Department of Radiation Oncology, Fudan University Shanghai Cancer Center, 200032 Shanghai, China; Department of Oncology, Shanghai Medical College of Fudan University, 200032 Shanghai, China; Shanghai Clinical Research Center for Radiation Oncology, 200032 Shanghai, China; Shanghai Key Laboratory of Radiation Oncology, 200032 Shanghai, China.
Department of Radiation Oncology, Fudan University Shanghai Cancer Center, 200032 Shanghai, China; Department of Oncology, Shanghai Medical College of Fudan University, 200032 Shanghai, China; Shanghai Clinical Research Center for Radiation Oncology, 200032 Shanghai, China.
Eur J Cancer. 2024 Dec;213:115098. doi: 10.1016/j.ejca.2024.115098. Epub 2024 Oct 26.
To investigate whether a bounce in plasma Epstein-Barr virus (EBV) DNA during posttreatment surveillance of nasopharyngeal carcinoma (NPC) informs the risk of clinical recurrence and its implication for early therapeutic intervention.
950 non-disseminated NPC patients with completed remission in 3 months after treatment were retrospectively screened. Detectable EBV DNA with no evidence of clinical relapse during follow-up was deemed as DNA bounce. The diagnostic and prognostic performance of EBV DNA bounce was assessed for subsequent failures.
Tumor recurrence occurred in 6.6 %, 10.1 % and 65.8 % in the group with persistently negative EBV DNA, single positive test and ≥ 2 positive tests, respectively. EBV DNA bounce over twice was associated with worse disease-free survival (DFS), locoregional recurrence-free survival (LRRFS), and distant metastasis-free survival (DMFS) than the other two groups. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy for the prediction of recurrence were 0.56, 0.95, 0.66, 0.93 and 0.90 using two positive tests, which were hence deemed as biological relapse. Serial cutoffs (EBV DNA 1 ≥ 40 copies/ml or EBV DNA 2 ≥100 copies/ml) further defined a high-risk subgroup with an eventual recurrence rate of 77.9 % and 3-year DFS of merely 20.5 %. Prophylactic medical intervention with capecitabine or S1 significantly improved the 3-year DFS when compared to those with observation.
The earliest two positive tests of EBV DNA represent a biomarker of biological relapse that allows early detection of clinical recurrence in EBV-related NPC. For high-risk biological relapse, preemptive intervention provides potential survival benefits.
研究鼻咽癌（NPC）治疗后监测中血浆 EBV 病毒（EBV）DNA 的反弹是否提示临床复发风险及其对早期治疗干预的意义。
回顾性筛选了 950 例治疗后 3 个月完全缓解的非播散性 NPC 患者。随访期间无临床复发证据的可检测 EBV DNA 被认为是 DNA 反弹。评估 EBV DNA 反弹对随后失败的诊断和预后性能。
在持续阴性 EBV DNA、单次阳性检测和≥2 次阳性检测组中，肿瘤复发分别为 6.6%、10.1%和 65.8%。EBV DNA 反弹超过两倍与无病生存（DFS）、局部区域无复发生存（LRRFS）和远处无转移生存（DMFS）较差相关。使用两次阳性检测预测复发的敏感性、特异性、阳性预测值（PPV）、阴性预测值（NPV）和准确性分别为 0.56、0.95、0.66、0.93 和 0.90，因此被视为生物学复发。连续截止值（EBV DNA 1≥40 拷贝/ml 或 EBV DNA 2≥100 拷贝/ml）进一步定义了一个高风险亚组，其最终复发率为 77.9%，3 年 DFS 仅为 20.5%。与观察相比，卡培他滨或 S1 的预防性医学干预显著提高了 3 年 DFS。
最早的两次 EBV DNA 阳性检测代表了生物学复发的生物标志物，可早期检测 EBV 相关 NPC 的临床复发。对于高危生物学复发，预防性干预提供了潜在的生存获益。
