Assuntos
Aprovação de Drogas/legislação & jurisprudência , Descoberta de Drogas/legislação & jurisprudência , Apoio à Pesquisa como Assunto/legislação & jurisprudência , United States Food and Drug Administration/legislação & jurisprudência , Análise Custo-Benefício , Difusão de Inovações , Aprovação de Drogas/economia , Descoberta de Drogas/economia , Descoberta de Drogas/tendências , Previsões , Custos de Cuidados de Saúde/legislação & jurisprudência , História do Século XXI , Humanos , Formulação de Políticas , Apoio à Pesquisa como Assunto/economia , Apoio à Pesquisa como Assunto/tendências , Estados Unidos , United States Food and Drug Administration/economia , United States Food and Drug Administration/tendênciasAssuntos
Neoplasias/prevenção & controle , Estresse Psicológico/prevenção & controle , Pesquisa Biomédica/métodos , Pesquisa Biomédica/tendências , Causas de Morte , Tratamento Farmacológico/métodos , Tratamento Farmacológico/tendências , Humanos , Neoplasias/mortalidade , Neoplasias/psicologia , Dor/prevenção & controle , Dor/psicologia , Estresse Psicológico/psicologiaAssuntos
Asiático , Neoplasias/etnologia , Neoplasias/prevenção & controle , Feminino , Humanos , MasculinoRESUMO
The intersection of two noble endeavors - the scientists' quest to understand life itself and the physicians' dedication to relieve suffering and prolong life - came into sharp focus in 1971 with the United States National Cancer Act. This focus has led to an exponential expansion of our understanding of cancer at the genetic, molecular and cellular levels, and concomitant advances in our ability to disrupt the disease process through prevention, early detection and successful treatment. At the National Cancer Institute we are committed to capitalize on these achievements. A new era is now within our grasp, a time when no one suffers or dies as a result of cancer.
Assuntos
National Institutes of Health (U.S.)/organização & administração , Neoplasias , Animais , Biotecnologia/organização & administração , Biotecnologia/tendências , Institutos de Câncer/organização & administração , Quimioprevenção , Ensaios Clínicos como Assunto , Biologia Computacional/organização & administração , Avaliação Pré-Clínica de Medicamentos , Perfilação da Expressão Gênica , Objetivos , Humanos , Camundongos , Neoplasias/diagnóstico , Neoplasias/epidemiologia , Neoplasias/genética , Neoplasias/prevenção & controle , Neoplasias/terapia , Proteômica , Pesquisa/organização & administração , Estados UnidosRESUMO
BACKGROUND: Abnormal expression of key proteins of the apoptotic pathway has been associated with poor prognosis, although there have been few studies of these correlations in patients with prostate carcinoma who are treated with radiotherapy. The current study examined the association between expression levels of Ki-67, bcl-2, bax, and bcl-x in pretreatment biopsy specimens and patient outcome after definitive radiotherapy alone. METHODS: Archival pretreatment prostate biopsy tumor tissue was retrieved from 106 patients with Stage T1-T3 prostate carcinoma who were treated at the University of Texas M. D. Anderson Cancer Center with external beam radiotherapy between 1987 and 1993. Expression levels of Ki-67 (MIB-1 staining; n = 106 patients), bcl-2 (n = 77 patients), bax (n = 70 patients), and bcl-x (both long and short splice variants; n = 72 patients) were determined by immunohistochemical staining. The Ki-67 labeling index (Ki67-LI) was available for all patients and was derived from the percentage of Ki-67 positive cells. Biochemical failure after radiotherapy was defined as three consecutive rises in prostate specific antigen level on follow-up. The median follow-up was 62 months. RESULTS: High Ki67-LI (> 3.5%) expression was observed in 33% of patients, overexpression of bcl-2 was observed in 16% of patients, altered bax expression was observed in 23% of patients, and altered bcl-x expression was observed in 53% of patients. There was no correlation found between the biomarkers. Kaplan-Meier survival estimates of freedom from biochemical failure (bNED) and the log-rank test revealed significantly lower rates in association with high Ki67-LI, positive bcl-2, and altered bax staining. No correlation was observed between bcl-x staining and bNED. Cox proportional hazards multivariate analysis confirmed that bcl-2 and bax were independent of pretreatment PSA level, Gleason score, disease stage, and Ki67-LI in predicting bNED. CONCLUSIONS: Abnormalities in the expression levels of bcl-2 and bax were associated with increased failure after patients were treated for prostate carcinoma with external beam radiotherapy. These biomarkers appeared to be useful in categorizing patient risk further, beyond Ki-67 staining and conventional clinical prognostic factors.
Assuntos
Biomarcadores Tumorais/análise , Carcinoma/metabolismo , Carcinoma/radioterapia , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/radioterapia , Biópsia , Humanos , Imuno-Histoquímica , Antígeno Ki-67/análise , Masculino , Proteínas Proto-Oncogênicas/análise , Proteínas Proto-Oncogênicas c-bcl-2/análise , Fatores de Tempo , Resultado do Tratamento , Proteína X Associada a bcl-2 , Proteína bcl-XRESUMO
PURPOSE: A randomized radiotherapy dose escalation trial was undertaken between 1993 and 1998 to compare the efficacy of 70 vs. 78 Gy in controlling prostate cancer. METHODS AND MATERIALS: A total of 305 Stage T1-T3 patients were entered into the trial and, of these, 301 with a median follow-up of 60 months, were assessable. Of the 301 patients, 150 were in the 70 Gy arm and 151 were in the 78 Gy arm. The primary end point was freedom from failure (FFF), including biochemical failure, which was defined as 3 rises in the prostate-specific antigen (PSA) level. Kaplan-Meier survival analyses were calculated from the completion of radiotherapy. The log-rank test was used to compare the groups. Cox proportional hazard regression analysis was used to examine the independence of study randomization in multivariate analysis. RESULTS: There was an even distribution of patients by randomization arm and stage, Gleason score, and pretreatment PSA level. The FFF rates for the 70- and 78 Gy arms at 6 years were 64% and 70%, respectively (p = 0.03). Dose escalation to 78 Gy preferentially benefited those with a pretreatment PSA >10 ng/mL; the FFF rate was 62% for the 78 Gy arm vs. 43% for those who received 70 Gy (p = 0.01). For patients with a pretreatment PSA
Assuntos
Neoplasias da Próstata/radioterapia , Idoso , Relação Dose-Resposta à Radiação , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , Antígeno Prostático Específico/sangue , Fatores de Tempo , Resultado do TratamentoRESUMO
PURPOSE: To determine the long-term disease-specific survival (DSS) and disease-free survival (DFS) rates after salvage cryotherapy for locally recurrent adenocarcinoma of the prostate and to identify pretreatment factors that have an impact on DSS and DFS. PATIENTS AND METHODS: Between July 1992 and January 1995, 131 patients who had received definitive radiation therapy (XRT) underwent salvage cryotherapy for locally recurrent adenocarcinoma of the prostate. Cryotherapy failure was defined as an increasing postcryotherapy prostate-specific antigen (PSA) level of > or = 2 ng/mL above the postcryotherapy nadir, a positive prostate biopsy, or radiographic evidence of metastatic disease. Clinical variables were studied to determine whether there was an association with the DSS and DFS. RESULTS: The median follow-up was 4.8 years. The 5-year DSS rates were 87% for patients with a precryotherapy Gleason score < or = 8 and 63% for those with Gleason scores of 9 and 10 (P =.012). The 5-year DFS rates were 57% for patients with a precryotherapy PSA level of < or = 10 ng/mL and 23% for those with a PSA level greater than 10 ng/mL (P =.0004). The 5-year DSS rates for patients with a pre-XRT clinical stage of T1 to T2 and those with a clinical stage of T3 to T4 were 94% and 72%, respectively (P =.0041). The 5-year DFS rates for these groups were 90% and 69%, respectively (P =.0057). CONCLUSION: Androgen-independent local recurrences, Gleason score, and pre-XRT clinical stage were important factors that had an impact on DSS and DFS. The subset of patients cured by salvage cryotherapy seems to be small, and patient selection is important.
Assuntos
Adenocarcinoma/terapia , Crioterapia , Recidiva Local de Neoplasia/terapia , Neoplasias da Próstata/terapia , Terapia de Salvação , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adenocarcinoma/radioterapia , Intervalo Livre de Doença , Humanos , Masculino , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Neoplasias da Próstata/radioterapia , Estudos Retrospectivos , Taxa de SobrevidaAssuntos
Neoplasias da Mama/diagnóstico por imagem , Mamografia/normas , Programas de Rastreamento/normas , Guias de Prática Clínica como Assunto , Adulto , Fatores Etários , Idoso , Feminino , Política de Saúde , Humanos , Pessoa de Meia-Idade , National Institutes of Health (U.S.) , Estados UnidosRESUMO
PURPOSE: To determine the significance of Ki-67/MIB1 staining as a marker of patient outcome for prostate cancer patients treated with radiotherapy. EXPERIMENTAL DESIGN: Pretreatment archival prostate biopsy tumor tissue was available from 106 stage T1-T4 prostate cancer patients treated with external beam radiotherapy between 1987 and 1993 at M. D. Anderson Cancer Center. Diagnosis was made from prostate needle biopsy in 64 cases and from transurethral resection of the prostate (TURP) in 42 cases. All patients had a pretreatment prostate-specific antigen (PSA), and no patient had evidence of metastasis. Immunohistochemical staining for MIB1 was used to determine the percentage of Ki-67-positive tumor cells, the Ki-67 labeling index (Ki67-LI). Biochemical failure after radiotherapy was defined as three rises in PSA on follow-up. Median follow-up was 62 months. RESULTS: The mean and median Ki67-LI for the entire cohort was 3.2 and 2.3. The mean and median Ki67-LIs for those diagnosed by needle biopsy were 3.2 and 2.3, and by TURP were 3.1 and 2.4. For all patients, mean Ki67-LI levels were significantly higher with stage T3/T4 disease, Gleason 7-10 disease, and in those that developed treatment failure. Similar relationships were observed when the Ki67-LI was dichotomized into low (< or =3.5%) and high (>3.5%) groups. Actuarial freedom from biochemical failure (bNED) when Ki67-LI was low and high was 76 and 33% at 5 years (P < 0.0001, log rank). Similar statistically significant differences were observed when the TURP and needle biopsy groups were analyzed separately. Cox proportional hazards regression showed that dichotomized Ki67-LI was an independent correlate of bNED, along with pretreatment PSA, Gleason score, and clinical stage. CONCLUSIONS: The Ki67-LI obtained from pretreatment prostate cancer tissue is a strong independent predictor of failure after radiotherapy using biochemical criteria. This prognostic factor was equally valuable for patients diagnosed by TURP or needle biopsy.
Assuntos
Antígeno Ki-67/análise , Neoplasias da Próstata/patologia , Biomarcadores Tumorais/análise , Estudos de Coortes , Humanos , Imuno-Histoquímica , Masculino , Análise Multivariada , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Antígeno Prostático Específico/análise , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/radioterapia , Análise de Sobrevida , Fatores de TempoAssuntos
Educação de Pacientes como Assunto , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/prevenção & controle , American Cancer Society , Aconselhamento , Medicina de Família e Comunidade , Humanos , Masculino , Programas de Rastreamento/métodos , Programas de Rastreamento/normas , Guias de Prática Clínica como Assunto , Estados UnidosRESUMO
Each year the American Cancer Society publishes a summary of existing recommendations for early cancer detection, including updates, and/or emerging issues that are relevant to screening for cancer. In last year's article, the guidelines regarding screening for the early detection of prostate, colorectal, and endometrial cancers were updated, as was the narrative pertaining to testing for early lung cancer detection. Although none of the ACS's guidelines were updated in 2001, work is proceeding on an update of screening recommendations for breast and cervical cancer and an update of these guidelines will be announced in the January/February 2003 issue of CA. As in previous issues, we review recommendations for the "cancer-related check-up," in which clinical encounters provide case-finding and health counseling opportunities. Finally, we provide an update of the most recent data pertaining to participation rates in cancer screening by age, gender, and ethnicity from the Centers for Disease Control and Prevention's Behavioral Risk Factor Surveillance System (BRFSS) and National Health Interview Survey (NHIS).