RESUMEN
PURPOSE: Our objective was to determine how positron emission tomography (PET)/CT had been used in the clinical treatment of malignant peripheral nerve sheath tumor (MPNST) patients at The University of Texas MD Anderson Cancer Center. METHODS: We reviewed a database of MPNST patients referred to MD Anderson Cancer Center during 1995-2011. We enrolled 47 patients who underwent PET/CT imaging. Disease stage was based on conventional imaging and PET/CT findings using National Comprehensive Cancer Network (NCCN) guidelines. Treatment strategies based on PET/CT and conventional imaging were determined by chart review. The maximum and mean standardized uptake values (SUVmax, SUVmean), metabolic tumor volume (MTV), total lesion glycolysis (TLG), change in SUVmax, change in MTV, and change in TLG were calculated from the PET/CT studies before and after treatment. Response prediction was based on imaging studies performed before and after therapy and categorized as positive or negative for residual tumor. Clinical outcome was determined from chart review. RESULTS: PET/CT was performed for staging in 16 patients, for restaging in 29 patients, and for surveillance in 2 patients. Of the patients, 88 % were correctly staged with PET/CT, whereas 75 % were correctly staged with conventional imaging. The sensitivity to detect local recurrence and distant metastasis at restaging was 100 and 100 % for PET/CT compared to 86 and 83 % for conventional imaging, respectively. PET/CT findings resulted in treatment changes in 31 % (5/16) and 14 % (4/29) of patients at staging and restaging, respectively. Recurrence, MTV, and TLG were prognostic factors for survival, whereas SUVmax and SUVmean were not predictive. For 21 patients who had imaging studies performed both before and after treatment, PET/CT was better at predicting outcome (overall survival, progression-free survival) than conventional imaging. A decreasing SUVmax ≥ 30 % and decrease in TLG and MTV were significant predictors for overall and progression-free survival. CONCLUSION: PET/CT is valuable in MPNST management because of its high accuracy in staging and high sensitivity and accuracy in restaging as well as improvements in treatment planning. MTV from baseline staging studies is predictive of survival. Additionally, change in SUVmax, TLG, and MTV accurately predicted outcomes after treatment.
Asunto(s)
Fluorodesoxiglucosa F18 , Imagen Multimodal , Neurilemoma/diagnóstico , Neurilemoma/terapia , Tomografía de Emisión de Positrones , Tomografía Computarizada por Rayos X , Adolescente , Adulto , Anciano , Niño , Femenino , Glucólisis , Humanos , Masculino , Persona de Mediana Edad , Neurilemoma/metabolismo , Neurilemoma/patología , Estudios Retrospectivos , Sensibilidad y Especificidad , Resultado del Tratamiento , Carga Tumoral , Adulto JovenRESUMEN
Neurofibromatosis type 2 (NF2) is a genetic condition characterized by inactivation of the NF2 tumor suppressor gene and the development of schwannomas. The NF2 gene product, merlin, is activated (dephosphorylated) by contact inhibition and promotes growth suppression. We investigated the effect of curcumin (diferuloylmethane), a molecule with anti-inflammatory and antitumorigenic properties, on human schwannoma cell growth and the regulation of merlin by curcumin in both NF2 cells and neuroblastoma (non-NF2) cells. Curcumin inhibited the growth of HEI-193 schwannoma cells in vitro and downregulated the phosphorylation of Akt and extracellular signal-regulated kinase 1/2. Curcumin also activated MYPT1-pp1δ (a merlin phosphatase), which was associated with dephosphorylation of merlin on serine 518, an event that results in the folding of merlin to its active conformation. In addition, curcumin induced apoptosis and generated reactive oxygen species in HEI-193 cells. Consequently, hsp70 was upregulated at the mRNA and protein levels, possibly serving as a mechanism of escape from curcumin-induced apoptosis and growth inhibition. Endogenous merlin and hsp70 proteins interacted in HEI-193 schwannoma and SK-N-AS neuroblastoma cells. The combination of curcumin and an hsp inhibitor synergistically suppressed schwannoma cell growth. Our results provide a rationale for combining curcumin and KNK437 in the treatment of NF2.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Compuestos de Bencidrilo/farmacología , Curcumina/farmacología , Proteínas de Choque Térmico/antagonistas & inhibidores , Neurofibromatosis 2/tratamiento farmacológico , Pirrolidinonas/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Apoptosis/efectos de los fármacos , Compuestos de Bencidrilo/uso terapéutico , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Curcumina/uso terapéutico , Resistencia a Antineoplásicos/genética , Sinergismo Farmacológico , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Proteínas del Choque Térmico HSP72/genética , Proteínas del Choque Térmico HSP72/metabolismo , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Humanos , Fosfatasa de Miosina de Cadena Ligera/metabolismo , Neurofibromatosis 2/genética , Neurofibromatosis 2/metabolismo , Neurofibromina 2/metabolismo , Fosforilación , Unión Proteica , Pirrolidinonas/uso terapéutico , Transducción de Señal/efectos de los fármacos , Regulación hacia Arriba/efectos de los fármacosRESUMEN
Although clinical syndromes of visual-spatial neglect have been well described in adults, clinical features of neglect associated with subcortical dysfunction are infrequently reported in children and have not been described in detail. Unilateral visual-spatial neglect in a 7-year-old male following removal of a right subcortical juvenile pilocytic astrocytoma is reported. Preoperative baseline neurocognitive assessment of the patient established intact attentional and intellectual functioning. Postoperatively visual-spatial neglect was observed that was not accounted for by the patient's visual field deficit. Consistent with classic features of attentional neglect, increases in attentional demands led to greater errors in performance. The risk of unilateral neglect following resection of subcortical tumors that abut the thalamus or disrupt thalamo-cortical projections was confirmed in a retrospective analysis of patients referred for neurocognitive testing at our site. It was concluded that the ventral thalamus may play a role in visual-spatial attention early in development.