Plasma Epstein-Barr Virus-Deoxyribonucleic Acid Copy Number Predicts Disease Progression in Stage I–III Pulmonary Lymphoepithelioma-Like Carcinoma

Abstract

Purpose: To investigate the predictive values of plasma Epstein-Barr Virus (EBV)-deoxyribonucleic acid (DNA) copy number on disease progression and survival in stage I-III pulmonary lymphoepithelioma-like carcinoma (LELC). Patients and Methods: Patients with pathologically confirmed, initially diagnosed or locally recurrent stage I-III pulmonary LELC, who received locally radical treatment and had plasma EBV-DNA results, were retrospectively reviewed. Risk factors of progression-free survival (PFS) and overall survival (OS) were assessed, including the predictive value of pre-and post-treatment EBV-DNA levels. The EBV-DNA change during follow-up was analyzed to determine its association with tumor progression and survival. Results: A total of 102 patients were included in analysis. Eighty-eight patients had initially-diagnosed and 14 had locally recurrent disease. There were 33 patients treated with radical surgery, 55 with definite radiotherapy and 14 with both. EBV-DNA was tested pre-treatment (N = 66), post-treatment (N = 93) and/or during follow-up (N = 58). Forty-one patients had complete EBV-DNA results of all three time points. The overall 2-year PFS and OS were 66.3 and 96.0%, respectively. Pre-treatment EBV-DNA copy number > 10,000 copies/mL was a risk factor of PFS (2-year PFS, > 10,000 vs. ≤ 10,000 copies/mL, 37.2 vs. 75.1%, p = 0.007). Positive post-treatment EBV-DNA also indicated a worse PFS in univariable (2-year PFS, > 0 vs. 0 copy/mL, 25.6 vs. 76.8%, p < 0.001) and multivariable analysis (HR = 3.44, 95% CI, 1.52-7.78; p = 0.003). In the follow-up set, an increasing EBV-DNA exceeding 1,000 copies/mL strongly predicted disease progression within 3 months, with a specificity of 97.5% (95% CI: 86.8-99.6%) and was associated with impaired OS (2-year OS, > 1,000 vs. ≤ 1,000 copies/mL, 72.9 vs. 100%, p < 0.001). Li et al. EBV-DNA as a Predicting Biomarker Conclusions: Regular testing of EBV-DNA is suggested for pulmonary LELC to predict disease progression. If EBV-DNA copy number was increasing and beyond 1,000 copies/mL during follow-up, intensive radiologic evaluations are recommended.

Clinical outcomes of non‐nasopharyngeal lymphoepithelial carcinoma treated with a combined modality approach: A single‐institution study

“…A related report of EBV‐DNA in LEC outside the nasopharynx is additionally documented in the literature. Li and co‐workers confirmed that increased plasma EBV‐DNA >1000 copies/ml is strongly predictive of pulmonary LEC progression within 3 months, with a specificity of 97.5% (95% CI: 86.8%–99.6%), and associated with impaired OS (2‐year OS, >1000 and ≤ 1000 copies/ml, 72.9% and 100%, p < 0.001) 34 . In the present study, we further investigated the prognostic value of plasma EBV‐DNA load in NNPLEC.…”

“…Li and co-workers confirmed that increased plasma EBV-DNA >1000 copies/ml is strongly predictive of pulmonary LEC progression within 3 months, with a specificity of 97.5% (95% CI: 86.8%-99.6%), and associated with impaired OS (2-year OS, >1000 and ≤ 1000 copies/ml, 72.9% and 100%, p < 0.001). 34 In the present study, we further investigated the prognostic value of plasma EBV-DNA load in NNPLEC. Notably, OS and PFS were significantly lower among patients with pretreatment plasma EBV-DNA loads of ≥2280 copies/ml relative to those with loads of <2280 copies/ml.…”

Prognostic significance of circulating Epstein‐Barr virus DNA in pulmonary lymphoepithelioma‐like carcinoma: A meta‐analysis and validation study

“…These seven studies (two prospective and five retrospective studies, published between 2004 and 2021) involved 795 patients 13,14,20,24–27 . The sample types used in these studies were plasma in four studies and serum in the other three studies.…”

“…In addition, the cut‐off value of EBV DNA used in this study was 236 copies/ml, which was much lower than that in other studies, and different cut‐off values had varied effects on the results. Furthermore, Li et al 20 demonstrated that pretreatment EBV DNA > 10 000 copies/ml or positive posttreatment EBV DNA predicted poor PFS but had no significant correlation with OS. This phenomenon could be attributed to the fact that only patients diagnosed with localized disease and who received radical treatments were included in the study.…”

“…A prospective study established a strong correlation between a high baseline EBV DNA copy number and disease progression of pulmonary LELC 14 . In addition, some studies have shown that pretreatment EBV DNA over 10 000 copies/ml or positive posttreatment EBV DNA strongly predicts disease progression in pulmonary LELC patients 20 …”