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弥漫大B细胞淋巴瘤(diffuse large B-cell lymphoma,DLBCL)是成人非霍奇金淋巴瘤(non-Hodgkin lymphoma,NHL)中最常见的一种类型,占全部NHL的30%~40%[1-2]。近年来,18F-FDG PET/CT作为一种全身、无创的功能代谢显像方法,对DLBCL患者预后评估的价值已得到公认[3-4]。但仍有约14%的治疗结束后PET/CT(end of treatment PET/CT,ePET/CT)评价为阴性的患者会出现疾病复发[5],因此,需要对这些患者进行进一步的风险分层,以制定更加具体化的治疗方案。本研究回顾性分析60例ePET/CT评价为阴性的患者,探究改良国际预后指标(national comprehensive cancer network-international prognostic index,NCCN-IPI)对这60例患者进一步预后分层的价值。
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收集2013年4月至2017年8月在苏州大学附属第一医院行18F-FDG PET/CT检查的经病理确诊的DLBCL患者60例,其中男性28例、女性32例,中位年龄51岁(16~81岁)。所有患者的具体临床资料结果及患者NCCN-IPI分组情况详见表1。
临床特征 病例数(例) 百分比(%) 性别 男 28 46.7 女 32 53.3 年龄 ≤60岁 43 71.7 >60岁 17 28.3 Ann Arbor分期 Ⅰ~Ⅱ期 32 53.3 Ⅲ~Ⅳ期 28 46.7 B症状 有 18 30.0 无 42 70.0 ECOG PS评分 <2分 55 91.7 ≥2分 5 8.3 LDH水平(U/L) ≤250 40 66.7 >250 20 33.3 累及重要脏器 是 24 40.0 否 36 60.0 NCCN-IPI分组 低危(0~1分)组 21 35.0 中低危(2~3分)组 25 41.7 中高危(4~5分)组 11 18.3 高危(≥6分)组 3 5.0 注:表中,B症状:不能解释的发热,体温>38 ℃;反复夜间盗汗;半年内不明原因体重减轻10%;ECOG PS:美国东部肿瘤协作组体力状况;LDH:乳酸脱氢酶;重要脏器包括骨髓、中枢神经系统、肝/胃肠道、肺;NCCN-IPI:改良国际预后指标。 表 1 60例弥漫大B细胞淋巴瘤患者的临床特征
Table 1. Clinical characteristics of 60 patients with diffuse large B-cell lymphoma
NCCN-IPI包括8个计分点:Ⅲ~Ⅳ期、美国东部肿瘤协作组体力状况(estern cooperative oncology group performance status,ECOG PS)评分≥2分以及骨髓、中枢神经系统、肝/胃肠道或肺侵犯,每项计1分;年龄40~60岁,计1分,60~75岁,计2分,>75岁,计3分;乳酸脱氢酶(lactate dehydrogenase,LDH)比率1~3,计1分,>3,计2分。总分为0~1分为低危;2~3分为中低危;4~5分为中高危;≥6分为高危。
患者入组标准:(1)临床资料完整,无并发其他恶性肿瘤;(2)经R-CHOP(利妥昔单抗+环磷酰胺+多柔比星+长春新碱+强的松)类方案化疗6周期以上;(3)ePET/CT评价为阴性的患者。
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扫描仪为美国GE 公司Discovery STE16 PET/CT仪,患者检查前禁食4~6 h以上,检查当日空腹血糖,控制在11.0 mmol/L以下,按 3.7~7.4 MBq/kg体重静脉注射18F-FDG,该显像剂由南京安迪科正电子技术有限公司提供,放化纯>95%。静卧休息1 h,期间嘱患者多饮水,检查前20 min排空膀胱,再饮水250 mL后开始检查。扫描范围自大腿中上段至颅顶(共6~8个床位)。CT扫描条件:电压120 kV,电流150 mA,层厚3.75 mm。PET 扫描条件:3 min/床位,三维模式采集。扫描完成后基于CT图像对PET图像进行衰减校正,采用迭代法重建获得横断面、冠状面、矢状面影像及PET和CT的融合图像。
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所有患者ePET/CT检查结果由一位有经验的核医学科主治医师进行阅片,由一位高年资主任医师审核,ePET/CT显像结果的判读方法采用 Deauville标准[6],其定义如下:1分,无摄取或摄取不超过本底;2分,摄取≤纵隔血池;3分,纵隔血池<摄取≤肝脏本底;4分,任何病灶部位的摄取值轻度高于肝脏本底;5分,任何病灶的摄取值明显高于肝脏本底(>2~3倍)或有任何新的病灶出现。依据上述方法,ePET/CT显像结果中,1~3分为阴性,4~5分为阳性。
通过门诊及电话随访患者生存情况,随访终点为2018年8月,中位随访时间34个月(14~69个月)。根据病理学、多种影像学检查及临床随访结果明确是否有肿瘤复发或进展。无进展生存(progression-free survival,PFS)时间为疾病确诊至首次出现疾病进展、复发或随访截止的时间。总生存(overall survival,OS)时间为疾病确诊至任何原因导致的死亡或随访截止的时间。生存时间以“月”计算。
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应用SPSS 19.0统计学软件进行生存曲线勾画及统计分析,预后分析及组间PFS和OS的比较采用Log-rank检验,P<0.05表示差异有统计学意义。
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截止随访结束,60例患者中10例出现疾病进展或复发,4例死亡,未达到中位PFS时间,平均PFS为(56.50±2.73)个月,未达到中位OS时间,平均OS为(61.98±1.92)个月,所有患者的2年PFS率为83.33%(50/60),2年OS率为96.67%(58/60)。预后分析结果显示,Ann Arbor分期、ECOG PS评分、NCCN-IPI影响患者PFS(均P<0.05);年龄、Ann Arbor分期、ECOG PS评分和NCCN-IPI影响患者OS(均P<0.05)(表2)。
相关因素 P值 PFS OS 性别 0.260 1.000 年龄 0.373 0.016 Ann Arbor分期 0.002 0.019 B症状 0.514 0.450 ECOG PS评分 0.001 0.010 LDH水平 0.644 0.424 累及重要脏器 0.162 0.604 NCCN-IPI 0.005 0.001 注:表中,PFS:无进展生存;OS:总生存;B症状:不能解释的发热,体温>38 ℃;反复夜间盗汗;半年内不明原因体重减轻10%;ECOG PS:美国东部肿瘤协作组体力状况;LDH:乳酸脱氢酶;重要脏器包括骨髓、中枢神经系统、肝/胃肠道、肺;NCCN-IPI:改良国际预后指标。 表 2 60例弥漫大B细胞淋巴瘤患者的相关预后因素分析
Table 2. Analysis of prognostic factors in 60 patients with diffuse large B-cell lymphoma
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NCCN-IPI评分结果显示,低危(0~1分)组占35.0%(21/60),中低危(2~3分)组占41.7%(25/60),中高危(4~5分)组占18.3%(11/60),高危(≥6分)组占5.0%(3/60)。在60例患者的ePET/CT评价均为阴性的情况下,低危组与中低危组、中高危组、高危组之间PFS差异均具有统计学意义(P=0.0272、0.0143、<0.0001),余各组PFS差异无统计学意义(均P>0.05);高危组与低危组、低中危组、中高危组之间OS差异均具有统计学意义(P=0.0098、0.0166、0.0045),余各组OS差异无统计学意义(均P>0.05)(图1)。
18F-FDG PET/CT联合改良国际预后指标(NCCN-IPI)对弥漫大B细胞淋巴瘤预后评估的价值分析
Prognostic value of 18F-FDG PET/CT combined with an enhanced international prognostic index (NCCN-IPI) in diffuse large B cell lymphoma
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摘要:
目的 探讨改良国际预后指标(NCCN-IPI)对治疗结束后18F-FDG PET/CT评价为阴性的弥漫大B细胞淋巴瘤(DLBCL)患者的预后分层价值。 方法 回顾性分析2013年4月至2017年8月在苏州大学附属第一医院经过6~8周期R-CHOP类方案化疗后,并经18F-FDG PET/CT评价为阴性的60例DLBCL患者的临床资料,其中男性28例、女性32例,中位年龄51岁(16~81岁)。采用NCCN-IPI进行危险度分层,采用 Log-rank 检验比较各组间无进展生存(PFS)期和总生存(OS)期的差异。 结果 所有患者2年PFS率为83.33%(50/60),2年OS率为96.67%(58/60)。根据NCCN-IPI评分,低危组占35.0%(21/60),低中危组占41.7%(25/60),中高危组占18.3%(11/60),高危组占5.0%(3/60)。低危组与其他组间PFS差异有统计学意义(P=0.0272、0.0143、<0.0001),高危组与其他组间OS差异有统计学意义(P=0.0098、0.0166、0.0045),余各组间PFS及OS差异无统计学意义(均P>0.05)。 结论 应用NCCN-IPI可以对治疗结束后18F-FDG PET/CT评价为阴性的DLBCL患者进行进一步的预后分层。 -
关键词:
- 弥漫大B细胞淋巴瘤 /
- 正电子发射断层显像计算机体层摄影术 /
- 国际预后指数
Abstract:Objective To investigate the prognostic stratification value of an enhanced international prognostic index (NCCN-IPI) in patients with diffuse large B-cell lymphoma (DLBCL) who are negative at the end of treatment with positron emission tomography computed tomography (PET/CT). Methods A retrospective analysis was conducted on 60 patients with DLBCL from April 2013 to August 2017 in the first affiliated hospital of Soochow university. There were 28 males and 32 females, with a median age of 51 years (16−81 years). Baseline characteristics were collected from all the patients who underwent six- to eight-cycle R-CHOP regimen chemotherapy and were negative by 18F-FDG PET/CT. The risk stratification was performed by NCCN-IPI, Log-rank test was used for comparison of the differences in progression-free survival (PFS) and overall survival (OS) between groups. Results The patients featured a median follow-up of 34 months (14–69 months). The two-year PFS and OS rates reached 83.33% (50/60) and 96.67% (58/60), respectively. On the basis of NCCN-IPI risk categorization, 35.0% (21/60), 41.7% (25/60), 18.3% (11/60) and 5.0% (3/60) patients belonged to the low-, low–intermediate-, high–intermediate-, and high-risk subgroups, respectively. A statistically significant difference was observed in the PFS between the low-risk group and the other groups (P=0.0272, 0.0143, <0.0001) and in the OS between the high-risk group and the other groups (P=0.0098, 0.0166, 0.0045). The difference between the PFS and OS of other components showed no statistical significance (all P>0.05). Conclusion Further prognostic stratification can be performed by NCCN-IPI in patients with DLBCL who are negative at the end of treatment by PET/CT. -
表 1 60例弥漫大B细胞淋巴瘤患者的临床特征
Table 1. Clinical characteristics of 60 patients with diffuse large B-cell lymphoma
临床特征 病例数(例) 百分比(%) 性别 男 28 46.7 女 32 53.3 年龄 ≤60岁 43 71.7 >60岁 17 28.3 Ann Arbor分期 Ⅰ~Ⅱ期 32 53.3 Ⅲ~Ⅳ期 28 46.7 B症状 有 18 30.0 无 42 70.0 ECOG PS评分 <2分 55 91.7 ≥2分 5 8.3 LDH水平(U/L) ≤250 40 66.7 >250 20 33.3 累及重要脏器 是 24 40.0 否 36 60.0 NCCN-IPI分组 低危(0~1分)组 21 35.0 中低危(2~3分)组 25 41.7 中高危(4~5分)组 11 18.3 高危(≥6分)组 3 5.0 注:表中,B症状:不能解释的发热,体温>38 ℃;反复夜间盗汗;半年内不明原因体重减轻10%;ECOG PS:美国东部肿瘤协作组体力状况;LDH:乳酸脱氢酶;重要脏器包括骨髓、中枢神经系统、肝/胃肠道、肺;NCCN-IPI:改良国际预后指标。 表 2 60例弥漫大B细胞淋巴瘤患者的相关预后因素分析
Table 2. Analysis of prognostic factors in 60 patients with diffuse large B-cell lymphoma
相关因素 P值 PFS OS 性别 0.260 1.000 年龄 0.373 0.016 Ann Arbor分期 0.002 0.019 B症状 0.514 0.450 ECOG PS评分 0.001 0.010 LDH水平 0.644 0.424 累及重要脏器 0.162 0.604 NCCN-IPI 0.005 0.001 注:表中,PFS:无进展生存;OS:总生存;B症状:不能解释的发热,体温>38 ℃;反复夜间盗汗;半年内不明原因体重减轻10%;ECOG PS:美国东部肿瘤协作组体力状况;LDH:乳酸脱氢酶;重要脏器包括骨髓、中枢神经系统、肝/胃肠道、肺;NCCN-IPI:改良国际预后指标。 -
[1] Tilly H, Vitolo U, Walewski J, et al. Diffuse large B-cell lymphoma (DLBCL): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up[J]. Ann Oncol, 2012, 23(S7): vii78−vii82. DOI: 10.1093/annonc/mds273. [2] Martelli M, Ferreri AJM, Agostinelli C, et al. Diffuse large B-cell lymphoma[J]. Crit Rev Oncol Hematol, 2013, 87(2): 146−171. DOI: 10.1016/j.critrevonc.2012.12.009. [3] Mylam KJ, El-Galaly TC, Hutchings M, et al. Prognostic impact of clinician-based interpretation of 18F-fluorodeoxyglucose positron emission tomography/computed tomography reports obtained in patients with newly diagnosed diffuse large B-cell lymphoma[J]. Leuk Lymphoma, 2014, 55(7): 1563−1569. DOI: 10.3109/10428194.2013.850165. [4] Cheson BD, Fisher RI, Barrington SF, et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification[J]. J Clin Oncol, 2014, 32(27): 3059−3067. DOI: 10.1200/JCO.2013.54.8800. [5] Adams HJA, Nievelstein RAJ, Kwee TC. Prognostic value of complete remission status at end-of-treatment FDG-PET in R-CHOP-treated diffuse large B-cell lymphoma: systematic review and meta-analysis[J]. Br J Haematol, 2015, 170(2): 185−191. DOI: 10.1111/bjh.13420. [6] Meignan M, Gallamini A, Meignan M, et al. Report on the first international workshop on interim-PET scan in lymphoma[J]. Leuk Lymphoma, 2009, 50(8): 1257−1260. DOI: 10.1080/10428190903040048. [7] 应志涛, 王雪鹃, 宋玉琴, 等. 弥漫大B细胞淋巴瘤患者规范治疗后行18F-FDG PET/CT检查的预后意义[J]. 中华血液学杂志, 2012, 33(10): 810−813. DOI: 10.3760/cma.j.issn.0253−2727.2012.10.005.
Ying ZT, Wang XJ, Song YQ, et al. Prognostic value of 18F-FDG PET/CT after first-line treatment in patients with diffuse large B cell lymphoma[J]. Chin J Hematol, 2012, 33(10): 810−813. DOI: 10.3760/cma.j.issn.0253−2727.2012.10.005.[8] 丁重阳, 李天女, 孙晋, 等. 化疗中期及终末期18F-FDG PET/CT显像对弥漫性大B细胞淋巴瘤患者预后评估价值[J]. 中华核医学与分子影像杂志, 2014, 34(6): 461−465. DOI: 10.3760/cma.j.issn.2095−2848.2014.06.010.
Ding CY, Li TN, Sun J, et al. Prognostic value of interim and post-therapy 18F-FDG PET/CT in patients with diffuse large B-cell lymphoma[J]. Chin J Nucl Med Mol Imaging, 2014, 34(6): 461−465. DOI: 10.3760/cma.j.issn.2095−2848.2014.06.010.[9] Pregno P, Chiappella A, Bellò M, et al. Interim 18-FDG-PET/CT failed to predict the outcome in diffuse large B-cell lymphoma patients treated at the diagnosis with rituximab-CHOP[J]. Blood, 2012, 119(9): 2066−2073. DOI: 10.1182/blood−2011−06−359943. [10] The International Non-Hodgkin's Lymphoma Prognostic Factors Project. A predictive model for aggressive non-Hodgkin's lymphoma[J]. N Engl J Med, 1993, 329(14): 987−994. DOI: 10.1056/NEJM199309303291402. [11] Sehn LH, Berry B, Chhanabhai M, et al. The revised international prognostic index (R-IPI) is a better predictor of outcome than the standard IPI for patients with diffuse large B-cell lymphoma treated with R-CHOP[J]. Blood, 2007, 109(5): 1857−1861. DOI: 10.1182/blood−2006−08−038257. [12] Zhou Z, Sehn LH, Rademaker AW, et al. An enhanced international prognostic index (NCCN-IPI) for patients with diffuse large B-cell lymphoma treated in the rituximab era[J]. Blood, 2014, 123(6): 837−842. DOI: 10.1182/blood−2013−09−524108. [13] 宋腾, 王华庆, 张会来, 等. 改良国际预后指数(NCCN-IPI)对R-CHOP方案治疗弥漫大B细胞淋巴瘤的预后评估(附168例临床分析)[J]. 中国肿瘤临床, 2015, 42(21): 1050−1055. DOI: 10.3969/j.issn.1000−8179.2015.21.977.
Song T, Wang HQ, Zhang HL, et al. Prognostic significance of an enhanced international prognostic index(NCCN-IPI)for patients with diffuse large B-cell lymphoma treated with R-CHOP: a case report of 168 patients[J]. Chin J Clin Oncol, 2015, 42(21): 1050−1055. DOI: 10.3969/j.issn.1000−8179.2015.21.977.[14] Bishton MJ, Hughes S, Richardson F, et al. Delineating outcomes of patients with diffuse large b cell lymphoma using the national comprehensive cancer network-international prognostic index and positron emission tomography-defined remission status; a population-based analysis[J]. Br J Haematol, 2016, 172(2): 246−254. DOI: 10.1111/bjh.13831. [15] Kanemasa Y, Shimoyama T, Sasaki Y, et al. Analysis of prognostic value of complete response by PET-CT and further stratification by clinical and biological markers in DLBCL patients[J]. Med Oncol, 2017, 34(2): 29. DOI: 10.1007/s12032−017−0885−6. [16] Adams HJA, de Klerk JMH, Fijnheer R, et al. Residual anatomical disease in diffuse large B-cell lymphoma patients with FDG-PET-based complete response after first-line R-CHOP therapy: does it have any prognostic value?[J]. J Comput Assist Tomogr, 2015, 39(5): 810−815. DOI: 10.1097/RCT.0000000000000270.