食管鳞癌调强放疗后急性放射性肺炎发生的临床和剂量学相关因素分析

doi:10.16150/j.1671-2870.2019.01.013

摘要/Abstract

摘要： 目的分析食管癌患者接受调强放疗（intensity modulated radiation theapy，IMRT）的体积剂量参数与放射性肺炎发生间的相关性，为临床治疗计划的制定提供参考依据。方法回顾性分析2013年1月至2016年12月我院88例接受食管癌IMRT患者的资料，收集临床数据和体积剂量参数V5~V40、肺平均剂量（mean lung dose， MLD）、全肺体积（total lung volume, TLV）、计划靶区（planning target volume，PTV），并与放疗后发生放射性肺炎情况进行相关性分析。结果中位随访18.7个月后显示，接受IMRT治疗患者的放射性肺炎中位发生时间为42 d，其中25例（28.4%）患者发生1度放射性肺炎，13例（14.8%）发生2度放射性肺炎，1例（1.1%出现3度放射性肺炎，无4度以上放射性肺炎发生。单因素分析显示，放射治疗的模式、食管癌根治术及剂量学参数V5、V10、V20、MLD与1度放射性肺炎的发生间具有相关性（P<0.05），仅剂量学参数V5、V10、V20、MLD与2度放射性肺炎的发生相关（P<0.05）。多因素分析显示，V5是发生1度放射性肺炎的独立预测因素，V10是发生2度以上放射性肺炎的独立预测因素，未发现与2度以上放射性肺炎相关的临床相关因素。结论食管癌接受IMRT治疗患者发生放射性肺炎的危险与V5、V10密切相关，制定IMRT治疗计划时应注意对低剂量体积参数的限制。

关键词: 放射性肺炎, 食管癌, 调强放疗, 体积剂量参数

Abstract:

Objective: To analyze the clinical and dosimetric factors associated with radiation-induced pneumonitis (RIP) in esophageal carcinoma patients treated with intensity modulated radiation therapy (IMRT) for developing a predictive model of RIP risk. Methods: Eighty-eight patients with histologically con?rmed esophageal carcinoma treated with IMRT from January 2013 to December 2016 were reviewed retrospectively. Clinical factors and dosimetric parameters were collected, and their correlations with risk of RIP were analyzed. Results: In total, twenty-five cases (28.4%) with grade 1 RIP, 13 (14.8%) with grade 2 RIP, and1 (1.1%) with grade 3 RIP (CTC 4.0) were observed. No grade 4 RIP was found.In univariate analysis, therapy modal of radiation, esophagectomy and dosimetric parameters V5, V10, V20 and mean lung dose (MLD) were significant factors for the development of RIP≥G1 (P<0.05). The V5, V10, V20, MLD were proved to be significant factors for the development of RIP≥G2 (P<0.05). By multivariate analysis, V5 was the only independent predictive factors for the development of RIP≥G1 (P<0.05); V10 was the only independent predictive factor for the development of RIP≥G2 (P<0.05). Conclusions: In comparison with MLD and V20, the widely used dosimetric parameters, our study showes that dosimetric parameters V5 and V10 could be the better predictor of RIP under the background of IMRT for esophageal carcinoma.

Key words: Radiation-induced pneumonitis, Esophageal cancer, Intensity modulated radiation therapy, Dosimetric parameter

中图分类号:

R541.7

郑磊, 赵胜光, 许赪, 蒋徐铭, 曹璐, 吴华玲, 陈佳艺. 食管鳞癌调强放疗后急性放射性肺炎发生的临床和剂量学相关因素分析[J]. 诊断学理论与实践, 2019, 18(1): 66-71.

ZHENG Lei, ZHAO Shengguang, XU Chen, JIANG Xu ming, CAO Lu, WU Hualing, CHEN Jiayi. Clinical and dosimetric factors associated with acute radiation-induced pneumonitis in esophageal carcinoma patients after intensity modulated radiation therapy (IMRT)[J]. Journal of Diagnostics Concepts & Practice, 2019, 18(1): 66-71.

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参考文献 17

[1]	Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019[J]. CA Cancer J Clin, 2019, 69(1):7-34.
[2]	Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015[J]. CA Cancer J Clin, 2016, 66(2):115-132.
[3]	Shirvani SM, Juloori A, Allen PK, et al. Comparison of 2 common radiation therapy techniques for definitive treatment of small cell lung cancer[J]. Int J Radiat Oncol Biol Phys, 2013, 87(1):139-147.
[4]	Lin SH, Wang L, Myles B, et al. Propensity score-based comparison of long-term outcomes with 3-dimensional conformal radiotherapy vs intensity-modulated radiotherapy for esophageal cancer[J]. Int J Radiat Oncol Biol Phys, 2012, 84(5):1078-1085.
[5]	Vogelius IR, Bentzen SM. A literature-based meta-analysis of clinical risk factors for development of radiation induced pneumonitis[J]. Acta Oncol, 2012, 51(8):975-983.
[6]	He J, Zeng ZC, Shi SM, et al. Clinical features, outcomes and treatment-related pneumonitis in elderly patients with esophageal carcinoma[J]. World J Gastroenterol, 2014, 20(36):13185-13190.
[7]	Kishida Y, Tsushima T, Endo M, et al. Risk Analysis of Pneumonitis in Taxane Therapy After Chemoradiotherapy for Patients With Metastatic or Recurrent Esophageal Cancer[J]. Am J Clin Oncol, 2018, 41(1):41-45.
[8]	Shaikh T, Churilla TM, Monpara P, et al. Risk of radiation pneumonitis in patients receiving taxane-based trimodality therapy for locally advanced esophageal cancer[J]. Pract Radiat Oncol, 2016, 6(6):388-394.
[9]	Zhao JK, Wu M, Kim CH, et al. Jiangsu Four Cancers Study: a large case-control study of lung, liver, stomach, and esophageal cancers in Jiangsu Province, China[J]. Eur J Cancer Prev, 2017, 26(4):357-364.
[10]	Kazerooni EA, Martinez FJ, Flint A, et al. Thin-section CT obtained at 10-mm increments versus limited three-level thin-section CT for idiopathic pulmonary fibrosis: correlation with pathologic scoring[J]. AJR Am J Roentgenol, 1997, 169(4):977-983.
[11]	Satoh K, Kobayashi T, Misao T, et al. CT assessment of subtypes of pulmonary emphysema in smokers[J]. Chest, 2001, 120(3):725-729.
[12]	Asakura H, Hashimoto T, Zenda S, et al. Analysis of dose-volume histogram parameters for radiation pneumonitis after definitive concurrent chemoradiotherapy for esophageal cancer[J]. Radiother Oncol, 2010, 95(2):240-244.
[13]	Nomura M, Kodaira T, Furutani K, et al. Predictive factors for radiation pneumonitis in oesophageal cancer patients treated with chemoradiotherapy without prophylactic nodal irradiation[J]. Br J Radiol, 2012, 85(1014):813-818.
[14]	Zhao Y, Chen L, Zhang S, et al. Predictive factors for acute radiation pneumonitis in postoperative intensity modulated radiation therapy and volumetric modulated arc therapy of esophageal cancer[J]. Thorac Cancer, 2015, 6(1):49-57.
[15]	Cunliffe A, Armato SG 3rd, Castillo R, et al. Lung texture in serial thoracic computed tomography scans: correlation of radiomics-based features with radiation therapy dose and radiation pneumonitis development[J]. Int J Radiat Oncol Biol Phys, 2015, 91(5):1048-1056.
[16]	Chen J, Hong J, Zou X, et al. Association between absolute volumes of lung spared from low-dose irradiation and radiation-induced lung injury after intensity-modulated radiotherapy in lung cancer: a retrospective analysis[J]. J Radiat Res, 2015, 56(6):883-888.
[17]	张丽, 汪志, 崔珍珍, 等. 简化适形调强技术与调强适形放疗在胸段食管癌放疗中的剂量学比较[J]. 安徽医学, 2018, 39(9):1048-1051.

评分	肺纤维化	肺气肿
0	无纤维化改变	肺内无过低密度区（low air areas, LAAs）
1	叶间裂增厚	散在的LAAs，最大径不超过5 mm
2	蜂窝样改变（伴或不伴叶间裂增厚）累及<25%的肺叶	毗邻的LAAs，最大径不超过10 mm
3	蜂窝样改变（伴或不伴叶间裂增厚）累及25%~49%的肺叶	LAAs>10 mm，互相连接成片状
4	蜂窝样改变（伴或不伴叶间裂增厚）累及50%~75%的肺叶	缺乏正常的肺间质结构
5	蜂窝样改变（伴或不伴叶间裂增厚）累及>75%的肺叶	-

分级	判断标准
1度	无症状，仅有影像学改变
2度	有症状，但不干扰日常生活
3度	有症状，影响日常生活，需要氧气治疗
4度	影响生命，需要呼吸机支持
5度	死亡

变量	病例总数	放射性肺炎≥1度的病例总数(%)	χ²值	P值	放射性肺炎≥2度的病例总数(%)	χ²值	P值
性别			1.667	0.2		3.192	0.078
男	74	35(47.3%)			14(18.9%)
女	14	4(28.6%)			0(00.0%)
年龄（岁）			0.040	0.843		0.222	0.639
≤70	73	32(43.8%)			11(15.1%)
>70	15	7(46.7%)			3(20.0%)
食管癌根治术			9.353	0.003		0.076	0.783
是	47	14(29.8%)			7(14.9%)
否	41	25(61.0%)			7(17.1%)
治疗模式			5.888	0.017		0.145	0.705
根治放疗	38	23(60.5%)			6(15.8%)
辅助放疗	31	10(32.3%)			4(12.9%)
姑息放疗	19	6(31.6%)			4(21.1%)
位置			3.658	0.058		0.074	0.786
上段	36	9(25.0%)			4(11.1%)
中段	39	25(64.1%)			9(23.1%)
下段	13	5(38.5%)			1(7.7%)
化疗			0.038	0.846		0.001	0.972
紫杉类为主	31	13 (41.9%)			4(12.9%)
氟尿类为主	38	19(50.0%)			8(21.1%)
无化疗	19	7(36.8%)			2(10.5%)
基线PF评分			2.15	0.146		0.317	0.575
0~2分	57	22(38.6%)			10(17.5%)
3~4分	31	17(54.8%)			4(12.9%)
基线PE评分			0.431	0.513		0.065	0.800
0~1分	53	25(47.2%)			8(15.1%)
2~4分	35	14(40.0%)			6(17.1%)
剂量(Gy)			2.594	0.111		0.213	0.645
≤55	49	18(36.7%)			7(14.3%)
>55	39	21(53.8%)			7(17.9%)

变量	放射性肺炎≥1度			P值	放射性肺炎≥2度		P值
变量	总量(88)	是(39)	否(49)	P值	是(14)	否(74)	P值
TLV(cm³)	3 480±941	3 351±791	3 582±1 042	0.257	3 301±817	35 14±964	0.396
PTV(cm³)	343±156	371±155	322±154	0.145	400±137	332±157	0.117
MLD(Gy)	10.91±2.81	12.42±2.36	9.71±2.56	0.001	12.78±2.78	10.56±2.69	0.013
V5	54.33±16.8	64.16±13.83	46.51±14.8	0.001	65.43±14.06	52.23±16.53	0.005
V10	39.34±13.11	45.77±12.68	34.22±11.13	0.001	49.13±12.69	37.49±12.42	0.005
V20	19.47±5.96	21.66±5.71	17.73±5.63	0.002	23.73±7.38	18.67±5.35	0.027
V30	8.32±3.59	8.94±3.66	7.83±3.5	0.155	8.49±3.86	8.29±3.57	0.861
V40	3.41±2.47	3.77±2.86	3.12±2.09	0.238	3.29±2.70	3.43±2.44	0.857

分级	变量	β	S.E	Wald	P值	Exp(B)	95%CI
放射性肺炎≥1度	V5	0.09	0.022	17.631	0.001	1.095	1.049~1.142
放射性肺炎≥2度	V10	0.068	0.025	7.407	0.006	1.071	1.019~1.125