Recurrent Nasopharyngeal Carcinoma Research Articles

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.

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.

RRFERV stabilizes TEAD1 expression to mediate nasopharyngeal cancer radiation resistance rendering tumor cells vulnerable to ferroptosis.

Long noncoding RNAs (lncRNAs) regulate various essential biological processes, including cell proliferation, differentiation, apoptosis, migration, and invasion. However, in nasopharyngeal carcinoma (NPC), the clinical significance and mechanisms of lncRNAs in malignant progression are unknown. RNA sequencing and bioinformatic analysis were used to determine the potential function of RRFERV (radiation-resistant but ferroptosis vulnerable), and its biological effects were investigated using in vitro and in vivo experiments. Western blotting, quantitative real-time reverse transcription PCR, RNA immunoprecipitation (RIP) assays, and flow cytometry detected RRFERV expression. Ferroptosis and lipid peroxidation were added to evaluate the relationship between it and radiotherapy resistance. LncRNA-RRFERV was both highly expressed in NPC tissues and radiation-resistant cells. RRFERV is associated with poor clinical outcomes of NPC patients and stabilizes TEAD1 by competitive binding with microRNA-615-5p and microRNA-1293. RRFERV-TEAD1 signaling axis leads to malignant progression and radiotherapy resistance of NPC. Furthermore, we observed that NPC radiotherapy resistance cells exist in a fragile oxidative stress equilibrium, which makes them more sensitive to ferroptosis inducers. Surprisingly, we found that RRFERV-TEAD1 signaling axis also plays a key role in mediating the lipid peroxidation levels of NPC radiotherapy resistance cells through transcriptional activation of ACSL4/TFRC. RRFERV serves as an independent prognostic factor in NPC. During the malignant progression of NPC caused by high expression of RRFERV, ferroptosis can be induced to effectively kill cancer cells and reverse the radiotherapy resistance of NPC cells, suggesting a potential treatment approach for recurrent and refractory NPC.

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.

Early recurrence as a pivotal event in nasopharyngeal carcinoma: identifying predictors and key molecular signals for survivors

PurposeThe duration of response to treatment is a significant prognostic indicator, with early recurrence (ER) often predicting poorer survival outcomes in nasopharyngeal carcinoma (NPC) survivors. This study seeks to elucidate the factors contributing to the onset of ER following radiotherapy in NPC survivors.MethodsThis investigation encompassed 2,789 newly diagnosed NPC patients who underwent radical intensity-modulated radiotherapy. Ordinal logistic regression analysis was employed to evaluate the independent predictors of earlier recurrence. A machine learning-based prediction model of NPC recurrence patterns was developed. Tumorous RNA-sequencing (in-house cohort: N = 192) and biological tipping point analysis were utilized to infer potential molecular mechanisms associated with ER.ResultsOur results demonstrated that ER within 24 months post-initial treatment was the optimal time frame for identifying early malignant progression in NPC survivors. The ER cohort (150 of 2,789, 5.38%) exhibited a notably short median overall survival of 48.6 months. Multivariate analyses revealed that male gender, T4 stage, local or regional residual disease, detectable pre- and post-radiotherapy EBV DNA, and the absence of induction chemotherapy were significant predictors of earlier recurrence. The machine learning-based predictive model further underscored the importance of tumor-related factors in NPC recurrence. Moreover, ER emerged as a pivotal stage in NPC progression, with 15 critical transition signals identified potentially associated with the negative modulation of the immune response.ConclusionsOur comprehensive analysis of NPC recurrence patterns has unveiled insights into the key factors driving ER and provided novel insights into potential early warning biomarkers and the mechanisms underlying NPC progression.

Comparative effectiveness and cost‐effectiveness of endoscopic nasopharyngectomy versus intensity‐modulated radiotherapy in the treatment of recurrent nasopharyngeal carcinoma: A microsimulation analysis

AbstractBackgroundNasopharyngeal carcinoma (NPC) is a significant health concern in southern China, like Guangdong and Hong Kong. This study aims to predict the effectiveness and cost‐effectiveness of two prevalent NPC treatments, intensity‐modulated radiotherapy (IMRT) and endoscopic nasopharyngectomy (ENPG).MethodsA microsimulation model was developed to project the long‐term outcomes of IMRT and ENPG, simulating 5000 patients with hypothetical locally recurrent NPC for each treatment option. The tumors of patients confined to the nasopharyngeal cavity, the post‐naris or nasal septum, the superficial parapharyngeal space, or the base wall of the sphenoid sinus. Analyses were performed from the healthcare system perspectives of Mainland China and the healthcare provider perspective of Hong Kong, with input parameters sourced from the existing literature and databases. The robustness of findings was evaluated through one‐way and probabilistic sensitivity analyses.ResultsFor DFS, ENPG showed a 29% reduction in risk with an HR of 0.71 (95% CI: 0.64–0.77) compared to IMRT. ENPG demonstrated a significant survival benefit in OS with an HR of 0.59 (95% CI: 0.54–0.65), equating to a 41% reduction in mortality risk. In Hong Kong, IMRT and ENPG yielded QALY gains of 4.59 and 6.29, respectively, with ENPG exhibiting an incremental cost‐effectiveness ratio (ICUR) of USD 13 057 per QALY. For Mainland China, ENPG denominated the IMRT and the ICUR was USD −1450 QALY. Probabilistic sensitivity analysis showed a 100% probability of ENPG being cost‐effective at the willingness‐to‐pay thresholds of USD 130 490 per QALY in Hong Kong and USD 12 741 per QALY in Mainland China.ConclusionThe analysis confirms that ENPG is more effective and cost‐effective than IMRT for treating recurrent NPC in both Hong Kong and Mainland China.

Alterations in nasal airflow and air conditioning after endoscopic nasopharyngectomy for recurrent nasopharyngeal carcinoma: a pilot computational fluid dynamics study

Endoscopic nasopharyngectomy represents a significant intervention for recurrent nasopharyngeal carcinoma (NPC). Various surgical techniques, including transnasal and transoral approaches, are employed. However, the impact of these procedures on nasal airflow dynamics is not well understood. This computational fluid dynamics (CFD) study aimed to investigate alterations in nasal airflow and air conditioning following endoscopic nasopharyngectomy. A 55-year-old male patient with recurrent NPC was selected, whose CT data were utilized for image reconstruction. A preoperative model and two postoperative models, including the transnasal and transoral approach models, were established. The airflow patterns and various CFD parameters were analyzed. In the postoperative models, the high-speed airflow went along the soft palate and into the nasopharyngeal outlet, and there was the low-speed turbulence in the expanded nasopharyngeal cavity. Compared to the preoperative model, the postoperative models exhibited reductions in surface-to-volume ratio, nasal resistance, airflow velocity and proportion of high wall shear stress regions in nasopharynx. The changing trends of nasopharyngeal air temperature and humidity in the preoperative and transoral models were consistent. The heating and humidification efficiency decreased in the transnasal model compared to the transoral model. The endoscopic nasopharyngectomy for recurrent NPC affects the nasal airflow and warming and humidification function. The transoral approach has less influence on aerodynamics of the upper airway compared to the transnasal approach. From a CFD perspective, the endoscopic nasopharyngectomy does not increase the risk of postoperative complications, including the empty nose syndrome and the carotid blowout syndrome.

1420: Prediction of necrosis based on deep learning for recurrent nasopharyngeal carcinoma radiotherapy

1420: Prediction of necrosis based on deep learning for recurrent nasopharyngeal carcinoma radiotherapy

Maintenance treatment with oral anticancer agents after first-line chemotherapy in patients with recurrent or metastatic nasopharyngeal carcinoma: a systematic review and meta-analysis.

Maintenance therapy following first-line chemotherapy is of particular significance in patients diagnosed with recurrent or metastatic nasopharyngeal carcinoma (NPC). We conducted a meta-analysis to investigate the impact of maintenance therapy (MT) on the survival prognosis of individuals with recurrent or metastatic NPC. The databases Embase, PubMed, and the Cochrane Library were thoroughly searched in a comprehensive manner. Prospective studies of MT for recurrent or metastatic NPC are required. Study endpoints included progression-free survival (PFS) and overall survival (OS). Two randomized controlled clinical trials, with a total of 294 participants, were analyzed. The maintenance therapy group consisted of 140 participants, while the remaining participants were in the non-maintenance therapy (non-MT) group. The MT group showed a notable enhancement in PFS compared to the non-MT group, with a hazard ratio(HR) of 0.44 and a 95% Confidence interval [CI] of 0.34-0.58 (p < 0.0001). Overall survival was also significantly improved (HR0.42, 95% CI 0.30-0.58; p < 0.0001). The incidence of grade 3 or 4 side effects in the MT group was leukopenia (2.9%), thrombocytopenia (0.7%), and anemia (4.3%), hand-foot syndrome (5.8%), and thrombocytopenia (0.7%). oral mucositis (1.5%), and nausea and vomiting (2.2%). Maintenance therapy with S-1 (tegafur/gimeracil/oltiracetam) or capecitabine following first-line chemotherapy significantly enhanced OS and PFS in patients with recurrent or metastatic nasopharyngeal carcinoma, while exhibiting minimal incidence of grade 3-4 side effects.

ADAR1-regulated miR-142-3p/RIG-I axis suppresses antitumor immunity in nasopharyngeal carcinoma

Following the initial treatment of nasopharyngeal carcinoma (NPC), tumor progression often portends an adverse prognosis for these patients. MicroRNAs (miRNAs) have emerged as critical regulators of tumor immunity, yet their intricate mechanisms in NPC remain elusive. Through comprehensive miRNA sequencing, tumor tissue microarrays and tissue samples analysis, we identified miR-142-3p as a significantly upregulated miRNA that is strongly associated with poor prognosis in recurrent NPC patients. To elucidate the underlying molecular mechanism, we employed RNA sequencing, coupled with cellular and tissue assays, to identify the downstream targets and associated signaling pathways of miR-142-3p. Our findings revealed two potential targets, CFL2 and WASL, which are directly targeted by miR-142-3p. Functionally, overexpressing CFL2 or WASL significantly reversed the malignant phenotypes induced by miR-142-3p both in vitro and in vivo. Furthermore, signaling pathway analysis revealed that miR-142-3p repressed the RIG-I-mediated immune defense response in NPC by inhibiting the nuclear translocation of IRF3, IRF7 and p65. Moreover, we discovered that ADAR1 physically interacted with Dicer and promoted the formation of mature miR-142-3p in a dose-dependent manner. Collectively, ADAR1-mediated miR-142-3p processing promotes tumor progression and suppresses antitumor immunity, indicating that miR-142-3p may serve as a promising prognostic biomarker and therapeutic target for NPC patients.

Gemcitabine, capecitabine, and tislelizumab in recurrent/metastatic nasopharyngeal carcinoma following prior anti-PD-1 therapy failure: A retrospective study

PurposeTo evaluate the effectiveness and safety of low-dose gemcitabine and metronomic capecitabine in combination with tislelizumab for patients with recurrent or metastatic nasopharyngeal carcinoma (RM-NPC) who have previously received other anti-PD-1 therapies. MethodsThis retrospective, observational study included patients with RM-NPC who had prior treatment with anti-PD-1 therapy and subsequently received tislelizumab along with low-dose gemcitabine and metronomic capecitabine between March 2019 and August 2023. Progression-free survival (PFS) was estimated using the Kaplan-Meier method. ResultsAmong 25 eligible patients, 8 (20%) achieved a complete response (CR). The objective response rate (ORR) was 68%, and the disease control rate (DCR) was 80%. The 1-year PFS rate was 78%. All patients experienced treatment-related adverse events, which were all grade 1 or 2. ConclusionThe combination of tislelizumab with low-dose gemcitabine and metronomic capecitabine demonstrated promising antitumor effectiveness in RM-NPC patients who had failed previous anti-PD-1 therapy, with a manageable safety profile.

Safety, tolerability, and immunogenicity of WGc-043 in subjects with EBV-positive cancers: Results from an investigator-initiated trial.

139 Background: The Epstein-Barr virus (EBV) persists and spreads after infection in humans, leading to the occurrence and metastasis of a variety of cancers, posing great challenges in the treatment of cancer.. Conventional cancer therapies tend to have limited success and significant side effects. Therefore, there is an urgent need to develop more safe and efficient treatments such as innovative mRNA vaccines, which provide a new approach to cancer immunotherapy. WGc-043, an mRNA vaccine targeting EBV-positive tumor associated antigens, was evaluated for safety, tolerability, and immunogenicity in a prospective, single-center, investigator-initiated study. Methods: The study included 12 patients aged ≥18 with EBV-positive recurrent or metastatic nasopharyngeal carcinoma. Eligibility criteria included at least one measurable lesion, ECOG performance status 0-1, expected survival greater than three months, and no autoimmune disease. Participants were divided into three dose cohorts (25 μg, 50 μg, 100 μg) and received five administrations followed by optional continued monthly treatment of WGc-043 by intramuscular injection. The study assessed safety by adverse event monitoring, immune response based on the peripheral blood and tumor tissue sample analysis and efficacy according to imaging guidelines and irRECIST version 1.1. Results: The study results demonstrated that WGc-043 had a favorable safety profile with only grade 1 or 2 adverse events and fever (4/12) reported as the most common adverse event. Notably, two patients achieved partial response (PR) and five patients had stable disease (SD), highlighting the potential clinical efficacy of WGc-043. In addition, most (91.7%) subjects showed a significant reduction in plasma EBV DNA levels after administration. Immunogenicity analysis using IFN-γ ELISpot showed that 8 (66.7%) of the 12 enrolled patients developed strong specific immune responses against EBV-associated antigens, indicating that WGc-043 is a potent immunotherapy. Conclusions: This exploratory study underscores the safety and potential efficacy of WGc-043 as an mRNA vaccine for EBV-associated cancers, demonstrating its ability to induce specific immune responses and achieve substantial disease control in a challenging patient population, although further studies in larger clinical trials are needed. These results not only support the advancement of WGc-043 as a candidate for immunotherapy in EBV-positive cancers, but also highlight the translational potential of mRNA vaccine technology in the oncology landscape. Clinical trial information: NCT05714748 . [Table: see text]

Establishment of a protocol for rapidly expanding Epstein–Barr-virus-specific cytotoxic T cells with enhanced cytotoxicity

BackgroundLytic Epstein–Barr virus (EBV) infection plays a major role in the pathogenesis of nasopharyngeal carcinoma (NPC). For patients with recurrent or metastatic NPC and resistant to conventional therapies, adoptive cell therapy using EBV-specific cytotoxic T cells (EBV-CTLs) is a promising option. However, the long production period (around 3 to 4 weeks) and low EBV-CTL purity (approximately 40% of total CD8 T cells) in the cell product limits the application of EBV-CTLs in clinics. Thus, this study aimed to establish a protocol for the rapid production of EBV-CTLs.MethodsBy culturing peripheral blood mononuclear cells (PBMCs) from EBV-seropositive donors with EBV-specific peptides and interleukin (IL)-2, IL-15, and interferon α (IFN-α) for 9 days, we identified that IL-15 can enhance IL-2-mediated CTL activation and significantly increase the yield of CTLs.ResultsWhen IFN-α was used in IL-2/IL-15-mediated CTL production from days 0 to 6, the productivity of EBV-CTLs and EBV-specific cytotoxicity significantly were reinforced relative to EBV-CTLs from IL-2/IL-15 treatment. Additionally, IFN-α-induced production improvement of virus-specific CTLs was not only the case for EBV-CTLs but also for cytomegalovirus-specific CTLs.ConclusionWe established a novel protocol to rapidly expand highly pure EBV-CTLs from PBMCs, which can produce EBV-CTLs in 9 days and does not require feeder cells during cultivation.

Failure patterns and individualized treatment plans of reirradiation for inoperable locally recurrent nasopharyngeal carcinoma

Re-irradiation with intensity-modulated radiotherapy (IMRT) remains the primary treatment modality for inoperable locally recurrent nasopharyngeal carcinoma (NPC). However, the rate of radiation-related late adverse effects is often substantially high. Therefore, we aimed to explore failure patterns and individualized treatment plans of re-irradiation for inoperable locally recurrent NPC. Ninety-seven patients who underwent IMRT were retrospectively analyzed. Sixty-two patients had clinical target volume of recurrence (rCTV) delineated, and thirty-five patients had only gross tumor volume of recurrence (rGTV) delineated. Twenty-nine patients developed second local failures after re-irradiation with IMRT (28 cases available). Among those patients, 64.3% (18/28) of patients and 35.7% (10/28) developed in-field or out-field, respectively. No statistical correlation was observed between target volume (rGTV or rCTV) and the local recurrence rate, local failure patterns, grade ≥ 3 toxicity, and survival. Multivariate analysis showed that recurrent T (rT) stage (HR 2.62, P = 0.019) and rGTV volume (HR 1.73, P = 0.037) were independent prognostic factors for overall survival (OS). Risk stratification based on rT stage and rGTV volume revealed that low risk group had a longer 3-year OS rate (66.7% vs. 23.4%), lower total grade ≥ 3 toxicity (P = 0.004), and lower re-radiation associated mortality rates (HR 0.45, P = 0.03) than high risk group. This study demonstrates that the delineation of rCTV may not be beneficial for re-irradiation using IMRT in locally recurrent NPC. Patients with low risk were most suitable for re-irradiation, with maximizing local salvage and minimizing radiation-related toxicities. More precise and individualized plans of re-irradiation are warranted.

Efficacy of endoscopic surgical management for recurrent nasopharyngeal carcinoma

Compared with re-radiotherapy or open surgery, endoscopic surgery for recurrent nasopharyngeal carcinoma has a better effect, which not only improves the overall survival rate, but also reduces serious complications, improves the quality of life and saves medical costs. With the advancement of modern surgical equipment and instruments, the deepening of anatomical research in the field of skull base, the improvement of surgical techniques and the development of multidisciplinary teamwork, the safety of endoscopic surgery and the rate of complete tumor resection will also increase. The indications for surgery are further expanded, and more patients with recurrent nasopharyngeal carcinoma benefit from endoscopic minimally invasive surgery. This article reviews the efficacy of endoscopic surgery for recurrent nasopharyngeal carcinoma, and then provides insights for the selection of clinical treatment strategies for recurrent nasopharyngeal carcinoma.

518 Local recurrence of nasopharyngeal carcinoma: re-irradiation, immunotherapy, surgery?

518 Local recurrence of nasopharyngeal carcinoma: re-irradiation, immunotherapy, surgery?

Early change of plasma Epstein-Barr virus DNA load and the viral lytic genome level could positively predict clinical outcome in recurrent or metastatic nasopharyngeal carcinoma receiving anti-programmed cell death 1 monotherapy

PurposePatients with recurrent or metastatic nasopharyngeal carcinoma (RM-NPC) have proven benefit from anti-programmed cell death 1 (anti-PD-1) monotherapy. Here, we retrospectively analyze the association of plasma Epstein-Barr virus (EBV) DNA load and tumor viral lytic genome with clinical outcome from 2 registered phase I trials.MethodsPatients with RM-NPC from Checkmate 077 (nivolumab phase I trial in China) and Camrelizumab phase I trial between March 2016 and January 2018 were enrolled. Baseline EBV DNA titers were tested in 68 patients and EBV assessment was performed in 60 patients who had at least 3 post-baseline timepoints of EBV data and at least 1 post-baseline timepoint of radiographic assessment. We defined “EBV response” as 3 consecutive timepoints of load below 50% of baseline, and “EBV progression” as 3 consecutive timepoints of load above 150% of baseline. Whole-exome sequencing was performed in 60 patients with available tumor samples.ResultsWe found that the baseline EBV DNA load was positively correlated with tumor size (spearman p < 0.001). Both partial response (PR) and stable disease (SD) patients had significantly lower EBV load than progression disease (PD) patients. EBV assessment was highly consistent with radiographic evaluation. Patients with EBV response had significantly improved overall survival (OS) than patients with EBV progression (log-rank p = 0.004, HR = 0.351 [95% CI: 0.171–0.720], median 22.5 vs. 11.9 months). The median time to initial EBV response and progression were 25 and 36 days prior to initial radiographic response and progression, respectively. Patients with high levels of EBV lytic genomes at baseline, including BKRF2, BKRF3 and BKRF4, had better progression-free survival (PFS) and OS.ConclusionIn summary, early clearance of plasma EBV DNA load and high levels of lytic EBV genes were associated with better clinical outcome in patients with RM-NPC receiving anti-PD-1 monotherapy.

Immune checkpoint inhibitor combined with chemotherapy versus chemotherapy alone in the first-line treatment for recurrent or metastatic nasopharyngeal carcinoma: a meta-analysis of random controlled trials.

Immune checkpoint inhibitor (ICI) monotherapy and chemotherapy (CT) have been used to treat recurrent or metastatic nasopharyngeal carcinoma (R/M-NPC), with demonstrated survival benefits and good safety. However, whether combination therapy is superior to CT alone remains unclear. We summarized the existing evidence comparing the effectiveness and toxicities of ICI combined with CT versus CT alone. Online databases was conducted for eligible randomized controlled trials (RCTs) published up to November 1, 2023. Progression-free survival (PFS) and overall survival (OS) were the primary endpoint. Objective response rates (ORRs) and adverse events (AEs) were the secondary endpoint. Three randomized controlled trials (Capture-1st, JUPITER-02, and RATIONALE-309) were included. First-line ICI therapy combined with CT showed significant improvement in PFS (hazard ratio[HR], 0.53; 95% confidence interval[CI]: 0.44-0.64), OS (HR, 0.63;95%CI: 0.49-0.81) and ORRs (odds ratio[OR], 1.79;95%CI: 1.30-2.46), when compared with CT alone. AEs ≥ grade 3 during treatment and treatment-related deaths were not significantly different between the two groups. In patients with R/M-NPC, ICI therapy combined with CT showed improved ORRs, PFS, and OS, with similar safety as CT alone.

Nab-paclitaxel, cisplatin, and capecitabine versus cisplatin and gemcitabine as first line chemotherapy in patients with recurrent or metastatic nasopharyngeal carcinoma: randomised phase 3 clinical trial

ObjectiveTo compare the effectiveness and safety of nab-paclitaxel, cisplatin, and capecitabine (nab-TPC) with gemcitabine and cisplatin as an alternative first line treatment option for recurrent or metastatic nasopharyngeal carcinoma.DesignPhase 3,...

Potential causal links of long-term exposure to PM2.5 and its chemical components with the risk of nasopharyngeal carcinoma recurrence: A 10-year cohort study in South China.

There is a lack of evidence from cohort studies on the causal association of long-term exposure to ambient fine particulate matter (PM2.5) and its chemical components with the risk of nasopharyngeal carcinoma (NPC) recurrence. Based on a 10-year prospective cohort of 1184 newly diagnosed NPC patients, we comprehensively evaluated the potential causal links of ambient PM2.5 and its chemical components including black carbon (BC), organic matter (OM), sulfate (SO4 2-), nitrate (NO3 -), and ammonium (NH4 +) with the recurrence risk of NPC using a marginal structural Cox model adjusted with inverse probability weighting. We observed 291 NPC patients experiencing recurrence during the 10-year follow-up and estimated a 33% increased risk of NPC recurrence (hazard ratio [HR]: 1.33, 95% confidence interval [CI]: 1.02-1.74) following each interquartile range (IQR) increase in PM2.5 exposure. Each IQR increment in BC, NH4 +, OM, NO3 -, and SO4 2- was associated with HRs of 1.36 (95%CI: 1.13-1.65), 1.35 (95%CI: 1.07-1.70), 1.33 (95%CI: 1.11-1.59), 1.32 (95%CI: 1.06-1.64), 1.31 (95%CI: 1.08-1.57). The elderly, patients with no family history of cancer, no smoking history, no drinking history, and those with severe conditions may exhibit a greater likelihood of NPC recurrence following exposure to PM2.5 and its chemical components. Additionally, the effect estimates of the five components are greater among patients who were exposed to high concentration than in the full cohort of patients. Our study provides solid evidence for a potential relationship between long-term exposure to PM2.5 and its components and the risk of NPC recurrence.