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In the randomized, phase 3 CheckMate 141 trial, nivolumab significantly improved overall survival (OS) versus investigator's choice (IC) of chemotherapy at primary analysis among 361 patients with recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) post-platinum therapy. Nivolumab versus IC as first-line treatment also improved OS among patients with R/M SCCHN who progressed on platinum therapy for locally advanced disease in the adjuvant or primary setting at 1-year follow-up. In the present long-term follow-up analysis of patients receiving first-line treatment, OS benefit with nivolumab (n = 50) versus IC (n = 26) was maintained (median: 7.7 months versus 3.3 months; hazard ratio: 0.56; 95% confidence interval, 0.34-0.94) at 2 years. No new safety signals were identified. In summary, this long-term 2-year analysis of CheckMate 141 supports the use of nivolumab as a first-line treatment for patients with platinum-refractory R/M SCCHN.
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Neoplasias de Cabeça e Pescoço , Nivolumabe , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Nivolumabe/uso terapêutico , Platina/uso terapêutico , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológicoRESUMO
BACKGROUND: Response patterns with immune checkpoint inhibitors may be different from those with chemotherapy. Therefore, assessment of response to immunotherapy with the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1, could result in premature treatment termination. The randomized, open-label, phase 3 CheckMate 141 trial (NCT02105636), which evaluated nivolumab in recurrent/metastatic squamous cell carcinoma of the head and neck after platinum therapy, allowed treatment beyond first RECIST-defined progression (TBP) according to protocol-specified criteria. METHODS: In CheckMate 141, patients with RECIST-defined progression who had a stable performance status and demonstrated clinical benefit without rapid disease progression were permitted to receive TBP with nivolumab at 3 mg/kg every 2 weeks until further progression, which was defined as an additional ≥10% increase in tumor volume. This post hoc analysis evaluated outcomes for patients who received TBP with nivolumab. RESULTS: Of 240 patients randomized to nivolumab, 146 experienced RECIST-defined progression. Sixty-two of these patients received TBP, and 84 discontinued treatment (no TBP). Among the 60 TBP patients evaluable for response, 15 (25%) had no change in their tumor burden, and 15 (25%) had reductions in target lesion size; 3 patients (5%) had reductions >30%. The median overall survival among TBP patients was 12.7 months (95% confidence interval, 9.7-14.6 months). No new safety signals were observed with TBP. Exploratory analyses of immune cell biomarkers suggested a potential relationship with initial and TBP responses. CONCLUSIONS: Tumor burden reduction was noted in a proportion of patients who received TBP with nivolumab in CheckMate 141. Additional research is warranted to identify factors predictive of a TBP benefit in this population.
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Antineoplásicos Imunológicos/uso terapêutico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Nivolumabe/uso terapêutico , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Neoplasias Pulmonares/secundário , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Carcinoma de Células Escamosas de Cabeça e Pescoço/secundário , Resultado do TratamentoRESUMO
Early presentation of gingival squamous cell carcinoma (GSCC) is at times misdiagnosed as a benign inflammatory or reactive oral condition. Some misdiagnosed patients undergo unnecessary, invasive dental procedures, resulting in delayed cancer diagnosis and an increased risk of accelerated disease progression due to disruption of the periosteum and cortical bone. The records of 58 patients with biopsy-proven GSCC were retrospectively reviewed. The sample included 32 patients who underwent an invasive dental procedure (IDP) prior to cancer diagnosis and 26 patients who did not undergo an IDP (non-case group). Patients from both groups initially presented with similar symptoms. The median duration of symptoms at initial clinical presentation was 6 months for the IDP group and 2 months for the non-case group. In IDP patients, symptoms worsened after the IDP was rendered, with 37.5% presenting with a severe-grade symptom. In both groups, the majority of lesions were found on the posterior mandible and had a histologic grading of moderately differentiated GSCC. The odds of the IDP group having late-stage disease were 2.94 times greater than the odds for the control group. Stage T3/T4 malignancy was diagnosed in 77.4% of the IDP patients versus 53.8% of non-case patients. Disease-specific mortality was comparable; however, surgical treatment was significantly more extensive in the IDP group than in the non-case group. The disruption of alveolar periosteum in undiagnosed oral cancer patients results in significant delay in diagnosis, necessitating more complicated treatment regimens because of local tumor progression.
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Carcinoma de Células Escamosas/patologia , Neoplasias Gengivais/patologia , Procedimentos Cirúrgicos Bucais/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/etiologia , Estudos de Casos e Controles , Progressão da Doença , Feminino , Neoplasias Gengivais/diagnóstico , Neoplasias Gengivais/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Adulto JovemRESUMO
There are suggestions of an inverse association between folate intake and serum folate levels and the risk of oral cavity and pharyngeal cancers (OPCs), but most studies are limited in sample size, with only few reporting information on the source of dietary folate. Our study aims to investigate the association between folate intake and the risk of OPC within the International Head and Neck Cancer Epidemiology (INHANCE) Consortium. We analyzed pooled individual-level data from ten case-control studies participating in the INHANCE consortium, including 5,127 cases and 13,249 controls. Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were estimated for the associations between total folate intake (natural, fortification and supplementation) and natural folate only, and OPC risk. We found an inverse association between total folate intake and overall OPC risk (the adjusted OR for the highest vs. the lowest quintile was 0.65, 95% CI: 0.43-0.99), with a stronger association for oral cavity (OR = 0.57, 95% CI: 0.43-0.75). A similar inverse association, though somewhat weaker, was observed for folate intake from natural sources only in oral cavity cancer (OR = 0.64, 95% CI: 0.45-0.91). The highest OPC risk was observed in heavy alcohol drinkers with low folate intake as compared to never/light drinkers with high folate (OR = 4.05, 95% CI: 3.43-4.79); the attributable proportion (AP) owing to interaction was 11.1% (95% CI: 1.4-20.8%). Lastly, we reported an OR of 2.73 (95% CI:2.34-3.19) for those ever tobacco users with low folate intake, compared with nevere tobacco users and high folate intake (AP of interaction =10.6%, 95% CI: 0.41-20.8%). Our project of a large pool of case-control studies supports a protective effect of total folate intake on OPC risk.
Assuntos
Anticarcinógenos/administração & dosagem , Suplementos Nutricionais , Ácido Fólico/administração & dosagem , Neoplasias Bucais/prevenção & controle , Neoplasias Faríngeas/prevenção & controle , Administração Oral , Estudos de Casos e Controles , Humanos , Neoplasias Bucais/epidemiologia , Neoplasias Faríngeas/epidemiologia , RiscoRESUMO
Low socioeconomic status has been reported to be associated with head and neck cancer risk. However, previous studies have been too small to examine the associations by cancer subsite, age, sex, global region and calendar time and to explain the association in terms of behavioral risk factors. Individual participant data of 23,964 cases with head and neck cancer and 31,954 controls from 31 studies in 27 countries pooled with random effects models. Overall, low education was associated with an increased risk of head and neck cancer (OR = 2.50; 95% CI = 2.02 - 3.09). Overall one-third of the increased risk was not explained by differences in the distribution of cigarette smoking and alcohol behaviors; and it remained elevated among never users of tobacco and nondrinkers (OR = 1.61; 95% CI = 1.13 - 2.31). More of the estimated education effect was not explained by cigarette smoking and alcohol behaviors: in women than in men, in older than younger groups, in the oropharynx than in other sites, in South/Central America than in Europe/North America and was strongest in countries with greater income inequality. Similar findings were observed for the estimated effect of low versus high household income. The lowest levels of income and educational attainment were associated with more than 2-fold increased risk of head and neck cancer, which is not entirely explained by differences in the distributions of behavioral risk factors for these cancers and which varies across cancer sites, sexes, countries and country income inequality levels.
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Consumo de Bebidas Alcoólicas/efeitos adversos , Educação , Neoplasias de Cabeça e Pescoço/etiologia , Renda/estatística & dados numéricos , Fumar/efeitos adversos , Estudos de Casos e Controles , Feminino , Seguimentos , Saúde Global , Humanos , Masculino , Metanálise como Assunto , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Fatores SocioeconômicosRESUMO
BACKGROUND: Over the last decade, microsurgeons have used a greater variety of more complex flaps. At the same time, microsurgeons have also become more interested in technology, such as indocyanine green (ICG) angiography, dynamic infrared thermography (DIRT), and photospectrometry, for preoperative planning and postoperative monitoring. These technologies are now migrating into the operating room, and are used to optimize flap design and to identify areas of hypoperfusion or problems with the anastomoses. Although relatively more has been published about ICG angiography, information is generally lacking about the intraoperative role of these techniques. METHODS: A systematic analysis of articles discussing intraoperative ICG angiography, DIRT, and photospectrometry was performed to better define the sensitivity, specificity, expected outcomes, and potential complications associated with these techniques. RESULTS: For intraoperative ICG angiography, the sensitivity was 90.9% (95% CI: 77.5-100) and the accuracy was 98.6% (95% CI: 97.6-99.7). The sensitivity of DIRT was 33% (95% CI: 11.3-64.6), the specificity was 100% (95% CI: 84.9-100), and the accuracy was 80% (95% CI: 71.2-89.7). The sensitivity of intraoperative photospectrometry was 92% (95% CI: 72.4-98.6), the specificity was 100% (95% CI: 98.8-100), and the accuracy was also 100% (95% CI: 98.7-100). CONCLUSION: These technologies for intraoperative perfusion assessment have the potential to provide objective data that may improve decisions about flap design and the quality of microvascular anastomoses. However, more work is needed to clearly document their value.
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Cuidados Intraoperatórios/métodos , Procedimentos de Cirurgia Plástica , Retalhos Cirúrgicos/irrigação sanguínea , Angiografia/métodos , Corantes , Humanos , Verde de Indocianina , Imagem Óptica , Sensibilidade e Especificidade , Termografia/métodosRESUMO
Lung cancer is the leading cause of cancer-related mortality globally and the American cancer society estimates approximately 226,160 new cases and 160,340 deaths from lung cancer in the USA in the year 2012. The majority of lung cancers are diagnosed in the later stages which impacts the overall survival. The 5-year survival rate for pathological st age IA lung cancer is 73% but drops to only 13% for stage IV. Thus, early detection through screening and prevention are the keys to reduce the global burden of lung cancer. This article discusses the current state of lung cancer screening, including the results of the National Lung Cancer Screening Trial, the consideration of implementing computed tomography screening, and a brief overview of the role of bronchoscopy in early detection and potential biomarkers that may aid in the early diagnosis of lung cancer.
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Enterococcus faecalis is a member of the intestinal and oral microbiota that may affect the etiology of colorectal and oral cancers. The mechanisms by which E. faecalis may contribute to the initiation and progression of these cancers remain uncertain. Epidermal growth factor receptor (EGFR) signaling is postulated to play a crucial role in oral carcinogenesis. A link between E. faecalis and EGFR signaling in oral cancer has not been elucidated. The present study aimed to evaluate the association between E. faecalis and oral cancer and to determine the underlying mechanisms that link E. faecalis to EGFR signaling. We report the high frequency of E. faecalis infection in oral tumors and the clinical association with EGFR activation. Using human oral cancer cells, we support the clinical findings and demonstrate that E. faecalis can induce EGFR activation and cell proliferation. E. faecalis activates EGFR through production of H(2)O(2), a signaling molecule that activates several signaling pathways. Inhibitors of H(2)O(2) (catalase) and EGFR (gefitinib) significantly blocked E. faecalis-induced EGFR activation and cell proliferation. Therefore, E. faecalis infection of oral tumor tissues suggests a possible association between E. faecalis infection and oral carcinogenesis. Interaction of E. faecalis with host cells and production of H(2)O(2) increase EGFR activation, thereby contributing to cell proliferation.
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Proliferação de Células , Enterococcus faecalis/metabolismo , Receptores ErbB/metabolismo , Peróxido de Hidrogênio/metabolismo , Linhagem Celular Tumoral , Células Endoteliais , Ensaio de Imunoadsorção Enzimática , Receptores ErbB/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/metabolismo , Neoplasias Bucais/microbiologia , Transdução de SinaisRESUMO
BACKGROUND: The International Lung Cancer Consortium (ILCCO) was established in 2004, based on the collaboration of research groups leading large molecular epidemiology studies of lung cancer that are ongoing or have been recently completed. This framework offered the opportunity to investigate the role of tobacco smoking in the development of bronchioloalveolar carcinoma (BAC), a rare form of lung cancer. METHODS: Our pooled data comprised seven case-control studies from the United States, with detailed information on tobacco smoking and histology, which contributed 799 cases of BAC and 15,859 controls. We estimated the odds ratio of BAC for tobacco smoking, using never smokers as a referent category, after adjustment for age, sex, race, and study center. RESULTS: The odds ratio of BAC for ever smoking was 2.47 (95% confidence interval [CI] 2.08, 2.93); the risk increased linearly with duration, amount, and cumulative cigarette smoking and persisted long after smoking cessation. The proportion of BAC cases attributable to smoking was 0.47 (95% CI 0.39, 0.54). CONCLUSIONS: This analysis provides a precise estimate of the risk of BAC for tobacco smoking.
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Adenocarcinoma Bronquioloalveolar/epidemiologia , Neoplasias Pulmonares/epidemiologia , Fumar/efeitos adversos , Adenocarcinoma Bronquioloalveolar/etiologia , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Neoplasias Pulmonares/etiologia , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fatores de RiscoRESUMO
Diabetes mellitus (DM) has been associated with the risk of several gastrointestinal cancers including liver, pancreas, colon and rectum. However, the evidence is inconclusive for gastric adenocarcinoma (GC). In the current review, we summarize 20 population-based cohort studies that compared GC incidence and mortality between diabetic and non-diabetic population. We discuss the shared risk factors and provide qualitative and quantitative (meta-analytic) summary of the current evidence evaluating the association by high-risk subgroups. The overall risk-estimate based on all studies did not show an increased risk of GC in diabetics. However, 2 cohort studies conducted in East Asian countries, where Helicobacter pylori infection and GC rates are higher, showed a higher risk of GC in diabetics. Additionally, high plasma glucose levels in the presence of Helicobacter pylori infection increased the risk of GC by over four times, suggesting a multiplicative effect. Results from the meta-analysis show that, the risk of GC was also higher in populations with greater prevalence of type 1 DM (relative risk = 1.60), suggesting an insulin-independent carcinogenic process in this subgroup. The risk of mortality due to GC was higher in diabetics compared to non-diabetics (relative risk = 1.62). Although the overall risk estimates do not show an association between DM and GC, complex interactions between infectious, molecular, demographic and host factors may convey a higher risk in certain subgroups. Future studies should be sufficiently powered for detailed subgroup analysis to elucidate the causative and mechanistic association between DM and GC.
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BACKGROUND: Inverse associations between cruciferous vegetable intake and lung cancer risk have been consistently reported. However, associations within smoking status subgroups have not been consistently addressed. METHODS: We conducted a hospital-based case-control study with lung cancer cases and controls matched on smoking status, and further adjusted for smoking status, duration, and intensity in the multivariate models. A total of 948 cases and 1743 controls were included in the analysis. RESULTS: Inverse linear trends were observed between intake of fruits, total vegetables, and cruciferous vegetables and risk of lung cancer (ORs ranged from 0.53-0.70, with P for trend < 0.05). Interestingly, significant associations were observed for intake of fruits and total vegetables with lung cancer among never smokers. Conversely, significant inverse associations with cruciferous vegetable intake were observed primarily among smokers, in particular former smokers, although significant interactions were not detected between smoking and intake of any food group. Of four lung cancer histological subtypes, significant inverse associations were observed primarily among patients with squamous or small cell carcinoma - the two subtypes more strongly associated with heavy smoking. CONCLUSIONS: Our findings are consistent with the smoking-related carcinogen-modulating effect of isothiocyanates, a group of phytochemicals uniquely present in cruciferous vegetables. Our data support consumption of a diet rich in cruciferous vegetables may reduce the risk of lung cancer among smokers.
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Anticarcinógenos/administração & dosagem , Brassicaceae , Comportamento Alimentar , Isotiocianatos/administração & dosagem , Neoplasias Pulmonares/etiologia , Neoplasias Pulmonares/prevenção & controle , Fumar/efeitos adversos , Verduras , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Razão de Chances , Sistema de Registros , Medição de Risco , Fatores de Risco , Abandono do Hábito de Fumar , Prevenção do Hábito de FumarRESUMO
BACKGROUND: The present study evaluated the 2-year survival of the Asian population in the CheckMate 141 trial. METHODS: The CheckMate 141 trial included patients with recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN). In the present study, 34 Asian patients (nivolumab group: 23 patients; investigator's choice of therapy [IC] group: 11 patients) were analyzed. RESULTS: The median overall survival (OS) was 12.1 and 6.2 months for the nivolumab and IC groups, respectively. The estimated 2-year OS rates were 22.7% and 0% for the nivolumab and IC groups, respectively. In the nivolumab group, the patients with any treatment-related adverse events (TRAEs), including skin-related disorders, showed better OS than the patients without any TRAEs. CONCLUSIONS: Nivolumab demonstrated prolonged OS benefits in the Asian population with platinum-refractory R/M SCCHN and a favorable safety profile. TRAEs, including skin-related disorders, may be favorable prognostic factors for nivolumab efficacy. CLINICAL TRIAL REGISTRATION: NCT02105636.
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Neoplasias de Cabeça e Pescoço , Nivolumabe , Seguimentos , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Nivolumabe/uso terapêutico , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológicoRESUMO
A limited number of studies have investigated diet in association with endometrial cancer (EC). We examined the association between intakes of selected food groups and nutrients with EC risk among 541 women with histologically confirmed EC and 541 women with an intact uterus and noncancer diagnoses seen at Roswell Park Cancer Institute between 1982 and 1998. Self-reported dietary and other epidemiologic data were collected by questionnaire. Unconditional logistic regression was used to estimate odds ratios (OR) and 95% CI, adjusting for age, BMI, hormone replacement therapy use, cigarette smoking, lifetime duration of menstruation, and total energy intake. We observed significant inverse associations for women in the highest vs. lowest quartiles of intake of total vegetables (OR, 0.51; 95% CI, 0.34-0.75), vitamin E (OR, 0.44; 95% CI, 0.27-0.70), dietary fiber (OR, 0.60; 95% CI, 0.39-0.94), beta-carotene (OR, 0.55; 95% CI, 0.37-0.82), lutein (OR, 0.52; 95% CI, 0.34-0.78), and folate (OR, 0.57; 95% CI, 0.36-0.91). Our results support that vegetables and related nutrients are associated with decreased risk of EC.
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Dieta , Neoplasias do Endométrio/epidemiologia , Verduras , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Humanos , Pessoa de Meia-Idade , Fatores de Risco , Inquéritos e QuestionáriosRESUMO
OBJECTIVES: Many patients with squamous cell carcinoma of the head and neck (SCCHN) are ≥65â¯years old; comorbidities and other age-related factors may affect their ability to tolerate traditional chemotherapy. Nivolumab is the only immunotherapy to significantly improve overall survival (OS) versus investigator's choice (IC) of single-agent chemotherapy at primary analysis in a phase 3 trial (CheckMate 141) in patients with recurrent/metastatic SCCHN post-platinum therapy. In this post hoc analysis, we report efficacy and safety by age. PATIENTS AND METHODS: Eligible patients were randomized 2:1 to nivolumab 3â¯mg/kg every 2â¯weeks (nâ¯=â¯240) or IC (methotrexate, docetaxel, or cetuximab nâ¯=â¯121). The primary endpoint of the trial was OS. For this analysis, outcomes were analyzed by ageâ¯<â¯65 and ≥65â¯years. The data cut-off date was September 2017 (minimum follow-up 24.2â¯months). RESULTS: At baseline, 68 patients (28.3%) receiving nivolumab and 45 patients (37.2%) receiving IC were ≥65â¯years. Baseline characteristics were generally similar across age groups. OS and tumor response benefits with nivolumab versus IC were maintained regardless of age. The 30-month OS rates of 11.2% (<65â¯years) and 13.0% (≥65â¯years) with nivolumab were more than tripled versus corresponding IC rates of 1.4% and 3.3%, respectively. The nivolumab arm had a lower rate of treatment-related adverse events versus IC regardless of age, consistent with the overall patient population. CONCLUSION: In CheckMate 141, nivolumab resulted in a higher survival versus IC in patients <65 and ≥65â¯years, with a manageable safety profile in both age groups. ClinicalTrials.gov: NCT02105636.
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Antineoplásicos Imunológicos/uso terapêutico , Nivolumabe/uso terapêutico , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Fatores Etários , Idoso , Antineoplásicos Imunológicos/farmacologia , Feminino , Humanos , Masculino , Metástase Neoplásica , Nivolumabe/farmacologiaRESUMO
OBJECTIVES: We report 2-year results from CheckMate 141 to establish the long-term efficacy and safety profile of nivolumab and outcomes by tumor PD-L1 expression in patients with recurrent or metastatic (R/M),platinum-refractory squamous cell carcinoma of the head and neck (SCCHN). METHODS: Patients with R/M SCCHN with tumor progression/recurrence within 6â¯months of platinum therapy were randomized 2:1 to nivolumab 3â¯mg/kg every 2â¯weeks or investigator's choice (IC). Primary endpoint: overall survival (OS). Data cutoff: September 2017. RESULTS: With 24.2â¯months' minimum follow-up, nivolumab (nâ¯=â¯240) continued to improve OS vs IC (nâ¯=â¯121), hazard ratio (HR)â¯=â¯0.68 (95% CI 0.54-0.86). Nivolumab nearly tripled the estimated 24-month OS rate (16.9%) vs IC (6.0%), and demonstrated OS benefit across patients with tumor PD-L1 expression ≥1% (HR [95% CI]â¯=â¯0.55 [0.39-0.78]) and â¯<â¯1% (HR [95% CI]â¯=â¯0.73 [0.49-1.09]), and regardless of tumor HPV status. Estimated OS rates at 18, 24, and 30â¯months with nivolumab were consistent irrespective of PD-L1 expression (<1%/≥1%). In the nivolumab arm, there were no observed differences in baseline characteristics or safety profile between long-term survivors and the overall population. Grade 3-4 treatment-related adverse event rates were 15.3% and 36.9% for nivolumab and IC, respectively. CONCLUSION: Nivolumab significantly improved OS at the primary analysis and demonstrated prolonged OS benefit vs IC and maintenance of a manageable and consistent safety profile with 2-year follow-up. OS benefit was observed with nivolumab irrespective of PD-L1 expression and HPV status. (Clinicaltrials.gov: NCT02105636).
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Antineoplásicos Imunológicos/uso terapêutico , Antígeno B7-H1/metabolismo , Metástase Neoplásica , Recidiva Local de Neoplasia , Nivolumabe/uso terapêutico , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Análise de Sobrevida , Antineoplásicos Imunológicos/efeitos adversos , Humanos , Nivolumabe/efeitos adversos , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologiaRESUMO
OBJECTIVE: The study aimed to evaluate symptoms described by patients with chronic rhinosinusitis with polypoid changes/nasal polyps and their correlation with computed tomography (CT), nasal endoscopy, and intranasal biomarkers. STUDY DESIGN: Prospective multicenter study symptom data from postsurgical adult chronic rhinosinusitis study participants with recurrent disease refractory to medical therapy were analyzed in comparison with objective data. METHODS: Using logistic regression analysis, participant-rated 16-question surveys from 258 participants were assessed for correlation with nasal endoscopy scores, CT percentage of sinus occlusion, and intranasal biomarkers of fungal antigens (Alternaria and Aspergillus), eosinophilic inflammation (eosinophil-derived neurotoxin [EDN] and major basic protein [MBP]), and inflammatory cytokines (interleukins 5 and 13). RESULTS: Study participant assessments revealed increased CT occlusion in participants presenting with greater inability to smell ( P < .019). Mucosal inflammation identified on nasal endoscopy was positively correlated with congestion ( P < .028), runny nose ( P < .002), and ear pain ( P < .007). Elevated EDN was positively correlated in patients with bothersome congestion ( P < .031) and runny nose ( P < .011). Sneezing was positively correlated with multiple markers: Alternaria ( P < .024), interleukin-13 ( P < .027), MBP ( P < .034), and interleukin-5 ( P < .019). CONCLUSION: Nasal endoscopy, not CT imaging, has the strongest correlation with the 2 cardinal symptoms of congestion and runny nose in CRS patients; these correlate with biomarkers of eosinophilic inflammation.
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Biomarcadores/análise , Endoscopia , Rinite/diagnóstico , Sinusite/diagnóstico , Tomografia Computadorizada por Raios X , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença Crônica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mucosa Nasal/química , Pólipos Nasais/diagnóstico , Pólipos Nasais/etiologia , Período Pós-Operatório , Estudos Prospectivos , Rinite/complicações , Rinite/diagnóstico por imagem , Rinite/cirurgia , Sinusite/complicações , Sinusite/diagnóstico por imagem , Sinusite/cirurgia , Falha de Tratamento , Adulto JovemRESUMO
OBJECTIVES/HYPOTHESIS: To evaluate subsite-specific differences in survival between squamous cell carcinomas of the base of tongue and tonsillar fossa in a modern cohort likely to have been treated with intensity-modulated radiation therapy, chemotherapy for stage III and IV, and have had a high incidence of human papillomavirus-associated tumors. STUDY DESIGN: Retrospective cohort analysis utilizing data from the Surveillance, Epidemiology, and End Results program of patients with base of tongue and tonsillar fossa squamous cell carcinoma from 2004 to 2011. METHODS: The cohort included 15,299 primary base of tongue and tonsillar fossa squamous cell carcinoma patients without distant metastases treated between 2004 and 2011. Subsite differences in overall survival and disease-specific survival were examined with Kaplan-Meier curves. Multivariate cox proportional hazard ratios were estimated for overall and disease-specific survival. RESULTS: The cohort included 7,220 (47.2%) base of tongue and 8,079 (52.8%) tonsillar fossa squamous cell carcinoma patients. Overall survival with all stages combined favored tonsillar fossa (P < .001) and remained superior when stratified by stage. In multivariate analyses adjusted for age, gender, race, and treatment, the hazard ratio for overall survival was superior for tonsillar fossa tumors compared to base of tongue tumors for all stages (stage 1, P = .041; stage 2, P = .006; stages 3 and 4, P < .001). Disease-specific survival also favored improved outcomes for tonsillar fossa. CONCLUSIONS: In this large modern cohort, overall and disease-specific survival favored outcomes in tonsillar fossa compared with base of tongue. Further study is required to evaluate factors that influence survival differences between tonsillar fossa and base of tongue despite modern therapy. LEVEL OF EVIDENCE: 4 Laryngoscope, 127:1087-1092, 2017.
Assuntos
Carcinoma de Células Escamosas/terapia , Neoplasias da Língua/terapia , Neoplasias Tonsilares/terapia , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/virologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Programa de SEER , Análise de Sobrevida , Neoplasias da Língua/mortalidade , Neoplasias da Língua/patologia , Neoplasias da Língua/virologia , Neoplasias Tonsilares/mortalidade , Neoplasias Tonsilares/patologia , Neoplasias Tonsilares/virologia , Estados Unidos/epidemiologiaRESUMO
OBJECTIVE: The purpose of this study was to determine association between cancer stem cells (CSCs) and their niche with progression of oral potentially malignant disorders. MATERIALS AND METHODS: Patients with histologically confirmed oral potentially malignant disorders, stratified into high/low risk lesions based on the degree of dysplasia and oral cancer were included in this study. Immunohistochemical profiling of markers of CSCs (CD44), endothelial cells (CD31) and CSC-vascular niche cross-talk (CXCR4 and SDF1) were carried out. Statistical analysis was performed to correlate the relationship of markers with histopathology grade (ANOVA, and χ2 test, unpaired t test) using GraphPad InStat v3.06. RESULTS: The study included 550 samples (349 patients) and analysis showed progressive increase in expression levels of CSC and its niche markers with increase in grade of dysplasia as compared to the normal cohort (pâ¯<â¯0.05). Co-expression analysis revealed that, in comparison to the normal cohort, a larger percentage of patients showed increased expression of CD31 and CD44 (CD31high/CD44high; pâ¯<â¯0.05) and of CXCR4 and SDF1 (CXCR4high/SDF1high; pâ¯=â¯0.04), suggesting an association of the CSCs and the vascular niche. Further, distribution of patients with CD44high/CXCR4high (pâ¯<â¯0.05) and CD31high/SDF1high (pâ¯=â¯0.01) was significantly increased in the high-risk group (18%), suggesting a correlation between CD44+/CXCR4+ cells, the vascular niche and progression of oral dysplastic lesions. CONCLUSION: The increased expression of CSCs, the vascular niche and their cross talk markers are associated with increase in severity of dysplasia suggesting their role in the progression of oral potentially malignant disorders and may hence be used in identifying high-risk OPMD.
Assuntos
Progressão da Doença , Neoplasias Bucais/patologia , Células-Tronco Neoplásicas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Quimiocina CXCL12/metabolismo , Estudos de Coortes , Feminino , Humanos , Receptores de Hialuronatos/metabolismo , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Células-Tronco Neoplásicas/metabolismo , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Receptores CXCR4/metabolismo , Estudos Retrospectivos , Adulto JovemRESUMO
OBJECTIVE: To evaluate the chemopreventive potential of aspirin against head and neck cancer. DESIGN: Hospital-based case-control study. SETTING: National Cancer Institute-designated comprehensive cancer center. Patients Individuals who received medical services at the Roswell Park Cancer Institute, Buffalo, NY, between 1982 and 1998 and who completed a comprehensive epidemiologic questionnaire. MAIN OUTCOME MEASURE: Aspirin use among 529 patients with head and neck cancer and 529 hospital-based control subjects matched by age, sex, and smoking status. RESULTS: Aspirin use was associated with a 25% reduction in the risk of head and neck cancer (adjusted odds ratio, 0.75; 95% confidence interval, 0.58-0.96). Consistent risk reductions were also noted in association with frequent and prolonged aspirin use. Further, a consistently decreasing trend in risk was noted with increasing duration of aspirin use (P(trend) = .005). Risk reduction was observed across all 5 primary tumor sites, with cancers of the oral cavity and oropharynx exhibiting greater risk reduction. When analyzed by smoking and alcohol exposure levels, participants moderately exposed to either showed a statistically significant 33% risk reduction (adjusted odds ratio, 0.67; 95% confidence interval, 0.50-0.91), whereas participants exposed to both heavy smoking and alcohol use did not benefit from the protective effect of aspirin. The reduction in risk was relatively more significant in women. CONCLUSIONS: Aspirin use is associated with reduced risk of head and neck cancer. This effect is more pronounced in individuals with low to moderate exposure to cigarette smoke or alcohol consumption.
Assuntos
Aspirina/uso terapêutico , Neoplasias de Cabeça e Pescoço/prevenção & controle , Consumo de Bebidas Alcoólicas/efeitos adversos , Estudos de Casos e Controles , Intervalos de Confiança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/prevenção & controle , Razão de Chances , Neoplasias Orofaríngeas/prevenção & controle , Fumar/efeitos adversos , Inquéritos e QuestionáriosRESUMO
OBJECTIVES/HYPOTHESIS: The effect of smoking and human papillomavirus (HPV) on overall survival (OS) of oropharyngeal squamous cell carcinoma (OPSCC) patients undergoing concurrent chemotherapy (CCRT) remains unclear. STUDY DESIGN: Retrospective review. METHODS: Clinical characteristics of OPSCC patients treated between 2008 and 2015 with CCRT were abstracted from medical records. OS curves and multivariate cox proportional hazard ratios (HRs) were examined. RESULTS: Of 120 evaluable patients, 71% had HPV+ tumors. Median follow-up duration for the entire cohort was 41.5 months (range = 6-88 months). HPV+ current smokers experienced significantly worse 5-year OS (73% alive vs. 36% alive, P = .01) and there was a similar trend in HPV- current smokers (66% alive vs. 31% alive, P = .28) compared to former/never smokers undergoing CCRT. In a multivariate cox proportional hazard model adjusted for age, gender, and overall tumor stage, HPV+ current smokers experienced nearly a fourfold increase in overall mortality in comparison to HPV+ never/former smokers (HR = 3.68, 95% CI = 1.35-10.0). Similarly, current smokers with HPV- tumors (HR = 6.80, 95% CI = 1.11-41.67) had increased mortality compared to never/former smokers. CONCLUSIONS: Current smoking is associated with poor prognosis, independent of HPV status, in CCRT-treated OPSCC patients. Current smoking produced an approximately four- to sevenfold increase in risk of mortality for HPV+ and HPV- patients, respectively. Regardless of pack years and HPV status, efforts should be made to achieve smoking cessation before CCRT. LEVEL OF EVIDENCE: 4. Laryngoscope, 126:2733-2738, 2016.