Recurrent/Metastatic Nasopharyngeal Carcinoma Treatment from Present to Future: Where Are We and Where Are We Heading?

OPINION STATEMENT: Nasopharyngeal carcinoma (NPC) is distinct in its anatomic location and biology from other epithelial head and neck cancer (HNC). There are 3 WHO subtypes, which considers the presence of Epstein-Barr virus (EBV) and other histopathology features. Despite the survival benefit obtained from modern treatment modalities and techniques specifically in the local and locally advanced setting, a number of patients with this disease will recur and subsequently die of distant metastasis, locoregional relapse, or both. In the recurrent setting, the ideal therapy approach continues to be a topic of discussion and current recommendations are platinum-based combination chemotherapy. Phase III clinical trials which led to the approval of pembrolizumab or nivolumab for head and neck squamous cell carcinoma (HNSCC) specifically excluded NPC. No immune checkpoint inhibitor therapy, to date, has been approved by the FDA to treat NPC although the National Comprehensive Cancer Network (NCCN) recommendations do include use of these agents. Hence, this remains the major challenge for treatment options. Nasopharyngeal carcinoma is challenging as it is really 3 different diseases, and much research is required to determine best options and sequencing of those options. This article is going to address the data to date and discuss ongoing research in EBV + and EBV - inoperable recurrent/metastatic NPC patients.

Survival benefit of induction chemotherapy for locally advanced nasopharyngeal carcinoma: prognosis based on a new risk estimation model.

BACKGROUND: Although the National Comprehensive Cancer Network (NCCN) Guidelines recommend CCRT+AC and IC + CCRT as level 2A evidence for treatment of the locoregionally advanced NPC (II-IVa), IC + CCRT+AC could also be an alternative but it is seldom used because of the low completion rates. This article aimed to compare the effectiveness of the three radiotherapy regimens using a large-scale retrospective study. METHODS: This retrospective single center analysis enrolled 1812 diagnosed NPC patients at Nanfang Hospital from January 2005 to December 2015 and only 729 patients met the inclusion criteria and were analyzed. Patients without distant metastasis, age of 18-70 years, Karnofsky scores of at least 70,stage III-IVb, and adequate adequate bone marrow, liver and renal function. Were enrolled. Adverse events and other categorical variables were compared by Pearson chi-square test or Fishier exact test. Time-to-event data were described with the Kaplan-Meier curves, time-to-event intervals compared with the log-rank test. We did multivariable analyses with the Cox proportional hazards model to test the independent signifi cance of diff erent factors. Cox proportional hazards model was used to estimate the ß regression coeffi cient, p value, and hazard ratio and its 95% CI for each of the selected risk predictors. RESULTS: The median follow-up time was 47 months. Kaplan-Meier analyses revealed no significant differences among three groups in 3-year failure-free survival (FFS, P = 0.225), 3-year overall survival (OS, P = 0.992), 3-year locoregional failure-free survival (LFFS, P = 0.549), and 3-year distant failure-free survival (DFFS, P = 0.174). Stratified survival analysis based on the risk scoring model revealed no differences in FFS, OS, LFFS, and DFFS between IC + CCRT and CCRT+AC groups for low-risk patients, however, the 3-year OS (88.3% vs. 77.6%, P = 0.049) and 3-year DFFS (84.0% vs.66.8%, P = 0.032) were respectively significantly better in IC + CCRT group compared with CCRT+AC group for high-risk patients. CONCLUSIONS: Compared with CCRT+AC, IC + CCRT lowers distant metastasis rate and improves OS among patients with locally advanced NPC in high risk group.

Efficacy and safety of two different adjuvant chemotherapy regimens in combination with concurrent chemoradiotherapy in treating patients with advanced nasopharyngeal carcinoma: A protocol for randomized controlled trial.

BACKGROUND: Concurrent chemoradiotherapy is widely utilised as a standardized primary method of treatment for patients with advanced nasopharyngeal carcinoma (NPC). However, the combination of concurrent chemoradiotherapy and adjuvant chemotherapy for treating NPC patients remain unclear. Therefore, this study attempts to elucidate the efficiency and safety of concurrent chemoradiotherapy combined with adjuvant chemotherapy (gemcitabine plus cisplatin versus 5-fluorouracil plus cisplatin) for treating patients with NPC. MATERIALS AND METHODS: This study is a randomized, multicentral, open-labelled trial to assess the clinical efficiency and safety of using concurrent chemoradiotherapy combined with adjuvant chemotherapy as a therapeutic measure for advanced NPC patients. A total of 50 patients will be randomly assigned into 2 groups, namely treatment-group-one and treatment-group-two. Eligible patients will be administered with concurrent chemoradiotherapy and subsequentially with adjuvant chemotherapy (gemcitabine plus cisplatin or 5-fluorouracil plus cisplatin). Moreover, the primary endpoint is a comparison of progression-free survival between concurrent chemoradiotherapy and subsequentially adjuvant gemcitabine and cisplatin and chemoradiotherapy, which is proceeded by adjuvant 5-fluorouracil and cisplatin in advanced NPC patients. Overall survival, overall response rate, incidence of acute and late toxicity, and adverse events are the minor endpoints. Statistical analyses will be performed with SPSS 25.0 software. DISCUSSION: The current research evaluates the clinical efficiency and safety of utilising concurrent chemoradiotherapy combined with adjuvant chemotherapy as a therapeutic strategy to treat advanced NPC patients. The work done in this study will provide a clinical basis for concurrent chemoradiotherapy in combination with adjuvant chemotherapy for treating advanced NPC. TRIAL REGISTRATION: DOI 10.17605/OSF.IO/5UPVM.

Effect of oral supplements on the nutritional status of nasopharyngeal carcinoma patients undergoing concurrent chemotherapy: A randomized controlled Phase II trial.

OBJECTIVES: The objectives of this study were to prospectively compare individualized dietary counseling with or without oral nutritional supplements (ONSs) in nasopharyngeal carcinoma (NPC) patients undergoing concurrent chemoradiotherapy (CCRT) in a Phase II, randomized trial. MATERIALS AND METHODS: Between June 2014 and August 2016, Stage II-IVb NPC patients were randomly enrolled. The primary endpoint was change in body weight between during CCRT, and the secondary endpoints were change in body mass index (BMI) and fat-free mass index (FFMI). RESULTS: Fifty-two patients were randomized; 19 patients in the control group and 23 in the ONS group were eligible for analysis. Weight, BMI, and body composition parameters significantly decreased from baseline to week 6. FFMI was significantly better in patients with ONS intake >2/3 planed than the control group (P = 0.028). Weight and BMI maintenance was slightly better in patients with total intake >2/3 planed (P = 0.170 and P= 0.229, respectively). The mean Patient-Generated Subjective Global Assessment score was also better in the ONS group at the end of CCRT (P = 0.053). CONCLUSIONS: ONSs with individualized dietary counseling may be beneficial in patients with enough intake, and further prospective studies with large groups of patients are warranted.

Highly Uniform Synthesis of Selenium Nanoparticles with EGFR Targeting and Tumor Microenvironment-Responsive Ability for Simultaneous Diagnosis and Therapy of Nasopharyngeal Carcinoma.

Rational design of multifunctional and smart drug-delivered nanoplatforms is a promising strategy to achieve simultaneous diagnosis, real-time monitoring, and therapy of cancers. Herein, highly uniform and stable selenium nanoparticles with epidermal growth factor receptor (EGFR) targeting and tumor microenvironment-responsive ability (Se-5Fu-Gd-P(Cet/YI-12)) were designed and synthesized by using EGFR as the targeting molecule, gadolinium chelate as the magnetic resonance imaging contrast agent, 5-fluorouracil (5Fu) and cetuximab as drug payloads, polyamidoamine (PAMAM) and 3,3'-dithiobis (sulfosuccinimidyl propionate) as the response agents of intratumoral glutathione, and pH for the treatment and diagnosis of nasopharyngeal carcinoma (NPC). This Se nanoplatform showed excellent magnetic resonance imaging capability and has the potential for its clinical application as a diagnostic agent for tumor tissue specimens. Additionally, in vitro cellular experiments showed that by means of introducing clinical targeted drugs and peptides not only validly increased the intracellular uptake of the Se nanoplatform in NPC cells but also enhanced its penetration ability toward CNE tumor spheroids, resulting in simultaneous inhibition of CNE cell growth, invasion, and migration. In addition, the sequentially triggered bioresponsive property of the nanoplatform in a tumor microenvironment effectively improved the targeting delivery and anticancer efficiency of payloads. Overall, this study not only provides a strategy for facile synthesis of highly uniform and stable nanomedicines and tailing of the bioresponsive property but also sheds light on its application in targeting theranosis of NPC.