Combined pre-treatment and middle-treatment Epstein-Barr virus DNA load contributes to prognostication and treatment modification in nasopharyngeal carcinoma patients

Abstract

Objective: To investigate whether pre-treatment and middle-treatment plasma Epstein-Barr virus (EBV) DNA loads are useful predictors of prognosis and indicators of therapy modification in nasopharyngeal carcinoma (NPC) patients undergoing radical concurrent chemoradiotherapy (CCRT).

Methods: Plasma EBV DNA load was measured by quantitative polymerase chain reaction before treatment (pre-DNA) and during the second cycle of DDP (mid-DNA). The primary endpoint was 5-year progression-free survival (PFS).

Results: A total of 775 NPC patients treated with CCRT were included. In total, 553 patients with pre-DNA <4000 copies/mL and 222 with ⩾4000 copies/mL. A total of 559 patients had mid-DNA undetectable and 216 had detectable. Multivariate analysis showed that pre- and mid-DNA were independent prognostic predictors of PFS [hazard ratio (HR), 2.035; 95% confidence interval (CI), 1.406-2.944; p < 0.001; HR, 1.597; 95% CI, 1.101-2.316; p = 0.014]. The area under the curve of the combination of pre-DNA and mid-DNA for 5-year PFS was higher than that of pre-DNA, mid-DNA, and tumor node metastasis (TNM) stage (0.679 versus 0.622, 0.608, 0.601). In the low-risk group (pre-DNA <4000 copies/mL and undetectable mid-DNA), patients receiving ⩽200 mg/m² showed similar efficacy as those receiving >200 mg/m² cumulative cisplatin dose (CCD) but were associated with fewer all-grade late toxicities. However, in the high-risk group (pre-DNA ⩾4000 copies/mL or detectable mid-DNA), patients receiving >200 mg/m² CCD showed a higher 5-year PFS (73.1% versus 58.6%, p = 0.027) and locoregional relapse-free survival (88.5% versus 76.1%, p = 0.028) than those receiving ⩽200 mg/m² CCD.

Conclusion: The combination of pre-DNA and mid-DNA could be particularly useful for guiding risk stratification and early treatment modification for NPC treated with CCRT. A total of 200 mg/m² cisplatin seemed to be the optimal dose for the low-risk patients, while >200 mg/m² cisplatin may be adequate to achieve satisfactory survival outcomes in the high-risk group.

Keywords: EBV DNA; concurrent chemotherapy; cumulative cisplatin dose; nasopharyngeal carcinoma.

Figure 1.

Flowchart for patient selection. NPC, nasopharyngeal carcinoma.

Figure 2.

Kaplan–Meier for PFS, DMFS, LRRFS, and OS for all 775 patients with NPC stratified by pre-DNA (<4000 versus ⩾4000 copies/mL; a–d) and mid-DNA (undetectable versus detectable; e–h). DMFS, distant metastasis-free survival; LRRFS, locoregional relapse-free survival; NPC, nasopharyngeal carcinoma; OS, overall survival; PFS, progression-free survival.

Figure 3.

Kaplan–Meier for PFS (a), DMFS (b), LRRFS (c), and OS (d) between the high- and low-risk groups. DMFS, distant metastasis-free survival; LRRFS, locoregional relapse-free survival; OS, overall survival; PFS, progression-free survival.

Figure 4.

ROC analysis comparing the prognostic value of pre-DNA, mid-DNA, the combination of pre-DNA and mid-DNA, and TNM stage in 5-year progression (a), 5-year metastasis (b), 5-year locoregional failure (c), and 5-year death (d). ROC, receiver operating curve.

Figure 5.

Kaplan–Meier for PFS (a), DMFS (b), LRRFS (c), and OS (d) curves for 445 NPC patients stratified by CCD ⩽200 and >200 mg/m² in a low-risk group. PFS (e), DMFS (f), LRRFS (g), and OS (h) curves for 330 NPC patients stratified by CCD ⩽200 and >200 mg/m² in the high-risk group. CCD, cumulative cisplatin dose; DMFS, distant metastasis-free survival; LRRFS, locoregional relapse-free survival; NPC, nasopharyngeal carcinoma; OS, overall survival; PFS, progression-free survival.