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1.
Lancet Oncol ; 2020 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-32534633

RESUMO

The speed and scale of the global COVID-19 pandemic has resulted in unprecedented pressures on health services worldwide, requiring new methods of service delivery during the health crisis. In the setting of severe resource constraint and high risk of infection to patients and clinicians, there is an urgent need to identify consensus statements on head and neck surgical oncology practice. We completed a modified Delphi consensus process of three rounds with 40 international experts in head and neck cancer surgical, radiation, and medical oncology, representing 35 international professional societies and national clinical trial groups. Endorsed by 39 societies and professional bodies, these consensus practice recommendations aim to decrease inconsistency of practice, reduce uncertainty in care, and provide reassurance for clinicians worldwide for head and neck surgical oncology in the context of the COVID-19 pandemic and in the setting of acute severe resource constraint and high risk of infection to patients and staff.

2.
Laryngoscope ; 2020 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-32427353

RESUMO

OBJECTIVES: The objective of this study is to determine the value of the anti- glycoprotein-N-acetylgalactosamine 3-beta-galactosyltransferase 1 (C1GALT1) autoantibody as a biomarker for distant metastasis and good response to immune checkpoint inhibitors in patients with head and neck squamous cell carcinoma (HNSCC). METHODS: In this retrospective study with a median follow-up of 55.7 months, 186 HNSCC patients were enrolled between July 2013 and August 2014. Data were analyzed between April 2018 and November 2019. Titers of autoantibody against the C1GALT1 peptide were measured by ELISA. Student t test, Kaplan-Meier analysis, and univariate and multivariate Cox proportional hazard models were used to evaluate the association of anti-C1GALT1 autoantibody titer with clinicopathologic factors, survival, and response to immunotherapy. RESULTS: Our results showed that high levels of the anti-C1GALT1 autoantibody is an independent marker for distant metastasis and poor disease-specific survivals in HNSCC patients. In 19 recurrent or metastatic (R/M) HNSCC patients who have received nivolumab or pembrolizumab, higher autoantibody titers are associated with a better treatment response. CONCLUSION: We propose that the anti-C1GALT1 autoantibody can serve as a novel biomarker for distant metastasis in HNSCC patients. It is also useful in individualized medicine for R/M HNSCC patients who are considering immunotherapy. LEVEL OF EVIDENCE: IV Laryngoscope, 2020.

3.
Cancer Med ; 9(5): 1867-1876, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31925935

RESUMO

BACKGROUND: The study aims are to evaluate the associations between nasopharyngeal carcinoma (NPC) risk and cigarette smoking and to explore the effects of cigarette smoking on Epstein-Barr virus (EBV) infection for NPC risk. METHODS: 1235 male NPC cases and 1262 hospital-based male controls matched to cases were recruited across six collaborative hospitals between 2010 and 2014. Using a standardized questionnaire, information on cigarette smoking and other potential risk factors for NPC was obtained. Blood was collected and used for anti-EBV VCA IgA and anti-EBV EA-EBNA1 IgA testing using standard methods. Unconditional logistic regression analysis was used to estimate odds ratio (OR) with 95% confidence interval (CI) for each risk factor after adjusting for confounders. RESULTS: 63.6% of cases and 44.0% of controls reported ever smoking cigarettes. After full adjustment, current smokers had a significant 1.60-fold (95% CI = 1.30-1.97) and former smokers a borderline significant 1.27-fold (95% CI = 1.00-1.60) increased NPC risk compared to never smokers. NPC risk increased with increasing duration, intensity, and pack-years of cigarette smoking but not with age at smoking initiation. Among controls, anti-EBV VCA IgA seropositivity rate was higher in current smokers than never smokers (14.0% vs 8.4%; OR = 1.82; 95% CI = 1.19-2.79). Mediation analyses showed that more than 90% of the cigarette smoking effect on NPC risk is mediated through anti-EBV VCA IgA. CONCLUSION: This study confirms the association between long-term cigarette smoking and NPC and demonstrates that current smoking is associated with seropositivity of anti-EBV VCA IgA antibodies.

4.
Sci Rep ; 10(1): 526, 2020 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-31949181

RESUMO

The clinical characteristics of oropharyngeal squamous cell carcinoma (OPSCC) may be different between endemic and non-endemic regions of betel nut chewing. The impact of combined alcohol drinking/betel quid chewing/cigarette smoking (ABC) exposure on the survival of OPSCC remains unclear. We reviewed the medical records of OPSCC patients between 1999 and 2013. Immunohistochemical staining of p16 and HPV genotype detection by DNA Polymerase chain reaction were both performed for each tumor. A total of 300 eligible patients including 74 HPV+ OPSCC patients and 226 HPV- OPSCC patients were enrolled. The 5-year disease-free survival rates for the HPV-, HPV+ OPSCC with and without ABC patients were 49.8%, 58.4% and 94%, respectively. The 5-year overall survival rates for the patients with HPV-, HPV+ OPSCC with and without ABC patients were 46%, 57.4% and 86%, respectively. Advanced locoregionally disease (T3/T4, N2/N3), HPV- OPSCC, combined 2 or all ABC exposure were the independent adverse prognostic factors for disease-free and overall survival. Therefore, our data suggest that in an endemic region of betel quid chewing, HPV- OPSCC comprises the majority of OPSCC and has a worse survival. Combined 2 or all ABC exposure had a significant negative impact on disease-free and overall survival.

5.
J Nurs Res ; 27(6): e50, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31688277

RESUMO

BACKGROUND: The increasing number of cancer survivors and the trend of shifting cancer treatments into outpatient clinics have increased rapidly the supportive care needs of patients with cancer. However, no brief assessment tool is available to screen for these needs. PURPOSE: In this study, we aimed to (a) translate and develop a nine-item Chinese version of the Supportive Care Needs Survey Screening Tool (SCNS-ST9-C) and (b) examine the psychometric properties of this tool in a sample of patients with head and neck cancer (HNC) in Taiwan. METHODS: In this two-phase instrument validation study, the SCNS-ST9-C was translated and evaluated for content, face validity, and feasibility in Phase I and was examined for internal consistency reliability and construct validity (including factor structure and theoretically supported correlations) on a sample of patients with HNC in Phase II. RESULTS: In Phase I, the SCNS-ST9-C was translated and developed by three bilingual doctoral-prepared nurse researchers (Chinese and English). A standardized score system ranging from 0 to 100 was built, with higher scores indicating higher unmet supportive care needs. Good content and face validity were confirmed by five cancer care experts and 20 patients with HNC, respectively. In Phase II, 116 subjects were recruited. A clear four-factor structure, which incorporated one of the original five dimensions (sexuality care needs, with one item) into the dimension of psychological and emotional care needs, was identified using exploratory factor analysis. Good internal consistency reliability for the overall SCNS-ST9-C was supported by a Cronbach's α of .75 and its four subscales (domains). Good construct validity was also confirmed by the theoretically supported correlations. Better performance status and longer time since treatment completion correlated negatively with the SCNS-ST9-C (i.e., lower unmet care needs), whereas higher distress (anxiety, depression, and symptoms) correlated positively with the SCNS-ST9-C (i.e., greater unmet care needs). Female patients reported higher overall unmet care needs and psychological and emotional care needs and higher scores on the care and support needs subscale than male patients. CONCLUSIONS: The SCNS-ST9-C is a brief, low-burden, and psychometrically valid instrument that may be applied in ethnically Chinese settings. This tool takes 1-2 minutes to complete. Further testing of the psychometrics of this instrument in different cancer populations is recommended.

7.
Head Neck ; 41 Suppl 1: 4-18, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31573752

RESUMO

BACKGROUND: Immune checkpoint inhibitors (ICIs) can reinvigorate T cells and activate the immune system to eliminate cancer cells. Head and neck squamous cell carcinoma (HNSCC) is a malignancy with a poor prognosis. The roles of ICIs for HNSCC treatments are emerging. METHOD: We reviewed the study results of Programmed-Death 1 (PD-1) and PD-ligand-1 (PD-L1) monoclonal antibodies for HNSCC. The ongoing trials of anti-PD-1 and anti-PD-L1 were also reviewed. RESULTS: Nivolumab showed a significant overall survival benefit in platinum-refractory HNSCC patients. For platinum-sensitive or first-line patients, pembrolizumab monotherapy (patients with PD-L1 Combined Positive Score ≥ 20) or pembrolizumab-platinum-fluorouracil improved overall survival vs the EXTREME (cetuximab-platinum-fluorouracil). Many HNSCC studies have combined anti-PD1/PD-L1 therapy with various anticancer agents or radiotherapy to improve treatment efficacy. CONCLUSION: ICIs demonstrate their efficacies for R/M HNSCC patients. The incorporation of ICIs showed a great impact on the treatment landscape of HNSCC.

8.
Oral Oncol ; 97: 1-6, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31421465

RESUMO

OBJECTIVES: Dysplastic changes at the surgical margin of oral squamous cell carcinoma (OSCC) could be encountered frequently. However, the impact of a dysplastic surgical margin on patients with OSCC remains unclear. MATERIALS AND METHODS: Retrospectively, we reviewed patients with OSCC who were diagnosed and treated at the National Taiwan University Hospital between January 2010 and December 2015. Patients were divided into four groups: clear (≥5 mm), close (<5 mm), positive, and dysplastic margins. RESULTS: Of 1642 patients, 596 had clear margin, 169 had positive margin, 707 had close margin, and 170 had dysplastic margin. The mean age at diagnosis was 55 ±â€¯11 years (range, 16-97 years). Dysplastic margins were frequently present in patients with primary T1/T2 OSCC (odds ratio [OR] = 1.7, p = 0.009), tumor without perineural invasion (OR = 1.48, p = 0.04), and tumor thickness ≤10 mm (OR = 1.94, p = 0.001). In patients with clear, close, positive, and dysplastic margins, the 5-year disease-free survival rates were 63.1%, 51%, 37.2%, and 54.7%, respectively; overall survival (OS) rates were 71.1%, 61.9%, 49%, and 72%, respectively. Disease-free and overall survival were not significantly different in patients with dysplastic and clear margins (p = 0.37 and p = 0.38, respectively). Adjuvant radiotherapy had no significant benefit for patients with dysplastic margins. Finally, a multivariate analysis showed that the presence of a dysplastic margin was not an independent risk factor for disease-free (p = 0.43) and overall survival (p = 0.71). CONCLUSIONS: The survival rates of the patients with OSCC who had dysplastic margin were significantly better than those with positive margin.

9.
Sci Rep ; 9(1): 9916, 2019 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-31289279

RESUMO

Genetic susceptibility is likely involved in nasopharyngeal carcinoma (NPC), a cancer caused by Epstein-Barr virus (EBV) infection. Understanding of genetic factors involved in NPC and how they contribute to EBV-induced carcinogenesis is limited. We conducted whole-exome capture/sequencing among 251 individuals from 97 multiplex families from Taiwan (205 affected, 21 obligate carriers, and 25 unaffected) using SeqCap EZ Human Exome Library v3.0 and Illumina HiSeq. Aligned sequences were filtered to identify likely-to-be-functional deleterious variants that co-segregated with disease. Ingenuity Pathway analysis was performed. Circulating magnesium levels were measured in 13 individuals in 2 families with NIPAL1 mutations and in 197 sporadic NPC cases and 237 controls. We identified variants in 12 genes likely involved in cancer pathogenesis, viral infection or immune responses to infection. These included genes postulated to be involved in magnesium transport (NIPAL1), EBV cell entry (ITGB6), modulation of EBV infection (BCL2L12, NEDD4L), telomere biology (CLPTM1L, BRD2, HNRNPU), modulation of cAMP signaling (RAPGEF3), DNA repair (PRKDC, MLH1), and Notch signaling (NOTCH1, DLL3). Pathway based analysis demonstrated enrichment for Notch signaling genes (p-value = 0.0006). Evaluation of individuals within NIPAL1 families suggested lower serum magnesium in NPC compared to unaffected members. A significant reduction in serum magnesium levels was observed among sporadic NPC cases compared to controls (7.1% NPC/1.7% controls below normal range; OR = 4.5; 95% CI = 1.4,14) and is consistent with findings demonstrating a role for magnesium channeling in T-cell responses to EBV. We identified novel genes associated with NPC that point to new areas of inquiry to better understand genetic factors that determine the fate of viral infections and/or otherwise predisposes to NPC.

10.
Cancer Epidemiol Biomarkers Prev ; 28(10): 1682-1686, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31270100

RESUMO

BACKGROUND: Genetic susceptibility is associated with nasopharyngeal carcinoma (NPC). We previously identified rare variants potentially involved in familial NPC and common variants significantly associated with sporadic NPC. METHODS: We conducted targeted gene sequencing of 20 genes [16 identified from the study of multiplex families, three identified from a pooled analysis of NPC genome-wide association study (GWAS), and one identified from both studies] among 819 NPC cases and 938 controls from two case-control studies in Taiwan (independent from previous studies). A targeted, multiplex PCR primer panel was designed using the custom Ion AmpliSeq Designer v4.2 targeting the regions of the selected genes. Gene-based and single-variant tests were conducted. RESULTS: We found that NPC was associated with combined common and rare variants in CDKN2A/2B (P = 1.3 × 10-4), BRD2 (P = 1.6 × 10-3), TNFRSF19 (P = 4.0 × 10-3), and CLPTM1L/TERT (P = 5.4 × 10-3). Such associations were likely driven by common variants within these genes, based on gene-based analyses evaluating common variants and rare variants separately (e.g., for common variants of CDKN2A/2B, P = 4.6 × 10-4; for rare variants, P = 0.04). We also observed a suggestive association with rare variants in HNRNPU (P = 3.8 × 10-3) for NPC risk. In addition, we validated four previously reported NPC risk-associated SNPs. CONCLUSIONS: Our findings confirm previously reported associated variants and suggest that some common variants in genes previously linked to familial NPC are associated with the development of sporadic NPC. IMPACT: NPC-associated genes, including CLPTM1L/TERT, BRD2, and HNRNPU, suggest a role for telomere length maintenance in NPC etiology.

11.
Cancer Epidemiol ; 59: 173-177, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30785070

RESUMO

BACKGROUND: Although tobacco involuntary smoking is an established risk factor for lung cancer, the association with head and neck cancer (HNC) is not established. We aimed to investigate this potential association in an East Asian population. METHODS: We conducted a multicenter case-control study in East Asia including eight centers. We restricted our analysis to never tobacco smokers (303 cases and 459 controls) and to never tobacco smokers/never alcohol drinkers (243 cases and 403 controls). RESULTS: Among never tobacco smokers, involuntary smoking was associated with a 1.47-fold increase in risk of HNC (95%CI = 1.02, 2.13) and a 1.8-fold increase in the risk of oral cavity cancer (95%CI = 1.14, 2.92). Among never tobacco smokers who were also never alcohol drinkers, increased risks were detected for more than 3 h per day of involuntary smoking exposure and for 15 or more years of exposure. A dose-response relation was suggested for frequency of exposure (p for trend = 0.014) and for years of exposure (p for trend = 0.010) for oral cavity cancer. We did not detect strong increases in the risk of the other HNC subsites. CONCLUSIONS: Our study supports the association between involuntary smoking and the risk of HNC. The association may be stronger for oral cavity cancer than for other HNC subsites.


Assuntos
Neoplasias de Cabeça e Pescoço/epidemiologia , Neoplasias Bucais/epidemiologia , Poluição por Fumaça de Tabaco/estatística & dados numéricos , Adulto , Idoso , Consumo de Bebidas Alcoólicas/epidemiologia , Estudos de Casos e Controles , Extremo Oriente/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Risco , Fumar/epidemiologia
12.
Head Neck ; 41(1): 92-102, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30552826

RESUMO

BACKGROUND: The smoking prevalence among men in China is high, but the head and neck cancer incidence rates are low. This study's purpose was to investigate the impact of tobacco, betel quid, and alcohol on head and neck cancer risk in East Asia. METHODS: A multicenter case-control study (921 patients with head and neck cancer and 806 controls) in East Asia was conducted. The odds ratio (OR) and 95% confidence interval (CI) were estimated using logistic regression. RESULTS: Head and neck cancer risks were elevated for tobacco (OR = 1.58), betel quid (OR = 8.23), and alcohol (OR = 2.29). The total attributable risk of tobacco and/or alcohol was 47.2%. Tobacco/alcohol appeared to account for a small proportion of head and neck cancer among women (attributable risk of 2.2%). Betel quid chewing alone accounted for 28.7% of head and neck cancer. CONCLUSIONS: Betel quid chewing is the strongest risk factor for oral cavity cancer in this Chinese population. Alcohol may play a larger role for head and neck cancer in this population than in European or U.S.

13.
Sci Rep ; 8(1): 16082, 2018 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-30382130

RESUMO

Using time-gated fluorescence lifetime imaging microscopy, significantly more signals from 3,6-bis(1-methyl-2-vinyl-pyridinium) carbazole diiodide (o-BMVC) foci, characterized by the longer fluorescent decay time of o-BMVC, were detected in six types of cancer cells than in three types of normal cells. Accumulating evidence suggested that the o-BMVC foci are mainly the G-quadruplex foci. The large contrast in the number of o-BMVC foci can be considered as a common signature to distinguish cancer cells from normal cells. Further study of tissue biopsy showed that the o-BMVC test provides a high accuracy for clinical detection of head and neck cancers.


Assuntos
Técnicas Biossensoriais/métodos , Carbazóis/química , Corantes Fluorescentes/química , Quadruplex G , Neoplasias de Cabeça e Pescoço/genética , Boca/metabolismo , Compostos de Piridínio/química , Estudos de Casos e Controles , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Microscopia de Fluorescência , Células Tumorais Cultivadas
14.
J Gen Virol ; 99(9): 1268-1273, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29975184

RESUMO

Epstein-Barr virus (EBV) is an obligatory factor in the development of nasopharyngeal carcinoma (NPC), and anti-EBV IgA antibodies are elevated many years prior to the development of NPC. Nearly all adults are infected with EBV, but only a few develop cancer, suggesting that additional co-factors, including genetic susceptibility, must be required for the disease to manifest. Individuals were selected from the Taiwan Family Study, a cohort of 3389 individuals from NPC multiplex families. Primary analyses were conducted among 671 individuals from 69 pedigrees with the strongest family history of disease (>3 NPC-affected family members). The likelihood that a given family member carried a NPC susceptibility variant was estimated using Mendelian segregation rules, assuming a dominant mode of inheritance. We compared anti-EBV IgA antibody seropositivity between family members predicted to be carriers of NPC-linked genetic variants and those with a lower likelihood of carrying such variants. Obligate carriers of NPC susceptibility variants (100 % predicted probability of harbouring the genetic mutation) were nine-fold more likely to be anti-EBV IgA positive compared to family members predicted not to carry disease-causing variants (OR=9.2; P-trend<0.001). This elevated risk was confirmed in analyses restricted to both unaffected individuals and pedigrees with EBV-related pathway variants identified through exome sequencing. Our data indicate that family members who are more likely to carry NPC susceptibility variants are also more likely to be anti-EBNA1 IgA seropositive. Genetic susceptibility associated with control over this common herpes virus is likely a co-factor in determining which EBV-infected adults develop NPC.


Assuntos
Anticorpos Antivirais/sangue , Carcinoma/genética , Predisposição Genética para Doença , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/virologia , Feminino , Variação Genética , Herpesvirus Humano 4 , Humanos , Imunoglobulina A/sangue , Masculino
15.
Oncogene ; 37(43): 5780-5793, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29930379

RESUMO

Core 1 ß1,3-galactosyltransferase (C1GALT1) controls the crucial step of GalNAc-type O-glycosylation and is overexpressed in various human malignancies. However, its role in head and neck squamous cell carcinoma (HNSCC) remains unclear. Here we demonstrate that C1GALT1 expression is upregulated in HNSCC tumors and is associated with adverse clinicopathologic features. Moreover, high C1GALT1 expression predicts poor disease-free and overall survivals. C1GALT1 overexpression enhances HNSCC cell viability, migration, and invasion, which can be reversed by erlotinib. Silencing of C1GALT1 suppresses the malignant behavior both in vitro and in vivo. Mass spectrometry and lectin pull-down assays demonstrate that C1GALT1 modifies O-glycans on EGFR. Blocking O-glycan elongation on EGFR by C1GALT1 knockdown decreases EGF-EGFR binding affinity and inhibits EGFR signaling, thereby suppressing malignant phenotypes. Using molecular docking simulations, we identify itraconazole as a C1GALT1 inhibitor that directly binds C1GALT1 and promotes its proteasomal degradation, leading to significant blockade of C1GALT1-mediated effects in HNSCC cells in vitro and in vivo. Collectively, our findings demonstrate a critical role of O-glycosylation in HNSCC progression and highlight the therapeutic potential of targeting C1GALT1 in HNSCC treatment.


Assuntos
Movimento Celular , Galactosiltransferases , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço/enzimologia , Itraconazol , Simulação de Acoplamento Molecular , Proteínas de Neoplasias , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Receptores ErbB/genética , Receptores ErbB/metabolismo , Feminino , Galactosiltransferases/antagonistas & inibidores , Galactosiltransferases/biossíntese , Galactosiltransferases/química , Galactosiltransferases/genética , Glicosilação/efeitos dos fármacos , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Itraconazol/química , Itraconazol/farmacologia , Masculino , Invasividade Neoplásica , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/química , Proteínas de Neoplasias/genética , Valor Preditivo dos Testes , Prognóstico
16.
Oral Oncol ; 81: 16-21, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29884409

RESUMO

Because of the anatomical location, patients with head and neck cancer (HNC) frequently experience dysphagia and malnutrition at the time of diagnosis and these conditions are often exacerbated after chemoradiotherapy. There is an emerging medical need to establish a consensus on nutritional intervention for these patients. A panel of 30 senior physicians and experts from multidisciplinary teams drafted clinical recommendations to improve the management of nutritional interventions in Taiwan and to provide updated treatment strategy recommendations in hope of improving the nutritional status of patients with HNC. This clinical review describes the resulting consensus document, including the impact of malnutrition on clinical outcomes, the role of prophylactic tube feeding, the choice of tube feeding, and the benefit of oral nutritional supplements in patients with HNC undergoing chemoradiotherapy. The outcomes of this review will support clinicians in their efforts to improve the nutritional status of patients with HNC.


Assuntos
Quimiorradioterapia , Consenso , Neoplasias de Cabeça e Pescoço/dietoterapia , Neoplasias de Cabeça e Pescoço/terapia , Nutrição Enteral , Humanos , Taiwan
17.
Cancer Med ; 2018 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-29905028

RESUMO

Conduct an accurate risk assessment of resected oral cavity squamous cell carcinoma (OSCC) patients by accessing a nationwide systemic investigation is pivotal to improve treatment outcomes. In this article, we tried to determine the impact of different prognostic factors for OSCC patients who received adjuvant radiotherapy (RT) after curative surgery, using Taiwan's national cancer registry database (TCR). A nationwide, large population-based study was conducted using TCR with patients identified from 2007 to 2015. The study variables included age, gender, cancer subsites, stage, histology grade, margin and extra-nodal extension (ENE) status, treatment type, surgery to RT interval (ORI), total RT treatment time (RTT), and RT dose. Univariate and multivariate analysis were performed to identify predictors of the variables associated with overall survival (OS), cause-specific survival (CSS), local-regional relapse-free survival (LRFS), and distant metastasis-free survival (DMFS). 8986 OSCC patients treated with surgery and adjuvant RT were analyzed. In multivariate analysis, worse outcomes were associated with males, older age, subsite in the oral tongue, advanced stage, higher histologic grade, involved margin, and positive ENE. ORI only showed an adverse trend in LRFS, when exceeding 7 weeks (P = .06). RTT >8 weeks was a significant poor predictor in OS, CSS and LRFS (P < .001). Extreme RT dose (>70 Gy or ≤50 Gy) also demonstrated an adverse impact on the outcomes. Prolonged RT treatment time and extreme RT doses were identified as significantly poor prognostic predictors in OSCC patients who received adjuvant RT after curative surgery.

18.
J Infect Dis ; 217(12): 1923-1931, 2018 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-29509907

RESUMO

Background: Little is known about variation in antibody responses targeting the full spectrum of Epstein-Barr virus (EBV) proteins and how such patterns inform disease risk. Methods: We used a microarray to measure immunoglobulin G (IgG) and immunoglobulin A (IgA) antibody responses against 199 EBV protein sequences from 5 EBV strains recovered from 289 healthy adults from Taiwan. We described positivity patterns, estimated the correlation between antibodies, and investigated the associations between environmental and genetic risk factors and variations in antibody responses. Results: Healthy adults were more likely to mount IgG antibody responses to EBV proteins (median positivity frequency, 46.5% for IgG and 17.3% for IgA; P = 1.6 × 10-46, by the Wilcoxon rank sum test). Responses against glycoproteins were particularly prevalent. The correlations between antibody responses of the same class were higher than correlations across classes. The mucosal exposure to proteins involved in EBV reactivation (as determined by the IgA response) was associated with smoking (P = .002, by the sequence kernel association test-combined), and approximately one quarter of adults displayed antibody responses associated with EBV-related cancer risk. Conclusions: These data comprehensively define the variability in human IgG and IgA antibody responses to the EBV proteome. Patterns observed can serve as the foundation for elucidating which individuals are at highest risk of EBV-associated clinical conditions and for identifying targets for effective immunodiagnostic tests.


Assuntos
Anticorpos Antivirais/imunologia , Infecções por Vírus Epstein-Barr/imunologia , Herpesvirus Humano 4/imunologia , Transporte Proteico/imunologia , Proteoma/imunologia , Antígenos Virais/imunologia , Humanos , Imunoglobulina A/imunologia , Imunoglobulina G/imunologia , Individualidade , Masculino , Taiwan
19.
Clin Cancer Res ; 24(6): 1305-1314, 2018 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-29301829

RESUMO

Background Epstein-Barr virus (EBV) is necessary for the development of nasopharyngeal carcinoma (NPC). By adulthood, approximately 90% of individuals test EBV-positive, but only a fraction develop cancer. Factors that identify which individuals are most likely to develop disease, including differential antibody response to the virus, could facilitate detection at early stages when treatment is most effective.Methods We measured anti-EBV IgG and IgA antibody responses in 607 Taiwanese individuals. Antibodies were measured using a custom protein microarray targeting 199 sequences from 86 EBV proteins. Variation in response patterns between NPC cases and controls was used to develop an antibody-based risk score for predicting NPC. The overall accuracy [area under the curve (AUC)] of this risk score, and its performance relative to currently used biomarkers, was evaluated in two independent Taiwanese cohorts.Findings Levels of 60 IgA and 73 IgG anti-EBV antibodies differed between stage I/IIa NPC cases and controls (P < 0.0002). Risk prediction analyses identified antibody targets that best discriminated NPC status-BXLF1, LF2,BZLF1, BRLF1, EAd, BGLF2, BPLF1, BFRF1, and BORF1. When combined with currently used VCA/EBNA1 IgA biomarkers, the resulting risk score predicted NPC with 93% accuracy (95% CI, 87%-98%) in the general Taiwanese population, a significant improvement beyond current biomarkers alone (82%; 95% CI, 75%-90%, P ≤ 0.01). This EBV-based risk score also improved NPC prediction in genetically high-risk families (89%; 95% CI, 82%-96%) compared with current biomarkers (78%; 95% CI, 66%-90%, P ≤ 0.03).Interpretation We identified NPC-related differences in 133 anti-EBV antibodies and developed a risk score using this microarray dataset that targeted immune responses against EBV proteins from all stages of the viral life cycle, significantly improving the ability to predict NPC. Clin Cancer Res; 24(6); 1305-14. ©2017 AACR.


Assuntos
Anticorpos Antivirais/imunologia , Detecção Precoce de Câncer , Infecções por Vírus Epstein-Barr/imunologia , Herpesvirus Humano 4/imunologia , Carcinoma Nasofaríngeo/diagnóstico , Adulto , Idoso , Estudos de Casos e Controles , Estudos Transversais , Detecção Precoce de Câncer/métodos , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/virologia , Feminino , Humanos , Imunoglobulina A/sangue , Imunoglobulina A/imunologia , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/epidemiologia , Carcinoma Nasofaríngeo/etiologia , Estadiamento de Neoplasias , Curva ROC , Medição de Risco , Taiwan/epidemiologia , Adulto Jovem
20.
Sci Rep ; 7(1): 10349, 2017 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-28871094

RESUMO

Given salvage treatment for recurrent nasopharyngeal carcinoma (NPC) remains a clinical dilemma, immunotherapy targeting NPC-specific immunosuppression may bring new hope. We analyzed the expression of CD8, CD4, Foxp3 and Tim-3 in lymphocytes, and of Galectin-9 in tumour cells between paired primary and recurrent NPC from 95 patients and we noted that there was significant increase in the expression of Galectin-9+ tumour cells (p < 0.001) and Foxp3+ lymphocytes (p < 0.001) but a significant decrease in the expression of CD8+ lymphocytes (p = 0.01) between paired primary and recurrent NPC. Of all patients, 53 patients (55.79%) and 57 patients (60%) had increased percentages of Galectin-9+ tumour cells and of Foxp3+ lymphocytes, respectively. Conversely, 42 patients (44.21%) had decreased percentages of CD8+ lymphocytes. The patients with high Galectin-9 expression in recurrent NPC frequently also had high Tim-3 (p = 0.04) and Foxp3 (p = 0.01), and low CD8 (p = 0.04) expression in lymphocytes. After multivariate analyses, low CD8 expression in lymphocytes was an independent risk factor for relapse-free survival (p = 0.002) and overall survival (p = 0.02). Our data suggests that recurrent NPC may had more immunologic advantage than primary NPC, especially the Galectin-9/Tim-3 pathway. The immunotherapies targeting Galectin-9/Tim-3/Foxp3 interaction may serve as a potential salvage treatment for recurrent NPC.


Assuntos
Galectinas/metabolismo , Receptor Celular 2 do Vírus da Hepatite A/metabolismo , Carcinoma Nasofaríngeo/metabolismo , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patologia , Microambiente Tumoral , Adulto , Idoso , Biomarcadores , Feminino , Expressão Gênica , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/imunologia , Carcinoma Nasofaríngeo/mortalidade , Neoplasias Nasofaríngeas/imunologia , Neoplasias Nasofaríngeas/mortalidade , Gradação de Tumores , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Razão de Chances , Prognóstico , Modelos de Riscos Proporcionais , Microambiente Tumoral/imunologia , Adulto Jovem
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