Prognostic potential of liquid biopsy tracking in the posttreatment surveillance of patients with nonmetastatic nasopharyngeal carcinoma

Abstract

BACKGROUND:The current study was performed to investigate whether circulating cell-free Epstein-Barr virus DNA (cfEBV DNA) would be useful for posttreatment surveillance in patients with nasopharyngeal carcinoma (NPC). METHODS: The authors identified a total of 1984 nondisseminated NPC patients from an institutional big-data research platform. Blood samples were collected within 3 months of the completion of radiotherapy and every 3 to 12 months thereafter for cfEBV DNA analysis. Patients were followed until disease recurrence was detected or for a median of 60 months. Diagnostic performance was assessed by calculating the sensitivity, specificity, and accuracy based on the clinical detection of disease recurrence by conventional surveillance modalities (imaging scans and pathological examination). RESULTS: During follow-up, a total of 767 patients (38.7%) had detectable cfEBV DNA. The recurrence rate among these patients was 63.8% (489 of 767 patients), which was significantly higher than that in patients with undetectable cfEBV DNA (8.6%; 105 of 1217 patients). cfEBV DNA sensitivity, specificity, and accuracy were 68.8%, 80.0%, and 78.2%, respectively, for local recurrence; 80.2%, 80.0%, and 85.9%, respectively, for regional recurrence; and 91.1%, 80.0%, and 92.8%, respectively, for distant metastasis. cfEBV DNA was found to have higher sensitivity for the detection of extrapulmonary metastases (94.9%-96.5%) compared with pulmonary metastases (78.4%). It is interesting to note that among the patients with disease recurrence with detectable cfEBV DNA, positive cfEBV DNA results preceded radiological and/or clinical evidence of disease recurrence by a median of 2.3 months (interquartile range, 0.1-9.5 months). In addition, of the 278 cfEBV DNA-positive patients who did not develop disease recurrence, 227 (81.7%) had transiently positive cfEBV DNA that fell to undetectable levels during long-term monitoring. CONCLUSIONS: Plasma cfEBV DNA in patients with NPC appears to be an early sign of tumor recurrence, especially extrapulmonary metastases.

Long-Term Monitoring of Dynamic Changes in Plasma EBV DNA For Improved Prognosis Prediction of Nasopharyngeal Carcinoma

“…The patients of Pattern 5 had the worst prognosis on progression, metastasis, recurrence and mortality, and the patients of Pattern 1 had the best prognosis. This conclusion was similar to other studies [30,31]. As to pattern 2 and pattern 3, the patients of pattern 2 had a better prognosis than those of pattern 3, consistent with Qu's meta-analysis that post-treatment EBV DNA level had greater impact than pretreatment EBV DNA on clinical outcomes of NPC [19].…”

“…In daily clinical practice, it is very important to early detect locoregional tumor recurrence post-treatment, because timely salvage treatment could improve survival outcome of these patients [32]. Chen's ndings showed that positive cell free EBV DNA results preceded radiological and/or clinical evidence of disease recurrence by a median of 2.3 months [31]. These ndings con rmed that plasma EBV DNA was a signi cant sensitive and non-invasive predictor of tumor recurrence.…”

Long‐term monitoring of dynamic changes in plasma EBV DNA for improved prognosis prediction of nasopharyngeal carcinoma

“…This conclusion was similar to other studies. 34,35 As to pattern 2 and pattern 3, the patients of pattern 2 had a better prognosis than those of pattern 3, consistent with Qu's meta-analysis that posttreatment EBV DNA level had greater impact than pretreatment EBV DNA on clinical outcomes of NPC. 19 Moreover, the patients of pattern 4 had a worse prognosis than those of pattern 2 and 3, the possible explanation was that these patients had a higher baseline and residual tumor load.…”

“…36 Chen's findings showed that positive cell free EBV DNA results preceded radiological and/or clinical evidence of disease recurrence by a median of 2.3 months. 35 These findings confirmed that plasma EBV DNA was a significant sensitive and noninvasive predictor of tumor recurrence. Based on our results, we suggested a long-term follow-up program according to dynamic changes in plasma EBV DNA.…”

Prognostication of Half-Life Clearance of Plasma EBV DNA in Previously Untreated Non-metastatic Nasopharyngeal Carcinoma Treated With Radical Intensity-Modulated Radiation Therapy

“…Recent emphasis has also focused on posttreatment EBV DNA as prognosticators (6,10,11,15,19,20,(26)(27)(28). Chen et al, in their recent study, further demonstrated the role of plasma EBV DNA in the detection of early disease recurrence among patients with NPC after treatment (29). Leung et al showed that detectable plasma EBV DNA titers at completion of 4 weeks of concurrent chemoradiation or radiation (mid-EBV DNA) was prognostic of a worse PFS and OS (9).…”