Asunto(s)
Azatioprina/administración & dosificación , Enfermedades de la Coroides , Ciclofosfamida/administración & dosificación , Metilprednisolona/administración & dosificación , Enfermedad Mixta del Tejido Conjuntivo , Arteria Retiniana/diagnóstico por imagen , Vasculitis Retiniana , Vena Retiniana/diagnóstico por imagen , Adolescente , Anticuerpos Antinucleares/sangre , Enfermedades de la Coroides/diagnóstico , Enfermedades de la Coroides/etiología , Enfermedades de la Coroides/terapia , Técnicas de Diagnóstico Oftalmológico , Femenino , Humanos , Inmunosupresores/administración & dosificación , Angiografía por Resonancia Magnética/métodos , Enfermedad Mixta del Tejido Conjuntivo/sangre , Enfermedad Mixta del Tejido Conjuntivo/diagnóstico , Enfermedad Mixta del Tejido Conjuntivo/tratamiento farmacológico , Enfermedad Mixta del Tejido Conjuntivo/fisiopatología , Vasculitis Retiniana/diagnóstico , Vasculitis Retiniana/etiología , Vasculitis Retiniana/fisiopatología , Vasculitis Retiniana/terapia , Resultado del Tratamiento , Agudeza VisualRESUMEN
PURPOSE: To report the outcomes of survival, local control, visual acuity, and eye retention in patients treated with repeat episcleral plaque brachytherapy (EPBT) for locally recurrent posterior uveal melanoma (PUM). DESIGN: Retrospective, interventional case series. METHODS: Setting: Institutional. PATIENT POPULATION: A total of 1201 patients that underwent iodine-125 (I-125) EPBT as primary treatment for PUM between 1985 and 2015. INCLUSION CRITERIA: Development of locally recurrent disease and retreatment with I-125 EPBT. OBSERVATION PROCEDURES: Clinical records review. MAIN OUTCOME MEASURES: Visual acuity, Kaplan-Meier estimates of survival, local control, metastasis, and loss of the eye over the duration of follow-up. RESULTS: Twenty-seven patients (13 men) met our inclusion criteria. Median (range) follow-up from initial treatment was 100 months (14-365 months), while median time to local recurrence was 43 months (9-185 months). Median (range) follow-up after retreatment was 47 months (3-120 months). Kaplan-Meier estimate for local control at 5 years was 77.2% (95% confidence interval [CI], 53.29%-89.91%). All marginal recurrences were successfully retreated whereas 6 of 15 patients with central recurrence developed subsequent re-recurrence following salvage EPBT. Median (range) visual acuity was 20/70 (20/20 to counting fingers at 1 foot) at time of recurrence and declined to counting fingers (20/25 to hand motion) at the most recent follow-up examination. Kaplan-Meier estimate for absence of metastatic disease at 5 years was 78.5% (95% CI, 54.77%-90.70%). CONCLUSIONS: Repeat I-125 EPBT offers a viable alternative to enucleation in patients with local recurrence of PUM, yielding high rates of local control with predictable decline in visual acuity.
Asunto(s)
Braquiterapia/métodos , Melanoma/radioterapia , Neoplasias de la Úvea/radioterapia , Adulto , Anciano , Anciano de 80 o más Años , Relación Dosis-Respuesta en la Radiación , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Radioisótopos de Yodo/uso terapéutico , Estimación de Kaplan-Meier , Masculino , Melanoma/diagnóstico , Melanoma/mortalidad , Persona de Mediana Edad , Recurrencia Local de Neoplasia/epidemiología , Estadificación de Neoplasias , Estudios Retrospectivos , Esclerótica , Tasa de Supervivencia/tendencias , Tennessee/epidemiología , Factores de Tiempo , Resultado del Tratamiento , Úvea/diagnóstico por imagen , Neoplasias de la Úvea/diagnóstico , Neoplasias de la Úvea/mortalidad , Agudeza VisualRESUMEN
Topotecan is a substrate of the ATP-binding cassette transporters P-glycoprotein (P-gp/MDR1) and breast cancer resistance protein (BCRP). To define the role of these transporters in topotecan penetration into the ventricular cerebrospinal fluid (vCSF) and brain parenchymal extracellular fluid (ECF) compartments, we performed intracerebral microdialysis on transporter-deficient mice after an intravenous dose of topotecan (4 mg/kg). vCSF penetration of unbound topotecan lactone was measured as the ratio of vCSF-to-plasma area under the concentration-time curves. The mean +/- SD ratios for wild-type, Mdr1a/b(-/-), Bcrp1(-/-), and Mdr1a/b(-/-)Bcrp1(-/-) mice were 3.07 +/- 0.09, 2.57 +/- 0.17, 1.63 +/- 0.12, and 0.86 +/- 0.05, respectively. In contrast, the ECF-to-plasma ratios for wild-type, Bcrp1(-/-), and Mdr1a/b(-/-)Bcrp1(-/-) mice were 0.36 +/- 0.06, 0.42 +/- 0.06, and 0.88 +/- 0.07. Topotecan lactone was below detectable limits in the ECF of Mdr1a/b(-/-) mice. When gefitinib (200 mg/kg) was preadministered to inhibit Bcrp1 and P-gp, the vCSF-to-plasma ratio decreased to 1.29 +/- 0.09 in wild-type mice and increased to 1.13 +/- 0.13 in Mdr1a/b(-/-)Bcrp1(-/-) mice, whereas the ECF-to-plasma ratio increased to 0.74 +/- 0.14 in wild-type and 1.07 +/- 0.03 in Mdr1a/b(-/-)Bcrp1(-/-) mice. Preferential active transport of topotecan lactone over topotecan carboxylate was shown in vivo by vCSF lactone-to-carboxylate area under the curve ratios for wild-type, Mdr1a/b(-/-), Bcrp1(-/-), and Mdr1a/b(-/-)Bcrp1(-/-) mice of 5.69 +/- 0.83, 3.85 +/- 0.64, 3.61 +/- 0.46, and 0.78 +/- 0.19, respectively. Our results suggest that Bcrp1 and P-gp transport topotecan into vCSF and out of brain parenchyma through the blood-brain barrier. These findings may help to improve pharmacologic strategies to treat brain tumors.