动态增强MRI定量参数评估骨肉瘤新辅助化疗疗效价值
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摘要
目的骨肉瘤患者新辅助化疗(neoadjuvant chemotherapy,NAC)疗效评估对于术后化疗方案的制定及预后判断具有重要意义。本研究旨在探讨动态增强MRI(dynamic contrast-enhanced MRI,DCE-MRI)定量参数在骨肉瘤NAC前后的变化及其疗效评估中的价值。方法对昆明医科大学第三附属医院·云南省肿瘤医院2015-06-01-2017-12-3017例原发性骨肉瘤患者,于NAC前、后进行常规MR及动态增强检查。将动态增强图像数据输入商用灌注软件包Omni-Kinetics 2.10计算化疗前、后定量灌注参数容量转移常数(volume transfer constant,Ktrans)、速率常数(rate constant,Kep)、血管外细胞外间隙容积分数(extravascular extracellular volume fraction,Ve)。同时,使用Siemens Sygno(MR B19)工作站及软件包计算化疗前、后肿瘤体积。依据Holscher法评价化疗疗效,并依此将病灶分为反应良好组和反应差组。采用配对样本t检验比较各组化疗前、后各灌注参数是否存在差异;采用独立样本t检验比较2组化疗前、后各灌注参数。结果化疗反应良好组7例,反应差组10例。反应良好组Ktrans(t=8.693,P<0.001)、Kep(t=3.362,P=0.015)在化疗前后差异有统计学意义;Ve在化疗前后差异无统计学意义,t=0.019,P=0.985。反应差组Ktrans(t=2.018,P=0.074)、Kep(t=1.701,P=0.123)和Ve(t=1.963,P=0.081)在化疗前后差异均无统计学意义。化疗前反应良好组和反应差组Ktrans(t=1.961,P=0.069)、Kep(t=1.488,P=0.177)和Ve(t=0.664,P=0.517)差异无统计学意义。化疗后反应差组Ktrans高于反应良好组,t=3.335,P=0.005;2组间Kep(t=1.034,P=0.317)、Ve(t=0.829,P=0.420)差异无统计学意义。由受试者工作特征(receiver operating characteristic curve,ROC)曲线分析可得,化疗后病灶Ktrans对化疗反应差的预测能力最高,其最佳临界值为0.831min-1,敏感度为80.0%(8/10),特异度为7/7,曲线下面积(area under curve,AUC)为0.943,P<0.05。结论骨肉瘤NAC反应良好者动态增强磁共振定量参数在化疗前、后存在较明显的变化,对预测骨肉瘤患者NAC疗效有一定价值;化疗后病灶Ktrans对病灶化疗反应情况具有较高的预测能力。
OBJECTIVE Evaluation of neoadjuvant chemotherapy(NAC)in patients with osteosarcoma is of great significance for the development of postoperative chemotherapy and prognosis.The aim of this study was to investigate the change of quantitative parameters of dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI)before and after NAC in osteosarcoma and to explore the value of DCE-MRI for assessing the response to NAC.METHODS Seventeen patients with osteosarcoma were examined in this study in the Third Affiliated Hospital of Kunming Medical University &Yunnan Cancer Hospital from June 1,2015 to December 30,2017.DCE and Magnetic resonance(MR)images were obtained from all patients before and after neoadjuvant chemotherapy.The quantitative perfusion data and the gross tumor volume pre-and post-chemotherapy was calculated.The data included Ktrans(volume transfer constant),Kep(reflux rate constant),and Ve(extravascular extracellular volume fraction).The chemotherapeutic efficacy was evaluated by Holscher's method.All lesions were divided into the good response group and the poor response group.Paired-samples T test was used to compare the perfusion parameters before and after chemotherapy.Independent-samples T test was used to compare the perfusion parameters between the good and poor response group.RESULTS There were seven cases with a good response to chemotherapy and ten cases with poor response.For the good response group,Ktrans(t=8.693,P<0.001)and Kep(t=3.362,P=0.015)were significantly decreased after neoadjuvant chemotherapy,but the Ve(t=0.019,P=0.985)has no statistical difference.There was no statistical difference in Ktrans(t=2.018,P=0.074),Kep(t=1.701,P=0.123),and Ve(t=1.963,P=0.081)pre-and post-chemotherapy for the poor response group.The grouping comparison before chemotherapy demonstrated that there was no statistical difference in all parameters between two groups,including Ktrans(t=1.961,P=0.069),Kep(t=1.488,P=0.177),Ve(t=0.664,P=0.517)respectively.The grouping comparison after chemotherapy:Ktrans(t=3.335,P=0.005)in the poor response group was higher than that of good response group;while Kep(t=1.034,P=0.317)and Ve(t=0.829,P=0.420)between the two groups had no statistical difference.Ktrans demonstrated higher sensitivity(80%,8/10)and specificity(7/7)in predicting chemotherapy response,with optimal threshold of 0.831 min-1 and area under the curve(AUC)of 0.943(P<0.05).CONCLUSIONS The quantitative parameters of DCE-MRI are changed significantly before and after neoadjuvant chemotherapy in osteosarcoma lesion,which can be used to evaluate the effect of NAC in patients with osteosarcoma.Ktrans value showed higher sensitivity and specificity in predicting chemotherapy response.
OBJECTIVE Evaluation of neoadjuvant chemotherapy(NAC)in patients with osteosarcoma is of great significance for the development of postoperative chemotherapy and prognosis.The aim of this study was to investigate the change of quantitative parameters of dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI)before and after NAC in osteosarcoma and to explore the value of DCE-MRI for assessing the response to NAC.METHODS Seventeen patients with osteosarcoma were examined in this study in the Third Affiliated Hospital of Kunming Medical University &Yunnan Cancer Hospital from June 1,2015 to December 30,2017.DCE and Magnetic resonance(MR)images were obtained from all patients before and after neoadjuvant chemotherapy.The quantitative perfusion data and the gross tumor volume pre-and post-chemotherapy was calculated.The data included Ktrans(volume transfer constant),Kep(reflux rate constant),and Ve(extravascular extracellular volume fraction).The chemotherapeutic efficacy was evaluated by Holscher's method.All lesions were divided into the good response group and the poor response group.Paired-samples T test was used to compare the perfusion parameters before and after chemotherapy.Independent-samples T test was used to compare the perfusion parameters between the good and poor response group.RESULTS There were seven cases with a good response to chemotherapy and ten cases with poor response.For the good response group,Ktrans(t=8.693,P<0.001)and Kep(t=3.362,P=0.015)were significantly decreased after neoadjuvant chemotherapy,but the Ve(t=0.019,P=0.985)has no statistical difference.There was no statistical difference in Ktrans(t=2.018,P=0.074),Kep(t=1.701,P=0.123),and Ve(t=1.963,P=0.081)pre-and post-chemotherapy for the poor response group.The grouping comparison before chemotherapy demonstrated that there was no statistical difference in all parameters between two groups,including Ktrans(t=1.961,P=0.069),Kep(t=1.488,P=0.177),Ve(t=0.664,P=0.517)respectively.The grouping comparison after chemotherapy:Ktrans(t=3.335,P=0.005)in the poor response group was higher than that of good response group;while Kep(t=1.034,P=0.317)and Ve(t=0.829,P=0.420)between the two groups had no statistical difference.Ktrans demonstrated higher sensitivity(80%,8/10)and specificity(7/7)in predicting chemotherapy response,with optimal threshold of 0.831 min-1 and area under the curve(AUC)of 0.943(P<0.05).CONCLUSIONS The quantitative parameters of DCE-MRI are changed significantly before and after neoadjuvant chemotherapy in osteosarcoma lesion,which can be used to evaluate the effect of NAC in patients with osteosarcoma.Ktrans value showed higher sensitivity and specificity in predicting chemotherapy response.
引文
[1]中国临床肿瘤学会(CSCO)骨肉瘤专家委员会,中国抗癌协会肉瘤专业委员会.经典型骨肉瘤临床诊疗专家共识[J].临床肿瘤学杂志,2012,17(10):931-933.
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[3]Duan C,Kallehauge JF,Bretthorst GL,et al.Are complex DCE-MRI models supported by clinical data[J].Magn Reson Med,2017,77(3):1329-1339.
[4]Chen J,Chen C,Xia C,et al.Quantitative free-breathing dynamic contrast-enhanced MRI in hepatocellular carcinoma using gadoxetic-acid:correlations with Ki67proliferation status,histological grades,and micro-vascular density[J].Abdom Radiol,2018,43(6):1393-1403.
[5]刘磊,庞新路,尚文俊,等.DCE-MRI鉴别诊断前列腺良恶性病变的临床价值[J].中国CT和MRI杂志,2018,16(4):120-122.
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[7]尤微,张世权,李伟,等.骨肉瘤动静脉双途径新辅助化疗后保肢术远期随访报告[J].中华肿瘤防治杂志,2018,25(8):561-565.
[8]Holscher HC,Bloem JL,Woude HJVD,et al.Can MRI predict the histopathological response in patients with osteosarcoma after the first cycle of chemotherapy?[J].Clin Radiol,1995,50(6):384-390.
[9]马焕,李鹍,李振辉,等.磁共振扩散加权成像评估骨肉瘤新辅助化疗疗效的价值[J].中华肿瘤防治杂志,2016,23(16):1095-1098.
[10]李瑞敏,顾雅佳,彭卫军,等.定量动态增强磁共振评估乳腺癌新辅助化疗疗效的应用研究[J].中国癌症杂志,2016,26(7):623-628.
[11]Ashraf A,Gaonkar B,Mies C,et al.Breast DCE-MRI kinetic heterogeneity tumor markers:preliminary associations with neoadjuvant chemotherapy response[J].Transl Oncol,2015,191(3):154-162.
[12]Alan J,O’Connor JPB,Parker GJM,et al.Imaging tumor vascular heterogeneity and angiogenesis using dynamic contrast-enhanced magnetic resonance imaging[J].Clin Cancer Res,2007,13(12):3449-3459.
[13]宋媛,丁爽,贾文霄.DCE-MRI评价肿瘤血管生成的实验研究[J].放射学实践,2014,29(6):640-643.
[14]Kim SH,Lee JM,Gupta SN,et al.Dynamic contrast-enhanced MRIto evaluate the therapeutic response to neoadjuvant chemo-radiation therapy in locally advanced rectal cancer[J].J Magn Reson Imaging,2014,40(3):730-737.
[15]Tong MD,Yiqun Sun BS,Gollub MJ,et al.Dynamic contrast-enhanced MRI:Use in predicting pathological complete response to neoadjuvant chemoradiation in locally advanced rectal cancer[J].J Magn Reson Imaging,2015,42(3):673-680.
[16]Kim JH,Chan KK,Park BK,et al.Dynamic contrast-enhanced 3-T MR imaging in cervical cancer before and after concurrent chemo-radiotherapy[J].Eur Radiol,2012,22(11):2533-2539.
[17]Park JJ,Kim CK,Park SY,et al.Assessment of early response to concurrent chemo-radiotherapy in cervical cancer:value of diffusion-weighted and dynamic contrast-enhanced MR imaging[J].Magn Recon Imaging,2014,32(8):993-1000.
[2]Sorace AG,Partridge SC,Li X,et al.Distinguishing benign and malignant breast tumors:preliminary comparison of kinetic modeling approaches using multi-institutional dynamic contrast-enhanced MRIdata from the International Breast MR Consortium 6883trial[J].JMed Imaging,2018,5(1):11-19.
[3]Duan C,Kallehauge JF,Bretthorst GL,et al.Are complex DCE-MRI models supported by clinical data[J].Magn Reson Med,2017,77(3):1329-1339.
[4]Chen J,Chen C,Xia C,et al.Quantitative free-breathing dynamic contrast-enhanced MRI in hepatocellular carcinoma using gadoxetic-acid:correlations with Ki67proliferation status,histological grades,and micro-vascular density[J].Abdom Radiol,2018,43(6):1393-1403.
[5]刘磊,庞新路,尚文俊,等.DCE-MRI鉴别诊断前列腺良恶性病变的临床价值[J].中国CT和MRI杂志,2018,16(4):120-122.
[6]Pickles MD,Lowry M,Manton DJ,et al.Prognostic value of DCE-MRI in breast cancer patients undergoing neoadjuvant chemotherapy:a comparison with traditional survival indicators[J].Eur Radiol,2014,25(4):1097-1106.
[7]尤微,张世权,李伟,等.骨肉瘤动静脉双途径新辅助化疗后保肢术远期随访报告[J].中华肿瘤防治杂志,2018,25(8):561-565.
[8]Holscher HC,Bloem JL,Woude HJVD,et al.Can MRI predict the histopathological response in patients with osteosarcoma after the first cycle of chemotherapy?[J].Clin Radiol,1995,50(6):384-390.
[9]马焕,李鹍,李振辉,等.磁共振扩散加权成像评估骨肉瘤新辅助化疗疗效的价值[J].中华肿瘤防治杂志,2016,23(16):1095-1098.
[10]李瑞敏,顾雅佳,彭卫军,等.定量动态增强磁共振评估乳腺癌新辅助化疗疗效的应用研究[J].中国癌症杂志,2016,26(7):623-628.
[11]Ashraf A,Gaonkar B,Mies C,et al.Breast DCE-MRI kinetic heterogeneity tumor markers:preliminary associations with neoadjuvant chemotherapy response[J].Transl Oncol,2015,191(3):154-162.
[12]Alan J,O’Connor JPB,Parker GJM,et al.Imaging tumor vascular heterogeneity and angiogenesis using dynamic contrast-enhanced magnetic resonance imaging[J].Clin Cancer Res,2007,13(12):3449-3459.
[13]宋媛,丁爽,贾文霄.DCE-MRI评价肿瘤血管生成的实验研究[J].放射学实践,2014,29(6):640-643.
[14]Kim SH,Lee JM,Gupta SN,et al.Dynamic contrast-enhanced MRIto evaluate the therapeutic response to neoadjuvant chemo-radiation therapy in locally advanced rectal cancer[J].J Magn Reson Imaging,2014,40(3):730-737.
[15]Tong MD,Yiqun Sun BS,Gollub MJ,et al.Dynamic contrast-enhanced MRI:Use in predicting pathological complete response to neoadjuvant chemoradiation in locally advanced rectal cancer[J].J Magn Reson Imaging,2015,42(3):673-680.
[16]Kim JH,Chan KK,Park BK,et al.Dynamic contrast-enhanced 3-T MR imaging in cervical cancer before and after concurrent chemo-radiotherapy[J].Eur Radiol,2012,22(11):2533-2539.
[17]Park JJ,Kim CK,Park SY,et al.Assessment of early response to concurrent chemo-radiotherapy in cervical cancer:value of diffusion-weighted and dynamic contrast-enhanced MR imaging[J].Magn Recon Imaging,2014,32(8):993-1000.