Prospective evaluation of plasma Epstein-Barr virus DNA clearance and fluorodeoxyglucose positron emission scan in assessing early response to chemotherapy in patients with advanced or recurrent nasopharyngeal carcinoma

Brigette Ma, Edwin P Hui, Ann King, Sing F Leung, Michael Km Kam, Frankie Mo, Leung Li, Ki Wang, Herbert Loong, Ashley Wong, Charles Ml Chan, K C Allen Chan, S C Cesar Wong, Y M Dennis Lo, Anthony Tc Chan, Brigette Ma, Edwin P Hui, Ann King, Sing F Leung, Michael Km Kam, Frankie Mo, Leung Li, Ki Wang, Herbert Loong, Ashley Wong, Charles Ml Chan, K C Allen Chan, S C Cesar Wong, Y M Dennis Lo, Anthony Tc Chan

Abstract

Background: Plasma Epstein-Barr virus (pEBV) DNA and fluorodeoxyglucose positron emission (PET) reflect tumour burden in advanced NPC. This study hypothesised that a dual endpoint based on assessing pEBV DNA clearance and PET response could predict early drug response.

Methods: Eligible patients underwent a computed tomography (CT) scan and dual PET-CT at baseline, a PET-CT at 4 weeks, and then a CT scan at 10 weeks after starting palliative or induction chemotherapy. Plasma EBV DNA clearance was determined.

Results: Fifty-eight out of 70 enrolled patients completed all imaging and 50/58 had falling pEBV DNA level, which allowed calculation of the clearance. At a median follow-up of 29.1 months, the dual endpoint (pEBV DNA clearance ≤ 10 days and > 50% drop in sum of SUVmax of target lesions) was an independent indicator of overall survival (hazard ratio (HR) = 0.135, 95% CI = 0.039 to 0.466, p = 0.0015) and progression-free survival (HR = 0.136, 95% CI = 0.048 to 0.385, p = 0002). This dual endpoint could predict subsequent response by Response Evaluation Criteria In Solid Tumours (RECIST) criteria at 10 weeks after chemotherapy.

Conclusions: Early PET-CT response and pEBV DNA clearance could predict survival and subsequent response. This dual endpoint is an innovative tool for assessing early drug response.

Trial registration: ClinicalTrials.gov NCT01365208.

Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Overall survival (OS) curves of responders (top curve, > 50% drop in sum of SUVmax of target lesions and plasma EBV DNA clearance of ≤ 10 days, 1-year OS 100%) versus non-responders (bottom curve, ≤ 50% drop in sum of SUVmax and plasma EBV DNA clearance of > 10 days, 1-year OS 81.9%) based on the dual endpoint (log-rank, p = 0.0003). For the evaluable cohort (n = 58), the number of death and progression are 30 and 35
Fig. 2
Fig. 2
Progression-free survival (PFS) curves of responders (top curve, > 50% drop in sum of SUVmax and plasma EBV DNA clearance of ≤ 10 days, 1-year PFS rate 86.2%) versus non-responders (bottom curve, ≤ 50% drop in SUVmax and plasma EBV DNA clearance of > 10 days, 1-year PFS 36.5%) based on the dual endpoint (log-rank p = 0.0047)

References

    1. Lee AW, Ma BB, Ng WT, Chan AT. Management of nasopharyngeal carcinoma: current practice and future perspective. J. Clin. Oncol. 2015;33:3356–3364. doi: 10.1200/JCO.2015.60.9347.
    1. Cao SM, et al. Neoadjuvant chemotherapy followed by concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: A phase III multicentre randomised controlled trial. Eur. J. Cancer. 2017;75:14–23. doi: 10.1016/j.ejca.2016.12.039.
    1. Sun Y, et al. Induction chemotherapy plus concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: a phase 3, multicentre, randomised controlled trial. Lancet Oncol. 2016;17:1509–1520. doi: 10.1016/S1470-2045(16)30410-7.
    1. Hui EP, et al. Randomised phase II trial of concurrent cisplatin-radiotherapy with or without neoadjuvant docetaxel and cisplatin in advanced nasopharyngeal carcinoma. J. Clin. Oncol. 2009;27:242–249. doi: 10.1200/JCO.2008.18.1545.
    1. Lee AW, et al. Preliminary results of trial NPC-0501 evaluating the therapeutic gain by changing from concurrent-adjuvant to induction-concurrent chemoradiotherapy, changing from fluorouracil to capecitabine, and changing from conventional to accelerated radiotherapy fractionation in patients with locoregionally advanced nasopharyngeal carcinoma. Cancer. 2015;121:1328–1338. doi: 10.1002/cncr.29208.
    1. Tan T, et al. Concurrent chemo-radiation with or without induction gemcitabine, Carboplatin, and Paclitaxel: a randomised, phase 2/3 trial in locally advanced nasopharyngeal carcinoma. Int. J. Radiat. Oncol. Biol. Phys. 2015;91:952–960. doi: 10.1016/j.ijrobp.2015.01.002.
    1. Wang WY, et al. Plasma EBV DNA clearance rate as a novel prognostic marker for metastatic/recurrent nasopharyngeal carcinoma. Clin. Cancer Res. 2010;16:1016–1024. doi: 10.1158/1078-0432.CCR-09-2796.
    1. Lo YM, et al. Kinetics of plasma Epstein-Barr virus DNA during radiation therapy for nasopharyngeal carcinoma. Cancer Res. 2000;60:2351–2355.
    1. Wahl RL, Jacene H, Kasamon Y, Lodge MA. From RECIST to PERCIST: evolving considerations for PET response criteria in solid tumours. J. Nucl. Med. 2009;50(Suppl 1):122S–150S. doi: 10.2967/jnumed.108.057307.
    1. Yen RF, et al. Early restaging whole-body (18)F-FDG PET during induction chemotherapy predicts clinical outcome in patients with locoregionally advanced nasopharyngeal carcinoma. Eur. J. Nucl. Med. Mol. Imaging. 2005;32:1152–1159. doi: 10.1007/s00259-005-1837-5.
    1. Young H, et al. Measurement of clinical and subclinical tumour response using [18F]-fluorodeoxyglucose and positron emission tomography: review and 1999 EORTC recommendations. European Organization for Research and Treatment of Cancer (EORTC) PET Study Group. Eur. J. Cancer. 1999;35:1773–1782. doi: 10.1016/S0959-8049(99)00229-4.
    1. Yu WL, Wong SM, Wang K, Ahuja AT. Accuracy of 18F-fluorodeoxyglucose positron emission tomography/computed tomography for detection of recurrent or metastatic colorectal carcinoma in patients with rising carcinoembryonic antigen levels. Hong. Kong J. Radiol. 2014;17:9–15. doi: 10.12809/hkjr1413186.
    1. Monteil J, et al. Chemotherapy response evaluation in metastatic colorectal cancer with FDG PET/CT and CT scans. Anticancer Res. 2009;29:2563–2568.
    1. Lastoria S, et al. Early PET/CT scan is more effective than RECIST in predicting outcome of patients with liver metastases from colorectal cancer treated with preoperative chemotherapy plus bevacizumab. J. Nucl. Med. 2013;54:2062–2069. doi: 10.2967/jnumed.113.119909.
    1. Ma B, et al. Identifying an early indicator of drug efficacy in patients with metastatic colorectal cancer—a prospective evaluation of circulating tumour cells, 18F-fluorodeoxyglucose positron-emission tomography and the RECIST criteria. Ann. Oncol. 2017;7:1576–1581. doi: 10.1093/annonc/mdx149.
    1. To EW, et al. Rapid clearance of plasma Epstein-Barr virus DNA after surgical treatment of nasopharyngeal carcinoma. Clin. Cancer Res. 2003;9:3254–3259.
    1. Yankeelov TE, et al. Quantitative imaging in cancer clinical trials. Clin. Cancer Res. 2016;22:284–290. doi: 10.1158/1078-0432.CCR-14-3336.
    1. Huang Y, et al. Prognostic value of pretreatment 18F-FDG PET-CT for nasopharyngeal carcinoma patients. Medicine (Baltim.) 2017;96:e6721. doi: 10.1097/MD.0000000000006721.
    1. Xie P, Yue JB, Fu Z, Feng R, Yu JM. Prognostic value of 18F-FDG PET/CT before and after radiotherapy for locally advanced nasopharyngeal carcinoma. Ann. Oncol. 2010;21:1078–1082. doi: 10.1093/annonc/mdp430.
    1. Chan SC, et al. Differential roles of 18F-FDG PET in patients with locoregional advanced nasopharyngeal carcinoma after primary curative therapy: response evaluation and impact on management. J. Nucl. Med. 2006;47:1447–1454.
    1. Yen TC, et al. 18F-FDG-PET for evaluation of the response to concurrent chemoradiation therapy with intensity-modulated radiation technique for Stage T4 nasopharyngeal carcinoma. Int. J. Radiat. Oncol. Biol. Phys. 2006;65:1307–1314. doi: 10.1016/j.ijrobp.2006.02.031.
    1. Qi S, Zhongyi Y, Yingjian Z, Chaosu H. 18F-FLT and 18F-FDG PET/CT in predicting response to chemoradiotherapy in nasopharyngeal carcinoma: preliminary results. Sci. Rep. 2017;7:40552. doi: 10.1038/srep40552.
    1. Ma BB, et al. Relationship between pretreatment level of plasma Epstein-Barr virus DNA, tumour burden, and metabolic activity in advanced nasopharyngeal carcinoma. Int. J. Radiat. Oncol. Biol. Phys. 2006;66:714–720. doi: 10.1016/j.ijrobp.2006.05.064.
    1. Ribassin-Majed L, et al. What is the best treatment of locally advanced nasopharyngeal carcinoma? An individual patient data network meta-analysis. J. Clin. Oncol. 2017;35:498–505. doi: 10.1200/JCO.2016.67.4119.

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