DOI QR코드

DOI QR Code

Clinical impact of pleural fluid carcinoembryonic antigen on therapeutic strategy and efficacy in lung adenocarcinoma patients with malignant pleural effusion

  • Jaehee Lee (Department of Internal Medicine, School of Medicine, Kyungpook National University) ;
  • Deok Heon Lee (Department of Thoracic and Cardiovascular Surgery, School of Medicine, Kyungpook National University) ;
  • Ji Eun Park (Department of Internal Medicine, School of Medicine, Kyungpook National University) ;
  • Yong Hoon Lee (Department of Internal Medicine, School of Medicine, Kyungpook National University) ;
  • Sun Ha Choi (Department of Internal Medicine, School of Medicine, Kyungpook National University) ;
  • Hyewon Seo (Department of Internal Medicine, School of Medicine, Kyungpook National University) ;
  • Seung Soo Yoo (Department of Internal Medicine, School of Medicine, Kyungpook National University) ;
  • Shin Yup Lee (Department of Internal Medicine, School of Medicine, Kyungpook National University) ;
  • Seung-Ick Cha (Department of Internal Medicine, School of Medicine, Kyungpook National University) ;
  • Jae Yong Park (Department of Internal Medicine, School of Medicine, Kyungpook National University) ;
  • Chang Ho Kim (Department of Internal Medicine, School of Medicine, Kyungpook National University)
  • 투고 : 2023.07.22
  • 심사 : 2023.12.01
  • 발행 : 2024.03.01

초록

Background/Aims: Epidermal growth factor receptor (EGFR) mutation is important in determining the treatment strategy for advanced lung cancer patients with malignant pleural effusion (MPE). Contrary to serum carcinoembryonic antigen (S-CEA) levels, the associations between pleural fluid CEA (PF-CEA) levels and EGFR mutation status as well as between PF-CEA levels and treatment efficacy have rarely been investigated in lung adenocarcinoma patients with MPE. Methods: This retrospective study enrolled lung adenocarcinoma patients with MPE and available PF-CEA levels and EGFR mutation results. The patients were categorized based on PF-CEA levels: < 10 ng/mL, 10-100 ng/mL, 100-500 ng/mL, and ≥ 500 ng/mL. The association between PF-CEA levels and EGFR mutation status as well as their therapeutic impact on overall survival was compared among the four groups. Results: This study included 188 patients. PF-CEA level was found to be an independent predictor of EGFR mutation but not S-CEA level. The EGFR mutation rates were higher as the PF-CEA levels increased, regardless of cytology results or sample types. Among EGFR-mutant lung adenocarcinoma patients receiving EGFR-tyrosine kinase inhibitor (TKI) treatment, those with high PF-CEA levels had significantly better survival outcomes than those with low PF-CEA levels. Conclusion: High PF-CEA levels were associated with high EGFR mutation rate and may lead to a favorable clinical outcome of EGFR-TKI treatment in EGFR-mutant lung adenocarcinoma patients with MPE. These findings highlight the importance of actively investigating EGFR mutation detection in patients with suspected MPE and elevated PF-CEA levels despite negative cytology results.

키워드

참고문헌

  1. Asciak R, Rahman NM. Malignant pleural effusion: from diagnostics to therapeutics. Clin Chest Med 2018;39:181-193. https://doi.org/10.1016/j.ccm.2017.11.004
  2. Wang S, Chen H, Zhong J, et al. Comparative study of EGFR mutations detected in malignant pleural effusion, plasma and tumor tissue in patients with adenocarcinoma of the lung. Lung Cancer 2019;135:116-122. https://doi.org/10.1016/j.lungcan.2019.05.018
  3. Maemondo M, Inoue A, Kobayashi K, et al. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med 2010;362:2380-2388. https://doi.org/10.1056/NEJMoa0909530
  4. Mitsudomi T, Morita S, Yatabe Y, et al. Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial. Lancet Oncol 2010;11:121-128. https://doi.org/10.1016/S1470-2045(09)70364-X
  5. Liu L, Xiong X. Clinicopathologic features and molecular biomarkers as predictors of epidermal growth factor receptor gene mutation in non-small cell lung cancer patients. Curr Oncol 2021;29:77-93. https://doi.org/10.3390/curroncol29010007
  6. Gao XC, Wei CH, Zhang RG, et al. 18F-FDG PET/CT SUVmax and serum CEA levels as predictors for EGFR mutation state in Chinese patients with non-small cell lung cancer. Oncol Lett 2020;20:61.
  7. Feng LX, Wang J, Yu Z, et al. Clinical significance of serum EGFR gene mutation and serum tumor markers in predicting tyrosine kinase inhibitor efficacy in lung adenocarcinoma. Clin Transl Oncol 2019;21:1005-1013. https://doi.org/10.1007/s12094-018-02014-6
  8. Zhu WY, Li HF, Fang KX, et al. Epidermal growth factor receptor mutations and their prognostic value with carcinoembryonic antigen in pathological T1 lung adenocarcinoma. Dis Markers 2018;2018:2942618.
  9. Cai Z. Relationship between serum carcinoembryonic antigen level and epidermal growth factor receptor mutations with the influence on the prognosis of non-small-cell lung cancer patients. Onco Targets Ther 2016;9:3873-3878. https://doi.org/10.2147/OTT.S102199
  10. Zhang Y, Jin B, Shao M, et al. Monitoring of carcinoembryonic antigen levels is predictive of EGFR mutations and efficacy of EGFR-TKI in patients with lung adenocarcinoma. Tumour Biol 2014;35:4921-4928. https://doi.org/10.1007/s13277-014-1646-1
  11. Feller-Kopman D, Light R. Pleural disease. N Engl J Med 2018;378:740-751. https://doi.org/10.1056/NEJMra1403503
  12. Lv YL, Liu HB, Yuan DM, Zhou L, Jin SX, Song Y. Carcinoembryonic antigen in pleural effusion of patients with lung adenocarcinoma: a predictive marker for EGFR mutation. Transl Cancer Res 2019;8:1027-1034.
  13. Zhao W, Zhou W, Rong L, et al. Epidermal growth factor receptor mutations and brain metastases in non-small cell lung cancer. Front Oncol 2022;12:912505.
  14. Han HS, Eom DW, Kim JH, et al. EGFR mutation status in primary lung adenocarcinomas and corresponding metastatic lesions: discordance in pleural metastases. Clin Lung Cancer 2011;12:380-386. https://doi.org/10.1016/j.cllc.2011.02.006
  15. Chiang CL, Shen CI, Huang HC, Chang HJ, Huang YT, Chiu CH. Cytology-based specimen triage for epidermal growth factor receptor mutation testing of malignant pleural effusions in non-small cell lung cancer. Front Oncol 2022;12:810124.
  16. Song Z, Wang W, Li M, Liu J, Zhang Y. Cytological-negative pleural effusion can be an alternative liquid biopsy media for detection of EGFR mutation in NSCLC patients. Lung Cancer 2019;136:23-29. https://doi.org/10.1016/j.lungcan.2019.08.004
  17. Villena V, Lopez-Encuentra A, Echave-Sustaeta J, Martin-Escribano P, Ortuno-de-Solo B, Estenoz-Alfaro J. Diagnostic value of CA 549 in pleural fluid. Comparison with CEA, CA 15.3 and CA 72.4. Lung Cancer 2003;40:289-294. https://doi.org/10.1016/S0169-5002(03)00120-X
  18. Porcel JM, Vives M, Esquerda A, Salud A, Perez B, Rodriguez-Panadero F. Use of a panel of tumor markers (carcinoembryonic antigen, cancer antigen 125, carbohydrate antigen 15-3, and cytokeratin 19 fragments) in pleural fluid for the differential diagnosis of benign and malignant effusions. Chest 2004;126:1757-1763. https://doi.org/10.1378/chest.126.6.1757
  19. Han J, Li Y, Cao S, et al. The level of serum carcinoembryonic antigen is a surrogate marker for the efficacy of EGFR-TKIs but is not an indication of acquired resistance to EGFR-TKIs in NSCLC patients with EGFR mutationsm. Biomed Rep 2017;7:61-66. https://doi.org/10.3892/br.2017.914
  20. Yanwei Z, Bo J, Yuqing L, et al. Serum carcinoembryonic antigen levels predicts the efficacy of EGFR-TKI in non-small cell lung cancer harboring EGFR mutations. J Cancer Res Ther 2016;12:254-258. https://doi.org/10.4103/0973-1482.153666
  21. Okamoto T, Nakamura T, Ikeda J, et al. Serum carcinoembryonic antigen as a predictive marker for sensitivity to gefitinib in advanced non-small cell lung cancer. Eur J Cancer 2005;41:1286-1290. https://doi.org/10.1016/j.ejca.2005.03.011
  22. Passaro A, Malapelle U, Del Re M, et al. Understanding EGFR heterogeneity in lung cancer. ESMO Open 2020;5:e000919.
  23. Marusyk A, Polyak K. Tumor heterogeneity: causes and consequences. Biochim Biophys Acta 2010;1805:105-117. https://doi.org/10.1016/j.bbcan.2009.11.002