113 Longitudinal assessment of plasma EBV-DNA in non-endemic EBV-related nasopharyngeal cancers (NPC)

• Published in: Radiotherapy and oncology Vol. 192; pp. S26 - S27
• Main Authors: Alfieri, Salvatore, Marceglia, Sara, Sciortino, Carolina, Bravo, Walter Ferrari, Piscitelli, Maria Luigia, Zucchini, Monica, Nuzzolese, Imperia, Romanò, Rebecca, Cavalieri, Stefano, Bergamini, Cristiana, Colombo, Elena, Carlo, Resteghini, Ottini, Arianna, Calareso, Giuseppina, Quattrone, Pasquale, Loris, De Cecco, Orlandi, Ester, Franceschini, Marzia, Iacovelli, Nicola Alessandro, Deganello, Alberto, Bossi, Paolo, Locati, Laura Deborah, Arienti, Flavio, Taverna, Francesca, Licitra, Lisa Francesca
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.03.2024
• Subjects: Biomarker; EBV-DNA; Nasopharyngeal carcinoma; Nasopharyngeal carcinoma; HPV or EBV related cancers; Biomarker; EBV-DNA
• ISSN: 0167-8140; 1879-0887
• DOI: 10.1016/S0167-8140(24)00438-9

Plasma Epstein Barr virus (EBV)-DNA is employed as a biomarker for EBER (EBV-encoded RNA) positive nasopharyngeal cancer (NPC) patients. In Europe, the use of plasma EBV-DNA is limited by the lack of harmonization among different European Conformity (CE)-marked EBV-DNA detection methods and BamHI-W, the latter being the gold standard assay in endemic areas. Our Institution demonstrated that three CE-marked (i.e., ELITech, Abbott, Artus) and BamHI-W assays significantly agreed in plasma EBV-DNA quantification in non-endemic NPC (1). In this setting, the role of plasma EBV-DNA was better defined only before curative treatment, (2) with undetectable baseline plasma EBV-DNA levels holding a positive prognostic significance in terms of disease-free survival (DFS) and overall survival (OS) (2). However, the value of CE-marked assays in Longitudinal assessment of plasma EBV-DNA (LEA) -alongside the curative management and follow-up of non-endemic NPC - is still lacking (1; 2). Herein, we present the results of the LEA study (Ethics Comittee n. 150/23) concerning the dynamics of plasma EBD-DNA viral load in a single-Institution cohort of non-endemic NPC patients. From 2012 to 2023 we retrospectively collected data of all EBER-positive NPC patients treated with curative intent at our Institution. All subjects underwent plasma EBV-DNA quantification at the following time-points: 1) pre-treatment (within 1 month since treatment start); 2) post-treatment (2A, early post-treatment, within 6 weeks after treatment completion and/or 2B, late post-treatment, within 16 weeks after treatment end); 3) follow-up phase. EBV-DNA results were classified as negative (if EBV-DNA was not detected) or positive (if EBV-DNA was detected and quantifiable or detected but not quantifiable) and were expressed as log IU/ml. Descriptive statistics were performed on all available data. The role of pre-treatment EBV-DNA as predictive factor for disease recurrence was assessed by estimating the Receiver Operating Characteristic (ROC) curve at different cut-offs. The predictive value of post-treatment (2A, 2B) EBV-DNA load was assessed considering its ability to forecast recurrence. For patients with both 2A and 2B available samples, the 2B value was considered for post-treatment analyses. At the data cut-off (Aug, 07th, 2023), 169 EBV-related NPC patients were identified. Median age at diagnosis was 50 years (range: 22-75). Most of them were male (72%) and staged as III/IV (84%) according to AJCC classification (VIII Ed.). Only two patients presented oligo-metastatic disease at distant sites, and they were not included in the final analyses on the predictive value of EBV-DNA. At a median follow-up of 66 months (range: 9-134), 41 patients (24.2%) recurred and 139 (82.2%) were still alive. Out of 167 evaluable patients, median viral load of pre-treatment plasma EBV-DNA was of 2.59 log IU/ml (range: 1.59-5.11), while it was undetectable only in six (3.5%) patients who did not recur. All 41 recurrences occurred in patients with pre-treatment detectable EBV-DNA. In addition, subjects with undetectable baseline EBV-DNA had almost significantly (p=0.07) higher DFS with respect to those who showed detectable baseline values (DFS: 66 vs. 47 months, respectively). For pre-treatment plasma EBV-DNA, the best cut-off in terms of disease recurrence prediction was not identified within total population (area under curve, AUC: 0.56) and in early (at 1-y) recurrent patients (n=20) (AUC: 0.58). Regarding the predictive value of post-treatment EBV-DNA measurement (2A, 2B; within 16 weeks), its accuracy, sensitivity, specificity were 78%, 61%, and 80%, respectively, with regards to recurrence detection at any time-point during the follow-up. Moreover, its negative predictive value (NPV) was 94%, which resulted stable across the first three years of follow-up (93% at 1st-y, 95% at 2nd-y, 95% at 3rd-y). On the other hand, its overall positive predictive value (PPV) was 27%, which progressively decreased during follow-up (40% at 1st-y, 34% at 2nd-y, 30% at 3rd-y). To our knowledge, this is the largest longitudinal evaluation of plasma EBV-DNA quantification in non-endemic EBV-related NPC patients. Undetectable pre-treatment plasma EBV-DNA confirmed its positive prognostic role. NPV of post-treatment (within 16 weeks since curative therapy end) plasma EBV-DNA was 94%, remaining stable during follow-up time (first 3 years) whereas its sensitivity and PPV were lower - 61% and 27%, respectively. The LEA study provides additional data on the significance of plasma EBV-DNA in non-endemic curable NPC, which can also guide clinicians towards a standardization of the timing of plasma EBV-DNA assessment in this setting.