Background: Few studies have evaluated the prognostic value of the integrated model consisting of gross tumor volume of lymph nodes (GTVnd) and pretreatment plasma Epstein–Barr virus DNA (pre-EBV DNA) in nasopharyngeal carcinoma (NPC) patients. Methods: A well-established big-data intelligence platform with 10,126 NPC patients was used for a retrospective review. A total of 1500 cases with cervical nodal metastases but without distant metastases were randomly assigned to a training ( n = 503) or test condition ( n = 997) for analyses. The cut-off point for the GTVnd derived from the receiver operating characteristic (ROC) curve was combined with the published cut-off point for pre-EBV DNA to develop an integrated model by which patients were classified into four groups. Results: Both GTVnd and pre-EBV DNA were independent prognostic factors. Regardless of whether patients received induction chemotherapy (IC), the 5-year distant metastasis-free survival (DMFS) (69.5%) and overall survival (OS) (68.4%) were significantly worse in those with both a GTVnd >20 ml and pre-EBV DNA >2000 copies/ml (all p-values < 0.001). In patients with IC, all others had better 5-year DMFS and OS; in patients without IC, those with either a GTVnd >20 ml or pre-EBV DNA >2000 copies/ml had the medium 5-year DMFS and OS, while patients with neither of them had the best. Conclusions: The integrated GTVnd and pre-EBV DNA model not only predicted DMFS and OS in NPC patients effectively, but was an indicator of timely adjustment of therapeutic strategies for NPC patients, especially those completing IC.
Epigenetic regulation plays an important role in the development and progression of nasopharyngeal carcinoma (NPC), but the epigenetic mechanisms underlying NPC metastasis remain poorly understood. Here, we demonstrate that hypermethylation of the UCHL1 promoter leads to its downregulation in NPC. Restoration of UCHL1 inhibited the migration and invasion of NPC cells in vitro and in vivo, and knockdown of UCHL1 promoted NPC cell migration and invasion in vitro and in vivo. Importantly, we found that UCHL1 interacts with CTTN, and may function as a ligase promoting CTTN degradation by increasing K48-linked ubiquitination of CTTN. Additionally, restoration of CTTN in NPC cells that overexpressed UCHL1 rescued UCHL1 suppressive effects on NPC cell migration and invasion, which indicated that CTTN is a functional target of UCHL1 in NPC. Our findings revealed that UCHL1 acts as a tumor suppressor gene in NPC and thus provided a novel therapeutic target for NPC treatment.
Objectives
To address whether sparing the medial retropharyngeal lymph node (MRLN) region from elective irradiation volume provides non-inferior local relapse-free survival versus standard radiotherapy in patients with nasopharyngeal carcinoma.
Design
Open-label, non-inferiority, multicentre, randomised, phase 3 trial.
Setting
Three Chinese hospitals between 20 November 2017 and 3 December 2018.
Participants
Adults (18-65 years) with newly diagnosed, non-keratinising, non-distant metastatic nasopharyngeal carcinoma without MRLN involvement.
Interventions
Randomisation was done centrally by the Clinical Trials Centre at Sun Yat-sen University Cancer Center. Eligible patients were randomly assigned (1:1; block size of four) to receive MRLN sparing radiotherapy or standard radiotherapy (both medial and lateral retropharyngeal lymph node groups), and stratified by institution and treatment modality as follows: radiotherapy alone; concurrent chemoradiotherapy; induction chemotherapy plus radiotherapy or concurrent chemoradiotherapy.
Main outcome measures
Non-inferiority was met if the lower limit of the one sided 97.5% confidence interval of the absolute difference in three year local relapse-free survival (MRLN sparing radiotherapy minus standard radiotherapy) was greater than −8%.
Results
568 patients were recruited: 285 in the MRLN sparing radiotherapy group; 283 in the standard radiotherapy group. Median follow-up was 42 months (interquartile range 39-45), intention-to-treat analysis showed that the three year local relapse-free survival of the MRLN sparing radiotherapy group was non-inferior to that of the standard radiotherapy group (95.3%
v
95.5%, stratified hazard ratio 1.04 (95% confidence interval 0.51 to 2.12), P=0.95) with a difference of −0.2% ((one sided 97.5% confidence interval –3.6 to ∞), P
non-inferiority
<0.001). In the safety set (n=564), the sparing group had a lower incidence of grade ≥1 acute dysphagia (25.5%
v
35.1%, P=0.01) and late dysphagia (24.0%
v
34.3%, P=0.008). Patient reported outcomes at three years after MRLN sparing radiotherapy were better in multiple domains after adjusting for the baseline values: global health status (mean difference −5.6 (95% confidence interval –9.1 to –2.0), P=0.002), role functioning (−5.5 (–7.4 to –3.6), P<0.001), social functioning (−6.2 (–8.9 to –3.6), P<0.001), fatigue (7.9 (4.0 to 11.8), P<0.001), and swallowing (11.0 (8.4 to 13.6), P<0.001). The difference in swallowing scores reached clinical significance (>10 points difference).
Conclusion
Compared with standard radiotherapy, MRLN sparing radiotherapy showed non-inferiority in terms of risk of local relapse with fewer radiation related toxicity and improved patient reported outcomes in patients with non-metastatic nasopharyngeal carcinoma.
Trial registration
ClinicalTrials.gov
NCT03346109
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.