RESUMEN
BACKGROUND: Detection of nodal metastasis is critical for the treatment and prognosis of head and neck cancer (HNC). Positron emission tomography/computed tomography (PET/CT) is increasingly being used to detect cervical lymph node involvement. AIM: The purposes of this study were to (1) investigate the diagnostic accuracy of PET/CT for the detection of neck metastasis in patients with HNC and (2) determine the effect of the time interval between surgery and PET/CT. METHODS: Fifty patients with head and neck squamous cell carcinoma who underwent PET/CT before surgery were included in this study. Preoperative PET/CT images that determined lymph node metastasis were compared with the histopathological analysis of neck dissection samples. Neck dissections were divided into three groups according to the time interval between surgery and PET/CT (0-2 weeks, >2-4 weeks, and >4 weeks). The concordance between PET/CT and histopathology was measured using the neck sides at different time intervals. The specificity, sensitivity, accuracy, negative predictive value (NPV), and positive predictive value (PPV) of PET/CT in detecting metastatic lymph nodes in the neck were calculated. RESULTS: A total of 79 neck dissections were included in the study as 29 (58%) of the patients underwent bilateral neck dissection. The overall accuracy of PET/CT in detecting nodal metastasis was highest for the 0-2 weeks interval (95.6%). During this time interval, the sensitivity, specificity, NPV, and PPV of PET/CT were 100%, 90.9%, 100%, and 92.3%, respectively. CONCLUSIONS: Although PET/CT is an important and reliable diagnostic method for detecting nodal metastases in patients with HNC, its reliability decreases as the time between surgeries increases. The optimal interval was 2 weeks; however, up to 4 weeks was acceptable.
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Fluorodesoxiglucosa F18 , Neoplasias de Cabeza y Cuello , Metástasis Linfática , Disección del Cuello , Tomografía Computarizada por Tomografía de Emisión de Positrones , Sensibilidad y Especificidad , Humanos , Masculino , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Femenino , Persona de Mediana Edad , Metástasis Linfática/diagnóstico por imagen , Neoplasias de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/cirugía , Neoplasias de Cabeza y Cuello/diagnóstico por imagen , Anciano , Adulto , Factores de Tiempo , Carcinoma de Células Escamosas de Cabeza y Cuello/cirugía , Carcinoma de Células Escamosas de Cabeza y Cuello/diagnóstico por imagen , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Carcinoma de Células Escamosas de Cabeza y Cuello/secundario , Carcinoma de Células Escamosas/cirugía , Carcinoma de Células Escamosas/diagnóstico por imagen , Carcinoma de Células Escamosas/patología , Ganglios Linfáticos/patología , Ganglios Linfáticos/diagnóstico por imagen , Radiofármacos , Valor Predictivo de las PruebasRESUMEN
INTRODUCTION: To examine the influence of adjuvant chemoradiation therapy (CRT) on survival, stratified by varying numbers and level involved of metastatic lymph nodes in patients with head and neck squamous cell carcinoma (HNSCC). METHODS: Patients who underwent surgery for metastatic, negative margin HNSCC without extranodal extension were retrospectively enrolled and divided into two groups based on adjuvant therapy received: radiotherapy (RT) and CRT. The impact of RT versus CRT, stratified by the number of positive lymph nodes and the level involved, on Disease-Free Survival (DFS) and Overall Survival (OS) was analyzed. RESULTS: Following propensity score matching, a total of 580 patients were included. The burden and level of lymph node metastasis were independent predictors of poorer survival. Among patients with no more than two positive lymph nodes or involvement of levels I-III, the addition of chemotherapy to RT did not demonstrate a significant improvement in prognosis. However, in patients with three or more positive lymph nodes, CRT showed improved DFS and OS compared to RT. In patients with involvement of levels IV-V, the addition of chemotherapy to RT resulted in a significant 24 % reduction in the risk of recurrence and a 20 % decrease in the risk of death. CONCLUSION: Incorporation of adjuvant chemoradiation can lead to a favorable prognosis in patients with metastatic HNSCC. This impact was notable in cases where there were three or more positive lymph nodes or involvement of levels IV-V.
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Quimioradioterapia Adyuvante , Neoplasias de Cabeza y Cuello , Metástasis Linfática , Puntaje de Propensión , Carcinoma de Células Escamosas de Cabeza y Cuello , Humanos , Masculino , Femenino , Persona de Mediana Edad , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Carcinoma de Células Escamosas de Cabeza y Cuello/secundario , Estudios Retrospectivos , Neoplasias de Cabeza y Cuello/terapia , Neoplasias de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/mortalidad , Anciano , Supervivencia sin Enfermedad , Tasa de Supervivencia , Adulto , Pronóstico , Ganglios Linfáticos/patologíaRESUMEN
AIMS: Cancer-associated fibroblasts (CAFs) have been shown to promote the metastasis of head and neck squamous cell carcinoma (HNSCC), but the underlying mechanisms remain unclear. The purpose of this study is to identify gene in CAFs that are associated with metastasis and to preliminarily validate its impact on the metastasis of HNSCC. MATERIALS AND METHODS: Scissor analysis was utilized to process single-cell and bulk RNA sequencing datasets, identifying genes associated with the metastasis of HNSCC through differential gene expression analysis. A risk model was constructed using LASSO regression analysis. Quantitative real time-PCR and Western blot were employed to measure mRNA and protein expressions, respectively. Multiplex immunohistochemistry (mIHC) was used to assess protein expression in CAFs. siRNA was utilized to achieve gene knockdown. CCK-8 and Transwell assays were employed to evaluate the biological characteristics of HNSCC cells. KEY FINDINGS: Compare to the nonmetastatic primary CAFs (nmCAFs), tissue inhibitors of metalloproteinase-1 (TIMP1) was founded to be overexpressed in the cells and tissues of metastatic primary CAFs (mCAFs). Knocking down TIMP1 in CAFs can signifucantly inhibit the proliferation, invasion, and migration of HNSCC cells. SIGNIFICANCE: CAFs facilitate HNSCC cell metastasis by upregulating TIMP1, highlighting TIMP1 as a potential therapeutic target in HNSCC metastasis management.
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Fibroblastos Asociados al Cáncer , Neoplasias de Cabeza y Cuello , Análisis de la Célula Individual , Carcinoma de Células Escamosas de Cabeza y Cuello , Inhibidor Tisular de Metaloproteinasa-1 , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Carcinoma de Células Escamosas de Cabeza y Cuello/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello/secundario , Neoplasias de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/metabolismo , Inhibidor Tisular de Metaloproteinasa-1/metabolismo , Inhibidor Tisular de Metaloproteinasa-1/genética , Análisis de la Célula Individual/métodos , Fibroblastos Asociados al Cáncer/metabolismo , Fibroblastos Asociados al Cáncer/patología , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Línea Celular Tumoral , Metástasis de la Neoplasia/genética , Movimiento Celular/genética , Análisis de Secuencia de ARN/métodos , Masculino , FemeninoRESUMEN
Transparent and precise endpoint definitions are a crucial aspect of clinical trial conduct and reporting, and are used to communicate the benefit of an intervention. Previous studies have identified inconsistencies in endpoint definitions across oncological clinical trials. Here, the Head and Neck Cancer International Group assessed endpoint definitions from phase 3 trials or trials considered practice-changing for patients with recurrent or metastatic mucosal head and neck squamous cell carcinoma, published between 2008 and 2021. We identify considerable and global heterogeneity in endpoint definitions, which undermines the interpretation of results and development of future studies. We show how fundamental components of even incontrovertible endpoints such as overall survival vary widely, highlighting an urgent need for increased rigour in reporting and harmonisation of endpoints.
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Consenso , Determinación de Punto Final , Neoplasias de Cabeza y Cuello , Recurrencia Local de Neoplasia , Carcinoma de Células Escamosas de Cabeza y Cuello , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Carcinoma de Células Escamosas de Cabeza y Cuello/mortalidad , Carcinoma de Células Escamosas de Cabeza y Cuello/secundario , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia , Recurrencia Local de Neoplasia/patología , Neoplasias de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/mortalidad , Neoplasias de Cabeza y Cuello/terapia , Determinación de Punto Final/normas , Ensayos Clínicos Fase III como Asunto , Metástasis de la NeoplasiaRESUMEN
INTRODUCTION: This systematic review aims to evaluate the role of biopsies in non-oropharyngeal subsites in patients with cervical metastasis from head and neck squamous cell carcinoma of unknown primary (HNSCCUP). METHODS: This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Articles that encompassed non-oropharyngeal biopsies in HNSCCUP as part of the diagnostic work-up were selected and analysed. RESULTS: A comprehensive search strategy was used to search relevant literature in PubMed from inception to October 2021. Eleven articles out of 860 were included, comprising 990 patients. There are no randomised control trials comparing the outcomes of survival and or locoregional control between patients who have or have not undergone non-targeted biopsies of non-oropharyngeal sub-sites for HNSCCUP. Several retrospective studies which showed an extremely low yield from random biopsies (range of yield, 0%-9%) of non-oropharyngeal subsites. Even targeted biopsies showed a low yield (range of yield, 0.6%-16.6%) from non-oropharyngeal subsites. The primary site identified for Epstein-Barr virus (EBV) positive cervical lymph nodes with an unknown primary is mainly the nasopharynx (51.7%). Narrow band imaging (NBI) (sensitivity range, 64%-91%) helps in the detection of primaries to target biopsies in non-oropharyngeal subsites. CONCLUSIONS: On the basis of this systematic review, it is not appropriate to offer biopsies of clinically and radiologically normal upper aerodigestive tract mucosa at non-oropharyngeal sites. Offer nasopharyngeal biopsies when the cervical node sampling reveals EBV-positive metastasis. Where available, NBI should be used to help detect and target biopsies in non-oropharyngeal subsites.
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Neoplasias Primarias Desconocidas , Carcinoma de Células Escamosas de Cabeza y Cuello , Humanos , Neoplasias Primarias Desconocidas/patología , Biopsia/métodos , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Carcinoma de Células Escamosas de Cabeza y Cuello/secundario , Neoplasias de Cabeza y Cuello/patologíaRESUMEN
De novo metastatic Head and Neck Squamous Cell Carcinoma (HNSCC) constitutes 10% of recurrent/metastatic (RM) cases. Radiotherapy (RT) has a crucial role in the treatment of locally advanced HNSCC, however its application on RM diseases is still limited. The advent of immune checkpoint inhibitors (ICIs) improves the survival of RM HNSCC, however median overall survival is still limited. Integration of locoregional RT with ICIs in de novo metastatic HNSCC represents a promising treatment option. This perspective aims to explore the role of the combination of locoregional and systemic treatment in improving outcomes for synchronous de novo metastatic HNSCC patients and highlights the principal crucial point in decision making.
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Neoplasias de Cabeza y Cuello , Carcinoma de Células Escamosas de Cabeza y Cuello , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia , Carcinoma de Células Escamosas de Cabeza y Cuello/secundario , Carcinoma de Células Escamosas de Cabeza y Cuello/radioterapia , Carcinoma de Células Escamosas de Cabeza y Cuello/mortalidad , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/terapia , Metástasis de la Neoplasia , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Recurrencia Local de NeoplasiaRESUMEN
BACKGROUND: To indirectly compare the safety of immune checkpoint inhibitors (ICIs) in the treatment of recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) by network meta-analysis (NMA). METHODS: Through August 1, 2023, we searched PubMed, Cochrane Library, Embase, Web of Science, and ClinicalTrials.gov for randomized clinical trials (RCTs) of ICI-based treatment for R/M HNSCC. Outcomes of interest included overall and organ-specific immune-related adverse events (irAEs). Addis 16.5 software was used to perform NMA. Confidence in Network Meta-Analysis (CINeMA) was used to assess confidence in the evidence. RESULTS: Nine RCTs were included in this NMA, involving a total of 4016 patients. The general safety of ICI-based treatments in descending order was as follows: Durvalumab + Tremelimumab, Camrelizumab + Chemotherapy, Durvalumab, Toripalimab + Chemotherapy, Pembrolizumab, Pembrolizumab + Chemotherapy, Nivolumab, Tremelimumab. There were differences in the toxicity profile among Toripalimab + Chemotherapy (dermatologic irAEs), Camrelizumab + Chemotherapy (hypothyroidism), Nivolumab + Ipilimumab (hyperthyroidism, pneumonitis), Pembrolizumab (nephrotoxicity), Pembrolizumab + Chemotherapy (colitis). ICI-based treatment increased the incidence of endocrine irAEs (hyperthyroidism and hypothyroidism) and pneumonitis compared to conventional therapy. Besides, the combination of dual ICIs resulted in a greater occurrence of irAEs compared to the use of a single ICI. CONCLUSIONS: The safety ranking of treatments based on ICIs is significantly influenced by specific irAEs. These irAEs, which vary in type and severity, play a crucial role in determining the overall safety profile of each ICI regimen. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42023460267.
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Neoplasias de Cabeza y Cuello , Inhibidores de Puntos de Control Inmunológico , Recurrencia Local de Neoplasia , Metaanálisis en Red , Carcinoma de Células Escamosas de Cabeza y Cuello , Humanos , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/patología , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como Asunto , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Carcinoma de Células Escamosas de Cabeza y Cuello/secundarioRESUMEN
OBJECTIVE: Evidence suggests that distant metastasis in head and neck squamous cell carcinoma is a spectrum of disease. Previous studies show that oligometastasis has favorable survival compared with polymetastasis. The quality of life of patients with oligometastasis remains unknown. To further solidify the position of oligometastasis as a separate entity, we hypothesized that oligometastatic patients experience better quality of life than polymetastatic patients. METHODS: Patients with distant metastasis were stratified into three groups: oligometastasis (≤3 metastatic foci in ≤2 anatomic sites), explosive metastasis (≥4 metastatic foci at one anatomic site), and explosive-disseminating metastasis (spread to ≥3 anatomic sites). Quality of life was assessed every 2 months post distant metastasis diagnosis. RESULTS: Between January 1, 2016, and December 31, 2021, a total of 161 patients with distant metastasis were identified, with a total of 397 measurements. In this group, 57 (35.4%) patients had oligometastasis, 35 (21.7%) patients had explosive metastasis, and 69 (42.9%) patients had explosive-disseminating metastasis. Their median post-distant metastasis survivals were 8.5 months, 3.2 months, and 3.2 months respectively (p < 0.001). A significantly better overall quality of life was observed in the oligometastasis group compared with the polymetastatic groups (+0.75 out of 7, p < 0.05). Furthermore, oligometastatic patients performed better in the subdomains of "physical functioning," "fatigue," and "pain." CONCLUSION: Results from this study underscore that subgroups exist regarding quality of life and survival within distant metastasis, with polymetastatic patients performing worse than oligometastatic patients. This highlights the significance of tailored interventions that consider the unique challenges faced by each metastatic group of patients. LEVEL OF EVIDENCE: 3, retrospective cohort study Laryngoscope, 134:3170-3176, 2024.
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Neoplasias de Cabeza y Cuello , Metástasis de la Neoplasia , Calidad de Vida , Carcinoma de Células Escamosas de Cabeza y Cuello , Humanos , Masculino , Femenino , Persona de Mediana Edad , Carcinoma de Células Escamosas de Cabeza y Cuello/mortalidad , Carcinoma de Células Escamosas de Cabeza y Cuello/secundario , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/mortalidad , Neoplasias de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/terapia , Neoplasias de Cabeza y Cuello/psicología , Neoplasias de Cabeza y Cuello/secundario , Anciano , Estudios Retrospectivos , AdultoRESUMEN
INTRODUCTION: Out of all cutaneous squamous cell carcinomas originating in the head and neck (HNCSCC), 2-4% are associated with parotid or cervical lymph node metastasis. The aim of this study is to analyse the prognostic factors of patients with HNCSCC with lymph node involvement treated surgically. Additionally, we aim to compare the prognostic capacity of the classification of these patients according to the 8th edition of the TNM, and an alternative classification proposed by O'Brien et al. PATIENTS AND METHODS: Retrospective review of 65 patients with HNCSCC with lymph node metastasis treated surgically during the period 2000-2020. RESULTS: During the study period we carried out 13 neck dissections and 52 parotidectomiesâ¯+â¯neck dissection in patients with lymph node metastases from a HNCSCC. The great majority of patients (89.2%) received post-operative radiotherapy. The 5â¯year disease-specific survival was 69.9%, and the overall survival it was 42.8%. The classification proposed by O'Brien et al., based on the parotid or cervical location of the lymph node metastases, and the size and number of the metastatic lymph nodes, had a better prognostic capacity than the TNM classification. CONCLUSIONS: The surgical treatment of lymph node metastases in patients with HNCSCC achieved a high disease control. The classification based on the location, size and number of lymph node metastases proposed by O'Brien et al had better prognostic capacity than the TNM classification.
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Metástasis Linfática , Disección del Cuello , Neoplasias Cutáneas , Carcinoma de Células Escamosas de Cabeza y Cuello , Humanos , Masculino , Estudios Retrospectivos , Femenino , Anciano , Persona de Mediana Edad , Neoplasias Cutáneas/cirugía , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/mortalidad , Carcinoma de Células Escamosas de Cabeza y Cuello/cirugía , Carcinoma de Células Escamosas de Cabeza y Cuello/mortalidad , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Carcinoma de Células Escamosas de Cabeza y Cuello/secundario , Anciano de 80 o más Años , Neoplasias de Cabeza y Cuello/cirugía , Neoplasias de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/mortalidad , Pronóstico , Adulto , Estadificación de Neoplasias , Neoplasias de la Parótida/cirugía , Neoplasias de la Parótida/patología , Neoplasias de la Parótida/secundario , Carcinoma de Células Escamosas/cirugía , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/secundario , Carcinoma de Células Escamosas/patologíaRESUMEN
OBJECTIVE: To evaluate the rates and patterns of distant metastasis in head and neck SCC at the time of presentation and to study the association between distant metastasis with pre-treatment, clinical, and pathological predictors of outcomes. METHOD: This is a retrospective study conducted in a tertiary care hospital. All patients with primary head and neck squamous cell carcinoma that had been evaluated at our institute between October 2018 and December 2020 were included in the study. Various clinical data were analysed and pattern of metastasis was studied. RESULT: Ten per cent (50 cases) of 501 studied patients had distant metastasis. The most common site of distant metastasis was lung. The rate of distant metastasis was high in patients with poorly differentiated cancers. By Kaplan-Meier analysis, the median survival duration after diagnosis of metastasis was four months. CONCLUSION: The rate of distant metastasis was 10 per cent in the study. Patients with poorly differentiated tumours, locally advanced primary lesions, higher nodal stage, particularly with extra nodal extension, and hypopharyngeal primary, tend to exhibit increased risk for distant metastasis at the time of presentation.
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Neoplasias de Cabeza y Cuello , Carcinoma de Células Escamosas de Cabeza y Cuello , Centros de Atención Terciaria , Humanos , Estudios Retrospectivos , Masculino , Femenino , Persona de Mediana Edad , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Carcinoma de Células Escamosas de Cabeza y Cuello/mortalidad , Carcinoma de Células Escamosas de Cabeza y Cuello/secundario , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia , Centros de Atención Terciaria/estadística & datos numéricos , Anciano , Neoplasias de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/mortalidad , Metástasis de la Neoplasia , Adulto , Estadificación de Neoplasias , Estimación de Kaplan-Meier , Anciano de 80 o más Años , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/mortalidadRESUMEN
BACKGROUND: LncRNA SRY-box transcription factor 2 overlapping transcript (SOX2-OT) is linked to multiple cancers, but its specific role and mechanism in head and neck squamous cell carcinoma (HNSCC) remain poorly understood. METHODS: We harnessed clinical data and HNSCC transcriptome profiles from UCSC Xena, TCGA, and GEO databases. Employing various algorithms, we assessed the correlation between SOX2-OT expression and the HNSCC immune microenvironment. Differential expression analysis identified immune-enriched miRNAs (DEmiRNAs) and mRNAs (DEmRNAs). Utilizing miRanda, miRWalk, and Cytoscape, we constructed a ceRNA network encompassing SOX2-OT, DEmiRNAs, and DEmRNAs. A Sankey diagram visualized pivotal SOX2-OT-miRNA-mRNA-pathways. Functional assays validated SOX2-OT silencing effects in HNSCC cells. Luciferase reporter assays verified SOX2-OT/let-7c-3p/SKP2 relationships. Additionally, a xenograft mouse model revealed SOX2-OT's impact on xenograft growth and lung metastasis. RESULTS: SOX2-OT expression demonstrated a predominantly positive correlation with B lineage and VTCN1, while manifesting a negative correlation with Neutrophil and CD47 in HNSCC tissues. We discerned a ceRNA network comprising 65 DEmiRNAs and 116 DEmRNAs, while a protein-protein interaction (PPI) network revealed 97 protein nodes among DEmRNAs. Notably, the Sankey diagram spotlighted six key DEmRNAs intricately linked to the SOX2-OT-regulated DEmiRNAs immune-related pathway. Experimental assays established that SOX2-OT silencing exerted inhibitory effects on cell proliferation, migration, tumor growth, and lung metastasis within HNSCC cells, both in vitro and in vivo. We identified let-7c-3p as a target miRNA of SOX2-OT and SKP2 as a target mRNA of let-7c-3p. CONCLUSIONS: Our study establishes the critical SOX2-OT/let-7c-3p/SKP2 axis as a pivotal regulator of HNSCC tumorigenesis and metastasis.
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Neoplasias de Cabeza y Cuello , MicroARNs , ARN Largo no Codificante , Carcinoma de Células Escamosas de Cabeza y Cuello , Animales , Humanos , Ratones , Biología Computacional , Regulación Neoplásica de la Expresión Génica , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/patología , Neoplasias Pulmonares/secundario , MicroARNs/genética , MicroARNs/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , ARN Mensajero/metabolismo , Factores de Transcripción SOXB1/genética , Factores de Transcripción SOXB1/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/secundario , Microambiente TumoralRESUMEN
BACKGROUND/AIM: This study evaluated the efficacy of nivolumab and pembrolizumab in treating platinum-sensitive recurrent or metastatic head and neck squamous cell carcinomas (R/M-HNSCC). PATIENTS AND METHODS: Platinum-sensitive patients with R/M-HNSCC were selected at Tokyo Medical University Hospital from May 1, 2017, to June 30, 2022. Patients with a history of treatment with nivolumab or pembrolizumab were included. Nivolumab was used in 21 cases and pembrolizumab in 15 cases. RESULTS: The median overall survival (OS) was 16.9 months in the nivolumab group and 19.2 months in the pembrolizumab group and no significant differences were observed between the two groups. The median progression-free survival (PFS) was 4.8 months in the nivolumab group and 9.3 months in the pembrolizumab group. No significant differences were observed between the two groups. The objective response rates (ORR) were 38% and 47% in the nivolumab and pembrolizumab groups, respectively. CONCLUSION: Nivolumab as well as pembrolizumab were found to be effective in platinum-sensitive patients with R/M-HNSCC. Nivolumab can be considered a potential treatment option for platinum-sensitive R/M-HNSCC in the future.
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Anticuerpos Monoclonales Humanizados , Neoplasias de Cabeza y Cuello , Inhibidores de Puntos de Control Inmunológico , Recurrencia Local de Neoplasia , Nivolumab , Carcinoma de Células Escamosas de Cabeza y Cuello , Nivolumab/uso terapéutico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Carcinoma de Células Escamosas de Cabeza y Cuello/secundario , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/patología , Metástasis de la Neoplasia , Anticuerpos Monoclonales Humanizados/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Compuestos de Platino/uso terapéutico , Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Resultado del TratamientoRESUMEN
Objective: To explore the diagnostic value of magnetic resonance imaging (MRI) combined with CXCR4 expression levels in lymph node metastasis of the head and neck squamous cell carcinoma (HNSCC). Methods: 289 patients with HNSCC were divided into lymph node metastasis group (LNM group, n = 171) and non-LNM group (n = 118) according to the pathological examination results. MRI was used to scan the patient's lesions and cervical lymph nodes, and ADC was measured by MRI diffusion weighting imaging. The expression of CXCR4 in tumor tissues was detected by qRT-PCR. Logistic regression was used to analyze the risk factors of HNSCC lymph node metastasis. ROC curve was used to analyze the diagnostic effects of MRI, CXCR4, and MRI combined with CXCR4 on HNSCC lymph node metastasis. Results: Compared with the non-LNM group, patients in the LNM group had a lower degree of pathological differentiation, and the positive rate of TNM staging and vascular invasion was higher. The signal intensity of T1WI and T2WI were low intensity and high intensity, respectively, and the ADC value was significantly reduced. At the same time, the expression level of CXCR4 in the tumor tissues of the LNM group was also significantly increased. In addition, compared with MRI and CXCR4 used alone, MRI combined with CXCR4 has a higher predictive value. Conclusion: MRI has a good effect in demonstrating lymph node metastasis. CXCR4 is significantly upregulated in lymph node metastasis tumor tissue. The combination of the two can be used for clinical diagnosis of HNSCC lymph node metastasis.
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Neoplasias de Cabeza y Cuello/diagnóstico por imagen , Neoplasias de Cabeza y Cuello/inmunología , Metástasis Linfática/diagnóstico por imagen , Metástasis Linfática/inmunología , Receptores CXCR4/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello/diagnóstico por imagen , Carcinoma de Células Escamosas de Cabeza y Cuello/inmunología , Anciano , Biomarcadores de Tumor/metabolismo , Biología Computacional , Femenino , Neoplasias de Cabeza y Cuello/patología , Humanos , Modelos Logísticos , Metástasis Linfática/patología , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Carcinoma de Células Escamosas de Cabeza y Cuello/secundarioRESUMEN
OBJECTIVE: GIT1 is identified as a novel tumor oncogene in breast cancer. In this article, we aimed to explore the role of GIT1 in the progression of head and neck squamous cell carcinoma (HNSCC). METHODS: GIT1 expression in HNSCC was detected by RT-qPCR, immunohistochemistry assay, and Western blot. HNSCC cell proliferation, migration, and invasion were examined by CCK-8 assay, Wound healing assay, and Transwell assay, respectively. Cell apoptosis was detected by flow cytometric analysis. RESULTS: In our study, GIT1 was notably upregulated in HNSCC tissues and cells. Moreover, GIT1 expression level had positive corelation with pathological grade and nodal status of HNSCC. Functional experiments showed that knockdown of GIT1 restrained HNSCC proliferation, invasion, migration, and EMT and facilitated cell apoptosis. Furthermore, GIT1 knockdown was found to restrain HNSCC tumor growth and lung metastasis. Additionally, PI3K/AKT/mTOR signal pathway inhibitors suppressed the effect of GIT1 on HNSCC cell progression. CONCLUSION: GIT1 was upregulated in HNSCC and facilitated HNSCC cell progression by inducing PI3K/AKT/mTOR signal pathway. Therefore, we suggested that GIT1 might be a potential target for HNSCC treatment.
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Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteínas de Ciclo Celular/metabolismo , Neoplasias de Cabeza y Cuello/metabolismo , Neoplasias de Cabeza y Cuello/patología , Carcinoma de Células Escamosas de Cabeza y Cuello/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello/secundario , Proteínas Adaptadoras Transductoras de Señales/antagonistas & inhibidores , Proteínas Adaptadoras Transductoras de Señales/genética , Anciano , Animales , Apoptosis , Proteínas de Ciclo Celular/antagonistas & inhibidores , Proteínas de Ciclo Celular/genética , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Biología Computacional , Femenino , Regulación Neoplásica de la Expresión Génica , Técnicas de Silenciamiento del Gen , Neoplasias de Cabeza y Cuello/genética , Xenoinjertos , Humanos , Masculino , Ratones , Ratones Desnudos , Persona de Mediana Edad , Invasividad Neoplásica , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Serina-Treonina Quinasas TOR/metabolismo , Regulación hacia ArribaRESUMEN
BACKGROUND/AIM: This study investigated the expression and survival rates of programmed cell death ligand 1 using the tumor proportion score (TPS)and combined positive score (CPS) for recurrent/metastatic head and neck cancer administered nivolumab. PATIENTS AND METHODS: Forty-seven patients with recurrent/metastatic head and neck cancer with a history of platinum-based chemotherapy who received nivolumab between June 1st, 2017, and January 31st, 2019 were included in this study. RESULTS: TPS and CPS were strongly correlated (r=0.546). When the TPS was high (≥40%), overall and progression-free survival were significantly better. The median overall survival was 8.5 months, median progression-free survival was not reached, and the 1-year progression-free survival rate was 71.4%. However, there was no significant difference in overall and progression-free survival between the groups with high CPS (≥20). CONCLUSION: This is the first report to show a strong correlation between TPS and CPS. High TPS (40% or higher) may be used as a predictor of prognosis and efficacy. Further studies are warranted to determine the use of the CPS as a biomarker.
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Antígeno B7-H1/antagonistas & inhibidores , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Nivolumab/uso terapéutico , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Antígeno B7-H1/análisis , Femenino , Neoplasias de Cabeza y Cuello/inmunología , Neoplasias de Cabeza y Cuello/mortalidad , Neoplasias de Cabeza y Cuello/patología , Humanos , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Nivolumab/efectos adversos , Supervivencia sin Progresión , Estudios Retrospectivos , Carcinoma de Células Escamosas de Cabeza y Cuello/inmunología , Carcinoma de Células Escamosas de Cabeza y Cuello/mortalidad , Carcinoma de Células Escamosas de Cabeza y Cuello/secundario , Factores de TiempoRESUMEN
BACKGROUND/AIM: There are no real-world comparative data of nivolumab doses of 3 mg/kg and 240 mg/body for recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). We investigated the efficacy and safety of nivolumab in treating recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) at different doses using real-world data. PATIENTS AND METHODS: R/M SCCHN patients who received nivolumab were divided into the 3 mg/kg and 240 mg/body groups and retrospectively examined for efficacy and safety. RESULTS: A total of 199 patients (3 mg/kg and 240 mg/body, 88 and 111 patients, respectively) were included. The 3 mg/kg vs. 240 mg/body groups had similar overall response rates (15% vs. 25, p=0.15), disease control rates (46% vs. 57%, p=0.15), overall survival (9.5 months vs. 10.9 months), and progression-free survival (3.7 months vs. 3.8 months, p=0.95). The incidence of immune-related adverse events was also similar in both groups. CONCLUSION: In R/M SCCHN patients, nivolumab showed similar efficacy and safety at doses of 3 mg/kg and 240 mg/body.
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Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Inhibidores de Puntos de Control Inmunológico/administración & dosificación , Recurrencia Local de Neoplasia , Nivolumab/administración & dosificación , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Neoplasias de Cabeza y Cuello/inmunología , Neoplasias de Cabeza y Cuello/mortalidad , Neoplasias de Cabeza y Cuello/patología , Humanos , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Masculino , Persona de Mediana Edad , Nivolumab/efectos adversos , Supervivencia sin Progresión , Estudios Retrospectivos , Carcinoma de Células Escamosas de Cabeza y Cuello/inmunología , Carcinoma de Células Escamosas de Cabeza y Cuello/mortalidad , Carcinoma de Células Escamosas de Cabeza y Cuello/secundario , Factores de Tiempo , Tokio , Adulto JovenRESUMEN
Nivolumab, an immune checkpoint inhibitor, is beneficial to patients with platinum-refractory recurrent or metastatic head and neck squamous cell carcinoma (R/M-HNSCC). However, platinum-sensitive R/M-HNSCC has not yet been studied. Hence, in this prospective study, we evaluated the efficacy and safety of nivolumab in patients with platinum-sensitive R/M-HNSCC. This prospective single-arm study was conducted in a single institution in Japan. Patients with platinum-sensitive R/M-HNSCC (defined as head and neck cancer that recurred or metastasized at least 6 months after platinum-based chemotherapy or chemoradiotherapy) were enrolled. The primary endpoint was overall survival (OS). The secondary endpoints were progression-free survival (PFS), overall response rate (ORR), immune-related adverse events (irAEs), and quality of life (QOL). This study was registered at the University Hospital Medical Information Network Clinical Trials Registry (UMIN000031324). Twenty-two patients with platinum-sensitive R/M-HNSCC were enrolled. The median OS was 17.4 months, and the 1-year OS rate was 73%. The median PFS was 9.6 months, 1-year PFS rate was 48%, and ORR was 36%. Sixteen irAEs were recorded in 12 patients; however, no grade 4 or 5 irAEs were observed. The QOL assessments revealed that nivolumab did not decrease the QOL of patients. Nivolumab is effective against platinum-sensitive R/M-HNSCC with acceptable safety.
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Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/patología , Nivolumab/farmacología , Nivolumab/uso terapéutico , Compuestos de Platino/farmacología , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Adulto , Anciano , Resistencia a Antineoplásicos , Femenino , Neoplasias de Cabeza y Cuello/mortalidad , Neoplasias de Cabeza y Cuello/secundario , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Compuestos de Platino/uso terapéutico , Estudios Prospectivos , Calidad de Vida , Seguridad , Carcinoma de Células Escamosas de Cabeza y Cuello/mortalidad , Carcinoma de Células Escamosas de Cabeza y Cuello/secundario , Tasa de Supervivencia , Factores de TiempoRESUMEN
BACKGROUND: Large cervical lymph nodes and the extranodal extension of metastatic lymph nodes are considered poor prognostic factors in head and neck squamous cell carcinoma (HNC). AIMS/OBJECTIVES: The efficacy of intra-arterial chemotherapy (iaCT) targeting lymph node (LN) in HNC was examined. MATERIALS AND METHODS: We performed a retrospective review of 41 patients with laryngeal and hypopharyngeal cancer showing metastatic cervical LN larger than 20 mm treated with iaCT with concurrent radiotherapy. The administration of cisplatin into LN was divided into three groups: no administration (NO), via the same artery as that supplying the primary tumor (SAME), and via a different artery from that supplying the primary tumor (DIFFERENT). RESULTS: A trend toward a more favorable three-year regional control in DIFFERENT compared to NO was observed, although the mean size of LN in DIFFERENT was larger than in the other groups. A better regional control was obtained in both DIFFERENT (p < .05) and DIFFERENT + SAME (p < .05) when overall rather than partial enhancement of lymph node by CT angiography was observed. Extranodal extension could be a factor predicting unfavorable regional control. CONCLUSIONS/SIGNIFICANCE: Targeting lymph node may be helpful to avoid neck dissection when iaCT was planned in HNC with relatively large LNs.
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Antineoplásicos/administración & dosificación , Cisplatino/administración & dosificación , Neoplasias Hipofaríngeas/patología , Neoplasias Laríngeas/patología , Metástasis Linfática/tratamiento farmacológico , Carcinoma de Células Escamosas de Cabeza y Cuello/secundario , Anciano , Femenino , Humanos , Neoplasias Hipofaríngeas/tratamiento farmacológico , Infusiones Intraarteriales/métodos , Neoplasias Laríngeas/tratamiento farmacológico , Metástasis Linfática/radioterapia , Masculino , Persona de Mediana Edad , Cuello , Estudios Retrospectivos , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Carcinoma de Células Escamosas de Cabeza y Cuello/patologíaRESUMEN
BACKGROUND/AIM: Prognostic factors of hypopharyngeal carcinoma have been reported previously. However, recurrent cases of this disease occurring within 6 months of treatment have been excluded or poorly documented in many studies. We aimed to evaluate the prognostic factors of hypopharyngeal carcinoma recurrence within 6 months. PATIENTS AND METHODS: A total of 120 patients were eligible for this retrospective study. Recurrent cases of hypopharyngeal carcinoma occurring within 6 months of treatment were evaluated and compared with non-recurrent cases. RESULTS: Recurrence within 6 months was detected in 28/50 cases. In univariate analyses, classification markers (pT≥4a and cN≥2b) were statistically significant prognostic factors for early recurrence (p=0.04 and p=0.04, respectively); however, only pT≥4a was predictive of recurrence in multivariate analyses (p=0.02). CONCLUSION: Risk stratification according to the prognostic factor pT≥4a will allow physicians to identify patients who should be followed meticulously within the first 6 months.