1095 - Combined Liquid Biopsy of On-Treatment Plasma Epstein-Barr Virus DNA with Clinical Stage to Guide Induction Chemotherapy Cycles in Locally Advanced Nasopharyngeal Carcinoma Patients: A Multicenter Development and Validation Study
Presenter(s)
L. Tang1, P. Ji1, J. Shen2, D. He1, L. Chen1, C. Huang1, G. Wang1, K. Li1, X. J. Du1, R. Guo3, and J. Zong4; 1Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, Guangdong, China, 2State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen Univ, Guangzhou, Guangdong, China, 3Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, China, 4Department of Radiation Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian, China
Purpose/Objective(s): Induction chemotherapy (ICT) followed by concurrent chemoradiotherapy (CCRT) is the standard treatment for locally advanced nasopharyngeal carcinoma (LA-NPC). However, the optimal number of ICT cycles for LA-NPC remains unclear. This retrospective study aims to develop and validate a strategy that combines clinical staging with plasma Epstein-Barr virus (EBV) DNA levels to guide the selection of ICT cycles for LA-NPC patients.
Materials/Methods: A total of 840 LA-NPC patients from center 1 were enrolled as the training cohort, and 448 patients from center 2 were involved for external validation. The included patients had a histological diagnosis of NPC of stages III-IVA (AJCC 8th edition). All patients completed 2–3 cycles of ICT followed by CCRT or radiotherapy, with plasma EBV-DNA levels tested after 2 cycles of ICT (EBV-DNA2ICT). Propensity score matching was performed to balance baseline characteristics. The primary endpoint was failure-free survival (FFS), the secondary end-points were overall survival (OS), distant metastasis-free survival (DMFS), and locoregional recurrence - free survival (LRRFS).
Results: In the center 1 cohort, detectable EBV-DNA2ICT was associated with poorer FFS, OS, DMFS, and LRRFS (p < 0.001, p = 0.001, p = 0.008, and p = 0.005, respectively), but no prognostic difference was observed between three cycles and two cycles of ICT. Subgroup analysis indicated that among stage III NPC patients, different EBV-DNA2ICT status showed no prognostic difference. Moreover, the Kaplan-Meier curve showed no significant differences in FFS, OS, DMFS, and LRRFS between the two-cycle and three-cycle ICT groups in stage III NPC patients, regardless of EBV-DNA2ICT status. While among stage IVA NPC patients, EBV-DNA2ICT identified a subgroup of detectable EBV-DNA2ICT patients with poorer prognosis that benefited from three cycles of ICT, showing improved FFS, OS, and LRRFS compared to two cycles (p =0.038, p = 0.027 and p = 0.049, respectively). Multivariate Cox regression analyses revealed that the number of ICT cycles were independent predictors for both FFS and OS (p=0.041 and p =0.041, respectively) in stage IVA patients with detectable EBV-DNA2ICT. Similar trend was observed in external cohorts, where three cycles of ICT significantly improved FFS and DMFS compared to two cycles (p = 0.034 and p = 0.043, respectively) for stage IVA NPC patients with detectable EBV-DNA2ICT.
Conclusion: Based on clinical staging, the incorporation of EBV-DNA2ICT can further guide the determination of the number of ICT cycles for LA-NPC patients.