-
Cell Reports. Medicine Nov 2023Locoregional radiotherapy added to chemotherapy has significantly improved survival in de novo metastatic nasopharyngeal carcinoma (mNPC). However, only 54% of de novo...
Locoregional radiotherapy added to chemotherapy has significantly improved survival in de novo metastatic nasopharyngeal carcinoma (mNPC). However, only 54% of de novo mNPC patients who received sequential chemoradiotherapy have complete or partial response 3 months after radiotherapy. This Simon's optimal two-stage design phase II study (NCT04398056) investigates whether PD-1 inhibitor could improve tumor control in combination with chemoradiation. The primary endpoint is objective response rate (ORR) at 3 months after radiotherapy. Twenty-two patients with primary mNPC are enrolled. The ORR at 3 months after radiotherapy is 81.8% (22.7% complete response, n = 5; 59.1% partial response, n = 13), and the disease control rate is 81.8%. The 3-year progression-free survival (PFS) rate is 44.9% (95% confidence interval 26.4%-76.3%). Fifteen patients (68.2%) experienced grade 3-4 adverse events. Patients with high baseline plasma Epstein-Barr virus DNA copy number (>10 cps/mL) show worse PFS. Addition of toripalimab to sequential chemoradiotherapy suggests promising tumor response in patients with primary mNPC.
Topics: Humans; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Chemoradiotherapy
PubMed: 37951218
DOI: 10.1016/j.xcrm.2023.101279 -
Pharmaceutical Biology Dec 2023Lucialdehyde B (LB), an effective triterpenoid isolated from (Leyss. ex Fr.) Karst. (Polyproraceae), exerts cytotoxic activity against nasopharyngeal carcinoma CNE2...
CONTEXT
Lucialdehyde B (LB), an effective triterpenoid isolated from (Leyss. ex Fr.) Karst. (Polyproraceae), exerts cytotoxic activity against nasopharyngeal carcinoma CNE2 cells.
OBJECTIVE
To investigate the antiproliferative and pro-apoptotic effects of LB on CNE2 cells and explore its underlying mechanisms.
MATERIALS AND METHODS
LB concentrations of 5-40 μg/mL were used. Cell proliferation was determined using MTT, CFSE, and colony formation assays. LB-induced apoptosis and cell cycle arrest were measured by flow cytometry after 48-h LB treatments. Fluorescence microscopy and flow cytometry were performed to measure the alteration of MMP, mPTP opening, ROS level, and Ca content in CNE2 cells. Western blotting was performed to evaluate the expression of mitochondrial apoptosis-related and Ras/ERK signaling proteins.
RESULTS
IC values of LB against CNE2 cells for 24, 48, and 72 h were 25.42 ± 0.87, 14.83 ± 0.93, and 11.60 ± 0.77 μg/mL, respectively. The CFSE assay showed that the cell proliferation index was 12.70 in the LB treatment group and 31.44 in the control group. LB significantly reduced clonogenic capacity, promoted cell apoptosis and induced cell cycle arrest at the G2/M phase. Our observations also revealed that LB induced ROS and calcium aggregation, opening of mPTP, MMP reduction, upregulation of mitochondrial apoptosis-related protein expression and inhibition of Ras/ERK signaling cascades.
DISCUSSION
LB suppresses proliferation and induces mitochondrial-dependent apoptosis in nasopharyngeal carcinoma CNE2 cells.
CONCLUSIONS
LB may have a potential use as a clinical drug candidate for nasopharyngeal carcinoma treatment.
Topics: Humans; Nasopharyngeal Carcinoma; Reactive Oxygen Species; Nasopharyngeal Neoplasms; Apoptosis; Triterpenes; Cell Proliferation; Cell Line, Tumor
PubMed: 37323017
DOI: 10.1080/13880209.2023.2220754 -
Molecular Cancer Aug 2022Genetic variants associated with acute side effects of radiotherapy in nasopharyngeal carcinoma (NPC) remain largely unknown.
BACKGROUND
Genetic variants associated with acute side effects of radiotherapy in nasopharyngeal carcinoma (NPC) remain largely unknown.
METHODS
We performed a two-stage genome-wide association analysis including a total of 1084 patients, where 319 individuals in the discovery stage were genotyped for 688,783 SNPs using whole genome-wide screening microarray. Significant variants were then validated in an independent cohort of 765 patients using the MassARRAY system. Gene mapping, linkage disequilibrium, genome-wide association analysis, and polygenic risk score were conducted or calculated using FUMA, LDBlockShow, PLINK, and PRSice software programs, respectively.
RESULTS
Five SNPs (rs6711678, rs4848597, rs4848598, rs2091255, and rs584547) showed statistical significance after validation. Radiotherapy toxicity was more serious in mutant minor allele carriers of all five SNPs. Stratified analysis further indicated that rs6711678, rs4848597, rs4848598, and rs2091255 correlated with skin toxicity in patients of EBV positive, late stage (III and IV), receiving both concurrent chemoradiotherapy and induction/adjuvant chemotherapy, and with OR values ranging from 1.92 to 2.66. For rs584547, high occurrence of dysphagia was found in A allele carriers in both the discovery (P = 1.27 × 10, OR = 1.55) and validation (P = 0.002, OR = 4.20) cohorts. Furthermore, prediction models integrating both genetic and clinical factors for skin reaction and dysphagia were established. The area under curve (AUC) value of receiver operating characteristic (ROC) curves were 0.657 (skin reaction) and 0.788 (dysphagia).
CONCLUSIONS
Rs6711678, rs4848597, rs4848598, and rs2091255 on chromosome 2q14.2 and rs584547 were found to be novel risk loci for skin toxicity and dysphagia in NPC patients receiving radiotherapy.
TRIAL REGISTRATION
Chinese Clinical Trial Register (registration number: ChiCTR-OPC-14005257 and CTXY-140007-2).
Topics: Chemoradiotherapy; Deglutition Disorders; Genetic Loci; Genome-Wide Association Study; Humans; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms
PubMed: 35999636
DOI: 10.1186/s12943-022-01631-8 -
BMC Public Health Nov 2022Pharynx and larynx cancers (PLCs) are the top killer cancers in head and neck and significantly affect the quality of life of patients. A detailed study examining the...
Global trend and risk factors of the disease burden for pharynx and larynx cancers between 1990 and 2019: a systematic analysis of the global burden of disease study 2019.
BACKGROUND
Pharynx and larynx cancers (PLCs) are the top killer cancers in head and neck and significantly affect the quality of life of patients. A detailed study examining the disease burden and risk factors of PLCs is lacking.
METHODS
Data on mortality and disability-adjusted life-years (DALYs) were extracted from the Global Burden of Disease Study 2019. The estimated annual percentage change (EAPC) of the age-standardized mortality rate was calculated using a generalized linear model with a Gaussian distribution. Mortality and DALYs were stratified according to the sociodemographic index (SDI), age, gender, and risk factors. The association between the SDI and mortality rate was measured using Spearman's correlation.
RESULTS
Between 1990 and 2019, the total number of deaths due to PLCs increased by 60.7% (95% confidence intervals: 39.32 to 66.8), from 192.38 thousand in 1990 to 309.16 thousand in 2019, and the total DALYs due to PLCs increased by 49.41% (95% confidence intervals: 30.15 to 53.27), from 5.91 million in 1990 to 8.83 million in 2019. The age-standardized mortality rate declined for larynx cancer (from 2.19 in 1990 to 1.49 in 2019) and nasopharynx cancer (1.26 to 0.86) but increased slightly for other pharynx cancer (1.25 to 1.37). The death number of PLCs was significantly higher in men aged 50 to 70 years, which accounts for 46.05% and 43.83% of the total deaths in 1990 and 2019, respectively. Low and low-middle countries had the greatest age-standardized mortality rate for larynx and other pharynx cancer, while low-middle and middle countries dominated for nasopharynx cancer. The leading risk factors for PLCs were smoking and alcohol use, which account for 37.92% and 58.84% in total DALYs rate of PLCs, and the influence of risk factors was significant in men.
CONCLUSION
The total number of deaths and DALYs due to PLCs increased from 1990 to 2019. Countries with relatively low SDI and middle-aged and older men had the greatest burden of PLCs. Building better health care systems in relatively low SDI countries and improving strategies of smoking and alcohol control should be a priority in health policy.
Topics: Male; Middle Aged; Humans; Aged; Laryngeal Neoplasms; Pharynx; Quality of Life; Global Burden of Disease; Cost of Illness; Pharyngeal Neoplasms; Risk Factors; Nasopharyngeal Neoplasms
PubMed: 36443799
DOI: 10.1186/s12889-022-14654-z -
Frontiers in Public Health 2023Higher educational attainment (EA) has proven to be beneficial for preventing and treating various types of cancers. Currently, there is little evidence on the... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Higher educational attainment (EA) has proven to be beneficial for preventing and treating various types of cancers. Currently, there is little evidence on the association between EA and prevention of oral cavity and pharyngeal cancer (OCPC).
METHODS
Several databases were searched until October 1, 2022, and a meta-analysis was performed. A Mendelian randomization (MR) study was conducted with EA (i.e., the exposure) data derived from the Social Science Genetic Association Consortium and 6,034 cases of OCPC (i.e., outcome) selected from the Integrative Epidemiology Unit genome-wide association study. Five methods were used to evaluate the causality between EA and OCPC. The leave-one-out sensitivity test, MR-Egger regression, and multivariable MR (MVMR) analysis were applied to evaluate the MR results.
RESULTS
The meta-analysis included 36 eligible studies. EA was significantly and negatively associated with OCPC risk (odds ratio [OR]: 0.439, 95% confidence interval [CI]: 0.383-0.503, < 0.001). MR analysis revealed that the risk of OCPC, oropharyngeal cancer, and oral cavity cancer decreased with an increase in education (OR: 0.349, 95% CI: 0.222-0.548, < 0.001; OR: 0.343, 95% CI: 0.198-0.597; < 0.001; OR: 0.342, 95% CI: 0.195-0.601, < 0.001, respectively). Even after correcting for mediators, high EA still significantly reduced the risk of OCPC (OR: 0.361, 95% CI: 0.281-0.463, < 0.001).
CONCLUSION
Both the meta-analysis and MR results demonstrated that high levels of EA can reduce the risk of OCPC in the general population.
Topics: Humans; Genome-Wide Association Study; Mendelian Randomization Analysis; Oropharyngeal Neoplasms; Educational Status; Databases, Factual
PubMed: 37124787
DOI: 10.3389/fpubh.2023.1132035 -
Medical Sciences (Basel, Switzerland) Oct 2023Malnutrition in esophageal and pharyngeal cancer patients constitutes a common and serious concern, which significantly reduces patients' prognoses. Cancers of the... (Review)
Review
May Nutritional Status Positively Affect Disease Progression and Prognosis in Patients with Esophageal and Pharyngeal Cancers? A Scoping Review of the Current Clinical Studies.
BACKGROUND
Malnutrition in esophageal and pharyngeal cancer patients constitutes a common and serious concern, which significantly reduces patients' prognoses. Cancers of the esophagus and the pharynx can considerably impair feeding in patients, resulting in severe undernutrition. This is a scoping review that intends to critically analyze the most well-designed clinical studies investigating the potential beneficial impact of diverse nutritional assessment tools on the prognosis of patients with esophageal and pharyngeal cancers.
METHODS
The most accurate and remarkable scientific databases were comprehensively explored utilizing relative keywords to detect clinical studies that investigate whether nutritional status may affect disease prognosis.
RESULTS
Several assessment tools have evaluated and highlighted the potential beneficial impact of nutritional status on disease progression and patients' prognosis in both esophageal and pharyngeal cancers. Regarding esophageal cancer, CONUT, PNI, PG-SGA, and NRS-2002 are more commonly used, while albumin is also frequently evaluated. Regarding pharyngeal cancers, fewer studies are currently available. PNI has been evaluated, and its significance as a factor for shorter survival' times has been highlighted. The Comprehensive Nutritional Index has also been evaluated with positive results, as well as NRS 2002, GPS, and body-weight status. However, there is currently a lack of studies with an adequate number of women with cancer. An international literature gap was identified concerning follow-up studies with adequate methodology.
CONCLUSIONS
Nutritional status may significantly affect disease progression and patients' survival, highlighting the significance of a great nutritional status in individuals with esophageal and pharyngeal cancers. Further large-scale and well-designed prospective surveys should be performed to verify the potential beneficial effects of adequate nourishment in people suffering from cancer of the esophagus and pharynx.
Topics: Humans; Female; Nutritional Status; Prospective Studies; Prognosis; Disease Progression; Esophageal Neoplasms; Pharyngeal Neoplasms
PubMed: 37873749
DOI: 10.3390/medsci11040064 -
The Lancet. Oncology Dec 2022The effects of the COVID-19 pandemic continue to constrain health-care staff and resources worldwide, despite the availability of effective vaccines. Aerosol-generating... (Review)
Review
International recommendations for plasma Epstein-Barr virus DNA measurement in nasopharyngeal carcinoma in resource-constrained settings: lessons from the COVID-19 pandemic.
The effects of the COVID-19 pandemic continue to constrain health-care staff and resources worldwide, despite the availability of effective vaccines. Aerosol-generating procedures such as endoscopy, a common investigation tool for nasopharyngeal carcinoma, are recognised as a likely cause of SARS-CoV-2 spread in hospitals. Plasma Epstein-Barr virus (EBV) DNA is considered the most accurate biomarker for the routine management of nasopharyngeal carcinoma. A consensus statement on whether plasma EBV DNA can minimise the need for or replace aerosol-generating procedures, imaging methods, and face-to-face consultations in managing nasopharyngeal carcinoma is urgently needed amid the current pandemic and potentially for future highly contagious airborne diseases or natural disasters. We completed a modified Delphi consensus process of three rounds with 33 international experts in otorhinolaryngology or head and neck surgery, radiation oncology, medical oncology, and clinical oncology with vast experience in managing nasopharyngeal carcinoma, representing 51 international professional societies and national clinical trial groups. These consensus recommendations aim to enhance consistency in clinical practice, reduce ambiguity in delivering care, and offer advice for clinicians worldwide who work in endemic and non-endemic regions of nasopharyngeal carcinoma, in the context of COVID-19 and other airborne pandemics, and in future unexpected settings of severe resource constraints and insufficiency of personal protective equipment.
Topics: Humans; COVID-19; Pandemics; Herpesvirus 4, Human; SARS-CoV-2; Nasopharyngeal Carcinoma; Epstein-Barr Virus Infections; DNA; Nasopharyngeal Neoplasms
PubMed: 36455583
DOI: 10.1016/S1470-2045(22)00505-8 -
Genes Jan 2024This study explores the potential causal association between proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors and tumor development using Mendelian...
This study explores the potential causal association between proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors and tumor development using Mendelian randomization (MR) based on drug targets. Instrumental variables within ±100 kb of the gene locus, impacting low-density lipoprotein cholesterol (LDL-C), were utilized for MR analysis. Coronary heart disease (CHD) served as a positive control to validate the causal relationship between PCSK9 inhibitors and various cancers. We employed reverse MR to address the reverse causation concerns. Data from positive controls and tumors were sourced from OpenGWAS. MR analysis suggested a negative causal relationship between PCSK9 inhibitors and both breast and lung cancers (95% 0.81~0.99, = 2.25 × 10; 95% 0.65~0.94, = 2.55 × 10). In contrast, a positive causal link was observed with gastric, hepatic, and oral pharyngeal cancers and cervical intraepithelial neoplasia (95% 1.14~1.75, = 1.88 × 10; 95% 1.46~2.53, = 1.16 × 10; 95% 4.49~6.33, = 3.36 × 10; 95% 4.56~7.12, = 6.91 × 10), without heterogeneity or pleiotropy ( > 0.05). Sensitivity analyses confirmed these findings. The results of MR of drug targets suggested no causal relationship between PCSK9 inhibitors and bladder cancer, thyroid cancer, pancreatic cancer, colorectal cancer, malignant neoplasms of the kidney (except for renal pelvis tumors), malignant neoplasms of the brain, and malignant neoplasms of the esophagus ( > 0.05). Reverse MR helped mitigate reverse causation effects. The study indicates a divergent causal relationship of PCSK9 inhibitors with certain cancers. While negatively associated with breast and lung cancers, a positive causal association was observed with gastric, hepatic, oral cavity, and pharyngeal cancers and cervical carcinoma in situ. No causal links were found with bladder, thyroid, pancreatic, colorectal, certain kidney, brain, and esophageal cancers.
Topics: Female; Humans; Proprotein Convertase 9; PCSK9 Inhibitors; Subtilisin; Mendelian Randomization Analysis; Proprotein Convertases; Breast Neoplasms; Lung Neoplasms; Pharyngeal Neoplasms; Carcinoma in Situ
PubMed: 38275613
DOI: 10.3390/genes15010132 -
Scientific Reports May 2023Positron emission tomography/computed tomography (PET/CT) with F-fluorodeoxyglucose (FDG) is widely used for management of nasopharyngeal carcinoma (NPC). Combining the... (Randomized Controlled Trial)
Randomized Controlled Trial
Positron emission tomography/computed tomography (PET/CT) with F-fluorodeoxyglucose (FDG) is widely used for management of nasopharyngeal carcinoma (NPC). Combining the radiomic features of pre- and post-treatment FDG PET images may improve tumor characterization and prognostic predication. We investigated prognostic value of radiomic features from pre- and post-radiotherapy FDG PET images in patients with NPC. Quantitative radiomic features of primary tumors were extracted from the FDG PET images of 145 NPC patients and the delta values were also calculated. The study population was divided randomly into two groups, the training and test sets (7:3). A random survival forest (RSF) model was adopted to perform analyses of progression-free survival (PFS) and overall survival (OS). There were 37 (25.5%) cases of recurrence and 16 (11.0%) cases of death during a median follow-up period of 54.5 months. Both RSF models with clinical variables and radiomic PET features for PFS and OS showed comparable predictive performance to RSF models with clinical variables and conventional PET parameters. Tumoral radiomic features of pre- and post-treatment FDG PET and the corresponding delta values may predict PFS and OS in patients with NPC.
Topics: Humans; Fluorodeoxyglucose F18; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Prognosis; Retrospective Studies
PubMed: 37231092
DOI: 10.1038/s41598-023-35582-x -
Signal Transduction and Targeted Therapy Oct 2020Nasopharyngeal carcinoma (NPC) is a malignant epithelial carcinoma of the head and neck region which mainly distributes in southern China and Southeast Asia and has a... (Review)
Review
Nasopharyngeal carcinoma (NPC) is a malignant epithelial carcinoma of the head and neck region which mainly distributes in southern China and Southeast Asia and has a crucial association with the Epstein-Barr virus. Based on epidemiological data, both incidence and mortality of NPC have significantly declined in recent decades grounded on the improvement of living standard and medical level in an endemic region, in particular, with the clinical use of individualized chemotherapy and intensity-modulated radiotherapy (IMRT) which profoundly contributes to the cure rate of NPC patients. To tackle the challenges including local recurrence and distant metastasis in the current NPC treatment, we discussed the implication of using targeted therapy against critical molecules in various signal pathways, and how they synergize with chemoradiotherapy in the NPC treatment. Combination treatment including targeted therapy and IMRT or concurrent chemoradiotherapy is presumably to be future options, which may reduce radiation or chemotherapy toxicities and open new avenues for the improvement of the expected functional outcome for patients with advanced NPC.
Topics: Combined Modality Therapy; Humans; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Radiotherapy, Intensity-Modulated; Signal Transduction
PubMed: 33093441
DOI: 10.1038/s41392-020-00340-2