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1.
Ann Surg Oncol ; 30(2): 1099-1109, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36305992

RESUMO

BACKGROUND: Studies suggest that adjuvant chemotherapy should be initiated at the earliest possible time. The Eastern Cooperative Oncology Group (ECOG) and Intergroup evaluated the effect of perioperative fluorouracil (5-FU) on overall survival (OS) for colon cancer. PATIENTS AND METHODS: This phase III trial randomized patients to receive continuous infusional 5-FU for 7 days starting within 24 h after curative resection (arm A) or no perioperative 5-FU (arm B). Patients with Dukes' B3 and C disease received adjuvant chemotherapy per standard of care. The primary endpoint of the trial was overall survival in patients with Dukes' B3 and C disease. The secondary objective was to determine whether a week of perioperative infusion would affect survival in patients with Dukes' B2 colon cancer with no additional chemotherapy. RESULTS: From August 1993 to May 2000, 859 patients were enrolled and 855 randomized (arm A: 427; arm B: 428). The trial was terminated early due to slow accrual. The median follow-up is 15.4 years (0.03-20.3 years). Among patients with Dukes' B3 and C disease, there was no statistically significant difference in OS [median 10.3 years (95% CI 8.4, 13.2) for perioperative chemotherapy and 9.3 years (95% CI 5.7, 12.3) for no perioperative therapy, one-sided log-rank p = 0.178, HR = 0.88 (95% CI 0.66, 1.16)] or disease-free survival (DFS). For patients with Dukes' B2 disease, there was also no significant difference in OS (median 16.1 versus 12.9 years) or DFS. There was no difference between treatment arms in operative complications. One week of continuous infusion of 5-FU was tolerable; 18% of arm A patients experienced grade 3 or greater toxicity.


Assuntos
Neoplasias do Colo , Fluoruracila , Humanos , Leucovorina , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/cirurgia , Neoplasias do Colo/patologia , Intervalo Livre de Doença , Quimioterapia Adjuvante , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Estadiamento de Neoplasias
2.
J Natl Compr Canc Netw ; 20(3): 224-234, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35276673

RESUMO

The NCCN Guidelines for Head and Neck Cancers address tumors arising in the oral cavity (including mucosal lip), pharynx, larynx, and paranasal sinuses. Occult primary cancer, salivary gland cancer, and mucosal melanoma (MM) are also addressed. The specific site of disease, stage, and pathologic findings guide treatment (eg, the appropriate surgical procedure, radiation targets, dose and fractionation of radiation, indications for systemic therapy). The NCCN Head and Neck Cancers Panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. These NCCN Guidelines Insights summarize the panel's most recent recommendations regarding management of HPV-positive oropharynx cancer and ongoing research in this area.


Assuntos
Neoplasias de Cabeça e Pescoço , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/terapia , Humanos
3.
J Natl Compr Canc Netw ; 18(7): 873-898, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32634781

RESUMO

Treatment is complex for patients with head and neck (H&N) cancers with specific site of disease, stage, and pathologic findings guiding treatment decision-making. Treatment planning for H&N cancers involves a multidisciplinary team of experts. This article describes supportive care recommendations in the NCCN Guidelines for Head and Neck Cancers, as well as the rationale supporting a new section on imaging recommendations for patients with H&N cancers. This article also describes updates to treatment recommendations for patients with very advanced H&N cancers and salivary gland tumors, specifically systemic therapy recommendations.


Assuntos
Neoplasias de Cabeça e Pescoço , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Oncologia , Guias de Prática Clínica como Assunto
4.
J Natl Compr Canc Netw ; 16(5): 479-490, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29752322

RESUMO

The NCCN Guidelines for Head and Neck (H&N) Cancers provide treatment recommendations for cancers of the lip, oral cavity, pharynx, larynx, ethmoid and maxillary sinuses, and salivary glands. Recommendations are also provided for occult primary of the H&N, and separate algorithms have been developed by the panel for very advanced H&N cancers. These NCCN Guidelines Insights summarize the panel's discussion and most recent recommendations regarding evaluation and treatment of nasopharyngeal carcinoma.


Assuntos
Neoplasias de Cabeça e Pescoço , Guias como Assunto , História do Século XXI , Humanos
5.
Cancer ; 123(23): 4653-4662, 2017 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-28786105

RESUMO

BACKGROUND: 13-Cis retinoic acid (13-CRA) is a synthetic vitamin A derivative. High-dose 13-CRA in patients with squamous cell cancers of the head and neck (SCCHNs) reduces the incidence of second primary tumors (SPTs). The authors report long-term results from a phase 3 randomized trial that compared treatment with low-dose 13-CRA versus placebo for patients who had early stage SCCHN, with a focus on the development of SPTs and overall survival (OS). METHODS: In total, 176 patients who received treatment for stage I/II SCCHN were randomized to receive either low-dose 13-CRA (weight-based dose of 7.5 mg or 10 mg) or placebo for 2 years. A competing-risk approach and the log-rank test were used to compare the time to SPT and OS, respectively, between groups. RESULTS: 13-CRA neither significantly reduced the cumulative incidence of SPT (P = .61) nor improved the time to SPT (hazard ratio [HR] for 13-CRA/placebo; 0.86; P = .61). Despite limited power, there was a trend toward improved OS for the 13-CRA arm (HR, 0.75; P = .14), particularly among patients whose index tumor was surgically excised (N = 26; HR, 0.50; P = .057) and among women (N = 39; HR, 0.44; P = .065) and never/former smokers (N = 129; HR, 0.61; P = .055), with a median follow-up of 16 years. The main 13-CRA related toxicities were dry skin and cheilitis. CONCLUSIONS: Treatment with low-dose 13-CRA for 2 years did not decrease the incidence of SPT; subset analysis indicates a potential survival advantage among patients who are women and never/former smokers. More targeted interventions based on clinical risk factors and molecular characterization of tumors may yield greater success in future prevention trials. Cancer 2017;123:4653-4662. © 2017 American Cancer Society.


Assuntos
Carcinoma de Células Escamosas/prevenção & controle , Fármacos Dermatológicos/uso terapêutico , Neoplasias de Cabeça e Pescoço/patologia , Isotretinoína/uso terapêutico , Segunda Neoplasia Primária/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/secundário , Método Duplo-Cego , Feminino , Seguimentos , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Segunda Neoplasia Primária/epidemiologia , Prognóstico , Estados Unidos/epidemiologia
6.
J Natl Compr Canc Netw ; 15(6): 761-770, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28596256

RESUMO

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Head and Neck Cancers provide treatment recommendations for cancers of the lip, oral cavity, pharynx, larynx, ethmoid and maxillary sinuses, and salivary glands. Recommendations are also provided for occult primary of the head and neck (H&N), and separate algorithms have been developed by the panel for very advanced H&N cancers. These NCCN Guidelines Insights summarize the panel's discussion and most recent recommendations regarding the increase in human papillomavirus-associated oropharyngeal cancer and the availability of immunotherapy agents for treatment of patients with recurrent or metastatic H&N cancer.


Assuntos
Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/terapia , Neoplasias de Cabeça e Pescoço/etiologia , Humanos
7.
J Natl Compr Canc Netw ; 13(7): 847-55; quiz 856, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26150579

RESUMO

These NCCN Guidelines Insights focus on recent updates to the 2015 NCCN Guidelines for Head and Neck (H&N) Cancers. These Insights describe the different types of particle therapy that may be used to treat H&N cancers, in contrast to traditional radiation therapy (RT) with photons (x-ray). Research is ongoing regarding the different types of particle therapy, including protons and carbon ions, with the goals of reducing the long-term side effects from RT and improving the therapeutic index. For the 2015 update, the NCCN H&N Cancers Panel agreed to delete recommendations for neutron therapy for salivary gland cancers, because of its limited availability, which has decreased over the past 2 decades; the small number of patients in the United States who currently receive this treatment; and concerns that the toxicity of neutron therapy may offset potential disease control advantages.


Assuntos
Neoplasias de Cabeça e Pescoço/radioterapia , Carbono/uso terapêutico , Guias como Assunto , Radioterapia com Íons Pesados/métodos , Humanos , Terapia por Captura de Nêutron/métodos , Terapia com Prótons/métodos
8.
J Natl Compr Canc Netw ; 12(10): 1454-87, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25313184

RESUMO

This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Head and Neck Cancers focuses on glottic laryngeal cancer, which is the most common type of laryngeal cancer and has an excellent cure rate. The lymphatic drainage of the glottis is sparse, and early stage primaries rarely spread to regional nodes. Because hoarseness is an early symptom, most glottic laryngeal cancer is early stage at diagnosis. Updates to these guidelines for 2014 include revisions to "Principles of Radiation Therapy" for each site and "Principles of Surgery," and the addition of a new section on "Principles of Dental Evaluation and Management."


Assuntos
Neoplasias de Cabeça e Pescoço/terapia , Terapia Combinada , Neoplasias de Cabeça e Pescoço/diagnóstico , Humanos , Estadiamento de Neoplasias , Qualidade de Vida
9.
Cancer ; 119(7): 1349-56, 2013 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-23225544

RESUMO

BACKGROUND: In head and neck cancer (HNC), 3-month post-treatment positron emission tomography (PET)/computed tomography (CT) reliably identifies persistent/recurrent disease. However, further PET/CT surveillance has unclear benefit. The impact of post-treatment PET/CT surveillance on outcomes is assessed at 12 and 24 months. METHODS: A 10-year retrospective analysis of HNC patients was carried out with long-term serial imaging. Imaging at 3 months included either PET/CT or magnetic resonance imaging, with all subsequent imaging comprised of PET/CT. PET/CT scans at 12 and 24 months were evaluated only if preceding interval scans were negative. Of 1114 identified patients, 284 had 3-month scans, 175 had 3- and 12-month scans, and 77 had 3-, 12-, and 24-month scans. RESULTS: PET/CT detection rates in clinically occult patients were 9% (15 of 175) at 12 months, and 4% (3 of 77) at 24 months. No difference in outcomes was identified between PET/CT-detected and clinically detected recurrences, with similar 3-year disease-free survival (41% vs 46%, P = .91) and 3-year overall survival (60% vs 54%, P = .70) rates. Compared with 3-month PET/CT, 12-month PET/CT demonstrated fewer equivocal reads (26% vs 10%, P < .001). Of scans deemed equivocal, 6% (5 of 89) were ultimately found to be positive. CONCLUSIONS: HNC patients with negative 3-month imaging appear to derive limited benefit from subsequent PET/CT surveillance. No survival differences were observed between PET/CT-detected and clinically detected recurrences, although larger prospective studies are needed for further investigation.


Assuntos
Imagem Multimodal , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/diagnóstico , Feminino , Neoplasias de Cabeça e Pescoço/diagnóstico , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Fatores de Tempo , Adulto Jovem
10.
J Natl Compr Canc Netw ; 11(8): 917-23, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23946171

RESUMO

These NCCN Guidelines Insights focus on nutrition and supportive care for patients with head and neck cancers. This topic was a recent addition to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Head and Neck Cancers. The NCCN Guidelines Insights focus on major updates to the NCCN Guidelines and discuss the new updates in greater detail. The complete version of the NCCN Guidelines for Head and Neck Cancers is available on the NCCN Web site (NCCN.org).


Assuntos
Neoplasias de Cabeça e Pescoço/terapia , Política Nutricional , Ingestão de Alimentos , Nutrição Enteral , Humanos , Padrões de Prática Médica
11.
J Clin Oncol ; 37(34): 3266-3274, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31618129

RESUMO

PURPOSE: We evaluated the addition of bevacizumab, a humanized monoclonal antibody that targets vascular endothelial growth factor, to platinum-based chemotherapy in recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS: Patients with chemotherapy-naïve (or with prior platinum as part of multimodal therapy completed ≥ 4 months earlier) recurrent or metastatic SCCHN were randomly assigned to receive a platinum-based chemotherapy doublet with or without bevacizumab 15 mg/kg given intravenously every 3 weeks until disease progression. Chemotherapy could be discontinued after six cycles if a maximum response was achieved. RESULTS: The study randomly assigned 403 patients. Median overall survival (OS) was 12.6 months with bevacizumab plus chemotherapy (BC) and 11.0 months with chemotherapy alone (hazard ratio, 0.87; 95% CI, 0.70 to 1.09; P = .22). At 2, 3, and 4 years, the OS rates were 25.2% v 18.1%, 16.4% v 10.0%, and 11.8% v 6.4% for BC versus chemotherapy, respectively. In an analysis of 365 eligible patients who started treatment, the hazard ratio was 0.82 (95% CI, 0.65 to 1.04; P = .10), with a median OS of 14.2 months on BC v 11.1 months on chemotherapy. Median progression-free survival with BC was 6.0 months v 4.3 months with chemotherapy (P = .0014). Overall response rates were 35.5% with BC and 24.5% with chemotherapy (P = .016). There was increased toxicity, including a higher rate of treatment-related grade 3 to 5 bleeding events (6.7% v 0.5%; P < .001) and treatment-related deaths (9.3% v 3.5%; P = .022) with BC versus chemotherapy. CONCLUSION: The addition of bevacizumab to chemotherapy did not improve OS but improved the response rate and progression-free survival with increased toxicities. These results encourage biomarker-driven studies of angiogenesis inhibitors with better toxicity profiles in select patients with SCCHN.


Assuntos
Antineoplásicos Imunológicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Bevacizumab/administração & dosagem , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Recidiva Local de Neoplasia , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Idoso , Antineoplásicos Imunológicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab/efeitos adversos , Progressão da Doença , Esquema de Medicação , Feminino , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Intervalo Livre de Progressão , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/secundário , Fatores de Tempo , Estados Unidos
12.
Int J Radiat Oncol Biol Phys ; 71(2): 393-400, 2008 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-18164839

RESUMO

PURPOSE: To determine long-term outcomes in patients receiving stereotactic radiotherapy (SRT) as a boost after external beam radiotherapy (EBRT) for locally advanced nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: Eight-two patients received an SRT boost after EBRT between September 1992 and July 2006. Nine patients had T1, 30 had T2, 12 had T3, and 31 had T4 tumors. Sixteen patients had Stage II, 19 had Stage III, and 47 had Stage IV disease. Patients received 66 Gy of EBRT followed by a single-fraction SRT boost of 7-15 Gy, delivered 2-6 weeks after EBRT. Seventy patients also received cisplatin-based chemotherapy delivered concurrently with and adjuvant to radiotherapy. RESULTS: At a median follow-up of 40.7 months (range, 6.5-144.2 months) for living patients, there was only 1 local failure in a patient with a T4 tumor. At 5 years, the freedom from local relapse rate was 98%, freedom from nodal relapse 83%, freedom from distant metastasis 68%, freedom from any relapse 67%, and overall survival 69%. Late toxicity included radiation-related retinopathy in 3, carotid aneurysm in 1, and radiographic temporal lobe necrosis in 10 patients, of whom 2 patients were symptomatic with seizures. Of 10 patients with temporal lobe necrosis, 9 had T4 tumors. CONCLUSION: Stereotactic radiotherapy boost after EBRT provides excellent local control for patients with NPC. Improved target delineation and dose homogeneity of radiation delivery for both EBRT and SRT is important to avoid long-term complications. Better systemic therapies for distant control are needed.


Assuntos
Neoplasias Nasofaríngeas/cirurgia , Radiocirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/radioterapia , Lesões por Radiação/patologia , Radiocirurgia/efeitos adversos , Dosagem Radioterapêutica , Lobo Temporal/efeitos da radiação , Resultado do Tratamento
15.
Clin Cancer Res ; 9(1): 59-67, 2003 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-12538452

RESUMO

PURPOSE: Tumor hypoxia modifies treatment efficacy and promotes tumor progression. Here, we investigated the relationship between osteopontin (OPN), tumor pO(2), and prognosis in patients with head and neck squamous cell carcinomas (HNSCC). EXPERIMENTAL DESIGN: We performed linear discriminant analysis, a machine learning algorithm, on the NCI-60 cancer cell line microarray expression database to identify a gene profile that best distinguish cell lines with high Von-Hippel Lindau (VHL) gene expression, an important regulator of hypoxia-related genes, from those with low expression. Plasma OPN levels in 15 volunteers, 31 VHL patients, and 54 HNSCC patients were quantitatively measured by ELISA. The relationships between plasma OPN levels, tumor pO(2) as measured by the Eppendorf microelectrode, freedom from relapse (FFR), and survival in HNSCC patients were evaluated. RESULTS: Microarray analysis indicated that OPN gene expression inversely correlated with that of VHL. These findings were confirmed by Northern blot analysis. ELISA studies and Western blot in a HNSCC cell line demonstrated that hypoxia exposure resulted in increased OPN secretion. Patients with VHL syndrome had significantly higher plasma OPN levels than healthy volunteers. Plasma OPN level inversely correlated with tumor pO(2) (P = 0.003, r = -0.42). OPN levels correlated with clinical outcomes. The 1-year FFR and survival rates were 80 and 100%, respectively, for patients with OPN levels 450 ng/ml (P = 0.002 and 0.0005). Multivariate analysis revealed that OPN was an independent predictor for FFR and survival. CONCLUSIONS: Plasma OPN levels appeared to correlate with tumor hypoxia in HNSCC patients and may serve as noninvasive tests to identify patients at high risk for tumor recurrence.


Assuntos
Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/diagnóstico , Neoplasias de Cabeça e Pescoço/sangue , Neoplasias de Cabeça e Pescoço/diagnóstico , Sialoglicoproteínas/sangue , Sialoglicoproteínas/genética , Proteínas Supressoras de Tumor , Ubiquitina-Proteína Ligases , Adulto , Idoso , Algoritmos , Northern Blotting , Western Blotting , Bases de Dados como Assunto , Progressão da Doença , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Hipóxia , Ligases/biossíntese , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Osteopontina , Oxigênio/metabolismo , Modelos de Riscos Proporcionais , Recidiva , Fatores de Tempo , Células Tumorais Cultivadas , Proteína Supressora de Tumor Von Hippel-Lindau
16.
Laryngoscope ; 115(4): 645-50, 2005 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15805874

RESUMO

OBJECTIVES/HYPOTHESIS: To determine the diagnostic accuracy and the ideal timing of fluoro-fluorodeoxyglucose positron-emission tomography (PET) in the posttreatment surveillance of head and neck mucosal squamous cell carcinoma (HNSCC). STUDY DESIGN: Retrospective chart review. METHODS: Our sample includes 103 adult patients with 118 posttreatment PET scans who had undergone treatment for HNSCC. We correlated PET results with surgical pathology and clinical outcome in the subsequent 6 months. RESULTS: For the detection of locoregional persistent or recurrent HNSCC, PET scans had a sensitivity of 82%, specificity of 92%, positive predictive value (PPV) of 64%, negative predictive value (NPV) of 97%, and overall accuracy of 90%. For the detection of distant metastases, PET scans had a sensitivity of 89%, specificity of 97%, PPV of 85%, NPV of 98%, and overall accuracy of 96%. PET scans of the head and neck region performed greater than 1 month after the completion of radiation compared with scans performed within 1 month had a significantly higher sensitivity of 95% versus 55% (P < .01) and NPV of 99% versus 90% (P < .01). CONCLUSION: PET is effective in detecting distant metastases in the posttreatment surveillance for HNSCC patients. A negative PET is highly reliable for all sites. However, a positive PET in the head and neck region is unreliable because of a high false-positivity rate. PET of the head and neck region has a statistically significant risk of a false-negative reading when performed within 1 month of radiation.


Assuntos
Carcinoma de Células Escamosas/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/secundário , Carcinoma de Células Escamosas/cirurgia , Feminino , Fluordesoxiglucose F18 , Seguimentos , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Recidiva Local de Neoplasia/diagnóstico por imagem , Neoplasia Residual , Valor Preditivo dos Testes , Compostos Radiofarmacêuticos , Radioterapia Adjuvante , Estudos Retrospectivos , Sensibilidade e Especificidade , Fatores de Tempo , Resultado do Tratamento
17.
Int J Radiat Oncol Biol Phys ; 56(2): 375-83, 2003 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-12738312

RESUMO

PURPOSE: To compare the Eppendorf PO2 histograph and the alkaline comet assay as methods of measuring tumor hypoxia in patients with head-and-neck squamous cell carcinomas. MATERIALS AND METHODS: As part of a larger clinical trial, 65 patients with head-and-neck squamous cell carcinoma nodal metastasis underwent tumor oxygenation measurements with Eppendorf PO2 histographs and comet assays, performed on fine-needle aspirates at 1 and 2 min after 5 Gy. Fifty-four patients had sufficient tumor cells for comet analysis at 1 min and 26 at both 1 and 2 min. Individual cells were examined for DNA single-strand breaks by alkaline gel electrophoresis, and the distribution of values was quantified using median tail moment (MTM). Nonirradiated tumor cells from pretreatment fine-needle aspirates received 5 Gy in vitro to establish the oxygenated response. RESULTS: There was a significant correlation between the 1- and 2-min MTM (slope = 0.77 +/- 0.03). There was no relationship between DNA damage in tumor cells irradiated in vitro and in vivo. No correlation was found between Eppendorf PO2 measurements and comet MTM. There was a statistically significant correlation between the treatment response in the node studied and comet MTMs, whereas no correlation was observed between treatment response and Eppendorf measurements. CONCLUSIONS: Comet assays are reproducible, as shown by biopsies at 1 and 2 min. Intertumor variation in the MTM is not a result of intrinsic radiosensitivity but of tumor hypoxia. There was no correlation between Eppendorf PO2 measurements and comet MTM. Comet assays were better than Eppendorf in predicting treatment response as an end point for short-term outcome. Longer follow-up is needed to determine the role of the comet assay as a predictor for locoregional tumor control and survivals.


Assuntos
Carcinoma de Células Escamosas/fisiopatologia , Hipóxia Celular , Neoplasias de Cabeça e Pescoço/fisiopatologia , Oxigênio/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/radioterapia , Cisplatino/administração & dosagem , Ensaio Cometa , Dano ao DNA , Feminino , Fluoruracila/administração & dosagem , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Masculino , Microeletrodos , Pessoa de Meia-Idade , Radiossensibilizantes/uso terapêutico , Tirapazamina , Triazinas/uso terapêutico
18.
Int J Radiat Oncol Biol Phys ; 56(4): 1046-54, 2003 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-12829140

RESUMO

PURPOSE: Treatment of nasopharyngeal carcinoma using conventional external beam radiotherapy (EBRT) alone is associated with a significant risk of local recurrence. Stereotactic radiosurgery (STR) was used to boost the tumor site after EBRT to improve local control. METHODS AND MATERIALS: Forty-five nasopharyngeal carcinoma patients received a STR boost after EBRT at Stanford University. Seven had T1, 16 had T2, 4 had T3, and 18 had T4 tumors (1997 American Joint Commission on Cancer staging). Ten had Stage II, 8 had Stage III, and 27 had Stage IV neoplasms. Most patients received 66 Gy of EBRT delivered at 2 Gy/fraction. Thirty-six received concurrent cisplatin-based chemotherapy. STR was delivered to the primary site 4-6 weeks after EBRT in one fraction of 7-15 Gy. RESULTS: At a medium follow-up of 31 months, no local failures had occurred. The 3-year local control rate was 100%, the freedom from distant metastasis rate was 69%, the progression-free survival rate was 71%, and the overall survival rate was 75%. Univariate and multivariate analyses revealed N stage (favoring N0-N1, p = 0.02, hazard ratio HR 4.2) and World Health Organization histologic type (favoring type III, p = 0.002, HR 13) as significant factors for freedom from distant metastasis. World Health Organization histologic type (p = 0.004, HR 10.5) and age (p = 0.01, HR 1.07/y) were significant factors for survival. Late toxicity included transient cranial nerve weakness in 4, radiation-related retinopathy in 1, and asymptomatic temporal lobe necrosis in 3 patients who originally had intracranial tumor extension. CONCLUSION: STR boost after EBRT provided excellent local control in nasopharyngeal carcinoma patients. The incidence of late toxicity was acceptable. More effective systemic treatment is needed to achieve improved survival.


Assuntos
Neoplasias Nasofaríngeas/radioterapia , Neoplasias Nasofaríngeas/cirurgia , Radiocirurgia/métodos , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Combinada , Fracionamento da Dose de Radiação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/tratamento farmacológico , Prognóstico , Radiocirurgia/efeitos adversos , Radioterapia/efeitos adversos
19.
Arch Otolaryngol Head Neck Surg ; 128(6): 698-702, 2002 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12049567

RESUMO

BACKGROUND: The alkaline comet assay is a microelectrophoretic technique for detecting single-strand DNA breaks, and may be used as an indirect measure of hypoxia by determining the radiation sensitivity of individual cells. OBJECTIVE: To assess the ability of the comet assay to estimate the rate of DNA repair after irradiation in patients with head and neck cancer. METHODS: The comet assay was used to evaluate DNA damage in fine-needle aspirates of lymph nodes containing metastatic squamous cell carcinoma in patients with head and neck cancer 1, 2, and 3 minutes after treatment with 500 rad (5 Gy) of irradiation. The amount of DNA damage (measured as the "tail moment" of the comet) is proportional to the number of DNA single-strand breaks after irradiation, which in turn depends on the oxygen concentration in each cell. RESULTS: The mean +/- SD of the median tail moment of the 1-minute postirradiation comets was 29.4 +/- 14.2 (n = 27). After 2 minutes, the mean median tail moment decreased to 25.4 +/- 13.6 (n = 25), representing a mean decrease of 11.9% in those patients with both 1- and 2-minute comet assays. Assuming a linear rate of repair, this decrease in DNA damage corresponds to a repair half-life of 4.2 minutes. A 3-minute assay was also performed on samples from a smaller number of patients (n = 9), with a mean value not significantly different from that of the 2-minute assay of the samples from this group. CONCLUSIONS: The comet assay is a promising tool for evaluating radiation sensitivity in individual cells. The rate of DNA repair early after irradiation is consistent with data in the literature.


Assuntos
Carcinoma de Células Escamosas/radioterapia , Ensaio Cometa , Reparo do DNA , DNA/efeitos da radiação , Neoplasias de Cabeça e Pescoço/radioterapia , Metástase Linfática/radioterapia , Tolerância a Radiação/genética , Adulto , Idoso , Biópsia por Agulha , Carcinoma de Células Escamosas/patologia , Hipóxia Celular/efeitos da radiação , Dano ao DNA , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Irradiação Linfática , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Fatores de Tempo
20.
Int J Radiat Oncol Biol Phys ; 83(3): 994-9, 2012 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-22137026

RESUMO

PURPOSE: To assess the role of a planned neck dissection (PND) after sequential chemoradiotherapy for patients with head-and-neck cancer with N2-N3 nodal disease. METHODS AND MATERIALS: We reviewed 90 patients with N2-N3 head-and-neck squamous cell carcinoma treated between 1991 and 2001 on two sequential chemoradiotherapy protocols. All patients received induction and concurrent chemotherapy with cisplatin and 5-fluorocuracil, with or without tirapazamine. Patients with less than a clinical complete response (cCR) in the neck proceeded to a PND after chemoradiation. The primary endpoint was nodal response. Clinical outcomes and patterns of failure were analyzed. RESULTS: The median follow-up durations for living and all patients were 8.3 years (range, 1.5-16.3 year) and 5.4 years (range, 0.6-16.3 years), respectively. Of the 48 patients with nodal cCR whose necks were observed, 5 patients had neck failures as a component of their recurrence [neck and primary (n = 2); neck, primary, and distant (n = 1); neck only (n = 1); neck and distant (n = 1)]. Therefore, PND may have benefited only 2 patients (4%) [neck only failure (n = 1); neck and distant failure (n = 1)]. The pathologic complete response (pCR) rate for those with a clinical partial response (cPR) undergoing PND (n = 30) was 53%. The 5-year neck control rates after cCR, cPR→pCR, and cPR→pPR were 90%, 93%, and 78%, respectively (p = 0.36). The 5-year disease-free survival rates for the cCR, cPR→pCR, and cPR→pPR groups were 53%, 75%, and 42%, respectively (p = 0.04). CONCLUSION: In our series, patients with N2-N3 neck disease achieving a cCR in the neck, PND would have benefited only 4% and, therefore, is not recommended. Patients with a cPR should be treated with PND. Residual tumor in the PND specimens was associated with poor outcomes; therefore, aggressive therapy is recommended. Studies using novel imaging modalities are needed to better assess treatment response.


Assuntos
Carcinoma de Células Escamosas/terapia , Quimiorradioterapia/métodos , Neoplasias de Cabeça e Pescoço/terapia , Esvaziamento Cervical/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/secundário , Cisplatino/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Neoplasia Residual , Tratamentos com Preservação do Órgão/métodos , Estudos Prospectivos , Taxa de Sobrevida , Tirapazamina , Resultado do Tratamento , Triazinas/administração & dosagem
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