-
食管癌是消化系统常见的恶性肿瘤之一,受其生物学特性的影响,食管癌的预后较差,易出现远处转移和(或)局部复发[1]。放疗是食管癌综合治疗中的重要手段,对局部晚期食管癌患者进行术前放疗,可有效地对食管病灶进行降期,提高术后的病理完全缓解(pathological complete response,pCR)率[2-3]。目前,放疗靶区的勾画主要依靠食管钡餐和胸部CT等共同决定,但无论哪种检查方法,都无法有效地将肿瘤信息直观地体现在靶区勾画中,易出现食管肿瘤包绕不完全和(或)危及器官受到过度照射的情况,直接影响患者的预后[4]。钛夹常用于消化道止血或穿孔,相关研究结果也证实,术前利用钛夹对肿瘤的边界进行定位可以提高手术过程中肿瘤的完整切除率[5],同时钛夹具有X射线不能穿透等特点,适用于肿瘤的放疗[6]。本研究对通过内镜下钛夹植入确定局部晚期食管癌术前放疗患者靶区勾画的上下界进行探讨,并分析该模式下放疗的效果。
-
36例患者在内镜下共植入72枚钛夹,且均可通过CT扫描观察到。自钛夹植入至放疗结束,所有患者均未出现出血、穿孔等不良反应。其中4例患者(11.1%)的上界钛夹在治疗过程中脱落,脱落时间为(16.4±3.6) d。所有患者均在放疗结束后4~6周接受食管癌根治术,术后R0切除率为100%,pCR率为52.8%(19/36)。
-
36例患者中,钛夹植入前后GTV长度一致的患者有4例,钛夹植入前GTV长度大于钛夹植入后GTV长度的患者有26例,仅有6例患者钛夹植入前的GTV长度小于钛夹植入后的GTV长度,32例患者钛夹植入前后GTV长度变化的情况见图1。36例患者钛夹植入前的GTV长度为(4.74±1.02) cm,大于钛夹植入后的(3.98±0.79) cm,二者的差异有统计学意义(t=9.472,P<0.05)。钛夹植入前的GTV为(28.87±3.21) cm3,大于钛夹植入后的(24.59±2.67) cm3,二者的差异有统计学意义(t=6.726,P<0.05)。钛夹植入前CTV为(72.46±6.37) cm3,大于钛夹植入后的(56.37±4.52) cm3,二者的差异有统计学意义(t=7.696,P<0.05)。
-
由表1可知,钛夹植入前双肺V10和V20、脊髓的受照剂量均显著高于钛夹植入后,且差异均有统计学意义(均P<0.05);钛夹植入前心脏的受照剂量高于钛夹植入后,但二者的差异无统计学意义(P>0.05)。
项目 双肺V10 (%) 双肺V20(%) 脊髓(Gy) 心脏(Gy) 钛夹植入前 21.64±1.57 14.87±2.32 28.87±3.21 6.47±0.68 钛夹植入后 17.32±0.96 11.69±1.84 24.59±2.67 6.24±0.72 t值 8.05 7.64 −2.43 1.37 P值 <0.01 <0.01 <0.01 0.62 注:V10为接受10 Gy照射剂量的肺体积占全肺总体积的百分比;V20为接受20 Gy照射剂量的肺体积占全肺总体积的百分比 表 1 36例食管癌患者钛夹植入前后危及器官受照剂量的 比较(
)$\bar x \pm s $ Table 1. Comparison of organ at risk radiation dose before and after implantation of titanium clips in 36 patients with esophageal cancer (
)$\bar x \pm s $ -
36例患者中,精确组和误差组的病例数分别为8例(22.2%)和28例(77.8%)。单因素Logistic回归分析结果显示,年龄、肿瘤位置、饮酒史、GTV长度与GTV的精确勾画存在相关性(均P<0.01),而与性别、ECOG评分、分化程度无相关性(均P>0.05)(表2)。
临床特征 精确组(n=8) 误差组(n=28) χ2值 P值 年龄 5.64 0.01 ≥50岁 2 20 <50岁 6 8 性别 0.55 0.45 男 6 17 女 2 12 肿瘤位置 11.57 <0.01 胸上段 5 3 胸中段 2 13 胸下段 1 12 饮酒史 13.33 <0.01 有 2 24 无 6 4 ECOG评分 0.02 0.87 0分 5 14 1分 3 14 GTV长度 8.23 <0.01 ≥5 cm 2 21 <5 cm 6 7 分化程度 0.04 0.97 低分化 3 12 中分化 2 9 高分化 3 7 注:ECOG为美国东部肿瘤协作组;GTV为大体肿瘤体积 表 2 影响食管癌患者GTV精确勾画的单因素Logistic 回归分析结果(例)
Table 2. Univariate Logistic regression analysis of influencing the precise delineation of gross tumor volume in patients with esophageal cancer (case)
-
将单因素Logistic回归分析中有统计学意义的年龄、肿瘤位置、饮酒史、GTV长度等纳入Cox多因素回归分析,结果显示,肿瘤位置和GTV长度是影响GTV精确勾画的独立危险因素(P<0.05,表3)。
变量 RR(95%CI) P值 年龄(≥50岁对<50岁) 0.487(0.265~1.310) 0.274 肿瘤位置
(上段对中下段)0.296(0.137~0.586) <0.001 GTV长度(≥5 cm对<5 cm) 2.313(1.280~4.875) 0.006 饮酒史(有对无) 0.872(0.473~1.662) 0.496 注:GTV为大体肿瘤体积;RR为相对危险度;CI为置信区间 表 3 影响食管癌患者GTV精确勾画的Cox多因素回归 分析结果
Table 3. Cox multivariate regression analysis of influencing the precise delineation of gross tumor volume in patients with esophageal cancer
内镜下钛夹植入对局部晚期食管癌术前放疗患者靶区勾画和剂量学参数的影响
Effect of endoscopic titanium clip labeling on target delineation and dosimetric parameters in preoperative radiotherapy for locally advanced esophageal carcinoma
-
摘要:
目的 探讨内镜下钛夹植入对局部晚期食管癌术前放疗患者靶区勾画和剂量学参数的影响。 方法 回顾性分析2018年1月至2019年12月于联勤保障部队第九〇〇医院经超声胃镜及组织病理学检查确诊为局部晚期食管鳞癌的36例患者的临床资料,其中男性23例、女性13例,年龄18~65(43.7±6.9)岁。放疗前所有患者均在内镜下分别于食管病灶的上界和下界行钛夹植入术,在钛夹植入前后均行CT扫描定位和靶区勾画,比较钛夹植入前后的大体肿瘤体积(GTV)长度、GTV、肿瘤临床体积(CTV)和危及器官受照剂量的差异。将36例患者按照GTV上界和下界的误差分为精确组(误差<1 cm)和误差组(误差≥1 cm),分析影响食管靶区勾画的因素。计量资料的比较采用配对样本t检验和独立样本t检验;采用χ2检验对精确组和误差组的临床病理特征进行单因素Logistic回归分析;采用Cox多因素回归模型分析影响靶区精确勾画的危险因素。 结果 36例患者均顺利在内镜下植入钛夹,4例(11.1%)出现上界钛夹脱落;术后病理完全缓解率为52.8%(19/36)。钛夹植入前患者GTV长度为(4.74±1.02) cm,大于钛夹植入后的(3.98±0.79) cm,二者的差异有统计学意义(t=9.472,P<0.05)。钛夹植入前患者的GTV和CTV分别为(28.87±3.21) cm3和(72.46±6.37) cm3,均大于钛夹植入后的(24.59±2.67) cm3和(56.37±4.52) cm3,且差异均有统计学意义(t=6.726、7.696,均P<0.05)。钛夹植入前的双肺V10、V20(接受10、20 Gy照射剂量的肺体积占全肺总体积的百分比)和脊髓的受照剂量均高于钛夹植入后[(21.64±1.57)%对(17.32±0.96)%、(14.87±2.32)%对(11.69±1.84)%、(28.87±3.21) Gy对(24.59±2.67) Gy],且差异均有统计学意义(t=8.05、7.64、−2.43,均P<0.01)。单因素Logistic回归分析结果显示,年龄、肿瘤位置、饮酒史、GTV长度与GTV的勾画精确度存在相关性(χ2=5.64、11.57、13.33、8.23,均P<0.01)。Cox多因素回归分析结果显示,肿瘤位置 [相对危险度(RR)=0.296,95%置信区间:0.137~0.586,P<0.001]和GTV长度(RR=2.313,95%置信区间:1.280~4.875,P<0.01)是影响GTV精确勾画的独立危险因素。 结论 内镜下钛夹植入在局部晚期食管癌术前放疗中具有重要价值,可精确引导CT定位下靶区勾画的范围并减少正常器官的受照剂量。 Abstract:Objective To investigate the effects of titanium clip implantation under endoscope on target delineation and dosimetric parameters in patients with locally advanced esophageal cancer treated with preoperative radiotherapy. Methods The clinical data of 36 patients with locally advanced esophageal squamous cell carcinoma confirmed by ultrasound gastroscopy and histopathology in the Joint Logistics Support Force Hospital 900 from January 2018 to December 2019 were retrospectively analyzed, including 23 males and 13 females, aged 18−65(43.7±6.9) years. All patients were treated with titanium clip implantation at the upper and lower boundaries of esophageal lesions under endoscopy before and after radiotherapy. CT scan localization and target delineation were performed before and after titanium clip implantation. Gross tumor volume (GTV) length, GTV, clinical target volume (CTV), and normal organ irradiation dose were compared before and after titanium clip implantation. The patients were divided into accurate group (error < 1 cm) and error group (error≥1 cm) according to the error value, and the influencing factors of esophageal target delineation were analyzed. Paired sample t-test and independent sample t-test were used to compare the error values of tumor length, diameter, upper bound and lower bound before and after titanium clip implantation, spinal cord, and heart as well as the difference of the average irradiation dose of double lung V10 and V20. χ2 test was used to analyze the clinical case characteristics of the accurate group and the error group by univariate logistic regression. Cox multivariate regression risk factor analysis was used to analyze the risk factors affecting the accurate delineation of the target area. Results Titanium clips were successfully placed under endoscope in all patients, but 4 cases (11.1%) had the upper boundary titanium clips falling off. The postoperative pathological complete response rate was 52.8% (19/36). The length of GTV before titanium clip implantation was (4.74±1.02) cm, which was higher than that after implantation (3.98±0.79) cm, and the difference was statistically significant (t=9.472, P<0.05). The GTV and CTV of the tumor before implantation were (28.87±3.21) cm3 and (72.46±6.37) cm3, respectively, which were higher than (24.59±2.67) cm3 and (56.37±4.52) cm3 after implantation. The differences were statistically significant (t=6.726, 7.696; both P<0.05). The irradiation doses of V10, V20 (the percentage of lung volume in total lung volume that received more than 10 Gy and 20 Gy irradiation dose, respectively), and spinal cord in both lungs before titanium clip implantation were higher than those after implantation ((21.64±1.57)% vs. (17.32±0.96)%, (14.87±2.32)% vs. (11.69±1.84)%, (28.87±3.21) Gy vs. (24.59±2.67) Gy), and the differences were statistically significant (t=8.05, 7.64, −2.43; all P<0.01). Univariate Logistic regression analysis showed that age, tumor location, drinking history, and GTV length were correlated with the accurate delineation of GTV (χ2=5.64, 11.57, 13.33, 8.23; all P<0.01). Cox multivariate regression analysis showed that tumor location and GTV length were independent risk factors affecting the accurate delineation of GTV (RR=0.296, 95%CI: 0.137~0.586; 2.313, 95%CI: 1.280~4.875; both P<0.01). Conclusions Endoscopic titanium clip implantation is of great value in preoperative radiotherapy for locally advanced esophageal cancer. It can accurately guide the delineation of the target area under CT localization and reduce the irradiation dose of normal organs. -
Key words:
- Esophageal neoplasms /
- Titanium clip /
- Radiotherapy /
- Target delineation /
- Radiation dose
-
表 1 36例食管癌患者钛夹植入前后危及器官受照剂量的 比较(
)$\bar x \pm s $ Table 1. Comparison of organ at risk radiation dose before and after implantation of titanium clips in 36 patients with esophageal cancer (
)$\bar x \pm s $ 项目 双肺V10 (%) 双肺V20(%) 脊髓(Gy) 心脏(Gy) 钛夹植入前 21.64±1.57 14.87±2.32 28.87±3.21 6.47±0.68 钛夹植入后 17.32±0.96 11.69±1.84 24.59±2.67 6.24±0.72 t值 8.05 7.64 −2.43 1.37 P值 <0.01 <0.01 <0.01 0.62 注:V10为接受10 Gy照射剂量的肺体积占全肺总体积的百分比;V20为接受20 Gy照射剂量的肺体积占全肺总体积的百分比 表 2 影响食管癌患者GTV精确勾画的单因素Logistic 回归分析结果(例)
Table 2. Univariate Logistic regression analysis of influencing the precise delineation of gross tumor volume in patients with esophageal cancer (case)
临床特征 精确组(n=8) 误差组(n=28) χ2值 P值 年龄 5.64 0.01 ≥50岁 2 20 <50岁 6 8 性别 0.55 0.45 男 6 17 女 2 12 肿瘤位置 11.57 <0.01 胸上段 5 3 胸中段 2 13 胸下段 1 12 饮酒史 13.33 <0.01 有 2 24 无 6 4 ECOG评分 0.02 0.87 0分 5 14 1分 3 14 GTV长度 8.23 <0.01 ≥5 cm 2 21 <5 cm 6 7 分化程度 0.04 0.97 低分化 3 12 中分化 2 9 高分化 3 7 注:ECOG为美国东部肿瘤协作组;GTV为大体肿瘤体积 表 3 影响食管癌患者GTV精确勾画的Cox多因素回归 分析结果
Table 3. Cox multivariate regression analysis of influencing the precise delineation of gross tumor volume in patients with esophageal cancer
变量 RR(95%CI) P值 年龄(≥50岁对<50岁) 0.487(0.265~1.310) 0.274 肿瘤位置
(上段对中下段)0.296(0.137~0.586) <0.001 GTV长度(≥5 cm对<5 cm) 2.313(1.280~4.875) 0.006 饮酒史(有对无) 0.872(0.473~1.662) 0.496 注:GTV为大体肿瘤体积;RR为相对危险度;CI为置信区间 -
[1] Siegel RL, Miller KD, Jemal AJ. Cancer statistics, 2020[J]. CA Cancer J Clin, 2020, 70(1): 7−30. DOI: 10.3322/caac.21590. [2] Pasquali S, Yim G, Vohra RS, et al. Survival after neoadjuvant and adjuvant treatments compared to surgery alone for resectable esophageal carcinoma: a network meta-analysis[J]. Ann Surg, 2017, 265(3): 481−491. DOI: 10.1097/SLA.0000000000001905. [3] Zhan M, Zheng HR, Yang Y, et al. Cost-effectiveness analysis of neoadjuvant chemoradiotherapy followed by surgery versus surgery alone for locally advanced esophageal squamous cell carcinoma based on the NEOCRTEC5010 trial[J]. Radiother Oncol, 2019, 141: 27−32. DOI: 10.1016/j.radonc.2019.07.031. [4] Zhang JQ, Zhang WC, Zhang BZ, et al. Clinical results of intensity-modulated radiotherapy for 250 patients with cervical and upper thoracic esophageal carcinoma[J]. Cancer Manag Res, 2019, 11: 8285−8294. DOI: 10.2147/CMAR.S203575. [5] Lin L, Wang M, Hong J, et al. Application of preoperative endoscopic ultrasonography-guided carbon nanoparticle tattooing combined with titanium clip labeling in esophagogastric junction adenocarcinoma[J]. Turk J Gastroenterol, 2019, 30(10): 935−936. DOI: 10.5152/tjg.2019.18427. [6] Lin N, Yu CW, Yang J, et al. Nano-carbon and titanium clip combined labeling assisted surgery before neoadjuvant radiotherapy and chemotherapy for rectal cancer[J]. Asian J Surg, 2020, 43(1): 383−384. DOI: 10.1016/j.asjsur.2019.09.003. [7] Neeman E, Gresham G, Ovasapians N, et al. Comparing physician and nurse Eastern Cooperative Oncology Group Performance Status (ECOG-PS) ratings as predictors of clinical outcomes in patients with cancer[J]. Oncologist, 2019, 24(12): e1460−e1466. DOI: 10.1634/theoncologist.2018-0882. [8] Wu AJ, Bosch WR, Chang DT, et al. Expert consensus contouring guidelines for intensity modulated radiation therapy in esophageal and gastroesophageal junction cancer[J]. Int J Radit Oncol Biol Phys, 2015, 92(4): 911−920. DOI: 10.1016/j.ijrobp.2015.03.030. [9] Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1)[J]. Eur J Cancer, 2009, 45(2): 228−247. DOI: 10.1016/j.ejca.2008.10.026. [10] Cai XW, Zeng Y, Feng W, et al. Randomized phase Ⅱ trial comparing tumor bed alone with tumor bed and elective nodal postoperative radiotherapy in patients with locoregionally advanced thoracic esophageal squamous cell carcinoma[J]. Dis Esophagus, 2019, 32(12): doz013. DOI: 10.1093/dote/doz013. [11] Zou BW, Pang J, Liu YM, et al. Postoperative chemoradiotherapy improves survival in patients with stage Ⅱ-Ⅲ esophageal squamous cell carcinoma: an analysis of clinical outcomes[J]. Thorac Cancer, 2016, 7(5): 515−521. DOI: 10.1111/1759-7714.12355. [12] Stiles BM, Kamel MK, Harrison SW, et al. Neoadjuvant therapy for locally advanced esophageal cancer should be targeted to tumor histology[J]. Ann Thorac Surg, 2019, 107(1): 187−193. DOI: 10.1016/j.athoracsur.2018.07.089. [13] Luo HS, Huang HC, Lin LX. Effect of modern high-dose versus standard-dose radiation in definitive concurrent chemo-radiotherapy on outcome of esophageal squamous cell cancer: a meta-analysis[J/OL]. Radiat Oncol, 2019, 14(1): 178[2020-10-17]. https://ro-journal.biomedcentral.com/articles/10.1186/s13014-019-1386-x. DOI: 10.1186/s13014-019-1386-x. [14] Machiels M, Jin P, Van Hooft JE, et al. Reduced inter-observer and intra-observer delineation variation in esophageal cancer radiotherapy by use of fiducial markers[J]. Acta Oncol, 2019, 58(6): 943−950. DOI: 10.1080/0284186X.2019.1588991. [15] Corsi F, Bossi D, Sartani A, et al. Radio-guided and clip-guided preoperative localization for malignant microcalcifications offer similar performances in breast-conserving surgery[J]. Breast J, 2019, 25(5): 865−873. DOI: 10.1111/tbj.13354. [16] Tamburini N, Grossi W, Sanna S, et al. Chest wall reconstruction using a new titanium mesh: a multicenters experience[J]. J Thorac Dis, 2019, 11(8): 3459−3466. DOI: 10.21037/jtd.2019.07.74. [17] Wegner U, Rainford S. Adverse reaction regarding titanium-based marker clip: case report of a potential complication[J]. Int Med Case Rep J, 2019, 12: 291−295. DOI: 10.2147/IMCRJ.S222484. [18] Wood MM, Warshaw EM. Hypersensitivity reactions to titanium: diagnosis and management[J]. Dermatitis, 2015, 26(1): 7−25. DOI: 10.1097/DER.0000000000000091. [19] Tan L, Feng J, Zhao Q, et al. Preoperative endoscopic titanium clip placement facilitates intraoperative localization of early-stage esophageal cancer or severe dysplasia[J/OL]. World J Surg Oncol, 2017, 15(1): 145[2020-10-17]. https://wjso.biomedcentral.com/articles/10.1186/s12957-017-1188-2. DOI: 10.1186/s12957-017-1188-2. [20] Bittermann G, Ermer M, Voss P, et al. Comparison of virtual and titanium clip marking of tumour resection margins for improved radiation planning in head and neck cancer surgery[J]. Int J Oral Maxillofac Surg, 2015, 44(12): 1468−1473. DOI: 10.1016/j.ijom.2015.07.013. [21] Han Y, Oakley E, Shafirstein G, et al. Reconstruction of a deformed tumor based on fiducial marker registration: a computational feasibility study[J]. Technol Cancer Res Treat, 2018, 17: 1533034618766792. DOI: 10.1177/1533034618766792. [22] Stieb S, McDonald B, Gronberg M, et al. Imaging for target delineation and treatment planning in radiation oncology: current and emerging techniques[J]. Hematol Oncol Clin North Am, 2019, 33(6): 963−975. DOI: 10.1016/j.hoc.2019.08.008. [23] Babic B, Fuchs HF, Bruns CJ. Neoadjuvant chemoradiotherapy or chemotherapy for locally advanced esophageal cancer?[J]. Chirurg, 2020, 91(5): 379−383. DOI: 10.1007/s00104-020-01150-6. [24] Chan KKW, Saluja R, Santos KD, et al. Neoadjuvant treatments for locally advanced, resectable esophageal cancer: a network meta-analysis[J]. Int J Cancer, 2018, 143(2): 430−437. DOI: 10.1002/ijc.31312. [25] Shapiro J, Van Lanschot JJB, Hulshof MCC, et al. Neoadjuvant chemoradiotherapy plus surgery versus surgery alone for oesophageal or junctional cancer (CROSS): long-term results of a randomised controlled trial[J]. Lancet Oncol, 2015, 16(9): 1090−1098. DOI: 10.1016/S1470-2045(15)00040-6. [26] Motoori M, Ito Y, Miyashiro I, et al. Impact of age on long-term survival in patients with esophageal cancer who underwent transthoracic esophagectomy[J]. Oncology, 2019, 97(3): 149−154. DOI: 10.1159/000500604. [27] Iuliano S, Minelli R, Vincenzi F, et al. Eosinophilic esophagitis in pediatric age, state of the art and review of the literature[J]. Acta Biomed, 2018, 89(S8): S20−26. DOI: 10.23750/abm.v89i8-S.7866. [28] Deka AC, Srinivasan V, Dutta AM, et al. Expression of elastic fiber in esophageal squamous carcinoma tissue[J]. J Cancer Res Ther, 2015, 11(2): 277−279. DOI: 10.4103/0973-1482.146119. [29] Yoshida T, Amato MBP, Grieco DL, et al. Esophageal manometry and regional transpulmonary pressure in lung injury[J]. Am J Respir Crit Care Med, 2018, 197(8): 1018−1026. DOI: 10.1164/rccm.201709-1806OC. [30] Defize IL, Boekhoff MR, Borggreve AS, et al. Tumor volume regression during neoadjuvant chemoradiotherapy for esophageal cancer: a prospective study with weekly MRI[J]. Acta Oncol, 2020, 59(7): 753−759. DOI: 10.1080/0284186X.2020.1759819. [31] Zhang MS, Wu AJ. Radiation techniques for esophageal cancer[J]. Chin Clin Oncol, 2017, 6(5): 45. DOI: 10.21037/cco.2017.06.33.