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Radiotherapy and Oncology : Journal of... Dec 2023Given the central role that radiation has in the management of head and neck squamous cell carcinoma of unknown primary origin, it is imperative to review how treatment...
PURPOSE
Given the central role that radiation has in the management of head and neck squamous cell carcinoma of unknown primary origin, it is imperative to review how treatment paradigms have been refined and continue to evolve in the modern era.
METHODS AND MATERIALS
This study was designed based on the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) statement. A literature search of peer-reviewed publications was undertaken to identify works pertaining to the use of radiation for squamous cell carcinoma of unknown primary origin presenting as cervical lymph node metastases. Articles published from January 2002 to January 2023 with full text available on PubMed and restricted to the English language and human subjects were included. The full bibliographies of identified articles were reviewed and irrelevant studies were removed.
RESULTS
While such breakthroughs as intensity-modulated radiotherapy, positron emission tomography, biomarker testing with immune-histochemistry, and minimally invasive surgical techniques such as transoral robotic surgery have fundamentally changed the approach to this disease in recent decades, controversies still exist with respect to the manner in which radiation is delivered. Although the incidence of head and neck unknown primary cancer is relatively low, questions regarding the necessity of comprehensive radiation using the age-old standard method of targeting the bilateral necks and entire pharyngeal axis to encompass all putative sites of mucosal disease persist.
CONCLUSIONS
Prospective evidence is lacking, and the available studies have been complicated by such factors as the relatively limited sample sizes, as well as the variability in work-up, treatment, inclusion criteria, and follow-up. Regardless, advances in science and technology have ushered in more precise approaches with a high degree of customization, particularly given the increased proportion of patients presenting with human papillomavirus-related disease.
Topics: Humans; Head and Neck Neoplasms; Human Papillomavirus Viruses; Meta-Analysis as Topic; Neoplasms, Unknown Primary; Papillomavirus Infections; Systematic Reviews as Topic
PubMed: 37844736
DOI: 10.1016/j.radonc.2023.109952 -
Head & Neck Nov 2022The aim of this meta-analysis was to determine the diagnostic test accuracy of sentinel lymph node biopsy (SLNB) in patients with oropharyngeal, laryngeal, and... (Meta-Analysis)
Meta-Analysis Review
The aim of this meta-analysis was to determine the diagnostic test accuracy of sentinel lymph node biopsy (SLNB) in patients with oropharyngeal, laryngeal, and hypopharyngeal squamous cell carcinoma (SCC). For this purpose, MEDLINE, EMBASE, and Web of Science were searched from inception to March 8, 2022. Included were studies evaluating diagnostic test accuracy of SLNB to identify cervical lymph node metastases with elective neck dissection or follow-up as reference. A bivariate generalized linear mixed model approach was used for the meta-analysis. Nineteen studies were eligible, evaluating 377 cases in total. The pooled estimates of sensitivity and negative predictive value were 0.93 (95% CI: 0.86-0.96) and 0.97 (95% CI: 0.94-0.98), respectively. The excellent accuracy of SLNB justifies a place in the diagnostic workup of patients with larynx and pharynx SCC. Randomized trials are required to demonstrate oncologic safety and benefits on treatment related morbidity and quality of life when omitting elective neck treatment based on SLNB.
Topics: Carcinoma, Squamous Cell; Diagnostic Tests, Routine; Head and Neck Neoplasms; Humans; Hypopharynx; Larynx; Lymph Nodes; Oropharynx; Quality of Life; Sentinel Lymph Node Biopsy; Squamous Cell Carcinoma of Head and Neck
PubMed: 36047597
DOI: 10.1002/hed.27175 -
Scientific Reports Sep 2021Early prediction of treatment response in nasopharyngeal carcinoma is clinically relevant for optimizing treatment strategies. This meta-analysis was performed to... (Meta-Analysis)
Meta-Analysis
Early prediction of treatment response in nasopharyngeal carcinoma is clinically relevant for optimizing treatment strategies. This meta-analysis was performed to evaluate whether apparent diffusion coefficient (ADC) from diffusion-weighted imaging (DWI) can predict treatment response of patients with nasopharyngeal carcinoma. A systematic search of PubMed-MEDLINE and Embase was performed to identify relevant original articles until July 22, 2021. We included studies which performed DWI for predicting locoregional treatment response in nasopharyngeal carcinoma treated with neoadjuvant chemotherapy, definitive chemoradiation, or radiation therapy. Hazard ratios were meta-analytically pooled using a random-effects model for the pooled estimates of overall survival, local relapse-free survival, distant metastasis-free survival and their 95% CIs. ADC showed a pooled sensitivity of 87% (95% CI 72-94%) and specificity of 70% (95% CI 56-80%) for predicting treatment response. Significant between-study heterogeneity was observed for both pooled sensitivity (I = 68.5%) and specificity (I = 92.2%) (P < 0.01). The pooled hazard ratios of low pretreatment ADC for assessing overall survival, local relapse-free survival, and distant metastasis-free survival were 1.42 (95% CI 1.09-1.85), 2.31 (95% CI 1.42-3.74), and 1.35 (95% CI 1.05-1.74), respectively. In patients with nasopharyngeal carcinoma, pretreatment ADC demonstrated good predictive performance for treatment response.
Topics: Chemoradiotherapy; Diffusion Magnetic Resonance Imaging; Disease-Free Survival; Feasibility Studies; Humans; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Nasopharynx; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Predictive Value of Tests; Prognosis; Risk Assessment
PubMed: 34556743
DOI: 10.1038/s41598-021-98508-5 -
BMC Cancer Apr 2021The clinical significance of tumor-stroma ratio (TSR) has been examined in many tumors. Here we systematically reviewed all studies that evaluated TSR in head and neck... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The clinical significance of tumor-stroma ratio (TSR) has been examined in many tumors. Here we systematically reviewed all studies that evaluated TSR in head and neck cancer.
METHODS
Four databases (Scopus, Medline, PubMed and Web of Science) were searched using the term tumo(u)r-stroma ratio. The preferred reporting items for systematic reviews and meta-analyses (PRISMA) were followed.
RESULTS
TSR was studied in nine studies of different subsites (including cohorts of nasopharyngeal, oral, laryngeal and pharyngeal carcinomas). In all studies, TSR was evaluated using hematoxylin and eosin staining. Classifying tumors based on TSR seems to allow for identification of high-risk cases. In oral cancer, specifically, our meta-analysis showed that TSR is significantly associated with both cancer-related mortality (HR 2.10, 95%CI 1.56-2.84) and disease-free survival (HR 1.84, 95%CI 1.38-2.46).
CONCLUSIONS
The assessment of TSR has a promising prognostic value and can be implemented with minimum efforts in routine head and neck pathology.
Topics: Carcinoma, Squamous Cell; Disease-Free Survival; Head and Neck Neoplasms; Humans; Laryngeal Neoplasms; Nasopharyngeal Neoplasms; Pharyngeal Neoplasms; Stromal Cells
PubMed: 33931044
DOI: 10.1186/s12885-021-08222-8 -
Head & Neck Oct 2022This systematic review and meta-analysis aims to estimate the prevalence and prognostic impact of retropharyngeal lymph node metastases (RLNMs) in oropharyngeal squamous... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This systematic review and meta-analysis aims to estimate the prevalence and prognostic impact of retropharyngeal lymph node metastases (RLNMs) in oropharyngeal squamous cell carcinoma (OPSCC).
METHODS
This meta-analysis was conducted according to PRISMA guidelines.
INCLUSION CRITERIA
studies with more than 20 patients reporting the prevalence or prognostic impact of RLNMs in OPSCC. Whenever available, data on HPV status and subsites were extracted.
RESULTS
Twenty-two articles were included. The overall prevalence of RLNMs in OPSCC was 13%, with no significant differences depending on HPV status. The highest prevalence was observed for posterior pharyngeal wall SCC (24%), followed by soft palate (17%), palatine tonsil (15%), and base of tongue (8%). RLNMs were associated with a significantly higher risk of death (HR:2.54;IC95%1.89-3.41) and progression (HR:2.44;IC95%1.80-3.30).
CONCLUSIONS
The prevalence of RLNMs in OPSCC was 13%, being higher in tumors of the posterior pharyngeal wall. RLNMs were associated with unfavorable outcomes.
Topics: Carcinoma, Squamous Cell; Head and Neck Neoplasms; Humans; Lymph Nodes; Lymphatic Metastasis; Oropharyngeal Neoplasms; Papillomavirus Infections; Prevalence; Prognosis; Retrospective Studies; Squamous Cell Carcinoma of Head and Neck
PubMed: 35913029
DOI: 10.1002/hed.27166 -
Cancers Apr 2020Head and neck squamous cell carcinoma (HNSCC) is one of the main neoformations of the head-neck region and is characterized by the presence of squamous carcinomatous... (Review)
Review
Head and neck squamous cell carcinoma (HNSCC) is one of the main neoformations of the head-neck region and is characterized by the presence of squamous carcinomatous cells of the multi-layered epithelium lining the oral cavity, larynx, and pharynx. The annual incidence of squamous cell carcinoma of the head and neck (HNSCC) comprises approximately 600,000 new cases globally. Currently, the 5-year survival from HNSCC is less than 50%. Surgical, radiotherapy, and chemotherapy treatments strongly compromise patient quality of life. MicroRNAs (miRNAs) are a family of small noncoding endogenous RNAs that function in regulating gene expression by regulating several biological processes, including carcinogenesis. The main upregulated microRNAs associated with oral carcinoma are miR-21, miR-455-5p, miR-155-5p, miR-372, miR-373, miR-29b, miR-1246, miR-196a, and miR-181, while the main downregulated miRNAs are miR-204, miR-101, miR-32, miR-20a, miR-16, miR-17, and miR-125b. miR-21 represents one of the first oncomirs studied. The present systematic review work was performed based on the preferred reporting items for systematic review and meta-analysis (PRISMA) protocol. A search was carried out in the PubMed and Scopus databases with the use of keywords. This search produced 628 records which, after the elimination of duplicates and the application of the inclusion and exclusion criteria, led to 7 included articles. The heterogeneity of the studies according to the odds ratio was high, with a Q value of 26.616 ( < 0.001), and the was 77.457% for specificity. The heterogeneity was high, with a Q value of 25.243 ( < 0.001) and the was 76.231% for sensitivity. The heterogeneity of data showed a Q value of 27.815 ( < 0.001) and the was 78.429%. Therefore, the random-effects model was selected. The diagnostic odds ratio was 7.620 (95% CI 3.613-16.070). The results showed that the sensitivity was 0.771 (95% CI 0.680-0.842) ( < 0.001) while, for specificity, we found 0.663 (95% CI 0.538-0.770) ( < 0.001). The negative likelihood ratio (NLR) was 0.321 (95% CI 0.186-0.554), and the positive likelihood ratio (PLR) was 2.144 (95% CI 1.563-2.943). The summary ROC plot demonstrates that the diagnostic test presents good specificity and sensitivity, and the area under the curve (AUC), as calculated from the graph, was 0.79.
PubMed: 32290144
DOI: 10.3390/cancers12040936 -
JAMA Network Open Feb 2023Ipsilateral neck radiotherapy (RT) is controversial in some patients with tonsil cancer due to concern for nodal failure within the contralateral nonirradiated neck... (Meta-Analysis)
Meta-Analysis
Association of Unilateral Radiotherapy With Contralateral Lymph Node Failure Among Patients With Squamous Cell Carcinoma of the Tonsil: A Systematic Review and Meta-analysis.
IMPORTANCE
Ipsilateral neck radiotherapy (RT) is controversial in some patients with tonsil cancer due to concern for nodal failure within the contralateral nonirradiated neck (hereinafter referred to as contralateral neck failure [CNF]).
OBJECTIVE
To determine the rate of CNF following ipsilateral neck RT in patients with tonsil cancer.
DATA SOURCES
Databases including PubMed, Embase, Web of Science, and Cochrane Library were queried for peer-reviewed, English language articles published between January 1, 1980, and December 31, 2021.
STUDY SELECTION
Studies reporting rates of CNF from at least 20 patients treated with ipsilateral neck RT. Studies were excluded if they lacked full text, reported results from databases or systematic reviews, or did not provide RT details.
DATA EXTRACTION AND SYNTHESIS
Data were extracted following the PRISMA reporting guideline. Study quality was assessed using criteria from a methodological index for nonrandomized studies. Pooled outcomes were estimated using random-effects models.
MAIN OUTCOMES AND MEASURES
Primary outcome was the pooled rate of CNF following ipsilateral neck RT. Secondary outcomes were the pooled rates of CNF by tumor and nodal staging categories from the 7th edition of the AJCC Cancer Staging Manual and rates of toxic effects.
RESULTS
A total of 17 studies (16 retrospective and 1 prospective) including 1487 unique patients were identified. The pooled risk of CNF was 1.9% (95% CI, 1.2%-2.6%). The rate of CNF by tumor (T) category was as follows: 1.3% (95% CI, 0.3%-2.3%) for T1; 3.0% (95% CI, 1.6%-4.4%) for T2; 11.3% (95% CI, 3.3%-19.2%) for T3; and 16.0% (95% CI, -7.8% to 39.8%) for T4. Patients with T3 to T4 tumors had a significantly higher rate of CNF than those with T1 to T2 tumors (11.5% [95% CI, 3.9%-19.1%] vs 1.8% [95% CI, 1.0%-2.6%]; P < .001). The rate of CNF by nodal (N) category was 1.2% (95% CI, 0.1%-2.2%) for N0; 4.8% (95% CI, 2.4%-7.2%) for N1; 3.1% (95% CI, 0.4%-5.8%) for N2a; 3.1% (95% CI, 1.2%-4.9%) for N2b; and 0 (95% CI, not applicable) for N3. Rates of CNF were similar for patients with N2b to N3 and N0 to N2a disease (3.0% [95% CI, 1.2%-4.7%] vs 1.7% [95% CI, 0.6%-2.8%], respectively; P = .07). Compared with bilateral RT, ipsilateral RT was associated with increased risk of CNF (log odds ratio, 1.29 [95% CI, 0.09-2.48]; P = .04). The crude rates of xerostomia of grade 3 or greater and feeding tube use were 0.9% (95% CI, -0.2% to 1.9%) and 13.3% (95% CI, 8.3%-18.3%), respectively.
CONCLUSIONS AND RELEVANCE
In this systematic review and meta-analysis, ipsilateral neck RT was associated with a low rate of CNF in patients with small, lateralized tonsil cancers. Bilateral neck RT was associated with lower risk of CNF compared with ipsilateral neck RT. Patients with tumors of a higher T category were at increased risk for CNF following ipsilateral neck RT, and advanced nodal stage was not associated with CNF. Rates of toxic effects appeared favorable in patients treated with ipsilateral neck RT.
Topics: Humans; Tonsillar Neoplasms; Retrospective Studies; Palatine Tonsil; Prospective Studies; Neoplasm Staging; Lymph Nodes; Carcinoma, Squamous Cell
PubMed: 36753275
DOI: 10.1001/jamanetworkopen.2022.55209 -
Frontiers in Bioscience (Landmark... Jul 2021: Several studies suggest that there is an association between the metastatic nodal tumor volume and the clinical outcome in patients with solid cancers. However,...
: Several studies suggest that there is an association between the metastatic nodal tumor volume and the clinical outcome in patients with solid cancers. However, despite the prognostic potential of nodal volume, a standardized method for estimating the nodal volumetric parameters is lacking. Herein, we conducted a systematic review of the published scientific literature towards investigating the prognostic value of nodal volume in the carcinomas of head and neck, taking into consideration the primary tumor site and the human papillomavirus (HPV) status. : For this purpose, the biomedical literature database PubMed/MEDLINE was searched for studies relevant to the relationship of nodal volume to the treatment outcome and survival in head and neck squamous cell carcinoma (HNSCC) patients. Collectively, based on stringent inclusion/exclusion criteria, 23 eligible studies were included in the present systematic review. : On the basis of our findings, nodal volume is suggested to be strongly associated with clinical outcomes in HNSCC patients. Of particular note, there is an indication that nodal volume is an independent factor for further risk stratification for recurrence-free survival in patients with squamous cell carcinoma of the pharynx (oropharynx and hypopharynx). Extranodal extension (ENE) and HPV status should be also taken into consideration in further studies.
Topics: Carcinoma, Squamous Cell; Head and Neck Neoplasms; Humans; Prognosis; Squamous Cell Carcinoma of Head and Neck; Tumor Burden
PubMed: 34340270
DOI: 10.52586/4937 -
Medicine Oct 2020Hypopharyngeal and esophageal squamous cell carcinoma (ESCC) are the most common double primary tumors with poor prognosis. Intensive work has been made to illuminate... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Hypopharyngeal and esophageal squamous cell carcinoma (ESCC) are the most common double primary tumors with poor prognosis. Intensive work has been made to illuminate the etiology, but the common carcinogenic mechanism remains unclear. Thus, we conducted the study to seek to find the common gene signatures and key functional pathways associated with oncogenesis and treatment in hypopharyngeal squamous cell carcinoma (HSCC) and ESCC by bioinformatic analysis.
METHODS
Three independent datasets (GSE2379, GSE20347, and GSE75241) were screened out from the Gene Expression Omnibus (GEO) database and the overlapping differentially expressed genes (DEGs) were identified using GEO2R online platform. Subsequently, the Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment analysis of DEGs were conducted using database for annotation, visualization and integrated discovery (DAVID). Meanwhile, the protein-protein interaction network (PPI) constructed by search tool for the retrieval of interacting genes (STRING) was visualized using Cytoscape. Afterwards, the most key module and hub genes were extracted from the PPI network using the Molecular Complex Detection plugin. Moreover, the gene expression profiling interactive analysis (GEPIA) was applied to verify the expression differences and conduct the survival analyses of hub genes. Finally, the interaction network of miRNAs and hub genes constructed by encyclopedia of RNA interactomes (ENCORI) was visualized using Cytoscape.
RESULTS
A total of 43 DEGs were identified, comprising 25 upregulated genes and 18 downregulated genes, which were mainly involved in the extracellular matrix-receptor interaction, collagen metabolic, epidermis development, cell adhesion, and PI3K/Akt signaling pathways. Subsequently, 12 hub genes were obtained and survival analysis demonstrated SERPINE1 and SPP1 were closely related to poor prognosis of patients with HSCC and ESCC. Finally, hsa-miR-29c-3p, hsa-miR-29a-3p, and hsa-miR-29b-3p were confirmed as the top 3 interactive miRNAs that target the most hub genes according to the interaction network of miRNAs and hub genes.
CONCLUSION
The common gene signatures and functional pathways identified in the study may contribute to understanding the molecular mechanisms involved in the carcinogenesis and progression of HSCC and ESCC, and provide potential diagnostic and therapeutic targets.
Topics: Biomarkers, Tumor; Carcinoma, Squamous Cell; Computational Biology; Databases, Genetic; Esophageal Neoplasms; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Gene Ontology; Humans; Pharyngeal Neoplasms; Prognosis
PubMed: 33080677
DOI: 10.1097/MD.0000000000022434 -
Cells Sep 2019To review the current knowledge regarding the involvement of human papilloma virus (HPV) infection and the immune system in the development of head and neck squamous...
OBJECTIVES
To review the current knowledge regarding the involvement of human papilloma virus (HPV) infection and the immune system in the development of head and neck squamous cell carcinoma (HNSCC).
METHODS
An electronic literature search was conducted to identify articles published between 1990 and 2019 pertaining to tumor-infiltrating immune cells (TICs) in HNSCC using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Issues of clinical relevance, including tumor location, the number of tumor samples, the inclusion of additional specimens (dysplastic or normal mucosa), tumor size, methods used for HPV detection, relationship between antigen expression and patient characteristics (age, gender, smoking, alcohol consumption, etc.), and prognostic data (overall survival (OS) and recurrence-free survival (RFS)) were assessed by four blinded investigators.
RESULTS
The search identified 335 relevant studies, of which 41 met the inclusion criteria. Of these, 7 studies focused on the peripheral blood immune cell concentration in patients with HNSCC according to HPV status, and 36 studies investigated TICs in the intraepithelial and/or stromal compartment(s) according to HPV status. The immune cells studied were CD8+ T cells (N = 19), CD4+ T cells (N = 7), regulatory T cells (Tregs, N = 15), macrophages (N = 13), myeloid-derived suppressor cells (MDSCs, N = 4), and Langerhans cells (LCs, N = 2).
CONCLUSIONS
Irrespective of tumor location, CD8+ and CD4+ T cells appear to play a key role in the development of HPV-related HNSCC, and their infiltration is likely associated with a significant impact on OS and RFS. To date, the roles and prognostic value of Tregs, macrophages, DCs and MDSCs remain unclear.
Topics: Carcinoma, Squamous Cell; Female; Head and Neck Neoplasms; Humans; Langerhans Cells; Macrophages; Male; Myeloid-Derived Suppressor Cells; Oropharyngeal Neoplasms; Oropharynx; Papillomaviridae; Papillomavirus Infections; Squamous Cell Carcinoma of Head and Neck; T-Lymphocytes, Regulatory
PubMed: 31510065
DOI: 10.3390/cells8091061