恶性孤立性肺结节患者预后因素分析

doi:10.19723/j.issn.1671-167X.2020.01.025

摘要/Abstract

摘要：

目的:探讨影响恶性孤立性肺结节患者术后生存的因素,为早期肺癌患者的预后危险分层提供参考。方法:选择2006年4月至2013年12月在北京大学第一医院诊治的影像学诊断为孤立性肺结节、经手术病理诊断为非小细胞肺癌Ⅰa期的患者,共172例,对临床及随访资料进行回顾,分析性别、年龄、症状、吸烟、合并症、肿瘤标志物、结节类型、手术方式、结节部位、病理类型、结节大小、分化程度、Ki-67表达水平、EGFR突变等因素对患者生存率的影响。采用Kaplan-Meier生存分析、Cox回归分析评估影响患者生存的预后因素。结果:恶性孤立性肺结节患者的术后3年总生存率为93.6%、5年总生存率为89.8%,Kaplan-Meier生存分析和Cox单因素回归分析显示男性患者的总生存率显著低于女性,老年和高Ki-67增殖指数同样与患者较差的总生存率相关(P<0.05)。Cox多因素分析显示,年龄大于等于65岁和高Ki-67增殖指数是恶性孤立性肺结节术后患者总生存率的独立危险因素(年龄:P=0.023, HR=3.531, 95%CI 1.190~10.472;Ki-67:P=0.004, HR=1.021, 95%CI 1.007~1.035)。结论:对于恶性孤立性肺结节(即Ⅰa期非小细胞肺癌)患者,年龄、性别、Ki-67表达水平是影响恶性孤立性肺结节患者生存的预后因素。将Ki-67增殖指数与临床病理学特征综合考虑可能有助于对恶性孤立性肺结节患者进行更准确的预后危险分层,从而指导治疗方案的制定。

关键词: 恶性孤立性肺结节, Ⅰa期非小细胞肺癌, 预后因素

Abstract:

Objective: To explore the prognosis factors that influence the postoperative survival rate in patients with malignant solitary pulmonary nodules and to provide a reference for the prognosis risk stratification of early lung cancer patients. Methods: In this study, we retrospectively reviewed 172 patients who were admitted to Peking University First Hospital from April 2006 to December 2013. All cases were radiologically defined as solitary pulmonary nodule and were pathologically confirmed to be stage Ⅰa non-small cell lung cancer after surgical procedure. The patients’ clinical and follow-up data were summarized and analyzed. The relevance between survival time and factors that may affect patients’ prognosis was evaluated, which included gender, age, clinical symptoms, smoking history, comorbidity index, tumor biomarkers, nodule type, type of surgery, nodule location, nodule histopathological type, nodule size, histopathological differentiation grade, proliferating cell nuclear antigen Ki-67 expression level and epidermal growth factor receptor (EGFR) gene mutation. Kaplan-Meier survival analysis, Cox univariant and multivariant regression analysis were conducted to evaluate the factors affecting prognosis. Results: The 3-year overall survival rate of the atients with malignant solitary pulmonary nodules was 93.6%, and the 5-year overall survival rate was 89.8%. Kaplan-Meier survival analysis and Cox univariant regression analysis showed that the overall survival rate of the male patients was significantly lower than that of the female patients. In addition, the elderly patients with histopathology characterized as high Ki-67 proliferation index were also associated with the worse overall survival (P<0.05). Cox multivariant regression analysis demonstrated that age more than 65 years as well as the high Ki-67 expression level were independent risk factors for overall survival in patients with malignant solitary pulmonary nodules (age: P=0.023, HR=3.531, 95%CI 1.190-10.472; Ki-67: P=0.004, HR=1.021, 95%CI 1.007-1.035). Conclusion: For patients with malignant solitary pulmonary nodules, with pathological defined as stage Ⅰa non-small cell lung cancer, age, gender and Ki-67 expression levels might be important prognostic factors. Comprehensive consideration of Ki-67 proliferation index and clinical pathological features may help to stratify the prognosis more accurately and guide the selection of appropriate therapeutic strategies, which needs to be verified by multi-center studies.

Key words: Malignant solitary pulmonary nodule, Stage Ⅰa non-small cell lung cancer, Prognosis factor

中图分类号:

R734.2

欧阳雨晴,倪莲芳,刘新民. 恶性孤立性肺结节患者预后因素分析[J]. 北京大学学报（医学版）, 2020, 52(1): 158-162.

Yu-qing OUYANG,Lian-fang NI,Xin-min LIU. Prognosis factors analysis of patients with malignant solitary pulmonary nodules[J]. Journal of Peking University(Health Sciences), 2020, 52(1): 158-162.

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参考文献 14

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Variables	Numbers
Gender
Male	88 (51.2%)
Female	84 (48.8%)
Age/years
<65	100 (58.1%)
≥65	72 (41.9%)
Symptom
Negtive	109 (63.4%)
Positive	63 (36.6%)
CCI
0	113 (65.7%)
≥1	59 (34.3%)
Smoking
No	117 (68.0%)
Yes	55 (32.0%)
Tumor markers
Normal	80 (55.9%)
Elevated	63 (44.1%)
Nodule type
GGO	34 (31.8%)
SSN/SN	73 (68.2%)
Surgical methods
Lobectomy	165 (95.9%)
Segmentectomy	7 (4.1%)
Surgical typs
Thoracotomy	129 (75.3%)
VATS	43 (24.7%)
Nodule location
Upper lobe	65 (37.8%)
Middle/lower lobe	107 (62.2%)
Nodule size
≤2 cm	102 (59.3%)
>2 cm	70 (40.7%)
Histological type
Adenocarcinoma	124 (71.1%)
Other	48 (28.9%)
Differentiation grade
Poor	24 (14.0%)
Moderate/well	148 (86.0%)
EGFR mutation
Negative	41 (65.1%)
Positive	22 (34.9%)

Items		3-year survival	5-year survival	HR(95%CI)	P
Gender	Male	90.9	84.1	0.302 (0.113-0.816)	0.018
Gender	Female	96.4	96.4
Age/years	<65	97.0	92.8	2.634 (1.124-6.176)	0.026
Age/years	≥65	88.9	85.5
Symptom	Negative	95.4	89.5	1.014 (0.433-2.376)	0.974
Symptom	Positive	90.5	90.5
CCI	0	93.8	91.3	1.342 (0.584-3.082)	0.488
CCI	≥1	93.2	86.7
Smoking	No	94.9	91.0	1.794 (0.800-4.021)	0.156
Smoking	Yes	90.9	87.0
Tumor markers	Normal	98.8	95.6	1.623 (0.587-4.488)	0.350
Tumor markers	Elevated	92.1	85.4
Nodule type	GGO	100.0	100.0	34.859 (0.071-17 033.177)	0.261
Nodule type	SSN/SN	94.5	91.3
Surgery type	Thoracotomu	96.1	91.9	1.627 (0.695-3.808)	0.262
Surgery type	VATS	86.0	83.7
Nodule location	Upper lobe	93.8	91.7	1.092 (0.719-1.657)	0.681
Nodule location	Middle/lower lobe	93.3	88.2
Nodule size	≤2 cm	97.1	94.1	1.861 (0.824-4.204)	0.135
Nodule size	>2 cm	88.6	83.5
Histological type	Adenocarcinoma	94.4	89.9	0.953 (0.402-2.260)	0.913
Histological type	Other	91.7	89.2
Differentiation grade	Poorly	79.2	73.9	0.434 (0.178-1.054)	0.065
Differentiation grade	Moderate/well	95.9	92.4
Ki-67	-	-	-	1.019 (1.005-1.033)	0.008
EGFR mutation	Negative	92.7	92.7	0.609 (0.063-5.856)	0.668
EGFR mutation	Positve	95.5	95.5

Variables	B	SE	Wald	HR	P
Age	1.261	0.555	5.171	3.531 (1.190-10.472)	0.023
Ki-67	0.021	0.007	8.384	1.021 (1.007-1.035)	0.004