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Background: Epstein–Barr virus (EBV) IgA serology for viral capsid antigen (VCA) and early antigen (EA) aids early detection of nasopharyngeal cancer (NPC), resulting in improved survival. We evaluated the diagnostic performance of a prefabricated immunofluorescent assay (IFA) for NPC screening in high‐risk individuals. Methods: Sera from 96 biopsy‐proven patients with NPC diagnosed at the outpatient clinic and 96 healthy family members were tested for EBV‐VCA IgA and EBV‐EA IgA using the prefabricated IFA from EUROIMMUN (EI) and the traditional immunofluorescence method. Results: The AUC of EI EBV‐VCA IgA and EBV‐EA IgA was 0.907 (95% confidence interval [CI]: 0.894–0.965) and 0.898 (95% CI: 0.848–0.947), respectively. Combined testing with the prefabricated assay at a threshold of VCA ≥1:320 or EA ≥1:10 showed 92.7% sensitivity and 81.2% specificity. Overall, the traditional EBV‐EA IgA assay demonstrated the best accuracy (sensitivity 91.7% and specificity 96.9%) at a threshold of ≥1:5. Conclusion: While the traditional IFA method was more accurate, the prefabricated IFA test kit can be a useful tool for NPC screening in high‐risk populations. [ABSTRACT FROM AUTHOR]

Background: This study evaluated health‐related quality of life (HRQoL) in the RATIONALE‐309 (NCT03924986) intent‐to‐treat (ITT) population and in a subgroup of patients with liver metastases. Methods: Patients were randomized 1:1 to tislelizumab + chemotherapy or placebo + chemotherapy. As the secondary endpoint, HRQoL was evaluated using seven selected scores from the EORTC QLQ‐C30 and QLQ Head and Neck Cancer module (QLQ‐H&N35). Results: Of 263 randomized patients in the ITT population (tislelizumab + chemotherapy n = 131, placebo + chemotherapy n = 132), 43% had liver metastases (tislelizumab + chemotherapy n = 56; placebo + chemotherapy n = 57). No differences in change in selected scores on the QLQ‐C30 from baseline to cycle 4 or cycle 8 were observed for the ITT or liver metastases subgroup. No differences in selected QLQ‐H&N35 scores were observed between the arms from baseline to cycle 4. In the ITT population and the liver metastases subgroup, a greater reduction from baseline to cycle 8 was observed in the tislelizumab + chemotherapy arm than the placebo + chemotherapy arm in QLQ‐H&N35 pain score. At cycle 8 in the liver metastases subgroup, the tislelizumab + chemotherapy arm experienced greater improvement in the QLQ‐H&N35 senses problems score than the placebo + chemotherapy arm. Differences in time to deterioration between arms were not observed. Conclusions: The current findings, along with improved survival and favorable safety, suggests that tislelizumab + chemotherapy represents a potential first‐line treatment for recurrent or metastatic nasopharyngeal cancer. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the outcomes and toxicities of adding neoadjuvant chemotherapy (NAC) to concurrent chemoradiotherapy (CCRT) in elderly (≥65 years) patients with locoregionally advanced nasopharyngeal carcinoma (LANPC, stage III‐IVa). Methods and Materials: Using an NPC‐specific database, 245 elderly patients with stage III‐IVa NPC, receiving CCRT +/− NAC, and an Adult Co‐morbidity Evaluation 27 (ACE‐27) score <2 were included. Recursive partitioning analysis (RPA) based on TNM stage and Epstein–Barr virus (EBV) DNA were applied for risk stratification. The primary end point was disease‐free survival (DFS). Results: Two risk groups were generated by the RPA model. In the high‐risk group (EBV DNA < 4000 copy/ml with stage IVa & EBV DNA ≥4000 copy/ml with stage III‐IVa), patients treated with NAC plus CCRT achieved improved 5‐year DFS rates compared to those who received CCRT alone (56.9% vs. 29.4%; p = 0.003). But we failed to observe the survival benefit of additional NAC in the low‐risk group (EBV DNA <4000 copy/ml with stage III). The most common severe acute toxic effects were leucopenia (46.8% vs. 24.4%) and neutropenia (43.7% vs. 20.2%) in the NAC plus CCRT group versus CCRT group with statistically significant differences. Conclusions: The addition of NAC to CCRT was associated with better DFS for the high‐risk group of elderly LANPC patients with ACE‐27 score <2. However, the survival benefit of additional NAC was not observed in low‐risk patients. [ABSTRACT FROM AUTHOR]

Background: Immunochemotherapy has become the first‐line treatment for initial diagnosed metastatic nasopharyngeal carcinoma (mNPC). Loco‐regional radiotherapy combined with systemic chemotherapy significantly improves the survival. However, the safety and efficacy of loco‐regional radiotherapy combined with immunochemotherapy remained unknown. Methods: Patients with de novo mNPC who received immunochemotherapy followed by loco‐regional radiotherapy were included from two cancer centers. Toxicity and treatment response were assessed using CTCAE 5.0 and RECIST 1.1, respectively. Overall survival (OS) and progression‐free survival (PFS) were analyzed using the Kaplan–Meier method. Results: From 2019 to 2021, a total of 16 patients were retrospectively analyzed. The median follow‐up was 28 months (range 14–47 months). No one died. One‐year, 2‐year, and 3‐year PFS rate was 93.8%, 58.4% and 50.1%, respectively. Radiotherapy‐related acute severe (grade 3 or higher) toxicity was dermatitis (1/16, 6.3%) and mucositis (2/16, 12.5%). Conclusions: Loco‐regional radiotherapy provided a promising efficacy with modest toxicity for patients with mNPC who received immunochemotherapy. [ABSTRACT FROM AUTHOR]

Objectives: To compare survival outcomes and toxic effects among patients with newly diagnosed nonmetastatic nasopharyngeal carcinoma (NPC) when treated with intensity‐modulated radiotherapy (IMRT) versus IMRT + carbon‐ion radiotherapy (CIRT). Methods: We performed a retrospective propensity score matching analysis (1:1) of patients treated with IMRT and IMRT + CIRT. Descriptive statistics were used to examine the baseline characteristics of the patients. Survival was estimated using the Kaplan–Meier method. Univariate and multivariable logistic regression analysis were used to identify the independent predictors of survival. We examined the association between risk factors and adverse events (AEs) using chi‐square tests. Cox model and logistic regression were used to analyze AEs. Results: Hundred and nine patients who received IMRT + CIRT were included and the median follow‐up time was 20.6 months (range: 4.6–82 months). There were no statistically significant differences in locoregional failure–free survival, distant metastasis–free survival, disease‐free survival, or overall survival between the two groups, but potentially better in IMRT + CIRT group (p > 0.05, respectively). Nodal boost was the only significant factor associated with LRFS and DFS on multivariable analysis. Thirty‐seven patients (34.0%) developed grade 3 acute OMs and no grade 4 acute OMs were observed in IMRT + CIRT group. All patients in IMRT + CIRT group developed grade 1 dermatitis; while in the match group, 76 patients developed grade 1 dermatitis, 27 patients developed grade 2 dermatitis, 5 patients developed grade 3 dermatitis, 1 patient developed grade 4 dermatitis. IMRT + CIRT treatment was associated with a significant trend of lower grades of OM and dermatitis (p < 0.05, respectively). Any severe (i.e., grade 3) chronic AEs, such as xerostomia, skin fibrosis, temporal lobe necrosis, osteoradionecrosis, or radiation‐induced optic neuropathy, was not observed. Conclusions: In this study, IMRT + CIRT was associated with significantly reduced acute toxicity burden compared with full course of IMRT, with excellent survival outcomes. Patients with persistent disease after treatment and treated with nodal boost had a worse outcome. More accurate assessments of IMRT + CIRT to primary nonmetastatic NPC patients will be imperative. [ABSTRACT FROM AUTHOR]

Background: The prevalence of gastroesophageal reflux disease (GERD) and laryngopharyngeal reflux (LPR) in post‐irradiated patients with nasopharyngeal carcinoma (NPC) is unknown. Materials and methods: In a cross‐sectional study, 31 NPC and 12 control patients completed questionnaires for GERD/LPR before esophageal manometry and 24‐h pH monitoring. The DeMeester score and reflux finding score (RFS) were used to define GERD and LPR, respectively. Risk factors were identified. Results: 51.6% of NPC and 8.3% of control patients, and 77.4% of NPC and 33% of control patients, were GERD‐positive and LPR‐positive, respectively. The GERD/LPR questionnaire failed to identify either condition in patients with NPC. No parameter differences in esophageal manometry or pneumonia incidence were noted between GERD/LPR‐positive and GERD/LPR‐negative patients. Post radiotherapy duration, high BMI, lack of chemotherapy, and dysphagia were positive risk factors for GERD/LPR. Conclusions: A high prevalence of GERD/LPR in patients with post‐irradiated NPC exists, but reflux symptoms are inadequate for diagnosis. [ABSTRACT FROM AUTHOR]

Background: Neighborhood socioeconomic deprivation impacts outcomes in various cancers. We examined this association in nasopharyngeal carcinoma (NPC) patients using the area deprivation index (ADI). Methods: We conducted a single‐institution retrospective cohort study on NPC patients treated with definitive radiotherapy from 1980 to 2023. ADI was used as the primary exposure measure. Higher ADI indicates higher levels of socioeconomic deprivation. Results: Of 561 patients, those with higher ADI (6–10 vs. 1–5) presented more commonly with AJCC stage III/IV compared to I/II (87% vs. 76%, p = 0.03). Increasing ADI decile score correlated with poorer overall survival (HR 1.14, 95% CI 1.01–1.28, p = 0.04). Local control was worse in patients from the most deprived quartile in the cohort ADI 5–10 (HR 2.11, 95% CI 1.01–4.41, p = 0.05). Conclusions: NPC patients from more disadvantaged neighborhoods undergoing radiotherapy had worse local control and survival outcomes. Interventions to address structural determinants of health and neighborhood disparities may improve these outcomes. [ABSTRACT FROM AUTHOR]

The diagnostic efficacy of the water swallow test (WST) is relatively robust for patients with neurogenic dysphagia; however, its diagnostic performance in identifying dysphagia among patients with HNC varies across studies. Our study aims to assess the diagnostic value of the WST for detecting dysphagia in patients with HNC. Systematic retrieval of studies on the use of WST for screening dysphagia in patients with HNC from databases up to August 1, 2023. Quality assessment of the included studies was performed using the Quality Assessment of Diagnostic Accuracy Studies‐2 (QUADAS‐2) tool. Calculate the pooled sensitivity, specificity, positive likelihood ratio (LR), negative LR, diagnostic odds ratio (DOR), and area under the receiver operating characteristic curve (AUC) to evaluate the screening ability of WST for dysphagia. A total of seven articles, encompassing eight study groups, were included, involving the analysis of 691 patients. The meta‐analysis results demonstrate that the WST has a combined sensitivity, specificity, positive LR, negative LR, DOR, and AUC for diagnosing dysphagia in patients with HNC of 0.82 (95% CI [0.64, 0.92]), 0.79 (95% CI [0.70, 0.86]), 4.00 (95% CI [2.51, 6.36]), 0.22 (95% CI [0.10, 0.50]), 17.94 (95% CI [5.56, 57.92]), and 0.86 (95% CI [0.83, 0.89]), respectively. Significant heterogeneity was observed among the included studies. Meta‐regression analysis showed that the pooled sensitivity of tumor sites and treatment was closely related, while the pooled specificity of treatment and version was closely related. The subgroup analysis showed that the WST's pooled sensitivity for diagnosing dysphagia in patients with nasopharyngeal cancer was 0.40 (95% CI [0.26, 0.56]), with an AUC of 0.50, lower than in other HNC sites. The WST performed better in surgical patients than in those undergoing radiotherapy (RT) or chemoradiotherapy (CRT), with lower sensitivity, specificity, and AUC values of 0.49 (95% CI [0.36, 0.61]), 0.66 (95% CI [0.59, 0.72]), and 0.64, respectively, for RT or CRT patients. The modified WST version showed different specificity values of 0.82 (95% CI [0.75, 0.87]), compared to the regular version of 0.68 (95% CI [0.61, 0.74]). Additionally, Deek's test indicated the absence of publication bias in this study (p = 0.32). The WST demonstrates favorable sensitivity and specificity in detecting dysphagia among patients with HNC. However, the diagnostic value may vary depending on factors such as tumor sites, treatment, and the specific version of the WST used. [ABSTRACT FROM AUTHOR]

Background: The effect of radiotherapy waiting time after last induction chemotherapy (IC‐RT) on prognosis of patients with locally advanced nasopharyngeal carcinoma (LANPC) needs further discussion. Methods: Three hundred and six patients with LANPC diagnosed pathologically by induction chemotherapy (IC) and radiotherapy (RT) from 2013 to 2018 were selected for this study. Results: The IC‐RT was a risk factor for the post‐treatment progression of LANPC (OR = 1.017 95%CI: 1.003–1.031), For patients with LANPC, the IC‐RT > 40 days significantly reduced 5‐year PFS (70% vs. 55%; p = 0.0012), 5‐year OS (84% vs. 73%; p = 0.028), 5‐year DMFS (80% vs. 66%; p = 0.003), 5‐year LRFS (77% vs. 67%; p = 0.012). Indicating that patients with stage IVa who IC‐RT > 40 days were found to be a significant predictor of aggravated PFS (HR = 2.69; 95%CI: 1.57–4.6), OS (HR = 2.55; 95%CI: 1.29–5.03), DMFS (HR = 3.07; 95%CI: 1.64–5.76) and LRFS (HR = 2.26; 95%CI: 1.21–4.21). Conclusion: The prognosis of patients will be adversely affected if the IC‐RT exceeds 40 days, especially for stage IVa patients. [ABSTRACT FROM AUTHOR]

Background: Brain metastasis is rare in nasopharyngeal carcinoma (NPC), with only anecdotal cases reported. Conducting a systematic study is crucial for improving the management of these patients. Materials and Methods: Forty‐one patients with brain metastasis were retrospectively included between February 2000 and February 2023. The clinical characteristics and treatment information of patients were analyzed. Overall survival (OS) was estimated by Kaplan–Meier survival analysis, and Cox proportional hazard regression analysis was performed to explore prognostic factors. Results: The median OS for patients was 11.2 months, with a 3‐year OS rate of 16.3%. The number of extracranial metastatic organs (HR = 5.533, P = 0.041) and the response of extracranial tumors to treatment (HR = 0.079, P = 0.003) were independent prognostic factors in the cohort. Conclusions: Brain metastasis in NPC is a devastating condition that commonly occurs through hematogenous dissemination. Systemic therapy remains fundamental treatment, while local therapy for brain metastases may further improve survival in selected patients. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to validate the feasibility of an endoscopic endonasal combined transoral medial approach for treating lesions in the nasopharynx, parapharyngeal space (PPS), and jugular foramen. Methods: Anatomical and imaging information of six patients who underwent surgery via this approach were reviewed and analyzed. Results: The feasibility and advantages of the endoscopic endonasal combined transoral medial approach, which uses an inside‐to‐outside medial surgical corridor, were identified. Total resection was achieved in 3 cases with benign tumors. Safe resection margins were obtained in 2 cases with recurrent nasopharyngeal carcinoma (NPC). Pathological biopsy of NPC lesion between the Eustachian tube and arterial sheath was achieved. The internal carotid artery (ICA) was accurately located and protected in all cases and no complications occurred. Conclusion: Lesions in the nasopharynx, PPS, and jugular foramen can be directly assessed via this approach. The ICA can be well identified during the surgery. [ABSTRACT FROM AUTHOR]

Objective: Endoscopic nasopharyngectomy (ENPG) with en bloc resection has been well accepted in resectable localized recurrent nasopharyngeal carcinoma (rNPC), but it is a difficult technique to master for most otorhinolaryngology head and neck surgeons. Ablation surgery is a new and simplified method to remove tumors. We designed a novel method using low‐temperature plasma radiofrequency ablation (LPRA) and evaluated the survival benefit. Methods: A total of 56 localized rNPC patients were explained in detail and retrospectively analyzed. The surgery method was ablated from the resection margin to the center of the tumor. The postmetastatic overall survival (OS), local relapse‐free survival (LRFS) rate, progression‐free survival (PFS) and distant metastasis‐free survival (DMFS) were analyzed using the Kaplan–Meier method and compared by the log‐rank test. Results: All surgeries were successfully performed without any severe postoperative complications or deaths. The median operation time of ablation and harvested NSFF respectively were 29 min (range, 15–100 min) and 101 min (range, 30–180 min). The average number of hospital days postoperation was 3 days (range, 2–5 days). All cases (100.0%) had radical ablation with negative resection margins. The nasopharyngeal defects were completely re‐epithelialized in 54 (96.4%) patients. As of the data cutoff (September 3, 2023), the median follow‐up time was 44.3 months (range, 17.1–52.7 months, 95% CI: 40.4–48.2). The 3‐year OS, LRFS, PFS and DMFS of the entire cohort were 92.9% (95% CI: 0.862–0.996), 89.3% (95% CI: 0.813–0.973), 87.5% (95% CI: 0.789–0.961), and 92.9% (95% CI: 0.862–0.996), respectively. Cycles of radiotherapy were independent risk factors for OS (p = 0.003; HR, 32.041; 95% CI: 3.365–305.064), LRFS (p = 0.002; HR, 10.762; 95% CI: 2.440–47.459), PFS (p = 0.004; HR, 7.457; 95% CI: 1.925–28.877), and DMFS (p = 0.002; HR, 34.776; 95% CI: 3.806–317.799). Conclusion: Radical endoscopic nasopharyngectomy by using low‐temperature plasma radiofrequency ablation is a novel, safe and simplified method to master and disseminate for treating resectable rNPC. However, further data and longer follow‐up time are needed to prove its efficacy. [ABSTRACT FROM AUTHOR]

Background: Nasopharyngeal carcinoma (NPC) is a common malignancy occurring in the head and neck. Identification of immune‐related methylated biomarkers might be helpful for NPC detection and prognostic evaluation. Methods: A co‐methylation network based on WGCNA was constructed to identify modules associated with NPC and immune cells. In combination with differentially expressed genes (DEGs) and immune‐related genes from ImmPort database, the candidate immune‐related methylated genes (IRMGs) were obtained. Results: Our combined analysis identified 12 IRMGs. Among them, both the methylation and mRNA expression of CCL28, CSK, and PRKCB were correlated with the infiltration of B cells. CD1D, CR2, and GDF10 were favorable markers. Demethylation experiments validated that downregulation of GDF10, PRKCB, SLC40A1, and TGFBR3 in NPC resulted from promoter hypermethylation. Additionally, a diagnostic model was developed and exhibited high discriminative accuracy. Conclusions: These results provided a group of immune‐related methylated biomarkers that may help with the diagnosis and prognosis of NPC. [ABSTRACT FROM AUTHOR]

Background: The combination of tislelizumab and gemcitabine plus cisplatin (GP) in the first‐line treatment of patients with recurrent or metastatic nasopharyngeal carcinoma (R/M NPC) has yielded significant results. However, it is not clear whether this treatment option is cost‐effective in China. The purpose of this study is to evaluate the cost‐effectiveness of tislelizumab plus GP for the first‐line treatment of R/M NPC from the perspective of the Chinese healthcare system. Methods: A partitioned survival model with three discrete health states was constructed to evaluate the cost‐effectiveness of tislelizumab plus GP versus GP in patients with R/M NPC. The target population enrolled in the RATIONALE‐309 trial had previously not treated for R/M NPC. Drug costs were obtained from relevant databases, and the remaining cost and health utility data were collected from the literature. The main outcomes include the expected life years, quality‐adjusted life years (QALYs), total cost, and incremental cost–benefit ratio (ICER). Results: The tislelizumab plus GP regimen produced an additional cost ($18392.76) and additional 1.57 QALYs compared with GP used alone. The ICER was $18392.75/QALYs. Sensitivity analysis showed that the analysis was robust and the utility of PD status was most sensitive to the model results. The possibility of tislelizumab plus GP being cost‐effective at the willingness‐to‐pay (WTP) threshold of $37 653/QALY was 99.8%. Subgroup analysis showed that high PD‐L1 expression had little impact on the ICER of this regimen. Conclusion: In patients with R/M NPC, the regimen of tislelizumab plus GP, as the first‐line treatment, is more cost‐effective than the GP regimen in China. [ABSTRACT FROM AUTHOR]

Background: To investigate the prevalence and predictive factors of xerostomia during induction chemotherapy (IC) in patients with nasopharyngeal carcinoma (NPC). Methods: We prospectively enrolled NPC patients who received IC between October 2020 and October 2021. The Visual Analogue Scale (VAS) and Xerostomia Inventory (XI) were used to evaluate the condition of xerostomia. The volume of the submandibular gland (SMG) was also calculated before and after IC. Results: Fifty‐two patients were enrolled in this study. Of these patients, 32.7% (n = 17) experienced xerostomia before IC. There were 32 (61.5%) patients suffered from xerostomia after IC, including 21 (40.4%) patients with newly diagnosed xerostomia after IC and 11 (21.1%) patients complained their xerostomia aggravated in those with xerostomia before IC. The median XI scores increased from 11 (standard deviation [SD], 2.930) to 18 (SD 3.995), 16 (SD 3.605), and 17 (SD 4.331) after the first, second, and third cycles of IC, respectively. The median score of VAS also increased from 0 to 4 during the following three cycles of IC. In those with IC‐related xerostomia, the SMG volume after IC was significantly decreased compared with those without IC‐related xerostomia (P = 0.001). The reduction of the SMG volume after IC was the independent risk factor for xerostomia (P = 0.002). Conclusion: Approximately two‐thirds of NPC patients suffered from IC‐related xerostomia and patients with a reduction of SMG volume after IC had a higher risk of xerostomia. [ABSTRACT FROM AUTHOR]

Background: To explore the value of early oral nutritional supplements (ONS) in patients with nasopharyngeal carcinoma (NPC) treated with concurrent chemoradiotherapy (CCRT). Methods: Patients with newly diagnosed II‐IVA stage NPC were analyzed and divided into Early and Routine ONS groups according to whether they received early ONS at the beginning of CCRT. Changes in nutritional indicators, incidence of treatment‐related toxicity, radiation interruption, and completion of CCRT were compared. Results: In total, 161 patients with NPC were analyzed, including 72 in the Early ONS group and 89 in the Routine ONS group. Multivariate analysis showed that early ONS was an independent protective factor for concurrent chemotherapy ≥2 cycles, and a protective factor against ≥grade 3 radiation‐induced oral mucositis (RIOM) and weight loss >5%. In stage III‐IVA patients, early ONS was beneficial in decreasing the risk of severe malnutrition. Conclusions: Early ONS can improve nutritional outcomes, reduce RIOM, and enhance treatment adherence. [ABSTRACT FROM AUTHOR]

Objective: Our objective was to establish a prognostic model for patients with de novo metastatic nasopharyngeal carcinoma (NPC) who received chemotherapy followed by locoregional radiotherapy (LRRT) to identify candidates for metastasis‐directed therapy (MDT). Methods: De novo metastatic NPC patients who received chemotherapy followed by LRRT were enrolled. Propensity score matching (PSM) method was used to compare overall survival (OS) for patients receiving LRRT alone and MDT plus LRRT. We developed a predictive model to predict survival and estimate the outcome of stratified therapy and identify suitable candidates for MDT. Results: A total of 107 patients received MDT plus LRRT and 178 received LRRT alone were enrolled. PSM analysis identified 107 patients in each cohort and showed that MDT plus LRRT was associated with a significant survival benefit (HR: 0.640; 95% CI, 0.29–0.956; p = 0.027). Based on five independent prognostic factors, including metastases number, serum lactate dehydrogenase, liver metastasis, C‐reactive protein, and tumor response, a prognostic model was established. All patients were stratified according to the prognostic score obtained by the prognostic model. In the low‐risk group, MDT plus LRRT group revealed a significant improvement for OS compared with LRRT alone group (5‐year OS, 69.9% vs. 57.8%, p = 0.020). However, no significant difference was observed between MDT plus LRRT group and LRRT alone in the high‐risk group (p = 0.75). Conclusion: MDT plus LRRT was associated with improved OS in patients with de novo metastatic NPC, especially low‐risk patients identified with a newly developed prognostic model. [ABSTRACT FROM AUTHOR]

Background: There are limited studies and no surveillance protocols on pituitary dysfunction for adults who underwent anterior skull base radiation. Methods: Cross‐sectional study of 50 consecutive patients with sinonasal or nasopharyngeal cancer who underwent definitive radiotherapy. The mean radiation doses, prevalence of pituitary dysfunction, and associated factors were calculated. Results: Pituitary hormone levels were abnormal in 23 (46%) patients, including 6 (12%) with symptomatic abnormalities requiring treatment. The most common hormonal abnormality was hyperprolactinemia (30%), central hypothyroidism (8%) and central hypogonadism (6%). Patients with abnormal pituitary hormone values received higher mean radiation doses to the pituitary gland (1143 cGy, P = 0.04), pituitary stalk (1129 cGy, P = 0.02), optic chiasm (1094 cGy, P = 0.01), and hypothalamus (900 cGy, P = 0.01). Conclusions: Nearly half of the patients had abnormal pituitary function, including over a tenth requiring treatment. There may be a dose‐dependent association between hormonal dysfunction and radiation. [ABSTRACT FROM AUTHOR]

The low positive predictive value (PPV) of early screening of nasopharyngeal carcinoma (NPC) is the problems that need to be solved urgently. The combination of cell‐free DNA (cfDNA) methylation testing and Epstein–Barr virus (EBV) serological testing is the key to solve this problem. This paper reviews recent advances in early screening for NPC and cfDNA methylation, with future perspectives. Pubmed was searched for the literature related to early screening of NPC and cfDNA methylation in the past 5 years. The results of these studies were summarized. Despite these efforts, the PPV is still low (10%). Previous studies have shown that cfDNA methylation analysis has good specificity and accuracy across a variety of tumors. The combination of cfDNA methylation and EBV detection helps to improve the PPV for early screening of NPC. The combination of cfDNA methylation and EBV serological testing is key to addressing the low PPV of NPC early screening. [ABSTRACT FROM AUTHOR]

Objectives: Recently updated results of randomized clinical trials (RCTs) have confirmed that toripalimab, camrelizumab, and tislelizumab plus chemotherapy (TOGP, CAGP, and TIGP) significantly prolonged survival compared to placebo plus chemotherapy (PLGP) in the first‐line treatment for recurrent or metastatic nasopharyngeal carcinoma (R/M‐NPC). However, the high cost of immunotherapies imposes a huge financial burden on patients and health care systems. Materials and methods: RCTs estimating immunotherapies for R/M‐NPC were searched. A Bayesian network meta‐analysis (NMA) was carried out; the main outcomes were hazard ratios (HRs) of overall survival (OS) and progression‐free survival (PFS). The cost and efficacy of four first‐line therapies were evaluated using the Markov model. The main outcome in the cost‐effectiveness analysis (CEA) was incremental cost‐utility ratios (ICURs). The model robustness was assessed by one‐way, three‐way, and probabilistic sensitivity analyses. Results: Three RCTs (JUPITER‐02, CAPTAIN‐1st, and RATIONALE‐309) involving 815 patients were included in the NMA. Compared with PLGP, chemo‐immunotherapies have significantly longer PFS and OS. Compared to the PLGP group, TOGP, CAGP, and TIGP groups resulted in additional costs of $48 339, $22 900, and $23 162, with additional 1.89, 0.73, and 0.960 QALYs, respectively, leading to the ICURs of $25 576/QALY, $31 370/QALY, and $31 729/QALY. Pairwise comparisons showed TOGP was the most cost‐effective option among chemo‐immunotherapy groups. Conclusion: From the Chinese payers' perspective, first‐line immunotherapy combination therapies provided significant survival and cost‐effectiveness superiority over chemotherapy alone for patients with R/M‐NPC at the WTP of $38 029/QALY. Among the three chemo‐immunotherapy groups, TOGP was the most cost‐effective option. [ABSTRACT FROM AUTHOR]

Background: To explore the patterns and risk factors of early thyroid dysfunction in nasopharyngeal carcinoma (NPC) patients within 1 year after intensity‐modulated radiation therapy (IMRT). Methods: Patients with NPC who received definitive IMRT between April 2016 and April 2020 were included. All patients had normal thyroid function before definitive IMRT. The chi‐square test, Student's T‐test, Mann–Whitney U test, Kaplan–Meier method, receiver operating characteristics curve, and Cox proportional hazard analysis were used for statistical analysis. Results: A total of 132 NPC patients were identified. Of these patients, 56 (42.4%) had hypothyroidism and 17 (12.9%) had hyperthyroidism. The median time to hypothyroidism and hyperthyroidism was 9 months (range, 1–12 months) and 1 month (range, 1–6 months) after definitive IMRT, respectively. In patients with hypothyroidism, 41 (73.2%) had subclinical hypothyroidism and 15 (26.8%) had clinical hypothyroidism. In those with hyperthyroidism, 12 patients (70.6%) had subclinical hyperthyroidism, and five patients (29.4%) had clinical hyperthyroidism. Age, clinical stage, thyroid volume, and V45 were independent risk factors for early radiation‐induced hypothyroidism within 1 year after IMRT. Patients aged <47 years, stage III/IV disease, or pre‐irradiation thyroid volume < 14 cm3 had higher risks of developing hypothyroidism. Conclusion: Primary subclinical hypothyroidism was the most common subtype of early thyroid dysfunction in NPC patients within 1 year after IMRT. Age, clinical stage, thyroid volume, and V45 were independent risk factors for early radiation‐induced hypothyroidism in NPC patients. [ABSTRACT FROM AUTHOR]

Background: Waldeyer lymphatic ring surrounds the nasopharynx and oropharynx, and no study to date has correlated its microbiome with the severity of oral mucositis (OM) in patients with nasopharyngeal carcinoma (NPC) receiving chemoradiotherapy. Methods: We performed 16S rRNA sequencing to characterize bacterial microbiome in tumor‐affected nasopharynx and the surrounding normal oropharynx. We plotted the abundance and diversity of bacterial taxa and their phylogenetic distance and networks to visualize and compare the differences in pretreatment overall bacterial communities between the nasopharynx and oropharynx in patients with NPC with varying degrees of chemoradiotherapy‐induced OM and quality of life. Results: We found microbial signatures in nasopharynx around NPC were not only dissimilar to those in the surrounding oropharynx but were almost unique to each patient. The genetic distance metrics further showed that different tumor microbiota distributions in the nasopharynx among patients with NPC were well‐correlated with OM severity and quality of life during chemoradiotherapy. Conclusions: At Waldeyer ring, the tumor‐associated microbiome risk profiles of the respiratory region of nasopharynx, but not commensal microbiota of the alimentary region of oropharynx, could be noninvasive biomarkers for OM susceptibility and might include drug targets for the prevention of chemoradiation‐induced OM in patients with Waldeyer ring‐derived NPC. [ABSTRACT FROM AUTHOR]

Background: To evaluate the impact of coronavirus disease 2019 (COVID‐19) pandemic on disease extent in patients with nasopharyngeal carcinoma (NPC) using 18 fuorodeoxyglucose (FDG) positron emission tomography (PET)/magnetic resonance imaging (MRI). Methods: This retrospective cohort study included biopsy‐proven, newly diagnosed NPC patients using whole‐body FDG PET/MR staging in two selected intervals: 1 May 2017 to 31 January 2020 (Group A, the pre‐COVID‐19 period), and 1 February 2020 to 30 June 2021 (Group B, the COVID‐19 period). Results: Three‐hundred and ninety patients were included. No significant difference was observed in terms of T classification, N classification, overall stage, N stations, and M stations between the two groups (p > 0.05). For the involved neck node levels, more patients had developed level Vc metastasis in the group B (p = 0.044). Conclusion: Although the overall stage was not affected, more patients with NPC had developed level Vc metastasis in the era of COVID‐19. [ABSTRACT FROM AUTHOR]

Background: A nomogram that incorporates tumor response at mid‐radiotherapy (mid‐RT) to predict the prognosis of locoregionally advanced nasopharyngeal carcinoma (LA‐NPC) has not been established. Methods: This study retrospectively reviewed 583 patients with LA‐NPC who underwent magnetic resonance imaging scans at mid‐RT (the fourth week of RT) between 2015 and 2019. Results: Primary tumor (PT) response at mid‐RT was found to predict disease‐free survival (DFS) and overall survival (OS). Independent factors from multivariable analysis to predict DFS and OS were assembled into nomograms with (nomograms Amid‐RT and Bmid‐RT) or without (nomograms Abaseline and Bbaseline) PT response. Internal validation revealed good performance of these nomograms in discrimination: C‐statistics = 0.761 for nomogram Amid‐RT and 0.809 for nomogram Bmid‐RT, which showed better discrimination performance than (C‐statistics: 0.755) nomogram Abaseline and (C‐statistics: 0.798) nomogram Bbaseline (Z‐statistic = 2.476, p < 0.05; Z‐statistic = 1.971, p < 0.05). Conclusion: The nomograms based on PT response at mid‐RT showed favorable predictive accuracy for DFS and OS in patients with LA‐NPC. [ABSTRACT FROM AUTHOR]

Objective: To retrospectively analyze the comprehensive treatment strategy for internal carotid artery blowout syndrome (CBS) by nasopharyngeal carcinoma (NPC). Methods: Of the 311 patients of NPC with carotid artery blowout syndrome admitted at our center from April 2018 to August 2022, 288 were enrolled. Results: The patients were divided into two groups: treatment group (266 cases) and control group (22 cases). After comprehensive treatment, the survival rate of the treatment group was significantly higher than that of the control group, especially within 6 months to the 1 year. Preventive intervention for CBS I type may have considerable benefits. And in the long run, this treatment strategy did not significantly increase the incidence of stroke in the treatment group. Conclusion: The comprehensive treatment strategy for ICA‐CBS of patients with NPC significantly reduced the mortality of asphyxia due to epistaxis, reduced the incidence of CBS during nasal endoscopy, and finally improved survival rate. [ABSTRACT FROM AUTHOR]

Objectives: To explore how well a unique combination of hemoglobin‐to‐platelet ratio (HPR) and pretreatment maximum mouth opening (MMO) predicts the prevalence of radiation‐induced trismus (RIT). Patients and methods: HPR and MMO cutoff values (0.54 and 40.7 mm) divided patients into two groups. To develop the novel HPR‐MMO index, four combinations of these factors were tested for predictive power: Group 1: HPR > 0.54 and MMO > 40.7 mm; Group 2: HPR ≤ 0.54 but MMO > 40.7 mm; Group 3: HPR > 0.54 but MMO ≤ 40.7 mm; Group 4: HPR ≤ 0.54 and MMO ≤ 40.7 mm. Results: Data of 198 patients with LA‐NPC was analyzed retrospectively. RIT rates for Groups 1 to 4 were 10.2%, 15.2%, 25%, and 59.4%. Groups 2 and 3 were merged to generate HPR‐MMO index because of statistically equivalent RIT rates: Low‐risk: HPR > 0.54 and MMO > 40.7 mm; Intermediate‐risk: HPR ≤ 0.54 but MMO > 40.7 mm or; HPR > 0.54 but MMO ≤ 40.7 mm; High‐risk: HPR ≤ 0.54 and MMO ≤ 40.7 mm. It was revealed that the low‐, high‐, and intermediate‐risk group's RIT rates; 10.2%, 59.4%, and 19.2%, respectively. Conclusion: The novel HPR‐MMO index may to classify LA‐NPC patients into low, intermediate, and high‐risk RIT groups. [ABSTRACT FROM AUTHOR]

Background: Factors that prompt litigation and influence outcomes for malpractice cases involving cancers of the upper aerodigestive tract are incompletely described. Methods: Westlaw, a national legal database, was searched for medical malpractice claims related to upper aerodigestive tract cancer for all years available. Results: Of the 122 cases meeting inclusion criteria, 106 (86.9%) involved allegations of failure to diagnose or delay in diagnosis. Tongue, larynx, and nasopharynx cancers were more frequently litigated than would be expected based on their incidence (tongue, 38.7% of aerodigestive tract litigation vs. 26.9% of aerodigestive tract cancers; larynx, 33.0% vs. 22.3%; nasopharynx, 10.4% vs. 4.6%). Payouts were made in over half of diagnosis failure lawsuits (56.6%), which carried an average award of $2840690 [IQR 850219–2537509]. Conclusions: An awareness of litigation on cancers of the upper aerodigestive tract holds the potential to improve patient care and help otolaryngologists avoid potential risks for litigation. [ABSTRACT FROM AUTHOR]

The objective of this study was to compare the outcomes of parent artery occlusion (PAO) versus stent‐assisted reconstruction in radiated nasopharyngeal carcinoma (NPC) patients with internal carotid artery (ICA) blowouts. A retrospective review from our institution (2011–2021) and systematic review of Pubmed and Embase (1995–2022) was performed. Twenty‐eight eligible studies were identified. Eighty‐six PAOs and 37 stent‐assisted reconstructions were analyzed, including 11 PAOs and 5 stents from our institution. Stents were associated with significantly higher incidence of overall re‐bleeding (16.2% [95% CI 7.4–31.9] vs. 4.6% [95% CI 1.3–13.5], p = 0.047), delayed stroke (5.4% [95% CI 1.3–19.4] vs. 0%, p = 0.034) and reduced median survival (7.1 [95% CI 3.8–14.0] months vs. 29.0 [95% CI 9.4–63.4] months, p = 0.017) compared to PAO. There were no significant differences in terms of overall stroke, infection, extruded/migrated foreign body, and peri‐procedure death. PAO is preferred over reconstructive treatment in patients with adequate collateral circulation. [ABSTRACT FROM AUTHOR]

Background: To identify patients at low risk of synchronous bone metastasis who should not receive bone scans when initially diagnosed with nasopharyngeal carcinoma (NPC). Methods: In total, 6652 patients were enrolled in the training cohort and 1919 patients in the multicenter external validation cohort. Logistic regression analyses were performed to assess independent predictors of synchronous bone metastasis for the nomogram model. Results: After risk stratification, 46.3% (3081/6652) patients were separated into the low‐risk group with an incidence of 0.71% for synchronous bone metastasis. The odds ratio of the intermediate and high‐risk groups was 5.61 and 23.82 times that of the low‐risk group, respectively. For patients with high EBV DNA, we recommend routine screening for N2‐3 female patients, but that all male subgroups are screened. Conclusions: Bone scans should not be routine. Patients in the low‐risk group should not be screened, which would avoid excessive radiation and economize iatrical resource. [ABSTRACT FROM AUTHOR]

Background: Most nasopharyngeal carcinoma (NPC) protocols define primary gross tumor volume (GTVnx) plus a range from 2 to 5 mm as the high‐dose clinical target volume (hd‐CTV). However, in China, hd‐CTV is defined as GTVnx plus 0 mm. Methods: A total of 40 patients with newly diagnosed nonmetastatic NPC (T1–T4 ten cases each) treated with IMRT were consecutively enrolled. Real and virtual treatment plans were designed according to the definitions of hd‐CTV recommended by China and Radiation Therapy Oncology Group (RTOG), respectively. Results: The hd‐CTV in China was significantly smaller than that of RTOG. Exposure doses to 5 mm subclinical involvement and OARs as well as NTCP in the China treatment plan were significantly lower than those of RTOG. Conclusion: It could be recommended to divide the hd‐CTV into GTV and subclinical target volume and to prescribe different doses for the GTV and subclinical involvement in the IMRT plan of NPC. [ABSTRACT FROM AUTHOR]

Background: We aimed to evaluate patients with nasopharyngeal carcinoma (NPC) in a nonendemic population. Methods: In a national, retrospective, multicenteric study, 563 patients treated with intensity modulated radiotherapy at 22 centers between 2015 and 2020 were analyzed. Results: Median age was 48 (9–83), age distribution was bimodal, 74.1% were male, and 78.7% were stage III‐IVA. Keratinizing and undifferentiated carcinoma rates were 3.9% and 81.2%. Patients were treated with concomitant chemoradiotherapy (48.9%), or radiotherapy combined with induction chemotherapy (25%) or adjuvant chemotherapy (19.5%). After 34 (6–78) months follow‐up, 8.2% locoregional and 8% distant relapse were observed. Three‐year overall survival was 89.5% and was lower in patients with age ≥50, male sex, keratinizing histology, T4, N3 and advanced stage (III‐IVA). Conclusions: Patients with NPC in Turkey have mixed clinical features of both east and west. Survival outcomes are comparable to other reported series; however, the rate of distant metastases seems to be lower. [ABSTRACT FROM AUTHOR]

Background: In intensity‐modulated radiation therapy (IMRT) for nasopharyngeal carcinoma (NPC), priority is often given minimize dose to the critical organs at risk (OARs) to avoid potential morbid sequelae. However, in T4 NPC, dosimetric inadequacy enforced by dose constraints on OARs may significantly impact tumor control. Methods: This was a single‐institute cohort that patients diagnosed between July 2005 and December 2010 with T4 NPC treated with IMRT. All patients were re‐classification according to the 7th‐AJCC stage. Results: Overall, the average doses such as Dmax, D1%, D2% and D1cc for various Central nervous system (CNS) OARs including brainstem, optic nerve, chiasm, temporal lobes and spinal cord were found to exceed published guidelines as RTOG0225. However, no clinical toxicities were seen during the follow‐up period except for 13% patients with temporal lobe necrosis. Conclusion: Our retrospective review showed that its feasible to maximize gross tumor volume dose coverage while exceeding most CNS OAR constraint standards, with ideal local control and no obvious increase of craniocerebral toxicity. [ABSTRACT FROM AUTHOR]

Background: To investigate the effect of nutritional status on radiation‐induced acute toxicities in nasopharyngeal carcinoma (NPC) patients before radiotherapy. Methods: Nutritional status of 228 patients with NPC who received intensity‐modulated radiotherapy was retrospectively analyzed by modified nutrition index (m‐NI). Cumulative grading score of six common acute toxicities were defined as total score for acute toxicities. Results: M‐NI ≤6 is a risk factor for xerostomia (p = 0.016, OR = 0.208, 95% CI 0.058–0.743), oral mucositis (p = 0.016, OR = 0.287, 95% CI 0.104–0.793), dysgeusia (p = 0.001, OR = 0.028, 95% CI 0.004–0.217), and dysphagia (p = 0.015, OR = 0.251, 95% CI 0.083–0.764) as well in patients with NPC. Total score of radiation‐induced acute toxicities of patients with malnutrition (13.6 ± 1.7) was significantly higher than that of patients with normal nutrition (12.0 ± 2.4) (t = −5.464, p < 0.001). Conclusions: NPC patients with malnutrition before radiotherapy develop more serious dysgeusia, oral mucositis, dysphagia, and xerostomia after intensity‐modulated radiotherapy. [ABSTRACT FROM AUTHOR]

Background: To develop a common follow‐up strategy for appropriate imaging examination at an appropriate time for nasopharyngeal carcinoma (NPC). Methods: Independent prognostic factors were identified by Cox regression analysis, and a nomogram model was developed. Random survival forest (RSF) model was constructed to depict probability of disease failure during a 5‐year follow‐up and establish a reasonable risk‐based follow‐up strategy. Results: The nomogram model finally categorized the patients into three risk groups. RSF model demonstrated distribution trends for local and regional recurrences, bone metastasis, liver metastasis, and lung metastasis of NPC. Adequate imaging at follow‐up should be considered between 10 and 21 months for patients at moderate‐risk of recurrence or metastasis and 7–36 months for those at high‐risk. Conclusions: The temporal distribution of incidence rates of recurrence or metastasis varied among different risk groups. We recommend implementing a focused and targeted imaging surveillance intervention at appropriate times to improve its efficiency and reduce costs. [ABSTRACT FROM AUTHOR]

Background: We routinely delineate the gross tumor volume (GTV) for the lymph nodes (LN) based on post‐induction chemotherapy (IC) MRI in nasopharyngeal carcinoma (NPC). Herein, we investigated the sufficiency of this method, particularly in high‐risk LNs. Methods: Eighty‐one LNs with a high‐risk of clinical extranodal extension and/or ≥3‐cm diameter in 58 patients were evaluated. A new GTV covering the pre‐IC LN volume was delineated for each LN. Results: The median volume reduction was 72.5% for the GTV and 53.1% for the planning target volume. After a median 43 months, the overall LN local control rate was 97.5%. The 2‐ and 5‐year LN recurrence‐free survival, overall survival, and disease‐free survival rate was 88.3% and 84.4%, 92.5% and 85.1%, and 86.8% and 79.2%, respectively. Conclusion: IC yields a significant reduction in nodal target volumes, and post‐IC nodal volume‐based radiotherapy provides excellent LC in NPC, even in high‐risk LNs. [ABSTRACT FROM AUTHOR]

The present study aimed to evaluate the effectiveness and safety of various salvage treatments to treat locally recurrent nasopharyngeal carcinoma (IrNPC). A comprehensive search was conducted to gather relevant research publications on salvage treatment for IrNPC. Specifically, 2‐, 3‐, and 5‐year overall survival were the primary outcome. A total of 89 studies with 101 cohorts were collected. Endoscopic nasopharyngectomy was found to be associated with a significantly improved 5‐year OS compared with CRT (p = 0.027) and IMRT (p = 0.016). Moreover, based on recurrence T classification, the 2‐, 3‐, and 5‐year OS were similar across different treatments. Endoscopic nasopharyngectomy was associated with a significant reduction in treatment‐related complications (grade ≥ 3) compared with IMRT (p < 0.001) and open nasopharyngectomy (p = 0.028). Endoscopic nasopharyngectomy may provide comparable treatment outcomes to re‐irradiation, while offering a better safety profile for selective patients with resectable IrNPC. [ABSTRACT FROM AUTHOR]

Background: American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) rT staging have great clinical impracticality. The aim of the present study was to establish a new rT staging to guide endoscopic surgery for the treatment of recurrent nasopharyngeal carcinoma (rNPC). Methods: This surgical rT staging (named Fudan rT staging) was constructed using two significant risk factors: the distance from the tumor margin to the internal carotid artery, and dural invasion. Log‐rank and receiver operating characteristic (ROC) curve analyses were used to evaluate its effectiveness. Results: Fudan rT staging can effectively separate the overall survival (OS) and progression‐free survival (PFS) of patients with rNPC according to the different rT stages (p < 0.05). In addition, ROC analysis showed that the Fudan rT staging exhibited enhanced prognostic value for OS and PFS compared with the AJCC/UICC rT staging. Conclusions: The innovative Fudan rT staging has a better predictive value for the survival of patients with rNPC than AJCC/UICC rT staging. [ABSTRACT FROM AUTHOR]

Background: Trifluoperazine (TFP) is a typical antipsychotic primarily used to treat schizophrenia. In this study, we aimed to evaluate whether TFP can be used as a therapeutic agent against nasopharyngeal carcinoma (NPC) and identify its underlying molecular mechanisms. Methods: We used NPC‐TW01, TW03, TW04, and BM to assess the anticancer effects of TFP by using cytotoxicity, wound healing, colony formation, and cell invasion assays. An in vivo animal study was conducted. RNA sequencing combined with Ingenuity Pathways Analysis was performed to identify the mechanism by which TFP influences NPC cells. Results: Our data revealed that TFP decreased NPC cell viability in a dose‐dependent manner. The invasion and migration of NPC tumor cells were inhibited by TFP. An in vivo study also demonstrated the anticancer effects of TFP. RNA sequencing revealed several anticancer molecular mechanisms following TFP administration. Conclusions: The antipsychotic drug TFP could be a potential therapeutic regimen for NPC treatment. [ABSTRACT FROM AUTHOR]

Background: To develop a model based on magnetic resonance imaging (MRI) radiomics and clinical features for predicting radiation‐induced temporal lobe injury (RTLI) in patients with nasopharyngeal carcinoma (NPC) after intensity‐modulated radiotherapy (IMRT). Methods: Two hundred and sixteen patients with NPC were retrospectively included. Radiomics features were extracted and selected. The logistic regression analysis was performed for prediction models construction. The area under the receiver operating characteristic curve (AUC) was calculated for performance evaluation. Results: Three radiomics features were selected to construct the radiomics signature (AUC of 0.94 and 0.92). The clinical‐radiomics model, integrating radiomics signature with T classification, achieved higher predictive performance in the training and validation cohorts (AUC of 0.95 and 0.93), as well as improved accuracy of the classification of RTLI outcomes (net reclassification improvement: 0.711; 95% CI: 0.57–0.86; p < 0.001). Conclusions: The clinical‐radiomics model and radiomics signature both showed great performance in predicting RTLI in patients with NPC. [ABSTRACT FROM AUTHOR]

Background: Nomograms specifically used to predict the prognosis of ascending type nasopharyngeal carcinoma (NPC) have not been constructed. Methods: Data of ascending type (T3‐4N0‐1M0) NPC from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015 were extracted. Results: Altogether 862 patients with ascending type NPC were enrolled, including 603 in training cohort and 259 in validation cohort. Age, marital status, pathology, grade, tumor size, T classification, and chemotherapy were the independent prognostic factors for overall survival (OS). Age, marital status, pathology, grade, and chemotherapy were the independent prognostic factors for cancer‐specific survival (CSS). In training cohort, the concordance index of the OS and CSS nomograms were 0.694 (95% confidence interval [CI], 0.677–0.711) and 0.678 (95%CI, 0.659–0.697), respectively, while those in validation cohort were 0.740 (95%CI, 0.715–0.765) and 0.708 (95%CI, 0.679–0.737), separately. Conclusion: The as‐constructed nomograms for ascending type NPC could provide accurate prognostic predictions of OS and CSS. [ABSTRACT FROM AUTHOR]

Background: We have previously reported our early experience in robotic‐assisted nasopharyngectomy. The current case series is a report of our experience in 33 robotic‐assisted nasopharyngectomy. Methods: Prospective series of patients who underwent robotic‐assisted nasopharyngectomy for local recurrent nasopharyngeal carcinoma from January 2010 to March 2019. Results: Thirty‐one patients underwent robotic‐assisted nasopharyngectomy with two additional second procedure for positive margin. Median age is 55 years (29–85). Twenty‐five patients had rT1 disease and six patients had tumor invaded sphenoid floor (rT3). Median operative time was 227 min and median blood loss was 200 ml. The median follow‐up period for all patients were 38 months. Four patients had local recurrence. Five‐year local control rate, overall survival, and disease‐free survival are 85.1%, 55.7%, and 69.1%, respectively. Conclusion: Robotic‐assisted nasopharyngectomy for recurrent nasopharyngectomy was showed to have a high local control rate. The operating time was comparable to open surgery. [ABSTRACT FROM AUTHOR]

Background: CircularRNAs (circRNAs) played vital roles in nasopharyngeal carcinoma (NPC). However, the impacts of circ_0004788 on the development of NPC have not been explored. Methods: Cell counting kit‐8 (CCK‐8), 5‐Ethynyl‐2′‐deoxyuridine (EdU) and colony formation assays were applied to determine cell proliferation. Wound healing, transwell invasion assay, tube formation assay, and flow cytometry were employed for the detection of cell migration, invasion, angiogenesis, and apoptosis, respectively. Xenograft tumor experiment was used to explore the biological role of circ_0004788 in NPC in vivo. Results: Circ_0004788 and fibroblast growth factor 2 (FGF2) were significantly elevated, and microRNA‐515‐5p (miR‐515‐5p) was dramatically decreased in NPC tissues and cells. The impacts of circ_0004788 knockdown on cell progression in NPC cells were reversed by miR‐515‐5p inhibitor, and FGF2 overexpression could block the suppressive effect of miR‐515‐5p on cell progression in NPC cells. Conclusion: Circ_0004788 knockdown restrained the progression of NPC via the miR‐515‐5p/FGF2 axis. [ABSTRACT FROM AUTHOR]

Background: Radioresistance challenges the clinical outcomes of nasopharyngeal carcinoma (NPC). The 3‐phosphoinositide‐dependent protein kinase 1 (PDK1) is a crucial kinase of PI3K/AKT signaling pathway which has been implicated in the process of radioresistance. However, the role of PDK1 in NPC remains largely unclear. Methods: The expression of PDK1 was determined by immunohistochemistry and Western blot. The effects of RNA interference and pharmacologic inhibitor of PDK1 in combination with irradiation were investigated. Results: Overexpression of PDK1 was correlated with poor prognosis in patients with NPC. PDK1 depletion enhanced radiosensitivity of NPC cells both in vitro and in vivo. Additionally, a specific PDK1 inhibitor also had the potential to enhance radiosensitivity in radioresistant NPC cells. Mechanistically, PDK1 depletion inhibited various targets of AKT including mTOR and GSK‐3β and reversed the epithelial–mesenchymal transition. Conclusions: These findings indicated that PDK1 might be a potential target for NPC. [ABSTRACT FROM AUTHOR]

Background: We investigated the survival impact and toxicity of maintenance metronomic chemotherapy in patients with metastatic/recurrent nasopharyngeal carcinoma (met/rec NPC). Methods: Ninety‐eight patients with met/rec NPC were first salvaged by IV cisplatin‐based chemotherapy and showed nonprogression disease; then maintenance metronomic chemotherapy for at least 12 months was recommended. We analyzed the treatment outcome between patients who received (n = 51) and did not receive (n = 47) maintenance chemotherapy. Results: Baseline patient characteristics showed no significant differences between both arms. Median overall survival for patients with and without maintenance chemotherapy was 36.0 and 12.3 months, respectively (p < 0.0001). Similarly, median progression‐free survival was 24.7 and 7.3 months, respectively (p < 0.0001). Furthermore, toxicities during maintenance oral chemotherapy period were usually mild. Transient grade 3 leucopenia (9.8%), anemia (3.9%), thrombocytopenia (7.8%), and no grade 4 toxicity were observed. Conclusion: After IV salvage chemotherapy, maintenance oral metronomic chemotherapy significantly improved overall and progression‐free survivals while demonstrating low toxicity in patients with met/rec NPC. [ABSTRACT FROM AUTHOR]

Background: To assess the prognostic value of the systemic inflammation response index (SIRI) combined with plasma load of Epstein–Barr virus (EBV) DNA in children and adolescents with locoregionally advanced nasopharyngeal carcinoma (CALANPC). Methods: A total of 205 consecutive patients with CALANPC were enrolled. We used recursive partitioning analysis (RPA) to classify patients into various risk groups, with a primary endpoint of overall survival (OS). Results: Elevated SIRI (≥1.53) and EBV DNA (≥4000 copy/ml) were significantly associated with inferior OS in CALANPC. RPA categorized patients into low‐ and high‐risk groups based on prognostic factors. Survival curves showed excellent discrimination in OS (95.3% vs 77.6%; p < 0.001) between the low‐ and high‐risk groups. A significant improvement was confirmed using the prognostic methods for conventional TNM staging systems (p < 0.05). Conclusions: The combination of SIRI with EBV DNA provided a more detailed understanding of patient risks, and enhanced risk discrimination in CALANPC. [ABSTRACT FROM AUTHOR]

Background: To evaluate the clinical significance of tumor response to induction chemotherapy (IC) in locoregionally advanced nasopharyngeal carcinoma (LANPC) patients and further to develop a nomogram for predicting survival prognosis. Methods: A total of 498 patients with stage III‐IVA NPC applying IC and concurrent chemotherapy were reviewed (training cohort, n = 376; validation cohort, n = 122). Results: Tumor response was an independent predictor for clinical outcomes. The nomogram included age, N stage, pretreatment Epstein–Barr virus DNA, lymphocyte‐to‐monocyte ratio, and tumor response achieved an ideal C‐index of 0.703 (95% CI 0.655–0.751) in the validation cohort for predicting overall survival (OS), which outperformed than that of the TNM system alone (C‐index, 0.670, 95% CI: 0.622–0.718). In addition, the nomogram could successfully classified patients into different risk groups. Conclusions: We established and validated a precise and convenient nomogram based on tumor response for predicting the OS of LANPC patients. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to investigate the effect of hypothyroidism and thyroxine replacement therapy on the prognosis of nasopharyngeal carcinoma (NPC) patients. Methods: The clinical data of 284 NPC patients, who received intensity‐modulated radiation therapy (IMRT) between January 2011 and December 2016, were retrospectively analyzed. Results: Hypothyroidism occurred in 38% of patients. Patients with hypothyroidism had significantly better disease‐free survival (DFS) (p = 0.002) and relapse‐free survival (RFS) (p = 0.008). Multivariate analysis showed that hypothyroidism was a positive independent prognostic factor (DFS and RFS). Among the patients with hypothyroidism, thyroxine replacement therapy did not yield inferior survival (DFS, RFS, all p > 0.05). Conclusions: The NPC patients with complete response are at risk of hypothyroidism, which is attributable to escalating dose. These patients experienced clinical hypothyroidism could be adequately treated with thyroid hormone replacement. Further investigation of the underlying biological mechanism and potential therapeutic implications are required. [ABSTRACT FROM AUTHOR]

Background: The prognostic significance of wait time between definite diagnosis and initial radical radiotherapy is not well established in patients with locoregionally advanced nasopharyngeal carcinoma (LA‐NPC) receiving both induction chemotherapy (IC) and concurrent chemoradiotherapy (CCRT). Methods: From 2010 to 2018, 648 patients with LA‐NPC treated with IC followed by CCRT were included. Results: A total of 172 pairs of patients with LA‐NPC were selected by propensity score matching (PSM). Compared to patients with an acceptable wait time (≤75 days), patients with a prolonged wait time (>75 days) had a significant lower 5‐year DMFS rate (86.6% vs. 74.1%, p = 0.006). Subgroup analyses indicated that the unfavorable effects of longer waiting times were mainly seen among stage IVa patients. Conclusions: A prolonged wait time (>75 days) between definite diagnosis and initial radical radiotherapy has negative prognostic effects on patients with LA‐NPC receiving IC plus CCRT, particularly those with IVa stage. [ABSTRACT FROM AUTHOR]

Background: We aimed to evaluate patients suitable for definitive radiation therapy (DRT) and liver local therapy (LLT) in addition to palliative chemotherapy (PCT) among those with de novo liver metastatic nasopharyngeal carcinoma (lmNPC). Methods: The overall survival (OS) and progression‐free survival (PFS) rates were calculated and compared in 610 patients with lmNPC. Results: Both the PCT+DRT and PCT+DRT+LLT groups had better survival outcomes than the PCT group. Among patients with complete response/partial response (CR/PR) after PCT, no significant differences in survival rates were observed between those treated with PCT+DRT and PCT+DRT+LLT (2‐year PFS: 27.0% vs. 32.9%, p = 0.263). Among patients with progressive disease/stable disease (PD/SD) after PCT, significantly better survival rates were observed in patients treated with PCT+DRT+LLT. Conclusions: DRT might benefit patients with lmNPC regardless of the tumor response after PCT. For patients with CR/PR, LLT might not be needed. For patients with PD/SD, LLT might improve survival outcomes. [ABSTRACT FROM AUTHOR]

Background: We attempted to identify the most reliable immune‐related index for predicting nasopharyngeal carcinoma (NPC) prognosis and to reveal its precise and integrated relationship with NPC progression. Method: One thousand seven hundred and six patients with newly diagnosed NPC (1320 from the primary cohort and 386 from the validated cohort) from January 2010 to March 2014 were enrolled. Clinical features and 12 immune‐related variables were analyzed. Results: A high absolute lymphocyte count (ALC; >3.2 × 109/L) correlated with a poor prognosis of patients with NPC. Significant OS differences were discovered between patients with high ALC and no ALC elevation (p < 0.05, in primary cohort), showing similar prognostic risk to patients with advanced NPC (p > 0.05, in validated cohort). ALC improved the predictive performance of the basic tumor‐node‐metastasis prognostic model (p = 0.025), which was reliably validated in the external independent cohort. Conclusion: High ALC is a surrogate marker for improved prognostic risk stratification in NPC. [ABSTRACT FROM AUTHOR]