PET/CT在脑胶质瘤放疗后复发与坏死鉴别诊断中的应用研究
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摘要
目的鉴别脑胶质瘤放疗后复发与坏死有重要临床意义,本研究应用正电子发射断层显像/X线计算机断层成像(Positron emission tomography/X-ray computed tomography ,PET/CT)评价11C-蛋氨酸(11C-methionine ,MET)在脑胶质瘤放疗后复发与坏死的鉴别诊断中的作用,同时观察放疗后复发脑胶质瘤的治疗疗效。
方法自2008年6月至2009年9月, 30例放疗后怀疑复发或坏死胶质瘤患者接受MET PET/CT检查。首次治疗时病理分级根据世界卫生组织(WHO)中枢神经系统分类方法,II级19例,III级9例,IV级2例。30例患者首次治疗均接受手术切除及辅助放疗,放疗剂量范围54-60Gy,中位剂量58Gy; 30例中17例接受了术后化疗。所有患者均接受MET PET/CT检查,放疗结束与PET/CT检查间隔时间范围5-90月,中位间隔时间13.5月。PET检查时患者年龄范围11-69岁,中位年龄41岁;男性21例,女性9例。PET/CT仪为Biograph HR16机型(Siemens,Germany),患者静脉注射740MBq的11C-MET后10分钟进行扫描,通过衰减校正后重建PET影像(3mm层厚)。蛋氨酸(MET)高代谢区被选做感兴趣区(Regions of interest,ROI),同时以同样大小的圆圈选定对侧灰质区多个ROIS,计算平均值,如果PET未发现异常,MRI异常区域相应的PET影像区域选定圆形ROI。SUV(标准摄取值)=(像素值/像素体积)(/注射的放射性核素活度/体积)×校正因子。L/N(the lesion-to-normal tissue ratio,病灶正常组织比)=病灶部位SUV平均值/对侧灰质SUV平均值。生存时间从PET/CT检查后开始计算。确立放疗后复发的诊断需根据手术切除或活检病理结果,放疗后坏死的诊断需根据手术病理结果或临床随访,在长时间(大于6个月)CT或MRI随访中显示病灶自发性缩小或稳定的患者诊断为放射性坏死。
结果30例患者均接受一次PET/CT检查并随访至2010年3月(中位随访11月)。PET/CT诊断19例复发,11例坏死。19例PET检查后考虑复发患者接受手术切除或立体定向活检,18例病理明确诊断为胶质瘤复发, 1例手术切除诊断为放疗后坏死。18例病理证实复发患者中1例复发前病理诊断为星形胶质细胞瘤Ⅱ级,复发后病理诊断为少枝胶质瘤伴室管膜分化(WHOⅡ级);10例复发后病理诊断无改变;7例复发前病理诊断为星形胶质细胞瘤Ⅱ级,复发后病理诊断为星形胶质细胞瘤Ⅲ级。11例PET/CT诊断为放疗后坏死,经长期随访(>6个月)后临床症状稳定及MRI或CT影像诊断病灶无增大。根据以上结果用四格表计算MET PET鉴别脑胶质瘤放疗后复发与坏死的敏感性,特异性和准确性分别为100%,91.7%和96.7%。全组仅复发组3例活检后死亡(1例未治疗病情进展后死亡,1例立体定向放疗和1例化疗后病情进展死亡)。复发组18例1年生存率82%,生存时间5-15月,中位生存时间8.5月。复发后手术切除患者与立体定向活检患者的生存率有明显差异(P=0.002)。
结论MET PET可有效鉴别脑胶质瘤放疗后复发与坏死;复发脑胶质瘤患者手术切除较活检生存获益的可能性更大。
Objective Differential diagnosis between tumor recurrence and radiation necrosis is important in the clinical management of glioma after radiotherapy.In this study,we evaluate the value of 11C-methionine positron emission tomography/ X-ray computed tomography (MET PET/CT) in differentiation of tumor recurrence from radiation necrosis and the therapeutic results of recurrent glioma.
Methods From June 2008 to September 2009, 30 patients who had previously been treated with radiotherapy were suspected to have recurrent glioma or radiation injury.MET PET was performed on these patients. According to the World Health Organization (WHO) classification, initial tumor histologies included 19 gradeⅡ, 9 gradeⅢand 2 gradeⅣ.30 patients had previously received operation and adjuvant radiotherapy,the dose of initial radiotherapy range from54 to60Gy(median dose 58Gy);only 17 received adjuvant chemotherapy after operation. The median time between initial radiotherapy and PET was 13.5 months,ranging from 5 to 90 months.There were 21 males and 9 females,the median patient age was 41 years ,ranging from 11 to 69 years. PET was carried out with Biograph HR16 scanner(Siemens,Germany),PET images were obtained as a static scan 10 minutes after injection of 740MBq MET.The PET images were reconstructed using measured attenuation reconstruction(3mm ).On PET scans,the portion of the tumor with the highest accumulation was selected as the region of interest(ROI),and several ROIs with the same diameter were located over the gray matter of the contralateral lobe.If no abnormality could be detected ,a circular ROI of the same size was located over the area corresponding to the MRI abnormality.The standardized uptake value(SUV) was caculated over the same tumor ROI as follows:SUV=[(pixel count/pixel volume)/(injected radioisotope activity/body weight)]×calibration factor. L/N(the lesion-to-normal tissue ratio )= SUVmean of the lesion/ SUVmean of the contrallateral gray matter. The survival time was calculated from the day of performing PET.The tumor recurrence was confirmed by correlating findings with subsequent histological analysis,the diagnosis of necrosis was based on histological analysis and the subsequent clinical follow-up(>6 months) and MRI/ CT in case without surgery or biopsy.
Results The follow-up investigation continued to March 2010(the median time 11 months).19 recurrence and 11 radiation necroses were shown in PET images.There are 19 cases considered to have recurrent tumor were eveluated by histopathological findings,18 showed viable glioma and 1 showed necrosis .Within 18 recurrent cases,1 case whose initial tumor hisyology was WHO grade II was pathologically confirmed as having oligodendroglioma mixed with ependymoma;10 cases had the same hisyology after recurrence;7 cases whose initial tumor histology was WHO grade II was pathologically confirmed as having anaplastic astrocytoma. While 11 cases were considered to have radiation necrosis because they exhibited stable neurological sympotoms with no sign of massive enlargement of the lesion on follow-up MRI/CT after 6 months.According to a 2×2 factorial analysis,the sensitivity、specificity and accuracy of MET PET for detecting tumor recurrence were 100% and 91.7% and 96.7% respectively. The 1-year overall survival (OS) rates was 82%,and the median survival time 8.5 months (5-15 months) within the subset of patients with recurrent glioma.Only 3 patients died after biopsy(1 without further therapy,1 with SRS and 1 with chemotherapy). There was significant difference of survival time between craniectomy and biopsy in 18 recurrent cases(P=0.002).
Conclusion PET is a powerful tool in differentiating brain tumor recurrence from radiation necrosis after radiotherapy and recurrent glioma may benefit more from craniectomy than biopsy.
方法自2008年6月至2009年9月, 30例放疗后怀疑复发或坏死胶质瘤患者接受MET PET/CT检查。首次治疗时病理分级根据世界卫生组织(WHO)中枢神经系统分类方法,II级19例,III级9例,IV级2例。30例患者首次治疗均接受手术切除及辅助放疗,放疗剂量范围54-60Gy,中位剂量58Gy; 30例中17例接受了术后化疗。所有患者均接受MET PET/CT检查,放疗结束与PET/CT检查间隔时间范围5-90月,中位间隔时间13.5月。PET检查时患者年龄范围11-69岁,中位年龄41岁;男性21例,女性9例。PET/CT仪为Biograph HR16机型(Siemens,Germany),患者静脉注射740MBq的11C-MET后10分钟进行扫描,通过衰减校正后重建PET影像(3mm层厚)。蛋氨酸(MET)高代谢区被选做感兴趣区(Regions of interest,ROI),同时以同样大小的圆圈选定对侧灰质区多个ROIS,计算平均值,如果PET未发现异常,MRI异常区域相应的PET影像区域选定圆形ROI。SUV(标准摄取值)=(像素值/像素体积)(/注射的放射性核素活度/体积)×校正因子。L/N(the lesion-to-normal tissue ratio,病灶正常组织比)=病灶部位SUV平均值/对侧灰质SUV平均值。生存时间从PET/CT检查后开始计算。确立放疗后复发的诊断需根据手术切除或活检病理结果,放疗后坏死的诊断需根据手术病理结果或临床随访,在长时间(大于6个月)CT或MRI随访中显示病灶自发性缩小或稳定的患者诊断为放射性坏死。
结果30例患者均接受一次PET/CT检查并随访至2010年3月(中位随访11月)。PET/CT诊断19例复发,11例坏死。19例PET检查后考虑复发患者接受手术切除或立体定向活检,18例病理明确诊断为胶质瘤复发, 1例手术切除诊断为放疗后坏死。18例病理证实复发患者中1例复发前病理诊断为星形胶质细胞瘤Ⅱ级,复发后病理诊断为少枝胶质瘤伴室管膜分化(WHOⅡ级);10例复发后病理诊断无改变;7例复发前病理诊断为星形胶质细胞瘤Ⅱ级,复发后病理诊断为星形胶质细胞瘤Ⅲ级。11例PET/CT诊断为放疗后坏死,经长期随访(>6个月)后临床症状稳定及MRI或CT影像诊断病灶无增大。根据以上结果用四格表计算MET PET鉴别脑胶质瘤放疗后复发与坏死的敏感性,特异性和准确性分别为100%,91.7%和96.7%。全组仅复发组3例活检后死亡(1例未治疗病情进展后死亡,1例立体定向放疗和1例化疗后病情进展死亡)。复发组18例1年生存率82%,生存时间5-15月,中位生存时间8.5月。复发后手术切除患者与立体定向活检患者的生存率有明显差异(P=0.002)。
结论MET PET可有效鉴别脑胶质瘤放疗后复发与坏死;复发脑胶质瘤患者手术切除较活检生存获益的可能性更大。
Objective Differential diagnosis between tumor recurrence and radiation necrosis is important in the clinical management of glioma after radiotherapy.In this study,we evaluate the value of 11C-methionine positron emission tomography/ X-ray computed tomography (MET PET/CT) in differentiation of tumor recurrence from radiation necrosis and the therapeutic results of recurrent glioma.
Methods From June 2008 to September 2009, 30 patients who had previously been treated with radiotherapy were suspected to have recurrent glioma or radiation injury.MET PET was performed on these patients. According to the World Health Organization (WHO) classification, initial tumor histologies included 19 gradeⅡ, 9 gradeⅢand 2 gradeⅣ.30 patients had previously received operation and adjuvant radiotherapy,the dose of initial radiotherapy range from54 to60Gy(median dose 58Gy);only 17 received adjuvant chemotherapy after operation. The median time between initial radiotherapy and PET was 13.5 months,ranging from 5 to 90 months.There were 21 males and 9 females,the median patient age was 41 years ,ranging from 11 to 69 years. PET was carried out with Biograph HR16 scanner(Siemens,Germany),PET images were obtained as a static scan 10 minutes after injection of 740MBq MET.The PET images were reconstructed using measured attenuation reconstruction(3mm ).On PET scans,the portion of the tumor with the highest accumulation was selected as the region of interest(ROI),and several ROIs with the same diameter were located over the gray matter of the contralateral lobe.If no abnormality could be detected ,a circular ROI of the same size was located over the area corresponding to the MRI abnormality.The standardized uptake value(SUV) was caculated over the same tumor ROI as follows:SUV=[(pixel count/pixel volume)/(injected radioisotope activity/body weight)]×calibration factor. L/N(the lesion-to-normal tissue ratio )= SUVmean of the lesion/ SUVmean of the contrallateral gray matter. The survival time was calculated from the day of performing PET.The tumor recurrence was confirmed by correlating findings with subsequent histological analysis,the diagnosis of necrosis was based on histological analysis and the subsequent clinical follow-up(>6 months) and MRI/ CT in case without surgery or biopsy.
Results The follow-up investigation continued to March 2010(the median time 11 months).19 recurrence and 11 radiation necroses were shown in PET images.There are 19 cases considered to have recurrent tumor were eveluated by histopathological findings,18 showed viable glioma and 1 showed necrosis .Within 18 recurrent cases,1 case whose initial tumor hisyology was WHO grade II was pathologically confirmed as having oligodendroglioma mixed with ependymoma;10 cases had the same hisyology after recurrence;7 cases whose initial tumor histology was WHO grade II was pathologically confirmed as having anaplastic astrocytoma. While 11 cases were considered to have radiation necrosis because they exhibited stable neurological sympotoms with no sign of massive enlargement of the lesion on follow-up MRI/CT after 6 months.According to a 2×2 factorial analysis,the sensitivity、specificity and accuracy of MET PET for detecting tumor recurrence were 100% and 91.7% and 96.7% respectively. The 1-year overall survival (OS) rates was 82%,and the median survival time 8.5 months (5-15 months) within the subset of patients with recurrent glioma.Only 3 patients died after biopsy(1 without further therapy,1 with SRS and 1 with chemotherapy). There was significant difference of survival time between craniectomy and biopsy in 18 recurrent cases(P=0.002).
Conclusion PET is a powerful tool in differentiating brain tumor recurrence from radiation necrosis after radiotherapy and recurrent glioma may benefit more from craniectomy than biopsy.
引文
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17. Cardinale RM, Bendict SH, Wu QW, et al. A comparison of three stereotactic radiotherapy techniques ; ARCS vs. noncoplanar fixed fields vs. intensitymodulation.Int J Radiat Oncol Biol Phys,1998,42(2):431-436.
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22. Shaw EG, Tatter SB, Lesser JL,et al. Current controversies in the radiotherapeutic management of adult low-grade glioma. Semin Oncol, 2004, 31(5): 653- 658.
23. Karim A B, Afra D, Cornu P, et al. Randomized trial on the efficacy of radiotherapy for cerebral low-grade glioma in the adult: European Organization for Research and Treatment of Cancer Study 22 845 with the Medical Research Council Study BRO4: an interim analysis. Int J Radiat Oncol Biol Phys, 2002, 52(2): 316- 324.
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26. Shaw E, Arusell R, Scheithauer B, et al. Prospective randomized trialof low- versus high- dose radiation therapy in adults with supratentorial low- grade glioma: initial report of a North Central Cancer TreatmentGroup/Radiation Therapy Oncology Group/Eastern CooperativeOncology Group study. J Clin Oncol, 2002, 20(9): 2267-2276.
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28. Jalali R, Budrukkar A, Sarin R, et al. High precision conformal radiotherapy employing conservative margins in childhood benign and low-grade brain tumours. Radiother Oncol, 2005, 74(1): 37- 44.
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