1、PET/CT在淋巴瘤中的應(yīng)用,復(fù)旦大學(xué)附屬腫瘤醫(yī)院 腫瘤內(nèi)科 郭 曄,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,內(nèi)容,背景介紹 PET/CT用于淋巴瘤的分期評(píng)估 PET/CT用于淋巴瘤治療后評(píng)估 PET/CT用于淋巴瘤治療中期評(píng)估,背景知識(shí),PET：正電子發(fā)射型計(jì)算機(jī)斷層顯象，是以人體解剖結(jié)構(gòu)為基礎(chǔ)，利用正電子核素標(biāo)記藥物的示蹤作用，顯示人體內(nèi)物質(zhì)代謝，細(xì)胞增殖，血流灌注及臟器功能狀態(tài)。缺點(diǎn)是不能準(zhǔn)確測(cè)量腫瘤大小 CT：顯示人體解剖結(jié)構(gòu)及形態(tài)學(xué)改變，有較強(qiáng)的空間分辨率 PET/CT：

2、PET和CT圖像同機(jī)融合，一次成象獲得全身PET和CT的圖象，將功能影象與解剖形態(tài)學(xué)優(yōu)化組合，兩者結(jié)合取長(zhǎng)補(bǔ)短,18FDG在腫瘤細(xì)胞中的攝取,FDG在常見(jiàn)淋巴瘤中的攝取,進(jìn)行FDG-PET的要求,Juweid ME, et al. J Clin Oncol 2007; 25:571-578.,PET圖像的解讀標(biāo)準(zhǔn) (視覺(jué)判斷法),Juweid ME, et al. J Clin Oncol 2007; 25:571-578.,5分類(lèi)法 (Deauville 標(biāo)準(zhǔn)),Barrington S, et al. J Clin Oncol 2014;32:3048,舉例：治療前,治療后：1分,Exam

3、ple of score 1: complete metabolic response with no uptake in normal-size lymph nodes at site of initial disease in left neck (arrow).,舉例：治療前,治療后：2分,Example of score 2: residual uptake of intensity mediastinal blood pool in lymph nodes in left axilla (arrow). Maximum standardized uptake value (SUVma

4、x) in lymph nodes was 1.2; SUVmax in mediastinal blood pool was 1.7.,舉例：治療前,治療后：3分,Example of score 3: residual uptake of intensity mediastinal blood pool but liver in residual mediastinal mass (arrow). Maximum standardized uptake value (SUVmax) in mass was 1.7; SUVmax in liver was 2.2.,舉例：治療前,治療后：4

5、分,Example of score 4: residual uptake of intensity liver in residual mediastinal mass (arrow). Maximum standardized uptake value (SUVmax) in mass was 4.5; SUVmax in liver was 3.2.,舉例：治療前,治療后：5分,Example of score 5: residual uptake in mediastinum with intensity markedly higher than normal liver. Maxim

6、um standardized uptake value (SUVmax) in mass was 13.0; SUVmax in liver was 2.3.,新的指南推薦級(jí)別,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 curr

7、ent 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,腫瘤緩解術(shù)語(yǔ),CT CR：complete response CRu：complete response unconfirmed PR：partial response SD：stable disease PD：progressive disease,PE

8、T/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,Interpretation of PET-CT scans,Staging of FDG-avid lymphomas is recommended usin

9、g 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 report

10、ing 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 r

11、epresents 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 Cli

12、n Oncol 2014;32:3048,PET結(jié)果假陽(yáng)性產(chǎn)生的原因,化療/放療后的壞死/炎癥反應(yīng) 化療間隔：至少3周（最佳6-8周） 放療間隔：8-12周 造血因子的骨髓刺激 增生的胸腺組織 某些攝取FDG的良性疾病 免疫細(xì)胞的影響 不規(guī)范的操作和圖像的解讀,內(nèi)容,背景介紹 PET/CT用于淋巴瘤的分期評(píng)估 PET/CT用于淋巴瘤治療后評(píng)估 PET/CT用于淋巴瘤治療中期評(píng)估,傳統(tǒng)CT分期評(píng)估的缺點(diǎn),僅根據(jù)病變/淋巴結(jié)的形態(tài)和大小決定臨床意義 對(duì)于結(jié)外病變的判斷能力不足 評(píng)估能力受掃描區(qū)域或部位的限制 需要增強(qiáng)掃描，無(wú)法用于碘過(guò)敏的患者,PET與CT用于分期評(píng)估的比較,PET分期評(píng)估的結(jié)果,

13、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 oc

14、cur 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; volumetri

15、c 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,內(nèi)容,背景介紹 PET/CT用于淋巴瘤的分期評(píng)估 PET/CT用于淋巴瘤治療后評(píng)估 PET/CT用于淋巴瘤治療中期評(píng)估,基于CT的I

16、WG標(biāo)準(zhǔn),1999年IWG制定了淋巴瘤療效評(píng)價(jià)和預(yù)后評(píng)估指南 IWG指南統(tǒng)一了原本各異的療效評(píng)估標(biāo)準(zhǔn) 該指南得到了臨床醫(yī)生和監(jiān)管機(jī)構(gòu)的廣泛認(rèn)可，并用于大量新藥的審批程序,Cheson BD, et al. J Clin Oncol 1999; 17:1244.,療效評(píng)估標(biāo)準(zhǔn),1999年，IWG國(guó)際工作小組發(fā)布了NHL療效評(píng)估標(biāo)準(zhǔn),Cheson BD, et al. J Clin Oncol 1999; 17:1244.,IWG標(biāo)準(zhǔn)的缺點(diǎn),無(wú)法區(qū)分腫瘤殘留抑或纖維化 CRu的解讀容易發(fā)生歧義 沒(méi)有針對(duì)骨髓以外結(jié)外病變的評(píng)價(jià),PET療效評(píng)估的陽(yáng)性和陰性預(yù)測(cè)值,基于PET的IHP標(biāo)準(zhǔn),Cheson

17、BD, et al. J Clin Oncol 2007; 25:579,2007年IHP制定了新的淋巴瘤療效評(píng)價(jià)標(biāo)準(zhǔn) IHP標(biāo)準(zhǔn)是對(duì)于IWG標(biāo)準(zhǔn)的改進(jìn)和補(bǔ)充 IHP標(biāo)準(zhǔn)適用于以治愈為目的的淋巴瘤類(lèi)型，特別是DLBCL和HL,IHP標(biāo)準(zhǔn)的淋巴瘤類(lèi)型推薦,Cheson BD, et al. J Clin Oncol 2007; 25:579,臨床試驗(yàn)中的療效定義,Cheson BD, et al. J Clin Oncol 2007; 25:579,新的PET療效定義,CMR: complete metabolic response Score 1, 2, or 3 with or withou

18、t a residual mass on 5PS 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 NMR: no metabolic response Score 4 or

19、 5 with no significant change in FDG uptake from baseline at interim or end of treatment 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.

20、 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-n

21、egative 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

22、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,內(nèi)容,背景介紹 PET/CT用于淋巴瘤的分期評(píng)估 P

23、ET/CT用于淋巴瘤治療后評(píng)估 PET/CT用于淋巴瘤治療中期評(píng)估,背景,淋巴瘤包括DLBCL是一個(gè)異質(zhì)性很大的疾病 現(xiàn)有的預(yù)后因素有助于判斷總體預(yù)后，但往往難以據(jù)此作出個(gè)體化的治療方案選擇 如何早期篩選出難治性或容易復(fù)發(fā)的患者，有助于盡早實(shí)施解救方案，如化療、移植或新的靶向藥物等，從而改善預(yù)后 如何早期篩選出預(yù)后良好的患者，有助于調(diào)整治療強(qiáng)度，從而減少遠(yuǎn)期毒性或第二原發(fā)腫瘤,重要的預(yù)后因素-治療敏感性,治療的敏感性即腫瘤緩解情況往往與預(yù)后具有相關(guān)性 治療后的緩解狀態(tài)有助于早期調(diào)整治療方案 對(duì)于腫瘤緩解狀態(tài)的判斷，PET/CT優(yōu)于普通增強(qiáng)CT PET/CT可以判斷腫瘤內(nèi)部的代謝情況，從而有助于

24、早期明確治療的敏感性,PET圖像的解讀方法,視覺(jué)判斷法 (IHP標(biāo)準(zhǔn)) 5分類(lèi)法 (Deauville標(biāo)準(zhǔn)) 半定量法 (SUVmax),視覺(jué)判斷法,103例DLBCL接受CHOP利妥昔單抗的治療 2-4個(gè)周期后行CT和PET評(píng)價(jià)療效,Dupuis J, et al. Ann Oncol 2009; 20(3):503-507.,系統(tǒng)性綜述,Terasawa T, et al. J Clin Oncol 2009;27(11):1906-1914,視覺(jué)判斷法存在的重要問(wèn)題,過(guò)低的結(jié)果判斷一致率,一致率：68%,一致率：71%,Horning SJ, et al. Blood 2010;115(

25、4):775-777,過(guò)高的假陽(yáng)性率,(假陽(yáng)性：87%),MSKCC 研究,Moskowitz CH, et al. J Clin Oncol 2010;28(11):1896-1903,掃描時(shí)間的重要性,Httmann A, et al. J Clin Oncol 2010;28(27):e488-e489,5分類(lèi)法 (Deauville 標(biāo)準(zhǔn)),Meignan M, et al. Leuk Lymphoma 2010;51(12):21712180,采用縱隔血池和肝臟作為參照的比較,Itti E, et al. J Nucl Med 2010;51(12):1857-1862,半定量法 (SUVmax),優(yōu)點(diǎn)： SUVmax的變化反映了腫瘤的動(dòng)態(tài)代謝 半定量標(biāo)準(zhǔn)有助于個(gè)體化判斷療效 與視覺(jué)判斷法/五分類(lèi)法相比減少了假陽(yáng)性的幾率 解讀的一致性和重復(fù)性較高 缺點(diǎn)： 需要強(qiáng)制性的