Clinical significance of baseline Epstein–Barr virus DNA for recurrent or metastatic primary pulmonary lymphoepithelioma-like carcinoma
Abstract
Background: This study aimed to evaluate the clinical significance of baseline Epstein–Barr virus (EBV) DNA in recurrent or metastatic primary pulmonary lymphoepithelioma-like carcinoma (PLELC). Methods: 75 patients with baseline EBV DNA were included. The relationships between baseline EBV DNA and clinical characteristics, survival and objective response rate were analyzed. Results: The baseline EBV DNA levels were related to the liver, chest wall, distant lymph node(s) or multiple sites of distant metastasis. The high baseline EBV DNA group (≥41,900 copies/ml) was related to shorter progression-free and overall survival in univariate analysis and remained significant for progression-free survival in multivariate analysis. Conclusion: The baseline EBV DNA is a valuable biomarker for predicting prognosis and reflecting tumor burden in recurrent or metastatic PLELC.
Tweetable abstract
In this study, the baseline plasma EBV DNA level was related to tumor burden, and it was an independent prognostic indicator for PFS in recurrent or metastatic primary pulmonary lymphoepithelioma-like carcinoma.
Papers of special note have been highlighted as: • of interest; •• of considerable interest
References
- 1. . Epstein-Barr virus related lymphoepithelioma-like carcinoma of lung. J. Surg. Oncol. 36(4), 280–283 (1987). • First study reported the relationship primary pulmonary lymphoepithelioma-like carcinoma and Epstein–Barr virus (EBV).
- 2. Capecitabine as salvage treatment for lymphoepithelioma-like carcinoma of lung. J. Thorac. Oncol. 4(9), 1174–1177 (2009).
- 3. Primary pulmonary lymphoepithelioma-like carcinoma: fifty-two patients with long-term follow-up. Cancer 118(19), 4748–4758 (2012). • A long-term follow-up for primary pulmonary lymphoepithelioma-like carcinoma.
- 4. Relationship between Epstein–Barr virus and lymphoepithelioma-like carcinoma of the lung: a clinicopathologic study of 6 cases and review of the literature. Hum. Pathol. 32(8), 863–872 (2001).
- 5. . Lymphoepithelioma-like carcinoma of the lung. Respirology 11(5), 539–545 (2006).
- 6. . Pathology and Genetics: Tumours of the Lung, Pleura, Thymus and Heart. IARC, Lyon, France (2004).
- 7. The 2015 World Health Organization Classification of Lung Tumors: impact of genetic, clinical and radiologic advances since the 2004 classification. J. Thorac. Oncol. 10(9), 1243–1260 (2015).
- 8. The 2021 WHO Classification of Lung Tumors: Impact of advances since 2015. J. Thorac. Oncol. 17(3), 362–387 (2022).
- 9. Multimodality treatment and long-term follow-up of the primary pulmonary lymphoepithelioma-like carcinoma. Clin. Lung Cancer 13(5), 359–362 (2012).
- 10. . Response of advanced stage recurrent lymphoepithelioma-like carcinoma to nivolumab. Immunotherapy 9(12), 955–961 (2017).
- 11. Clinical features and prognosis of pulmonary lymphoepithelioma-like carcinoma: summary of eighty-five cases. Clin. Lung Cancer 20(3), e329–e337 (2019).
- 12. The clinicopathological features and prognosis of primary pulmonary lymphoepithelioma-like carcinoma: a systematic review and meta-analysis. PLOS ONE 15(10), e0240729 (2020).
- 13. Pulmonary lymphoepithelioma-like carcinoma: a Surveillance, Epidemiology, and End Results database analysis. J. Thorac. Dis. 7(12), 2330–2338 (2015).
- 14. The genomic landscape of Epstein–Barr virus-associated pulmonary lymphoepithelioma-like carcinoma. Nat. Commun. 10(1), 3108 (2019). • Original article providing a comprehensive genomic landscape of primary pulmonary lymphoepithelioma-like carcinoma.
- 15. Molecular characteristics of primary pulmonary lymphoepithelioma-like carcinoma based on integrated genomic analyses. Signal Transduct. Target Ther. 6(1), 6 (2021).
- 16. Quantification of plasma Epstein–Barr virus DNA in patients with advanced nasopharyngeal carcinoma. N. Engl. J. Med. 350(24), 2461–2470 (2004).
- 17. The prognostic value of plasma Epstein–Barr viral DNA and tumor response to neoadjuvant chemotherapy in advanced-stage nasopharyngeal carcinoma. Int. J. Radiat. Oncol. Biol. Phys. 93(4), 862–869 (2015).
- 18. Circulating Epstein–Barr virus DNA in serum of patients with lymphoepithelioma-like carcinoma of the lung: a potential surrogate marker for monitoring disease. Clin. Cancer Res. 8(4), 986–994 (2002). • First study reported the clinical value of EBV DNA for primary pulmonary lymphoepithelioma-like carcinoma.
- 19. Clinical significance of plasma Epstein–Barr virus DNA in pulmonary lymphoepithelioma-like carcinoma (LELC) patients. J. Thorac. Oncol. 13(2), 218–227 (2018). •• The prospective study about the clinical significance of baseline EBV DNA level for patients with stage I to IV primary pulmonary lymphoepithelioma-like carcinoma.
- 20. Plasma Epstein–Barr virus-deoxyribonucleic acid copy number predicts disease progression in stage I–III pulmonary lymphoepithelioma-like carcinoma. Front Oncol. 10, 1487 (2020).
- 21. Prognostic significance of circulating Epstein–Barr virus DNA in pulmonary lymphoepithelioma-like carcinoma: a meta-analysis and validation study. J. Med. Virol. 95(1), e28349 (2023).
- 22. Efficacy and safety of gemcitabine and capecitabine combination for patients with previously treated advanced primary pulmonary lymphoepithelioma-like carcinoma: a retrospective single-arm cohort study. Transl. Lung Cancer Res. 12(1), 96–108 (2023).
- 23. 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. Thorac. Oncol. 11(1), 39–51 (2016).
- 24. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur. J. Cancer 45(2), 228–247 (2009).
- 25. Comparison of plasma Epstein–Barr virus (EBV) DNA levels and serum EBV immunoglobulin A/virus capsid antigen antibody titers in patients with nasopharyngeal carcinoma. Cancer 100(6), 1162–1170 (2004).
- 26. Association of unrecognized obstructive sleep apnea with postoperative cardiovascular events in patients undergoing major noncardiac surgery. JAMA 321(18), 1788–1798 (2019).
- 27. Computed tomography characteristics of primary pulmonary lymphoepithelioma-like carcinoma in 41 patients. Eur. J. Radiol. 82(8), 1343–1346 (2013).
- 28. Primary lymphoepithelioma-like carcinoma of ocular adnexa: clinicopathologic features and treatment. Curr. Oncol. 20(2), e113–e122 (2013).
- 29. Primary lymphoepithelioma-like carcinoma of salivary gland: sixty-nine cases with long-term follow-up. Head Neck. 36(9), 1305–1312 (2014).
- 30. . Clonal Epstein–Barr virus in lymphoepithelioma-like carcinoma of the lung. Am. J. Surg. Pathol. 17(7), 678–682 (1993).
- 31. Plasma Epstein–Barr virus DNA and residual disease after radiotherapy for undifferentiated nasopharyngeal carcinoma. J. Natl. Cancer Inst. 94(21), 1614–1619 (2002).
- 32. Clinical implications of plasma Epstein–Barr virus DNA in early-stage extranodal nasal-type NK/T-cell lymphoma patients receiving primary radiotherapy. Blood 120(10), 2003–2010 (2012).
- 33. Prospective observation: clinical utility of plasma Epstein–Barr virus DNA load in EBV-associated gastric carcinoma patients. Int. J. Cancer 146(1), 272–280 (2020).
- 34. Clinical utility of Epstein–Barr virus DNA and other liquid biopsy markers in nasopharyngeal carcinoma. Cancer Commun. (Lond) 40(11), 564–585 (2020).
- 35. Combination of tumor volume and Epstein–Barr virus DNA improved prognostic stratification of stage II nasopharyngeal carcinoma in the intensity modulated radiotherapy era: a large-scale cohort study. Cancer Res. Treat. 50(3), 861–871 (2018).
- 36. Clinical role of circulating Epstein–Barr virus DNA as a tumor marker in lymphoepithelioma-like carcinoma of the lung. Ann. N.Y. Acad. Sci. 1022(1), 263–270 (2004).
- 37. Metabolic tumor volume predicts overall survival in patients with primary pulmonary lymphoepithelioma-like carcinoma. Oncol. Lett. 18(6), 6143–6149 (2019).
- 38. First-line platinum-based chemotherapy and survival outcomes in locally advanced or metastatic pulmonary lymphoepithelioma-like carcinoma. Lung Cancer 137, 100–107 (2019). • The research about the prognostic values of the first-line therapeutic regimens and EBV DNA for locally advanced or metastatic pulmonary lymphoepithelioma-like carcinoma.
- 39. Comparison of immunotherapy, chemotherapy, and chemoimmunotherapy in advanced pulmonary lymphoepithelioma-like carcinoma: a retrospective study. Front Oncol. 12, 820302 (2022).
- 40. Exploration of immunotherapy in advanced pulmonary lymphoepithelioma-like carcinoma. Int. J. Cancer 152(11), 2338–2350 (2023).
- 41. PD-1 inhibition plus platinum-based chemotherapy (PBC) or PBC alone in the first-line treatment of locally advanced or metastatic pulmonary lymphoepithelioma-like carcinoma. Front Immunol. 13, 1015444 (2022).