RESUMO
BACKGROUND: The TNM Classification of Malignant Tumours (TNM) staging system is the primary means of determining a prognosis for gastric adenocarcinoma (GC). However, tumor behavior in the individual patient is unpredictable and in spite of treatment advances, a classification of 'advanced stage' still portends a poor prognosis. Thus, further insights from molecular analyses are needed for better prognostic stratification and determination of new therapeutic targets. METHODS: A total of fifty-one fresh frozen tumor samples from patients with histopathologically confirmed diagnoses of GC, submitted to surgery with curative intent, were included in the study. Total RNA was extracted from an initial group of fifteen samples matched for known prognostic factors, categorized into two subgroups, according to patient overall survival: poor (<24 months) or favorable (at or above 24 months), and hybridized to Affymetrix Genechip human genome U133 plus 2.0 for genes associated with prognosis selection. Thirteen genes were selected for qPCR validation using those initial fifteen samples plus additional thirty-six samples. RESULTS: A total of 108 genes were associated with poor prognosis, independent of tumor staging. Using systems biology, we suggest that this panel reflects the dampening of immune/inflammatory response in the tumor microenvironment level and a shift to Th2/M2 activity. A gene trio (OLR1, CXCL11 and ADAMDEC1) was identified as an independent marker of prognosis, being the last two markers validated in an independent patient cohort. CONCLUSIONS: We determined a panel of three genes with prognostic value in gastric cancer, which should be further investigated. A gene expression profile suggestive of a dysfunctional inflammatory response was associated with unfavorable prognosis.
Assuntos
Adenocarcinoma/genética , Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica/imunologia , Neoplasias Gástricas/genética , Transcriptoma/imunologia , Microambiente Tumoral/genética , Proteínas ADAM/genética , Adenocarcinoma/imunologia , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/imunologia , Quimiocina CXCL11/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Análise de Sequência com Séries de Oligonucleotídeos , Prognóstico , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Receptores Depuradores Classe E/genética , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Análise de Sobrevida , Microambiente Tumoral/imunologiaRESUMO
PURPOSE: Oral mucositis is a major complication of concurrent chemoradiotherapy (CRT) in head-and-neck cancer patients. Low-level laser (LLL) therapy is a promising preventive therapy. We aimed to evaluate the efficacy of LLL therapy to decrease severe oral mucositis and its effect on RT interruptions. METHODS AND MATERIALS: In the present randomized, double-blind, Phase III study, patients received either gallium-aluminum-arsenide LLL therapy 2.5 J/cm(2) or placebo laser, before each radiation fraction. Eligible patients had to have been diagnosed with squamous cell carcinoma or undifferentiated carcinoma of the oral cavity, pharynx, larynx, or metastases to the neck with an unknown primary site. They were treated with adjuvant or definitive CRT, consisting of conventional RT 60-70 Gy (range, 1.8-2.0 Gy/d, 5 times/wk) and concurrent cisplatin. The primary endpoints were the oral mucositis severity in Weeks 2, 4, and 6 and the number of RT interruptions because of mucositis. The secondary endpoints included patient-reported pain scores. To detect a decrease in the incidence of Grade 3 or 4 oral mucositis from 80% to 50%, we planned to enroll 74 patients. RESULTS: A total of 75 patients were included, and 37 patients received preventive LLL therapy. The mean delivered radiation dose was greater in the patients treated with LLL (69.4 vs. 67.9 Gy, p = .03). During CRT, the number of patients diagnosed with Grade 3 or 4 oral mucositis treated with LLL vs. placebo was 4 vs. 5 (Week 2, p = 1.0), 4 vs. 12 (Week 4, p = .08), and 8 vs. 9 (Week 6, p = 1.0), respectively. More of the patients treated with placebo had RT interruptions because of mucositis (6 vs. 0, p = .02). No difference was detected between the treatment arms in the incidence of severe pain. CONCLUSIONS: LLL therapy was not effective in reducing severe oral mucositis, although a marginal benefit could not be excluded. It reduced RT interruptions in these head-and-neck cancer patients, which might translate into improved CRT efficacy.
Assuntos
Carcinoma de Células Escamosas/radioterapia , Quimiorradioterapia/efeitos adversos , Neoplasias de Cabeça e Pescoço/radioterapia , Lasers Semicondutores/uso terapêutico , Terapia com Luz de Baixa Intensidade/métodos , Estomatite/prevenção & controle , Adenocarcinoma de Células Claras/radioterapia , Adenocarcinoma de Células Claras/secundário , Adulto , Idoso , Peso Corporal , Brasil , Carcinoma/radioterapia , Cisplatino , Transtornos de Deglutição/etiologia , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Estudos Prospectivos , Dosagem Radioterapêutica , Estomatite/etiologia , Estomatite/patologia , Falha de Tratamento , Adulto JovemRESUMO
BACKGROUND: Previous knowledge of cervical lymph node compromise may be crucial to choose the best treatment strategy in oral squamous cell carcinoma (OSCC). Here we propose a set four genes, whose mRNA expression in the primary tumor predicts nodal status in OSCC, excluding tongue. MATERIAL AND METHODS: We identified differentially expressed genes in OSCC with and without compromised lymph nodes using Differential Display RT-PCR. Known genes were chosen to be validated by means of Northern blotting or real time RT-PCR (qRT-PCR). Thereafter we constructed a Nodal Index (NI) using discriminant analysis in a learning set of 35 patients, which was further validated in a second independent group of 20 patients. RESULTS: Of the 63 differentially expressed known genes identified comparing three lymph node positive (pN +) and three negative (pN0) primary tumors, 23 were analyzed by Northern analysis or RT-PCR in 49 primary tumors. Six genes confirmed as differentially expressed were used to construct a NI, as the best set predictive of lymph nodal status, with the final result including four genes. The NI was able to correctly classify 32 of 35 patients comprising the learning group (88.6%; p = 0.009). Casein kinase 1alpha1 and scavenger receptor class B, member 2 were found to be up regulated in pN + group in contrast to small proline-rich protein 2B and Ras-GTPase activating protein SH3 domain-binding protein 2 which were upregulated in the pN0 group. We validated further our NI in an independent set of 20 primary tumors, 11 of them pN0 and nine pN + with an accuracy of 80.0% (p = 0.012). CONCLUSIONS: The NI was an independent predictor of compromised lymph nodes, taking into the consideration tumor size and histological grade. The genes identified here that integrate our "Nodal Index" model are predictive of lymph node metastasis in OSCC.
Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/secundário , Proteínas de Transporte/metabolismo , Caseína Quinase Ialfa/metabolismo , Proteínas Ricas em Prolina do Estrato Córneo/metabolismo , Proteínas de Membrana Lisossomal/metabolismo , Neoplasias Bucais/genética , Receptores Depuradores/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/patologia , DNA Helicases , Feminino , Expressão Gênica , Marcadores Genéticos , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Modelos Genéticos , Neoplasias Bucais/patologia , Proteínas de Ligação a Poli-ADP-Ribose , RNA Helicases , Proteínas com Motivo de Reconhecimento de RNA , RNA Mensageiro/metabolismo , Reprodutibilidade dos TestesRESUMO
BACKGROUND: The purpose of this study was to analyze the cost-effectiveness of cisplatin-based chemoradiation compared to radiation therapy (RT) alone to treat patients with advanced head and neck cancer in Brazil. METHODS: Data were collected retrospectively from the medical records of 33 patients treated with RT alone (strategy 1) and from 29 patients treated with cisplatin-based chemoradiation (strategy 2). The Brazilian National Health System (Sistema Único de Saúde [SUS]) reimbursement parameters perspective was considered, and the effectiveness was measured in years of disease-free life gained. One-way sensitivity analysis was performed to determine robustness of this study. RESULTS: In strategy 1, there were 31% of the patients who lived without disease progression for more than 13 months after treatment, compared to 58% of patients in strategy 2. According to SUS parameters, the total cost per patient in strategy 1 was $1,167.00 U.S. dollars and in strategy 2, it was $2,058.00 U.S. dollars. Incremental cost-effectiveness ratio (ICER) was $3,303.00 U.S. dollars per life-year gained. CONCLUSION: Cisplatin-based chemoradiation proved to be more cost-effective than RT alone.
Assuntos
Carcinoma de Células Escamosas/terapia , Quimiorradioterapia/economia , Efeitos Psicossociais da Doença , Neoplasias de Cabeça e Pescoço/terapia , Radioterapia/economia , Idoso , Idoso de 80 Anos ou mais , Brasil , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Cisplatino/economia , Cisplatino/uso terapêutico , Estudos de Coortes , Intervalos de Confiança , Análise Custo-Benefício , Feminino , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Modelos Econômicos , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Prognóstico , Radioterapia/métodos , Estudos Retrospectivos , Medição de Risco , Estatísticas não Paramétricas , Análise de Sobrevida , Resultado do TratamentoRESUMO
Adjuvant cisplatin-based chemoradiation improves survival in HNSCC patients presenting with risk features. ERCC1 (excision repair cross-complementation group 1) is associated with resistance to chemo- and radiation therapy and may have a prognostic value in HNSCC patients. Here we studied ERCC1 expression and the polymorphism T19007C as prognostic markers in these patients. This is a retrospective and translational analysis, where ERCC1 protein expression was evaluated by immunohistochemistry, using an H-score, and mRNA expression was determined by RT-PCR. T19007C genotypes were detected by PCR-RFLP carried out using DNA template extracted from normal lymph nodes. A high H-score was seen in 32 patients (54%), who presented better 5-year overall survival (5-y OS: 50% vs. 18%, HR 0.43, p=0.026). Fifteen out of 45 patients (33%), with high mRNA expression, presented better 5-year overall survival (OS) (86% vs. 30%, HR 0.26, p=0.052). No OS difference was detected among T19007C genotypes. High H-score and mRNA expression remained significant as favorable prognostic factors in a multivariate analysis. Collectively, our results suggest that high ERCC1 expression seems to be associated with better OS rates in HNSCC patients submitted to adjuvant cisplatin-based chemoradiation.
Assuntos
Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Endonucleases/genética , Endonucleases/metabolismo , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma/diagnóstico , Carcinoma/genética , Carcinoma/mortalidade , Carcinoma/terapia , Carcinoma de Células Escamosas , Quimioterapia Adjuvante , Cisplatino/administração & dosagem , Terapia Combinada , Procedimentos Cirúrgicos do Sistema Digestório , Feminino , Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias de Células Escamosas/diagnóstico , Neoplasias de Células Escamosas/genética , Neoplasias de Células Escamosas/mortalidade , Neoplasias de Células Escamosas/terapia , Polimorfismo de Fragmento de Restrição , Polimorfismo de Nucleotídeo Único/fisiologia , Prognóstico , RNA Mensageiro/metabolismo , Radioterapia Adjuvante , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Análise de SobrevidaRESUMO
BACKGROUND: To test if the expression of Smad1-8 mRNAs were predictive of survival in patients with oral squamous cell carcinoma (SCC). PATIENTS AND METHODS: We analyzed, prospectively, the expression of Smad1-8, by means of Ribonuclease Protection Assay in 48 primary, operable, oral SCC. In addition, 21 larynx, 10 oropharynx and 4 hypopharynx SCC and 65 matched adjacent mucosa, available for study, were also included. For survival analysis, patients were categorized as positive or negative for each Smad, according to median mRNA expression. We also performed real-time quantitative PCR (QRTPCR) to asses the pattern of TGFbeta1, TGFbeta2, TGFbeta3 in oral SCC. RESULTS: Our results showed that Smad2 and Smad6 mRNA expression were both associated with survival in Oral SCC patients. Cox Multivariate analysis revealed that Smad6 positivity and Smad2 negativity were both predictive of good prognosis for oral SCC patients, independent of lymph nodal status (P = 0.003 and P = 0.029, respectively). In addition, simultaneously Smad2- and Smad6+ oral SCC group of patients did not reach median overall survival (mOS) whereas the mOS of Smad2+/Smad6- subgroup was 11.6 months (P = 0.004, univariate analysis). Regarding to TGFbeta isoforms, we found that Smad2 mRNA and TGFbeta1 mRNA were inversely correlated (p = 0.05, R = -0.33), and that seven of the eight TGFbeta1+ patients were Smad2-. In larynx SCC, Smad7- patients did not reach mOS whereas mOS of Smad7+ patients were only 7.0 months (P = 0.04). No other correlations were found among Smad expression, clinico-pathological characteristics and survival in oral, larynx, hypopharynx, oropharynx or the entire head and neck SCC population. CONCLUSION: Smad6 together with Smad2 may be prognostic factors, independent of nodal status in oral SCC after curative resection. The underlying mechanism which involves aberrant TGFbeta signaling should be better clarified in the future.
Assuntos
Biomarcadores Tumorais/análise , Carcinoma de Células Escamosas/metabolismo , Neoplasias Bucais/metabolismo , Proteína Smad2/biossíntese , Proteína Smad6/biossíntese , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/mortalidade , Feminino , Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/genética , Neoplasias Bucais/mortalidade , Prognóstico , RNA Mensageiro/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Proteína Smad2/genética , Proteína Smad6/genética , Fator de Crescimento Transformador beta1/biossíntese , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta2/biossíntese , Fator de Crescimento Transformador beta2/genética , Fator de Crescimento Transformador beta3/biossíntese , Fator de Crescimento Transformador beta3/genéticaRESUMO
PURPOSE: Erlotinib, an oral tyrosine kinase inhibitor, is active against head-and-neck squamous cell carcinoma (HNSCC) and possibly has a synergistic interaction with chemotherapy and radiotherapy. We investigated the safety and efficacy of erlotinib added to cisplatin and radiotherapy in locally advanced HNSCC. METHODS AND MATERIALS: In this Phase I/II trial 100 mg/m(2) of cisplatin was administered on Days 8, 29, and 50, and radiotherapy at 70 Gy was started on Day 8. During Phase I, the erlotinib dose was escalated (50 mg, 100 mg, and 150 mg) in consecutive cohorts of 3 patients, starting on Day 1 and continuing during radiotherapy. Dose-limiting toxicity was defined as any Grade 4 event requiring radiotherapy interruptions. Phase II was initiated 8 weeks after the last Phase I enrollment. RESULTS: The study accrued 9 patients in Phase I and 28 in Phase II; all were evaluable for efficacy and safety. No dose-limiting toxicity occurred in Phase I, and the recommended Phase II dose was 150 mg. The most frequent nonhematologic toxicities were nausea/vomiting, dysphagia, stomatitis, xerostomia and in-field dermatitis, acneiform rash, and diarrhea. Of the 31 patients receiving a 150-mg daily dose of erlotinib, 23 (74%; 95% confidence interval, 56.8%-86.3%) had a complete response, 3 were disease free after salvage surgery, 4 had inoperable residual disease, and 1 died of sepsis during treatment. With a median 37 months' follow-up, the 3-year progression-free and overall survival rates were 61% and 72%, respectively. CONCLUSIONS: This combination appears safe, has encouraging activity, and deserves further studies in locally advanced HNSCC.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/radioterapia , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/radioterapia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Brasil , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Terapia Combinada/efeitos adversos , Terapia Combinada/métodos , Intervalos de Confiança , Esquema de Medicação , Toxidermias/etiologia , Cloridrato de Erlotinib , Feminino , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Neoplasias Hipofaríngeas/tratamento farmacológico , Neoplasias Hipofaríngeas/mortalidade , Neoplasias Hipofaríngeas/patologia , Neoplasias Hipofaríngeas/radioterapia , Neoplasias Laríngeas/tratamento farmacológico , Neoplasias Laríngeas/mortalidade , Neoplasias Laríngeas/patologia , Neoplasias Laríngeas/radioterapia , Masculino , Pessoa de Meia-Idade , Neoplasias Orofaríngeas/tratamento farmacológico , Neoplasias Orofaríngeas/mortalidade , Neoplasias Orofaríngeas/patologia , Neoplasias Orofaríngeas/radioterapia , Quinazolinas/administração & dosagem , Quinazolinas/efeitos adversos , Dosagem Radioterapêutica , Terapia de Salvação/métodos , Taxa de SobrevidaRESUMO
This study evaluated the efficacy of low-level laser therapy (LLLT) and aluminum hydroxide (AH) in the prevention of oral mucositis (OM). A prospective, comparative and non-randomized study was conducted with 25 patients with head and neck cancer subjected to radiotherapy (RT) or radiochemotherapy (RCT). Twelve patients received LLLT (830 nm, 15 mW, 12 J/cm²) daily from the 1st day until the end of RT before each sessions during 5 consecutive days, and the other 13 patients received AH 310 mg/5 mL, 4 times/day, also throughout the duration of RT, including weekends. OM was measured using an oral toxicity scale (OTS) and pain was measured using the visual analogue scale (VAS). EORTC questionnaires were administered to the evaluate impact of OM on quality of life. The LLLT group showed lower mean OTS and VAS scores during the course of RT. A significant difference was observed in pain evaluation in the 13th RT session (p=0.036). In both groups, no interruption of RT was needed. The prophylactic use of both treatments proposed in this study seems to reduce the incidence of severe OM lesions. However, the LLLT was more effective in delaying the appearance of severe OM.
Assuntos
Hidróxido de Alumínio/administração & dosagem , Neoplasias de Cabeça e Pescoço/complicações , Terapia com Luz de Baixa Intensidade/métodos , Antissépticos Bucais/uso terapêutico , Estomatite/prevenção & controle , Terapia Combinada , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Estudos Prospectivos , Lesões por Radiação/etiologia , Lesões por Radiação/radioterapia , Radioterapia/efeitos adversos , Estomatite/etiologia , Resultado do TratamentoRESUMO
This study evaluated the efficacy of low-level laser therapy (LLLT) and aluminum hydroxide (AH) in the prevention of oral mucositis (OM). A prospective, comparative and non-randomized study was conducted with 25 patients with head and neck cancer subjected to radiotherapy (RT) or radiochemotherapy (RCT). Twelve patients received LLLT (830 nm, 15 mW, 12 J/cm²) daily from the 1st day until the end of RT before each sessions during 5 consecutive days, and the other 13 patients received AH 310 mg/5 mL, 4 times/day, also throughout the duration of RT, including weekends. OM was measured using an oral toxicity scale (OTS) and pain was measured using the visual analogue scale (VAS). EORTC questionnaires were administered to the evaluate impact of OM on quality of life. The LLLT group showed lower mean OTS and VAS scores during the course of RT. A significant difference was observed in pain evaluation in the 13th RT session (p=0.036). In both groups, no interruption of RT was needed. The prophylactic use of both treatments proposed in this study seems to reduce the incidence of severe OM lesions. However, the LLLT was more effective in delaying the appearance of severe OM.
Este estudo avaliou a eficácia da terapia do laser de baixa potência (LBP) e hidróxido de alumínio (HA) na prevenção da mucosite oral (MO). Um estudo prospectivo, comparativo e não-aleatorizado foi conduzido com 25 pacientes com câncer de cabeça e pescoço submetidos a radioterapia (RT) ou radioquimioterapia (RT/QT). Doze pacientes receberam LBP (830 nm, 15 mW, 12 J/cm²) diariamente desde o primeiro dia até o final da RT antes de cada sessão durante 5 dias consecutivos, e os outros 13 pacientes receberam HA 310 mg/5 mL, 4 vezes ao dia, também por toda a duração da RT, incluindo finais de semana. MO foi mensurada usando uma escala de toxicidade oral (ETO) e dor foi mensurada usando a escala visual analógica (EVA). Questionários da EORTC foram administrados para a avaliação do impacto da MO na qualidade de vida. O grupo LBP mostrou menores médias dos escores da ETO e EVA durante o curso da RT. Uma diferença significante foi observada na avaliação da dor na 13ª sessão de RT (p=0,036). Em ambos os grupos, nenhuma interrupção da RT foi necessária. O uso profilático de ambos os tratamentos propostos neste estudo parece reduzir a incidência de lesões severas de MO. No entanto, o LBP foi mais efetivo no atraso do aparecimento da MO severa.
Assuntos
Humanos , Hidróxido de Alumínio/administração & dosagem , Neoplasias de Cabeça e Pescoço/complicações , Terapia com Luz de Baixa Intensidade/métodos , Antissépticos Bucais/uso terapêutico , Estomatite/prevenção & controle , Terapia Combinada , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/radioterapia , Estudos Prospectivos , Lesões por Radiação/etiologia , Lesões por Radiação/radioterapia , Radioterapia/efeitos adversos , Estomatite/etiologia , Resultado do TratamentoRESUMO
OBJECTIVES: To explore the prognostic role of plasma levels of osteopontin (OPN), a phosphoglycoprotein with adhesive properties, in patients with head and neck squamous cell carcinoma (HNSCC) undergoing concomitant chemoradiotherapy. Previous studies have proposed OPN level as a prognostic factor in several cancers. DESIGN: Prospective analysis of plasma OPN levels, before and within 12 weeks after treatment, in a cohort of patients with HNSCC undergoing platinum-based chemoradiotherapy at our center. SETTING: Academic center. PATIENTS: Sixty-nine patients diagnosed as having HNSCC. INTERVENTIONS: Plasma levels of OPN were assessed before the start and after the conclusion of chemoradiotherapy by using an enzyme-linked immunosorbency assay kit. Chemoradiotherapy was exclusive (n = 52) or adjuvant to surgery (n = 17). MAIN OUTCOME MEASURES: Levels of OPN were correlated with clinicopathological characteristics, response to treatment, and overall survival. RESULTS: Pretreatment plasma OPN levels were higher in patients with advanced T and N stages compared with patients with early stages (P = .009 and .07, respectively). Mean (SD) plasma levels of OPN measured before (102.5 [68.1] ng/mL) and after (104.0 [53.6] ng/mL) treatment did not differ (P = .18, paired t test). Pretreatment and posttreatment levels of OPN were lower in patients who achieved a complete response compared with those who failed to respond (75.0 [41.5] vs 131.2 [82.9] ng/mL [P = .005] and 86.8 [40.5] vs 141.6 [58.4] ng/mL [P = .004], respectively). Patients with high pretreatment OPN levels (>82.1 ng/mL) had shorter survival time (P < .001). Posttreatment OPN levels were marginally (P = .10) associated with survival time in univariate analysis. CONCLUSIONS: In patients with HNSCC undergoing chemoradiotherapy, a low pretreatment plasma OPN level is associated with treatment response and better survival. Modulation of OPN levels by chemoradiotherapy may also be associated with outcome. Further studies with serial measurement of OPN levels are warranted in these patients.
Assuntos
Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/radioterapia , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/radioterapia , Osteopontina/sangue , Adulto , Idoso , Análise de Variância , Biomarcadores Tumorais/sangue , Carcinoma de Células Escamosas/sangue , Distribuição de Qui-Quadrado , Feminino , Neoplasias de Cabeça e Pescoço/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Análise de Sobrevida , Resultado do TratamentoRESUMO
Vandetanib (ZACTIMA) is a once-daily oral anticancer drug that selectively inhibits vascular endothelial growth factor receptor, epidermal growth factor receptor, and rearranged during transfection signaling. This randomized (1:1), double-blind study evaluated vandetanib (100 mg/day) or placebo in combination with docetaxel (D; 75 mg/m(2) every 3 weeks) and prednisolone (P; 2 x 5 mg/day) in 86 patients with metastatic hormone-refractory prostate cancer (mHRPC). The primary assessment was prostate-specific antigen (PSA) response (confirmed reduction of >or=50% from baseline) and a greater number of patients showed a PSA response with placebo + DP (67%) versus vandetanib + DP (40%); hazard ratio = 2.23 (one-sided 80% confidence limit = 2.90; one-sided p = 0.99). More patients experienced progression events (disease progression or death from any cause) with vandetanib + DP (65%) versus placebo + DP (60%); hazard ratio = 1.13 (one-sided 80% confidence limit = 1.44; one-sided p = 0.67). The overall incidence of adverse events was similar in both groups, although more patients experienced adverse events, leading to permanent discontinuation with vandetanib + DP (28%) versus placebo + DP (12%). However, the safety and tolerability profile for vandetanib was similar to that previously reported; adverse events that occurred more frequently in the vandetanib + DP arm were hypertension (14% vs. 2%), erythematous rash (14% vs. 2%), and exfoliative rash (12% vs. 2%). In this study of patients with mHRPC, vandetanib + DP did not demonstrate any efficacy benefit, compared with placebo + DP.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Intervalo Livre de Doença , Docetaxel , Método Duplo-Cego , Humanos , Masculino , Pessoa de Meia-Idade , Piperidinas/administração & dosagem , Piperidinas/efeitos adversos , Prednisolona/administração & dosagem , Prednisolona/efeitos adversos , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Quinazolinas/administração & dosagem , Quinazolinas/efeitos adversos , Taxoides/administração & dosagem , Taxoides/efeitos adversos , Resultado do TratamentoRESUMO
BACKGROUND: Advanced gastric cancer carries a poor-prognosis. The best extent of the node dissection and the value of postoperative adjuvant treatments remain open questions.AIM: To study the efficacy of adjuvant chemoradiation and the prognostic value of some clinico-pathological variables in gastric cancer previously submitted to surgery.METHODS: Retrospective single institution study of 69 patients with histological diagnoses of gastric adenocarcinoma, consecutively submitted to radical surgery with curative intent in a five years period. Lymph node dissection was either D1 or D2 at the surgeon's description. All patients were submitted to adjuvant chemoradiation according to MacDonald et al.2. Treatment discontinuation and early deaths were considered as serious toxic events. Clinical-pathological variables (the extent D level of the node dissection, T/N-stage, histological subtype, margin status, number of the dissected nodes) were correlated to the results. Overall survival was estimated according to the Kaplan-Meier method and the curves were compared by the log-rank test.RESULTS: Patients characteristics: 48 male/21 female, median age 56,4 y (30-79). In 25 patients, the extent of node dissection was D1, in 41 was D2 and D0 in 3. Staging (n): T2 (16); T3 (49); T4 (4); No (11); N1 (29); N2 (20); N3 (8); Nx (1). Histological subtype: intestinal (45), diffuse (19) and unknown (5). Margins were free in 57 patients, the median number of dissected nodes was 31 (0-120). They were treated with linear acelerator 6 MV photons, AP/PA fields with 45Gy in 5 weeks in 90% of the patients and the treatment was done in a mean time of 19,2 weeks. In the median follow-up of 19,3mo (8-52,5mo), 52 patients with more than 24 months of follow-up occurred 38 deaths. The median overall survival for all patients was 22,2 months. Seven (10%) patients presented serious toxic events and treatment was discontinued...
RACIONAL: Câncer gástrico avançado é sempre acompanhado de pobre prognóstico. A melhor forma de ser realizada a linfadenectomia e o valor da radioquimioterapia adjuvante ainda estão em tela de juízo.OBJETIVO: Estudar a eficácia da terapia adjuvante e o valor prognóstico de algumas variáveis clínico-patológicas nos pacientes submetidos à ressecção cirúrgica de seus tumores.MÉTODOS: Estudo retrospectivo de uma única instituição hospitalar incluindo 69 pacientes com diagnóstico histológico de adenocarcinoma gástrico consecutivamente submetidos à operação radical com intenção curativa no período de cinco anos. Linfadenectomia foi tanto D1 como D2 e em todos os pacientes foi aplicado o protocolo quimioradioterápico proposto por Macdonald et al.2. Interrupção do tratamento bem como mortes precoces foram consideradas eventos tóxicos sérios. Variáveis clínico-patológicas (extensão do D, estadiamento T/N, subtipos histológicos e número de linfonodos ressecados), foram correlacionados com os resultados. A sobrevida total foi estimada de acordo com o método de Kaplan-Meier.RESULTADOS: Foram 48 homens e 21 mulheres, com idade média de 56,4 anos. Em 25 pacientes a extensão da linfadenectomia foi D1; em 41, D2 e em 3, D0. O estadiamento T2 foi em 16 pacientes; T3 em 49; T4 em 4; N0 em 11; N1 em 29; N2 em 20; N3 em 8; Nx em 1. O subtipo histológico intestinal ocorreu em 45; o difuso em 19 e desconhecido em 5. Em 57 pacientes as margens estavam livres de tumor e foram ressecados em média 31 linfonodos. Foram tratados por acelerador linear 6 MV, AP/PA campos com 45Gy em cinco semanas em 90% dos casos com média de tratamento de 19,2 semanas. No tempo médio de seguimento de 19,3 meses, entre 52 pacientes com mais de 24 meses foram observadas 38 mortes. O tempo médio geral de sobrevida do grupo como um todo foi de 22,2 meses. Sete (10%) apresentaram eventos tóxicos sérios e o tratamento foi interrompido...
Assuntos
Humanos , Masculino , Feminino , Adenocarcinoma , Estadiamento de Neoplasias , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/radioterapia , Prognóstico , Quimioterapia Adjuvante , SeguimentosRESUMO
PURPOSE: The third-generation nonsteroidal aromatase inhibitors (AIs) are increasingly used as adjuvant and first-line advanced therapy for postmenopausal, hormone receptor-positive (HR+) breast cancer. Because many patients subsequently experience progression or relapse, it is important to identify agents with efficacy after AI failure. MATERIALS AND METHODS: Evaluation of Faslodex versus Exemestane Clinical Trial (EFECT) is a randomized, double-blind, placebo controlled, multicenter phase III trial of fulvestrant versus exemestane in postmenopausal women with HR+ advanced breast cancer (ABC) progressing or recurring after nonsteroidal AI. The primary end point was time to progression (TTP). A fulvestrant loading-dose (LD) regimen was used: 500 mg intramuscularly on day 0, 250 mg on days 14, 28, and 250 mg every 28 days thereafter. Exemestane 25 mg orally was administered once daily. RESULTS: A total of 693 women were randomly assigned to fulvestrant (n = 351) or exemestane (n = 342). Approximately 60% of patients had received at least two prior endocrine therapies. Median TTP was 3.7 months in both groups (hazard ratio = 0.963; 95% CI, 0.819 to 1.133; P = .6531). The overall response rate (7.4% v 6.7%; P = .736) and clinical benefit rate (32.2% v 31.5%; P = .853) were similar between fulvestrant and exemestane respectively. Median duration of clinical benefit was 9.3 and 8.3 months, respectively. Both treatments were well tolerated, with no significant differences in the incidence of adverse events or quality of life. Pharmacokinetic data confirm that steady-state was reached within 1 month with the LD schedule of fulvestrant. CONCLUSION: Fulvestrant LD and exemestane are equally active and well-tolerated in a meaningful proportion of postmenopausal women with ABC who have experienced progression or recurrence during treatment with a nonsteroidal AI.
Assuntos
Androstadienos/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Estradiol/análogos & derivados , Recidiva Local de Neoplasia/tratamento farmacológico , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Método Duplo-Cego , Estradiol/uso terapêutico , Feminino , Fulvestranto , Humanos , Estimativa de Kaplan-Meier , Placebos , Pós-Menopausa , Qualidade de Vida , Receptores de Estrogênio/metabolismoRESUMO
Unresectable head and neck squamous cell carcinoma (HNSCC), non-metastatic, comprises a heterogeneous group of patients (pts), formed of stage III and IV pts. Since the available literature had not distinguished among these two groups, we prospectively addressed whether the recommended regimen involving cisplatin 100 mg/m2 concurrent to conventionally delivered radiotherapy (RT) is feasible in stage IV pts, based on the efficacy and safety of this regimen. A total of 30 pts were enrolled onto this study. Chemoradiation (CRT) consisted of RT 70 Gy, delivered in 35 daily fractions of 2 Gy, in 7 weeks, concurrent to cisplatin 100 mg/m2 on days 1, 22 and 43. Supportive treatment was provided as needed. Twenty-eight pts had tumors staged as T4 and 20 had N2 or N3 cervical involvement. The most common primary sites were the oral cavity and the oropharynx (23 pts). We observed six complete responses and 12 partial responses, with an overall response rate of 60%. A high rate of treatment-related toxicities was observed, with three deaths during CRT, and 26 pts suffering from one or more grade 3/4 toxicities, mainly dysphagia, mucositis, dermatitis, vomiting, infection or anemia. A prolonged treatment time was observed (63 days), as a result of unplanned treatment breaks. The lack of requirement of red blood cell transfusion was favorably related to the response to the treatment (93% vs. 50%, P=0.033). For the whole population, with a median follow-up of 20.8 months, the median progression-free survival (PFS) was 8.0 months, and the median overall survival (OS) was 17.3 months. Longer median PFS and OS were seen in responding pts (12.8 vs. 4.1 months, P=0.0001; and not reached (NR) vs. 10.4 months, P=0.0037, respectively), as well as in those pts not requiring red blood cell transfusion (12.8 vs. 3.9 months, P=0.0162; and NR vs. 10.4 months, P=0.0176, respectively). In conclusion, this concurrent CRT regimen is hardly delivered in stage IV, unresectable, locally advanced HNSCC pts, due to treatment-related toxicities and longer RT duration. As a subset of pts may benefit from this regimen, adequate patient selection and aggressive supportive measures are essential.
Assuntos
Antineoplásicos/administração & dosagem , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/radioterapia , Cisplatino/administração & dosagem , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/radioterapia , Adulto , Idoso , Antineoplásicos/efeitos adversos , Carcinoma de Células Escamosas/patologia , Cisplatino/efeitos adversos , Estudos de Coortes , Terapia Combinada , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Estudos de Viabilidade , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de NeoplasiasRESUMO
A avaliação de qualidade de vida tornou-se uma importante ferramenta na avaliação do impacto da doença, saúde e tratamento. A identificação dos efeitos da doença e tratamento na vida dos pacientes pode resultar em mudanças nos procedimentos terapêuticos e de reabilitação e, conseqüentemente, pode auxiliar o médico e o paciente na decisão terapêutica. Nos últimos 15 anos, muitos instrumentos para avaliar a qualidade de vida específica para pacientes com câncer de cabeça e pescoço foram validados. Os questionários são multidimensionais, variando quanto ao número de questões globais divididas em domínios físico, sócio-familiar, funcional e emocional ou, ainda, em questões específicas relacionadas à aparência, dor, fala, mastigação, deglutição, paladar e saliva, entre outros. Os questionários são auto-aplicativos podendo ser ocasionalmente aplicados por entrevistadores treinados e refletem os efeitos da presença do tumor, do tratamento e a habilidade do paciente em lidar com as seqüelas após o tratamento. O objetivo deste estudo é apresentar e discutir os questionários de qualidade de vida específica para o câncer de cabeça e pescoço mais utilizados em estudos da área e validados na população brasileira.
Measuring quality of life is an important toll in the evaluation of the impact of the disease, health and treatment in a population. The identification and description of the effects due to the disease and treatment in the life of the patients may result in changes on the treatment planning and rehabilitation and so can assist both the physician and patient in deciding the treatment. In the last 15 years many questionnaires have been validated to evaluate the specific quality of life related to head and neck cancer. The questionnaires are multidimensional, evaluating the global and specific quality the life based on domains that include many aspects: physical, socio-familial, functional, emotional, and yet questions related to the treatment including appearance, pain, speech, mastication, swallowing, saliva among others. These questionnaires are mainly self-reported, it also may be done, occasionally, a trained interviewer, and reflect the effects of the disease, its treatment and the ability of the patient to copy with the disease and its sequels. The aim of this study is to present and discuss the quality of life questionnaires specific for head and neck cancer that are widely used and are validated in the Brazilian population.
RESUMO
PURPOSE OF REVIEW: As part of the multidisciplinary approach to head and neck cancer patients, radiation therapy plays an essential role, improving locoregional control. Radiation therapy-induced xerostomia is a late side-effect that increases the risk for developing dental caries and compromises oral mucosal integrity, resulting in oral pain, loss of taste, difficulties with swallowing and chewing, sleep disorders and worse quality of life. This review focuses on evaluation, prevention and management of radiation therapy-induced xerostomia. RECENT FINDINGS: In terms of xerostomia prevention, some clinical trials evaluating amifostine and intensity-modulated radiation therapy have shown positive results. Pilocarpine is a useful agent as a treatment of radiation-induced xerostomia in head and neck cancer patients. SUMMARY: Despite some advances in radiation therapy-induced xerostomia prevention, its treatment is an area in which advances are urgently needed.