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多发性骨髓瘤(multiple myeloma,MM)是一种浆细胞增殖异常的恶性疾病,约占血液系统恶性肿瘤的10%[1]。MM患者的临床特征及预后差异很大,建立精准的预后评估体系是制定个性化治疗方案和改善预后的关键。
高危细胞遗传学异常(high-risk cytogenetic abnormalities,HRCA)是MM分期的重要指标,与其临床特征具有一定的相关性[2]。近年来,18F-FDG PET/CT作为一种将解剖结构和功能显像相结合的影像学检查方法,已被国际骨髓瘤工作组推荐应用于初诊MM患者的预后评估[3],但目前关于MM患者的18F-FDG PET/CT影像学表现与HRCA相关性的研究较少。本研究旨在分析MM的18F-FDG PET/CT影像学表现与HRCA的相关性,并初步探讨18F-FDG PET/CT影像学表现与HRCA联合应用在MM患者预后评估中的价值。
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44例MM患者的临床特征:年龄<65岁26例、≥65岁18例;无HRCA 25例、有HRCA 19例;R-ISS分期Ⅰ期+Ⅱ期21例、Ⅲ期23例;mSMART 3.0分期标危组16例、高危组28例。18F-FDG PET/CT影像学表现:FLs个数≤3共12例(典型病例的18F-FDG PET/CT显像结果见图1)、>3共32例;SUVmax≤4.2共11例、>4.2共33例;无EMD 共32例、有EMD共12例(图2)。随访结果:44例MM患者均无失访,其中11例出现疾病进展或复发,6例病死。
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由表1可知,FLs个数≤3或>3在有无HRCA分组、不同R-ISS分期和不同mSMART 3.0分期间的差异均有统计学意义(均P<0.05);有无EMD在不同mSMART 3.0分期和有无HRCA分组间的差异均有统计学意义(均P<0.05);SUVmax≤4.2或>4.2在分期和有无HRCA分组间的差异均无统计学意义(均P>0.05)。
因素 例数(%) FLs个数≤3或>3 SUVmax≤4.2或>4.2 无或有EMD χ2值 P值 χ2值 P值 χ2值 P值 性别 0.243 0.622 0.759 0.384 0.744 0.388 男 23(52.3) 女 21(47.7) 年龄 1.200 0.273 1.128 0.479 0.001 1.000 <65岁 26(59.1) ≥65岁 18(40.9) HRCA 8.167 0.004 0.001 1.000 6.808 0.009 无 25(56.8) 有 19(43.2) R-ISS分期 4.919 0.027 0.030 0.862 3.416 0.065 Ⅰ期+Ⅱ期 21(47.7) Ⅲ期 23(52.3) mSMART 3.0分期 8.472 0.004 0.131 0.717 4.061 0.044 标危 16(36.4) 高危 28(63.6) 注:FDG为氟脱氧葡萄糖;PET为正电子发射断层显像术;CT为计算机体层摄影术;HRCA为高危细胞遗传学异常;FLs为局灶病变;SUVmax为最大标准化摄取值;EMD为髓外病变;R-ISS为修订版国际分期系统;mSMART为Mayo骨髓瘤分层级风险调整治疗 表 1 44例初诊多发性骨髓瘤患者18F-FDG PET/CT影像学表现与临床特征、HRCA和分期的比较
Table 1. Comparison of 18F-FDG PET/CT imaging findings with clinical features, high-risk cytogenetic abnormalities and stages in 44 patients newly diagnosed with multiple myeloma
由表2可知,FLs个数>3是HRCA、R-ISS分期和mSMART 3.0分期的独立危险因素(均P<0.05)。EMD不是HRCA、R-ISS分期和mSMART 3.0分期的独立危险因素(均P>0.05)。SUVmax>4.2不是HRCA、R-ISS分期和mSMART 3.0分期的独立危险因素(χ2=0.042~1.357,均P>0.05)。
因素 局灶病变个数>3 有髓外病变 OR值 95%CI P值 OR值 95%CI P值 HRCA 10.952 1.195~100.393 0.034 4.900 0.981~24.483 0.053 R-ISS分期 5.000 1.127~22.181 0.034 2.805 0.592~13.300 0.194 mSMART 3.0分期 10.714 2.269~50.598 0.003 7.184 0.653~79.021 0.107 注:HRCA为高危细胞遗传学异常;R-ISS为修订版国际分期系统;mSMART为Mayo骨髓瘤分层级风险调整治疗;CI 为置信区间 表 2 影响44例初诊多发性骨髓瘤患者HRCA和分期的独立危险因素的分析结果
Table 2. Analysis of independent risk factors affecting high-risk cytogenetic abnormalities and staging in 44 patients newly diagnosed with multiple myeloma
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Log-rank检验结果显示,有无EMD和有无HRCA组间在PFS期和OS期的差异均有统计学意义(均P<0.05,图3)。
图 3 44例初诊多发性骨髓瘤患者的Kaplan-Merier生存曲线
Figure 3. Kaplan-Merier survival curves of 44 patients newly diagnosed with multiple myeloma
Cox比例风险模型多因素分析结果显示,EMD是PFS期和OS期的独立预后不良因素;HRCA是PFS期的独立预后不良因素(均P<0.05,表3)。
因素 无进展生存期 总生存期 OR值 95%CI P值 OR值 95%CI P值 髓外病变 4.466 1.084~18.396 0.038 6.520 1.174~36.211 0.032 高危细胞遗传学异常 8.458 1.671~42.812 0.010 − − 0.155 注: CI 为置信区间;−表示无此项数据 表 3 影响44例初诊多发性骨髓瘤患者预后的Cox比例风险模型多因素的分析结果
Table 3. Analysis of Cox proportional hazards model multiple factors affecting the prognosis of 44 patients newly diagnosed with multiple myeloma
至随访结束,无EMD且无HRCA或仅存在两者之一的患者均未达到中位PFS期和中位OS期,同时存在EMD和HRCA患者的中位PFS期为11个月(P<0.001),中位OS期为17个月(P=0.005),同时存在EMD和HRCA的患者预后较无EMD且无HRCA或仅存在两者之一的患者预后差(图3)。
初诊多发性骨髓瘤患者18F-FDG PET/CT影像学表现与高危细胞遗传学异常的相关性及预后评估
Correlation and prognosis evaluation of 18F-FDG PET/CT imaging findings with high-risk cytogenetic abnormalities in newly diagnosed multiple myeloma patients
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摘要:
目的 探讨初诊多发性骨髓瘤(MM)患者的18F-氟脱氧葡萄糖(FDG) PET/CT影像学表现与高危细胞遗传学异常(HRCA)的相关性及二者联合应用于MM患者预后评估中的价值。 方法 回顾性分析2016年6月至2020年11月于汕头市中心医院经骨髓组织病理学检查和实验室检查确诊为MM并于治疗前行18F-FDG PET/CT显像的44例患者的临床资料和影像学资料,其中男性23例、女性21例,年龄38~91(61.1±9.6)岁。根据荧光原位杂交检测结果将患者分为有HRCA组和无HRCA组;根据国际骨髓瘤工作组发布的修订版国际分期系统(R-ISS)分期标准将患者分为Ⅰ期+Ⅱ期和Ⅲ期2组;根据Mayo骨髓瘤分层级风险调整治疗(mSMART)3.0危险度分层标准将患者分为标危组和高危组。分析所有患者的18F-FDG PET/CT显像资料,根据局灶病变(FLs)个数≤3或>3、最大标准化摄取值(SUVmax)≤4.2或>4.2和有无髓外病变(EMD)分别将患者各分为2组。随访结束后统计患者的无进展生存(PFS)期和总生存(OS)期。采用χ2检验比较MM患者的18F-FDG PET/CT影像学表现与临床特征、HRCA和分期的差异;采用多因素Logistic回归分析MM患者HRCA、R-ISS分期和mSMART 3.0分期的独立危险因素;采用Kaplan-Merier和Log-rank检验比较组间PFS期和OS期的差异;采用Cox比例风险回归模型分析MM患者PFS期和OS期的独立预后不良因素。 结果 FLs个数≤3或>3在不同R-ISS分期、不同mSMART 3.0分期和有无HRCA组间的差异均有统计学意义(χ2=4.919、8.472、8.167,均P<0.05);有无EMD在不同mSMART 3.0分期和有无HRCA组间的差异均有统计学意义(χ2=4.061、6.808,均P<0.05)。FLs个数>3是HRCA、R-ISS分期和mSMART 3.0分期的独立危险因素(OR=10.952、5.000、10.714,95%CI:1.195~100.393、1.127~22.181、2.269~50.598,均P<0.05)。有无EMD和有无HRCA组间PFS期和OS期的差异均有统计学意义(PFS期:χ2=8.572、9.023,均P<0.01;OS期:χ2=6.030、4.877,均P<0.05)。EMD是PFS期和OS期的独立预后不良因素(OR=4.466、6.520,95%CI:1.084~18.396、1.174~36.211,均P<0.05);HRCA是PFS期的独立预后不良因素(OR=8.458,95%CI:1.671~42.812,P<0.05)。截至随访结束,无EMD且无HRCA或仅存在两者之一的患者,均未达到中位PFS期和中位OS期;同时存在EMD和HRCA的患者中位PFS期为11个月(χ2=20.903,P<0.001),中位OS期为17个月(χ2=10.656,P<0.01)。 结论 初诊MM的患者的18F-FDG PET/CT影像学表现与HRCA存在相关性,二者联合应用对MM患者的预后评估有一定的预测价值。 -
关键词:
- 多发性骨髓瘤 /
- 氟脱氧葡萄糖F18 /
- 正电子发射断层显像术;体层摄影术,X线计算机 /
- 细胞遗传学 /
- 预后
Abstract:Objective To investigate the correlation between 18F-fluorodeoxyglucose (FDG) PET/CT imaging findings and high-risk cytogenetic abnormalities (HRCA) in patients newly diagnosed with multiple myeloma (MM), and the value of both combined applications in evaluating the prognosis of patients with MM. Methods The clinical and imaging data of 44 patients with MM diagnosed by bone marrow histopathology and laboratory examination and who underwent 18F-FDG PET/CT imaging before treatment in Shantou Central Hospital from June 2016 to November 2020 were retrospectively analyzed, including 23 males and 21 females, aged 38–91 (61.1±9.6) years old. Patients were divided into the HRCA group and the non-HRCA group according to the result of fluorescence in situ hybridization. Patients were divided into stage Ⅰ+Ⅱ group and stage Ⅲ group according to the Revised-International Staging System (R-ISS) issued by the International Myeloma Working Group. Patients were divided into two groups, a standard-risk group, and a high-risk group according to the Mayo Stratification of Myeloma and Risk-adapted Therapy (mSMART) 3.0 risk stratification criteria. Through the analysis of the 18F-FDG PET/CT imaging data, patients were divided into ≤3 groups and >3 groups according to the number of focal lesions (FLs), divided into ≤4.2 groups and >4.2 groups according to maximum standardized uptake value (SUVmax), divided into extramedullary disease (EMD) group and non-EMD group according to the presence of EMD lesions, respectively. Gather data on progression-free survival (PFS) and overall survival (OS) begins from the first follow-up. Imaging findings with clinical features, HRCA, and prognostic stages were compared using the χ2 test. The independent risk factors of HRCA and stages were analyzed using the multivariate logistic regression analysis. The differences between PFS and OS among the groups were compared using the Kaplan-Meier method and Log-rank test. The independent risk factors of PFS and OS were analyzed using the Cox proportional hazards regression model. Results FLs≤3 or >3 varied among groups of R-ISS, mSMART 3.0, and HRCA (χ2=4.919, 8.472, 8.167; all P<0.05). EMD or non-EMD varied among groups of mSMART 3.0 and HRCA (χ2=4.061, 6.808; both P<0.05). FLs>3 were independent risk factors for HRCA, R-ISS, and mSMART 3.0 (OR=10.952, 5.000, 10.714; 95%CI: 1.195–100.393, 1.127–22.181, 2.269–50.598; all P<0.05). PFS and OS varied among groups of EMD and HRCA (PFS: χ2=8.572, 9.023; both P<0.01 and OS: χ2=6.030, 4.877; both P<0.05). EMD was an independent poor prognosis factor for both PFS and OS (OR=4.466, 6.520; 95%CI: 1.084–18.396, 1.174–36.211; both P<0.05). HRCA was an independent poor prognosis factor for PFS (OR=8.458, 95%CI: 1.671–42.812, P<0.05). By the end of follow-up, patients without EMD and HRCA or only one of them had not reached median PFS and median OS; median PFS for patients with both EMD and HRCA was 11 months (χ2=20.903, P<0.001) and median OS were 17 months (χ2=10.656, P<0.01). Conclusion There is a significant correlation between 18F-FDG PET/CT imaging findings and HRCA in patients newly diagnosed with MM, and the combination of both has a certain predictive value for the prognosis of patients with MM. -
表 1 44例初诊多发性骨髓瘤患者18F-FDG PET/CT影像学表现与临床特征、HRCA和分期的比较
Table 1. Comparison of 18F-FDG PET/CT imaging findings with clinical features, high-risk cytogenetic abnormalities and stages in 44 patients newly diagnosed with multiple myeloma
因素 例数(%) FLs个数≤3或>3 SUVmax≤4.2或>4.2 无或有EMD χ2值 P值 χ2值 P值 χ2值 P值 性别 0.243 0.622 0.759 0.384 0.744 0.388 男 23(52.3) 女 21(47.7) 年龄 1.200 0.273 1.128 0.479 0.001 1.000 <65岁 26(59.1) ≥65岁 18(40.9) HRCA 8.167 0.004 0.001 1.000 6.808 0.009 无 25(56.8) 有 19(43.2) R-ISS分期 4.919 0.027 0.030 0.862 3.416 0.065 Ⅰ期+Ⅱ期 21(47.7) Ⅲ期 23(52.3) mSMART 3.0分期 8.472 0.004 0.131 0.717 4.061 0.044 标危 16(36.4) 高危 28(63.6) 注:FDG为氟脱氧葡萄糖;PET为正电子发射断层显像术;CT为计算机体层摄影术;HRCA为高危细胞遗传学异常;FLs为局灶病变;SUVmax为最大标准化摄取值;EMD为髓外病变;R-ISS为修订版国际分期系统;mSMART为Mayo骨髓瘤分层级风险调整治疗 表 2 影响44例初诊多发性骨髓瘤患者HRCA和分期的独立危险因素的分析结果
Table 2. Analysis of independent risk factors affecting high-risk cytogenetic abnormalities and staging in 44 patients newly diagnosed with multiple myeloma
因素 局灶病变个数>3 有髓外病变 OR值 95%CI P值 OR值 95%CI P值 HRCA 10.952 1.195~100.393 0.034 4.900 0.981~24.483 0.053 R-ISS分期 5.000 1.127~22.181 0.034 2.805 0.592~13.300 0.194 mSMART 3.0分期 10.714 2.269~50.598 0.003 7.184 0.653~79.021 0.107 注:HRCA为高危细胞遗传学异常;R-ISS为修订版国际分期系统;mSMART为Mayo骨髓瘤分层级风险调整治疗;CI 为置信区间 表 3 影响44例初诊多发性骨髓瘤患者预后的Cox比例风险模型多因素的分析结果
Table 3. Analysis of Cox proportional hazards model multiple factors affecting the prognosis of 44 patients newly diagnosed with multiple myeloma
因素 无进展生存期 总生存期 OR值 95%CI P值 OR值 95%CI P值 髓外病变 4.466 1.084~18.396 0.038 6.520 1.174~36.211 0.032 高危细胞遗传学异常 8.458 1.671~42.812 0.010 − − 0.155 注: CI 为置信区间;−表示无此项数据 -
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