Volume 44 Issue 4
Jun.  2020
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Article Navigation >  Int J Radiat Med Nucl Med  > 2020,  44 > 4: (205-211)  

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Performance and analysis of vertebral 99Tcm-MDP uptake after chest tumor radiotherapy

  • 1.

    School of Medicine and Life Science, University of Jinan-Shandong Academy of Medical Science, Jinan 250200, China

  • 2.

    Department of Nuclear Medicine, Shandong Cancer Hospital Affiliated to Shandong University, Jinan 250117, China

  • Objective To analyze the changes in vertebral 99Tcm-medronate (MDP) uptake and the correlation with clinical radiotherapy parameters in chest tumor patients. Methods A retrospective study was conducted in 110 patients (including 62 males and 48 females aged 58.2 ± 11.9 years) who underwent chest tumor radiotherapy in Shandong Cancer Hospital from April 20, 2014 to October 31, 2018, and whole-body bone scan was performed before and after radiotherapy. The clinical information, tumor factors, and radiotherapy plan were analyzed using semiquantitative analysis. The results of the bone scan were divided into normal and abnormal vertebral uptake groups. In accordance with the time interval of bone imaging before and after radiotherapy, the patients were further classified into groups, namely, 60–120 (23 cases), 121–180 (30 cases), 181–240 (27 cases), and 241–365 (30 cases) days. The comparison among groups were analyzed using the χ2 test, and the statistical results were analyzed using the binary classification logistic regression. The change in the vertebral body 99Tcm-MDP uptake and the correlation with clinical radiotherapy parameters in chest tumor patients were discussed. The (T/Nbefore) − (T/Nafter)/(T/Nbefore) was calculated, and the receiver operating characteristic curve was drawn. The best diagnosis threshold of vertebral 99Tcm-MDP uptake abnormality was found. Results In 110 patients, 48 (43.6%) had local poor vertebral radioactivity uptake with minimum, maximum, and average vertebral exposure doses of 1039.5, 4488.7, and (2139.5±839.8) cGy, respectively. The shortest, longest, and median imaging interval was 61, 326, and 160 days, respectively. The remaining 62 patients (56.4%) had no obvious abnormal radioactive uptake. The degree of vertebral body uptake was correlated with the radiotherapy dose (χ2=4.401, P=0.036), radiotherapy frequency (χ2=2.241, P=0.027), vertebral body irradiation dose (χ2=5.913, P=0.015), and imaging interval before and after radiotherapy (χ2=12.542, P=0.013). No statistical correlation with age, gender, body mass index, single radiotherapy dose, planning target volume, planning target volume dose, vertebral irradiation volume, and distance from the radiotherapy center to the vertebral center was observed. In the grouped imaging intervals and compared groups, a difference was observed among 60–120, 121–180 days and 181–240, 241–365 days in vertebral body uptake (χ2=3.850–15.492, all P>0.05), and the abnormal vertebral 99Tcm-MDP uptake at intervals less than 180 days accounted for 66.7% (32/48). The sensitivity and specificity of evaluating the 99Tcm-MDP uptake abnormality were 74.6% and 82.9%, respectively. The area under the curve was 0.934 by the the receiver operating characteristic curve, indicating that (T/Nbefore)−(T/Nafter)/(T/Nbefore) was good at evaluating the change rate of vertebral 99Tcm-MDP uptake, and the optimal diagnostic threshold for vertebral 99Tcm-MDP uptake abnormality was 0.161. Conclusions Early imaging time after radiotherapy results in high detection rate of vertebral injury. The change in vertebral body 99Tcm-MDP uptake can reflect the degree of radioactive vertebral damage to some extent.
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Performance and analysis of vertebral 99Tcm-MDP uptake after chest tumor radiotherapy

    Corresponding author: Guoren Yang, guorenyang@163.com
  • 1. School of Medicine and Life Science, University of Jinan-Shandong Academy of Medical Science, Jinan 250200, China
  • 2. Department of Nuclear Medicine, Shandong Cancer Hospital Affiliated to Shandong University, Jinan 250117, China
  • Received Date: 2019-02-19
  • Available Online: 2020-04-01

Abstract:  Objective To analyze the changes in vertebral 99Tcm-medronate (MDP) uptake and the correlation with clinical radiotherapy parameters in chest tumor patients. Methods A retrospective study was conducted in 110 patients (including 62 males and 48 females aged 58.2 ± 11.9 years) who underwent chest tumor radiotherapy in Shandong Cancer Hospital from April 20, 2014 to October 31, 2018, and whole-body bone scan was performed before and after radiotherapy. The clinical information, tumor factors, and radiotherapy plan were analyzed using semiquantitative analysis. The results of the bone scan were divided into normal and abnormal vertebral uptake groups. In accordance with the time interval of bone imaging before and after radiotherapy, the patients were further classified into groups, namely, 60–120 (23 cases), 121–180 (30 cases), 181–240 (27 cases), and 241–365 (30 cases) days. The comparison among groups were analyzed using the χ2 test, and the statistical results were analyzed using the binary classification logistic regression. The change in the vertebral body 99Tcm-MDP uptake and the correlation with clinical radiotherapy parameters in chest tumor patients were discussed. The (T/Nbefore) − (T/Nafter)/(T/Nbefore) was calculated, and the receiver operating characteristic curve was drawn. The best diagnosis threshold of vertebral 99Tcm-MDP uptake abnormality was found. Results In 110 patients, 48 (43.6%) had local poor vertebral radioactivity uptake with minimum, maximum, and average vertebral exposure doses of 1039.5, 4488.7, and (2139.5±839.8) cGy, respectively. The shortest, longest, and median imaging interval was 61, 326, and 160 days, respectively. The remaining 62 patients (56.4%) had no obvious abnormal radioactive uptake. The degree of vertebral body uptake was correlated with the radiotherapy dose (χ2=4.401, P=0.036), radiotherapy frequency (χ2=2.241, P=0.027), vertebral body irradiation dose (χ2=5.913, P=0.015), and imaging interval before and after radiotherapy (χ2=12.542, P=0.013). No statistical correlation with age, gender, body mass index, single radiotherapy dose, planning target volume, planning target volume dose, vertebral irradiation volume, and distance from the radiotherapy center to the vertebral center was observed. In the grouped imaging intervals and compared groups, a difference was observed among 60–120, 121–180 days and 181–240, 241–365 days in vertebral body uptake (χ2=3.850–15.492, all P>0.05), and the abnormal vertebral 99Tcm-MDP uptake at intervals less than 180 days accounted for 66.7% (32/48). The sensitivity and specificity of evaluating the 99Tcm-MDP uptake abnormality were 74.6% and 82.9%, respectively. The area under the curve was 0.934 by the the receiver operating characteristic curve, indicating that (T/Nbefore)−(T/Nafter)/(T/Nbefore) was good at evaluating the change rate of vertebral 99Tcm-MDP uptake, and the optimal diagnostic threshold for vertebral 99Tcm-MDP uptake abnormality was 0.161. Conclusions Early imaging time after radiotherapy results in high detection rate of vertebral injury. The change in vertebral body 99Tcm-MDP uptake can reflect the degree of radioactive vertebral damage to some extent.

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  • 胸部肿瘤在我国的发病率较高，主要包括肺癌、乳腺癌、食管癌、纵隔肿瘤及胸部转移瘤等，胸部放疗是主要治疗手段之一[1]，但在取得良好放疗效果的同时，也容易引起邻近相关脏器和组织的放射性毒性损伤，如放射性肺炎、放射性食管炎、放射性心脏损伤[2-3]及椎体损伤等，影响患者的治疗效果、预后和生存质量。本研究观察胸部肿瘤患者放疗前后椎体对99Tcm-MDP摄取程度的改变，并分析其与临床及肿瘤放疗因素的相关性，评估患者骨骼及骨髓的损伤，以期为临床治疗方案的制定及调整提供参考，保护靶器官免受放射性损伤，提高患者后期生存质量。

1.   资料与方法

    1.1.   临床资料

  • 收集2014年4月20日至2018年12月31日在山东省肿瘤医院确诊为胸部肿瘤且进行三维适形或调强放疗，并于放疗前后在核医学科行全身骨显像的患者110例，其中男性62例、女性48例，年龄（58.2±11.9）岁。在110例患者中，共有肺癌57例、食管癌14例、乳腺癌17例、胸部转移瘤12例和纵隔肿瘤10例。治疗前均由患者或其监护人签署了知情同意书。

    纳入标准：均经过病理学结果确诊且放疗资料完善；放疗前经临床和相关辅助检查排除骨转移及椎体病变；放疗前脊柱功能基本正常，KPS（Karnofsky）评分≥70分；放疗前后骨显像时间间隔为60~365 d。排除标准：心肺功能异常或合并其他部位肿瘤病变；放疗及其他辅助检查资料不完善；放疗前后骨显像间隔时间>1年。

    • 1.2.   显像方法及放疗计划

  • 全身骨显像：检查仪器为荷兰Philips公司 Bright view XCT SPECT/CT仪，配置低能高分辨率准直器。患者经肘前静脉注射显像剂99Tcm-MDP（北京原子高科股份有限公司提供）740~925 MBq（20~25 mCi），2~4 h后按照SPECT/CT仪显像规范进行图像采集[4]。SPECT扫描参数：矩阵256×256，能峰140 keV，窗宽20%。

    放疗计划：患者均采用常规仰卧位，双手抱肘置于额上，采用荷兰飞利浦大孔径CT模拟定位，范围由下颌至肝下缘。CT扫描参数：管电压120 kV，管电流220 mAs，层厚3 mm，层间距3 mm。定位CT影像学资料直接传输至美国Varian公司的Eclipse13.5计划系统，根据ICRU（international commission on radiation units）第50号及第62号报告定义勾画大体肿瘤体积、计划靶体积（planning target volume，PTV）及临床靶区[5]。

    采用美国Varian公司的Trilogy直线加速器6MV-X线实施三维适形或调强放疗，共面4~7个野，95%等剂量线覆盖PTV，处方剂量为30~70 Gy，单次照射剂量为1.5~3.0 Gy，1次/d，5次/周，治疗次数为10~40次。

    根据三维剂量分布计算剂量体积直方图，危及器官剂量限制性因素包括：肺V20<30%，食管V55<50%，心脏V40<40%，脊髓Dmax<4500 cGy（肺V20：接受照射剂量≥20 Gy的肺体积占正常肺体积的百分比；食管V55：接受照射剂量≥55 Gy的食管体积占其总体积的百分比；心脏V40：接受照射剂量≥40 Gy的心脏体积占其总体积的百分比；脊髓Dmax：脊髓的最大受照剂量）[5]。在本研究中，脊椎的最小受照剂量为80.0 cGy、最大受照剂量为4488.7 cGy。

    • 1.3.   受照椎体对99Tcm-MDP摄取的评价

  • 由2名具有10年以上工作经验的核医学科副主任医师进行半定量分析，根据受照椎体对99Tcm-MDP摄取的程度作出诊断。（1）视觉分析：根据视觉观察将患者分为椎体99Tcm-MDP摄取正常组和异常组，意见不统一时寻求上级医师的意见。（2）半定量分析：以全身骨扫描后位像为标准，由同一操作者通过Philips后台工作处理站勾画ROI，采用矩形勾画框，ROI面积为（341±57）cm2，测量患者放疗前T/N前及放疗后T/N后，T为靶区受照中心3个完整椎体的99Tcm-MDP摄取值，N为靶区外3个正常椎体的99Tcm-MDP摄取值，统计患者的临床资料、放疗剂量、放疗次数、单次放疗剂量、PTV、PTV受照剂量、椎体受照体积、椎体受照剂量、放疗靶区中心至椎体中心的水平距离及放疗前后全身骨显像时间间隔等参数，评估椎体对99Tcm-MDP摄取改变的影响因素。按照放疗前后骨显像时间间隔进行分组：60~120 d组（23例）、121~180 d组（30例）、181~240 d组（27例）、241~365 d组（30例），并进行组间比较，分析其与99Tcm-MDP摄取变化的关系。

    • 1.4.   统计学方法

  • 采用SPSS 22.0软件对数据进行统计学分析。符合正态分布的计量资料以$\bar x $±s表示，组间比较采用χ2检验。采用二分类Logistic回归分析临床相关因素与放射性核素摄取程度的相关性，计算（T/N前）−（T/N后）/（T/N前），并绘制ROC曲线，计算AUC，评估椎体对99Tcm-MDP摄取率异常的最佳诊断阈值。P <0.05为差异有统计学意义，α=0.05（双侧）。

2.   结果

    2.1.   半定量分析结果

  • 在110例患者中，48例（43.6%）患者出现不同程度的椎体99Tcm-MDP摄取减低，出现摄取异常的椎体受照剂量为1039.5~4488.7（2139.5±839.8）cGy（典型病例的相关图像见图1），放疗前后骨显像时间间隔最短为61 d，最长为326 d，中位时间为160 d；其余62例（56.4%）患者未见放射性摄取异常。椎体99Tcm-MDP摄取程度与总放疗剂量（χ2=4.401，P=0.036）、放疗次数（χ2=2.241，P=0.027）、椎体受照剂量（χ2=5.913，P=0.015）及放疗前后骨显像时间间隔（χ2=12.542，P=0.013）有统计学相关性，与年龄、性别、体重指数、单次放疗剂量、PTV、PTV剂量、椎体受照体积及放疗靶区中心至椎体中心的距离无统计学相关性（表1）。

    Figure 1.  Whole-body bone scan before radiotherapy (figure A) and after radiotherapy (figure B), radiotherapy target area (figure C-E) and dose volume histogram (F, G) of a right lung cancer with mediastinal and hilar lymph node metastasis patient

    临床因素椎体99Tcm-MDP摄取减低χ2值P值95%CI
    是（n=48）否（n=62）
    男性/女性（例） 25/23 37/25 0.694 0.405 0.568~4.058
    年龄（岁） 58.1±10.1 58.4±13.2 0.991 0.320 0.936~1.022
    体重指数（kg/m2） 22.5±3.7 23.5±3.4 0.288 0.591 0.836~1.108
    总放疗剂量（cGy） 5159.2±911.5 4487.7±1287.1 4.401 0.036 1.000~1.008
    单次剂量（cGy） 205.8±19.6 220.7±43.6 3.284 0.070 0.870~1.005
    放疗次数（次） 26 22 2.241 0.027 0.240-1.062
    PTV（cm3） 340.2 573.7 0.544 0.461 0.998~1.001
    PTV剂量（cGy） 4083.1±1158.7 3932.4±1319.7 0.002 0.963 1.000~1.000
    椎体受照体积（cm3） 46.6±17.3 50.1±22.2 0.013 0.910 0.979~1.025
    椎体受照剂量（cGy） 2139.5±839.8 1332.5±723.0 5.913 0.015 1.000~1.001
    放疗靶区中心至椎体中心的
    　距离（cm）    		 6.6±2.9 6.4±3.3 0.814 0.367 0.916~1.267
    放疗前后骨显像时间间隔（d） 160.3±61.1 209.8±76.4 12.542 0.013 0.995~1.004
    　注：表中，MDP：亚甲基二膦酸盐；PTV：计划靶体积；CI：可变区间

    Table 1.  Correlation analysis of clinical factors and 99Tcm-MDP uptake of vertebral body

    60~120 d、121~180 d组分别与181~240 d、241~365 d组相比，椎体对99Tcm-MDP的摄取差异有统计学意义（χ2=3.850~15.429，均P<0.05）（表2）。时间间隔<180 d出现椎体99Tcm-MDP摄取异常的患者较多，占总摄取异常患者的66.7%（32/48）。

    组别例数99Tcm-MDP摄取减低99Tcm-MDP摄取正常
    60~120 d组 23 52.2%（12/23） 47.8%（11/23）
    121~180 d组 30 66.7%（20/30） 33.3%（10/30）
    181~240 d组 27 40.7%（11/27）a, b 59.3%（16/27）
    241~365 d组 30 16.7%（5/30）a, b 83.3%（25/30）
    总计 110 43.6%（48/110） 56.4%（62/110）
    注：表中，a：与60~120 d组比较，差异均有统计学意义（χ2=3.850、7.534，P=0.045、0.006）；b：与121~180 d组比较，差异均有统计学意义（χ2=15.429、0.065，P=0.001、0.041）。MDP：亚甲基二膦酸盐

    Table 2.  Comparison of vertebral body radionuclide uptake between different bone imaging intervals before and after radiotherapy

    • 2.2.   图像特征

  • 椎体对99Tcm-MDP摄取异常的灵敏度为74.6%，特异度为82.9%；通过ROC曲线分析得到AUC为0.934（图2），表明（T/N前）−（T/N后）/（T/N前）对评估椎体99Tcm-MDP摄取改变率的效果较佳。椎体对99Tcm-MDP摄取异常的最佳诊断阈值为0.161。

    Figure 2.  Receiver operator characteristic curve of 99Tcm-methylene diphosphonate uptake rate

3.   讨论

  • 全身骨显像是核医学科较常见的检查项目，可明确地显示病变部位及骨骼代谢情况[6-7]，在疾病的早期诊断方面具有独特的优势。显像剂99Tcm-MDP的摄取程度受骨代谢疾病、骨肿瘤、肿瘤骨转移及放疗等多种因素的影响[8]。我们通过研究放疗前后椎体99Tcm-MDP的摄取程度发现，43.6%（48/110）的患者出现了椎体对99Tcm-MDP的摄取降低，表现为椎体的放射性辐射损伤，引起该行为改变的最短时间为61 d，最长时间为326 d，中位时间为160 d。放射性辐射损伤机制有两种，其一为近期效应，射线直接照射引起骨细胞及造血干细胞损伤坏死、小血管变性坏死，造成局部血液循环障碍，显像剂无法进行钙离子交换，导致骨骼对99Tcm-MDP的摄取减少[9]；其二为远期效应，个体在接受长期慢照射累积后出现椎体辐射损伤[10-11]。放疗后椎体摄取99Tcm-MDP的程度受放疗剂量、椎体受照剂量、放疗次数及放疗前后骨显像时间间隔等多种因素的影响。

    本研究结果显示，椎体对99Tcm-MDP摄取正常与异常患者的总放疗剂量和椎体受照剂量的差异均有统计学意义；有48例患者出现椎体放射性摄取减低，总受照剂量为（5159.2±911.5）cGy，椎体受照剂量为（2139.5±839.8） cGy。临床研究结果显示，骨骼及脊髓处于照射路径或照射野内时，在一定范围内，随着照射剂量的增加，引起患者骨骼代谢异常的生理学效应越明显，因此，椎体摄取99Tcm-MDP的改变可在一定程度上反映患者骨细胞及脊髓的损伤程度[12-16]，在临床放疗计划实施过程中，应尽量避免椎体处于照射野或照射路径内，尽可能保护椎体免受射线损伤。椎体放射性损伤也与放疗次数密切相关（P＝0.027），单次照射剂量在一定范围内（1.8~2.5 cGy），放疗次数越多，椎体出现放射性损伤的概率越大；少数研究结果显示，单次大剂量分割治疗可引起急性骨细胞损伤，总剂量相同时，增加分割次数（2次/d）可降低骨细胞损伤的生物学效应[17]。本研究中单次照射剂量为1.5~3.0 Gy，1次/d，5次/周，治疗次数为10~40次，未出现单次大剂量分割及小剂量分割的治疗方式，因此，此类因素是否对椎体摄取99Tcm-MDP造成影响有待进一步研究。此外，本研究结果显示，放疗后椎体摄取99Tcm-MDP的改变与放疗前后骨显像时间间隔也有一定的联系（P=0.013）。林端瑜等[18]通过对41例放疗患者的研究发现，5例患者在放疗后2~3个月照射野骨骼出现核素浓聚灶，半年左右出现放射性摄取减低，之后逐渐恢复正常或处于放射性摄取减低状态。我们对显像时间进行分组发现，显像时间间隔＜180 d时，66.7%（32/48）的患者出现椎体摄取异常，而＞180 d后，约66.7%（41/62）的患者椎体摄取正常，这可能是由于部分患者放疗后未引起放射性损伤，或显像时间间隔过长，骨细胞损伤已恢复，因此导致组间分析存在一定的误差，这有待今后进一步研究。

    此外，陈永盛[5]研究发现，放疗后椎体辐射损伤与肿瘤的靶区勾画相关，靶体积越大，正常器官受辐射损伤的风险越高。本研究结果表明，椎体对99Tcm-MDP摄取的改变与PTV无统计学相关性（P=0.461），大体肿瘤体积由于部分数据存在缺失，与其相关性未纳入统计，因此关于椎体受照损伤与靶区大小的关系有待进一步证实。

    在本研究中我们发现，放疗前后椎体对99Tcm-MDP摄取的减低可在一定程度上反映患者骨细胞及骨髓的损伤，同时为同步放化疗方案的制定及调整提供参考。此外，本研究仍存在一些不足之处，首先，本研究为回顾性分析，部分患者临床详细治疗计划（如放化疗的方式、勾画大体肿瘤体积等）存在缺失，未将其纳入统计学分析；其次，患者放疗前后骨显像时间间隔长短不一，在此期间老年患者因自身机体代谢（如骨质疏松、骨质增生等）及日常行为改变等相关因素对椎体的影响未完全排除。总之，对于胸部肿瘤患者的放疗应根据病灶具体情况选择合适的放疗时机、合理的照射靶区和放疗剂量，尽量避免椎体处于照射野或照射路径内，在获得最佳治疗效果的同时尽可能避免椎体的放射性损伤。

    利益冲突　本研究由署名作者按以下贡献声明独立开展，不涉及任何利益冲突。

    作者贡献声明　卢婷婷负责论文的撰写和修改；王雪负责数据的整理和分析；王晓慧、霍宗伟负责图像的获取和处理；杨国仁负责研究命题的提出及指导。

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