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1.
J Biomed Nanotechnol ; 16(1): 111-124, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31996290

RESUMO

Radiation therapy is a mainstay in the therapeutic management of Head and Neck Squamous Cell Carcinoma (HNSCC). Despite significant progress in this field, radioresistance still accounts for most treatment failures. Gadolinium-based nanoparticles (GBNs) have shown great promises as radiosensitizers but the underlying sensitizing mechanism is still largely unknown with regards to the disparities obtained in in vitro studies. In this study, we show that a new formulation of GBNs, AGuIX®, can radiosensitize HNSCC after cell uptake and further accumulation in lysosomes. Although radiation alone triggered late apoptosis and mitochondrial impairment, the pre-treatment with GBNs led to complex DNA damage and a specific increase of autophagic cell death. In addition, a significant radio-enhancement effect was obtained after the pre-conditioning of cells with a glutathione inhibitor before GBNs treatment and radiation exposure. Overall, our results provide additional information on the radio-enhancing properties of GBNs in the management of radioresistant HNSCC.


Assuntos
Autofagia , Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Carcinoma de Células Escamosas de Cabeça e Pescoço , Apoptose , Linhagem Celular Tumoral , Gadolínio , Humanos , Nanopartículas Metálicas
2.
Immunity ; 52(1): 183-199.e9, 2020 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-31924475

RESUMO

Head and neck squamous cell carcinoma (HNSCC) arises through exposure to environmental carcinogens or malignant transformation by human papillomavirus (HPV). Here, we assessed the transcriptional profiles of 131,224 single cells from peripheral and intra-tumoral immune populations from patients with HPV- and HPV+ HNSCC and healthy donors. Immune cells within tumors of HPV- and HPV+ HNSCC displayed a spectrum of transcriptional signatures, with helper CD4+ T cells and B cells being relatively divergent and CD8+ T cells and CD4+ regulatory T cells being relatively similar. Transcriptional results were contextualized through multispectral immunofluorescence analyses and evaluating putative cell-cell communication based on spatial proximity. These analyses defined a gene expression signature associated with CD4+ T follicular helper cells that is associated with longer progression-free survival in HNSCC patients. The datasets and analytical approaches herein provide a resource for the further study of the impact of immune cells on viral- and carcinogen-induced cancers.


Assuntos
Linfócitos B/imunologia , Linfócitos T CD8-Positivos/imunologia , Neoplasias de Cabeça e Pescoço/imunologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Reguladores/imunologia , Alphapapillomavirus/imunologia , Diferenciação Celular/imunologia , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/virologia , Humanos , Imunoterapia , Intervalo Livre de Progressão , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia
3.
Anticancer Res ; 40(1): 349-356, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892586

RESUMO

BACKGROUND/AIM: Follicle-stimulating hormone receptor (FSHr), expressed on endothelial cells of vessels in different malignant tumors, has been recently investigated as a potential pan-receptor of cancer treatment. However, the expression of this receptor has also been confirmed in other tissues under pathological conditions including cancer. The aim of the presented pilot study was to evaluate the expression of FSHr in head and neck squamous cancer (HNSCC). PATIENTS AND METHODS: A total of 28 HNSCC patient samples were immunohistochemically analyzed for the presence of FSHr using a commercially available primary antibody. RESULTS: FSHr was detected not only in the tumor tissue, but also in the basal layer or dysplastic parts of squamous mucosa and also in fibroblasts surrounding the tumor tissue. CONCLUSION: FSHr is present on different benign or malignant mesenchymal and epithelial structures in HNSCC. A brief literature review revealed a wider role of FSHr in the development of neoplasia.


Assuntos
Receptores do FSH/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Animais , Linhagem Celular Tumoral , Feminino , Humanos , Imuno-Histoquímica , Camundongos , Projetos Piloto
4.
HNO ; 68(2): 106-110, 2020 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-31915880

RESUMO

Due to late diagnosis and poor treatment response, advanced head and neck squamous cell carcinoma (HNSCC) belongs to the tumor diseases with highest mortality worldwide. Although many biomarkers have been investigated over the past years, none have yet become established in clinical practice. There is thus an urgent need to introduce noninvasive liquid biopsies that not only give information about cancer activity but also enable early conclusions regarding treatment response. This underlines the biological importance of exosomes from the blood of HNSCC patients. Isolation of exosomes from cell line supernatants and human plasma can easily be performed by size-exclusion chromatography. Thus, protein content, expression patterns, and immunomodulatory effects on immune cells can be evaluated. Further separation of exosomes by cell of origin enables more detailed examination of tumor-derived exosomes (TEX) and exosomes from immune cells. The etiology of the disease, e.g., human papillomavirus (HPV) status, disease activity (active vs. no evident disease), and response to immunotherapies can be detected by exosomal protein expression and immunosuppressive effects of exosomes on different immune cell subtypes. In conclusion, the presented studies can make an essential contribution to the establishment of exosomes as liquid biopsies for head and neck cancer diagnosis and treatment monitoring.


Assuntos
Exossomos , Neoplasias de Cabeça e Pescoço , Biópsia Líquida , Carcinoma de Células Escamosas de Cabeça e Pescoço , Neoplasias de Cabeça e Pescoço/diagnóstico , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico
5.
HNO ; 68(2): 94-99, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31996933

RESUMO

Cancer stem cell (CSC)-related therapy resistance has become a new obstacle to the successful application of cancer treatment and head and neck squamous cell carcinoma (HNSCC) is no exception to this finding. Head and neck squamous cell carcinoma is highly immune-suppressive, and recently the immune suppression and invasion of HNSCC-CSCs have been characterized. These characteristics have received research and clinical attention because they would enable the stratification of patients into specific cancer subtypes and, consequently, the establishment of new therapeutic approaches with improved efficacy. This review discusses the feasibility of CSC-targeted strategies and their incorporation with nanotechnology to improve the efficacy of cancer immunotherapy.


Assuntos
Neoplasias de Cabeça e Pescoço , Imunoterapia , Carcinoma de Células Escamosas de Cabeça e Pescoço , Linhagem Celular Tumoral , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Células-Tronco Neoplásicas , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia
6.
J Cancer Res Clin Oncol ; 146(2): 381-389, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31960186

RESUMO

PURPOSE: To evaluate the prevalence of two recurrent somatic mutations (-124 C>T and -146 C>T) within the promoter of the gene encoding telomerase reverse transcriptase (TERT) as well as their relationship with TERT level, telomeres length, and outcome in patients with head and neck squamous cell carcinomas (HNSCCs). METHODS: We evaluate the prevalence of TERT promoter mutations, TERT levels, and telomere length in paired cancer tissue and adjacent mucosa (AM) in a series of HNSCCs. RESULTS: Cancer tissue and AM specimens from 105 patients were analyzed. Telomere length and TERT mRNA levels were estimated using real-time polymerase chain reaction. TERT promoter mutations were assessed using Sanger sequencing. Out of 105 cases, 101 were considered suitable for the analysis. TERT promoter harbored mutations in 12 tumors (11.9%), with -124 C>T and -146 C>T accounting for 83.3% and 16.7% of the alterations, respectively. No mutations were detected in AM samples. The prevalence of TERT promoter mutations was significantly higher in oral cavity SCCs (10 out of 27 tumors; 37%), and telomere length in AM was shorter in patients with tumors carrying TERT promoter mutations than in patients with unmutated TERT promoter cancers (p = 0.023). TERT levels in tumor did not significantly differ according to the mutational status of TERT promoter. No significant association was found between TERT promoter status and overall survival. CONCLUSION: TERT promoter mutations are most likely a late event in tumor development, occurring in a context of critically short telomeres, mostly in patients with oral cavity SCC. TERT levels, but not TERT promoter mutational status impact clinical outcome.


Assuntos
Neoplasias de Cabeça e Pescoço/genética , Mutação , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Telomerase/genética , Telômero/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Regiões Promotoras Genéticas , Estudos Prospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Análise de Sobrevida , Telomerase/metabolismo , Telômero/genética , Telômero/patologia
7.
J Appl Oral Sci ; 28: e20190166, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31800875

RESUMO

other: Oral and oropharyngeal cancer is considered a public health problem in several countries due to its high incidence and mortality rate. OBJECTIVE: This study aimed to analyze oral and oropharyngeal cancer mortality in Uruguay from 1997 to 2014 by age, sex and country region. METHODOLOGY: A time series ecological study using secondary data was performed. Data on mortality due to oral and oropharyngeal cancers were obtained from the Vital Statistics Department of Uruguay's Ministry of Public Health. RESULTS: The cumulative mortality rate due to oral and oropharyngeal cancer over the study period was of 19.26/100,000 persons in women and 83.61/100.000 in men, with a mean annual rate of 1.75/100,000 in women and 7.60/100,000 in men. Mortality rate from both sites during the study period was 4.34 times higher in men than in women. Malignant neoplasms of other parts of the tongue and base of tongue showed the highest mortality rate. The means of the annual coefficients of deaths were higher for the age groups between 50 and 69 years. Higher mortality rates of oral and oropharyngeal cancer were observed in Artigas (4.63) and Cerro Largo (3.75). CONCLUSIONS: Our study described a high mortality rate for oral and oropharyngeal cancer in Uruguay from 1997 to 2014. According to the country's health department, men, tongue cancer, and oral cavity had higher mortality rates, with some variation. Prevention strategies with control of risk factors and early diagnosis are necessary to improve survival in the Uruguayan population.


Assuntos
Neoplasias Orofaríngeas/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Neoplasias Orofaríngeas/patologia , Fatores de Risco , Distribuição por Sexo , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Fatores de Tempo , Neoplasias da Língua/mortalidade , Neoplasias da Língua/patologia , Uruguai/epidemiologia , Adulto Jovem
8.
J Cancer Res Clin Oncol ; 146(1): 33-41, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31728618

RESUMO

PURPOSE: Concurrent chemoradiotherapy (CCRT) is one of the standard treatments for patients with advanced head and neck squamous cell carcinoma (HNSCC). However, CCRT may lead to decreased quality of life (QoL) and treatment compliance. This study aimed to determine the effects of PG2 (Astragalus polysaccharides) injection on CCRT-associated adverse events (AEs) and patients' compliance with the CCRT course. METHODS: In this phase II double-blind randomized placebo-controlled trial, PG2 injection (sterile powder form) or placebo was administrated three times per week in parallel with CCRT to patients with HNSCC. The chemotherapy regimen included 50 mg/m2 cisplatin every 2 weeks with daily tegafur-uracil (300 mg/m2) and leucovorin (60 mg/day). RESULTS: The study was terminated prematurely due to the successful launch of a newly formulated PG2 injection (lyophilized form). A total of 17 patients were enrolled. The baseline demographics and therapeutic compliance were comparable between the CCRT/PG2 and CCRT/placebo groups. During CCRT, severe treatment-associated AEs were less frequent in the CCRT/PG2 group than in the CCRT/placebo group. Furthermore, less QoL fluctuations from the baseline during CCRT were noted in the CCRT/PG2 group than in the CCRT/placebo group, with a significant difference in the pain, appetite loss, and social eating behavior. The tumor response, disease-specific survival and overall survival did not differ between the two groups. CONCLUSION: This preliminary study demonstrated PG2 injection exhibited an excellent safety profile, and has potential in ameliorating the deterioration in QoL and the AEs associated with active anticancer treatment among patients with advanced pharyngeal or laryngeal HNSCC under CCRT. Further research in patients with other cancer types or treatment modalities may widen PG2's application in clinical settings.


Assuntos
Neoplasias Laríngeas/tratamento farmacológico , Neoplasias Laríngeas/radioterapia , Neoplasias Faríngeas/tratamento farmacológico , Neoplasias Faríngeas/radioterapia , Polissacarídeos/administração & dosagem , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Astrágalo (Planta) , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos , Cisplatino/administração & dosagem , Método Duplo-Cego , Feminino , Humanos , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Tegafur/administração & dosagem , Uracila/administração & dosagem
9.
J Oral Pathol Med ; 49(1): 9-13, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31385634

RESUMO

Squamous cell carcinoma (SCC) is the most common non-cutaneous head and neck (H&N) malignancy. Referrals for suspected SCC are seen by oral and maxillofacial surgery (OMFS) surgeons and represent the bulk of 2-week wait referrals. The diagnosis and treatment of SCC is heavily influenced by national and international guidelines. The majority of research and funding is directed towards this condition. This has led to continuous changes to update these guidelines. However, there remain areas of controversy and conflicting evidence. This article summarises articles pertinent to pathologists between 2016 and 2018 published in the leading British OMFS journal. A total of 22 published articles relating to the histopathology of non-cutaneous H&N SCC were selected.


Assuntos
Carcinoma de Células Escamosas de Cabeça e Pescoço , Humanos , Metástase Linfática , Estadiamento de Neoplasias , Neoplasias Cutâneas
10.
Oncology ; 98(1): 42-47, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31437849

RESUMO

INTRODUCTION: Smoking induces inflammation and an immune response. A cancer-related inflammatory response has been seen in smoking and nonsmoking head and neck squamous cell carcinoma (HNSCC) patients. OBJECTIVES: The aim of this study was to analyze the possible separated effects of smoking or HNSCC on 18 inflammatory or immune regulatory biomarkers. METHODS: Fifty-one nonsmoking and 36 smoking pretreated HNSCC patients and 101 nonsmoking and 39 smoking controls were included in this study. The levels of 18 inflammatory or immune regulatory biomarkers were analyzed. A multivariable linear regression model was used to predict the impact of smoking and HNSCC on the levels of the biomarkers. RESULTS: Smoking had the highest impact on total WBC, IFN-γ, and MCP-1 levels. The highest impact of HNSCC was found on neutrophils, neutrophil-to-lymphocyte ratio, HsCRP, MIP-1b, and TNF-α levels. CONCLUSION: IdentifyingHNSCC or smoking-related inflammatory biomarkers might contribute to the understanding of the immune response in HNSCC patients. This study could provide information of inflammatory biomarkers in HNSCC patients.


Assuntos
Biomarcadores/sangue , Fumar Cigarros , Mediadores da Inflamação/sangue , Carcinoma de Células Escamosas de Cabeça e Pescoço/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Fumar Cigarros/efeitos adversos , Citocinas/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/etiologia , Carga Tumoral , Adulto Jovem
11.
Int J Radiat Oncol Biol Phys ; 106(1): 157-166, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31580929

RESUMO

PURPOSE: Previous studies have found that patients with head and neck cancer (HNC) with a higher relative hazard for recurrence versus competing mortality (ω+ ratio) are more likely to benefit from intensive therapy. Nomograms to predict this ratio (ω scores) can be useful to guide clinical management; however, comorbidity and other risk factors are frequently lacking from trial samples. METHODS AND MATERIALS: In this study of 7117 US veterans, we evaluated the ability of a ω score nomogram developed from clinical trial data to stratify patients with HNC treated with radiation therapy by their relative risk of cancer progression versus competing mortality. We then fit generalized competing event models to determine the effect of comorbidity and other covariates on the ω+ ratio. RESULTS: The ω score was effective in stratifying patients with HNC according to their risk for cancer recurrence relative to competing mortality, especially among patients aged >70 years. Patients with ω score ≥0.80 were more likely to receive intensive therapy compared with patients with a ω score <0.80 (66 vs. 54%; P < .001). On multivariable generalized competing event regression, T2-4 category (relative hazard ratio [RHR], 1.08; 95% confidence interval [CI], 1.01-1.16), N2-3 category (RHR, 1.07; 95% CI, 1.01-1.15), and being employed (RHR, 1.11; 95% CI, 1.03-1.20) were associated with increased ω+ ratio, and increasing age (RHR, 0.83; 95% CI, 0.78-0.89), Charlson comorbidity index ≥2 (RHR, 0.85; 95% CI, 0.79-0.91), being a current smoker (RHR, 0.90; 95% CI, 0.84-0.96), and lower body mass index (RHR, 0.89; 95% CI, 0.84-0.95) were associated with a decreased ω+ ratio. CONCLUSIONS: The ω scores are effective in stratifying patients with HNC and are correlated with the intensity of treatment given. The ω scores incorporating comorbidity and other risk factors could help identify patients with HNC most likely to benefit from intensive therapy.


Assuntos
Neoplasias de Cabeça e Pescoço/radioterapia , Recidiva Local de Neoplasia , Nomogramas , Seleção de Pacientes , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Fatores Etários , Idoso , Comorbidade , Intervalos de Confiança , Progressão da Doença , Emprego , Feminino , Neoplasias de Cabeça e Pescoço/classificação , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Radioterapia de Intensidade Modulada , Análise de Regressão , Fatores de Risco , Fumantes , Carcinoma de Células Escamosas de Cabeça e Pescoço/classificação , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Magreza/complicações , Veteranos/estatística & dados numéricos
12.
J Clin Pathol ; 73(1): 17-22, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31300530

RESUMO

OBJECTIVE: Cutaneous squamous cell carcinoma (cSCC) is the second most common malignancy, most frequently affecting the head and neck. Treatment often requires surgery and can have significant functional morbidity. Research into disease pathogenesis and second line medical management of cSCC is limited. We assess genetic mutations in high-risk, primary head and neck cutaneous squamous cell carcinomas (HNcSCC) that may hinder or be beneficial for use of targeted therapy in disease management. METHODS: Genetic alterations and variant allele frequencies (VAFs) were analysed using a clinically relevant 48 gene panel in 10 primary high-risk non-metastatic treatment-naïve HNcSCC to evaluate applicability of targeted therapeutics. Variants present at all VAFs were evaluated for pathogenicity. Somatic mutation patterns of individual tumours were analysed. RESULTS: High-risk HNcSCC showed a high proportion (82%) of C to T transitions in keeping with ultraviolet-mediated damage. There was significant intratumour genetic heterogeneity in this cohort (MATH scores 20-89) with the two patients <45 years of age showing highest intratumour heterogeneity. TP53 was altered at VAF >22% in all cases, and mutations with highest VAF were observed in tumour suppressor genes in 80%. 70% of cases demonstrated at least one mutation associated with treatment resistance (KIT S821F, KIT T670I, RAS mutations at codons 12 and 13). CONCLUSION: We demonstrate high proportion tumour suppressor loss of function mutations, high intratumour genetic heterogeneity, and presence of well recognised resistance mutations in treatment naïve primary HNcSCC. These factors pose challenges for successful utilisation of targeted therapies.


Assuntos
Biomarcadores Tumorais/genética , Heterogeneidade Genética , Neoplasias de Cabeça e Pescoço/genética , Mutação , Neoplasias Cutâneas/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Tomada de Decisão Clínica , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Predisposição Genética para Doença , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Seleção de Pacientes , Fenótipo , Medicina de Precisão , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Transcriptoma
13.
J Oncol Pharm Pract ; 26(1): 240-243, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31042137

RESUMO

Recurrent or metastatic disease occurs in two-thirds of head and neck squamous cell carcinomas and it is associated with poor prognosis. Systemic treatment with platinum-based chemotherapy in combination with the epidermal growth factor receptor-targeting monoclonal antibody cetuximab represents a preferred option for these patients. Upon the achievement of tumor response by combined treatment, maintenance with single-agent cetuximab is usually administered with the aim of prolonging disease control at the price of reasonable toxicity. Although rarely, however, cetuximab needs to be discontinued in the absence of disease progression because of intolerable side effects. Here we describe the case of a 66-year-old man with a metastatic cancer of oral cavity, who had to discontinue maintenance cetuximab and who achieved prolonged disease control with metronomic capecitabine. We suggest that capecitabine could be an effective and safe maintenance option in case of cetuximab intolerance.


Assuntos
Capecitabina/uso terapêutico , Neoplasias Bucais/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cetuximab/efeitos adversos , Cetuximab/uso terapêutico , Humanos , Masculino , Neoplasias Bucais/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia
14.
Anticancer Res ; 39(12): 6819-6827, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31810948

RESUMO

BACKGROUND/AIM: This Japanese multiple-center retrospective study aimed to examine the real-world treatment outcomes of the EXTREME regimen as a first-line therapy for recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). PATIENTS AND METHODS: A total of 100 R/M SCCHN patients treated with the EXTREME regimen as first-line therapy were analyzed. The treatment outcomes were evaluated to compare patient and treatment characteristics with overall survival. RESULTS: Patients treated with carboplatin-based EXTREME regimen showed similar overall survival with less adverse effects compared to that of patients using cisplatin. The post-progression survival was significantly longer in patients treated with second-line treatment following the EXTREME regimen than in those without second-line treatment. CONCLUSION: The carboplatin-based EXTREME regimen was more feasible with similar treatment outcomes compared to cisplatin-based EXTREME regimen. In addition, subsequent lines of therapy contributed to improvement of survival for R/M SCCHN patients.


Assuntos
Antineoplásicos/administração & dosagem , Carboplatina/administração & dosagem , Cisplatino/administração & dosagem , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Carboplatina/uso terapêutico , Cisplatino/uso terapêutico , Ensaios Clínicos como Assunto , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
16.
Lancet ; 394(10212): 1915-1928, 2019 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-31679945

RESUMO

BACKGROUND: Pembrolizumab is active in head and neck squamous cell carcinoma (HNSCC), with programmed cell death ligand 1 (PD-L1) expression associated with improved response. METHODS: KEYNOTE-048 was a randomised, phase 3 study of participants with untreated locally incurable recurrent or metastatic HNSCC done at 200 sites in 37 countries. Participants were stratified by PD-L1 expression, p16 status, and performance status and randomly allocated (1:1:1) to pembrolizumab alone, pembrolizumab plus a platinum and 5-fluorouracil (pembrolizumab with chemotherapy), or cetuximab plus a platinum and 5-fluorouracil (cetuximab with chemotherapy). Investigators and participants were aware of treatment assignment. Investigators, participants, and representatives of the sponsor were masked to the PD-L1 combined positive score (CPS) results; PD-L1 positivity was not required for study entry. The primary endpoints were overall survival (time from randomisation to death from any cause) and progression-free survival (time from randomisation to radiographically confirmed disease progression or death from any cause, whichever came first) in the intention-to-treat population (all participants randomly allocated to a treatment group). There were 14 primary hypotheses: superiority of pembrolizumab alone and of pembrolizumab with chemotherapy versus cetuximab with chemotherapy for overall survival and progression-free survival in the PD-L1 CPS of 20 or more, CPS of 1 or more, and total populations and non-inferiority (non-inferiority margin: 1·2) of pembrolizumab alone and pembrolizumab with chemotherapy versus cetuximab with chemotherapy for overall survival in the total population. The definitive findings for each hypothesis were obtained when statistical testing was completed for that hypothesis; this occurred at the second interim analysis for 11 hypotheses and at final analysis for three hypotheses. Safety was assessed in the as-treated population (all participants who received at least one dose of allocated treatment). This study is registered at ClinicalTrials.gov, number NCT02358031. FINDINGS: Between April 20, 2015, and Jan 17, 2017, 882 participants were allocated to receive pembrolizumab alone (n=301), pembrolizumab with chemotherapy (n=281), or cetuximab with chemotherapy (n=300); of these, 754 (85%) had CPS of 1 or more and 381 (43%) had CPS of 20 or more. At the second interim analysis, pembrolizumab alone improved overall survival versus cetuximab with chemotherapy in the CPS of 20 or more population (median 14·9 months vs 10·7 months, hazard ratio [HR] 0·61 [95% CI 0·45-0·83], p=0·0007) and CPS of 1 or more population (12·3 vs 10·3, 0·78 [0·64-0·96], p=0·0086) and was non-inferior in the total population (11·6 vs 10·7, 0·85 [0·71-1·03]). Pembrolizumab with chemotherapy improved overall survival versus cetuximab with chemotherapy in the total population (13·0 months vs 10·7 months, HR 0·77 [95% CI 0·63-0·93], p=0·0034) at the second interim analysis and in the CPS of 20 or more population (14·7 vs 11·0, 0·60 [0·45-0·82], p=0·0004) and CPS of 1 or more population (13·6 vs 10·4, 0·65 [0·53-0·80], p<0·0001) at final analysis. Neither pembrolizumab alone nor pembrolizumab with chemotherapy improved progression-free survival at the second interim analysis. At final analysis, grade 3 or worse all-cause adverse events occurred in 164 (55%) of 300 treated participants in the pembrolizumab alone group, 235 (85%) of 276 in the pembrolizumab with chemotherapy group, and 239 (83%) of 287 in the cetuximab with chemotherapy group. Adverse events led to death in 25 (8%) participants in the pembrolizumab alone group, 32 (12%) in the pembrolizumab with chemotherapy group, and 28 (10%) in the cetuximab with chemotherapy group. INTERPRETATION: Based on the observed efficacy and safety, pembrolizumab plus platinum and 5-fluorouracil is an appropriate first-line treatment for recurrent or metastatic HNSCC and pembrolizumab monotherapy is an appropriate first-line treatment for PD-L1-positive recurrent or metastatic HNSCC. FUNDING: Merck Sharp & Dohme.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Cetuximab/uso terapêutico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Idoso , Antimetabólitos Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Fluoruracila/uso terapêutico , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade
17.
HNO ; 67(12): 898-904, 2019 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-31701170

RESUMO

BACKGROUND: The contributions presented at this year's ASCO conference on treatment of recurrent or metastatic head and neck squamous cell carcinoma (R/M-HNSCC) focused on systemic therapies, as in recent years. Two phase III studies-TPExtreme and Keynote-048-are expected to change clinical practice in first-line treatment of R/M-HNSCC. MATERIALS AND METHODS: Abstracts and presentations from this year's ASCO Annual Meeting on R/M-HNSCC were screened and checked for clinical relevance. RESULTS: TPExtreme, a randomized phase III trial, could show less toxicity and similar overall survival in patients treated with docetaxel, cisplatin, and cetuximab (TPEx regimen) compared to standard first-line therapy with the Extreme regimen (cisplatin, 5­fluorouracil [5-FU], cetuximab), albeit failing its endpoint of significantly improved survival. The randomized phase III Keynote-048 study could show a significant survival benefit in all patients treated with pembrolizumab, 5­FU, and cis-/carboplatin compared to Extreme. When selected patients (PD-L1 CPS ≥1 and ≥20) were treated with pembrolizumab monotherapy, they showed increased overall response rates in contrast to patients treated with Extreme. CONCLUSION: Based on the results of Keynote-048, pembrolizumab ± chemotherapy gained FDA approval as first-line treatment for R/M-HNSCC in the USA. Approval in Europe is expected soon and will probably have a strong impact on clinical routine.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias de Cabeça e Pescoço , Carcinoma de Células Escamosas de Cabeça e Pescoço , Cetuximab , Congressos como Assunto , Europa (Continente) , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Humanos , Recidiva Local de Neoplasia , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico
18.
Anticancer Res ; 39(11): 6041-6047, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31704830

RESUMO

BACKGROUND/AIM: We have previously reported that alternate-day S-1 had comparable effects and milder adverse events than the respective consecutive-day regimen in head and neck cancer (HNC) patients. The aim of this study was to investigate the anticancer effects of both regimens and underlying mechanisms in vitro. MATERIALS AND METHODS: Two head and neck squamous cell carcinoma (HNSCC) cell lines were treated with 5-FU given on an alternate-day or consecutive-day schedule. The relative inhibition (RI) of tumor growth was calculated. Cell cycle distributions and cyclin expression following 5-FU treatment were analyzed. RESULTS: The RI of both regimens was almost identical. The percentage of cells in S phase was significantly increased in the alternate-day group compared to the consecutive-day group (p<0.001). CONCLUSION: The cytotoxic effect of alternate-day was equivalent to that of consecutive-day. S-phase arrest was more prominently observed with the alternate-day regimen, which may help maintain 5-FU sensitivity in head and neck cancer cells.


Assuntos
Antimetabólitos Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Fluoruracila/farmacologia , Neoplasias de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Esquema de Medicação , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Humanos , Técnicas In Vitro , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Células Tumorais Cultivadas
19.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 37(5): 516-520, 2019 Oct 01.
Artigo em Chinês | MEDLINE | ID: mdl-31721500

RESUMO

OBJECTIVE: This study aimed to construct a network of programmed celldeath ligand 1 (PD-L1) co-expression genes and screen potential biomarkers for PD-L1 expression in head and neck squamous cell carcinoma (HNSCC) by bioinformatics analysis. Moreover, the genes and pathways participating in PD-L1 and regulating the tumor immune status were determined. METHODS: The HNSCC transcriptomic dataset in TCGA was selected to retrieve gene sets on the cBioPortal platform, where PD-L1 co-expressional genes were acquired. With these genes, GO-BP, KEGG, and string analyses were performed in R clusterProfiler. Cytoscape was used for network analysis and hub gene screening. RESULTS: A total of 117 co-expression genes were obtained, most of which were enriched in immune regulation and response to viral processes. Node degree analysis indicated that STAT1, IFNG, CXCL10, CCR5, FCGR3A, CXCL9, GBP5, CD86, GZMB, IRF1 were the highest connected genes and functioned as hub genes. Survival analysis of these hub genes resulted in CCR5, CXCL9, and GZMB as the prognostic biomarkers for patients with HNSCC, all of which were involved in immune regulation and their expression levels were related to PD-L1 (Pearson correlation coefficient was 0.30, 0.35, 0.39; P<0.01). High expression levels of these three hub genes were protective factors in patients with HNSCC. CONCLUSIONS: PD-L1 co-expression hub genes are related to immunity, among which CCR5, CXCL9, and GZMB are prognostic markers with the possibility to be involved in programmed cell death protein 1 (PD-1)/PD-L1-induced tumor immune escape. These genes provide new clues to study the mechanism and precision target medicine of PD-1/PD-L1 in HNSCC.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Carcinoma de Células Escamosas de Cabeça e Pescoço , Antígeno B7-H1 , Biologia Computacional , Humanos , Receptores de IgG
20.
Medicine (Baltimore) ; 98(45): e17883, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31702662

RESUMO

RATIONALE: Of all the parts of the larynx, the glottis has the highest frequency of cancer. With disease progression, the vocal cord movement is affected and for advanced stages its anatomical and functional preservation is rarely achievable, if at all. PATIENT CONCERNS: Here we describe a 72-year-old patient who presented with hoarseness for a year and was only able to whisper. DIAGNOSIS: A computed tomography (CT) scan of the vocal cords (without contrast) showed higher density tissue. Histological examination disclosed a well-differentiated verrucous squamous cell carcinoma of the glottis. INTERVENTIONS: The patient was treated with the oncolytic ECHO-7 virus Rigvir without any of the standard treatments. OUTCOMES: As shown by CT scans, the patient has been stabilized, and the laryngeal functions are preserved with the virotherapy still ongoing. The patient was diagnosed over 4.2 years ago. LESSONS: Considering the present patient being treated with Rigvir without any standard treatment, the results suggest that Rigvir therapy could be a possible treatment for glottic cancer.


Assuntos
Neoplasias Laríngeas/terapia , Terapia Viral Oncolítica/métodos , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Idoso , Glote/diagnóstico por imagem , Glote/patologia , Humanos , Neoplasias Laríngeas/diagnóstico por imagem , Neoplasias Laríngeas/patologia , Masculino , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico por imagem , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Tomografia Computadorizada por Raios X , Resultado do Tratamento
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