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JPMA. the Journal of the Pakistan... Aug 2023Dysphagia is a medical condition that makes it difficult for a person to eat or swallow. It is estimated that 590 million people worldwide have dysphagia. The causes are... (Review)
Review
Dysphagia is a medical condition that makes it difficult for a person to eat or swallow. It is estimated that 590 million people worldwide have dysphagia. The causes are varied and include neurological disorders like stroke and motor neuron disease, head and neck cancer, neuromuscular diseases, inflammatory diseases such as dermatomyositis, dementia, cervical spinal cord injury, and anterior vertebral ossification. The assessment and screening of dysphagia consists of a questionnaire-based interview, mealtime observation, and, if deemed necessary by a screening test or instrumental examination by specialists. Treatment is based on the diagnosis, patients' cognition and information gathered by screening and clinical evaluation. Patient's function can be improved only when treatment is comprehensive and includes compensatory feeding using an adjusted swallowing diet, compensatory posture adjustment, and nutritional improvement. We present a brief overview of the assessment and management strategies for dysphagia.
Topics: Humans; Cognition; Deglutition; Deglutition Disorders; Medicine; Posture
PubMed: 37697781
DOI: 10.47391/JPMA.23-61 -
JAMA Nov 2023There are currently no therapies approved by the US Food and Drug Administration for nasopharyngeal carcinoma (NPC). Gemcitabine-cisplatin is the current standard of... (Comparative Study)
Comparative Study Randomized Controlled Trial
IMPORTANCE
There are currently no therapies approved by the US Food and Drug Administration for nasopharyngeal carcinoma (NPC). Gemcitabine-cisplatin is the current standard of care for the first-line treatment of recurrent or metastatic NPC (RM-NPC).
OBJECTIVE
To determine whether toripalimab in combination with gemcitabine-cisplatin will significantly improve progression-free survival and overall survival as first-line treatment for RM-NPC, compared with gemcitabine-cisplatin alone.
DESIGN, SETTING, AND PARTICIPANTS
JUPITER-02 is an international, multicenter, randomized, double-blind phase 3 study conducted in NPC-endemic regions, including mainland China, Taiwan, and Singapore. From November 10, 2018, to October 20, 2019, 289 patients with RM-NPC with no prior systemic chemotherapy in the RM setting were enrolled from 35 participating centers.
INTERVENTIONS
Patients were randomized (1:1) to receive toripalimab (240 mg [n = 146]) or placebo (n = 143) in combination with gemcitabine-cisplatin for up to 6 cycles, followed by maintenance with toripalimab or placebo until disease progression, intolerable toxicity, or completion of 2 years of treatment.
MAIN OUTCOME
Progression-free survival as assessed by a blinded independent central review. Secondary end points included objective response rate, overall survival, progression-free survival assessed by investigator, duration of response, and safety.
RESULTS
Among the 289 patients enrolled (median age, 46 [IQR, 38-53 years; 17% female), at the final progression-free survival analysis, toripalimab treatment had a significantly longer progression-free survival than placebo (median, 21.4 vs 8.2 months; HR, 0.52 [95% CI, 0.37-0.73]). With a median survival follow-up of 36.0 months, a significant improvement in overall survival was identified with toripalimab over placebo (hazard ratio [HR], 0.63 [95% CI, 0.45-0.89]; 2-sided P = .008). The median overall survival was not reached in the toripalimab group, while it was 33.7 months in the placebo group. A consistent effect on overall survival, favoring toripalimab, was found in subgroups with high and low PD-L1 (programmed death-ligand 1) expression. The incidence of all adverse events, grade 3 or greater adverse events, and fatal adverse events were similar between the 2 groups. However, adverse events leading to discontinuation of toripalimab or placebo (11.6% vs 4.9%), immune-related adverse events (54.1% vs 21.7%), and grade 3 or greater immune-related adverse events (9.6% vs 1.4%) were more frequent in the toripalimab group.
CONCLUSIONS AND RELEVANCE
The addition of toripalimab to chemotherapy as first-line treatment for RM-NPC provided statistically significant and clinically meaningful progression-free survival and overall survival benefits compared with chemotherapy alone, with a manageable safety profile. These findings support the use of toripalimab plus gemcitabine-cisplatin as the new standard of care for this patient population.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT03581786.
Topics: Adult; Female; Humans; Male; Middle Aged; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Cisplatin; Double-Blind Method; Gemcitabine; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Neoplasm Recurrence, Local; United States; Internationality
PubMed: 38015220
DOI: 10.1001/jama.2023.20181 -
International Journal of Oncology Aug 2023Nasopharyngeal carcinoma (NPC) is an epithelial tumor located in the nasopharynx and is highly associated with Epstein‑Barr virus (EBV) infection. Although... (Review)
Review
Nasopharyngeal carcinoma (NPC) is an epithelial tumor located in the nasopharynx and is highly associated with Epstein‑Barr virus (EBV) infection. Although radiotherapy alone can cure ~90% of patients with early‑stage disease, >70% of patients with NPC have locoregionally advanced or metastatic disease at the first diagnosis due to the insidious and aggressive nature of NPC. After comprehensive radiochemotherapy, 20‑30% of patients with advanced NPC still fail treatment, mainly due to recurrence and/or metastasis (R/M). Conventional salvage treatments, such as radiotherapy, chemotherapy and surgery, are suboptimal and frequently accompanied by severe adverse effects and limited efficacy. In recent years, immunotherapy has emerged as a promising treatment modality for R/M NPC. An increasing number of clinical studies have investigated the safety and efficacy of immunotherapy for advanced NPC and have shown considerable progress. In the present review, the rationale for the use of immunotherapy to treat NPC was summarized and the current status, progress and challenges of NPC clinical research on different immunotherapeutic approaches were highlighted, including immune checkpoint inhibitors, vaccines, immunomodulators, adoptive cell transfer and EBV‑specific monoclonal antibodies. The comprehensive overview of immunotherapy in NPC may provide insight for clinical practice and future investigation.
Topics: Humans; Nasopharyngeal Carcinoma; Epstein-Barr Virus Infections; Nasopharyngeal Neoplasms; Herpesvirus 4, Human; Immunotherapy
PubMed: 37417358
DOI: 10.3892/ijo.2023.5545 -
JAMA Oncology Oct 2023Lip, oral, and pharyngeal cancers are important contributors to cancer burden worldwide, and a comprehensive evaluation of their burden globally, regionally, and...
The Global, Regional, and National Burden of Adult Lip, Oral, and Pharyngeal Cancer in 204 Countries and Territories: A Systematic Analysis for the Global Burden of Disease Study 2019.
IMPORTANCE
Lip, oral, and pharyngeal cancers are important contributors to cancer burden worldwide, and a comprehensive evaluation of their burden globally, regionally, and nationally is crucial for effective policy planning.
OBJECTIVE
To analyze the total and risk-attributable burden of lip and oral cavity cancer (LOC) and other pharyngeal cancer (OPC) for 204 countries and territories and by Socio-demographic Index (SDI) using 2019 Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study estimates.
EVIDENCE REVIEW
The incidence, mortality, and disability-adjusted life years (DALYs) due to LOC and OPC from 1990 to 2019 were estimated using GBD 2019 methods. The GBD 2019 comparative risk assessment framework was used to estimate the proportion of deaths and DALYs for LOC and OPC attributable to smoking, tobacco, and alcohol consumption in 2019.
FINDINGS
In 2019, 370 000 (95% uncertainty interval [UI], 338 000-401 000) cases and 199 000 (95% UI, 181 000-217 000) deaths for LOC and 167 000 (95% UI, 153 000-180 000) cases and 114 000 (95% UI, 103 000-126 000) deaths for OPC were estimated to occur globally, contributing 5.5 million (95% UI, 5.0-6.0 million) and 3.2 million (95% UI, 2.9-3.6 million) DALYs, respectively. From 1990 to 2019, low-middle and low SDI regions consistently showed the highest age-standardized mortality rates due to LOC and OPC, while the high SDI strata exhibited age-standardized incidence rates decreasing for LOC and increasing for OPC. Globally in 2019, smoking had the greatest contribution to risk-attributable OPC deaths for both sexes (55.8% [95% UI, 49.2%-62.0%] of all OPC deaths in male individuals and 17.4% [95% UI, 13.8%-21.2%] of all OPC deaths in female individuals). Smoking and alcohol both contributed to substantial LOC deaths globally among male individuals (42.3% [95% UI, 35.2%-48.6%] and 40.2% [95% UI, 33.3%-46.8%] of all risk-attributable cancer deaths, respectively), while chewing tobacco contributed to the greatest attributable LOC deaths among female individuals (27.6% [95% UI, 21.5%-33.8%]), driven by high risk-attributable burden in South and Southeast Asia.
CONCLUSIONS AND RELEVANCE
In this systematic analysis, disparities in LOC and OPC burden existed across the SDI spectrum, and a considerable percentage of burden was attributable to tobacco and alcohol use. These estimates can contribute to an understanding of the distribution and disparities in LOC and OPC burden globally and support cancer control planning efforts.
Topics: Adult; Female; Humans; Male; Global Burden of Disease; Global Health; Incidence; Lip; Pharyngeal Neoplasms; Quality-Adjusted Life Years; Risk Factors; Tobacco Use
PubMed: 37676656
DOI: 10.1001/jamaoncol.2023.2960 -
Current Treatment Options in Oncology Sep 2023Nasopharyngeal carcinoma (NPC) is distinct in its anatomic location and biology from other epithelial head and neck cancer (HNC). There are 3 WHO subtypes, which... (Review)
Review
Nasopharyngeal carcinoma (NPC) is distinct in its anatomic location and biology from other epithelial head and neck cancer (HNC). There are 3 WHO subtypes, which considers the presence of Epstein-Barr virus (EBV) and other histopathology features. Despite the survival benefit obtained from modern treatment modalities and techniques specifically in the local and locally advanced setting, a number of patients with this disease will recur and subsequently die of distant metastasis, locoregional relapse, or both. In the recurrent setting, the ideal therapy approach continues to be a topic of discussion and current recommendations are platinum-based combination chemotherapy. Phase III clinical trials which led to the approval of pembrolizumab or nivolumab for head and neck squamous cell carcinoma (HNSCC) specifically excluded NPC. No immune checkpoint inhibitor therapy, to date, has been approved by the FDA to treat NPC although the National Comprehensive Cancer Network (NCCN) recommendations do include use of these agents. Hence, this remains the major challenge for treatment options. Nasopharyngeal carcinoma is challenging as it is really 3 different diseases, and much research is required to determine best options and sequencing of those options. This article is going to address the data to date and discuss ongoing research in EBV + and EBV - inoperable recurrent/metastatic NPC patients.
Topics: Humans; Nasopharyngeal Carcinoma; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Neoplasm Recurrence, Local; Head and Neck Neoplasms; Nasopharyngeal Neoplasms
PubMed: 37318724
DOI: 10.1007/s11864-023-01101-3 -
Journal of Critical Care Feb 2024Dysphagia is common in intensive care unit (ICU) patients, yet it remains underrecognized and often unmanaged despite being associated with life-threatening... (Review)
Review
BACKGROUND
Dysphagia is common in intensive care unit (ICU) patients, yet it remains underrecognized and often unmanaged despite being associated with life-threatening complications, prolonged ICU stays and hospitalization.
PURPOSE
To propose an expert opinion for the diagnosis and management of dysphagia developed from evidence-based clinical recommendations and practitioner insights.
METHODS
A multinational group of dysphagia and critical care experts conducted a literature review using a modified ACCORD methodology. Based on a fusion of the available evidence and the panel's clinical experience, an expert opinion on best practice management was developed.
RESULTS
The panel recommends adopting clinical algorithms intended to promote standardized, high-quality care that triggers timely systematic dysphagia screening, assessment, and treatment of extubated and tracheostomized patients in the ICU.
CONCLUSIONS
Given the lack of robust scientific evidence, two clinical management algorithms are proposed for use by multidisciplinary teams to improve early systematic detection and effective management of dysphagia in ICU patients. Additionally, emerging therapeutic options such as neurostimulation have the potential to improve the quality of ICU dysphagia care.
Topics: Humans; Deglutition Disorders; Expert Testimony; Critical Care; Mass Screening; Intensive Care Units
PubMed: 37924574
DOI: 10.1016/j.jcrc.2023.154447 -
European Journal of Pediatrics Dec 2023This study aims to provide a comparison of the current recommendations about the management of acute pharyngitis. A literature search was conducted from January 2009 to... (Review)
Review
This study aims to provide a comparison of the current recommendations about the management of acute pharyngitis. A literature search was conducted from January 2009 to 2023. Documents reporting recommendations on the management of acute pharyngitis were included, pertinent data were extracted, and a descriptive comparison of the different recommendations was performed. The quality of guidelines was assessed through the AGREE II instrument. Nineteen guidelines were included, and an overall moderate quality was found. Three groups can be distinguished: one group supports the antibiotic treatment of group A β-hemolytic Streptococcus (GABHS) to prevent acute rheumatic fever (ARF); the second considers acute pharyngitis a self-resolving disease, recommending antibiotics only in selected cases; the third group recognizes a different strategy according to the ARF risk in each patient. An antibiotic course of 10 days is recommended if the prevention of ARF is the primary goal; conversely, some guidelines suggest a course of 5-7 days, assuming the symptomatic cure is the goal of treatment. Penicillin V and amoxicillin are the first-line options. In the case of penicillin allergy, first-generation cephalosporins are a suitable choice. In the case of beta-lactam allergy, clindamycin or macrolides could be considered according to local resistance rates. Conclusion: Several divergencies in the management of acute pharyngitis were raised among guidelines (GLs) from different countries, both in the diagnostic and therapeutic approach, allowing the distinction of 3 different strategies. Since GABHS pharyngitis could affect the global burden of GABHS disease, it is advisable to define a shared strategy worldwide. It could be interesting to investigate the following issues further: cost-effectiveness analysis of diagnostic strategies in different healthcare systems; local genomic epidemiology of GABHS infection and its complications; the impact of antibiotic treatment of GABHS pharyngitis on its complications and invasive GABHS infections; the role of GABHS vaccines as a prophylactic measure. The related results could aid the development of future recommendations. What is Known: • GABHS disease spectrum ranges from superficial to invasive infections and toxin-mediated diseases. • GABHS accounts for about 25% of sore throat in children and its management is a matter of debate. What is New: • Three strategies can be distinguished among current GLs: antibiotic therapy to prevent ARF, antibiotics only in complicated cases, and a tailored strategy according to the individual ARF risk. • The impact of antibiotic treatment of GABHS pharyngitis on its sequelae still is the main point of divergence; further studies are needed to achieve a global shared strategy.
Topics: Child; Adult; Humans; Streptococcus pyogenes; Streptococcal Infections; Pharyngitis; Anti-Bacterial Agents; Hypersensitivity
PubMed: 37819417
DOI: 10.1007/s00431-023-05211-w -
Journal of Experimental & Clinical... Feb 2024In recent years, the development of adjunctive therapeutic hyperthermia for cancer therapy has received considerable attention. However, the mechanisms underlying...
BACKGROUND
In recent years, the development of adjunctive therapeutic hyperthermia for cancer therapy has received considerable attention. However, the mechanisms underlying hyperthermia resistance are still poorly understood. In this study, we investigated the roles of cold‑inducible RNA binding protein (Cirbp) in regulating hyperthermia resistance and underlying mechanisms in nasopharyngeal carcinoma (NPC).
METHODS
CCK-8 assay, colony formation assay, tumor sphere formation assay, qRT-PCR, Western blot were employed to examine the effects of hyperthermia (HT), HT + oridonin(Ori) or HT + radiotherapy (RT) on the proliferation and stemness of NPC cells. RNA sequencing was applied to gain differentially expressed genes upon hyperthermia. Gain-of-function and loss-of-function experiments were used to evaluate the effects of RNAi-mediated Cirbp silencing or Cirbp overexpression on the sensitivity or resistance of NPC cells and cancer stem-like cells to hyperthermia by CCK-8 assay, colony formation assay, tumorsphere formation assay and apoptosis assay, and in subcutaneous xenograft animal model. miRNA transient transfection and luciferase reporter assay were used to demonstrate that Cirbp is a direct target of miR-377-3p. The phosphorylation levels of key members in ATM-Chk2 and ATR-Chk1 pathways were detected by Western blot.
RESULTS
Our results firstly revealed that hyperthermia significantly attenuated the stemness of NPC cells, while combination treatment of hyperthermia and oridonin dramatically increased the killing effect on NPC cells and cancer stem cell (CSC)‑like population. Moreover, hyperthermia substantially improved the sensitivity of radiation‑resistant NPC cells and CSC‑like cells to radiotherapy. Hyperthermia noticeably suppressed Cirbp expression in NPC cells and xenograft tumor tissues. Furthermore, Cirbp inhibition remarkably boosted anti‑tumor‑killing activity of hyperthermia against NPC cells and CSC‑like cells, whereas ectopic expression of Cirbp compromised tumor‑killing effect of hyperthermia on these cells, indicating that Cirbp overexpression induces hyperthermia resistance. ThermomiR-377-3p improved the sensitivity of NPC cells and CSC‑like cells to hyperthermia in vitro by directly suppressing Cirbp expression. More importantly, our results displayed the significantly boosted sensitization of tumor xenografts to hyperthermia by Cirbp silencing in vivo, but ectopic expression of Cirbp almost completely counteracted hyperthermia-mediated tumor cell-killing effect against tumor xenografts in vivo. Mechanistically, Cirbp silencing-induced inhibition of DNA damage repair by inactivating ATM-Chk2 and ATR-Chk1 pathways, decrease in stemness and increase in cell death contributed to hyperthermic sensitization; conversely, Cirbp overexpression-induced promotion of DNA damage repair, increase in stemness and decrease in cell apoptosis contributed to hyperthermia resistance.
CONCLUSION
Taken together, these findings reveal a previously unrecognized role for Cirbp in positively regulating hyperthermia resistance and suggest that thermomiR-377-3p and its target gene Cirbp represent promising targets for therapeutic hyperthermia.
Topics: Animals; Humans; Nasopharyngeal Neoplasms; Sincalide; Nasopharyngeal Carcinoma; MicroRNAs; Neoplastic Stem Cells; Hyperthermia, Induced; Cell Line, Tumor; Cell Proliferation; Gene Expression Regulation, Neoplastic; Diterpenes, Kaurane
PubMed: 38419081
DOI: 10.1186/s13046-024-02983-3 -
The Lancet. Oncology Aug 2023Most newly diagnosed oropharyngeal and hypopharyngeal cancers are treated with chemoradiotherapy with curative intent but at the consequence of adverse effects on... (Randomized Controlled Trial)
Randomized Controlled Trial
Dysphagia-optimised intensity-modulated radiotherapy versus standard intensity-modulated radiotherapy in patients with head and neck cancer (DARS): a phase 3, multicentre, randomised, controlled trial.
BACKGROUND
Most newly diagnosed oropharyngeal and hypopharyngeal cancers are treated with chemoradiotherapy with curative intent but at the consequence of adverse effects on quality of life. We aimed to investigate if dysphagia-optimised intensity-modulated radiotherapy (DO-IMRT) reduced radiation dose to the dysphagia and aspiration related structures and improved swallowing function compared with standard IMRT.
METHODS
DARS was a parallel-group, phase 3, multicentre, randomised, controlled trial done in 22 radiotherapy centres in Ireland and the UK. Participants were aged 18 years and older, had T1-4, N0-3, M0 oropharyngeal or hypopharyngeal cancer, a WHO performance status of 0 or 1, and no pre-existing swallowing dysfunction. Participants were centrally randomly assigned (1:1) using a minimisation algorithm (balancing factors: centre, chemotherapy use, tumour type, American Joint Committee on Cancer tumour stage) to receive DO-IMRT or standard IMRT. Participants and speech language therapists were masked to treatment allocation. Radiotherapy was given in 30 fractions over 6 weeks. Dose was 65 Gy to primary and nodal tumour and 54 Gy to remaining pharyngeal subsite and nodal areas at risk of microscopic disease. For DO-IMRT, the volume of the superior and middle pharyngeal constrictor muscle or inferior pharyngeal constrictor muscle lying outside the high-dose target volume had a mandatory 50 Gy mean dose constraint. The primary endpoint was MD Anderson Dysphagia Inventory (MDADI) composite score 12 months after radiotherapy, analysed in the modified intention-to-treat population that included only patients who completed a 12-month assessment; safety was assessed in all randomly assigned patients who received at least one fraction of radiotherapy. The study is registered with the ISRCTN registry, ISRCTN25458988, and is complete.
FINDINGS
From June 24, 2016, to April 27, 2018, 118 patients were registered, 112 of whom were randomly assigned (56 to each treatment group). 22 (20%) participants were female and 90 (80%) were male; median age was 57 years (IQR 52-62). Median follow-up was 39·5 months (IQR 37·8-50·0). Patients in the DO-IMRT group had significantly higher MDADI composite scores at 12 months than patients in the standard IMRT group (mean score 77·7 [SD 16·1] vs 70·6 [17·3]; mean difference 7·2 [95% CI 0·4-13·9]; p=0·037). 25 serious adverse events (16 serious adverse events assessed as unrelated to study treatment [nine in the DO-IMRT group and seven in the standard IMRT group] and nine serious adverse reactions [two vs seven]) were reported in 23 patients. The most common grade 3-4 late adverse events were hearing impairment (nine [16%] of 55 in the DO-IMRT group vs seven [13%] of 55 in the standard IMRT group), dry mouth (three [5%] vs eight [15%]), and dysphagia (three [5%] vs eight [15%]). There were no treatment-related deaths.
INTERPRETATION
Our findings suggest that DO-IMRT improves patient-reported swallowing function compared with standard IMRT. DO-IMRT should be considered a new standard of care for patients receiving radiotherapy for pharyngeal cancers.
FUNDING
Cancer Research UK.
Topics: Humans; Male; Female; Middle Aged; Radiotherapy, Intensity-Modulated; Deglutition Disorders; Quality of Life; Head and Neck Neoplasms; Chemoradiotherapy
PubMed: 37423227
DOI: 10.1016/S1470-2045(23)00265-6 -
Ugeskrift For Laeger Nov 2023
Topics: Humans; Pharyngitis; Pain
PubMed: 37987453
DOI: No ID Found