New concepts of “minimal residual disease” and “biomarker failure” in nasopharyngeal carcinoma

Background

Nasopharyngeal carcinoma (NPC) has been proven as an EBV-associated cancer. Circulating EBV DNA can be detected in more than 90% newly diagnosed NPC patients. We tried to propose two new concepts of “minimal residual disease” and “biomarker failure” in NPC .

Methods

The first retrospective cohort included 931 previously untreated, biopsy-proven NPC patients who finished curative radiotherapy (RT) with/without chemotherapy. Plasma EBV DNA was measured one week after RT. We analyzed the subsequent relapse rate and survival outcome in patients with persistently detectable or undetectable EBV DNA. The second prospective cohort enrolled 441 NPC patients who finished curative RT and in clinical remission state. Plasma EBV DNA was monitored once every 2-3 months. We evaluated the diagnostic yields on subsequent treatment failure according to EBV DNA blood tests.

Results

Among the first cohort, 125 of 931 cases (13.4%) have post-RT detectable EBV DNA signals but in very low copy number. We observed a significantly higher relapse rate (64.8% vs. 21.3%, P 

Conclusions

NPC patients with post-RT persistently detectable EBV DNA may be regarded as potential existence of “minimal residual disease” and warrant future adjuvant therapy trials. Patients with blood tests showing EBV DNA-positive during follow-up should be regarded as “biomarker failure” and candidates for future trials of early intervention.

Clinical trial identification

CG11133 and CE12111 of the Taichung Veterans General Hospital, Taiwan.

Legal entity responsible for the study

Department of Radiation Oncology, Taichung Veterans General Hospital, Taiwan

Funding

The Grant from the Ministry of Science and Technology (MOST 103-2314-B-075A-005 -MY3), Taichung Veterans General Hospital (TCVGH-1027102C, 1037103C, 1047106C), and Bodok's Trading Co., Ltd., Taiwan.

Disclosure

All authors have declared no conflicts of interest.