基于术前CT征象构建肾透明细胞癌患者总生存期的列线图

doi:10.3760/cma.j.cn371439-20190923-00061

摘要/Abstract

摘要：

目的探讨肾透明细胞癌(ccRCC)患者术前CT征象影响总生存期的独立危险因素并绘制列线图。方法回顾性分析空军军医大学第一附属医院2011年10月至2015年12月术前行CT扫描并最终经病理学证实的ccRCC患者238例。由两名影像科医生对每例患者的CT征象进行评价,并收集患者的一般资料、肾功能检查以及世界卫生组织/国际泌尿病理协会(WHO/ISUP)分级。绘制Kaplan-Meier生存曲线,采用log-rank检验比较生存率。采用Cox比例风险回归进行单变量和多变量分析,并根据多变量分析结果绘制列线图,采用Bootstrap 1000法内部验证后计算C-指数。结果 238例患者经3~74个月随访后,死亡组32例,截尾组206例。死亡组患者的肿瘤直径为(65.70±27.29)mm,大于截尾组的(46.25±26.16)mm,差异有统计学意义(t=-3.889,P<0.001)。死亡组患者肿瘤坏死(χ²=45.716,P<0.001)、区域淋巴结肿大(χ²=43.342,P<0.001)、肾周脂肪侵犯(χ²=19.324,P<0.001)的发生率均高于截尾组患者。不同肿瘤直径的ccRCC患者其生存率差异有统计学意义(χ²=17.108,P<0.001)。肿瘤组织出现坏死患者的生存率较无坏死患者低(χ²=48.195,P<0.001);区域淋巴结肿大患者的生存率低于无区域淋巴结肿大的患者(χ²=47.232,P<0.001);出现肾周脂肪侵犯患者的生存率低于未侵犯的患者(χ²=19.964,P<0.001)。不同WHO/ISUP分级ccRCC患者的生存率差异有统计学意义(χ²=27.765,P<0.001)。多变量Cox比例风险回归分析结果显示,CT征象中的肿瘤直径(HR=2.90,95%CI为1.37~6.14,P=0.006)、坏死(HR=8.88,95%CI为3.33~23.69,P<0.001)及区域淋巴结肿大(HR=4.48,95%CI为2.04~9.86,P<0.001)是ccRCC患者死亡的独立危险因素。列线图的C-指数为0.870。结论术前CT征象与ccRCC患者的生存率存在相关性,其中肿瘤直径、肿瘤出现坏死以及区域淋巴结肿大是其死亡的独立危险因素,其列线图具有较高的准确性。

关键词: 肾肿瘤, 腺癌,透明细胞, 体层摄影术,螺旋计算机, 列线图表

Abstract:

Objective To explore the independent risk factors of preoperative CT findings affecting the overall survival of patients with clear cell renal cell carcinoma (ccRCC) and to draw a nomogram. Methods The retrospective study was performed on 238 patients with ccRCC who underwent preoperative CT scan and were pathologically confirmed in First Affiliated Hospital of Air Force Medical University from October 2011 to December 2015. CT findings of each patient were evaluated by two radiologists, and general information, renal function examination, and World Health Organization/International Society for Urology and Pathology (WHO/ISUP) grading were collected. The Kaplan-Meier survival curve was plotted, and survival rates were compared using log-rank test. Cox proportional hazard regression was used for univariate and multivariate analysis, and the nomogram was drawn according to the results of multivariate analysis, and the C-index was calculated after internal validation by Bootstrap 1000. Results After 3-74 months of follow-up for 238 patients, 32 cases were in the death group and 206 cases were in the censored group. The tumor diameter of the death group [(65.70±27.29) mm] was larger than that of the censored group [(46.25±26.16) mm], with a statistically significant difference (t=-3.889, P<0.001). The incidence rate of tumor necrosis (χ²=45.716, P<0.001), regional lymph node enlargement (χ²=43.342, P<0.001) and perirenal fat invasion (χ²=19.324, P<0.001) in the death group were higher than those in the censored group. Survival rates were different in patients with different tumor diameter of ccRCC, with a statistically significant difference (χ²=17.108, P<0.001). The survival rate of patients with tumor necrosis was lower than those without necrosis (χ²=48.195, P<0.001). The survival rate of patients with regional lymph node enlargement was lower than those without regional lymph node enlargement (χ²=47.232, P<0.001). The survival rate of patients with perirenal fat invasion was lower than those without perirenal fat invasion (χ²=19.964, P<0.001). Survival rates were also different in ccRCC patients with different WHO/ISUP grades, with a statistically significant difference (χ²=27.765, P<0.001). In Cox multivariate analysis, tumor diameter (HR=2.90, 95%CI: 1.37-6.14, P=0.006), necrosis (HR=8.88, 95%CI: 3.33-23.69, P<0.001) and regional lymph node enlargement (HR=4.48, 95%CI: 2.04-9.86, P<0.001) in CT findings were independent risk factors for death in patients with ccRCC. The C-index of nomogram was 0.870. Conclusion Preoperative CT findings are correlated with survival rate of patients with ccRCC, in which tumor diameter, tumor necrosis and regional lymph node enlargement are independent risk factors for death, and the nomograms has high accuracy.

Key words: Kidney neoplasms, Adenocarcinoma,clear cell, Tomography,spiral computed, Nomogram

王佳丽, 韩冬, 陈英, 张亚敏, 艾美梅. 基于术前CT征象构建肾透明细胞癌患者总生存期的列线图[J]. 国际肿瘤学杂志, 2020, 47(8): 480-486.

Wang Jiali, Han Dong, Chen Ying, Zhang Yamin, Ai Meimei. Construction of a nomogram of overall survival of patients with clear cell renal cell carcinoma based on preoperative CT findings[J]. Journal of International Oncology, 2020, 47(8): 480-486.

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参考文献 22

[1]	黄毅, 阴雷, 黄海, 等. 128例20~40岁肾细胞癌患者的临床病理特征及预后分析[J]. 中华泌尿外科杂志, 2014,35(10):731-733. DOI: 10.3760/cma.j.issn.1000-6702.2014.10.003.
[2]	Keegan KA, Schupp CW, Chamie K, et al. Histopathology of surgically treated renal cell carcinoma: survival differences by subtype and stage[J]. J Urol, 2012,188(2):391-397. DOI: 10.1016/j.juro.2012.04.006. doi: 10.1016/j.juro.2012.04.006 pmid: 22698625
[3]	Cumberbatch MG, Rota M, Catto JW, et al. The role of tobacco smoke in bladder and kidney carcinogenesis: a comparison of exposures and meta-analysis of incidence and mortality risks[J]. Eur Urol, 2016,70(3):458-466. DOI: 10.1016/j.eururo.2015.06.042. doi: 10.1016/j.eururo.2015.06.042 pmid: 26149669
[4]	Pedrosa I, Sun MR, Spencer M, et al. MR imaging of renal masses: correlation with findings at surgery and pathologic analysis[J]. Radiographics, 2008,28(4):985-1003. DOI: 10.1148/rg.284065018.
[5]	Hötker AM, Karlo CA, Zheng J, et al. Clear cell renal cell carcinoma: associations between CT features and patient survival[J]. AJR Am J Roentgenol, 2016,206(5):1023-1030. DOI: 10.2214/AJR.15.15369. doi: 10.2214/AJR.15.15369
[6]	张进, 王共先, 郭剑明, 等. 肾细胞癌随访5年生存分析及预后相关因素的多中心研究[J]. 中华泌尿外科杂志, 2015,36(2):113-117. DOI: 10.3760/cma.j.issn.1000-6702.2015.02.009.
[7]	Nguyen MM, Gill IS. Effect of renal cancer size on the prevalence of metastasis at diagnosis and mortality[J]. J Urol, 2009,181(3):1020-1027. DOI: 10.1016/j.juro.2008.11.023. pmid: 19150563
[8]	任金武, 马聪敏, 张立红, 等. 基于Logistic判别模型初步分析肾透明细胞癌CT征象与预后的关系[J]. 临床放射学杂志, 2018,37(5):789-792. DOI: 10.13437/j.cnki.jcr.2018.05.018.
[9]	Chow WH, Shuch B, Linehan WM, et al. Racial disparity in renal cell carcinoma patient survival according to demographic and clinical characteristics[J]. Cancer, 2013,119(2):388-394. DOI: 10.1002/cncr.27690. pmid: 23147245
[10]	Ku JH, Moon KC, Kwak C, et al. External validation of an international multicenter study to predict survival in Korean patients with pT2N0M0 renal cell carcinoma[J]. Urology, 2009,74(2):359-363. DOI: 10.1016/j.urology.2009.02.037. pmid: 19501879
[11]	文娟娟, 周晓军. 肾细胞癌预后的影响因素[J]. 中华病理学杂志, 2013,42(12):850-853. DOI: 10.3760/cma.j.issn.0529-5807.2013.12.019.
[12]	Phillips CK, Taneja SS. The role of lymphadenectomy in the surgical management of renal cell carcinoma[J]. Urol Oncol, 2004,22(3):214-224. DOI: 10.1016/j.urolonc.2004.04.028.
[13]	Patard JJ, Leray E, Rodriguez A, et al. Correlation between symptom graduation, tumor characteristics and survival in renal cell carcinoma[J]. Eur Urol, 2003,44(2):226-232. DOI: 10.1016/s0302-2838(03)00216-1. pmid: 12875943
[14]	Novara G, Ficarra V, Antonelli A, et al. Validation of the 2009 TNM version in a large multi-institutional cohort of patients treated for renal cell carcinoma: are further improvements needed?[J]. Eur Urol, 2010,58(4):588-595. DOI: 10.1016/j.eururo.2010.07.006.
[15]	Steffens S, Janssen M, Roos FC, et al. Incidence and long-term prognosis of papillary compared to clear cell renal cell carcinoma-a multicentre study[J]. Eur J Cancer, 2012,48(15):2347-2352. DOI: 10.1016/j.ejca.2012.05.002.
[16]	Oh S, Sung DJ, Yang KS, et al. Correlation of CT imaging features and tumor size with Fuhrman grade of clear cell renal cell carcinoma[J]. Acta Radiol, 2017,58(3):376-384. DOI: 10.1177/0284185116649795. doi: 10.1177/0284185116649795 pmid: 27235451
[17]	Delahunt B, Egevad L, Samaratunga H, et al. Gleason and Fuhrman no longer make the grade[J]. Histopathology, 2016,68(4):475-481. DOI: 10.1111/his.12803. doi: 10.1111/his.12803 pmid: 26266664
[18]	Lam JS, Shvarts O, Said JW, et al. Clinicopathologic and molecular correlations of necrosis in the primary tumor of patients with renal cell carcinoma[J]. Cancer, 2005,103(12):2517-2525. DOI: 10.1002/cncr.21127. doi: 10.1002/cncr.21127 pmid: 15880379
[19]	Sengupta S, Lohse CM, Leibovich BC, et al. Histologic coagulative tumor necrosis as a prognostic indicator of renal cell carcinoma aggressiveness[J]. Cancer, 2005,104(3):511-520. DOI: 10.1002/cncr.21206. doi: 10.1002/cncr.21206 pmid: 15973740
[20]	Khor LY, Dhakal HP, Jia X, et al. Tumor necrosis adds prognostically significant information to grade in clear cell renal cell carcinoma: a study of 842 consecutive cases from a single institution[J]. Am J Surg Pathol, 2016,40(9):1224-1231. DOI: 10.1097/PAS.0000000000000690.
[21]	Delahunt B, Cheville JC, Martignoni G, et al. The International Society of Urological Pathology (ISUP) grading system for renal cell carcinoma and other prognostic parameters[J]. Am J Surg Pathol, 2013,37(10):1490-1504. DOI: 10.1097/PAS.0b013e31-8299f0fb. pmid: 24025520
[22]	Rioux-Leclercq N, Karakiewicz PI, Trinh QD, et al. Prognostic ability of simplified nuclear grading of renal cell carcinoma[J]. Cancer, 2007,109(5):868-874. DOI: 10.1002/cncr.22463. doi: 10.1002/cncr.22463 pmid: 17262800

参数	截尾组 (n=206)	死亡组 (n=32)	t/χ²值	P值
年龄(岁)	52.08±12.49	54.50±14.17	-1.000	0.318
性别
女	61	9	0.029	0.864
男	145	23
肉眼血尿
无	178	27	0.001	0.972
有	28	5
胁腹部疼痛
无	153	23	0.083	0.774
有	53	9
腹部肿块
无	180	30	0.556	0.456
有	26	2
实验室检查
胱抑素C(mg/L)	1.03±0.28	1.20±0.28	-3.269	0.001
血肌酐(μmol/L)	77.32±21.45	77.41±24.86	-0.020	0.984
尿酸(μmol/L)	364.31±93.93	339.84±116.75	1.324	0.187
WHO/ISUP分级
Ⅰ级	47	2
Ⅱ级	130	15	24.806	<0.001
Ⅲ级	26	11
Ⅳ级	3	4

参数	HR值	95%CI	P值
年龄	1.02	0.99~1.05	0.270
性别	1.09	0.50~2.35	0.833
肉眼血尿	1.25	0.48~3.26	0.642
胁腹部疼痛	1.14	0.52~2.45	0.749
腹部肿块	0.49	0.12~2.04	0.324
胱抑素C	3.62	1.64~7.96	0.001
血肌酐	1.00	0.98~1.02	0.936
尿酸	1.00	0.99~1.00	0.211
WHO/ISUP分级
Ⅰ级	参考		<0.001
Ⅱ级	2.70	0.62~11.81	0.188
Ⅲ级	9.06	2.00~41.00	0.004
Ⅳ级	17.81	3.26~97.44	0.001
肿瘤直径(≥57.9 mm)	4.13	1.99~8.57	<0.001
位置	1.34	0.66~2.71	0.422
相对密度
低密度	参考		0.402
等密度	1.19	0.51~2.78	0.692
高密度	1.90	0.71~5.06	0.200
坏死	12.39	5.15~34.79	<0.001
钙化	1.50	0.65~3.47	0.344
区域淋巴结肿大	8.79	4.16~18.57	<0.001
肾周脂肪侵犯	4.89	2.26~10.58	<0.001