Neutrophil-to-lymphocyte ratio as a prognostic marker for head and neck squamous cell carcinoma treated with immune checkpoint inhibitors: Meta-analysis.

We investigated the prognostic impact of the neutrophil-to-lymphocyte ratio (NLR) in patients with head and neck squamous cell carcinoma (HNSCC) treated with immune checkpoint inhibitors (ICIs). We systematically searched electronic databases and identified articles reporting an association between NLR and treatment results in patients with HNSCC treated with ICIs. Hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) and odds ratios (ORs) for response and disease control were extracted. Pooled HRs and ORs were estimated using random-effects models. Fourteen studies involving 929 patients were included. A higher NLR was associated with poor OS (HR 2.03, 95% confidence interval [CI] 1.50-2.74), PFS (HR 2.15, 95% CI 1.44-3.21), response (OR 0.49, 95% CI 0.26-0.93), and disease control (OR 0.30, 95% CI 0.12-0.74). The NLR predicts treatment results with ICIs in patients with HNSCC.

Gene Transfer of Skeletal Muscle-Type Myosin Light Chain Kinase via Adeno-Associated Virus 6 Improves Muscle Functions in an Amyotrophic Lateral Sclerosis Mouse Model.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that shows progressive muscle weakness. A few treatments exist including symptomatic therapies, which can prolong survival or reduce a symptom; however, no fundamental therapies have been found. As a therapeutic strategy, enhancing muscle force is important for patients' quality of life. In this study, we focused on skeletal muscle-specific myosin regulatory light chain kinase (skMLCK), which potentially enhances muscle contraction, as overexpression of skMLCK was thought to improve muscle function. The adeno-associated virus serotype 6 encoding skMLCK (AAV6/skMLCK) and eGFP (control) was produced and injected intramuscularly into the lower limbs of SOD1G37R mice, which are a familial ALS model. AAV6/skMLCK showed the successful expression of skMLCK in the muscle tissues. Although the control did not affect the muscle force in both of the WT and SOD1G37R mice, AAV6/skMLCK enhanced the twitch force of SOD1G37R mice and the tetanic force of WT and SOD1G37R mice. These results indicate that overexpression of skMLCK can enhance the tetanic force of healthy muscle as well as rescue weakened muscle function. In conclusion, the gene transfer of skMLCK has the potential to be a new therapy for ALS as well as for other neuromuscular diseases.

Prognostic impact of sarcopenia in patients with head and neck cancer treated with surgery or radiation: A meta-analysis.

BACKGROUND: The objective of this study was to compare the prognostic impact of sarcopenia in patients with head and neck cancer (HNC) treated with surgery or radiation. METHODS: We systematically searched electronic databases to identify articles reporting the impact of sarcopenia on the prognosis of patients with HNC. Hazard ratios (HRs) and 95% confidence intervals (CIs) for overall survival (OS), disease-free survival (DFS), and disease-specific survival (DSS) were extracted and pooled. HR according to treatment modality were estimated using random-effects models. Statistical analyses were carried out using the Comprehensive Meta-Analysis software. RESULTS: In total, 18 studies enrolling 3,233 patients were included. Sarcopenia was associated with poor OS in both surgery and radiotherapy groups (hazard ratio [HR] 2.50, 95% confidence interval [CI] 1.95-3.21; HR 1.63, 95% CI 1.40-1.90, respectively). The HR was significantly higher in the surgery group than in the radiotherapy group (p = 0.004), with similar results obtained for DFS (HR 2.59, 95% CI 1.56-4.31; HR 1.56, 95% CI 1.24-1.97 for the surgery and radiotherapy groups, respectively) and DSS (HR 2.96, 95% CI 0.73-11.95; HR 2.67, 95% CI 1.51-4.73 for the surgery and RT groups, respectively). CONCLUSIONS: Sarcopenia was a poor prognostic factor for HNC, regardless of the treatment modality. However, the adverse effects of sarcopenia on survival were more prominent in the surgery group than in the radiotherapy group. Sarcopenia assessment is required for appropriate treatment decision-making.

Predictive impact of sarcopenia in solid cancers treated with immune checkpoint inhibitors: a meta-analysis.

Sarcopenia, which is characterized by a decrease in muscle quantity or quality, is commonly observed in patients with cancer. Recent research has reported contradictory results on the association between sarcopenia and the efficacy of immune checkpoint inhibitors (ICIs). We conducted a systematic review and meta-analysis to investigate this discrepancy. We systematically searched three electronic databases to identify articles reporting on the association between sarcopenia and treatment outcomes in patients with solid cancers who received ICIs. The outcomes assessed were hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), and odds ratios (ORs) for objective response rate (ORR), disease control rate (DCR), and toxicity. Pooled estimates and their 95% confidence intervals (CIs) were calculated. A total of 2501 patients from 26 studies were analysed. Sarcopenia was observed in 44.7% (95% CI: 38.2-51.3) of the patients and was significantly associated with poor survival (HR = 1.55, 95% CI = 1.32-1.82 for OS and HR = 1.61, 95% CI = 1.35 to 1.93 for PFS). The HRs (95% CIs) for OS according to the diagnostic measures used were 1.97 (0.88-4.41) for psoas muscle index (PMI), 1.41 (0.87-2.28) for skeletal muscle density (SMD), and 1.43 (1.23-1.67) for skeletal mass index (SMI). The HRs (95% CIs) for PFS were 1.86 (1.08-3.21) for PMI, 1.27 (0.94-1.71) for SMD, and 1.38 (1.11-1.71) for SMI. Poor radiological response to ICI therapy was observed in patients with sarcopenia (OR = 0.52, 95% CI = 0.34-0.80 for ORR and OR = 0.45, 95% CI = 0.30-0.67 for DCR). The ORs for ORR (95% CIs) were 0.56 (0.15-2.05) for PMI and 0.78 (0.56-1.09) for SMI. The oncologic outcomes associated with melanoma and non-small cell lung cancer (NSCLC) were comparable with those observed overall (HR for OS = 2.02, 95% CI = 1.26-3.24 for melanoma and HR for OS = 1.61, 95% CI = 1.19-2.18 for NSCLC). In contrast, the occurrence of severe toxicity was not associated with sarcopenia (OR = 1.13, 95% CI = 0.51-2.52). Poor survival and poor response in patients with sarcopenia indicate a negative association between sarcopenia and efficacy of ICIs. Sarcopenia's predictive ability is consistent across various tumour types. For the selection of patients who may respond to ICIs pre-therapeutically, the presence of sarcopenia should be assessed in clinical practice.

The CR9 element is a novel mechanical load-responsive enhancer that regulates natriuretic peptide genes expression.

Enhancers regulate gene expressions in a tissue- and pathology-specific manner by altering its activities. Plasma levels of atrial and brain natriuretic peptides, encoded by the Nppa and Nppb, respectively, and synthesized predominantly in cardiomyocytes, vary depending on the severity of heart failure. We previously identified the noncoding conserved region 9 (CR9) element as a putative Nppb enhancer at 22-kb upstream from the Nppb gene. However, its regulatory mechanism remains unknown. Here, we therefore investigated the mechanism of CR9 activation in cardiomyocytes using different kinds of drugs that induce either cardiac hypertrophy or cardiac failure accompanied by natriuretic peptides upregulation. Chronic treatment of mice with either catecholamines or doxorubicin increased CR9 activity during the progression of cardiac hypertrophy to failure, which is accompanied by proportional increases in Nppb expression. Conversely, for cultured cardiomyocytes, doxorubicin decreased CR9 activity and Nppb expression, while catecholamines increased both. However, exposing cultured cardiomyocytes to mechanical loads, such as mechanical stretch or hydrostatic pressure, upregulate CR9 activity and Nppb expression even in the presence of doxorubicin. Furthermore, the enhancement of CR9 activity and Nppa and Nppb expressions by either catecholamines or mechanical loads can be blunted by suppressing mechanosensing and mechanotransduction pathways, such as muscle LIM protein (MLP) or myosin tension. Finally, the CR9 element showed a more robust and cell-specific response to mechanical loads than the -520-bp BNP promoter. We concluded that the CR9 element is a novel enhancer that responds to mechanical loads by upregulating natriuretic peptides expression in cardiomyocytes.

Clinical significance of cervical and ocular vestibular evoked myogenic potentials in benign paroxysmal positional vertigo: a meta-analysis.

PURPOSE: As the pathological cause of benign paroxysmal positional vertigo (BPPV), the dislocation or degeneration of otoconia in the utricle and saccule is suggested. Vestibular evoked myogenic potential (VEMP) could reflect otolithic dysfunction due to these etiologies of BPPV. The aim of this study was to validate the clinical significance of cervical (c) and ocular (o) VEMP in BPPV by a meta-analysis of previous articles. METHODS: Articles related to BPPV with data on cVEMP and oVEMP were collected. The following keywords were used to search PubMed and Scopus for English language articles: benign paroxysmal positional vertigo or BPPV and vestibular evoked myogenic potential or VEMP. RESULTS: The p13 latency in cVEMP and n1 latency in oVEMP were slightly but significantly prolonged in BPPV patients compared to control patients. AR in oVEMP of BPPV patients also showed higher value than that of control patients. However, the n23 latency and AR in cVEMP and p1 latency in oVEMP showed no significant difference between BPPV and control patients. Furthermore, latencies in VEMPs also showed no significant difference between an affected and a non-affected ear in BPPV patients. CONCLUSIONS: Our results indicated that otolith dysfunction of BPPVs was detected by latencies in VEMPs, and AR in oVEMP more sensitively reflects the difference between affected and non-affected ears in BPPV patients. The otolith dysfunction of BPPV might be induced by the systemic condition. However, the differences of latencies between BPPV patients and control patients were too small to use VEMPs as a prognostic predictor.

Sphenopalatine artery surgery for refractory idiopathic epistaxis: Systematic review and meta-analysis.

OBJECTIVES: Epistaxis, especially posterior epistaxis, is occasionally refractory to treatment. In these cases, sphenopalatine artery surgeries, including cauterization and ligation, are required. Previous reports have demonstrated treatment results for these procedures but failed to provide high-level evidence. The aim of this study was to quantify the rates of failure and perioperative complications of these procedures by using a meta-analysis technique. METHODS: We systematically searched electronic databases and identified articles regarding epistaxis, sphenopalatine artery ligation, or cauterization. Pooled rebleeding and complication rates were calculated by using a random effects model. RESULTS: A total of 896 cases of sphenopalatine ligation or cauterization for epistaxis were analyzed. Pooled rebleeding rates for the entire cohort, cauterization group, and ligation group were 13.4% (95% confidence interval [CI] 10.0-17.8, P < 0.001), 7.2% (95% CI 4.6-11.0, P < 0.001), and 15.1% (95% CI 9.8-22.5, P < 0.001), respectively. Pooled perioperative complication rates for the entire cohort, cauterization group, and ligation group were 8.7% (95% CI 4.9-15.1, P < 0.001), 10.2% (95% CI 3.8-24.5, P < 0.001), and 6.4% (95% CI 1.8-20.9, P < 0.001), respectively. CONCLUSION: Overall, sphenopalatine surgery for refractory epistaxis is an effective method because of its low rates of failure and complications. Cauterization is more effective than ligation, whereas complications are comparable between the two procedures. Laryngoscope, 129:1731-1736, 2019.

Change in endolymphatic hydrops 2 years after endolymphatic sac surgery evaluated by MRI.

OBJECTIVE: This study was performed to determine whether endolymphatic sac surgery improves vestibular and cochlear endolymphatic hydrops 2 years after sac surgery and to elucidate the relationship between the degree of improvement of endolymphatic hydrops and the changes in vertigo symptoms, the hearing level, and the summating potential/action potential ratio (-SP/AP ratio) by electrocochleography (ECochG) in patients with Ménière's disease (MD). METHODS: Twenty-one patients with unilateral MD who underwent sac surgery were included in this study. All patients underwent gadolinium-enhanced magnetic resonance imaging (Gd-MRI) before and 2 years after sac surgery. We evaluated the difference in vestibular and cochlear endolymphatic hydrops between before and after surgery in both ears and compared these findings with the frequency of vertigo attacks, hearing level, and ECochG findings. RESULTS: In affected ears, the presence of vestibular endolymphatic hydrops and the frequency of vertigo attacks significantly decreased after surgery. However, affected ears showed no significant improvement in the presence of cochlear endolymphatic hydrops or the -SP/AP ratio by ECochG; there was also no significant improvement or deterioration in the hearing level. CONCLUSION: The present findings suggest that sac surgery reduces vestibular endolymphatic hydrops and prevents aggravation of cochlear endolymphatic hydrops, and these changes lead to a reduction of vertigo attacks and suppress the progression of hearing impairment associated with vertigo attacks.

Platelet count and platelet-lymphocyte ratio as prognostic markers for head and neck squamous cell carcinoma: Meta-analysis.

BACKGROUND: Thrombocytosis is associated with the prognosis of various types of cancer. The purpose of this study was to quantify the prognostic impact of platelet count and platelet-lymphocyte ratio (PLR) in head and neck squamous cell carcinoma (HNSCC). METHODS: We systematically searched electronic databases and identified articles reporting an association between platelet count or PLR and HNSCC prognosis. Hazard ratios (HRs) and 95% confidence intervals (CIs) for overall survival (OS) were extracted, and the pooled HRs were estimated using random effect models. RESULTS: Eight studies that enrolled 4096 patients and 9 studies that enrolled 2327 patients were included in the platelet count and PLR analyses, respectively. A platelet count greater than the cutoff value was associated with poor OS (HR 1.81; 95% CI 1.16-2.82) and any PLR greater than the cutoff value was associated with poor OS (HR 1.64; 95% CI 1.13-2.37). CONCLUSION: Elevated platelet count and PLR are associated with poor prognosis in patients with HNSCC.

A case of adult congenital laryngeal cleft asymptomatic until hypopharynx cancer treatment.

Laryngeal cleft is an anomaly of failed posterior closure of the larynx. Most cases are diagnosed and need treatment early in life due to respiratory and swallowing problems. We report an unusual case of a 66-year-old man with an asymptomatic laryngeal cleft until treatment for hypopharyngeal cancer. During concurrent chemoradiotherapy (CCRT), despite reduced tumor volume, he presented severe dysphagia and dyspnea, followed by severe pneumonia twice. Because CCRT had to be discontinued, a pharyngolaryngectomy was performed for the cancer treatment. The resected specimen showed total removal of the tumor and a total longitudinal cleft of the cricoid cartilage, classified as a type III laryngeal cleft by the Benjamin and Inglis' classification. A review of computed tomography images indicated that the redundant mucosa from bilateral edges closed the separation of the posterior cricoid cartilage and narrowed the laryngeal airway during CCRT. Adult presentations of laryngeal cleft are quite rare with only ten reported cases in English literature; the present case is of the oldest patient. Undiagnosed cases with laryngeal cleft may exist asymptomatically or without severe symptoms. The awareness of this condition may increase its diagnosis as a cause of diseases such as aspiration and recurrent pneumonia even in adult patients.

Prognostic role of neutrophil-to-lymphocyte ratio in head and neck cancer: A meta-analysis.

BACKGROUND: Neutrophils play substantial roles in cancer progression. Previous reports demonstrated the prognostic impact of the pretreatment neutrophil-to-lymphocyte ratio (NLR) in various types of solid cancers. The purpose of this study was to quantify the prognostic impact of NLR on head and neck squamous cell carcinoma (HNSCC). METHODS: We systematically searched electronic databases, identified articles regarding NLR and HNSCC mortality, and extracted hazard ratios (HRs) and 95% confidence intervals (CIs). Pooled HRs for overall survival (OS) and disease-specific survival (DSS) were estimated using random effect models. RESULTS: Nineteen studies enrolling 3770 patients were included in the analyses. Overall, NLR greater than the cutoff value was associated with poorer OS and DSS (HR 1.69; 95% CI 1.47-1.93; P < .001 and HR 1.88; 95% CI 1.20-2.95; P = .006, respectively). CONCLUSION: Elevated NLR predicts worse outcomes in patients with HNSCC.

A high jugular bulb and poor development of perivestibular aqueductal air cells are not the cause of endolymphatic hydrops in patients with Ménière's disease.

OBJECTIVE: The presence of endolymphatic hydrops in the inner ear, which can be detected with gadolinium-enhanced magnetic resonance imaging (Gd-MRI), is widely recognized as the main pathological cause of Ménière's disease (MD). However, the precise mechanisms underlying the development of endolymphatic hydrops remains unclear. One hypothesis proposes a relationship between the presence of a high jugular bulb (HJB) and MD, which disrupts the vestibular aqueduct leading to the development of endolymphatic hydrops. This study sought to identify anatomical features in MD patients using computed tomography (CT) images of the temporal bone. METHODS: Fifty-nine MD patients meeting the AAO-HNS diagnostic criteria and exhibiting endolymphatic hydrops in Gd-MRI were enrolled between July 2009 and December 2015. We only included MD patients who showed unilateral endolymphatic hydrops in Gd-MRI. Sixty-six patients with otosclerosis or facial palsy were also enrolled as control participants. In both groups, patients with other pathologies (e.g., chronic otitis media or cholesteatoma) and patients <16years old were excluded. HJB was defined as a JB that was observable in the axial CT image at the level where the round window could be visualized. JB surface area was measured on the axial image at the level where the foramen spinosum could be visualized. Finally, to investigate the relationship between the pneumatization of perivestibular aqueductal air cells and the existence of endolymphatic hydrops, the development of the air cells was rated using a three-grade evaluation system and the distance between the posterior semicircular canal (PSCC) and the posterior fossa dura was measured. RESULTS: The presence of HJB was observed in 22 of 59 affected sides of MD patients and in 17 healthy sides. The likelihood that HJB was detected on an affected side (22/39) was not significantly above chance (50%). The HJB detection rate did not significantly differ between the three groups (MD affected side, MD healthy side, and control patients). Furthermore, there were no significant group differences in JB surface area, distance between the PSCC and posterior fossa dura, or the development of perivestibular aqueductal air cells. CONCLUSION: We did not find any relationship between the anatomy of the temporal bones and the existence of endolymphatic hydrops. Moreover, we found no evidence suggesting that HJB or poor development of perivestibular aqueductal air cells were the cause of endolymphatic hydrops in MD patients.

Pretreatment serum lactate dehydrogenase as a prognostic indicator for oral cavity squamous cell carcinoma.

OBJECTIVES: To examine whether lactate dehydrogenase (LDH) can predict the prognosis of oral cavity squamous cell carcinoma (OSCC) and to determine the optimal cut-off values for LDH. METHODS: This retrospective study included 184 patients with OSCC, treated with surgery between 2006 and 2014. The association between LDH and T, N classification was investigated using the Mann-Whitney test. Cut-off values for LDH were determined with a recursive partitioning analysis (RPA). Survival rates were estimated using the Kaplan-Meier method. A Cox hazard model was used to assess the prognostic capability of LDH. RESULTS: There was no association between LDH and T or N classification (p = .657, .619, respectively). RPA determined the cut-off values for LDH as 160 and 220 IU/L. The five year survival for low-, moderate-, and high-LDH groups were 87.7, 73.7, and 50.9%, respectively (p < .001). The hazard ratios (HRs) for death in moderate- and high-LDH groups were 2.92 (95%CI =1.02-12.30, p = .001) and 7.36 (95%CI =2.54-31.20, p < .001), respectively. The model including LDH-based stratification (Akaike's information criterion (AIC) = 516) was better than the model including clinical stage (AIC =528). CONCLUSION: Pretreatment serum LDH is an independent prognostic factor for overall survival in patients with OSCC.

Age-adjusted Charlson Comorbidity Index predicts prognosis of laryngopharyngeal cancer treated with radiation therapy.

OBJECTIVES: To examine the ability of comorbidity indices to predict the prognosis of laryngopharyngeal cancer and their association with treatment modalities. METHODS: This retrospective study included 198 patients with laryngeal, hypopharyngeal, and oropharyngeal cancers. The effect of comorbidity indices on overall survival between surgery and (chemo)-radiation therapy ((C)RT) groups was analyzed. The cumulative incidence rates for cancer mortality and other mortalities according to the age-adjusted Charlson Comorbidity Index (ACCI) and Charlson Comorbidity Index (CCI) were compared. RESULTS: Univariate survival analyses showed a significant association between the ACCI and overall survival in the (C)RT group, but not in the surgery group. The association between the CCI and overall survival was not significant in either group. In multivariate analyses, a high ACCI score was an independent prognostic factor in the (C)RT group (HR 2.89, 95% confidence interval (CI) 1.28-6.49), but not in the surgery group (HR 1.39, 95%CI 0.27-5.43). The higher ACCI group had increased mortality from other causes compared with the lower ACCI group (5-year cumulative incidence, 8.5% and 17.8%, respectively, p = .003). CONCLUSION: The ACCI was a better prognostic factor than the CCI. Surgery may be more beneficial than radiation for patients with a high ACCI.

Development and validation of a new comorbidity index for patients with head and neck squamous cell carcinoma in Japan.

Due to habitual drinking and smoking and advanced age at diagnosis, patients with head and neck squamous cell carcinoma (HNSCC) frequently present with comorbidities. Several comorbidity indices have been developed and validated for HNSCC. However, none have become the standard method. In this study, we developed a new comorbidity index for Japanese patients with HNSCC, which was validated against an independent data set. A Cox proportional hazards analysis of 698 patients identified dementia, connective tissue diseases, and second primary malignancies in the oesophagus, head and neck, lungs, and stomach as prognostic comorbidities for overall survival. The Osaka head and neck comorbidity index (OHNCI) was generated from the weighted points of these comorbidities. In the independent data set, the 5-year overall survival rates for the low, moderate, and high scoring OHNCI groups were 62.1%, 64.3%, and 37.7%, respectively. In the multivariate analysis, the high scoring OHNCI group was an independent prognostic factor for overall survival (hazard ratio: 1.81, 95% confidence interval: 1.05-3.13; P = 0.031). The model including the OHNCI exhibited a higher prognostic capability compared to those including other commonly used comorbidity indices. The OHNCI could become the primary choice for comorbidity assessment in patients with HNSCC in Japan.

Surgery With or Without Postoperative Radiation Therapy for Early-stage External Auditory Canal Squamous Cell Carcinoma: A Meta-analysis.

OBJECTIVE: External auditory canal squamous cell carcinoma (EACSCC) is a rare disease with no standard treatment supported by high-level evidence. The aim of this study was to investigate EACSCC prognoses according to treatment modality and thus determine the optimal intervention for early-stage disease. DATA SOURCES: PubMed, Scopus, and Ichushi-Web searches of the English and Japanese-language literature published between January 1, 2006 and December 31, 2016 were performed using the key words "external auditory canal cancer" and "temporal bone cancer." STUDY SELECTION: Articles related to EACSCC that include the 5-year overall survival rate or individual patient data for histological types, follow-up periods, and final outcomes were enrolled. DATA EXTRACTION: Sex, age, Moody's modified Pittsburgh stage, type of treatment modality, type of operation, follow-up period, and 5-year survival rates were extracted. DATA SYNTHESIS: Twenty articles were used for the aggregate meta-analysis using a random-effects model, and 18 articles that reported 99 patients with early-stage EACSCC were used for the individual patient data meta-analysis. CONCLUSION: The 5-year overall survival rate of early-stage EACSCC was 77%. Postoperative radiation therapy (PORT) was performed in 45% of stage I patients and 68% of stage II patients. Survival analysis of all patients showed no differences between the surgery-only and PORT groups; however, PORT exhibited a better prognosis than surgery alone among patients with stage I disease (p = 0.003, log-rank test). This result indicated that PORT can be the standard therapy for stages I and II EACSCC.

Prognostic role of neutrophil-lymphocyte ratio in nasopharyngeal carcinoma: A meta-analysis.

BACKGROUND: Inflammatory markers are used to predict prognosis of nasopharyngeal carcinoma (NPC). Previous reports of neutrophil-to-lymphocyte ratio (NLR) and NPC mortality are inconsistent. This study aimed to quantify the prognostic impact of NLR on NPC. METHODS: The primary outcome was overall survival (OS), and the secondary outcomes were disease-specific survival (DSS), progression-free survival (PFS) and distant metastasis-free survival (DMFS). We systematically searched electronic databases, identified articles reporting an association between NLR and NPC prognosis. Hazard ratios (HRs) and 95% confidence intervals (CIs) were extracted, and pooled HRs for each outcome were estimated using random effect models. RESULTS: Nine studies enrolling 5397 patients were included in the analyses. NLR greater than the cutoff value was associated with poor overall survival (HR 1.51, 95% CI 1.27-1.78), disease-specific survival (HR 1.44, 95% CI 1.22-1.71), progression-free survival (HR 1.53, 95% CI 1.22-1.90), and distant metastasis-free survival (HR 1.83, 95% CI 1.14-2.95). CONCLUSIONS: Elevated NLR predicts worse OS, DSS, PFS and DMFS in patients with NPC.