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摘要:目的
探讨脊柱骨转移患者在千伏级机载锥形束CT(KV-CBCT)引导下的摆位误差。
方法收集行脊柱骨转移放射治疗的患者118例,其中颈椎17例,胸椎62例,腰椎39例。采用医科达公司直线加速器和瓦里安公司EDGE直线加速器附带的KV-CBCT进行扫描。CBCT图像采用骨窗模式与CT参考图像配准。本研究共采集973次数据,分别记录三维线性误差。
结果对脊柱骨转移的患者分别按部位、身高、体重、BMI分组,发现仅按部位分组的患者摆位误差差异有统计学意义(P<0.05)。
结论按部位分组,在三维方向上,颈椎的摆位效果优于胸椎和腰椎;胸椎在头脚方向的摆位效果优于腰椎,而腰椎在左右方向优于胸椎。不需要根据脊柱骨转移患者的BMI外放或缩小外放边界,而需要根据脊柱骨转移的部位不同更改外放边界。
Abstract:ObjectiveTo investigate the setup error in patients with spinal bone metastasis who underwent radiotherapy under the guidance of kilovoltage cone-beam CT (KV-CBCT).
MethodsA total of 118 patients with spinal metastasis who underwent radiotherapy, including 17 cases of cervical spine, 62 cases of thoracic spine, and 39 cases of lumbar spine, were collected. KV-CBCT scans were performed using the linear accelerators from Elekta and Varian’s EDGE system. CBCT images were registered with reference CT images in the bone window mode. A total of 973 data were collected, and 3D linear errors were recorded.
ResultsThe patients with spinal bone metastasis were grouped by site, height, weight, and BMI. The P value of the patients grouped only by site was P<0.05, which was statistically significant.
ConclusionWhen grouped by site in the 3D direction, the positioning effect of cervical spine is better than that of thoracic and lumbar spine. The positioning effect of the thoracic spine is better in the head and foot direction but worse in the left and right direction compared with that of the lumbar spine. Instead of extending or narrowing the margin according to the BMI of patients with spinal metastasis, the margin must be changed according to the site of spinal bone metastasis.
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Key words:
- Cone beam CT /
- Spinal bone metastasis /
- Radiotherapy /
- Setup error /
- Influencing factors /
- BMI
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0 引言
骨转移、肺转移、肝转移是恶性肿瘤最常见的转移部位,每年大约18.8/105的恶性肿瘤患者出现骨转移。脊柱是癌症晚期患者常见的转移部位[1-2],癌症死亡患者中,约40%~80%存在骨转移。脊柱转移的患者20%以上伴有神经损害。75%的骨转移发生于乳腺癌、肺癌、肾癌、前列腺癌、甲状腺癌和多发性骨髓瘤。随着医学技术的发展,医疗手段的不断提高,放射治疗已然成为骨转移患者的主要治疗手段[3-5]。脊柱肿瘤的放射治疗需要精确地传递,以便使肿瘤靶区获得高剂量,同时保护临近的脊髓。如果脊髓剂量过高,患者存在发生放射性脊髓炎的风险[6];如果剂量过低,则会导致硬膜外疾病的剂量不足增加治疗失败的风险[7]。放疗计划设计过程需要临床靶区(Clinical target volume, CTV)外扩一定范围获得计划靶区(Planning target volume, PTV),CTV外扩至 PTV的范围取决于靶区形状、靶区治疗过程中的变化、器官运动情况和摆位误差[8-9]。本研究对锥形束计算机断层扫描(Cone beam computed tomography, CBCT)引导下的118例脊柱骨转移患者的摆位误差进行分析,对其中的影响因素进行探讨。
1 资料与方法
1.1 患者入组情况
收集中国医学科学院肿瘤医院2017年6月—2024年6月行脊柱骨转移放射治疗的患者共计139例。
1.2 纳入与排除标准
纳入标准:(1)无放疗禁忌证;(2)KPS评分≥80分;(3)恶性肿瘤伴有脊柱骨转移;(4)经医生评估后需行放射治疗者。排除标准:(1)临床资料不完整;(2)CBCT扫描次数≤3次。本研究通过伦理委员会的审查(伦理批号:23/459-4202)。
1.3 体位固定CT模拟定位及CBCT图像的获取及配准
所有患者行仰卧体位固定,颈椎肿瘤患者体位固定根据患者个体情况采用不同方式固定,包括头颈肩碳纤底板联合个体化头颈肩热塑面膜和头颈肩碳纤底板联合发泡胶固定,胸椎肿瘤及腰椎肿瘤患者体位固定采用碳纤底板联合个体化热塑定位膜。患者均被固定在科莱瑞迪固定板上行CT定位扫描(Philips Brilliance Big Bore或Siemens SOMTOM Definition AS 40),CT定位扫描层厚和层距均为5 mm,靶区由富有多年临床经验的医师勾画,由主任医师负责审核;通过Pinnacle TPS进行计划设计并由资深物理师进行剂量审核。放射治疗前由两名技师按照要求摆位并进行KV级CBCT扫描,第一次CBCT配准均采用骨窗模式与计划参考图像进行自动匹配,再人工进行局部匹配,并经医师确认匹配结果。分别获得平移左右方向(Lateral, LAT)、头脚方向(Longitudinal, LNG)、腹背方向(Vertical, VRT)三个方向的摆位误差。
1.4 统计学方法
采用R 4.4.1软件进行数据处理及统计学分析,采用秩和检验判断各方向之间摆位误差的差异,P<0.05为差异具有统计学意义。符合正态分布的计量资料以均数±标准差($\bar x \pm s$)表示,行t检验;计数资料以频数(n)、百分率(%)表示,行χ2检验,P<0.05为差异具有统计学意义。将患者按部位分为颈椎、胸椎和腰椎组;将患者按身高分为<170 cm和≥170 cm组;将患者按体重分为体重<70 kg和≥70 kg组;将患者按BMI分为BMI<24 kg/m2和BMI≥24 kg/m2组。
2 结果
2.1 患者一般信息
2017年6月—2024年6月行脊柱骨转移放射治疗的患者共139例,排除21例患者(临床数据缺失1例,CBCT次数≤3次的20例),实际入组118例患者。其中颈椎17例,胸椎62例,腰椎39例。年龄13~84岁,平均年龄58.8岁,中位年龄59岁。男性76例,女性42例。均行CBCT引导放射治疗,其中容积旋转调强放疗(Volumetric modulated arc therapy, VMAT) 114例,调强放疗(Intensity modulated radiotherapy, IMRT) 4例。118例脊柱骨转移患者的基本特征,见表1。
表 1 118例脊柱骨转移患者的基本特征Table 1 Basic characteristics of 118 patients with spinal bone metastasesBasic characteristics n(%)(n=118) Age (years) Mean (standard deviation) 58.7±12.1 Median (min-max) 59.0 (13.0-84.0) Gender Male 76 (64.4%) Female 42 (35.6%) Diagnostic results Lung cancer bone metastasis 59 (50.0%) Bone metastases from abdominal tumors 24 (20.3%) Bone metastases from other tumors 11 (9.3%) Bone metastases from breast tumors 8 (6.8%) Bone metastases from head and neck tumors 9 (7.6%) Bone metastases from chest tumors 7 (5.9%) Fixture Expanded polystyrene (EPS) 1 (0.8%) Head, neck and shoulder brace 20 (16.9%) Flat rack on the chest and abdomen 85 (72.0%) Unibody frame 12 (10.2%) Site Cervical vertebra 17 (14.4%) Thoracic vertebra 62 (52.5%) Lumbar vertebra 39 (33.1%) Height (cm) <170 58 (49.2%) ≥170 60 (50.8%) Weight (kg) <70 69 (58.5%) ≥70 49 (41.5%) BMI (kg/m2) <24 67 (56.8%) ≥24 51 (43.2%) 2.2 三维方向的摆位误差平均值和最大值
2.2.1 按部位分组
颈椎在VRT、LNG和LAT的摆位误差分别为(0.13±0.08) cm、(0.19±0.09) cm和(0.15±0.06) cm。颈椎组在三维方向上的摆位误差平均值和最大值均小于胸椎和腰椎组,胸椎组在VRT和LNG上的摆位误差平均值和最大值均小于腰椎组,而腰椎组在LAT的摆位误差平均值和最大值小于胸椎组。并且颈、胸和腰椎三维方向的摆位误差平均值和最大值比较,差异有统计学意义(P<0.05),说明颈椎的摆位误差较小,见表2、图1。
表 2 不同分组的摆位误差三维方向的平均值和最大值Table 2 Mean and maximum values of setup errors in 3D direction for different subgroupsGroups Number of patients VRT LNG LAT Mean Max Mean Max Mean Max Overall 118 0.19±0.09 0.37±0.18 0.27±0.13 0.54±0.24 0.21±0.12 0.43±0.23 Site Cervical vertebra 17 0.13±0.08 0.28±0.18 0.19±0.09 0.34±0.14 0.15±0.06 0.32±0.11 Thoracic vertebra 62 0.19±0.10 0.35±0.17 0.28±0.13 0.56±0.24 0.24±0.14 0.47±0.28 Lumbar vertebra 39 0.21±0.09 0.43±0.17 0.30±0.13 0.59±0.23 0.20±0.08 0.40±0.14 P 0.002 0.003 0.007 <0.001 0.009 0.011 Height (cm) <170 58 0.18±0.10 0.37±0.19 0.26±0.12 0.50±0.22 0.22±0.13 0.43±0.28 ≥170 60 0.19±0.09 0.36±0.17 0.28±0.13 0.57±0.25 0.21±0.10 0.42±0.17 P 0.500 0.850 0.400 0.180 0.890 0.670 Weight (kg) <70 69 0.19±0.10 0.37±0.19 0.26±0.12 0.50±0.22 0.21±0.13 0.43±0.27 ≥70 49 0.19±0.09 0.36±0.16 0.30±0.13 0.59±0.24 0.21±0.11 0.43±0.15 P 0.740 0.880 0.062 0.042 0.850 0.260 BMI ( kg/m2) BMI<24 67 0.17±0.09 0.34±0.18 0.27±0.13 0.54±0.25 0.21±0.14 0.43±0.27 BMI≥24 51 0.20±0.10 0.40±0.17 0.28±0.12 0.53±0.22 0.21±0.08 0.43±0.14 P 0.120 0.082 0.890 0.890 0.450 0.180 Notes: LAT: Lateral; LNG: Longitudinal; VRT: Vertical. 2.2.2 按身高分组
<170 cm和≥170 cm组患者分别为58例和60例,各个方向的平均值和最大值比较均没有统计学意义(P>0.05)。说明身高对脊柱的摆位误差没有影响,见表2。
2.2.3 按体重分组
体重<70 kg和≥70 kg组患者分别为69例和49例,两组仅有LNG的摆位误差最大值差异有统计学意义(P<0.05),<70 kg的LNG误差更小。而其余方向的摆位误差比较差异均没有统计学意义(均P>0.05)。说明体重对脊柱的摆位误差没有影响,见表2、图1。
2.2.4 按BMI分组
BMI<24 kg/m2和BMI≥24 kg/m2组患者分别为67例和51例,各个方向的摆位误差平均值和最大值比较差异均没有统计学意义(P>0.05)。说明BMI对于脊柱的摆位误差没有影响,见表2。
2.3 CBCT三维方向≥3 mm和≥5 mm的次数和比例
本研究共计扫描973次CBCT图像。按部位分组中,颈、胸、腰椎组分别采集162次、494次和317次图像。颈椎组三维方向≥3 mm和≥5 mm的比例远远小于胸椎和腰椎组(P<0.05)。结果显示颈椎组在三维方向的摆位误差均小于胸椎和腰椎组;而胸椎组在LNG的摆位效果优于腰椎组,腰椎组在LAT的摆位效果优于胸椎组。按身高分组中,身高<170 cm的和身高≥170 cm的患者分别进行468次和505次CBCT,两组各方向摆位误差比较,差异均没有统计学意义(均P>0.05)。说明身高对脊柱的摆位误差没有影响。按体重分组中,体重<70 kg和体重≥70 kg组患者分别进行565次和408次CBCT,两组仅有LNG≥3 mm的比例间差异有统计学意义(P<0.05),<70 kg的患者的LNG摆位误差更小,其余方向摆位误差两组比较均没有统计学意义(均P>0.05)。按BMI分组中,BMI<24 kg/m2和BMI≥24 kg/m2组患者分别进行526次和447次CBCT,两组在各方向摆位误差上比较,差异没有统计学意义(均P>0.05)。说明BMI对于脊柱的摆位误差没有影响,见表3。
表 3 不同分组的CBCT三维方向≥3 mm和≥5 mm的次数和比例Table 3 Frequency and proportion of CBCT 3D linear deviations ≥3 mm and ≥5 mm in different subgroupsGroups Number
of CBCTVRT≥3 mm
(n(%))VRT≥5 mm
(n(%))LNG≥3 mm
(n(%))LNG≥5 mm
(n(%))LAT≥3 mm
(n(%))LAT≥5 mm
(n(%))Site Cervical vertebra 162 16 (9.9) 6 (93.7) 38 (23.5) 2 (1.2) 19 (11.7) 2 (1.2) Thoracic vertebra 494 110 (22.3) 22 (4.5) 200 (40.5) 78 (15.8) 155 (31.4) 49 (9.9) Lumbar vertebra 317 69 (21.8) 19 (6.0) 139 (43.8) 60 (18.9) 70 (22.1) 15 (4.7) P 0.002 0.465 <0.001 <0.001 <0.001 <0.001 Height (cm) <170 468 86 (18.4) 29 (6.2) 166 (35.5) 63 (13.5) 121 (25.9) 30 (6.4) ≥170 505 109 (21.6) 18 (3.6) 211 (41.8) 77 (15.2) 123 (24.4) 36 (7.1) P 0.242 0.078 0.051 0.483 0.642 0.751 Weight (kg) <70 565 110 (19.5) 31 (5.5) 199 (35.2) 72 (12.7) 147 (26.0) 38 (6.7) ≥70 408 85 (20.8) 16 (3.9) 178 (43.6) 68 (16.7) 97 (23.8) 28 (6.9) P 0.657 0.331 0.010 0.104 0.471 >0.999 BMI ( kg/m2) <24 526 93 (17.7) 24 (4.6) 207 (39.4) 81 (15.4) 132 (25.1) 40 (7.6) ≥24 447 102 (22.8) 23 (5.1) 170 (38.0) 59 (13.2) 112 (25.1) 26 (5.8) P 0.056 0.785 0.722 0.377 >0.999 0.328 3 讨论
放射治疗是一个团队协作的过程,需要医师、物理师和技师三方的协作。在治疗中患者的摆位受到多方面因素的影响(比如患者呼吸动度,治疗师视觉误差,治疗床、机架的机械精度等),可重复性是现代放疗所追求的关键[10]。骨转移灶往往为多发,其好发部位为肋骨、胸椎、腰椎、骨盆。骨转移瘤的主要症状是逐步加重的疼痛,晚期可有病理性骨折、脊髓和神经压迫,甚至出现高钙血症。放射治疗一直是脊柱骨转移的首选治疗方法,原发肿瘤治疗方法的进步延长了患者的生存期,尽管放射治疗对这些患者的作用是姑息性的,但合适剂量的放疗以及精确的可重复性摆位,可以很大程度地缓解脊柱骨转移患者的疼痛[11-12]。Yoon等[13]研究表示,旋转误差会导致靶区覆盖率下降,发生1°的旋转误差,2.5 cm3的靶区覆盖率降至84%,若是发生2°旋转误差,则覆盖率降至62%。和胸腹部肿瘤相比,脊柱骨转移的患者需要更精确的摆位及治疗。诸多研究[14-17]认为对于肺癌、乳腺癌、鼻咽癌、全中枢等实质性肿瘤,应根据患者不同BMI指数更改外放边界,但对脊柱骨性肿瘤的研究较少,本研究补充了这一方面。本研究认为BMI指数对脊柱骨转移患者摆位误差没有影响,不需要根据患者的BMI指数更改外放边界。本研究结果显示按颈、胸和腰椎分组后,应根据脊柱骨转移部位的不同更改外放边界。认为颈椎的摆位效果要好于胸椎和腰椎,不管是三维各个方向的平均值还是最大值,亦或是≥3 mm和≥5 mm的比例,都是颈椎的摆位效果要优于胸椎和腰椎,这可能是由于体位的不同导致的,颈椎患者为平躺于固定板上手臂垂于两侧,而胸腰椎患者需要手部上举,重复性不及颈椎导致,该结论与江萍等[18]的研究结果一致。在LNG,胸椎的摆位效果要优于腰椎;而在LAT,腰椎的摆位效果要优于胸椎,这可能是因为胸椎和腰椎的生理弯曲程度不同,旋转动度范围不同,在摆位重复性上有一定差异导致,本结论与农惠惠等[19]和周庆祥等[20]的研究结果不一致,而与黄蕤等[21]的研究结果一致。
本研究存在以下局限性:颈胸腰椎采用不同体位装置固定,没有深入分析体位装置的不同对颈胸腰椎固定的影响,但既往的研究[22-23]证明了不同装置对摆位误差的影响,并且刘丽丽等[24]的研究证明了使用真空垫能更好的贴合脊柱骨转移患者的体位。虽然本文认为在CBCT引导下的放射治疗可以有效避免靶区缺量,但笔者认为在光学体表的引导下可以有效辅助摆位验证,可以与CBCT进行互为表里的验证,从而更能发挥放射治疗的有效性。本研究没有对脊柱骨转移的具体分期进行进一步分析,这也是局限性之一。另外增加病例数,也会使研究更加准确。
Competing interests: The authors declare that they have no competing interests.利益冲突声明:所有作者均声明不存在利益冲突。作者贡献:秦文华、张涛:课题设计、资料与统计学分析、论文撰写与修改冯鑫、王增洲、褚尚楠、王宏、吴诗雨、陈诚、郇福奎、梁斌:数据收集、研究实施、论文撰写与讨论 -
表 1 118例脊柱骨转移患者的基本特征
Table 1 Basic characteristics of 118 patients with spinal bone metastases
Basic characteristics n(%)(n=118) Age (years) Mean (standard deviation) 58.7±12.1 Median (min-max) 59.0 (13.0-84.0) Gender Male 76 (64.4%) Female 42 (35.6%) Diagnostic results Lung cancer bone metastasis 59 (50.0%) Bone metastases from abdominal tumors 24 (20.3%) Bone metastases from other tumors 11 (9.3%) Bone metastases from breast tumors 8 (6.8%) Bone metastases from head and neck tumors 9 (7.6%) Bone metastases from chest tumors 7 (5.9%) Fixture Expanded polystyrene (EPS) 1 (0.8%) Head, neck and shoulder brace 20 (16.9%) Flat rack on the chest and abdomen 85 (72.0%) Unibody frame 12 (10.2%) Site Cervical vertebra 17 (14.4%) Thoracic vertebra 62 (52.5%) Lumbar vertebra 39 (33.1%) Height (cm) <170 58 (49.2%) ≥170 60 (50.8%) Weight (kg) <70 69 (58.5%) ≥70 49 (41.5%) BMI (kg/m2) <24 67 (56.8%) ≥24 51 (43.2%) 表 2 不同分组的摆位误差三维方向的平均值和最大值
Table 2 Mean and maximum values of setup errors in 3D direction for different subgroups
Groups Number of patients VRT LNG LAT Mean Max Mean Max Mean Max Overall 118 0.19±0.09 0.37±0.18 0.27±0.13 0.54±0.24 0.21±0.12 0.43±0.23 Site Cervical vertebra 17 0.13±0.08 0.28±0.18 0.19±0.09 0.34±0.14 0.15±0.06 0.32±0.11 Thoracic vertebra 62 0.19±0.10 0.35±0.17 0.28±0.13 0.56±0.24 0.24±0.14 0.47±0.28 Lumbar vertebra 39 0.21±0.09 0.43±0.17 0.30±0.13 0.59±0.23 0.20±0.08 0.40±0.14 P 0.002 0.003 0.007 <0.001 0.009 0.011 Height (cm) <170 58 0.18±0.10 0.37±0.19 0.26±0.12 0.50±0.22 0.22±0.13 0.43±0.28 ≥170 60 0.19±0.09 0.36±0.17 0.28±0.13 0.57±0.25 0.21±0.10 0.42±0.17 P 0.500 0.850 0.400 0.180 0.890 0.670 Weight (kg) <70 69 0.19±0.10 0.37±0.19 0.26±0.12 0.50±0.22 0.21±0.13 0.43±0.27 ≥70 49 0.19±0.09 0.36±0.16 0.30±0.13 0.59±0.24 0.21±0.11 0.43±0.15 P 0.740 0.880 0.062 0.042 0.850 0.260 BMI ( kg/m2) BMI<24 67 0.17±0.09 0.34±0.18 0.27±0.13 0.54±0.25 0.21±0.14 0.43±0.27 BMI≥24 51 0.20±0.10 0.40±0.17 0.28±0.12 0.53±0.22 0.21±0.08 0.43±0.14 P 0.120 0.082 0.890 0.890 0.450 0.180 Notes: LAT: Lateral; LNG: Longitudinal; VRT: Vertical. 表 3 不同分组的CBCT三维方向≥3 mm和≥5 mm的次数和比例
Table 3 Frequency and proportion of CBCT 3D linear deviations ≥3 mm and ≥5 mm in different subgroups
Groups Number
of CBCTVRT≥3 mm
(n(%))VRT≥5 mm
(n(%))LNG≥3 mm
(n(%))LNG≥5 mm
(n(%))LAT≥3 mm
(n(%))LAT≥5 mm
(n(%))Site Cervical vertebra 162 16 (9.9) 6 (93.7) 38 (23.5) 2 (1.2) 19 (11.7) 2 (1.2) Thoracic vertebra 494 110 (22.3) 22 (4.5) 200 (40.5) 78 (15.8) 155 (31.4) 49 (9.9) Lumbar vertebra 317 69 (21.8) 19 (6.0) 139 (43.8) 60 (18.9) 70 (22.1) 15 (4.7) P 0.002 0.465 <0.001 <0.001 <0.001 <0.001 Height (cm) <170 468 86 (18.4) 29 (6.2) 166 (35.5) 63 (13.5) 121 (25.9) 30 (6.4) ≥170 505 109 (21.6) 18 (3.6) 211 (41.8) 77 (15.2) 123 (24.4) 36 (7.1) P 0.242 0.078 0.051 0.483 0.642 0.751 Weight (kg) <70 565 110 (19.5) 31 (5.5) 199 (35.2) 72 (12.7) 147 (26.0) 38 (6.7) ≥70 408 85 (20.8) 16 (3.9) 178 (43.6) 68 (16.7) 97 (23.8) 28 (6.9) P 0.657 0.331 0.010 0.104 0.471 >0.999 BMI ( kg/m2) <24 526 93 (17.7) 24 (4.6) 207 (39.4) 81 (15.4) 132 (25.1) 40 (7.6) ≥24 447 102 (22.8) 23 (5.1) 170 (38.0) 59 (13.2) 112 (25.1) 26 (5.8) P 0.056 0.785 0.722 0.377 >0.999 0.328 -
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