弥漫性大B细胞淋巴瘤预后因素研究进展

弥漫性大B细胞淋巴瘤（DLBCL）是最常见的侵袭性非霍奇金B细胞淋巴瘤，具有高度异质性，识别高危患者尤为重要，目前已经发现多种因素影响其预后。笔者根据国内外的研究进展，从临床特征、分子生物学特征和PET/CT多方面对影响DLBCL患者预后的因素进行综述。     

PET/CT不同评价体系在弥漫性大B细胞淋巴瘤预后评估中的应用

弥漫性大B细胞淋巴瘤(DLBCL)是发病率较高的淋巴造血系统疾病,该病进展较快、病死率较高。如何通过现有的检查技术精确地对患者进行预后评估是研究者们面临的一大难题。目前,PET/CT以其能同时提供解剖及功能图像的独特优势,广泛地应用于淋巴瘤的治疗监测及预后评估中,但采用哪种评价体系对图像进行判读的准确率更高仍存在较大争议。笔者综述了PET/CT定性、半定量及其他新的评价体系在DLBCL预后评估中的应用价值。     

化疗结束时 18F-FDG PET/CT Lugano淋巴瘤疗效评估标准与弥漫性大B细胞淋巴瘤预后的关系

目的:探讨化疗结束时 18F-FDG PET/CT Lugano淋巴瘤疗效评估标准与弥漫性大B细胞淋巴瘤(DLBCL)患者预后的关系。 方法:回顾性分析2013年7月至2021年1月于河北医科大学第四医院诊治并于化疗结束时行 18F-FDG PET/CT的DLBCL患者131例[男63...     

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

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。     

18F-FDG PET/CT代谢参数MTV在弥漫大B细胞淋巴瘤预后预测中的研究进展

弥漫大B细胞淋巴瘤（DLBCL）是最常见的血液系统恶性肿瘤之一,常规采用利妥昔单抗联合环磷酰胺+阿霉素+长春新碱+泼尼松的治疗方案已将DLBCL的治愈率提高,但是不同患者的预后差异较大,目前预测预后的方法存在一定的局限性。18F-氟脱氧葡萄糖（FDG）PET/CT已广泛应用于DLBCL的诊疗中,其代谢参数代谢肿瘤体积（MTV）是DLBCL预后强有力的预测因子,但如何将MTV更好地应用于临床尚存在一些争议,笔者就MTV在DLBCL预后预测中的研究进展进行综述。     

18F-FDG PET/CT对化疗中期弥漫性大B细胞淋巴瘤患者预后判断的价值

目的 探讨18F-氟脱氧葡萄糖（FDG）PET/CT参数对化疗中期弥漫性大B细胞淋巴瘤（DLBCL）患者预后判断的价值。 方法 回顾性分析2011年1月至2020年1月河北医科大学第四医院112例DLBCL患者的临床资料和化疗3~4周期后（中期）18F-FDG PET/CT显像资料，其中男性60例、女性52例，年龄16~79（49.5±16.6）岁。以最大标准化摄取值（SUV_max）的40%为阈值勾画感兴趣区（ROI），获得病灶的SUV_max、全身所有病灶总的代谢肿瘤体积（TMTV）、总的糖酵解总量（TTLG），在CT图像上测量6个靶病灶的最大垂直径乘积之和（SPD）。采用受试者工作特性（ROC）曲线计算各代谢参数和解剖测量参数预测患者无进展生存（PFS）期和总生存（OS）期的最佳临界值。采用Kaplan-Meier法进行生存分析，采用Log-rank检验进行单因素分析，采用Cox比例风险回归模型对单因素分析有统计学意义的预后影响因素进行多因素分析。 结果 112例DLBCL患者中，在随访期间25例（22.3%）出现疾病进展、14例（12.5%）死亡。18F-FDG PET/CT 参数SUV_max、TMTV、TTLG和SPD预测DLBCL患者PFS期的最佳临界值分别为1.75、6.40 cm3、9.30 g和3.53 cm2，曲线下面积（AUC）分别为0.712、0.652、0.680、0.728（95%CI:0.596~0.829、0.518~0.787、0.549~0.811、0.619~0.837，均P<0.05）；预测OS期的最佳临界值分别为3.75、17.80 cm3、19.05 g和5.67 cm2，AUC分别为0.727、0.686、0.727、0.757（95%CI:0.578~0.877、0.512~0.861、0.559~0.896、0.622~0.891，均P<0.05）。单因素分析结果显示，年龄、美国东部肿瘤协作组（ECOG）评分、国际预后指数评分、美国国家综合癌症网络-国际预后指数评分、Deauville评分以及SUV_max、TMTV、TTLG、SPD均是DLBCL患者PFS期（χ2=5.152~22.998，均P<0.05）和OS期的影响因素（χ2=4.735~19.687，均P<0.05）；乳酸脱氢酶（LDH）水平是OS期的影响因素（χ2=4.154，P<0.05），但不是PFS期的影响因素（χ2=2.223，P>0.05）。多因素分析结果显示，年龄、ECOG评分、TTLG是影响DLBCL患者PFS期的独立危险因素（HR=0.331、0.262、0.281，95%CI:0.145~0.753、0.113~0.605、0.119~0.666，均P<0.01）；LDH水平、SPD是影响DLBCL患者OS期的独立危险因素（HR=0.594、1.922，95%CI:0.360~0.979、1.123~3.290，均P<0.05）。 结论 18F-FDG PET/CT参数 SUV_max、TMTV、TTLG、SPD对化疗中期DLBCL患者预后有较好的判断价值。     

~(18)F-FDG PET/CT在弥漫大B细胞淋巴瘤诊断和化疗中期疗效评价的研究

目的应用氟标记的氟代脱氧葡萄糖(~(18)F-FDG)正电子发射计算机断层显像及传统CT显像在弥漫大B细胞淋巴瘤(DLBCL)化疗中期治疗前分期及治疗2～4疗程后疗效评价,应用新的肿瘤评价系统PERCIST标准草案(PER-CIST),将病例图像进行归一化和标准化后进行疗效评估。方法回顾分析我院2011年9月～2015年9月,在本科检查经病理确诊DLBCL 66例,均为初诊患者。66例患者均进行国际预后指数评分及分期,评价初诊患者分期及临床分期。在治疗前及化疗2～4个周期后行~(18)F-FDG PET/CT显像及CT显像,依据中国DLBCL诊断与治疗指南(2013年版),所有患者均根据行免疫化疗(R-CH0P)治疗方案,根据疗效分为有效组及无效组。PET/CT与传统影像CT比较灵敏度、特异性、准确率、阳性预测值及阴性预测值及化疗前后最大病灶标准化摄取值(SUVmax)。应用肿瘤评价系统PERCIST标准,对66例患者中21例行图像处理,得到完全代谢缓解(CMR)和代谢恶化(PMD)等对疗效进行评价。结果 1)本研究~(18)F-FDG PET/CT与CT二者在灵敏度、准确率、阳性预测值及阴性预测值等方面比较,PET/CT比CT分别提高了17. 77%、21. 44%、5. 6%、86. 2%,差异均有统计学意义(X~2=36. 43,P=0. 00;X~2=45. 62,P=0. 00;X~2=6. 25,P=0. 01;X~2=30. 78,P=0. 00); 2) 66例DLBCL患者化疗后:CT评价中的19名PR患者中,10位患者在PET/CT疗效评价标准中为重新修定为CR; CT评价27例CR患者中,8位患者PET/CT发现新增病灶; 3) DLBCL患者行化疗前、2～4疗程化疗后病灶SUVmax之间差异具有统计学意义(t=3. 58,P 0. 05),治疗有效组SUVmax呈下降趋势,无效组呈上升趋势; 4)应用肿瘤评价系统PERCIST标准疗效评价,能够更好的从定量水平观察病变代谢水平变化,评价肿瘤是否有活性,进行中期疗效评价。结论在化疗中期对DLBCL患者行~(18)F-FDG PET/CT显像对临床诊断、分期及疗效评价有较大的临床价值。     

恶性淋巴瘤的多模态显像研究进展

医学影像学技术在肿瘤的临床分期、再分期、疗效评价甚至预后判断中发挥着重要作用,多模态影像技术（如PET/CT和PET/MR）近年来发展的非常迅速。18F-FDG PET/CT已广泛用于亲和18F-FDG的恶性淋巴瘤的初始分期以及疗效评估,治疗期间使用18F-FDG PET/CT评估治疗反应的价值尚不确定,初步的研究认为PET/MR应用于淋巴瘤的分期是可行的。笔者就多模态显像PET/CT、PET/MR在淋巴瘤中的研究现状及进展进行综述。     

基于18F-FDG PET代谢参数及临床参数的列线图生存预测模型预测弥漫大B细胞淋巴瘤患者预后的价值

目的 构建基于18F-氟脱氧葡萄糖（FDG）PET代谢参数及临床参数的列线图生存预测模型，并验证其对弥漫大B细胞淋巴瘤（DLBCL）患者预后的预测价值。 方法 回顾性分析2011年3月至2019年11月于南京大学医学院附属鼓楼医院以及南京医科大学第一附属医院经组织病理学检查确诊的383例未经治疗的DLBCL患者的18F-FDG PET/CT影像学资料和临床资料，其中男性204例、女性179例，年龄19~93（47.3±14.9）岁。按照7∶3的比例采用随机数字表法将患者分为训练组（n=268例）和验证组（n=115例）。勾画并计算患者总肿瘤代谢体积（TMTV）和病灶糖酵解总量（TLG）。采用Kaplan Meier生存分析、单因素和多因素Cox比例风险回归模型对患者无进展生存（PFS）期及总生存（OS）期进行预后分析并构建生存预测模型。通过训练组和验证组的校准曲线、一致性指数（C-index）以及临床决策曲线分析（DCA）对预测模型进行评估。 结果 训练组单因素分析结果显示，年龄、乳酸脱氢酶（LDH）水平、美国东部肿瘤协作组行为状态（ECOG PS）评分、Ann Abor分期、大包块、TMTV及TLG为预测PFS期的危险影响因素（HR=1.670~3.277，均P<0.05）；年龄、LDH水平、B症状、ECOG PS评分、Ann Abor分期、大包块、TMTV及TLG为预测OS期的危险影响因素（HR=1.661~4.193，均P<0.05）。训练组多因素分析结果表明，年龄、LDH水平、Ann Abor分期及TLG是预测DLBCL患者PFS期和OS期的独立影响因素（HR=1.589~3.367，均P<0.05）。校准曲线显示，该预测模型具有较好的预测一致性；C-index评估结果显示，训练组和验证组预测模型具有较高的准确性（PFS期:0.724对0.762； OS期:0.749对0.753）。临床DCA结果表明，预测模型可以给患者带来更多的临床获益。 结论 基于18F-FDG PET代谢参数TLG及临床参数（年龄、LDH水平、Ann Abor分期）生存预测模型能够很好地对DLBCL患者进行预后评估，为精准个性化治疗提供可能。     

眼眶淋巴瘤多模态影像分析

【摘要】目的：探讨眼眶淋巴瘤多模态影像学特征。方法：回顾性分析27例经病理证实为眼眶淋巴瘤患者的治疗前MRI、CT增强扫描及18F-FDG PET/CT影像。评估内容包括病灶的MRI特征、CT增强扫描特征及最大标准摄取值（SUVmax）。结果：总共收集27例（34眶）患者,其中25例（31眶）行眼眶MR扫描,10例（13眶）行CT增强扫描及18F-FDG PET/CT扫描。病变多位于眶隔前区（15.38%）、泪腺区（23.08%）及肌锥区（21.54%）。病灶在压脂T2WI上,11例呈均匀稍高信号,13例呈等信号,1例呈混杂高信号;压脂T1WI上,24例呈等信号,1例呈稍低信号;压脂T1WI增强扫描上,15例呈中度均匀强化,8例为轻度均匀强化,2例为不均匀强化;7例可见骨质破坏。10例行CT增强扫描及18F-FDG PET/CT扫描患者中,病理组织类型为黏膜相关淋巴组织边缘区B细胞（MALT）淋巴瘤5例,弥漫大B细胞淋巴瘤（DLBCL）5例,其中1例DLBCL患者在CT上表现为不均匀密度,其余9例表现为均匀密度。两种病理类型病灶的△CT值差异无统计学意义（统计值0.60,P>0.05）。DLBCL与MALT淋巴瘤病灶的SUVmax差异具有统计学意义［6.40（5.40～7.10） vs. 11.40（9.63～25.60）,P=0.009］。结论：眼眶淋巴瘤病变多位于眶隔前区、泪腺区及肌锥区。MRI上病灶压脂T1WI多呈等信号,压脂T2WI呈等或稍高信号,增强扫描呈轻到中度强化;在CT上表现为均匀密度,增强扫描呈轻到中度强化,病灶的强化程度对鉴别DLBCL和MALT淋巴瘤无帮助。在18F-FDG PET/CT中,DLBCL的SUVmax较高,病灶的SUVmax 有助于鉴别DLBCL和MALT淋巴瘤。     

18F-FDG-PET/MRI in lymphoma patients

The introduction of hybrid PET/MRI imaging using integrated systems into clinical practice has opened up the possibility of reducing the radiation dose from hybrid imaging by eliminating the contribution from computed tomography. Studies comparing the possibilities of PET/CT and PET/MRI imaging demonstrated it is possible to use the advantages of the high contrast resolution of magnetic resonance for soft tissue and bone marrow along with PET records in a quality comparable to PET/CT imaging. The significant feature for PET imaging in Hodgkińs lymphoma is that it is a tissue with high levels of radiopharmaceutical accumulation, which decreases proportionally after successful therapeutic effect, the effect of therapy is assessed using Deauville score system on interim examinations. While the efficacy of prognosis determined using the Deauville scale in HL is widely accepted, it turns out that in DLBCL, the prognostic value of PET imaging is bound to the evaluation of subtypes. PET/MRI scanning can be used to evaluate a relapse if follicular lymphoma has already been treated, or to confirm transformation into more aggressive forms. In children and adults with Burkitt's lymphoma, negative findings after induction therapy have a high negative predictive value for relapse prognosis.     

Interim FDG PET/CT as a prognostic factor in diffuse large B-cell lymphoma

Purpose

Interim ¹⁸F-FDG PET performed early during the course of therapy in diffuse large B-cell lymphoma (DLBCL) is a good predictor of outcome. However, interpretation criteria for interim PET for the evaluation of tumour response are still not clearly defined. The study aim was to assess whether interim PET can predict overall survival (OS) and progression-free survival (PFS) in DLBCL patients following three different sets of parameters, two qualitative (visual) methods and one semiquantitative.

Methods

A total of 50 newly diagnosed DLBCL patients were prospectively enrolled in this study. All patients had a PET/CT scan at diagnosis and an interim PET/CT scan after the second or third cycle of chemotherapy. Three methods of evaluation for the interim PET/CT were used: a qualitative three-point scoring (3-PS) method, a qualitative 5-PS method and a semiquantitative method (ΔSUV_max). The degree of correlation between therapy response seen on FDG PET and PFS and OS was determined.

Results

The analysis of the visual 3-PS method showed no statistically significant difference in PFS and OS. The estimated 5-year PFS and OS were 79 % and 92 %, respectively, in patients with an interim PET scan showing uptake not greater than in the liver versus 50 % in patients with uptake greater than in the liver, and this difference was statistically significant. The optimal cut-off value of ΔSUV_max that could predict the PFS and OS difference in patients with DLBCL was 76 % (95 % CI 62.7–89.2 %) and 75 % (95 % CI, 54.6–95.4 %), respectively.

Conclusion

Our results support the use of liver uptake as an indicator in the qualitative evaluation of interim PET, or a ΔSUV_max greater than 75 % in semiquantitative analysis. Interim PET may predict PFS and OS and could be considered in the prognostic evaluation of DLBCL.     

Perspectives of molecular imaging and radioimmunotherapy in lymphoma

Successful treatment of Hodgkin lymphomas and non-Hodgkin lymphomas depends on accurate staging and prognostic estimations, as well as evaluation of response to therapy as early after initiation as possible. We focus on several aspects of molecular imaging and therapy that affect the management of patients who have lymphoma. First, we review prior use of gallium-67 citrate for evaluation of lymphoma patients, mainly from a historical perspective, since it was the mainstream lymphoma functional imaging tracer for decades. Next, we review current clinical uses of 18F Fluoro-2-Deoxyglucose (18F FDG) PET and PET/CT for evaluation of lymphoma patients and use of radioimmunotherapy in lymphoma. Finally, we discuss advances in molecular imaging that may herald the next generation of PET radiotracers after 18F FDG.     

18F-FDG PET/CT在弥漫性大B细胞淋巴瘤疗效评价中的临床价值

目的 探讨18F-FDG PET/CT在弥漫性大B细胞淋巴瘤（DLBCL）化疗早期及化疗后疗效评价中的临床价值。 方法 回顾性分析采用美罗华联合环磷酰胺+多柔比星+长春新碱+泼尼松方案或环磷酰胺+多柔比星+长春新碱+泼尼松方案化疗的34例DLBCL患者的PET/CT结果。所有患者分别在化疗前、化疗6疗程后行PET/CT,比较化疗前后病灶最大标准化摄取值（SUV_max）及病灶最大直径（D_max）;其中12例患者于化疗前、第2疗程结束后、第4疗程结束后行PET/CT,比较3组间的SUV_max与D_max。对在化疗6疗程后行PET/CT显像已达到完全缓解的8例和部分缓解的10例患者进行临床随访,观察1年无进展生存期（PFS）。 结果 ①34例患者化疗前和6疗程化疗后,SUV_max之间和D_max之间的差异均有统计学意义（t=3.58和2.96,P均 < 0.05）。② 12例患者在化疗前、第2疗程结束后、第4疗程结束后,SUV_max之间和D_max之间的差异均有统计学意义（F=18.64和4.33,P均 < 0.05）;第2疗程结束后与化疗前相比,病灶D_max未见显著变化（t=1.05,P > 0.05）,SUV_max显著降低（t=5.37,P < 0.05）;第4疗程结束后与化疗前相比,SUV_max之间和D_max之间的差异均具有统计学意义（t=8.56和3.90,P均 < 0.05）。③对18例患者进行的随访发现,完全缓解的8例中,PFS > 1年者6例,PFS < 1年者2例;部分缓解的10例中,PFS > 1年者2例,PFS < 1年者8例。 结论 在DLBCL化疗早期及化疗后的疗效评价上,PET比CT更灵敏,以两种显像方法相结合的PET/CT在淋巴瘤疗效评价上具有较高的临床价值。     

Different predictive values of interim <Superscript>18</Superscript>F-FDG PET/CT in germinal center like and non-germinal center like diffuse large B-cell lymphoma

Purpose

Diffuse large B-cell lymphoma (DLBCL) is a pathologically heterogeneous disease with different prognoses according to its molecular profiles. Despite the broad usage of ¹⁸F-fluoro-2-dexoxy-d-glucose (FDG) positron emission tomography/computed tomography (PET/CT), previous studies that have investigated the value of interim ¹⁸F-FDG PET/CT in DLBCL have given the controversial results. The purpose of this study was to evaluate the prognostic value of interim ¹⁸F-FDG PET/CT in DLBCL according to germinal center B cell-like (GCB) and non-GCB molecular profiling.

Methods

We enrolled 118 newly diagnosed DLBCL patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP). Interim ¹⁸F-FDG PET/CT scans performed after 2 or 3 cycles of R-CHOP treatment were evaluated based on the Lugano response criteria. Patients were grouped as GCB or non-GCB molecular subtypes according to immunohistochemistry results of CD10, BCL6, and MUM1, based on Hans’ algorithm.

Results

In total 118 DLBCL patients, 35 % were classified as GCB, and 65 % were classified as non-GCB. Interim PET/CT was negative in 70 %, and positive in 30 %. During the median follow-up period of 23 months, the positive interim ¹⁸F-FDG PET/CT group showed significantly inferior progression free survival (PFS) compared to the negative interim ¹⁸F-FDG PET/CT group (P = 0.0004) in entire patients. A subgroup analysis according to molecular profiling demonstrated significant difference of PFS between the positive and negative interim ¹⁸F-FDG PET groups in GCB subtype of DLBCL (P = 0.0001), but there was no significant difference of PFS between the positive and negative interim ¹⁸F-FDG PET groups in non-GCB subtype of DLBCL.

Conclusions

Interim ¹⁸F-FDG PET/CT scanning had a significant predictive value for disease progression in patients with the GCB subtype of DLBCL treated with R-CHOP, but not in those with the non-GCB subtype. Therefore, molecular profiles of DLBCL should be considered for interim ¹⁸F-FDG PET/CT practice.

     

Diagnostic and prognostic impact of 18F-FDG PET/CT in follicular lymphoma

Purpose

The aim of this study was to assess the usefulness of positron emission tomography/computed tomography in staging, prognosis evaluation and restaging of patients with follicular lymphoma.

Methods

A retrospective study was performed on 45 patients with untreated biopsy-proven follicular lymphoma who underwent ¹⁸F-fluorodeoxyglucose PET/CT (FDG PET/CT) and CT before and after chemoimmunotherapy induction treatment (rituximab combined with cyclophosphamide, doxorubicin, vincristine and prednisone).

Results

PET/CT detected more nodal (+51%) and extranodal (+89%) lesions than CT. PET/CT modified Ann Arbor staging in eight patients (18%). Five patients (11%) initially considered as being early stage (I/II) were eventually treated as advanced stage (III/IV). In this study, an initial PET/CT prognostic score was significantly more accurate than the Follicular Lymphoma International Prognostic Index score in identifying patients with poor prognosis (i.e. patients with incomplete therapeutic response or early relapse). The accuracy of PET/CT for therapeutic response assessment was higher than that of CT (0.97 vs 0.64), especially due to its ability to identify inactive residual masses. In addition, post-treatment PET/CT was able to predict patients’ outcomes. The median progression-free survival was 48 months in the PET/CT-negative group as compared with 17.2 months for the group with residual uptake (p?<?10^?4).

Conclusion

FDG PET/CT is useful for staging and assessing the prognosis and therapeutic response of patients with follicular lymphoma.     

PET/CT在结外NK/T细胞淋巴瘤诊治中的应用进展

结外自然杀伤/T细胞淋巴瘤（ENKTL）是一种与EB病毒感染相关的非霍奇金淋巴瘤亚型,其侵袭性强,预后不良。准确的诊断和分期、及时的疗效及预后评估对患者治疗策略的制定至关重要。随着18F-FDG PET/CT在淋巴瘤中的广泛应用,其在ENKTL中的价值也越来越受到重视,笔者对PET/CT在ENKTL诊治中的应用进展进行综述。