Combined Real-time Liquid Biopsy With TNM Stage to Guide Induction Chemotherapy Cycles in Nasopharyngeal Carcinoma: A Development and Validation Study.

Abstract

The optimal number of induction chemotherapy (IC) cycles for locally advanced nasopharyngeal carcinoma (LA-NPC) is uncertain. This retrospective study proposes and validates a strategy combining clinical staging with post-cycle-2 plasma Epstein-Barr virus (EBV)-DNA status to guide IC cycle selection. Patients with LA-NPC from Sun Yat-sen University Cancer Center (center 1) formed the training cohort, and those from Fujian Cancer Hospital (center 2) comprised the external validation cohort. All received 2 to 3 IC cycles plus (chemo)radiation therapy, with plasma EBV-DNA measured after cycle-2 (post-IC2-EBV-DNA). Failure-free survival (FFS) was compared between 2- versus 3-cycle IC and stratified by recursive partitioning analysis. The training and validation cohorts comprised 794 and 448 patients, evenly divided between 3- and 2-cycle IC. In the training cohort, recursive partitioning analysis stratified patients into 3 distinct prognostic groups. Among the low-risk group (undetectable post-IC2-EBV-DNA), FFS was comparable between the 3- and 2-cycle IC (83.8% vs 87.3%, P = .647). In the detectable cohort, patients with stage IVA disease (high-risk group) who received 3-cycle IC had improved 5-year FFS versus 2-cycle (74.0% vs 56.8%; P = .013), whereas no difference was observed in stage III (intermediate-risk group) (75.9% vs 83.1%; P = .269). Findings were confirmed in the external validation cohort. This retrospective study indicates that patients with stage IVA LA-NPC with detectable EBV-DNA after 2 IC cycles benefit from a third cycle, whereas no clear benefit of a third cycle is observed in patients with stage III or in those with undetectable post-IC2-EBV-DNA.