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2.
Semin Vasc Surg ; 29(3): 120-125, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27989317

RESUMO

Hostile infrarenal aortic neck anatomy presents a challenge for the endovascular treatment of abdominal aortic aneurysm. Open surgical repair has been seen as the gold standard treatment for juxtarenal abdominal aortic aneurysm; however, endovascular techniques are now becoming more prevalent, particularly in patients deemed high risk for morbidity and mortality with open repair. The morphology of an aneurysm is a determinant of long-term outcomes, and short aneurysm necks are associated with poorer outcomes and a higher rate of secondary reinterventions. Parallel grafts have been used in combination with endovascular aneurysm repair to elongate the sealing zone into the paravisceral segment of the aorta. This technique is associated with a risk of proximal Type I endoleak due to "guttering." This risk may be decreased when parallel grafts are used in combination with endovascular aneurysm sealing and, as such, this technique may represent an alternative to current techniques for the treatment of juxtarenal abdominal aortic aneurysm, such as the use of conventional bifurcated grafts (with or without parallel grafts) and fenestrated endovascular stent grafts.


Assuntos
Aneurisma da Aorta Abdominal/cirurgia , Implante de Prótese Vascular/instrumentação , Prótese Vascular , Procedimentos Endovasculares/instrumentação , Stents , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aortografia/métodos , Implante de Prótese Vascular/efeitos adversos , Angiografia por Tomografia Computadorizada , Endoleak/etiologia , Endoleak/prevenção & controle , Procedimentos Endovasculares/efeitos adversos , Humanos , Desenho de Prótese , Sistema de Registros , Fatores de Risco , Resultado do Tratamento
3.
Ann Oncol ; 27(5): 908-13, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26884588

RESUMO

BACKGROUND: Efforts to reduce the late toxicity associated with chemoradiation (CRT) for locally advanced head and neck squamous cell cancer (LA-HNSCC) have focused on radiotherapy (RT) dose de-escalation. In this phase I/II protocol investigating the addition of everolimus to induction chemotherapy (IC), we incorporated a novel response-adapted volume de-escalation (RAVD) approach using IC response to guide the extent of RT volume reduction. PATIENTS AND METHODS: Patients with measurable LA-HNSCC received two cycles of IC (cisplatin, paclitaxel, cetuximab ± everolimus). Patients with ≥50% reduction in the sum of tumor diameters [good response (GR)] received TFHX (paclitaxel, fluorouracil, hydroxyurea, and 1.5 Gy twice daily RT every other week) to a dose of 75 Gy with the single planning target volume (PTV1) encompassing exclusively gross disease. Patients with <50% response [non-response (NR)] were treated with TFHX encompassing PTV1 and the next nodal station at risk (PTV2) to a dose of 45 Gy followed by a sequential boost to PTV1 to a dose of 75 Gy. RESULTS: Ninety-four patients were enrolled. Randomization to everolimus was discontinued on interim analysis after 50 patients due to futility. IC response was evaluable in 89 patients. Thirty-seven patients (41.6%) had GR and 52 (58.4%) had NR. There was a trend for improved progression-free (P = 0.086) but not overall survival (P = 0.94) for GR versus NR. The 2-year PFS and OS were 86.0% and 83.5% for GR and 68.7% and 85.4% for NR, respectively. NR were significantly more likely to undergo G-tube placement during treatment (50.0% GR versus 73.5% NR, P = 0.040) and be G-tube dependent at 6-month follow-up (5.7% GR versus 32.6% NR, P = 0.005). CONCLUSIONS: The addition of everolimus to IC was not beneficial. The elimination of elective nodal coverage in patients with GR to IC did not appear to compromise outcomes and resulted in significantly decreased late toxicity. Further investigation of RAVD is warranted. CLINICALTRIALSGOV: NCT01133678.


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 , Adulto , Idoso , Carcinoma de Células Escamosas/patologia , Quimiorradioterapia/efeitos adversos , Terapia Combinada , Everolimo/administração & dosagem , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Quimioterapia de Indução , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Indução de Remissão
4.
Ann Oncol ; 26(1): 198-205, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25361984

RESUMO

BACKGROUND: Human papillomavirus (HPV) has emerged as a causative agent and positive prognostic factor for oropharyngeal (OP) head and neck squamous cell cancer (HNSCC). This prompts inquiry into whether therapy improvements or increasing incidence of HPV drives the apparent improvements in HNSCC outcomes observed in non-randomized clinical trials. PATIENTS AND METHODS: We reviewed all locoregionally advanced HNSCC patients treated with chemotherapy and radiation in prospective institutional trials at a single institution. Patients were divided into three groups (1, 2, 3) according to treatment time period (1993-1998, 1999-2003, 2004-2010, respectively). We reasoned that if a favorable trend was observed over time in OP but not non-OP patients, HPV status may be confounding treatment effects, whereas this would be unlikely if both subgroups improved over time. RESULTS: Four hundred and twenty-two patients were identified with OP (55.7%) and non-OP (44.3%) HNSCC. Five-year OP overall survival (OS) improved from 42.3% (group 1) to 72.5% (group 2), and 78.4% (group 3), adjusted P = 0.0084. Non-OP 5-year OS was 51.0% (group 1), 58.8% (group 2), and 66.3% (group 3), adjusted P = 0.51. Five-year recurrence-free survival (RFS) improved for OP groups from 42.3% to 68.4% to 75.8% (adjusted P = 0.017). Non-OP 5-year RFS was 42.9%, 53.6%, and 61.7% for sequential groups (adjusted P = 0.30). Five-year OP distant failure-free survival (DFFS) improved from 42.3% to 71.1% to 77.8% (adjusted P = 0.011). Five-year non-OP DFFS was 46.9%, 57.1%, and 66.0% for sequential groups (adjusted P = 0.38). CONCLUSIONS: Over the past two decades, OP HNSCC outcomes improved significantly, while non-OP outcomes only trended toward improvement. Although our patients are not stratified by HPV status, improving OP outcomes are likely at least partly due to the increasing HPV incidence. These data further justify trial stratification by HPV status, investigations of novel approaches for carcinogen-related HNSCC, and current de-intensification for HPV-related HNSCC.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Orofaríngeas , Infecções por Papillomavirus/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/virologia , Feminino , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Neoplasias Orofaríngeas/diagnóstico por imagem , Neoplasias Orofaríngeas/tratamento farmacológico , Neoplasias Orofaríngeas/virologia , Papillomaviridae , Estudos Prospectivos , Radiografia , Fumar , Carcinoma de Células Escamosas de Cabeça e Pescoço , Resultado do Tratamento
5.
Oral Oncol ; 49(3): 277-82, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23102863

RESUMO

PURPOSE: Current standard therapy for nasopharyngeal carcinoma (NPC) is concurrent chemoradiation based on randomized data. However, limited randomized data exist to support the addition of induction chemotherapy (ICT). METHODS: 58 Patients with NPC were treated from 1990 to 2010. All patients received platinum-based ICT. All 58 patients were treated with chemoradiation, 57 in a week-on/week-off (WOWO) fashion. Concurrent chemotherapy included hydroxyurea/5-fluorouracil for all patients. Median radiation dose was 70 Gy. No patient received adjuvant chemotherapy. RESULTS: AJCC 2009 stage was II=13, III=21, IVa=13, and IVb=11. Median follow-up for surviving patients was 66 months. Response to ICT was complete response (CR) 17% and partial response (PR) 64%. The CR rate after chemoradiation was 96%. Five-year actuarial freedom from local failure (FFLF), freedom from distant failure (FFDF), cause-specific survival (CSS), and overall survival (OS) was 98%, 90%, 90%, and 76%, respectively. Analysis of pediatric patients (n=9) demonstrated 5-year actuarial FFLF, FFDF, CSS, and OS of 100%, 88%, 80%, and 80%, respectively. CONCLUSIONS: ICT followed by concurrent chemoradiation demonstrates excellent FFLF, FFDF, CSS, and OS with tolerable toxicity. Induction chemotherapy followed by concurrent chemoradiation for patients with NPC should be explored further in a randomized setting.


Assuntos
Carcinoma/tratamento farmacológico , Quimiorradioterapia/métodos , Quimioterapia de Indução/métodos , Neoplasias Nasofaríngeas/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma/radioterapia , Carcinoma/secundário , Quimioterapia Adjuvante , Criança , Intervalo Livre de Doença , Feminino , Fluoruracila/administração & dosagem , Seguimentos , Humanos , Hidroxiureia/administração & dosagem , Masculino , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/radioterapia , Terapia Neoadjuvante , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Platina/administração & dosagem , Dosagem Radioterapêutica , Indução de Remissão , Taxa de Sobrevida , Resultado do Tratamento , Adulto Jovem
6.
Ann Oncol ; 24(3): 769-76, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23104721

RESUMO

BACKGROUND: AdGV.EGR.TNF.11D (TNFerade™ Biologic) is a replication-deficient adenoviral vector expressing human tumor necrosis factor alpha (TNF-α) under the control of the chemoradiation-inducible EGR-1 promoter. TNF-α has been shown to function as a radiation sensitizer. We conducted a phase I dose escalation study to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of TNFerade™ Biologic, when added to chemoradiotherapy in poor prognosis patients with recurrent, previously irradiated head and neck cancer (HNC). METHODS: TNFerade™ Biologic was injected intratumorally on day 1 of each 14-day cycle and dose-escalated in log increments from 4 × 10(9) to 4 × 10(11) PU. Daily radiation, infusional 5-fluorouracil (5-FU), and hydroxyurea were given on days 1-5 for seven cycles (FHX). Tumor biopsies were obtained before, during, and after treatment. RESULTS: Fourteen patients were treated. DLT was reached at a dose level of 3 (4 × 10(11) PU) with three thrombotic events. The response rate was 83.3%. The median survival was 9.6 months. One patient (7.1%) remained alive 3 years after treatment. Biopsies were obtained in 90% of patients. Nearly all tumors expressed adenovirus receptors, TNF-α, and TNF-α receptors. Adenoviral DNA was detected in three biopsies from one patient. CONCLUSIONS: TNFerade™ Biologic can be safely integrated with FHX chemoradiotherapy at an MTD of 4 × 10(10) PU. Monitoring for thrombotic events is indicated.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/terapia , DNA/administração & dosagem , Neoplasias de Cabeça e Pescoço/terapia , Radiossensibilizantes/administração & dosagem , Adulto , Idoso , Carcinoma de Células Escamosas/mortalidade , Quimiorradioterapia , DNA/genética , Fracionamento da Dose de Radiação , Feminino , Fluoruracila/administração & dosagem , Terapia Genética , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Hidroxiureia/administração & dosagem , Estimativa de Kaplan-Meier , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Planejamento da Radioterapia Assistida por Computador , Radioterapia de Intensidade Modulada , Retratamento , Carcinoma de Células Escamosas de Cabeça e Pescoço , Resultado do Tratamento
7.
Ann Oncol ; 22(11): 2501-2507, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21385883

RESUMO

BACKGROUND: Concurrent chemoreirradiation therapy (CRRT) offers a therapeutic option for patients with locoregionally recurrent squamous cell carcinoma of the head and neck (SCCHN). We hypothesized that response to induction chemotherapy (IC) would improve outcome and predict increased survival. PATIENTS AND METHODS: Subjects with recurrent SCCHN not amenable to standard therapy were eligible. IC consisted of two 28-day cycles of gemcitabine and pemetrexed on days 1 and 14, followed by surgical resection, if appropriate, and/or CRRT consisting of carboplatin, pemetrexed, and single daily fractionated radiotherapy. RESULTS: Thirty-five subjects were enrolled, 31 were assessable for response, with 11 responders [response rate = 35%; 95% confidence interval (CI) 19.2-54.6]. Among 24 subjects who started CRRT, 11 were assessable for radiographic response, 4 complete response, 2 partial response, and 5 progressive disease. Median progression-free survival and overall survival (OS) were 5.5 months (95% CI 3.6-8.3) and 9.5 months (95% CI 7.2-15.4), respectively. One-year OS was 43% (95% CI 26% to 58%). Subjects who responded to IC had improved survival (P = 0.02). Toxic effects included mucositis, dermatitis, neutropenia, infection, hemorrhage, dehydration, and pain. CONCLUSIONS: The combination of pemetrexed plus gemcitabine was active and well tolerated in recurrent SCCHN. Response to IC may help stratify prognosis and offer an objective and dynamic metric in recurrent SCCHN patients being considered for CRRT.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/radioterapia , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/radioterapia , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/radioterapia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma de Células Escamosas/cirurgia , Terapia Combinada/efeitos adversos , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/análogos & derivados , Feminino , Glutamatos/administração & dosagem , Glutamatos/efeitos adversos , Guanina/administração & dosagem , Guanina/efeitos adversos , Guanina/análogos & derivados , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Quimioterapia de Indução , Masculino , Pessoa de Meia-Idade , Pemetrexede , Estudos Prospectivos , Radioterapia/efeitos adversos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Gencitabina
8.
Ann Oncol ; 22(10): 2304-9, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21330337

RESUMO

INTRODUCTION: We conducted a randomized phase II study to evaluate the impact of adding bevacizumab (B) to 5-fluorouracil (5-FU), hydroxyurea (HU), and radiotherapy (FHX) for intermediate-stage and select T4 head and neck squamous cell cancers (HNSCC). PATIENTS AND METHODS: Eligible patients had newly diagnosed HNSCC. Randomization was 2:1 in favor of BFHX. All patients received 500 mg HU p.o. b.i.d., 600 mg/m(2)/day continuous infusion 5-FU, and b.i.d. radiotherapy with or without bevacizumab 10 mg/kg administered on day 1 of each 14-day cycle. Patients received five cycles consisting of chemoradiotherapy for 5 days followed by 9 days without therapy. RESULTS: Twenty-six patients were enrolled (19 BFHX and 7 FHX). The study was halted following unexpected locoregional progression. Two-year survival was 68%; 89% treated with FHX and 58% (95% confidence interval 33% to 78%) treated with BFHX. Two-year locoregional control was 80% after chemoradiotherapy and 85% after surgical salvage. All locoregional progression occurred in T4 tumors randomized to BFHX. Two patients receiving BFHX died during therapy, and one died shortly after therapy. No catastrophic bleeding events were seen. CONCLUSIONS: Locoregional progression seen in T4N0-1 tumors treated with BFHX was unexpected and led to study termination. The addition of bevacuzimab to chemoradiotherapy for HNSCC should be limited clinical trials.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , 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 , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/administração & dosagem , Bevacizumab , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Terapia Combinada , Progressão da Doença , Intervalo Livre de Doença , Feminino , Fluoruracila/administração & dosagem , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Hidroxiureia/administração & dosagem , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Dosagem Radioterapêutica , Carcinoma de Células Escamosas de Cabeça e Pescoço
9.
Eur J Vasc Endovasc Surg ; 41(2): 264-6, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21130009

RESUMO

INTRODUCTION: Thorascopic sympathectomy is a widely used procedure for the treatment of intractable palmar hyperhidrosis. REPORT: A 24-year-old woman who underwent thorascopic sympathectomy for hyperhidrosis in 2005 presented on more than 30 occasions with recurrent right distal upper limb ischaemia secondary to repetitive episodes of vasospasm. The patient did not have preoperative symptoms consistent with Raynaud's syndrome. We observed a reduction in the symptomatic relief offered by Iloprost treatment over a period of five years. DISCUSSION: This is the first report of distal upper limb ischaemia following thorascopic sympathectomy. We highlight the development of resistance to repeated Iloprost infusions that we observed in this case.


Assuntos
Hiperidrose/cirurgia , Isquemia/etiologia , Espasmo/etiologia , Simpatectomia/efeitos adversos , Toracoscopia/efeitos adversos , Extremidade Superior/irrigação sanguínea , Doenças Vasculares/etiologia , Resistência a Medicamentos , Feminino , Humanos , Iloprosta/administração & dosagem , Infusões Parenterais , Isquemia/diagnóstico por imagem , Isquemia/tratamento farmacológico , Radiografia , Recidiva , Espasmo/diagnóstico por imagem , Espasmo/tratamento farmacológico , Simpatectomia/métodos , Resultado do Tratamento , Doenças Vasculares/diagnóstico por imagem , Doenças Vasculares/tratamento farmacológico , Vasodilatadores/administração & dosagem , Adulto Jovem
10.
Ann Oncol ; 19(10): 1787-94, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18539617

RESUMO

BACKGROUND: We hypothesized induction chemotherapy (IndCT) would improve distant control (DC) without compromising locoregional control (LRC) for locoregionally advanced head and neck cancer patients. Additionally, we systematically lowered radiotherapy (RT) doses attempting to maintain LRC while decreasing toxicity. PATIENTS AND METHODS: Stages III-IV (M0) locoregionally advanced head and neck cancer patients received carboplatin/paclitaxel (Taxol) IndCT followed by four or five cycles consisting of 5 days of paclitaxel, fluorouracil, hydroxyurea, and BID RT followed by a nine day break. RT dose to gross disease (high risk), intermediate, and low-risk volumes were reduced from cohort A (n = 68): 75, 60, and 45 Gy; to cohort B (n = 64): 75, 54, and 39 Gy; then cohort C (n = 90): 72, 51, and 36 Gy. RESULTS: A total of 222 patients accrued from November 1998 to September 2002. Median follow-up is 56 months. In all, 93/96/76% achieved a complete response to concurrent chemoradiotherapy (CRT) in cohort A/B/C. Three- and 5-year overall survivals (OSs) are 68% and 62%, respectively. Five-year LRC and DC are 91% and 87%, respectively. Response to IndCT predicted for OS, LRC, and time to progression (TTP). Cohort C patients had similar OS (P = 0.95), LRC, and DC, but worse (TTP) (P = 0.027). CONCLUSIONS: IndCT before CRT reduces distant progression while maintaining high LRC. The cohort B schedule provides the best therapeutic ratio. A randomized trial investigating IndCT before CRT has been initiated.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/radioterapia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/radioterapia , Estudos de Coortes , Terapia Combinada , Intervalo Livre de Doença , Relação Dose-Resposta à Radiação , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Hidroxiureia/administração & dosagem , Hidroxiureia/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Indução de Remissão
11.
Ann Oncol ; 19(9): 1650-4, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18467314

RESUMO

BACKGROUND: Randomized trials established chemoradiotherapy as standard treatment for advanced laryngeal cancer. Patients with large-volume T4 disease (LVT4) were excluded from these trials. The purpose of this study was to report T4 laryngeal cancer patient outcome, including those with LVT4 disease, treated with chemoradiotherapy. PATIENTS AND METHODS: This study is a retrospective subset analysis of 32 patients with T4 laryngeal carcinoma including LVT4 tumors treated on three consecutive protocols investigating paclitaxel (Taxol), 5-fluorouracil, hydroxyurea, and 1.5-Gy twice daily (BID) radiotherapy (TFHX). RESULTS: Median follow-up is 43 months. Four-year locoregional control (LRC), disease-free survival (DFS), overall survival (OS), and laryngectomy-free survival (LFS) was 71%, 67%, 53%, and 86%, respectively. Four patients required laryngectomy for recurrent or persistent disease. Of disease-free patients with >or=1 year follow-up, 90% demonstrated normal or understandable speech. None required laryngectomy for complications. Among LVT4 patients, 4-year LRC, DFS, OS, and LFS was 71%, 65%, 56%, and 81%, respectively. Induction chemotherapy improved 4-year LRC (90% versus 46%, P = 0.03) and DFS (84% versus 42%, P = 0.03). CONCLUSIONS: Promising control and functional outcomes are achieved with TFHX for T4 laryngeal patients. LVT4 disease had outcomes similar to patients with less advanced disease treated on Radiation Therapy Oncology Group 91-11. Induction chemotherapy improved outcomes, warranting further investigation.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/radioterapia , Neoplasias Laríngeas/tratamento farmacológico , Neoplasias Laríngeas/radioterapia , Adulto , Idoso , Área Sob a Curva , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Terapia Combinada , Feminino , Fluoruracila/administração & dosagem , Seguimentos , Humanos , Hidroxiureia/administração & dosagem , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Neoplasias Laríngeas/mortalidade , Neoplasias Laríngeas/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Preservação de Órgãos/métodos , Paclitaxel/administração & dosagem , Probabilidade , Qualidade de Vida , Dosagem Radioterapêutica , Estudos Retrospectivos , Medição de Risco , Análise de Sobrevida , Resultado do Tratamento
12.
Phys Rev Lett ; 95(5): 052003, 2005 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-16090867

RESUMO

A high statistics measurement of the D(s)+ lifetime from the Fermilab fixed-target FOCUS photoproduction experiment is presented. We describe the analysis of the two decay modes, D(s)+ --> phi(1020)pi+ and D(s)+ -->K*(892)0K+, used for the measurement. The measured lifetime is 507.4 +/- 5.5(stat) +/- 5.1(syst) fs using 8961 +/- 105 D(s)+ --> phi(1020)pi+ and 4680 +/- 90 D(s)+ --> K*(892)0K+ decays. This is a significant improvement over the present world average.

13.
Ann Oncol ; 15(8): 1179-86, 2004 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-15277256

RESUMO

BACKGROUND: Locoregionally advanced, stage IV head and neck cancer has traditionally carried a poor prognosis. We sought to assess changes in patterns of failure, prognostic factors for recurrence, and overall outcome, using two different strategies of chemoradiotherapy conducted in prospective, multi-institutional phase II trials. PATIENTS AND METHODS: Three hundred and thirty-seven stage IV patients were treated from 1989 to 1998. We compared locoregional and distant recurrence rates, overall survival and progression-free survival from two different treatment strategies: intensive induction chemotherapy followed by split-course chemoradiotherapy (type 1, n=127), or intensified, split-course, hyperfractionated multiagent chemoradiotherapy alone (type 2, n=210). Univariate and multivariate analyses of 12 chosen covariates were assessed separately for the two study types. RESULTS: The pattern of failure varied greatly between study types 1 and 2 (5-year locoregional failure of 31% and 17% for study types 1 and 2, respectively, P=0.01; 5-year distant failure rate of 13% and 22% for study types 1 and 2, P=0.03). Combined 5-year overall survival was 47% [95% confidence interval (CI) 41% to 53%) and progression-free survival was 60% (95% CI 55% to 66%). Both treatment strategies yielded similar survival rates. Poor overall survival and distant recurrence were best predicted by advanced nodal stage. Locoregional recurrence was extremely rare for patients with T0-T3 tumor stage, regardless of lymph-node stage. CONCLUSIONS: This analysis suggests that pattern of failure in primary head and neck cancer may be dependent upon treatment strategy. Randomized clinical trials of induction chemotherapy are warranted as a means to determine if a decrease in distant metastases can lead to an increase in survival rates in the setting of effective chemoradiotherapy for locoregional control. Additionally, this analysis provides impetus for randomized clinical trials of organ preservation chemoradiotherapy in sites outside the larynx and hypopharynx.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/radioterapia , Adulto , Idoso , Ensaios Clínicos Fase II como Assunto , Terapia Combinada , Intervalo Livre de Doença , Fracionamento da Dose de Radiação , Feminino , Fluoruracila/administração & dosagem , Seguimentos , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Hidroxiureia/administração & dosagem , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Prognóstico , Estudos Prospectivos
14.
Ann Oncol ; 14(8): 1306-11, 2003 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12881397

RESUMO

BACKGROUND: Our aim was to explore the use of concurrent chemoradiotherapy in the management of patients with squamous cell carcinoma of the head and neck from an occult primary (HNCOP). PATIENTS AND METHODS: From 1991 to 2000, 25 patients with T0N2M0 or T0N3M0 HNCOP were entered into five sequential phase II clinical trials. Chemoradiotherapy consisted of a split course of radiotherapy with concurrent 5-fluorouracil and hydroxyurea either alone or with cisplatin, or paclitaxel. Two of the five protocols incorporated induction chemotherapy. RESULTS: Nodal stage was N2a in five patients (20%), N2b in 13 (52%), N2c in one (4%) and N3 in six (24%). Twenty-two patients (88%) underwent neck dissection; 14 of 22 patients underwent neck dissection before initiating protocol therapy. Total radiation doses of 55-75 Gy (median 60 Gy) were delivered; radiation fields included the potential sites of mucosal primaries and the neck bilaterally. Selected patients received a radiation boost to the involved neck. With a median follow-up of 3.9 years, three patients have progressed (one local, two distant) and seven patients have died. Deaths were due to disease progression (three) or unrelated causes (four). No metachronous primaries developed. The 5-year progression-free and overall survival was 87% and 75%, respectively. CONCLUSION: Combined-modality treatment with intensive chemoradiotherapy results in excellent disease control and long-term survival for patients with N2-N3 HNCOP and compares favorably with traditional therapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma de Células Escamosas/secundário , Carcinoma de Células Escamosas/terapia , Neoplasias de Cabeça e Pescoço/secundário , Neoplasias de Cabeça e Pescoço/terapia , Neoplasias Primárias Desconhecidas/patologia , Adolescente , Adulto , Idoso , Carcinoma de Células Escamosas/mortalidade , Terapia Combinada , Intervalo Livre de Doença , Feminino , Seguimentos , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Probabilidade , Doses de Radiação , Radioterapia Adjuvante , Medição de Risco , Análise de Sobrevida , Resultado do Tratamento
15.
J Clin Oncol ; 19(7): 1961-9, 2001 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-11283128

RESUMO

PURPOSE: To improve local disease control and survival with organ preservation, we conducted a phase II multi-institutional trial with a concomitant taxane-based chemotherapy and hyperfractionated radiation regimen. PATIENTS AND METHODS: Sixty-four patients with locally advanced squamous cancers (stage IV, 98%; N2/3, 81%) were treated on an intensive regimen consisting of 5-day (120-hour) infusions of paclitaxel (20 mg/m(2)/d) and fluorouracil (600 mg/m(2)/d), oral hydroxyurea 500 mg every 12 hours for 11 doses, and radiation 1.5 Gy bid (T-FH2X). Chemoradiation was administered concomitantly on days 1 to 5 of each 14-day cycle. A full treatment course consisted of five cycles during a 10-week period to a total radiation dose of 72 to 75 Gy. RESULTS: The median follow-up for the group is 34 months. At 3 years, progression-free survival is 63%, locoregional control is 86%, and systemic control is 79%; overall survival is 60%. Seventeen patients died of recurrent cancer, two died of second primary cancers, and four died of other causes. Side effects observed include anemia (22% required transfusion), leucopenia (34%, grade 3 to 4), and mucositis (84%, grade 3 to 4). Organ preservation principles were maintained. At 1 year posttreatment, 61% of patients had severe xerostomia and 47% had compromised swallowing. There was little disturbance of speech quality in 97% of patients at the same follow-up point. CONCLUSION: T-FH2X is a highly active and tolerable concomitant chemotherapy and hyperfractionated radiation regimen that induces sustained local tumor control and holds promise for improved survival with organ preservation in high-risk patients. Identification of less toxic therapy and improved distant disease control are needed. T-FH2X should be tested in a randomized trial and compared with a less intensive concomitant regimen that uses once-daily radiation fractionation.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/terapia , Neoplasias de Cabeça e Pescoço/terapia , Administração Oral , Adulto , Idoso , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/radioterapia , Terapia Combinada/efeitos adversos , Fracionamento da Dose de Radiação , Feminino , Fluoruracila/administração & dosagem , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Hidroxiureia/administração & dosagem , Illinois/epidemiologia , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Paclitaxel/administração & dosagem , Qualidade de Vida , Análise de Sobrevida
16.
Cancer J ; 7(2): 140-8, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11324767

RESUMO

PURPOSE: Locoregionally advanced oropharyngeal cancer has been conventionally treated with either surgery and adjuvant radiotherapy or radiotherapy alone, and clinical and functional outcomes have been poor. Chemoradiotherapy has been demonstrated to improve functional outcome and disease control over conventional treatment in recent randomized head and neck trials. Herein, we report overall survival, progression-free survival, and patterns of failure in locoregionally advanced oropharyngeal cancer treated with induction chemotherapy with or without conservative surgery followed by concomitant chemoradiation. MATERIALS AND METHODS: Three cycles of induction chemotherapy consisting of cisplatin, 5-fluorouracil, leucovorin, and interferon alpha-2b (PFL-IFN) were followed by conservative, organ-sparing surgery for residual disease. All patients then proceeded to concomitant chemoradiation consisting of seven or eight cycles of 5-fluorouracil, hydroxyurea, and a total radiotherapy dose of roughly 7,000 cGy. RESULTS: Sixty-one patients with predominantly stage IV disease were treated. Clinical complete response was observed in 65% of patients after induction therapy. The median follow-up was 68.0 months for survivors and 39.0 months for all patients. At 5 years, overall survival is 51%, progression-free survival is 64%, locoregional control is 70%, and distant control is 89%. Locoregional recurrence accounted for 80% of all initial failures. Only five radical surgeries (none were total glossectomy) were performed for initial disease control. Treatment-related toxicity accounted for four deaths. CONCLUSION: PFL-IFN given with 5-fluorouracil, hydroxyurea, and radiotherapy produces a high rate of cures with organ preservation in a disease group that has traditionally fared poorly. Local and distant disease control and survival rates exceed those observed with more standard treatment approaches involving surgery and radiotherapy. Further investigation into chemoradiotherapy as a curative modality for this disease is warranted.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/radioterapia , Terapia Neoadjuvante , Neoplasias Orofaríngeas/tratamento farmacológico , Neoplasias Orofaríngeas/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/secundário , Carcinoma de Células Escamosas/cirurgia , Cisplatino/administração & dosagem , Intervalo Livre de Doença , Esquema de Medicação , Feminino , Fluoruracila/administração & dosagem , Humanos , Hidroxiureia/administração & dosagem , Interferon alfa-2 , Interferon-alfa/administração & dosagem , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Neoplasias Orofaríngeas/mortalidade , Neoplasias Orofaríngeas/patologia , Neoplasias Orofaríngeas/cirurgia , Proteínas Recombinantes , Análise de Sobrevida , Resultado do Tratamento
17.
Midwifery ; 17(1): 2-10, 2001 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11207100

RESUMO

OBJECTIVE: to examine women's attitudes to being questioned by their midwife, during and after pregnancy, about exposure to violence. DESIGN: an explorative study using content analysis of one open-ended question. SETTING: all antenatal clinics in Uppsala, a medium-sized Swedish university town. PARTICIPANTS: all women registered for antenatal care before 32 weeks of pregnancy, during a period of 6 months. MEASUREMENTS: all women were assessed regarding abuse, using the Abuse Assessment Screen (McFarlane 1993) twice during pregnancy and once again more than four weeks after the birth. On the last occasion the women were asked to respond to an open-ended written question worded: 'Please describe how you felt about being questioned by your midwife at the antenatal clinic concerning violence' Those women who reported violence and those who did not were compared regarding their attitude to being asked about violence. FINDINGS: 879 women were presented with the open-ended question. Eighty per cent found the questioning acceptable, 12% neither acceptable nor unacceptable, 5% both acceptable and unacceptable, and only 3% found it unacceptable. There was no difference between those who reported abuse and those who did not, as to whether the questioning was unacceptable. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: the findings suggest that most pregnant women are not averse to being asked, by their midwife, about exposure to violence. As part of the identification of risk factors that is carried out in every pregnancy, the midwife should ask about exposure to violence at the antenatal clinic. To feel confident when raising the subject of abuse, midwives must be taught about the nature of intimate-partner violence, and appropriate referral and intervention strategies.


Assuntos
Atitude Frente a Saúde , Mulheres Maltratadas/psicologia , Relações Enfermeiro-Paciente , Maus-Tratos Conjugais/psicologia , Adulto , Feminino , Humanos , Bem-Estar Materno , Pesquisa Metodológica em Enfermagem , Gravidez , Cuidado Pré-Natal/métodos , Qualidade de Vida , Fatores de Risco , Inquéritos e Questionários/normas , Suécia
18.
J Psychosom Obstet Gynaecol ; 22(4): 189-97, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11840572

RESUMO

All women registered for antenatal care within a Swedish municipality during a 6-month period were assessed regarding acts of violence. The Abuse Assessment Screen was used on two occasions during pregnancy, and once between 4 and 20 weeks after delivery. The efficacy of repeated interviews was investigated, and characteristics of abused and non-abused women were compared. The participation rate was 93% (1038 women). Physical abuse by a close acquaintance or relative during or shortly after pregnancy was reported by 1.3%, and by 2.8% when the year preceding pregnancy was included. The lifetime prevalence of emotional, physical or sexual abuse was 19.4%. Repeated questioning increased the detection of abuse. Women abused during pregnancy reported more preceding ill-health and more elective abortions than non-abused women. Intervention against sexual violence has been on the political agenda in Sweden for several decades. Even so, physical abuse is a risk factor comparable in frequency to obstetric complications such as gestational diabetes and pre-eclampsia. Routines need to be established to make questioning about violence an integral part of the standardized screening for risk factors during pregnancy.


Assuntos
Programas de Rastreamento , Gravidez/estatística & dados numéricos , Maus-Tratos Conjugais/estatística & dados numéricos , Violência/estatística & dados numéricos , Aborto Induzido/estatística & dados numéricos , Adolescente , Adulto , Criança , Abuso Sexual na Infância/estatística & dados numéricos , Estudos Transversais , Feminino , Humanos , Incidência , Complicações na Gravidez/epidemiologia , Complicações na Gravidez/etiologia , Resultado da Gravidez , Cuidado Pré-Natal , Estupro/estatística & dados numéricos , Fatores de Risco
19.
Arch Otolaryngol Head Neck Surg ; 126(8): 950-6, 2000 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10922226

RESUMO

OBJECTIVES: To evaluate the necessity, technical feasibility, and complication rate of neck dissection performed on patients with head and neck cancer after 5 cycles of concomitant chemoradiotherapy (CRT) and to justify a selective neck dissection (SND) approach and define the optimal timing of post-CRT neck dissection. DESIGN AND SETTING: Retrospective analysis in an academic university medical center. PATIENTS: Sixty-nine eligible patients with advanced (stage III and IV) head and neck cancer who have undergone 1 of 4 CRT protocols. Patients ranged in age from 36 to 75 years, and surgical procedures were performed over a 4-year period. Follow-up ranged from 6 to 64 months. INTERVENTION: Neck dissection (most commonly unilateral SND) performed within 5 to 17 weeks after CRT completion. MAIN OUTCOME MEASURES: Complication rate and incidence of positive pathology (viable cancer) in pathologic neck dissection specimens. RESULTS: Seven (10%) of 69 patients developed wound healing complications, 4 (6%) of whom required surgical intervention for ultimate closure. There were no wound infections. Other complications occurred in 11 (16%) of 69 patients and included need for tracheotomy, nerve transection and paresis, and permanent hypocalcemia. Twenty-four (35%) of 69 patients revealed microscopic residual disease. Ten (50%) of 20 patients with N3 neck disease had positive pathology, whereas 14 (36%) of 39 patients with N2 disease had viable carcinoma in the dissection specimen (P =.09 by chi(2) analysis). There was no significant relation between radiologic complete response or partial response and residual microscopic cancer. In 1 patient, disease recurred in the neck after dissection. Mean follow-up time was 30.3 months. CONCLUSIONS: (1) Neck dissection for patients with N2 or greater neck disease after CRT is necessary to eradicate residual disease. (2) The complication rate of SND after CRT with hyperfractionated radiotherapy is low. (3) SNDs are technically feasible when performed within the "window" between the acute and chronic CRT injury (4-12 weeks). (4) SNDs, rather than more radical procedures, appear to be therapeutically appropriate in this group of patients because of the low incidence of disease recurrence in the neck.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias de Cabeça e Pescoço , Esvaziamento Cervical , Adulto , Idoso , Terapia Combinada , Estudos de Viabilidade , Feminino , Seguimentos , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/radioterapia , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Linfonodos/cirurgia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Doses de Radiação , Estudos Retrospectivos , Fatores de Tempo , Cicatrização
20.
Ann Oncol ; 11(6): 721-8, 2000 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10942062

RESUMO

BACKGROUND: Concomitant chemoradiotherapy is an effective treatment modality for advanced head and neck cancer, but improved regimens are needed. We sought to define the toxicities, recommended phase II dose, and outcome of a combination chemotherapy regimen with concomitant hyperfractionated radiotherapy in patients with poor prognosis cancers of the head and neck, including those having received prior curative intent radiotherapy. PATIENTS AND METHODS: From 1995 until 1997, 54 patients were treated, 25 of whom had received a prior full course of radiotherapy to the head and neck. Patients were treated with 5-fluorouracil (5-FU) 600 mg/m2/day continuous infusion x 5 days (days 1-5), hydroxyurea, 500 mg p.o. bid x 11 doses (days 1-6) and paclitaxel (60-150 mg/m2) by one-hour infusion on day 2 using a dose escalation strategy. Radiotherapy was given concomitantly on days 2-6, 150 cGy bid. Each of 4-5 cycles was delivered every other week. RESULTS: The MTD of paclitaxel was 100 mg/m2. The regimen was feasible; radiotherapy was delivered at a median of 7300 cGy and 83% of patients received > or = 80% planned dose intensity. Hematological toxicity, with granulocyte colony stimulating factor, was very mild. Dose limiting toxicities were mucositis and dermatitis. Despite poor prognosis, two-year survival was 45%. CONCLUSIONS: The recommended phase II dose of this regimen is 5-FU 600 mg/m2/day x 120 hours (days 1-5), hydroxyurea 500 mg p.o. b.i.d. x 11 doses (days 1-6), paclitaxel 100 mg/m2 over one hour on day 2, and radiotherapy 150 cGy b.i.d. days 2-6. Concomitant chemotherapy and re-irradiation was feasible on this protocol and resulted in long-term survival in patients without other curative intent options.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/radioterapia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Terapia Combinada , Feminino , Fluoruracila/administração & dosagem , Humanos , Hidroxiureia/administração & dosagem , Masculino , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Prognóstico , Proteínas Recombinantes
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