Nasopharyngeal Carcinoma Research Articles

Liquid biopsy with plasma Epstein-Barr virus DNA characterizes biological relapse for the prediction of cancer recurrence in non-disseminated nasopharyngeal carcinoma

PurposeTo investigate whether a bounce in plasma Epstein-Barr virus (EBV) DNA during posttreatment surveillance of nasopharyngeal carcinoma (NPC) informs the risk of clinical recurrence and its implication for early therapeutic intervention. Methods950 non-disseminated NPC patients with completed remission in 3 months after treatment were retrospectively screened. Detectable EBV DNA with no evidence of clinical relapse during follow-up was deemed as DNA bounce. The diagnostic and prognostic performance of EBV DNA bounce was assessed for subsequent failures. ResultsTumor recurrence occurred in 6.6 %, 10.1 % and 65.8 % in the group with persistently negative EBV DNA, single positive test and ≥ 2 positive tests, respectively. EBV DNA bounce over twice was associated with worse disease-free survival (DFS), locoregional recurrence-free survival (LRRFS), and distant metastasis-free survival (DMFS) than the other two groups. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy for the prediction of recurrence were 0.56, 0.95, 0.66, 0.93 and 0.90 using two positive tests, which were hence deemed as biological relapse. Serial cutoffs (EBV DNA 1 ≥ 40 copies/ml or EBV DNA 2 ≥100 copies/ml) further defined a high-risk subgroup with an eventual recurrence rate of 77.9 % and 3-year DFS of merely 20.5 %. Prophylactic medical intervention with capecitabine or S1 significantly improved the 3-year DFS when compared to those with observation. ConclusionsThe earliest two positive tests of EBV DNA represent a biomarker of biological relapse that allows early detection of clinical recurrence in EBV-related NPC. For high-risk biological relapse, preemptive intervention provides potential survival benefits.

How enteral nutrition modes influence nasopharyngeal carcinoma survivors with late dysphagia after radiotherapy: a randomized controlled study.

Palliation to late dysphagia after radiotherapy for nasopharyngeal carcinoma (NPC) continues to be a challenge. Intermittent oro-esophageal tube feeding (IOE) is an emerging enteral nutrition mode that can address nutrition and quality of life issues related to nasogastric tube feeding (NGT). This study aims to investigate the effect of IOE versus NGT in late dysphagia after radiotherapy for NPC. This randomized controlled study included 82 NPC survivors with late dysphagia after radiotherapy. The subjects were randomized divided into the IOE and NGT groups (n1 = n2 = 41). Both groups received standard-of-care rehabilitation. Enteral nutrition supports were administered through IOE or NGT accordingly. This study lasted 2weeks for each participant. The primary outcome was nutritional status including albumin, hemoglobin, total serum protein, and body mass index. The secondary outcomes were (i) the functional oral intake scale (FOIS), (ii) the penetration-aspiration scale (PAS), (iii) oral transit time (OTT), (iv) hyoid pause time (HPT), (v) pharyngeal transport time (PTT), and (vi) swallowing-quality of life (SWAL-QoL). Three cases quitted the study halfway and there were no significant baseline differences between the IOE (n = 40) and NGT (n = 39) groups. Both time and group effects were significant in all nutritional indicators. The time effect was significant in the FOIS levels, OTT and PTT, while the group effect was not. Either time or group effect were insignificant in the PAS levels and HPT. Both group and time effects were significant in the SWAL-QoL total scores (zGroup = 5.080, P < 0.001; zTime = 18.005, P < 0.001). The significance of time and group effects varied across different dimensions of the SWAL-QoL. Rehabilitation interventions can improve swallowing function among NPC survivors with late dysphagia after radiotherapy. In this population who received standard-of-care rehabilitation, IOE is more conducive to the improvement of nutritional status, and swallowing-related quality of life. ClinicalTrials.gov Identifier: NCT06301763.

Analysis of the epidemiology and clinical characteristics of Epstein-Barr virus infection.

The Epstein-Barr virus (EBV) is responsible for a spectrum of human diseases and demonstrates a considerable prevalence among various populations. Advances in molecular epidemiological research have enhanced our comprehension of EBV-related pathologies. In this study, our objective was to examine the epidemiological profile and clinical features of EBV infection in Chongqing, China. We enrolled patients suspected of EBV-related diseases who were admitted to the First Affiliated Hospital of Chongqing Medical University between May 2013 and November 2022. Inclusion criteria were based on those who underwent EBV-specific immunofluorescence or plasma EBV-DNA testing. Among 13 584 inpatients, the overall seropositivity rates for EBNA-1-IgG, EBV-VCA-IgM, EBV-EA-IgG, EBV-EA-IgA, EBV-VCA-IgA, and EBV-DNA were 91.89%, 7.22%, 18.00%, 16.19%, 30.78%, and 18.00%, respectively. The seropositivity rate for EBNA-1-IgG steadily increased with age. The seropositivity rate for VCA-IgM, an indicator of acute EBV infection, was highest in patients aged 11-20 years at 26.41%, decreasing to 2%-6% in older patients. Additionally, among 205 outpatients, the EBV-DNA positivity rate was 14.15%. In 3670 individuals from health check-up centers, the seropositivity rates for EBV-EA-IgA and EBV-VCA-IgA were 11.96% and 28.09%, respectively, and the EBV-DNA positivity rate was 11.92%, all of which were lower than those in inpatients. Among the 762 EBV-DNA positive inpatients, adults aged 31-40 years were the least affected, with a seropositivity rate of 12.00%, which increased with age. The most common diseases associated with primary EBV infection were infectious mononucleosis (IM) (35.49%), followed by EBV infection (14.15%) and pneumonia (7.19%). The most common diseases associated with EBV reactivation were pneumonia (16.80%), nasopharyngeal carcinoma (NPC) (11.02%), and autoimmune diseases (7.04%). Patients with hemophagocytic lymphohistiocytosis (HLH) had the highest viral load, significantly higher than those with NPC, pneumonia, and liver cirrhosis. This large-scale retrospective study explores the epidemiological characteristics and disease spectrum of EBV infection across all age groups. The findings contribute to the improvement of diagnostic and management strategies for EBV infection.

Concurrent Chemoradiotherapy versus Radiotherapy Alone in the Treatment of Stage II and T3N0M0 Nasopharyngeal Carcinoma: A Systematic Review and Meta-Analysis

AimsThe efficacy of concurrent chemoradiotherapy (CCRT) for Stage II and T3N0 nasopharyngeal carcinoma (NPC), particularly during the shift from two-dimensional conventional radiotherapy (2DCRT) to intensity-modulated radiotherapy (IMRT) is debated.Therefore this study aims to systematically evaluate and meta-analyze survival benefits of CCRT versus radiotherapy alone for Stage II and T3N0 NPC, stratified by radiotherapy techniques. Materials and methodsAs of April 1, 2024, we conducted an exhaustive literature search across databases such as PubMed, Embase, Cochrane Library, and Web of Science, with the aim of identifying and screening studies that compare the efficacy of CCRT versus radiotherapy alone in the treatment of Stage II and T3N0 NPC. ResultsA total of 10 studies encompassing 5015 patients were included in this comprehensive analysis. The findings indicate that, apart from progression-free survival (PFS), CCRT did not improve survival outcomes, including overall survival (OS), distant metastasis-free survival (DMFS), local recurrence-free survival (LRRFS), and failure-free survival (FFS), with all P values exceeding 0.05. Concurrently, the incidence of grade ≥3 adverse events associated with CCRT was significantly elevated (odds ratio [OR] = 3.77, 95% confidence interval [CI] = 2.75–5.15, P < 0.0001). Subgroup analysis revealed that, compared with RT, the combination of 2DCRT with concurrent chemotherapy significantly improved OS (hazard ratio [HR] = 0.57, 95% CI = 0.46–0.71, P < 0.00001), PFS (HR = 0.65, 95% CI=0.53–0.78, P < 0.00001), DMFS (HR = 0.54, 95% CI = 0.37–0.79, P = 0.002), and LRRFS (HR = 0.63, 95% CI = 0.49–0.82, P = 0.0005). In contrast, the combination of IMRT with concurrent chemotherapy failed to demonstrate improvements in OS, PFS, DMFS, or LRRFS, with all P values exceeding 0.05. ConclusionIn contrast with RT, CCRT did not enhance survival in stage II and T3N0 NPC patients, yet caused more adverse reactions. 2DCRT combined with concurrent chemotherapy significantly improved OS, PFS, DMFS, and LRRFS, while IMRT with concurrent chemotherapy showed no clinical benefits.

Role of PET/CT in improving the cost effectiveness of nimotuzumab in nasopharyngeal carcinoma.

This study aims to use the maximum standardised uptake value (SUVmax) of 18F-fluorodeoxyglucose positron emission tomography to improve the cost effectiveness of nimotuzumab (NTZ) in locoregionally advanced nasopharyngeal carcinoma (LA-NPC). Two hundred and forty-eigh patients with LA-NPC, who met the inclusion criteria, were recruited from January 2012 to June 2019. The survival differences and independent factors were assessed using the Kaplan-Meier method and by Cox proportional hazards regression analysis. A cost effectiveness analysis was performed. The optimal cut-off value for SUVmax was 12.92. Multivariable analysis indicated a prognostic significance of overall survival (OS) for the NTZ treatment (p = 0.023) and SUVmax (p = 0.014). The exploratory subgroup survival analysis revealed that LA-NPC patients with SUVmax > 12.92 treated with concurrent chemoradiotherapy (CCRT) and NTZ had a significantly improved 3-year OS compared to patients treated with CCRT alone (96.2 vs 73.2%, p = 0.047). Furthermore, the treatment cost for NTZ was $6,317.61. This incurred an additional cost of $274.68 for every 1% increase in OS. For patients with LA-NPC with SUVmax > 12.92, the addition of NTZ to CCRT can improve OS and is cost effective.

Single-cell transcriptome analysis reveals evolving tumour microenvironment induced by immunochemotherapy in nasopharyngeal carcinoma.

Combinatory therapeutic strategy containing immunochemotherapy as part of induction therapy components is one of the current trends in the treatment of high-risk metastatic locally advanced nasopharyngeal carcinoma (NPC). However, the mechanism underlying the heterogeneity of response at the single-cell level has not been underexplored. 18 bulks and 11 single-cell RNA sequencing from paired before-treatment and on-treatment samples in patients with treatment-naive high-risk metastatic locally advanced NPCs were obtained. Following quality control, a total of 87191 cells were included in the subsequence bioinformatics analysis. Immunochemotherapy was associated with on-treatment tumour microenvironment (TME) remodelling, including upregulation of anti-TMEs signatures, downregulation of pro-TMEs signatures, reversing CD8+ T exhaustion, and repolarizing proinflammatory TAMs. For the patients achieving a complete response, the cytotoxic activity of CD8+ T cells was stimulated and more interferon-gamma was provided, which would be the key for TAMs proinflammatory repolarization and eventually promote the CD8+ T cells maturation in turn. Among patients who did not reach complete response, differentiation and hypoxia signatures for endothelial cells were elevated after therapy. These patients exhibited higher levels of immune checkpoint genes in malignant cells at the baseline (before treatment), and decreased tumour antigen presentation activity, which may underlie the resistance mechanism to therapy. This study pictures a map of TME modulation following immunochemotherapy-based combination induction therapy and provides potential future approaches. Immunochemotherapy remodeled T cell phenotypes. For the patients achieving complete response, more interferon gamma was provided by CD8+ T cells after therapy, which would be the key for TAMs pro-inflammatory repolarization and eventually promote the CD8+ T cells maturation in turns. Among patients who did not reach complete response, malignant cells exhibited higher level of immune checkpoint genes before therapy, and decreased tumor antigen presentation activity, which may underlie the resistance mechanism to therapy.

Chronic Invasive Fungal Sinusitis Mimicking Malignancy Post-Radiotherapy: A Case Report.

Invasive fungal sinusitis is a life-threatening form of fungal rhinosinusitis. Due to the aggressive clinical presentation and radiological appearance, there is diagnostic difficulty in differentiating invasive fungal sinusitis from a malignant process. This is even more challenging in oncological patients who have undergone previous head and neck radiotherapy, due to possibility of a recurrence of primary malignancy and radiation-induced neoplasms. We report a rare case of invasive fungal sinusitis mimicking a malignancy in a post-radiotherapy patient.Our patient was a 68-year-old male, 25-years post-radiotherapy for nasopharyngeal carcinoma. He presented with a 3-month history of purulent sputum and right facial paraesthesia. Magnetic resonance imaging showed an irregular destructive enhancing mass of the greater wing of right sphenoid and pterygoid bone with extensive extension into nearby structures. In view of extensive local and bony invasion, and a history of radiotherapy, initial suspicions were that of primary malignancy, specifically radiation-induced sarcoma, and recurrence of nasopharyngeal carcinoma. He underwent transpterygoid biopsy of the lesion, and histopathology demonstrated Aspergillus species, with no malignancy identified.Our report highlights the diagnostic difficulties in the post-radiotherapy cancer patient presenting with symptoms suggestive of aggressive sino-nasal disease. Invasive fungal sinusitis closely mimics the clinical and radiological findings of several neoplastic processes. We discuss the clinical and radiological characteristics of pathologies that may mimic invasive fungal sinusitis. Histological examination remains the gold standard for diagnosis, and early fungal staining is crucial. Furthermore, one should not presume the initial histopathological diagnosis to be confirmatory of isolated fungal disease. Repeat radiological investigations for disease resolution and histopathologic re-evaluation if required should be performed, keeping in mind possibility of coexisting malignancy.

73 - Residual/recurrent nasopharyngeal carcinoma and nasopharyngeal lymphoma: Dual-parameters differentiation based on apparent diffusion coefficient and standardized uptake value of 18F-FDG PET/MRI

73 - Residual/recurrent nasopharyngeal carcinoma and nasopharyngeal lymphoma: Dual-parameters differentiation based on apparent diffusion coefficient and standardized uptake value of 18F-FDG PET/MRI

A phase 2 trial of gemcitabine plus toripalimab for cisplatin-ineligible patients with recurrent or metastatic nasopharyngeal carcinoma

Cisplatin is a cornerstone chemotherapy for nasopharyngeal carcinoma (NPC); however, certain patients are ineligible for cisplatin-based regimens. This phase 2 trial (NCT04405622) evaluated the efficacy and safety of gemcitabine and toripalimab in previously untreated patients with recurrent or metastatic NPC who were either ineligible for cisplatin or had experienced severe adverse events from prior cisplatin-based treatments. Patients received gemcitabine (1,000mg/m2) and toripalimab (240mg) every three weeks for six cycles, followed by toripalimab monotherapy for up to two years. The primary endpoint was the incidence of grade ≥3 adverse events, while secondary endpoints included objective response rate (ORR) and overall survival (OS). Of 30 screened patients, 21 were enrolled. No treatment-related fatalities occurred, with the most frequent adverse events being headache and nausea. The ORR was 61.9%, coupled with a disease control rate of 100%. Overall, gemcitabine plus toripalimab demonstrated low toxicity and promising efficacy for this specific patient cohort.

ABO blood types and head and neck cancer: a systematic review with meta-analysis of observational studies

ObjectivesThis research aims to explore the correlation between ABO blood groups and neoplasms in the head and neck region, specifically investigating the susceptibility of different blood groups to tumours.DesignSystematic review...

Synthesis of New Fluorinated Tubastatin A Derivatives Based on Cyclopentane/Cyclohexane with Good Anti‐tumor Activity in Vitro

AbstractTwo series of novel fluorinated Tubastatin A derivatives based on cyclopentane or cyclohexane substitution were first time synthesized by 5 steps at high yield. The influence of the cycloalkanes substituted N‐methylpiperidine and/or fluorinated group on the cap group of Tubastatin A for the in vitro anti‐tumor activity of seven different tumor cell lines (human hepatoma cells Bel7402 and HepG2, human nasopharyngeal carcinoma cells CNE2 and SUNE1, human breast cancer cells MDA‐MB‐231 and MCF‐7, and human pancreatic cancer cells SW1990) was investigated. Compared with Tubastatin A, these novel derivatives with fluorinated groups on the benzene ring of the cap group enhance activity, and modification of the N‐methylpiperidine to cycloalkanes of the cap group improves solubility. The most promising compound trifluoromethyl and cyclohexane substituted derivative, N‐hydroxy‐4‐((6‐(trifluoromethyl)‐1,2,3,4‐tetrahydro‐9H‐carbazol‐9‐yl)methyl) benza‐mide (6 h), had a wide range of anti‐tumor cell range, the IC50 value for human pancreatic cancer cell line SW1990 was 1.17 μM. Hence, fluorinated groups and cyclohexane result in a wide range of anti‐tumor cell range and good anti‐cancer activity.

P74-1 Case of nasopharyngeal carcinoma with intracranial extension presenting as an occult primary with bilateral neck masses

P74-1 Case of nasopharyngeal carcinoma with intracranial extension presenting as an occult primary with bilateral neck masses

236 - Developing a Traffic Light Protocol for Nasopharyngeal Carcinoma CBCT Escalation: To Improve Radiation Therapists’ Accuracy Rate of CBCT Escalation to Radiation Oncologists

236 - Developing a Traffic Light Protocol for Nasopharyngeal Carcinoma CBCT Escalation: To Improve Radiation Therapists’ Accuracy Rate of CBCT Escalation to Radiation Oncologists

A Randomised, Multicentre, Phase II Trial of Camrelizumab with or without Metastasis-directed Stereotactic Body Radiotherapy in Recurrent or Metastatic Nasopharyngeal Carcinoma

PurposeTo investigate the efficacy of metastasis-directed therapy (MDT) when added to camrelizumab (Cam) in patients with recurrent or metastatic nasopharyngeal carcinoma (R/M-NPC). MethodsWe conducted a randomised, controlled, multicentre, phase II trial in 3 centres from China (NCT04830267). Patients with R/M-NPC, without prior exposure to immunotherapy, who presented with ≥2 lesions, and at least 1 measurable lesion were randomised 1:1 to either Cam alone or Cam plus MDT (Cam+MDT). Patients randomised to the MDT group must have 1 lesion that is amendable to stereotactic body radiotherapy (SBRT) prescribed to 27Gy in 3 fractions every other day. Primary endpoint was objective response rate (ORR) of unirradiated lesions by RECIST v1.1. ResultsBetween April 2021 and August 2023, 39 patients were randomly assigned to receive either Cam (n=20) or Cam+MDT (n=19). 17/39 (43.6%) patients had oligometastatic disease (≤3 lesions); 18/39 (46.2%) had liver involvement; 3/39 (7.7%) had locoregional recurrent disease. ORR of unirradiated lesions did not differ between the treatment groups (26.3% [Cam+MDT] vs 30.0% [Cam], P=1.0). DCR of unirradiated lesions was 73.7% in the Cam+MDT group compared with 60.0% in the Cam group (P=0.571). After a median follow-up of 25.8 months, median progression-free survival was 9.3 (95% CI: 6.2-NR) months in the Cam+MDT group and 8.8 (95% CI: 3.3-NR) months in the Cam group (P=0.750). Exploratory analyses suggested a longer overall survival (OS) with Cam+MDT for patients with >3 lesions (HR 0.23 [95% CI: 0.07-0.77], P=0.009). G3 and above adverse events were comparable between the treatment groups (15.8% [Cam+MDT] vs 20.0% [Cam]). Overall rate of capillary proliferation was 17.9% (7/39) on the trial. ConclusionsOur study did not meet its primary endpoint of superior ORR of unirradiated lesions with the addition of MDT to Cam in patients with R/M-NPC.

Relationship between changes in nutritional status during treatment and overall survival of newly diagnosed nasopharyngeal carcinoma patients

PurposeThis study investigates the relationship between changes in nutritional status during treatment and overall survival in NPC patients. MethodUsing a prospective cohort design, the electronic health records of newly diagnosed NPC patients from a medical center in Taiwan (from January 1, 2018, to March 31, 2024) were analyzed. A total of 73 newly diagnosed NPC patients were tracked; nutritional indicators such as body mass index (BMI), prealbumin levels, and Patient-Generated Subjective Global Assessment (PG-SGA) scores were recorded at four time points: one week before treatment, the first week of treatment, and four and eight weeks after treatment began. ResultsThe study found that most patients experienced a decrease in BMI (B = -0.62, p < .001) and prealbumin levels (B = -0.79, p = .015) during treatment, although BMI remained in the overweight range and prealbumin stayed within normal levels. PG-SGA scores increased (B = 1.01, p < .001), indicating a shift from low to moderate nutritional risk. Univariate Cox regression analysis showed that the Charlson Comorbidity Index (HR=1.86, 95% CI: 1.38–2.51), NPC stage (HR=15.67, 95% CI: 2.07–118.61), treatment method (HR=2.96, 95% CI: 1.45–6.04), prealbumin (HR=2.95, 95% CI: 1.46–5.99), and PG-SGA score trajectories (HR=2.85, 95% CI: 1.27–6.40) were associated with overall survival. However, multivariate analysis revealed that the survival of NPC patients was only associated with CCI and NPC stage. ConclusionsThe study underscores the importance of monitoring nutritional status changes during treatment, particularly prealbumin and PG-SGA trajectories.

P109-7 Defining a group of oligometastatic nasopharyngeal carcinoma patients with improved survival outcomes

P109-7 Defining a group of oligometastatic nasopharyngeal carcinoma patients with improved survival outcomes

Overweight, obesity, and nasopharyngeal carcinoma risk: A case–control study in Oran, Algeria

Overweight, obesity, and nasopharyngeal carcinoma risk: A case–control study in Oran, Algeria

422 - Developing and validating a multi-omics prediction model for severe acute oral mucositis in nasopharyngeal carcinoma patients undergoing radiation therapy

422 - Developing and validating a multi-omics prediction model for severe acute oral mucositis in nasopharyngeal carcinoma patients undergoing radiation therapy

Fractal Analysis of Mandible in Panoramic Radiographs of Patients Received Radiotherapy for Nasopharyngeal Carcinoma

PurposeThis study aimed to assess the impact of radiotherapy on the internal structure complexity of mandibular cortical and trabecular bone and to determine the duration required for a return to healthy values post-radiotherapy. Materials and MethodsPanoramic radiographs from patients undergoing radiotherapy for nasopharyngeal carcinoma were analyzed before and after treatment. Four groups were formed based on post-radiotherapy radiography timing (0-6 months, 6-12 months, 12-24 months, and 24-36 months), comprising a total of 59 cases and 118 radiographs. Fractal analysis was conducted on four bilateral regions (ROI) in both trabecular and cortical bone on each radiograph. Additionally, measurements of inferior alveolar canal width and mandibular cortical width were performed. Mean and maximum radiation dose values to the mandible were measured, and their correlation with changes in fractal dimension, inferior alveolar canal width, and mandibular cortical width values was assessed. ResultsFractal dimension values in regions over trabecular bone showed a statistically significant decrease in all groups, although no significant difference was observed among the four groups. In ROI-4 from cortical bone, a significant fractal dimension decrease was noted in all groups except the 0-6 month group. The magnitude of fractal dimension decrease was higher in the 12-24 and 24-36 month groups compared to the 0-6 month group. inferior alveolar canal width and mandibular cortical width values significantly decreased post-radiotherapy in all groups, with a consistent decrease across the groups. ConclusionsRadiotherapy induces a reduction in the internal complexity of trabecular and cortical bone structures in the mandible. Osteoradionecrosis risk persists even three years post-radiotherapy, suggesting a cautious approach to interventional procedures on the bone.

Metachronous Second Primary in the Form of Nasopharyngeal Carcinoma Following Treatment of Small Cell Neuroendocrine Carcinoma of the Head and Neck: Dual Tracer PET/CT Findings Highlighting SSTR2 Expression and Its Theranostic Implications

AbstractPatients of head and neck squamous cell carcinoma (HNSCC) experience increased risk of developing second primary cancer (SPC) necessitating active surveillance during their disease course. SPCs are associated with poor prognosis and are the leading cause of long-term morbidity and mortality impacting survival of patients with HNSCC. Small cell neuroendocrine carcinoma (SmNEC) is a rare but aggressive neoplasm with poor prognosis and high risk of local recurrence and distant metastasis. We report an exceedingly rare case of nasopharyngeal carcinoma (NPC) presenting as a recurrence in the form of metachronous second primary to primary SmNEC 9 years after chemotherapy. The dual tracer positron emission tomography and computed tomography (PET/CT) imaging approach ([68Ga]Ga-DOTATATE-PET/CT with 18F-FDG-PET/CT) was explored in such metachronous NPCs, and the findings are illustrated with its potential for theranostic applications. NPC is a rare malignancy with significant geographical variations in incidence rates. Somatostatin receptor 2 (SSTR2) expression in NPC is well documented and can serve as a potential theragnostic marker in advanced NPC where the successful outcome is minimal with currently available treatment modalities.