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1.
Nat Commun ; 12(1): 1047, 2021 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-33594075

RESUMO

Despite the success of checkpoint blockade in some cancer patients, there is an unmet need to improve outcomes. Targeting alternative pathways, such as costimulatory molecules (e.g. OX40, GITR, and 4-1BB), can enhance T cell immunity in tumor-bearing hosts. Here we describe the results from a phase Ib clinical trial (NCT02274155) in which 17 patients with locally advanced head and neck squamous cell carcinoma (HNSCC) received a murine anti-human OX40 agonist antibody (MEDI6469) prior to definitive surgical resection. The primary endpoint was to determine safety and feasibility of the anti-OX40 neoadjuvant treatment. The secondary objective was to assess the effect of anti-OX40 on lymphocyte subsets in the tumor and blood. Neoadjuvant anti-OX40 was well tolerated and did not delay surgery, thus meeting the primary endpoint. Peripheral blood phenotyping data show increases in CD4+ and CD8+ T cell proliferation two weeks after anti-OX40 administration. Comparison of tumor biopsies before and after treatment reveals an increase of activated, conventional CD4+ tumor-infiltrating lymphocytes (TIL) in most patients and higher clonality by TCRß sequencing. Analyses of CD8+ TIL show increases in tumor-antigen reactive, proliferating CD103+ CD39+ cells in 25% of patients with evaluable tumor tissue (N = 4/16), all of whom remain disease-free. These data provide evidence that anti-OX40 prior to surgery is safe and can increase activation and proliferation of CD4+ and CD8+ T cells in blood and tumor. Our work suggests that increases in the tumor-reactive CD103+ CD39+ CD8+ TIL could serve as a potential biomarker of anti-OX40 clinical activity.


Assuntos
Epitopos/imunologia , Terapia Neoadjuvante , Receptores OX40/antagonistas & inibidores , Carcinoma de Células Escamosas de Cabeça e Pescoço/imunologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Biópsia , Linfócitos T CD8-Positivos/imunologia , Proliferação de Células , Células Clonais , Intervalo Livre de Doença , Papillomavirus Humano 16/fisiologia , Humanos , Estimativa de Kaplan-Meier , Ativação Linfocitária/imunologia , Subpopulações de Linfócitos/imunologia , Linfócitos do Interstício Tumoral/imunologia , Terapia Neoadjuvante/efeitos adversos , Receptores de Antígenos de Linfócitos T/metabolismo , Receptores OX40/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/sangue , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Células Estromais/metabolismo
2.
Laryngorhinootologie ; 100(1): 23-29, 2021 01.
Artigo em Alemão | MEDLINE | ID: mdl-33401320

RESUMO

An increasing amount of evidence suggests the existence of a stem cell-like population in head and neck squamous cell carcinoma (HNSCC). These cells have been termed cancer stem cells (CSC) due to the shared properties with somatic stem cells, such as the ability to self-renew and differentiate. Furthermore, the CSC are thought to be resistant to antineoplastic treatments and are therefore clinically relevant. As with somatic stem cells, CSC are thought to reside in a specialized supportive microenvironment, called the stem cell niche. One possible strategy to target the CSC could be through affecting functions of the stem cell niche.Stromal cell-derived factor-1 (SDF-1) is a multifunctional cytokine, which is secreted by e. g. stromal cells within the niche. SDF-1 is known to be the major regulator of stem cell trafficking between the niche and the peripheral vascular system. It elicits the chemotactic activity through interaction with a transmembrane receptor CXCR4, expressed by CSC. The SDF-1-CXCR4-axis is thought to play a crucial role in the interaction between CSC and their supportive cells in the tumor niche. A better understanding of these interactions could help in gaining further insight into the pathophysiology of progression/recurrence of malignant diseases and aid in finding new strategies for therapy.Specialized cell culture models are of advantage for deciphering the mechanisms of interaction between CSC and their niche. We anticipate that the recent technological advancements in bioprinting and the development of complex 3D cell culture model systems will contribute to our understanding of these mechanisms and to the establishment of individualized therapies.Here were provide an overview of the current knowledge on the CSC-tumor stem cell niche interactions in HNSCC with a focus on the SDF-1-CXCR4 axis.


Assuntos
Neoplasias de Cabeça e Pescoço , Nicho de Células-Tronco , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Recidiva Local de Neoplasia , Células-Tronco Neoplásicas , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Microambiente Tumoral
3.
Anticancer Res ; 41(1): 477-484, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33419846

RESUMO

BACKGROUND/AIM: Patients with unresectable head-and-neck cancer (SCCHN) unable to tolerate radiochemotherapy may receive unconventionally fractionated radiotherapy. This retrospective study compared both treatments. PATIENTS AND METHODS: Eight patients unsuitable for chemotherapy were assigned to accelerated fractionation with concomitant boost (AF-CB, 69.6 Gy/39 fractions) over 5.5 weeks (group A) and 72 patients to cisplatin-based radiochemotherapy (70 Gy/35 fractions) over 7 weeks (group B). Groups were matched (cancer site, gender, age, performance score, T-/N-stage, histologic grade) and compared for loco-regional control (LRC), metastases-free survival (MFS), overall survival (OS) and toxicities. RESULTS: LRC, MFS, OS and radiation-related toxicities were not significantly different between groups A and B. Improved outcomes were associated with favorable cancer site, better performance score and T3-stage. In group B, toxicity led to reduction/discontinuation of chemotherapy in 38.9% and interruptions of radiotherapy >7 days in 19.3% of patients. CONCLUSION: AF-CB appeared a reasonable alternative for patients who cannot safely receive radio-chemotherapy for unresectable SCCHN.


Assuntos
Quimiorradioterapia , Fracionamento da Dose de Radiação , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Idoso , Quimiorradioterapia/métodos , Terapia Combinada , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Dosagem Radioterapêutica , Resultado do Tratamento
4.
Cancer Sci ; 112(3): 978-988, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33368875

RESUMO

Cancer is characterized by an accumulation of somatic mutations that represent a source of neoantigens for targeting by antigen-specific T cells. Head and neck squamous cell carcinoma (HNSCC) has a relatively high mutation burden across all cancer types, and cellular immunity to neoantigens likely plays a key role in HNSCC clinical outcomes. Immune checkpoint inhibitors (CPIs) have brought new treatment options and hopes to patients with recurrent and/or metastatic HNSCC. However, many patients do not benefit from CPI therapies, highlighting the need for novel immunotherapy or combinatorial strategies. One such approach is personalized cancer vaccination targeting tumor-associated antigens and tumor-specific antigens, either as single agents or in combination with other therapies. Recent advances in next-generation genomic sequencing technologies and computational algorithms have enabled efficient identification of somatic mutation-derived neoantigens and are anticipated to facilitate the development of cancer vaccine strategies. Here, we review cancer vaccine approaches against HNSCC, including fundamental mechanisms of a cancer vaccine, considerations for selecting appropriate antigens, and combination therapies.


Assuntos
Antígenos de Neoplasias/genética , Vacinas Anticâncer/uso terapêutico , Neoplasias de Cabeça e Pescoço/terapia , Medicina de Precisão/métodos , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Antígenos de Neoplasias/imunologia , Antineoplásicos Imunológicos/uso terapêutico , Vacinas Anticâncer/genética , Vacinas Anticâncer/imunologia , Ensaios Clínicos como Assunto , Terapia Combinada/métodos , Análise Mutacional de DNA , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/imunologia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Imunogenicidade da Vacina , Mutação , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/imunologia , Resultado do Tratamento , Vacinas de DNA/genética , Vacinas de DNA/imunologia , Vacinas de DNA/uso terapêutico , Vacinas de Subunidades/genética , Vacinas de Subunidades/imunologia , Vacinas de Subunidades/uso terapêutico
5.
BMJ Case Rep ; 13(12)2020 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-33334769

RESUMO

Squamous cell carcinoma (SCC) of the lip typically has a good prognosis when diagnosed at an early stage and treated properly. We present a 65-year-old man with a 3-month history of an ulcerative lesion of the lower lip. On physical examination, he had an ulceration of approximately 5×5 cm in the mucosa of the lower lip, extending through 50% of the lip, and multiple mandibular and neck lymph nodes. The biopsy confirmed SCC of the lip. Surgical treatment was recommended, but the patient was lost to follow-up. The patient eventually returned to the hospital for medical treatment. However, the physical examination, and the images obtained showed progression of the disease. Chemotherapy was started with improvement in the primary site, but he then developed a large submental mass compatible with SCC. The tumour was considered incurable at that time. Palliative radiation therapy was offered; however, he refused any further procedures or treatment.


Assuntos
Neoplasias Labiais/diagnóstico , Lábio/patologia , Metástase Linfática/diagnóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico , Idoso , Biópsia , Humanos , Neoplasias Labiais/patologia , Neoplasias Labiais/terapia , Metástase Linfática/terapia , Masculino , Cuidados Paliativos , Carcinoma de Células Escamosas de Cabeça e Pescoço/secundário , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia
6.
HNO ; 68(12): 922-926, 2020 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-33044581

RESUMO

BACKGROUND: The pathogenesis of head and neck squamous cell carcinoma (HNSCC) is a complex and multistage process which results from the interaction of exogenous and endogenous cellular processes. Each of these processes leaves a characteristic pattern of mutations on the tumor genome, a so-called mutational signature. STATE OF THE ART: The subject of current studies is to decipher specific signatures of mutational processes operating during HNSCC pathogenesis and to address their prognostic value. Computational analysis of genomic sequencing data by The Cancer Genome Atlas (TCGA) revealed mutational signatures 1, 2, 4, 5, 7, and 13 as the main players in HNSCC pathogenesis. Signature 16 was first discovered in human papillomavirus (HPV)-negative oral and oropharyngeal tumors. In many studies, an association of signature 16 with alcohol and tobacco consumption as well as with an unfavorable prognosis was described.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Orofaríngeas , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/terapia , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Mutação/genética , Infecções por Papillomavirus/complicações , Prognóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia
7.
Medicine (Baltimore) ; 99(36): e21785, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32899005

RESUMO

BACKGROUND: Concurrent cisplatin with radiotherapy (CRT) or concurrent cetuximab with radiotherapy (BRT) improves outcomes in locally advanced head and neck squamous cell carcinoma (HNSCC) compared with radiotherapy alone. Nevertheless, a detailed comparison between CRT and BRT in locally advanced HNSCC is required due to inconclusive results. METHODS: A comprehensive literature search was conducted on PubMed, Web of Science, Cochrane databases, and EMBASE. Studies that evaluated CRT vs BRT in locally advanced HNSCC were included. The primary outcome that was overall survival (OS), whereas the secondary outcomes were progression-free survival (PFS), locoregional control (LRC), and distant metastasis-free survival (DMFS). Pooled hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) were used to evaluate prognosis. All the analyses were performed using Stata Statistical Software 12.0. RESULTS: Twenty-three studies, with a total of 8701 patients, were considered eligible and included in this meta-analysis. Our results revealed that patients treated with CRT had longer OS (HR = 0.51, 95%CI, 0.41-0.64, P < .001), PFS (HR = 0.37, 95%CI, 0.23-0.60, P < .001), LRC (HR = 0.46, 95%CI, 0.37-0.57, P < .001), and DMFS (HR = 0.56, 95%CI, 0.40-0.77, P < .001) than those treated with BRT. Furthermore, the results of the subgroup analyses were consistent with the primary analysis. CONCLUSIONS: CRT has a better OS, PFS, LRC, and DMFS than BRT in locally advanced HNSCC, and should be the preferred treatment for patients with the disease.


Assuntos
Cetuximab/uso terapêutico , Cisplatino/uso terapêutico , Neoplasias de Cabeça e Pescoço/terapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Idoso , Quimiorradioterapia/métodos , Intervalo Livre de Doença , Feminino , 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
8.
Medicine (Baltimore) ; 99(39): e22244, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32991419

RESUMO

The aim of the present study is to investigate the association of treatment package time with the survival outcomes and clinical parameters in patients with oropharyngeal squamous cell carcinoma.A total of 49 patients who underwent definitive treatment were enrolled. The treatment package time was calculated in days from the start of any treatment to the completion of all treatments, including postoperative treatment and salvage surgery for residual tumor.On univariate analyzes, treatment package time ≥118 days, sake index ≥60, Brinkman index ≥450, maximum standardized uptake value ≥42.45, and the presence of synchronous cancer were significantly associated with shorter oropharyngeal squamous cell carcinoma-specific survival. Moreover, a treatment package time of ≥118 days was significantly correlated with shorter overall survival and distant metastasis-free survival. On multivariate analyzes, Brinkman index ≥450 was significantly associated with shorter oropharyngeal squamous cell carcinoma-specific and locoregional recurrence-free survival, and the presence of synchronous cancer was significantly associated with shorter overall and distant metastasis-free survival.In conclusion, a relatively long treatment package time was a predictor of low survival outcomes in oropharyngeal squamous cell carcinoma by univariate analysis.


Assuntos
Neoplasias Orofaríngeas/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Orofaríngeas/terapia , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Análise de Sobrevida , Fatores de Tempo
9.
Jpn J Clin Oncol ; 50(10): 1089-1096, 2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-32776100

RESUMO

Squamous cell carcinoma of the head and neck is characterized by an immunosuppressive environment and evades immune responses through multiple resistance mechanisms. A breakthrough in cancer immunotherapy employing immune checkpoint inhibitors has evolved into a number of clinical trials with antibodies against programmed cell death 1 (PD-1), its ligand PD-L1 and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) for patients with squamous cell carcinoma of the head and neck. CheckMate141 and KEYNOTE-048 were practice-changing randomized phase 3 trials for patients with platinum-refractory and platinum-sensitive recurrent or metastatic squamous cell carcinoma of the head and neck, respectively. Furthermore, many combination therapies using anti-CTLA-4 inhibitors, tyrosine kinase inhibitors and immune accelerators are currently under investigation. Thus, the treatment strategy of recurrent or metastatic squamous cell carcinoma of the head and neck is becoming more heterogeneous and complicated in the new era of individualized medicine. Ongoing trials are investigating immunotherapeutic approaches in the curative setting for locoregionally advanced disease. This review article summarizes knowledge of the role of the immune system in the development and progression of squamous cell carcinoma of the head and neck, and provides a comprehensive overview on the development of immunotherapeutic approaches in both recurrent/metastatic and locoregionally advanced diseases.


Assuntos
Imunoterapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Ensaios Clínicos como Assunto , Resistencia a Medicamentos Antineoplásicos , Humanos , Metástase Neoplásica , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia
10.
Anticancer Res ; 40(8): 4207-4214, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32727746

RESUMO

BACKGROUND/AIM: To assess factors that predict detection of tumors and oncologic outcomes in head and neck squamous cell carcinoma of unknown primary (SCCUP). PATIENTS AND METHODS: This was a retrospective cohort study at a single tertiary care institution. RESULTS: The primary site was detected at examination under anesthesia (EUA) in 92 (51.1%) patients. The primary site was detected by directed biopsies in 60 (65%), palatine tonsillectomy in 28 (30.4%), and lingual tonsillectomy in 4 patients (4.3%). Four of eight lingual tonsillectomies were positive (50%). Primary locations included: palatine tonsils (51, 28.3%), base of tongue (37, 20.6%), larynx (4, 2.2%), oral cavity (3, 1.67%) and nasopharynx (1, 0.6%). Human papillomavirus (HPV) positive status (HR=0.26, p=0.004) and treatment with chemoradiation (CRT) (HR=0.38, p=0.004) were associated with better disease free survival (DFS). CONCLUSION: A primary site was located after aggressive investigation in approximately half of the patients. More research is warranted towards the use of lingual tonsillectomy. Predictors of favorable prognosis included HPV positive status and treatment with CRT.


Assuntos
Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/secundário , Neoplasias Primárias Desconhecidas/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/secundário , Idoso , Intervalo Livre de Doença , Feminino , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia
11.
J Cancer Res Ther ; 16(3): 680-682, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32719291

RESUMO

Distant metastases in squamous cell carcinoma of the head and neck are uncommon, and the incidence rises with neck node metastasis. The lung, liver, and bones are the common possible sites for distant metastasis. Cutaneous and cardiac metastases are extremely rare situations with aggressive behaviors and present in the late course of the disease. Here, we report a case of anterior tongue cancer with cutaneous, bone, cardiac, lung, and soft tissue of right suprascapular area metastases after a gap of 2 years of follow-up of completion of treatment with radical surgery and adjuvant concurrent chemoradiation therapy. The present case developed such type of aggressive distant metastases without any locoregional recurrence and died within 6 months of diagnosis of distant metastases.


Assuntos
Carcinoma de Células Escamosas/patologia , Neoplasias Cardíacas/secundário , Neoplasias Cutâneas/secundário , Neoplasias da Língua/patologia , Adulto , Carcinoma de Células Escamosas/terapia , Terapia Combinada , Neoplasias Cardíacas/terapia , Humanos , Masculino , Prognóstico , Neoplasias Cutâneas/terapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Neoplasias da Língua/terapia
12.
Crit Rev Oncol Hematol ; 153: 103041, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32629362

RESUMO

The immune checkpoint inhibitors, a class of drugs able to block immune suppressive pathways in order to prime an anticancer immunity, revolutionized standard of care in platinum-refractory recurrent and/or metastatic head and neck carcinoma (R/M HNSCC). The PD-1/ PD-L1 axis is involved in the genesis, maintenance and progression of HNSCC and represents the target of checkpoint inhibitors. HNSCC is an immunosuppressive disease with a high inflammatory component in tumor microenvironment. Recent clinical trials showed that only a small subset of patients really benefits from immunotherapy. This review aims to highlight the five W-points of immunotherapy: why immunotherapy is promising in HNSCC, what is currently available in daily clinical practice, when immunotherapy can be integrated into the therapeutic strategy, where it can be useful according to predictive response biomarker, who, among patients, could get the best benefit from immunotherapy and how improve the achieved results.


Assuntos
Neoplasias de Cabeça e Pescoço/terapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Humanos , Fatores Imunológicos , Imunoterapia , Microambiente Tumoral
13.
JAMA Netw Open ; 3(6): e207199, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32602907

RESUMO

Importance: Nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin, are commonly prescribed medications with anti-inflammatory and antiplatelet properties used long term to decrease the risk of cardiovascular events. A recent study showed that aspirin was associated with improved survival in patients with head and neck squamous cell carcinoma (HNSCC) who were treated with surgery. Objective: To examine whether use of NSAIDs during definitive chemoradiation therapy (CRT) was associated with improved outcomes in patients with HNSCC. Design, Setting, and Participants: This cohort study analyzed patients with HNSCC who were treated with CRT at a single institution between January 1, 2005, and August 1, 2017. Patient and tumor characteristics included age, race/ethnicity, smoking status, alcohol use, comorbidities (respiratory, cardiovascular, immune, renal, endocrine), disease stage, human papillomavirus status, and treatment duration. Data were analyzed from May 1, 2019, to March 17, 2020. Exposures: Patients were dichotomized by NSAID use during treatment. Main Outcomes and Measures: The association of NSAID use with patterns of failure, disease-specific survival (DSS), and overall survival (OS) was examined using multivariate Cox proportional hazard regression models. Survival estimates for OS and DSS were generated using Kaplan-Meier survival curves. Results: A total of 460 patients (median [interquartile range] age, 60 [53.9-65.6] years; 377 [82.0%] men) were included in the analysis. Among these patients, 201 (43.7%) were taking NSAIDs during treatment. On univariate analysis, NSAID use (hazard ratio [HR], 0.63; 95% CI, 0.43-0.92; P = .02) was associated with better OS. On Cox regression analysis, after backward selection adjustment for potentially confounding factors (age, smoking status, primary tumor site, human papillomavirus status, diabetes, stroke, hyperlipidemia), NSAID use remained significantly associated with better OS (HR, 0.59; 95% CI, 0.38-0.90; P = .02). NSAID use was associated with significantly better OS at 5 years compared with patients who did not take concurrent NSAIDs (63.6% [56 of 88 patients]; 95% CI, 58%-73% vs 56.1% [83 of 148 patients]; 95% CI, 50%-63%; P = .03). NSAID use was not associated with better DSS in univariate (HR, 0.82; 95% CI, 0.48-1.41; P = .47) or multivariate (HR, 0.98; 95% CI, 0.57-1.70; P = .44) analysis. NSAID use was not associated with better response to treatment (HR, 1.44; 95% CI, 0.91-2.27; P = .12) or distant failure (HR, 1.12; 95% CI, 0.68-1.84; P = .65). Change in local control with NSAID use was not statistically significant (HR, 0.59; 95% CI, 0.31-1.10; P = .10). Conclusions and Relevance: This cohort study suggests a possible OS advantage for patients taking NSAIDs during chemoradiation for HNSCC. Further studies examining this association are warranted.


Assuntos
Anti-Inflamatórios não Esteroides , Neoplasias de Cabeça e Pescoço , Carcinoma de Células Escamosas de Cabeça e Pescoço , Idoso , Aspirina , Quimiorradioterapia , Feminino , Neoplasias de Cabeça e Pescoço/epidemiologia , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/epidemiologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia
14.
Oral Oncol ; 109: 104849, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32599499

RESUMO

OBJECTIVE: Surgery is the preferred treatment modality for oral squamous cell carcinoma (OSCC). However, due to limited resources, re-assessment of treatment paradigms in the wake of the Coronavirus Disease 2019 (COVID-19) pandemic is urgently required. In this rapid review, we described contemporary oncological outcomes for OSCC using non-surgical modalities. METHODS: A systematic literature search was conducted for articles published between January 1, 2010 and April 1, 2020 on MEDLINE and Cochrane CENTRAL. Studies were included if they contained patients with OSCC treated with either neoadjuvant, induction, or definitive radiotherapy, chemotherapy, immunotherapy, or combination thereof, and an outcome of overall survival. RESULTS: In total, 36 articles were included. Definitive radiotherapy or chemoradiotherapy were the focus of 18 articles and neoadjuvant chemotherapy or chemoradiotherapy were the focus of the other 18 articles. In early stage OSCC, definitive radiotherapy, with or without concurrent chemotherapy, was associated with a significantly increased hazard of death compared to definitive surgery (HR: 2.39, 95% CI: 1.56-3.67, I2: 63%). The hazard of death was non-significantly increased with definitive chemoradiotherapy in studies excluding early disease (HR: 1.98, 95% CI: 0.85-4.64, I2: 84%). Two recent randomized control trials have been conducted, demonstrating no survival advantage to neoadjuvant chemotherapy. CONCLUSION: This review suggests that primary radiotherapy and chemoradiotherapy are inferior to surgical management for OSCC. Strategies for surgical delay warranting consideration are sparse, but may include several neoadjuvant regimens, recognizing these regimens may not offer a survival benefit over definitive surgery alone.


Assuntos
Antineoplásicos/uso terapêutico , Quimiorradioterapia , Infecções por Coronavirus/epidemiologia , Neoplasias Bucais/terapia , Terapia Neoadjuvante , Pneumonia Viral/epidemiologia , Radioterapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Antineoplásicos Imunológicos/uso terapêutico , Betacoronavirus , Assistência à Saúde , Gerenciamento Clínico , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/terapia , Recursos em Saúde , Humanos , Mortalidade , Neoplasias Bucais/mortalidade , Pandemias , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade
15.
Ann Otol Rhinol Laryngol ; 129(12): 1243-1246, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32517491

RESUMO

OBJECTIVES: LMNA-associated familial partial lipodystrophy (FPLD) is a rare autosomal dominant A-type laminopathy characterized by variable loss and redistribution of subcutaneous adipose tissue, dyslipidemia, and insulin resistance. Though A-type lamins play a key role in nuclear membrane structure and regulation of cell proliferation, an association between cancer and LMNA-associated FPLD has not been reported. METHODS AND RESULTS: This report outlines the case of two biological sisters with LMNA-associated FPLD who developed hypopharyngeal squamous cell carcinoma in the absence of any other risk factors for head and neck cancer. CONCLUSION: These observations prompt further investigation into the potential role of A-type lamins in the development and progression of head and neck cancers.


Assuntos
Neoplasias Hipofaríngeas/complicações , Lipodistrofia Parcial Familiar/complicações , Irmãos , Carcinoma de Células Escamosas de Cabeça e Pescoço/complicações , Adulto , Quimiorradioterapia , Neoplasias Esofágicas/complicações , Carcinoma de Células Escamosas do Esôfago/complicações , Evolução Fatal , Feminino , Gastrostomia , Humanos , Neoplasias Hipofaríngeas/patologia , Neoplasias Hipofaríngeas/terapia , Lamina Tipo A/genética , Laringectomia , Lipodistrofia Parcial Familiar/genética , Faringectomia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Traqueostomia
16.
Anticancer Res ; 40(5): 2645-2655, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32366409

RESUMO

BACKGROUND/AIM: Two-thirds of head and neck squamous cell carcinoma (HNSCC) patients present with locally advanced (LA) stages and have a poor survival rate. The aim of this study was to investigate the roles of the long non-coding RNAs MALAT1 on radiation and cisplatin sensitivity of HNSCC cells. MATERIALS AND METHODS: Clonogenic, cell viability, and apoptosis assays were performed in cells following MALAT1 knockdown using CRISPR/Cas9 system. RESULTS: MALAT1 was overexpressed in HNSCC cell lines as compared to a non-tumorigenic cell line. The number of colonies formed after radiation was significantly reduced in MALAT1 knockdown cells. The IC50 value of cisplatin in MALAT1 knockdown cells was lower than that of the control cells. MALAT1 knockdown resulted in cell cycle arrest at G2/M phase, DNA damage and apoptotic cell death. CONCLUSION: MALAT1 knockdown enhanced the sensitivity of HNSCC cells to radiation and cisplatin partly through the induction of G2/M cell cycle arrest resulting in DNA damage and apoptosis.


Assuntos
Cisplatino/uso terapêutico , RNA Longo não Codificante/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Apoptose/genética , Pontos de Checagem do Ciclo Celular/genética , Linhagem Celular Tumoral , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , Humanos , RNA Longo não Codificante/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia
17.
PLoS One ; 15(5): e0232639, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32442178

RESUMO

INTRODUCTION: In this study, we investigate the role of radiomics for prediction of overall survival (OS), locoregional recurrence (LRR) and distant metastases (DM) in stage III and IV HNSCC patients treated by chemoradiotherapy. We hypothesize that radiomic analysis of (peri-)tumoral tissue may detect invasion of surrounding tissues indicating a higher chance of locoregional recurrence and distant metastasis. METHODS: Two comprehensive data sources were used: the Dutch Cancer Society Database (Alp 7072, DESIGN) and "Big Data To Decide" (BD2Decide). The gross tumor volumes (GTV) were delineated on contrast-enhanced CT. Radiomic features were extracted using the RadiomiX Discovery Toolbox (OncoRadiomics, Liege, Belgium). Clinical patient features such as age, gender, performance status etc. were collected. Two machine learning methods were chosen for their ability to handle censored data: Cox proportional hazards regression and random survival forest (RSF). Multivariable clinical and radiomic Cox/ RSF models were generated based on significance in univariable cox regression/ RSF analyses on the held out data in the training dataset. Features were selected according to a decreasing hazard ratio for Cox and relative importance for RSF. RESULTS: A total of 444 patients with radiotherapy planning CT-scans were included in this study: 301 head and neck squamous cell carcinoma (HNSCC) patients in the training cohort (DESIGN) and 143 patients in the validation cohort (BD2DECIDE). We found that the highest performing model was a clinical model that was able to predict distant metastasis in oropharyngeal cancer cases with an external validation C-index of 0.74 and 0.65 with the RSF and Cox models respectively. Peritumoral radiomics based prediction models performed poorly in the external validation, with C-index values ranging from 0.32 to 0.61 utilizing both feature selection and model generation methods. CONCLUSION: Our results suggest that radiomic features from the peritumoral regions are not useful for the prediction of time to OS, LR and DM.


Assuntos
Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/terapia , Recidiva Local de Neoplasia/diagnóstico por imagem , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico por imagem , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimiorradioterapia , Estudos de Coortes , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Tomografia Computadorizada por Raios X/métodos
18.
19.
Crit Rev Oncol Hematol ; 150: 102966, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32371338

RESUMO

BACKGROUND: Despite multiple modalities used to management of head and neck squamous cell carcinoma (HNSCC), disease control remains unsatisfactory. Immunotherapy is emerging as a novel therapeutic approach. This systematic review assesses clinical data regarding immunotherapy efficacy and safety. METHODS: Data from 11 clinical trials testing immunotherapy in HNSCC were assessed. We performed the meta-analysis to correlate the overall survival (OS), response rate (RR), adverse effects, HPV status, and PD-L1 expression. RESULTS: Immunotherapy extended OS (hazard ratio = 0.77, p < 0.0001) and RR significantly (risk ratio = 1.41, p = 0.02). Patients with HPV-positive HNSCC exhibited a better RR (risk ratio = 1.29, p = 0.24) and OS (11.5 vs. 6.3 months). PD-L1 positive tumors showed a higher OS (9.9 vs. 6.5 months). Moreover, immunotherapy caused less adverse effects than standard therapy. CONCLUSION: Our results indicate the benefit of immunotherapy for improving RR and OS of HNSCC patients. The benefit is higher in patients with HPV and PD-L1 positive tumors.


Assuntos
Neoplasias de Cabeça e Pescoço/terapia , Imunoterapia/métodos , Infecções por Papillomavirus/virologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/virologia , Humanos , Imuno-Histoquímica , Fatores Imunológicos , Terapia de Alvo Molecular , Papillomaviridae , Infecções por Papillomavirus/imunologia , Infecções por Papillomavirus/terapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia , Resultado do Tratamento
20.
Int J Oral Sci ; 12(1): 16, 2020 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-32461587

RESUMO

With the understanding of the complex interaction between the tumour microenvironment and immunotherapy, there is increasing interest in the role of immune regulators in the treatment of head and neck squamous cell carcinoma (HNSCC). Activation of T cells and immune checkpoint molecules is important for the immune response to cancers. Immune checkpoint molecules include cytotoxic T lymphocyte antigen 4 (CTLA-4), programmed death 1 (PD-1), T-cell immunoglobulin mucin protein 3 (TIM-3), lymphocyte activation gene 3 (LAG-3), T cell immunoglobin and immunoreceptor tyrosine-based inhibitory motif (TIGIT), glucocorticoid-induced tumour necrosis factor receptor (GITR) and V-domain Ig suppressor of T cell activation (VISTA). Many clinical trials using checkpoint inhibitors, as both monotherapies and combination therapies, have been initiated targeting these immune checkpoint molecules. This review summarizes the functional mechanism and use of various immune checkpoint molecules in HNSCC, including monotherapies and combination therapies, and provides better treatment options for patients with HNSCC.


Assuntos
Neoplasias de Cabeça e Pescoço/terapia , Fatores Imunológicos/uso terapêutico , Imunoterapia/métodos , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Microambiente Tumoral
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