Risk factors and the predictive model for occult lymph node metastasis in cT1N0M0 stage squamous cell lung cancer_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

JIAO Zhenhua ,  YU Jun

Department of Thoracic Surgery, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, 430030, P. R. China;

Corresponding author：

YU Jun, Email: 270384568@qq.com

Keywords：

Squamous cell lung cancer; lymph node metastasis; risk factors; logistic model

DOI：

10.7507/1007-4848.202404028

Video：

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Objective To investigate the risk factors for lymph node metastasis in cT1N0M0 stage squamous cell lung cancer and develop a logistic regression model to predict lymph node metastasis. Methods A retrospective study was conducted on patients with cT1N0M0 stage lung squamous cell carcinoma in our department from August 2017 to October 2022. The correlation between basic clinical data, imaging data, and pathological data and lymph node metastasis was analyzed. Univariate and multivariate logistic regression analyses were employed for risk factor analysis. Receiver operating characteristic curves and the Hosmer-Lemeshow test were utilized to evaluate the model’s discrimination and calibration. The Bootstrap method with 1 000 resamples was employed for internal validation of the model. Results Tumor location of central-type, tumor differentiation, cytokeratin 19 fragment (CYFRA21-1) levels, and tumor size were independent risk factors for lymph node metastasis in cT1N0M0 stage squamous cell lung cancer. The optimal cutoff values for tumor size and CYFRA21-1 levels were determined to be 2.05 cm and 4.20 ng/mL, respectively. The combination of tumor location, CYFRA21-1 levels, and tumor size demonstrates superior predictive capability compared to any individual factor. Conclusion Tumor location of central-type, poorly differentiated tumors, CYFRA21-1 levels, and tumor size are risk factors for lymph node metastasis in cT1N0M0 stage lung squamous cell carcinoma. The combined predictive model has certain guiding significance for intraoperative lymph node resection strategies in cT1N0M0 stage lung squamous cell carcinoma.

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17.	Cao J, Xu J, He Z, et al. Prognostic impact of lymphadenectomy on outcomes of sublobar resection for stage ⅠA non-small cell lung cancer≤2 cm. J Thorac Cardiovasc Surg, 2018, 156(2): 796-805.
18.	Handa Y, Tsutani Y, Mimae T, et al. Appropriate extent of lymphadenectomy in segmentectomy: A multicenter study. Jpn J Clin Oncol, 2021, 51(3): 451-458.
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24.	Thai AA, Solomon BJ, Sequist LV, et al. Lung cancer. Lancet, 2021, 398(10299): 535-554.
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26.	Tsutani Y, Murakami S, Miyata Y, et al. Prediction of lymph node status in clinical stage ⅠA squamous cell carcinoma of the lung. Eur J Cardiothorac Surg, 2015, 47(6): 1022-1026.
27.	Huang L, Li W, Zhao L, et al. Risk factors of lymph node metastasis in lung squamous cell carcinoma of 3 cm or less in diameter. Medicine (Baltimore), 2017, 96(29): e7563.
28.	Fan J, Yao J, Si H, et al. Frozen sections accurately predict the IASLC proposed grading system and prognosis in patients with invasive lung adenocarcinomas. Lung Cancer, 2023 Apr: 178: 123-130.178-123.
29.	Xu L, Su H, Hou L, et al. The IASLC proposed grading system accurately predicts prognosis and mediastinal nodal metastasis in patients with clinical stage Ⅰ lung adenocarcinoma. Am J Surg Pathol, 2022, 46(12): 1633-1641.
30.	李淼, 王长利. 中央型和周围型肺鳞癌患者淋巴结转移的影响因素分析. 天津医药, 2018, 46(6): 635-639.
31.	Dezube AR, Mazzola E, Deeb A, et al. Mandatory nodal evaluation during resection of clinical T1a non-small cell lung cancers. Ann Thorac Surg, 2022, 113(5): 1583-1590.
32.	Wang K, Xue M, Qiu J, et al. Genomics analysis and nomogram risk prediction of occult lymph node metastasis in non-predominant micropapillary component of lung adenocarcinoma measuring ≤ 3 cm. Front Oncol, 2022, 12: 945997.

1. Xia C, Dong X, Li H, et al. Cancer statistics in China and United States, 2022: Profiles, trends, and determinants. Chin Med J (Engl), 2022, 135(5): 584-590.
2. de Koning HJ, van der Aalst CM, de Jong PA, et al. Reduced lung-cancer mortality with volume CT screening in a randomized trial. N Engl J Med, 2020, 382(6): 503-513.
3. Walter JE, Heuvelmans MA, de Jong PA, et al. Occurrence and lung cancer probability of new solid nodules at incidence screening with low-dose CT: Analysis of data from the randomised, controlled NELSON trial. Lancet Oncol, 2016, 17(7): 907-916.
4. Howington JA, Blum MG, Chang AC, et al. Treatment of stage Ⅰ and Ⅱ non-small cell lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest, 2013, 143(5 Suppl): e278S-e313S.
5. Kuroda H, Sakata S, Takahashi Y, et al. Subsegmental resection preserves regional pulmonary function: A focus on thoracoscopy. Thorac Cancer, 2021, 12(7): 1033-1040.
6. Iwata H, Shirahashi K, Mizuno Y, et al. Feasibility of segmental resection in non-small-cell lung cancer with ground-glass opacity. Eur J Cardiothorac Surg, 2014, 46(3): 375-379.
7. Qu X, Wang K, Zhang T, et al. Long-term outcomes of stageⅠ NSCLC (≤3 cm) patients following segmentectomy are equivalent to lobectomy under analogous extent of lymph node removal: A PSM based analysis. J Thorac Dis, 2017, 9(11): 4561-4573.
8. Altorki NK, Yip R, Hanaoka T, et al. Sublobar resection is equivalent to lobectomy for clinical stage 1A lung cancer in solid nodules. J Thorac Cardiovasc Surg, 2014, 147(2): 754-762.
9. Saji H, Okada M, Tsuboi M, et al. Segmentectomy versus lobectomy in small-sized peripheral non-small-cell lung cancer (JCOG0802/WJOG4607L): A multicentre, open-label, phase 3, randomised, controlled, non-inferiority trial. Lancet, 2022, 399(10335): 1607-1617.
10. Mattioli S, Ruffato A, Puma F, et al. Does anatomical segmentectomy allow an adequate lymph node staging for cT1a non-small cell lung cancer? J Thorac Oncol, 2011, 6(9): 1537-1541.
11. Ma W, Zhang ZJ, Li Y, et al. Comparison of lobe-specific mediastinal lymphadenectomy versus systematic mediastinal lymphadenectomy for clinical stage T₁aN₀M₀ non-small cell lung cancer. J Cancer Res Ther, 2013, 9 Suppl 2: S101-5.9-2.
12. Ishiguro F, Matsuo K, Fukui T, et al. Effect of selective lymph node dissection based on patterns of lobe-specific lymph node metastases on patient outcome in patients with resectable non-small cell lung cancer: A large-scale retrospective cohort study applying a propensity score. J Thorac Cardiovasc Surg, 2010, 139(4): 1001-1006.
13. Chida M, Minowa M, Karube Y, et al. Worsened long-term outcomes and postoperative complications in octogenarians with lung cancer following mediastinal lymph-node dissection. Interact Cardiovasc Thorac Surg, 2009, 8(1): 89-92.
14. Allen MS, Darling GE, Pechet TT, et al. Morbidity and mortality of major pulmonary resections in patients with early-stage lung cancer: initial results of the randomized, prospective ACOSOG Z0030 trial. Ann Thorac Surg, 2006, 81(3): 1013-1019.
15. Rahim MK, Okholm TLH, Jones KB, et al. Dynamic CD8+ T cell responses to cancer immunotherapy in human regional lymph nodes are disrupted in metastatic lymph nodes. Cell, 2023, 186(6): 1127-1143.
16. Cerfolio RJ, Bryant AS, Minnich DJ. Complete thoracic mediastinal lymphadenectomy leads to a higher rate of pathologically proven N2 disease in patients with non-small cell lung cancer. Ann Thorac Surg, 2012, 94(3): 902-906.
17. Cao J, Xu J, He Z, et al. Prognostic impact of lymphadenectomy on outcomes of sublobar resection for stage ⅠA non-small cell lung cancer≤2 cm. J Thorac Cardiovasc Surg, 2018, 156(2): 796-805.
18. Handa Y, Tsutani Y, Mimae T, et al. Appropriate extent of lymphadenectomy in segmentectomy: A multicenter study. Jpn J Clin Oncol, 2021, 51(3): 451-458.
19. Wang X, Cao L, Li S, et al. Combination of PD-L1 expression and NLR as prognostic marker in patients with surgically resected non-small cell lung cancer. J Cancer, 2019, 10(26): 6703-6710.
20. Wei B, Jin X, Lu G, et al. A novel nomogram to predict lymph node metastasis in cT1 non-small-cell lung cancer based on PET/CT and peripheral blood cell parameters. BMC Pulm Med, 2023, 23(1): 44.
21. Mandaliya H, Jones M, Oldmeadow C, et al. Prognostic biomarkers in stageⅣ non-small cell lung cancer (NSCLC): Neutrophil to lymphocyte ratio (NLR), lymphocyte to monocyte ratio (LMR), platelet to lymphocyte ratio (PLR) and advanced lung cancer inflammation index (ALI). Transl Lung Cancer Res, 2019, 8(6): 886-894.
22. Song B, Shi P, Xiao J, et al. Utility of red cell distribution width as a diagnostic and prognostic marker in non-small cell lung cancer. Sci Rep, 2020, 10(1): 15717.
23. Chen JL, Wu JN, Lv XD, et al. The value of red blood cell distribution width, neutrophil-to-lymphocyte ratio, and hemoglobin-to-red blood cell distribution width ratio in the progression of non-small cell lung cancer. PLoS One, 2020, 15(8): e0237947.
24. Thai AA, Solomon BJ, Sequist LV, et al. Lung cancer. Lancet, 2021, 398(10299): 535-554.
25. Travis WD, Brambilla E, Nicholson AG, et al. The 2015 World Health Organization classification of lung tumors: Impact of genetic, clinical and radiologic advances since the 2004 classification. J Thorac Oncol, 2015, 10(9): 1243-1260.
26. Tsutani Y, Murakami S, Miyata Y, et al. Prediction of lymph node status in clinical stage ⅠA squamous cell carcinoma of the lung. Eur J Cardiothorac Surg, 2015, 47(6): 1022-1026.
27. Huang L, Li W, Zhao L, et al. Risk factors of lymph node metastasis in lung squamous cell carcinoma of 3 cm or less in diameter. Medicine (Baltimore), 2017, 96(29): e7563.
28. Fan J, Yao J, Si H, et al. Frozen sections accurately predict the IASLC proposed grading system and prognosis in patients with invasive lung adenocarcinomas. Lung Cancer, 2023 Apr: 178: 123-130.178-123.
29. Xu L, Su H, Hou L, et al. The IASLC proposed grading system accurately predicts prognosis and mediastinal nodal metastasis in patients with clinical stage Ⅰ lung adenocarcinoma. Am J Surg Pathol, 2022, 46(12): 1633-1641.
30. 李淼, 王长利. 中央型和周围型肺鳞癌患者淋巴结转移的影响因素分析. 天津医药, 2018, 46(6): 635-639.
31. Dezube AR, Mazzola E, Deeb A, et al. Mandatory nodal evaluation during resection of clinical T1a non-small cell lung cancers. Ann Thorac Surg, 2022, 113(5): 1583-1590.
32. Wang K, Xue M, Qiu J, et al. Genomics analysis and nomogram risk prediction of occult lymph node metastasis in non-predominant micropapillary component of lung adenocarcinoma measuring ≤ 3 cm. Front Oncol, 2022, 12: 945997.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Latest ArticlesRisk factors and the predictive model for occult lymph node metastasis in cT1N0M0 stage squamous cell lung cancer

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