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      Recent advances in the management of nasopharyngeal carcinoma

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          Abstract

          Over the last few years, certain areas in the management nasopharyngeal carcinoma (NPC) that have an impact on the care of these patients have evolved, particularly with regard to liquid biopsies, minimally invasive surgery, and advances in chemotherapy and immunotherapy. Beyond its proven role in the diagnostics, surveillance, and treatment of NPC, liquid biopsy with plasma Epstein–Barr virus DNA in the screening of high-risk populations for NPC is strongly supported by recent evidence. Surgery of the nasopharynx is reserved for locally recurrent NPC, and in recent years there have been great strides in minimally invasive techniques with survival rates similar to those of open techniques in treating NPC. Induction chemotherapy in a recent pooled analysis was shown to be superior to concurrent chemotherapy alone for locoregionally advanced NPC. Finally, immunotherapy with a PD-1 inhibitor in NPC has been shown to have 1-year overall survival rates comparable to those of other patients with heavily pre-treated metastatic or recurrent NPC. In this commentary, we discuss these recent advances and their potential in the clinical management of patients with NPC.

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          Most cited references33

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          The prevalence and prevention of nasopharyngeal carcinoma in China

          Nasopharyngeal carcinoma (NPC) has remarkable epidemiological features, including regional, racial, and familial aggregations. The aim of this review is to describe the epidemiological characteristics of NPC and to propose possible causes for the high incidence patterns in southern China. Since the etiology of NPC is not completely understood, approaches to primary prevention of NPC remain under consideration. This situation highlights the need to conduct secondary prevention, including improving rates of early detection, early diagnosis, and early treatment in NPC patients. Since the 1970's, high-risk populations in southern China have been screened extensively for early detection of NPC using anti–Epstein-Barr virus (EBV) serum biomarkers. This review summarizes several large screening studies that have been conducted in the high-incidence areas of China. Screening markers, high-risk age range for screening, time intervals for blood re-examination, and the effectiveness of these screening studies will be discussed. Conduction of prospective randomized controlled screening trials in southern China can be expected to maximize the cost-effectiveness of early NPC detection screening.
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            Antitumor Activity of Nivolumab in Recurrent and Metastatic Nasopharyngeal Carcinoma: An International, Multicenter Study of the Mayo Clinic Phase 2 Consortium (NCI-9742)

            Purpose This multinational study evaluated the antitumor activity of nivolumab in nasopharyngeal carcinoma (NPC). Tumor and plasma-based biomarkers were investigated in an exploratory analysis. Patients and Methods Patients with multiply pretreated recurrent or metastatic NPC were treated with nivolumab until disease progression. The primary end point was objective response rate (ORR) and secondary end points included survival and toxicity. The expression of programmed death-ligand 1 (PD-L1) and human leukocyte antigens A and B in archived tumors and plasma clearance of Epstein-Barr virus DNA were correlated with ORR and survival. Results A total of 44 patients were evaluated and the overall ORR was 20.5% (complete response, n = 1; partial response, n = 8). Nine patients received nivolumab for > 12 months (20%). The 1-year overall survival rate was 59% (95% CI, 44.3% to 78.5%) and 1-year progression-free survival (PFS) rate was 19.3% (95% CI, 10.1% to 37.2%). There was no statistical correlation between ORR and the biomarkers; however, a descriptive analysis showed that the proportion of patients who responded was higher among those with PD-L1 positive tumors (> 1% expression) than those with PD-L1-negative tumors. The loss of expression of one or both human leukocyte antigen class 1 proteins was associated with better PFS than when both proteins were expressed (1-year PFS, 30.9% v 5.6%; log-rank P = .01). There was no association between survival and PD-L1 expression or plasma Epstein-Barr virus DNA clearance. There was no unexpected toxicity to nivolumab. Conclusion Nivolumab has promising activity in NPC and the 1-year overall survival rate compares favorably with historic data in similar populations. Additional evaluation in a randomized setting is warranted. The biomarker results were hypothesis generating and validation in larger cohorts is needed.
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              The genomic landscape of nasopharyngeal carcinoma.

              Nasopharyngeal carcinoma (NPC) has extremely skewed ethnic and geographic distributions, is poorly understood at the genetic level and is in need of effective therapeutic approaches. Here we determined the mutational landscape of 128 cases with NPC using whole-exome and targeted deep sequencing, as well as SNP array analysis. These approaches revealed a distinct mutational signature and nine significantly mutated genes, many of which have not been implicated previously in NPC. Notably, integrated analysis showed enrichment of genetic lesions affecting several important cellular processes and pathways, including chromatin modification, ERBB-PI3K signaling and autophagy machinery. Further functional studies suggested the biological relevance of these lesions to the NPC malignant phenotype. In addition, we uncovered a number of new druggable candidates because of their genomic alterations. Together our study provides a molecular basis for a comprehensive understanding of, and exploring new therapies for, NPC.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Writing – Original Draft Preparation
                Role: ConceptualizationRole: SupervisionRole: Writing – Review & Editing
                Journal
                F1000Res
                F1000Res
                F1000Research
                F1000Research
                F1000 Research Limited (London, UK )
                2046-1402
                21 November 2018
                2018
                : 7
                : F1000 Faculty Rev-1829
                Affiliations
                [1 ]Department of Chemical Pathology, Li Ka Shing Institute of Health Sciences, State Key Laboratory in Oncology in South China, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong
                [2 ]Department of Otorhinolaryngology, Head and Neck Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong
                Author notes

                No competing interests were disclosed.

                Author information
                https://orcid.org/0000-0002-9480-4637
                Article
                10.12688/f1000research.15066.1
                6249636
                30519454
                a5295ad9-19c5-4f3a-94cb-7ac40a32392a
                Copyright: © 2018 Lam WKJ and Chan JYK

                This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 19 November 2018
                Funding
                The author(s) declared that no grants were involved in supporting this work.
                Categories
                Review
                Articles

                nasopharyngeal carcinoma,ebv dna,robotic surgery,endoscopic surgery,nasopharyngectomy,immunotherapy

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