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在非小细胞肺癌(non-small cell lung cancer,NSCLC)的远处转移中,骨转移较为多见,其早期隐匿但晚期多伴有疼痛、病理性骨折等症状,严重影响了患者的生活质量。临床上99Tcm-MDP全身骨显像是诊断骨转移的首选方法,但其具有灵敏度较高但特异度较低的局限。SPECT/CT同机断层融合显像可以对异常放射性浓聚灶进行局部CT扫描,从而得到病灶局部的骨盐代谢及解剖结构的融合图像,提高诊断的灵敏度和准确率[1]。血清癌胚抗原(carcinoembryonic antigen,CEA)和可溶性细胞角蛋白19片段(cytokeratin-19-fragment,CYFRA21-1)是临床常用的辅助诊断NSCLC的肿瘤标志物。笔者旨在研究SPECT/CT断层融合显像联合血清肿瘤标志物在诊断NSCLC骨转移中的应用。
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骨转移患者68例,未发生骨转移患者75例,骨转移发生率47.5%,其中腺癌50例,鳞癌18例。腺癌M1组13例,M2组7例,M3组30例;鳞癌M1组8例,M2组7例,M3组3例。腺癌骨转移发生率高于鳞癌,差异有统计学意义(73.5% vs. 26.5%,χ2=10.56,P<0.05)。
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最终68例确诊为骨转移的病例共有586处骨转移病灶,其中,腺癌骨转移病灶为526处,磷癌为60处,二者间骨转移病灶数差异有统计学意义(χ2=19.23,P < 0.05)。将患者发生骨转移的部位划分为颅骨、脊柱、胸部、四肢骨及骨盆,腺癌患者转移灶发生率最高的部位为脊柱35.9%(189/526),其次为胸部32.7%(172/526)、骨盆17.4%(92/526)、四肢骨8.4%(44/526)和颅骨5.5%(29/526);鳞癌患者转移灶发生率最高的部位为胸部51.7%(31/60)、其次为脊柱26.7%(16/60)、四肢骨16.7%(10/60)、骨盆3.3%(2/60)和颅骨1.7%(1/60)。
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NSCLC骨转移及未发生骨转移患者血清CEA水平中位数分别为8.39 ng/mL和3.22 ng/mL(Z=4.98,P<0.05)、CYFRA21-1水平中位数分别为3.95 ng/mL和2.93 ng/mL(Z=2.55,P<0.05)。骨转移患者的血清CEA、CYFRA21-1水平高于未发生骨转移的患者,差异具有统计学意义。
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NSCLC骨转移患者血清CEA与骨转移灶的数目无显著相关性(r=0.141,P>0.05),CYFRA21-1与骨转移灶的数目具有一定相关性(r=0.502,P<0.01)。
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全身骨显像、SPECT/CT同机断层融合显像与血清CEA、CYFRA21-1等肿瘤标志物在诊断骨转移中的价值对比如表 1所示。结果表明,全身骨显像在诊断NSCLC骨转移中的灵敏度、特异度、准确率与血清CEA(χ2=0.93、0.03、0.03,均P>0.05)及CYFRA21-1(χ2=1.16、0.03、0.54,均P>0.05)相比差异无统计学意义;SPECT/CT同机断层融合显像诊断NSCLC骨转移的灵敏度、特异度、准确率均高于血清CEA(χ2=4.09、23.08、24.33,均P<0.05),SPECT/CT同机断层融合显像诊断NSCLC骨转移的特异度、准确率高于CYFRA21-1(χ2=20.28、12.55,均P<0.05)及全身骨显像(χ2=21.66、16.05,均P<0.05)。SPECT/CT同机断层融合显像诊断NSCLC骨转移的灵敏度与血清CYFRA21-1(χ2=0,P>0.05)、全身骨显像(χ2=1.16,P>0.05)的差异无统计学意义。而SPECT/CT同机断层融合显像联合血清肿瘤标志物诊断骨转移的灵敏度、特异度、准确率分别高于血清CEA(χ2=18.89、38.89、24.33,均P<0.05)、CYFRA21-1(χ2=6.89、35.50、39.17,均P<0.05)及单独应用全身骨显像(χ2=12.55、37.17、47.45,均P<0.05),SPECT全身骨显像联合血清肿瘤标志物诊断NSCLC骨转移的灵敏度、准确率高于单独应用SPECT/CT同机断层融合显像(χ2=6.89、9.53,均P<0.05),单独应用SPECT/CT同机断层融合显像与SPECT全身骨显像联合血清肿瘤标志物诊断骨转移瘤的特异度差异无统计学意义(χ2=3.25,P>0.05)。
诊断方法 灵敏度 特异度 准确率 血清CEA (47/68)69.1%a (35/75)46.7%a (82/143)57.3%a CYFRA21-1 (57/68)83.8%b (37/75)49.3%b (94/143)65.7%b 全身骨显像 (52/68)76.4%c (36/75)48.0%c (88/143)58.7%c SPECT/CT同机断层融合 (57/68)83.8%d (63/75)84.0% (120/143)83.9%d SPECT/CT同机断层融合+血清肿瘤标志物 (66/68)97.0% (70/75)93.3% (136/143)95.1% 注:表中,a:与SPECT/CT同机断层融合、SPECT/CT同机断层融合+血清肿瘤标志物比较,灵敏度(χ2=4.09、18.89,均P < 0.05)、特异度(χ2=23.08、38.89,均P < 0.05)和准确率(χ2=24.33、24.33,均P < 0.05)差异具有统计学意义;b:与SPECT/CT同机断层融合+血清肿瘤标志物比较,灵敏度(χ2=6.89,P < 0.05)差异具有统计学意义;与SPECT/CT同机断层融合、SPECT/CT同机断层融合+血清肿瘤标志物比较,特异度(χ2=20.28、35.50,均P < 0.05)、准确率(χ2=12.55、39.17,均P < 0.05)差异具有统计学意义;c:与SPECT/CT同机断层融合+血清肿瘤标志物比较,灵敏度(χ2=12.55,P < 0.05)差异具有统计学意义;与SPECT/ CT同机断层融合、SPECT/CT同机断层融合+血清肿瘤标志物比较,特异度(χ2= 21.66、37.17,均P < 0.05)、准确率(χ2=16.05、47.45,均P < 0.05)差异具有统计学意义;d:与SPECT/CT同机断层融合+血清肿瘤标志物比较,灵敏度(χ2=6.89,P < 0.05)、准确率(χ2=9.53,P < 0.05)差异具有统计学意义;CEA:癌胚抗原;CYFRA21-1:可溶性细胞角蛋白19片段;SPECT/CT:单光子发射计算机体层摄影术。 表 1 血清CEA、CYFRA21-1、全身骨显像、SPECT/CT同机断层融合显像在诊断非小细胞肺癌骨转移中价值的对比
Table 1. Diagnostic value of serum CEA, CYFRA21-1, whole body bone imaging and SPECT/CT tomographic fusion imaging in diagnosis of non-small cell lung cancer bone metastasis
SPECT/CT断层融合显像联合血清CEA、CYFRA21-1在诊断非小细胞肺癌骨转移中的应用
Application of SPECT/CT tomographic fusion imaging combined with serum CEA and CYFRA21-1 in the diagnosis of bone metastasis of non-small cell lung cancer
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摘要:
目的研究SPECT/CT断层融合显像联合血清肿瘤标志物癌胚抗原(CEA)、可溶性细胞角蛋白19片段(CYFRA21-1)在诊断非小细胞肺癌(NSCLC)骨转移中的应用。 方法选取143例经病理确诊为NSCLC的患者(腺癌88例,鳞癌55例),抽取其静脉血测定血清CEA、CYFRA21-1的水平,并行全身骨显像和SPECT/CT融合显像。血清CEA、CYFRA21-1之间的比较采用Mann-Whitney U秩和检验。血清CEA、CYFRA21-1水平与骨转移数目的相关性采用Spearman相关性分析;肺腺癌和肺鳞癌骨转移的发生率、骨转移灶数目、全身骨显像、SPECT/CT同机断层融合显像与血清CEA、CYFRA21-1单用或联合应用诊断骨转移的灵敏度、特异度和准确率的比较采用χ2检验。 结果68例患者证实发生骨转移,病灶共有586个。腺癌骨转移发生率(50/88)高于鳞癌(18/55)(χ2=10.56,P < 0.05);腺癌骨转移病灶数比例(526/586)大于鳞癌(χ2=19.23,P < 0.05);骨转移患者的血清CEA(Z=4.98,P < 0.05)、CYFRA21-1(Z=2.55,P < 0.05)水平高于未发生骨转移患者;NSCLC骨转移患者血清CEA与骨转移灶的数目无显著相关性(r=0.141,P>0.05),而CYFRA21-1与骨转移灶的数目具有一定相关性(r=0.502,P < 0.01)。血清CEA、CYFRA21-1水平诊断NSCLC骨转移具有一定的灵敏度(69.1%、83.8%),但特异度(47.6%、49.3%)、准确率(57.3%、65.7%)较低,而SPECT/CT同机断层融合显像在诊断NSCLC骨转移时具有较高的灵敏度(83.8%)、特异度(84.0%)、准确率(83.9%),高于血清CEA(χ2=4.09、23.08、24.33,均P < 0.05),特异度和准确率高于CYFRA21-1(χ2=20.28、12.55,均P < 0.05)及全身骨显像(χ2=21.66、16.05,均P < 0.05)。而SPECT/CT同机断层融合显像联合血清CEA及CYFRA21-1诊断NSCLC骨转移的灵敏度(97.0%)、特异度(93.3%)、准确率(95.1%)分别高于血清CEA(χ2=18.89、38.89、24.33,均P < 0.05)、CYFRA21-1(χ2=6.89、35.50、39.17,均P < 0.05)、单独应用全身骨显像(χ2=12.55、37.17、47.45,均P < 0.05),灵敏度、准确率高于单独应用SPECT/CT同机断层融合显像(χ2=6.89、9.53,均P < 0.05)。 结论SPECT/CT断层融合显像联合血清CEA、CYFRA21-1诊断NSCLC骨转移的发生具有较高的灵敏度、特异度、准确率,在临床工作中具有一定的应用价值。 -
关键词:
- 癌,非小细胞肺 /
- 肿瘤转移 /
- 单光子发射计算机体层摄影术 /
- 癌胚抗原 /
- 可溶性细胞角蛋白19片段
Abstract:ObjectiveThis study aims to study the role of SPECT/CT tomographic fusion imaging in combination with serum tumor markers such as CEA and CYFRA21-1 to diagnose bone metastasis of NSCLC. MethodsA total of 143 patients with pathologically confirmed NSCLC were selected as study subjects(adenocarcinoma 88 cases, squamous cell 55 cases). Venous blood samples were collected to determine the serum levels of CEA and CYFRA21-1, and a whole body bone scan and SPECT/CT tomographic fusion imaging was performed. SPSS 22.0 software was used to compare serum CEA with CYFRA21-1 with the Mann-Whitney U rank sum test. Spearman correlation analysis was used to correlate serum CEA and CYFRA21-1 levels with the number of bone metastases. Sensitivity, specificity, and accuracy in the diagnosis of bone metastases were needed to detect the incidence of bone metastases in lung adenocarcinoma and squamous cell carcinoma of the lung via whole-body bone imaging and SPECT/CT fusion imaging with serum and serum CEA and CYFRA21-1(alone or in combination with the χ2 test). Results68 patients demonstrated bone metastasis with a total of 586 lesions. The incidence of bone metastasis of adenocarcinoma(50/88) was higher than that of squamous cell carcinoma(18/55)(χ2=10.56, P < 0.05). The ratio of bone metastatic lesions in adenocarcinoma patients was greater than that in squamous carcinoma(526/586)(χ2=19.23, P < 0.05). The serum levels of CEA(Z=4.98, P < 0.05) and CYFRA21-1(Z=2.55, P < 0.05) in patients with bone metastases were higher than in those without bone metastases. However, no significant correlation was found between serum CEA and bone metastases in non-small cell lung cancer patients with bone metastases(r=0.141, P>0.05), but there was a certain correlation between CYFRA21-1 and the number of bone metastases(r=0.502, P < 0.01). Serum CEA and CYFRA21-1 levels were sensitive in the diagnosis of NSCLC bone metastasis(69.1%, 83.8%), but had low specificity(47.6%, 49.3%) and accuracy(57.3%, 65.7%) was low. The SPECT/CT tomographic fusion imaging in the diagnosis of NSCLC bone metastasis had high sensitivity(83.8%), specificity(84.0%), and accuracy(83.9%) were higher than serum CEA(χ2=4.09、23.08、24.33, all P < 0.05), specificity and accuracy were higher than CYFRA21-1 (χ2=20.28、12.55, both P < 0.05) and whole body bone scan(χ2=21.66、16.05, both P < 0.05). The sensitivity(97.0%), specificity(93.3%), and accuracy(95.1%) of SPECT/CT tomographic fusion imaging combined with serum CEA and CYFRA21-1 in the diagnosis of NSCLC bone metastasis were higher than those of whole body bone scan(χ2=12.55、37.17、47.45, all P < 0.05), serum CEA(χ2=18.89、38.89、24.33, all P < 0.05), CYFRA21-1 (χ2=6.89、35.50、39.17, all P < 0.05), sensitivity and accuracy were higher than SPECT/CT tomographic fusion imaging(χ2=6.89、9.53, both P < 0.05) applied individually. ConclusionsSPECT/CT tomographic fusion imaging combined with serum CEA and CYFRA21-1 diagnosis of NSCLC bone metastases had clinical value because of high sensitivity, specificity, and accuracy. -
表 1 血清CEA、CYFRA21-1、全身骨显像、SPECT/CT同机断层融合显像在诊断非小细胞肺癌骨转移中价值的对比
Table 1. Diagnostic value of serum CEA, CYFRA21-1, whole body bone imaging and SPECT/CT tomographic fusion imaging in diagnosis of non-small cell lung cancer bone metastasis
诊断方法 灵敏度 特异度 准确率 血清CEA (47/68)69.1%a (35/75)46.7%a (82/143)57.3%a CYFRA21-1 (57/68)83.8%b (37/75)49.3%b (94/143)65.7%b 全身骨显像 (52/68)76.4%c (36/75)48.0%c (88/143)58.7%c SPECT/CT同机断层融合 (57/68)83.8%d (63/75)84.0% (120/143)83.9%d SPECT/CT同机断层融合+血清肿瘤标志物 (66/68)97.0% (70/75)93.3% (136/143)95.1% 注:表中,a:与SPECT/CT同机断层融合、SPECT/CT同机断层融合+血清肿瘤标志物比较,灵敏度(χ2=4.09、18.89,均P < 0.05)、特异度(χ2=23.08、38.89,均P < 0.05)和准确率(χ2=24.33、24.33,均P < 0.05)差异具有统计学意义;b:与SPECT/CT同机断层融合+血清肿瘤标志物比较,灵敏度(χ2=6.89,P < 0.05)差异具有统计学意义;与SPECT/CT同机断层融合、SPECT/CT同机断层融合+血清肿瘤标志物比较,特异度(χ2=20.28、35.50,均P < 0.05)、准确率(χ2=12.55、39.17,均P < 0.05)差异具有统计学意义;c:与SPECT/CT同机断层融合+血清肿瘤标志物比较,灵敏度(χ2=12.55,P < 0.05)差异具有统计学意义;与SPECT/ CT同机断层融合、SPECT/CT同机断层融合+血清肿瘤标志物比较,特异度(χ2= 21.66、37.17,均P < 0.05)、准确率(χ2=16.05、47.45,均P < 0.05)差异具有统计学意义;d:与SPECT/CT同机断层融合+血清肿瘤标志物比较,灵敏度(χ2=6.89,P < 0.05)、准确率(χ2=9.53,P < 0.05)差异具有统计学意义;CEA:癌胚抗原;CYFRA21-1:可溶性细胞角蛋白19片段;SPECT/CT:单光子发射计算机体层摄影术。 -
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