OBJECTIVE: This study was designed to assess the efficacy and safety of cadonilimab monotherapy, a first-in-class, bi-specific PD-1/CTLA-4 antibody, in patients with previously treated recurrent or metastatic nasopharyngeal carcinoma (R/M-NPC).
METHODS: This multicenter, open-label, single-arm, phase II clinical trial enrolled patients with R/M-NPC who had failed first-line platinum-based chemotherapy and second-line single agent or combined chemotherapy, and immunotherapy-naive. Patients received cadonilimab for 6 mg/kg once every 2 weeks (Q2W). The primary endpoint was objective response rate (ORR) in full analysis set (FAS) assessed by investigators according to RECIST v.1.1. The secondary endpoint included progression-free survival (PFS), overall survival (OS), duration of response (DoR), time to response (TTR) and safety.
RESULTS: A total of 23 patients were assessed. The median time from first dose to data cutoff was 16.56 (range, 0.8-25.2) months. ORR was 26.1 % (95 %CI:10.2-48.4). The ORR were 44.4 % (95 %CI: 13.7-78.8) and 14.3 % (95 %CI:1.8-42.8) in patients with tumor PD-L1 expression ≥50 % and <50 %, respectively. ORR was achieved in 40.0 % (95 %CI:12.2-73.8) of patients with EBV-DNA level <4000 IU/ml (n = 10) and 15.4 % (95 %CI:1.9-45.4) of those with ≥4000 IU/ml. The median PFS was 3.71 months (95 %CI: 1.84-9.30). respectively. Median OS was not reached, and the 12-month OS rate was 79.7 % (95 % CI:54.5-91.9). Only two patients (8.3 %) experienced Grade ≥3 treatment-related adverse events (TRAEs) with hypothyroidism (30.4 %), rash (21.7 %) and pruritus (21.7 %) being the most prevalent TRAEs.
CONCLUSIONS: Cadonilimab monotherapy demonstrated a promising efficacy and manageable toxicity in patients with previously treated R-M/NPC and provide an efficacious salvage treatment option.

Nasopharyngeal carcinoma (NPC) is the most prevalent head and neck cancer in Indonesia, with 100% Epstein-Barr virus (EBV) infection in tumor cells. NPC is rare in the Netherlands. The involvement of EBV in NPC pathogenesis is reflected by early onset aberrant IgA antibody responses to various EBV proteins. Screening for elevated EBV-IgA levels is proposed for NPC risk assessment in endemic countries but is poorly studied in nonendemic regions. This study analyzed the overall diversity (immunoblot) as well as the prevalence and normalized levels of IgA responses to immunodominant peptide epitopes of EBV proteins VCA P18, EBNA 1, and Zebra (Zta) (N-terminus, P 125, P 130, full-length recombinant Zebra) in Indonesian (n=50) and Dutch (n=50) patients with NPC. The results confirmed that elevated levels of IgA-VCA P18 and IgA-EBNA 1 were found in both NPC populations, but that IgA-Zta was more variable. IgA-Zta responses were more pronounced in Indonesian NPC cases, reflecting more frequent EBV reactivation overall. IgA-VCA P18 and IgA-EBNA are independent tumor markers and are both necessary for NPC risk assessment. Overall, these results confirmed the diagnostic benefit of combined IgA-VCA P18/-EBNA 1 testing for NPC risk assessment in endemic and nonendemic populations.

Epstein Barr Virus (EBV) is implicated in the carcinogenesis of nasopharyngeal carcinoma (NPC) and currently associated with at least 1% of global cancers. The differential prognosis analysis of NPC in EBV genotypes remains to be elucidated. Medical, radiological, pathological, and laboratory reports of 146 NPC patients were collected retrospectively over a 6-year period between 2015 and 2020. From the pathology archives, DNA was extracted from tumor blocks and used for EBV nuclear antigen 3C (EBNA-3C) genotyping by nested polymerase chain reaction (PCR). We found a high prevalence of 96% of EBV infection in NPC patients with a predominance of genotype I detected in 73% of NPC samples. Histopathological examination showed that most of the NPC patients were in the advanced stages of cancer: stage III (38.4%) or stage IV-B (37.7%). Only keratinized squamous cell carcinoma was significantly higher in EBV negative NPC patients compared with those who were EBV positive (OR = 0.01, 95%CI = (0.004-0.32; p = 0.009)), whereas the majority of patients (91.8%) had undifferentiated, non-keratinizing squamous cell carcinoma, followed by differentiated, non-keratinizing squamous cell carcinoma (7.5%). Although NPC had metastasized to 16% of other body sites, it was not associated with EBV infection, except for lung metastasis. A statistically significant reverse association was observed between EBV infection and lung metastasis (OR = 0.07, 95%CI = (0.01-0.51; p = 0.008)). Although 13% of NPC patients died, the overall survival (OS) mean time was 5.59 years. Given the high prevalence of EBV-associated NPC in our population, Saudi could be considered as an area with a high incidence of EBV-associated NPC with a predominance of EBV genotype I. A future multi-center study with a larger sample size is needed to assess the true burden of EBV-associated NPC in Saudi Arabia.

BACKGROUND: Numerous clinical studies have validated plasma EBV DNA as a reliable biomarker for nasopharyngeal carcinoma (NPC) screening, tumor load monitoring, and prognosis prediction in endemic regions. However, the clinical relevance of plasma EBV DNA as a biomarker for NPC in non-endemic areas is still unclear.
METHODS: The pretreatment plasma EBV DNA of 1405 newly diagnosed NPC patients from three major regional hospitals in non-endemic areas were analyzed retrospectively. The medical records of 244 age- and gender-matched healthy individuals were reviewed. EBV DNA was detected using Polymerase Chain Reaction (PCR). Based on the baseline of 400 and 0 copies/mL, the distribution characteristics of the pretreatment EBV DNA load in different clinical stages and geographic regions were analyzed. The diagnostic value of pretreatment plasma EBV DNA for NPC with two baselines was evaluated using the ROC curve.
RESULTS: NPC patients had a significantly higher pretreatment EBV DNA level than healthy controls (P＜0.001). Pretreatment EBV DNA was closely associated with clinical and TNM stages in non-endemic areas, as it was in endemic areas. However, when 400 copies/mL set as the detection baseline, the sensitivity and specificity for NPC diagnosis were 40.8 % and 100 %, respectively (AUC = 0.704, cut off = 200.5 copies/mL). This sensitivity was lower than that reported in endemic regions (41.5 % - 97.1 %). Lower sensitivity may result in false negatives, missing diagnoses during NPC screening. Further investigation revealed that 39.7 % (558/1405) of NPC patients had detectable EBV DNA and S amplification curves. Optimizing the detection limit to 0 copies/mL, the sensitivity could be improved to 80.5 % (AUC = 0.901).
CONCLUSIONS: In non-endemic areas, the clinical significance of plasma EBV DNA as a biomarker for NPC was restricted due to the low detection limit of 400 copies/mL. More efficient nucleic acid extraction and detection methods are needed to optimize the detection limit and increase the clinical application of plasma EBV DNA for NPC.

UNASSIGNED: Cancer of the nasopharynx has remarkable geographic and ethnic variation in incidence and outcomes globally. Recent advances in diagnostic and therapeutic technologies provide new opportunities for early detection and improved outcomes. This study aimed to determine the incidence, demographics, outcomes and time trends of cancer of the nasopharynx in Aotearoa New Zealand over the last 25 years.
UNASSIGNED: In a population-based, national registry cohort study of notifications of malignant neoplasms of the nasopharynx made to the New Zealand Cancer Registry between 1994 and 2018, age-specific and age-standardised incidence rates and survival outcomes were evaluated.
UNASSIGNED: 577 registrations of nasopharyngeal cancer from between 1994 and 2018 were analysed; median age at diagnosis 54 years; 72.4% male; 37.4% Asian, 24.3% New Zealand European, 25.3% Pacific peoples, 13.0% Māori. Age-standardised annual incidence remained low (<1/100,000 person-years) and stable from 1994 to 2018. Age-standardised incidence rates in Pacific peoples, Asian and Māori were 21 (95% CI 12.07-35.21)-, 17 (10.95-25.33)- and 4 (2.79-7.07)-fold higher, respectively, than New Zealand Europeans. Epstein-Barr virus-related morphologies predominated keratinising squamous cell carcinoma and not-otherwise-specified morphological subtypes. Ten-year overall survival rate for the cohort was 49.2% (95% CI 44.7-53.5). Older age at diagnosis (65-94 years), Māori or Pacific ethnicity, keratinising squamous cell carcinoma and distant disease were associated with shorter overall survival, whereas younger age at diagnosis (10-29 years), and Asian ethnicity were associated with longer survival.
UNASSIGNED: Aotearoa New Zealand has a distinct profile of nasopharyngeal cancer, with age, ethnicity and morphology among the main determinants of incidence and survival.
UNASSIGNED: None.

Background There is a dearth of research on successful interventions to improve nurse-physician communication (NPC). An important step is identifying what matters to bedside nurses and their perceptions of effective NPC communications and actions. Methods We conducted three focus groups with a total of 19 medical unit nurses across two hospitals in one academic medical center in the United States. Using a convenience sampling strategy, five to eight nurses voluntarily participated in each focus group. The recording was transcribed verbatim and two independent coders performed coding and resolved any discrepancies in codes. Qualitative content analysis was pursued to identify themes and associated quotes. Results The presence of direct communication between physicians and nurses was identified as the first theme and perceived by nurses as very important. Additional themes related to physician communication and attributes emerged including collegiality and respect (e.g., engaging nurses as partners in patient care), attentiveness and responsiveness (e.g., listening carefully and addressing concerns), and directness and support (e.g., backing nurses up in difficult situations). Effective NPC is further facilitated by organizational structure, relationship development separate from patient care, and consistent/timely use of technology. Conclusions Hospital bedside nurses provided valuable insight into improved physician communication and what attributes contribute to more effective NPC. Most importantly, they emphasized the significance of physicians in supporting them with difficult patients.

Niemann-Pick disease type C (NPC) is an autosomal recessive neurovisceral disease characterized by progressive neurodegeneration with variable involvement of multisystemic abnormalities. Crohn\'s disease (CD) is an inflammatory bowel disease (IBD) with a multifactorial etiology influenced by variants in NOD2. Here, we investigated a patient with plausible multisystemic overlapping manifestations of both NPC and CD. Her initial hospitalization was due to a prolonged fever and non-bloody diarrhea. A few months later, she presented with recurrent skin tags and anal fissures. Later, her neurological and pulmonary systems progressively deteriorated, leading to her death at the age of three and a half years. Differential diagnosis of her disease encompassed a battery of clinical testing and genetic investigations. The patient\'s clinical diagnosis was inconclusive. Specifically, the histopathological findings were directed towards an IBD disease. Nevertheless, the diagnosis of IBD was not consistent with the patient\'s subsequent neurological and pulmonary deterioration. Consequently, we utilized a genetic analysis approach to guide the diagnosis of this vague condition. Our phenotype-genotype association attempts led to the identification of candidate disease-causing variants in both NOD2 and NPC1. In this study, we propose a potential composite digenic impact of these two genes as the underlying molecular etiology. This work lays the foundation for future functional and mechanistic studies to unravel the digenic role of NOD2 and NPC1.

To evaluate the efficiency of local radiotherapy to metastatic lesions in patients with metastatic nasopharyngeal carcinoma (mNPC).
The overall survival was observed and compared for mNPC patients who received local radiotherapy versus nonradiotherapy to metastatic lesions by using the Kaplan-Meier method and Cox analysis.
One hundred and nine patients with NPC were involved in this study, with 61 (56.0%) received radiotherapy to metastatic sites and 48 (44.0%) did not receive radiotherapy to metastatic sites. The 2- and 5-year OS for patients who received local radiotherapy to metastatic lesions were 65.8% and 35.7%, and for patients who did not receive radiotherapy to metastatic lesions were 45.3% and 26.2%. The multivariable adjusted hazard radios for local radiotherapy versus nonradiotherapy to metastatic lesions were 0.482 (95% confidence interval is 0.278-0.834, p = 0.009).
Local radiotherapy to metastatic lesions might be a protective factor for patients with mNPC.

UNASSIGNED: To analyze the therapeutic effect and prognostic factors of nasopharyngeal carcinoma (NPC) patients with distant metastases at initial diagnosis receiving induction chemotherapy with intensity-modulated radiotherapy (IMRT).
UNASSIGNED: A total of 129 patients who underwent platinum-based induction chemotherapy followed by definitive IMRT with or without concurrent or adjuvant chemotherapy for newly diagnosed distant metastatic NPC in our center between March 2008 and November 2018 were retrospectively analyzed. 41 patients underwent local therapy for metastatic sites. Kaplan-Meier method was used to estimate survival rates, Log-rank test and Cox proportional hazards model were used to figure out independent prognostic factors of overall survival (OS).
UNASSIGNED: A total of 66 patients had been dead (median follow-up time, 51.5 months). The median overall survival (OS) time was 54.2 months (range, 7-136 months), and the 1-year, 2-year, 3-year, 5-year overall survival rates were 88.0%,71.0%,58.0%, and 47.0%. Multivariate analysis found that the factors correlated with poor overall survival were pre-treatment serum lactate dehydrogenase (SLDH) >180U/L, chemotherapy cycles<4, and M1 stage subdivision (M1b, single hepatic metastasis and/or multiple metastases excluding the liver; and M1c, multiple hepatic metastases). The 5-year OS rates for M1a, M1b and M1c were 62.6%,40.4% and 0%, respectively.
UNASSIGNED: Platinum-containing induction chemotherapy combined with IMRT seemed to be advantageous to prolong survival for some NPC patients with synchronous metastases at initial diagnosis. The independent factors to prognosticate OS were pre-treatment SLDH, number of chemotherapy cycles, and M1 subcategories. Prospective clinical trials are needed to confirm the result.

Aim: Given a lack of standard of care treatment for recurrent/metastatic nasopharyngeal carcinoma (R/M NPC), we assessed treatment patterns and overall survival in the real-world setting. Materials & methods: A retrospective chart review was conducted in patients who initiated first-line systemic therapy in Taiwan and South Korea between January 2012 and June 2013 with follow-up through December 2015. Results: Among 154 R/M NPC patients, all patients in Taiwan (n = 104) had distant metastases, whereas in South Korea (n = 50) 42% had distant metastases. Patients with distant metastases generally received systemic therapy only (71%) for whom median overall survival was 23 months (95% CI: 18-32). Conclusion: Prognosis in R/M NPC with distant metastases remains poor, underscoring the need for more efficacious treatments.
Lay abstract Nasopharyngeal carcinoma is an invasive cancer affecting the area behind the nose and above the back of throat. When this cancer returns or spreads to another part of the body, patients receive chemotherapy options with the goal of prolonging survival. To understand chemotherapy approaches used in everyday practice and their effectiveness, we conducted a review of medical records in Taiwan and South Korea. We studied 154 patients who started a first chemotherapy between January 2012 and June 2013 and followed patients through December 2015. Patients whose cancer spread in another part of their body generally received chemotherapy without radiation and lived 23 months on average. Our findings show that more effective treatments must be developed to help prolong survival.