The 8 edition of the American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) stage classification (TNM) for nasopharyngeal carcinoma (NPC) was launched. It remains unknown if incorporation of non-anatomic factors into the stage classification would better predict survival. We prospectively recruited 518 patients with non-metastatic NPC treated with radical IMRT +/- chemotherapy based on the 8 edition TNM. Recursive partitioning analysis (RPA) incorporating pretreatment plasma EBV DNA derived new stage groups. Multivariable analyses to calculate adjusted hazard ratios (AHRs) derived another set of stage groups. 5-year progression-free survival (PFS), overall survival (OS) and cancer-specific survival (CSS) were: stage I (PFS 100%, OS 90%, CSS 100%), II (PFS 88%, OS 84%, CSS 95%), III (PFS 84%, OS 84%, CSS 90%) and IVA (PFS 71%, OS 75%, CSS 80%) (p < 0.001, p = 0.066, and p = 0.002 respectively). RPA derived 4 new stages: RPA-I (T1-T4N0-N2 & EBV DNA <500 copies/ml) (PFS 94%, OS 89%, CSS 96%), RPA-II (T1-T4N0-N2 & EBV DNA ≥500 copies/ml) (PFS 80%, OS 83%, CSS 89%), RPA-III (T1-T2N3) (PFS 64%, OS 83%, CSS 83%) and RPA-IVA (T3-T4N3) (PFS 63%, OS 60% and CSS 68%) (all with p < 0.001). AHR using covariate adjustment also yielded a valid classification (I: T1-T2N0-N2; II: T3-T4N0-N2 or T1-T2N3, and III: T3-T4N3) (all with p < 0.001). However, RPA stages better predicted survival for PS and CSS after bootstrapping replications. Our RPA-based stage groups revealed better survival prediction compared to the 8 edition TNM and the AHR stage groups. This article is protected by copyright. All rights reserved.

No abstract

No abstract

Background Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC) in endemic regions may have undetectable plasma EBV DNA. Methods We prospectively recruited 518 patients with non-metastatic NPC and measured their pre-treatment plasma EBV DNA. The stage distribution and prognosis between pre-treatment plasma EBV DNA-negative (0–20 copies/ml) and EBV DNA-positive (>20 copies/ml) patients following radical treatment were compared. Results Seventy-eight patients (15.1%) were plasma EBV DNA-negative, and 62 in this subset (12.0%) had 0 copy/ml. Only 23/78 (29.5%) plasma EBV DNA-negative patients with advanced NPC (stage III-IVA) had strong EBV encoded RNA (EBER) positivity (score 3) in their tumours compared to 342/440 (77.7%) EBV DNA-positive patients of the same stages (p < 0.001). Though EBV DNA-negative patients had more early-stage disease (p < 0.001) and smaller volumes of the primary tumour and the positive neck nodes (p < 0.001), they had similar 5-year overall survival and cancer-specific survival to those EBV DNA-positive counterparts by stage. Similar results were also seen when plasma EBV DNA cut-off was set at 0 copy/ml. Conclusions Patients with low-volume NPC may not be identified by plasma/serum tumour markers and caution should be taken in its utility as a screening tool for NPC even in endemic regions. Clinical trial registration Clinicaltrials.gov Identifier: NCT02476669.