淋巴结转移特征对pN1期非小细胞肺癌术后局部转移的影响

doi:10.3877/cma.j.issn.1674-0785.2022.05.002

目的

探讨pN1期非小细胞肺癌术后局部转移的高危因素，寻找术后辅助放疗的潜在获益者。

方法

入组2009年11月至2016年12月在北京大学肿瘤医院胸外二科接受肺癌根治手术的pN1期非小细胞肺癌患者。收集患者临床、病理及随访资料，采用单因素分析与多因素分析的方法，探究淋巴结被膜外侵犯、淋巴结转移度、多站转移、转移淋巴结位置分布等淋巴结转移特征对于局部区域复发的影响，主要研究终点为无局部复发生存。

结果

共纳入257例患者，其中男性159例，女性98例，年龄（58.5±8.5）岁（35~80岁）。中位随访时间58个月（5~131个月）。全部患者中，1、3、5年总生存率分别为97.7%、77.1%、70.1%；1、3、5年无复发生存率分别为79.3%、55.6%、45.3%；1、3、5年无局部复发生存率分别为88.2%、76.0%、69.7%；1、3、5年无远处转移生存率分别为84.4%、58.9%、48.7%。多因素分析显示，淋巴结被膜外侵犯（HR=1.96，95%CI：1.09~3.51，P=0.024）与淋巴结转移度＞0.1（HR 2.28，95%CI：1.03~5.07，P=0.043）是术后局部复发的独立危险因素。

结论

淋巴结被膜外侵犯与淋巴结转移度＞0.1的pN1期非小细胞肺癌是术后局部区域复发的高危人群，其有可能成为术后辅助放疗的潜在获益者。

关键词: 癌，非小细胞肺, 局部区域复发, 淋巴结被膜外侵犯, 淋巴结转移度

Objective

To explore therisk factors forlocoregional recurrence in stage pN1non-small cell lung cancer patients, and identify potential candidates for adjuvant radiotherapy.

Methods

Patients diagnosed with stage pN1 non-small cell lung cancer who received radical surgery atBeijing Cancer Hospital between November 2009 and December 2016 were enrolled. The clinical, pathological, and surveillancedata of the patients were collected. The primary endpoint was locoreginal recurrence free survival (LRFS). Lymph node characteristics including extracapsular extension, lymph node ratio, multistation metastasis, distribution of metastaticlymph nodes, etc. were analysed by univariate and multivariate analyses.

Results

A total of 257 patients were enrolled, among whom 159 were male and 98 were female. The median age was (58.5±8.5) years (range: 35~80 years). The median follow-up time was 58months(range: 5~131 months). The 5-year LRFS rate for the entire cohort was 69.7%. Multivariate analysis demonstratedthat extracapsular extension (HR=1.96, 95%CI: 1.09~3.51, P=0.024) and lymph node ratio >0.1 (HR=2.28, 95%CI: 1.03~5.07, P=0.043) were significantly correlated with lower LRFS.

Conclusion

Extracapsular extension and lymph node ratio >0.1 are risk factors for locoregional recurrence in stage pN1non-small cell lung cancer. Patients carrying those risk factors might potentially benefit from adjuvant radiotherapy.

Key words: Carcinoma, non-small-cell lung, Locoreginal recurrence, Extracapsular extension, Lymph node ratio

表1 N1期非小细胞肺癌患者局部复发危险因素的单因素及多因素分析结果

	变量	例数	局部区域无复发生存率（%）			单因素分析		多因素分析
	变量	例数	1年	3年	5年	χ²值	P值	HR（95%CI）	P值
年龄（岁）						0.112	0.738
＜65		196	88.1	76.5	70.2
≥65		61	88.4	74.6	68.0
性别						0.508	0.476
男		159	88.4	73.8	66.8
女		98	87.8	79.2	74.0
吸烟史						0.118	0.731
无		118	87.3	77.3	72.0
有		139	94.2	89.0	67.5
原发灶位置						6.160	0.013
上叶		137	92.7	80.4	76.6
中/下叶		120	83.0	70.9	61.5			1.30（0.74-2.27）	0.359
术前CEA						4.693	0.030
正常		195	90.1	78.6	73.1
升高		62	82.2	67.8	58.7			1.50（0.85-2.67）	0.163
病理类型						0.721	0.697
腺癌		168	87.4	74.7	69.2
鳞癌		79	89.9	77.9	68.8
其他		10	90.0	90.0	90.0
T分期						1.564	0.458
T1		143	88.8	77.7	73.2
T2		75	86.3	74.8	65.3
≥T3		39	89.4	71.8	64.3
侵犯脏层胸膜						0.160	0.689
否		157	88.4	76.8	70.6
是		100	89.9	74.8	68.1
脉管癌栓						1.471	0.225
否		184	87.3	76.8	72.4
是		73	90.4	74.1	62.5
术式						0.001	0.969
肺叶切除术		244	87.4	76.2	70.0
全肺切除术		17	100	73.7	65.5
新辅助治疗						0.440	0.507
否		204	87.6	76.0	68.7
是		53	90.6	76.0	73.5
辅助治疗						1.306	0.253
否		73	93.1	79.5	75.6
是		184	86.3	74.7	67.5
淋巴结转移度						11.118	0.004
≤0.05		70	95.7	88.2	83.1
0.05~0.1		84	92.8	76.4	70.0			1.60（0.58~4.38）	0.362
＞0.1		103	79.3	67.2	60.0			3.10（1.09~8.80）	0.034
转移淋巴结站数						6.389	0.011
1		159	91.7	80.9	76.0
≥2		98	82.5	68.1	59.1			0.70（0.30~1.64）	0.407
阳性淋巴结分布						14.434	0.001
肺内		174	93.6	79.0	73.0
肺门/叶间		38	89.5	83.8	80.0			0.75（0.30~1.91）	0.548
都有		45	72.9	57.3	45.8			1.91（0.87~4.21）	0.108
淋巴结被膜外侵犯						11.854	0.003
否			93.9	87.4	80.1
是			77.3	63.4	58.7			2.20（1.23~3.92）	0.008
无资料			92.2	72.2	65.7
活检N2淋巴结个数						3.212	0.073
＜8		77	85.7	79.1	63.6
≥8		180	91.0	79.0	72.4			1.31（0.73~2.35）	0.370

表1 N1期非小细胞肺癌患者局部复发危险因素的单因素及多因素分析结果

	变量	例数	局部区域无复发生存率（%）			单因素分析		多因素分析
	变量	例数	1年	3年	5年	χ²值	P值	HR（95%CI）	P值
年龄（岁）						0.112	0.738
＜65		196	88.1	76.5	70.2
≥65		61	88.4	74.6	68.0
性别						0.508	0.476
男		159	88.4	73.8	66.8
女		98	87.8	79.2	74.0
吸烟史						0.118	0.731
无		118	87.3	77.3	72.0
有		139	94.2	89.0	67.5
原发灶位置						6.160	0.013
上叶		137	92.7	80.4	76.6
中/下叶		120	83.0	70.9	61.5			1.30（0.74-2.27）	0.359
术前CEA						4.693	0.030
正常		195	90.1	78.6	73.1
升高		62	82.2	67.8	58.7			1.50（0.85-2.67）	0.163
病理类型						0.721	0.697
腺癌		168	87.4	74.7	69.2
鳞癌		79	89.9	77.9	68.8
其他		10	90.0	90.0	90.0
T分期						1.564	0.458
T1		143	88.8	77.7	73.2
T2		75	86.3	74.8	65.3
≥T3		39	89.4	71.8	64.3
侵犯脏层胸膜						0.160	0.689
否		157	88.4	76.8	70.6
是		100	89.9	74.8	68.1
脉管癌栓						1.471	0.225
否		184	87.3	76.8	72.4
是		73	90.4	74.1	62.5
术式						0.001	0.969
肺叶切除术		244	87.4	76.2	70.0
全肺切除术		17	100	73.7	65.5
新辅助治疗						0.440	0.507
否		204	87.6	76.0	68.7
是		53	90.6	76.0	73.5
辅助治疗						1.306	0.253
否		73	93.1	79.5	75.6
是		184	86.3	74.7	67.5
淋巴结转移度						11.118	0.004
≤0.05		70	95.7	88.2	83.1
0.05~0.1		84	92.8	76.4	70.0			1.60（0.58~4.38）	0.362
＞0.1		103	79.3	67.2	60.0			3.10（1.09~8.80）	0.034
转移淋巴结站数						6.389	0.011
1		159	91.7	80.9	76.0
≥2		98	82.5	68.1	59.1			0.70（0.30~1.64）	0.407
阳性淋巴结分布						14.434	0.001
肺内		174	93.6	79.0	73.0
肺门/叶间		38	89.5	83.8	80.0			0.75（0.30~1.91）	0.548
都有		45	72.9	57.3	45.8			1.91（0.87~4.21）	0.108
淋巴结被膜外侵犯						11.854	0.003
否			93.9	87.4	80.1
是			77.3	63.4	58.7			2.20（1.23~3.92）	0.008
无资料			92.2	72.2	65.7
活检N2淋巴结个数						3.212	0.073
＜8		77	85.7	79.1	63.6
≥8		180	91.0	79.0	72.4			1.31（0.73~2.35）	0.370

图1 N1期非小细胞肺癌患者总生存（OS）及无复发生存（RFS）的生存曲线

图2 N1期非小细胞肺癌患者无局部区域复发生存（LRFS）及无远处转移生存（DMFS）的生存曲线

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Effect of lymph node metastasis characteristics on local regional recurrence in stage pN1 non-small cell lung cancer

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Effect of lymph node metastasis characteristics on local regional recurrence in stage pN1 non-small cell lung cancer