RESUMO
PURPOSE: To evaluate the treatment outcomes of low-dose whole brain radiation therapy (WBRT)-based differential radiation therapy (RT) for metastatic brain tumors. METHODS: A total of 242 targets (metastatic brain lesions) were analyzed in the present study. Median WBRT dose and number of fractions were 25 (range 25-35) Gy and 10 (range 8-15) fractions, respectively. A median normalized total dose (NTD) of 1.8 Gy (NTD(1.8Gy)) to the metastatic lesion was 45 (range 27-64.8) Gy. We numbered and contoured each metastatic lesion sequentially using computed tomography fused with serial magnetic resonance imaging to evaluate volumetric changes. RESULTS: The 6-month and 1-year freedom from remote intracranial failure rates were 87.7 and 58.5 %, respectively. The 6-month actuarial local control (LC) rate was 93.4 %. Tumor diameter was a major determinant for LC, and tumor histology was a significant parameter predicting the volume reduction rate. With overall complete response (CR) rate of 56.6 % after RT, CR rate, if the target was more than 1 cm in size, was 25 % with a median NTD(1.8Gy) of 45 Gy, requiring dose escalation to achieve better target regression. CONCLUSIONS: Low-dose WBRT with selective boost was feasible and effective. Our results pose the rationale of future trial of differential radiation therapy (RT), which prescribes different radiation dose according to the tumor density in metastatic brain tumors.
Assuntos
Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundário , Irradiação Craniana , Fracionamento da Dose de Radiação , Neoplasias/radioterapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/mortalidade , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias/mortalidade , Neoplasias/patologia , Estudos Retrospectivos , Taxa de Sobrevida , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Adulto JovemRESUMO
Everolimus allows calcineurin-inhibitor reduction without loss of efficacy and may improve renal-transplant outcomes. In a 24-month, open-label study, 833 de novo renal-transplant recipients were randomized to everolimus 1.5 or 3.0 mg/day (target troughs 3-8 and 6-12 ng/mL, respectively) with reduced-exposure CsA, or mycophenolic acid (MPA) 1.44 g/day plus standard-exposure CsA. Patients received basiliximab +/- corticosteroids. The primary endpoint was composite efficacy failure (treated biopsy-proven acute rejection, graft loss, death or loss to follow-up) and the main safety endpoint was renal function (estimated glomerular filtration rate [eGFR], by Modification of Diet in Renal Disease [MDRD]) at Month 12 (last-observation-carried-forward analyses). Month 12 efficacy failure rates were noninferior in the everolimus 1.5 mg (25.3%) and 3.0 mg (21.9%) versus MPA (24.2%) groups. Mean eGFR at Month 12 was noninferior in the everolimus groups versus the MPA group (54.6 and 51.3 vs 52.2 mL/min/1.73 m(2) in the everolimus 1.5 mg, 3.0 mg and MPA groups, respectively; 95% confidence intervals for everolimus 1.5 mg and 3.0 mg vs MPA: -1.7, 6.4 and -5.0, 3.2, respectively). The overall incidence of adverse events was comparable between groups. The use of everolimus with progressive reduction in CsA exposure, up to 60% at 1 year, resulted in similar efficacy and renal function compared with standard-exposure CsA plus MPA.
Assuntos
Transplante de Rim/métodos , Ácido Micofenólico/administração & dosagem , Corticosteroides , Adulto , Anticorpos Monoclonais , Basiliximab , Biópsia , Inibidores Enzimáticos , Everolimo , Feminino , Humanos , Imunossupressores/farmacologia , Rim/efeitos dos fármacos , Rim/patologia , Rim/fisiopatologia , Testes de Função Renal , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/uso terapêutico , Proteínas Recombinantes de Fusão , Segurança , Sirolimo/efeitos adversos , Sirolimo/análogos & derivados , Resultado do TratamentoRESUMO
Over the last decades, the incidence of ultraviolet B (UVB)-related skin problems has been increasing. Damages induced by UVB radiation are related to mutations that occur as a result of direct DNA damage and/or the production of reactive oxygen species. We investigated the anti-oxidant effects of a Polygonum multiflorum thumb extract against skin damage induced by UVB irradiation. Female SKH-1 hairless mice were divided into three groups: control (N = 7), distilled water- (N = 10), and P. multiflorum extract-treated (PM, N = 10) groups. The PM (10 g) was extracted with 100 mL distilled water, cryo-dried and 9.8 g was obtained. The animals received a topical application of 500 microL distilled water or PM extract (1, 2, 4, 8, and 16%, w/v, dissolved in distilled water) for 30 min after UVB irradiation (wavelength 280-320 nm, 300 mJ/cm(2); 3 min) of the dorsal kin for 14 days, and skin immunohistochemistry and Cu,Zn-superoxide dismutase (SOD1) activity were determined. SOD1 immunoreactivity, its protein levels and activities in the skin were significantly reduced by 70% in the distilled water-treated group after UVB irradiation compared to control. However, in the PM extract-treated groups, SOD1 immunoreactivity and its protein and activity levels increased in a dose-dependent manner (1-16%, w/v, PM extract) compared to the distilled water-treated group. SOD1 protein levels and activities in the groups treated with 8 and 16%, w/v, PM extract recovered to 80-90% of the control group levels after UVB. These results suggest that PM extract strongly inhibits the destruction of SOD1 by UV radiation and probably contains anti-skin photoaging agents.
Assuntos
Antioxidantes/uso terapêutico , Polygonum/química , Lesões Experimentais por Radiação/prevenção & controle , Pele/efeitos da radiação , Superóxido Dismutase/metabolismo , Raios Ultravioleta/efeitos adversos , Administração Tópica , Animais , Western Blotting , Feminino , Camundongos , Camundongos Pelados , Extratos Vegetais/uso terapêutico , Lesões Experimentais por Radiação/metabolismo , Superóxido Dismutase-1RESUMO
Over the last decades, the incidence of ultraviolet B (UVB)-related skin problems has been increasing. Damages induced by UVB radiation are related to mutations that occur as a result of direct DNA damage and/or the production of reactive oxygen species. We investigated the anti-oxidant effects of a Polygonum multiflorum thumb extract against skin damage induced by UVB irradiation. Female SKH-1 hairless mice were divided into three groups: control (N = 7), distilled water- (N = 10), and P. multiflorum extract-treated (PM, N = 10) groups. The PM (10 g) was extracted with 100 mL distilled water, cryo-dried and 9.8 g was obtained. The animals received a topical application of 500 æL distilled water or PM extract (1, 2, 4, 8, and 16 percent, w/v, dissolved in distilled water) for 30 min after UVB irradiation (wavelength 280-320 nm, 300 mJ/cm²; 3 min) of the dorsal kin for 14 days, and skin immunohistochemistry and Cu,Zn-superoxide dismutase (SOD1) activity were determined. SOD1 immunoreactivity, its protein levels and activities in the skin were significantly reduced by 70 percent in the distilled water-treated group after UVB irradiation compared to control. However, in the PM extract-treated groups, SOD1 immunoreactivity and its protein and activity levels increased in a dose-dependent manner (1-16 percent, w/v, PM extract) compared to the distilled water-treated group. SOD1 protein levels and activities in the groups treated with 8 and 16 percent, w/v, PM extract recovered to 80-90 percent of the control group levels after UVB. These results suggest that PM extract strongly inhibits the destruction of SOD1 by UV radiation and probably contains anti-skin photoaging agents.