Pattern of lymph node metastasis in the lung lobe of NSCLC and selection of lymph node dissection methods in complete video-assisted thoracoscopic lobectomy surgery

doi:10.3760/cma.j.cn371439-20240422-00095

Abstract

Abstract:

Objective To explore the pattern of lymph node metastasis in the lung lobes of stage Ⅱa non-small cell lung cancer （NSCLC） and the lymph node dissection method during complete video-assisted thoracoscopic lobectomy surgery （cVATS）. Methods A total of 244 patients with NSCLC who underwent cVATS treatment at Nanjing Tongren Hospital Affiliated to Southeast University School of Medicine from January 2015 to November 2018 were selected. Patients admitted from January 2015 to April 2018 were defined as the training set （n=183）， and patients admitted from May 2018 to November 2018 were defined as the validation set （n=61）. The training set was used to build the model， and the validation set was used to evaluate the performance of the model. In the training set， patients were divided into systematic meditational lymphadenectomy （SML） group （n=93） and lobe-specific systematic node dissection （LSND） group （n=90） based on lymph node dissection methods.The lymph node metastasis rate of patients in the training set was calculated， and the clinical data of patients with （n=55） and without （n=128） lymph node metastasis were compared. Multivariate logistic regression was used to analyze the influencing factors of lymph node metastasis， and a nomogram prediction model was constructed based on the results of the multivariate analysis， and the model was validated. Clinical data， perioperative clinical indicators， overall survival （OS）， and incidence of postoperative complications were compared between the SML group and LSND group in the training set. Results In the training set， the lymph node metastasis rate of 183 patients with NSCLC was 30.05% （55/183）， with a total of 328 metastatic lymph nodes； from the 2nd to the 13th groups of lymph nodes， the 10th （15.60%， 44/282）， the 11th （22.79%， 98/430）， and the 12th to the 13th （15.25%， 61/400） groups had the highest lymph node metastasis rate. Multivariate analysis showed that maximum tumor diameter （OR=2.71， 95%CI： 1.82-4.09， P<0.001）， CT imaging features （OR=2.49， 95%CI： 1.59-6.99， P=0.001）， degree of differentiation （OR=2.06， 95%CI： 1.11-3.81， P=0.010）， serum carcinoembryonic antigen （CEA）（OR=1.87， 95%CI： 1.42-2.58， P=0.015）， and pleural invasion （OR=1.81， 95%CI： 1.07-3.07， P=0.021） were all independent influencing factors for the occurrence of lymph node metastasis in Ⅱa NSCLC patients. The C-index of the training set and the validation set were 0.91 （95%CI： 0.88-0.97） and 0.89 （95%CI： 0.84-0.96）， respectively， and the calibration curves of the two sets were well fitted to the ideal curves. Receiver operating characteristic curve analysis showed that， the area under curve of the nomogram prediction model used for differential diagnosis of patients in the training and validation sets were 0.92 （95%CI： 0.87-0.96） and 0.91 （95%CI： 0.85-0.98）， respectively. There were statistically significant differences in surgical time [（203.08±38.26） min vs. （177.14±22.18） min， t=5.59， P<0.001]， intraoperative blood loss [（458.14±65.04） ml vs. （426.08±26.58） ml， t=4.34， P<0.001]， thoracic drainage volume [（1 200.14±226.58） ml vs. （1 114.38±164.34） ml， t=2.92， P=0.004]， extubation time [（6.57±1.28） d vs. （5.02±1.12） d， t=8.71， P<0.001]， hospital stay [（15.02±1.29） d vs. （12.08±1.57） d， t=13.86， P<0.001） between the SML group and the LSND group in the training set. There was no statistically significant difference in OS rate between two groups of patients at 1 year （96.77% vs. 96.67%）， 3 years （84.95% vs. 86.67%）， and 5 years （75.27% vs. 77.78%）（χ²=0.16， P=0.689）. There was a statistically significant difference in the overall incidence of adverse reactions [18.28%（17/93） vs. 7.78%（7/90）] between two groups of patients （χ²=4.43， P=0.035）. Conclusion Intrapulmonary segment lymph node accounts for a considerable proportion in the metastasis process of NSCLC， with the highest degree of lymph node metastasis rate in groups 10， 11， and 12-13. Maximum tumor diameter， CT imaging features， degree of differentiation， serum CEA， and pleural invasion are all independent influencing factors for the occurrence of lymph node metastasis in NSCLC patients. Compared with SML， LSND has less trauma and a lower incidence of adverse reactions.

Key words: Carcinoma， non-small-cell lung, Lymphatic Metastasis, Complete video-assisted thoracoscopic lobectomy surgery

Wang Qingbei, Zhu Lin, Wu Zhengguo. Pattern of lymph node metastasis in the lung lobe of NSCLC and selection of lymph node dissection methods in complete video-assisted thoracoscopic lobectomy surgery[J]. Journal of International Oncology, 2024, 51(9): 569-577.

Figures/Tables 10

References 18

[1]	Matsuzawa R, Morise M, Kinoshita F, et al. Non-invasive early prediction of immune checkpoint inhibitor efficacy in non-small-cell lung cancer patients using on-treatment serum CRP and NLR[J]. J Cancer Res Clin Oncol, 2023, 149(7): 3885-3893. DOI: 10.1007/s00432-022-04300-x.
[2]	Dechow T, Riera-Knorrenschild J, Hackanson B, et al. First-line nab-paclitaxel plus carboplatin for patients with advanced non-small cell lung cancer: final results of the NEPTUN study[J]. Int J Cancer, 2023, 153(1): 141-152. DOI: 10.1002/ijc.34467. pmid: 36757197
[3]	Cao J, Zhang C, Zhang X, et al. The clinical outcomes of thoracoscopic versus open lobectomy for non-small-cell lung cancer after neoadjuvant therapy: a multi-center retrospective cohort study[J]. Clin Lung Cancer, 2024, 25(3): e153-e160. DOI: 10.1016/j.cllc.2023.12.008.
[4]	Nakanishi R, Okuda K, Yokota K, et al. Complex video-assisted thoracoscopic surgery lobectomy for locally advanced lung cancer: a prospective feasibility study[J]. Surg Today, 2022, 52(11): 1582-1590. DOI: 10.1007/s00595-022-02491-x. pmid: 35320417
[5]	Merritt RE, Abdel-Rasoul M, D'Souza DM, et al. Comparison of the long-term oncologic outcomes of robotic-assisted and video-assisted thoracoscopic lobectomy for resectable non-small cell lung carcinoma[J]. J Robot Surg, 2022, 16(6): 1281-1288. DOI: 10.1007/s11701-022-01368-y. pmid: 35032309
[6]	Zhu G, Wang JA, Xiao D, et al. Spectral CT for preoperative diagnosis of N₂ station lymph node metastasis in solid T₁ non-small cell lung cancer[J]. Eur J Radiol, 2024, 177: 111553. DOI: 10.1016/j.ejrad.2024.111553.
[7]	Goldstraw P, Chansky K, Crowley J, et al. The IASLC lung cancer staging project: proposals for revision of the TNM stage groupings in the forthcoming (eighth) edition of the TNM classification for lung cancer[J]. J Thorac Oncol, 2016, 11(1): 39-51. DOI: 10.1016/j.jtho.2015.09.009. pmid: 26762738
[8]	Castenmiller SM, de Groot R, Guislain A, et al. Effective generation of tumor-infiltrating lymphocyte products from metastatic non-small-cell lung cancer (NSCLC) lesions irrespective of location and previous treatments[J]. Immunooncol Technol, 2022, 15: 100090. DOI: 10.1016/j.iotech.2022.100090.
[9]	Zhao Y, Mao Y, He J, et al. Lobe-specific lymph node dissection in clinical stage ⅠA solid-dominant non-small-cell lung cancer: a propensity score matching study[J]. Clin Lung Cancer, 2021, 22(2): e201-e210. DOI: 10.1016/j.cllc.2020.09.012.
[10]	Zhang D, Chen X, Zhu D, et al. Intrapulmonary lymph node metastasis is common in clinically staged ⅠA adenocarcinoma of the lung[J]. Thorac Cancer, 2019, 10(2): 123-127. DOI: 10.1111/1759-7714.12908.
[11]	Wang Z, Xiang J, Gui Z, et al. Unilateral TNM T₁ and T₂ papillary thyroid carcinoma with lateral cervical lymph node metastasis: total thyroidectomy or lobectomy?[J]. Endocr Pract, 2020, 26(10): 1085-1092. DOI: 10.4158/EP-2020-0125.
[12]	Pei JP, Zhang R, Zhang NN, et al. Screening and validation of a novel T stage-lymph node ratio classification for operable colon cancer[J]. Ann Transl Med, 2021, 9(20): 1513. DOI: 10.21037/atm-21-3170.
[13]	Xu H, Zhao W, Guo W, et al. Prediction model combining clinical and MR data for diagnosis of lymph node metastasis in patients with rectal cancer[J]. J Magn Reson Imaging, 2021, 53(3): 874-883. DOI: 10.1002/jmri.27369.
[14]	Jianlong B, Pinyi Z, Xiaohong W, et al. Risk factors for lymph node metastasis and surgical scope in patients with cN₀ non-small cell lung cancer: a single-center study in China[J]. J Cardiothorac Surg, 2021, 16(1): 304. DOI: 10.1186/s13019-021-01695-5.
[15]	Iizuka S, Kawase A, Oiwa H, et al. A risk scoring system for predicting visceral pleural invasion in non-small lung cancer patients[J]. Gen Thorac Cardiovasc Surg, 2019, 67(10): 876-879. DOI: 10.1007/s11748-019-01101-x.
[16]	Peng L, Deng HY, Yang Y. Lobe-specific lymph node dissection for clinical stage ⅠA non-small-cell lung cancer: what do we know?[J]. Clin Lung Cancer, 2021, 22(5): 478-479. DOI: 10.1016/j.cllc.2021.02.007.
[17]	Deng HY, Qin CL, Li G, et al. Can lobe-specific lymph node dissection be an alternative to systematic lymph node dissection in treating early-stage non-small cell lung cancer: a comprehensive systematic review and meta-analysis?[J]. J Thorac Dis, 2018, 10(5): 2857-2865. DOI: 10.21037/jtd.2018.04.137.
[18]	Ye T, Deng L, Wang S, et al. Lung adenocarcinomas manifesting as radiological part-solid nodules define a special clinical subtype[J]. J Thorac Oncol, 2019, 14(4): 617-627. DOI: 10.1016/j.jtho.2018.12.030. pmid: 30659988

一般临床资料	训练集（n=183）	验证集（n=61）	t/χ²值	P值
年龄（岁）	66.31±5.24	65.78±6.19	0.65	0.514
性别
男	85（46.45）	27（44.26）	0.09	0.767
女	98（53.55）	34（55.74）	0.09	0.767
病理类型
腺癌	92（50.27）	31（50.82）
鳞状细胞癌	87（47.54）	28（45.90）	0.50	0.805
肉瘤样癌	4（2.19）	2（3.28）

转移区域	淋巴结		淋巴结转移率（%）
转移区域	总数	转移数	淋巴结转移率（%）
第2组	303	19	6.27
第3组	105	13	12.38
第4组	459	24	5.23
第5组	101	15	14.85
第6组	55	3	5.45
第7组	501	44	8.78
第8组	21	1	4.76
第9组	88	6	6.82
第10组	282	44	15.60
第11组	430	98	22.79
第12~13组	400	61	15.25

临床资料	淋巴结转移患者（n=55）	淋巴结未转移患者（n=128）	χ²值	P值
年龄（岁）
<65	34	96	3.25	0.071
≥65	21	32	3.25	0.071
性别
男	33	52	5.81	0.016
女	22	76	5.81	0.016
吸烟
是	34	88	0.83	0.362
否	21	40	0.83	0.362
病理类型
腺癌	21	71
鳞状细胞癌	32	55	5.14	0.056
肉瘤样癌	2	2
脉管瘤栓
是	5	2	4.06	0.044
否	50	126	4.06	0.044
肿瘤最大径（cm）
<1	1	32
1~2	23	63	22.20	<0.001
>2	31	33
CT影像特征
单纯肺部磨玻璃结节	0	57
混合性结节	24	49	45.16	<0.001
实性结节	31	22
肿瘤位置1
左肺	22	40	1.32	0.252
右肺	33	88	1.32	0.252
肿瘤位置2
上叶	28	73
中叶	4	13	1.48	0.476
下叶	23	42
分化程度
低	44	45
中	11	54	33.70	<0.001
高	0	29
肿瘤分型
中央型	34	18	43.13	<0.001
周围型	21	110	43.13	<0.001
血清CEA（ng/L）
<3.5	29	108	20.48	<0.001
≥3.5	26	20	20.48	<0.001
胸膜受侵
是	22	25	8.44	0.004
否	33	103	8.44	0.004
淋巴结清扫方式
SML	30	63	0.44	0.509
LSND	25	65	0.44	0.509

变量	β值	SE值	Wald χ²值	OR值	95%CI	P值
性别	-0.48	0.29	2.66	0.62	0.12~1.07	0.124
脉管瘤栓	-1.35	0.77	3.12	0.26	0.05~1.15	0.078
肿瘤最大径（cm）
1~2	0.64	0.72	0.79	1.90	0.62~13.86	0.409
>2	1.00	0.21	22.76	2.71	1.82~4.09	<0.001
CT影像特征
混合性结节	-1.50	0.76	3.87	0.22	0.97~4.15	0.064
实性结节	0.91	0.28	10.66	2.49	1.59~6.99	0.001
分化程度
中	1.02	1.92	0.28	2.77	0.28~26.69	0.513
低	0.72	0.28	6.55	2.06	1.11~3.81	0.010
肿瘤分型	0.02	0.02	1.25	1.02	0.97~1.03	0.367
血清CEA	0.63	0.26	5.98	1.87	1.42~2.58	0.015
胸膜受侵	0.60	0.26	5.46	1.81	1.07~3.07	0.021

临床资料	SML组（n=93）	LSND组（n=90）	χ²值	P值	临床资料	SML组（n=93）	LSND组（n=90）	χ²值	P值
年龄（岁）					肿瘤位置1
<65	70	60	1.65	0.200	左肺	31	31	0.03	0.874
≥65	23	30	1.65	0.200	右肺	62	59	0.03	0.874
性别					肿瘤位置2
男	49	36	2.96	0.085	上叶	50	51
女	44	54	2.96	0.085	中叶	7	10	1.24	0.537
吸烟					下叶	36	29
是	64	58	0.39	0.530	分化程度
否	29	32	0.39	0.530	低	47	42
病理类型					中	35	30	2.31	0.316
腺癌	40	52			高	11	18
鳞状细胞癌	51	36	4.21	0.123	肿瘤分型
肉瘤样癌	2	2			中央型	28	24	0.27	0.606
脉管瘤栓					周围型	65	66	0.27	0.606
是	4	3	0.12	0.733	血清CEA（ng/L）
否	89	87	0.12	0.733	<3.5	72	65	0.66	0.418
肿瘤最大径（cm）					≥3.5	21	25	0.66	0.418
<1	16	17			胸膜受侵
1~2	46	40	0.46	0.794	是	20	27	1.73	0.189
>2	31	33			否	73	63	1.73	0.189
CT影像特征					淋巴结转移
单纯肺部磨玻璃结节	32	25			是	30	25	0.44	0.509
混合性结节	37	36	1.30	0.523	否	63	65	0.44	0.509
实性结节	24	29