RESUMEN
These NCCN Guidelines Insights focus on some of the major updates to the 2014 NCCN Guidelines for Thyroid Carcinoma. Kinase inhibitor therapy may be used to treat thyroid carcinoma that is symptomatic and/or progressive and not amenable to treatment with radioactive iodine. Sorafenib may be considered for select patients with metastatic differentiated thyroid carcinoma, whereas vandetanib or cabozantinib may be recommended for select patients with metastatic medullary thyroid carcinoma. Other kinase inhibitors may be considered for select patients with either type of thyroid carcinoma. A new section on "Principles of Kinase Inhibitor Therapy in Advanced Thyroid Cancer" was added to the NCCN Guidelines to assist with using these novel targeted agents.
Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéutico , Neoplasias de la Tiroides/tratamiento farmacológico , Adenocarcinoma/patología , Anilidas/uso terapéutico , Carcinoma Neuroendocrino , Guías como Asunto , Humanos , Metástasis de la Neoplasia , Niacinamida/análogos & derivados , Niacinamida/uso terapéutico , Compuestos de Fenilurea/uso terapéutico , Piridinas/uso terapéutico , Sorafenib , Neoplasias de la Tiroides/patologíaRESUMEN
PURPOSE: Mutations in the RET proto-oncogene and vascular endothelial growth factor receptor (VEGFR) activity are critical in the pathogenesis of medullary thyroid cancer (MTC). Sorafenib, a multikinase inhibitor targeting Ret and VEGFR, showed antitumor activity in preclinical studies of MTC. PATIENTS AND METHODS: In this phase II trial of sorafenib in patients with advanced MTC, the primary end point was objective response. Secondary end points included toxicity assessment and response correlation with tumor markers, functional imaging, and RET mutations. Using a two-stage design, 16 or 25 patients were to be enrolled onto arms A (hereditary) and B (sporadic). Patients received sorafenib 400 mg orally twice daily. RESULTS: Of 16 patients treated in arm B, one achieved partial response (PR; 6.3%; 95% CI, 0.2% to 30.2%), 14 had stable disease (SD; 87.5%; 95% CI, 61.7% to 99.5%), and one was nonevaluable. In a post hoc analysis of 10 arm B patients with progressive disease (PD) before study, one patient had PR of 21+ months, four patients had SD >or= 15 months, four patients had SD Asunto(s)
Bencenosulfonatos/uso terapéutico
, Carcinoma Medular/tratamiento farmacológico
, Inhibidores de Proteínas Quinasas/uso terapéutico
, Piridinas/uso terapéutico
, Neoplasias de la Tiroides/tratamiento farmacológico
, Administración Oral
, Adulto
, Anciano
, Bencenosulfonatos/administración & dosificación
, Bencenosulfonatos/efectos adversos
, Biomarcadores de Tumor/metabolismo
, Carcinoma Medular/enzimología
, Carcinoma Medular/genética
, Carcinoma Medular/mortalidad
, Carcinoma Medular/secundario
, Supervivencia sin Enfermedad
, Femenino
, Humanos
, Estimación de Kaplan-Meier
, Imagen por Resonancia Magnética
, Masculino
, Persona de Mediana Edad
, Mutación
, Niacinamida/análogos & derivados
, Compuestos de Fenilurea
, Tomografía de Emisión de Positrones
, Inhibidores de Proteínas Quinasas/administración & dosificación
, Inhibidores de Proteínas Quinasas/efectos adversos
, Proto-Oncogenes Mas
, Proteínas Proto-Oncogénicas c-ret/antagonistas & inhibidores
, Proteínas Proto-Oncogénicas c-ret/genética
, Piridinas/administración & dosificación
, Piridinas/efectos adversos
, Receptores de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores
, Sorafenib
, Neoplasias de la Tiroides/enzimología
, Neoplasias de la Tiroides/genética
, Neoplasias de la Tiroides/mortalidad
, Neoplasias de la Tiroides/patología
, Factores de Tiempo
, Tomografía Computarizada por Rayos X
, Resultado del Tratamiento
, Estados Unidos
, Adulto Joven
RESUMEN
BACKGROUND: The functional results of cryopreserved heterotopic parathyroid autotransplantation (CHPA) are not well defined. The authors evaluated the outcomes of delayed CHPA for the treatment of surgically induced hypoparathyroidism. METHODS: Since November 1991, 448 parathyroid samples from 436 patients were cryopreserved at our institution. Of these, 29 patients underwent 34 CHPA procedures, with placement of 20 to 25 pieces of parathyroid tissue (approximately 50 to 75 mg) into the forearm. Outcomes were determined based on peripheral parathyroid hormone (PTH) levels and, where available, PTH gradients between grafted and nongrafted arms. Graft function results were defined as completely functional (patients with normal PTH and calcium levels off all calcium/vitamin D supplementation), partially functional (normal PTH levels and mild hypocalcemia on calcium supplementation), or nonfunctional (low PTH levels and dependent on calcium/vitamin D supplementation). RESULTS: Of the 29 patients with CHPA, prospective data were available for 26 patients undergoing 30 CHPA procedures (9 patients with MEN 1, 4 with MEN 2A, 1 with MEN 2B, and 12 with sporadic hyperparathyroidism). The mean follow-up interval was 2 years. Twelve of 26 patients (46%) had completely functional grafts, 6 patients (23%) had partially functional grafts, and the remaining 8 patients (31%) had nonfunctional grafts. No patient with CHPA had graft-dependent recurrent hyperparathyroidism. Of the 14 patients (15 autografts) with MEN, 7 patients (50%) had fully functional grafts, and 2 patients (14%) had partially functional grafts. The mean cryopreservation period was 7.9 months (range, 1 week to 22 months) for functional autografts and 15.3 months (range, 2 weeks to 106 months) for nonfunctional autografts (P < .01). CONCLUSIONS: Based on these data and those in previous studies, approximately 60% of delayed, cryopreserved parathyroid autografts are functional. In this study 40% autografts (46% of patients) achieved full competency off supplements. Some patients have evidence of graft function with normal PTH levels but are not normocalcemic. Results were similar for patients with MEN and nonhereditary hyperparathyroidism. The duration of cryopreservation was a significant indicator of graft failure, and no functional autograft was observed beyond 22 months of preservation. CHPA is a useful treatment modality for patients with postoperative hypocalcemia after thyroid or parathyroid surgery, who do not respond to immediate parathyroid autotransplantation.
Asunto(s)
Criopreservación , Hipoparatiroidismo/cirugía , Glándulas Paratiroides/fisiopatología , Glándulas Paratiroides/trasplante , Recuperación de la Función/fisiología , Trasplante Heterotópico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Hipoparatiroidismo/sangre , Masculino , Persona de Mediana Edad , Músculo Esquelético , Hormona Paratiroidea/sangre , Estudios Prospectivos , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Minimally invasive parathyroidectomy (MIP) using local/regional anesthesia has become an accepted treatment for selected patients with primary hyperparathyroidism (HPT) and can be performed in the ambulatory setting. METHODS: From 1999 to 2004, 139 consecutive patients at our institution with HPT caused by a single localized parathyroid adenoma underwent MIP through a 2.5- to 3-cm incision. Anesthesia included preoperative local/regional blocks with moderate intravenous sedation. Patient follow-up data were reviewed retrospectively. RESULTS: All 139 MIP patients had biochemical HPT and a single adenoma localized by sestamibi scan alone (n = 119; 86%) or combined with other imaging (n = 20; 14%). The mean adenoma size was 1,184 +/- 1,091 mg. Total calcium and parathyroid hormone levels were 11.3 +/- 0.8 mg/dL and 451 pg/mL preoperatively, respectively, decreasing to 9.4 +/- 0.6 mg/dL and 34 pg/mL postoperatively, respectively. Of MIP cases, 117 (84%) were completed with local/regional anesthesia, and 22 (16%) used general anesthesia (4 local/regional conversions). The mean operative time when reported was 56 +/- 21 minutes (n = 28). Same-day discharges occurred for 120 (86%) patients, whereas 16 patients were observed overnight and 3 patients were observed for 48 hours. Operative cure was achieved in 137 (98.6%) patients (follow-up period, 15.2 +/- 12.4 mo) with 1 morbidity (0.7%). CONCLUSIONS: Outpatient MIP is safe and effective in selected patients. A low morbidity (0.7% in this series), rapid recovery, and high biochemical cure rate (98.6%) parallels 4-gland exploration under general anesthesia.