Cancer Res Treat.  2018 Jul;50(3):861-871. 10.4143/crt.2017.237.

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

• Chen QY
• Guo SY
• Tang LQ
• Lu TY
• Chen BL
• Zhong QY
• Zou MS
• Tang QN
• Chen WH
• Guo SS
• Liu LT
• Li Y
• Guo L
• Mo HY
• Sun R
• Luo DH
• Zhao C
• Cao KJ
• Qian CN
• Guo X
• Zeng MS
• Mai HQ

• KMID: 2417875
• DOI: http://doi.org/10.4143/crt.2017.237

Abstract

PURPOSE
Little is known about combination of the circulating Epstein-Barr viral (EBV) DNA and tumor volume in prognosis of stage II nasopharyngeal carcinoma (NPC) patients in the intensity modulated radiotherapy (IMRT) era. We conducted this cohort study to evaluate the prognostic values of combining these two factors.
MATERIALS AND METHODS
By Kaplan-Meier, we compare the differences of survival curves between 385 patients with different EBV DNA or tumor volume levels, or with the combination of two biomarkers mentioned above.
RESULTS
Gross tumor volume of cervical lymph nodes (GTVnd, p < 0.001) and total tumor volume (GTVtotal, p < 0.001) were both closely related to pretreatment EBV DNA, while gross tumor volume of nasopharynx (GTVnx, p=0.047) was weakly related to EBV DNA. EBV DNA was significantly correlated with progress-free survival (PFS, p=0.005), locoregional-free survival (LRFS, p=0.039), and distant metastasis-free survival (DMFS, p=0.017), while GTVtotal, regardless of GTVnx and GTVnd, had a significant correlation with PFS and LRFS. The p-values of GTVtotal for PFS and LRFS were 0.008 and 0.001, respectively. According to GTVtotal and pretreatment EBV DNA level, patients were divided into a low-risk group (EBV DNA 0 copy/mL, GTVtotal < 30 cm³; EBV DNA 0 copy/mL, GTVtotal ≥ 30 cm³; or EBV DNA > 0 copy/mL, GTVtotal < 30 cm³) and a high-risk group (EBV DNA > 0 copy/mL, GTVtotal ≥ 30 cm³). When patients in the low-risk group were compared with those in the high-risk group, 3-year PFS (p=0.003), LRFS (p=0.010), and DMFS (p=0.031) rates were statistically significant.
CONCLUSION
Pretreatment plasma EBV DNA and tumor volume were both closely correlated with prognosis of stage II NPC patients in the IMRT era. Combination of EBV DNA and tumor volume can refine prognosis and indicate for clinical therapy.

Keyword

Nasopharyngeal carcinoma; Tumor burden; Epstein-Barr virus; Intensity modulated radiotherapy; Prognosis

MeSH Terms

Biomarkers
Cohort Studies*
DNA*
Herpesvirus 4, Human*
Humans
Lymph Nodes
Nasopharynx
Plasma
Prognosis
Radiotherapy*
Tumor Burden*
Biomarkers
DNA

Figure

• 

  Fig. 1. Progression-free survival by Kaplan-Meier analysis, comparing the undetectable Epstein-Barr virus (EBV) DNA group with the detectable EBV DNA group (A), larger and smaller gross target volume of nasopharynx (GTVnx)+gross target volume of cervical lymph node (GTVnd) (GTVtotal) group (B), GTVnx group (C), and GTVnd group (D).

• 

  Fig. 2. Progression-free survival (A), distant metastasis-free survival (B), and locoregional-free survival (C) by Kaplan-Meier analysis, comparing the low-risk group (Epstein-Barr virus [EBV] DNA 0 copy/mL, gross target volume of nasopharynx+ gross target volume of cervical lymph node [GTVtotal] < 30 cm3or ≥ 30 cm3; or EBV DNA > 0 copy/mL, GTVtotal < 30 cm3) and high-risk group (EBV DNA > 0 copy/mL, GTVtotal ≥ 30 cm3).

• 

  Fig. 3. Differences between low-risk group (Epstein-Barr virus [EBV] DNA 0 copy/mL, gross target volume of nasopharynx+gross target volume of cervical lymph node [GTVtotal] < 30 cm3or ≥ 30 cm3; or EBV DNA > 0 copy/mL, GTVtotal < 30 cm3) and high-risk group (EBV DNA > 0 copy/mL, GTVtotal ≥ 30 cm3) in patients treated with intensity modulated radiotherapy (A) and concurrent chemoradiotherapy (B) for progression-free survival by Kaplan-Meier analysis.

Reference

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