价 34 PET疗效评估的阳性和阴性预测值 35 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 36 IHP标准的淋巴瘤类型推荐 Cheson BD, et al. J Clin Oncol 2007; 25:579 37 临床试验中的疗效定义 Cheson BD, et al. J Clin Oncol 2007; 25:579 38 新的 PET疗效定义 n CMR: complete metabolic response Score 1, 2, or 3 with or without a residual mass on 5PS n PMR: partial metabolic response Score 4 or 5 with reduced uptake compared with baseline and residual mass(es) of any size At interim, these findings suggest responding disease At end of treatment, these findings indicate residual disease n NMR: no metabolic response Score 4 or 5 with no significant change in FDG uptake from baseline at interim or end of treatment n PMR: progressive metabolic disease Score 4 or 5 with an increase in intensity of uptake from baseline and/or New FDG-avid foci consistent with lymphoma at interim or end-of-treatment assessment Cheson BD, et al. J Clin Oncol 2014;32:3059 39 Role of PET at end of treatment 1. 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) 2. 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) 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) 4. 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 40 内容 n 背景介绍 n PET/CT用于淋巴瘤的分期评估 n PET/CT用于淋巴瘤治疗后评估 n PET/CT用于淋巴瘤治疗中期评估 41 背景 n 淋巴瘤包括 DLBCL是一个异质性很大的疾病 n 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 n 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 n 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 42 重要的预后因素 -治疗敏感性 n 治疗的敏感性即肿瘤缓解情况往往与预后 具有相关性 n 治疗后的缓解状态有助于早期调整治疗方 案 n 对于肿瘤缓解状态的判断， PET/CT优于普 通增强 CT n PET/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 43 PET图像的解读方法 n 视觉判断法 (IHP标准 ) n 5分类法 (Deauville标准 ) n 半定量法 ( SUVmax) 44 视觉判断法 n 103例 DLBCL接受 CHOP利妥昔单抗的治疗 n 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. 45 系统性综述 Terasawa T, et al. J Clin Oncol 2009;27(11):1906-1914 46 视觉判断法存在的重要问题 47 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 48 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 49 扫描时间的重要性 Httmann A, et al. J Clin Oncol 2010;28(27):e488-e489 50 5分类法 (Deauville 标准 ) Meignan M, et al. Leuk Lymphoma 2010;51(12):21712180 分值分值 定义定义 结果结果 1 无摄取无摄取 阴性阴性 2 摄取摄取 纵隔纵隔 阴性阴性 3 摄取摄取 纵隔但纵隔但 肝脏肝脏 阴性阴性 4 摄取摄取 肝肝 (中度中度 ) 阳性阳性 5 摄取摄取 肝肝 (明显明显 )和和 /或出现新区域摄取或出现新区域摄取 阳性阳性 X 新区域摄取不太可能与淋巴瘤相关新区域摄取不太可能与淋巴瘤相关 NA 51 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 52 半定量法 ( SUVmax) 优点： nSUVmax的变化反映了肿瘤的动态代谢 n半定量标准有助于个体化判断疗效 n与视觉判断法 /五分类法相比减少了假阳性的几率 n解读的一致性和重复性较高 缺点： n需要