RESUMEN
â¢There is a lack of prospective level I evidence for the use of PBT for most adult cancers including oropharyngeal squamous cell carcinoma (OPSCC).â¢TORPEdO is the UK's first PBT clinical trial and aims to determine the benefits of PBT for OPSCC.â¢Training and support has been provided before and during the trial to reduce variations of contouring and radiotherapy planning.â¢There is a strong translational component within TORPEdO. Imaging and physics data along with blood, tissue collection will inform future studies in refining patient selection for IMPT.
RESUMEN
In this case report, the authors describe a patient who underwent an endovascular abdominal aortic aneurysm repair complicated by more than a 2-year delay in healing of the left inguinal fold access site. Providers initially suspected a chronic infection or foreign body reaction, but eventually the patient was diagnosed with superficial granulomatous pyoderma. Once the correct etiology was determined and appropriate treatment begun, the access site healed within 3 weeks.
Asunto(s)
Aneurisma de la Aorta Abdominal/cirugía , Implantación de Prótesis Vascular/efectos adversos , Procedimientos Endovasculares/efectos adversos , Piodermia/diagnóstico , Dehiscencia de la Herida Operatoria/diagnóstico , Cicatrización de Heridas , Anciano de 80 o más Años , Humanos , Masculino , Piodermia/etiología , Piodermia/terapia , Dehiscencia de la Herida Operatoria/etiología , Dehiscencia de la Herida Operatoria/terapiaRESUMEN
BACKGROUND: Brain metastases occur in up to 75% of patients with advanced melanoma. Most are treated with whole-brain radiotherapy (WBRT), with limited effectiveness. Vandetanib, an inhibitor of vascular endothelial growth factor receptor, epidermal growth factor receptor and rearranged during transfection tyrosine kinases, is a potent radiosensitiser in xenograft models. We compared WBRT with WBRT plus vandetanib in the treatment of patients with melanoma brain metastases. METHODS: In this double-blind, multi-centre, phase 2 trial patients with melanoma brain metastases were randomised to receive WBRT (30 Gy in 10 fractions) plus 3 weeks of concurrent vandetanib 100 mg once daily or placebo. The primary endpoint was progression-free survival in brain (PFS brain). The main study was preceded by a safety run-in phase to confirm tolerability of the combination. A post-hoc analysis and literature review considered barriers to recruiting patients with melanoma brain metastases to clinical trials. RESULTS: Twenty-four patients were recruited, six to the safety phase and 18 to the randomised phase. The study closed early due to poor recruitment. Median PFS brain was 3.3 months (90% confidence interval (CI): 1.6-5.6) in the vandetanib group and 2.5 months (90% CI: 0.2-4.8) in the placebo group (P=0.34). Median overall survival (OS) was 4.6 months (90% CI: 1.6-6.3) and 2.5 months (90% CI: 0.2-7.2), respectively (P=0.54). The most frequent adverse events were fatigue, alopecia, confusion and nausea. The most common barrier to study recruitment was availability of alternative treatments. CONCLUSIONS: The combination of WBRT plus vandetanib was well tolerated. Compared with WBRT alone, there was no significant improvement in PFS brain or OS, although we are unable to provide a definitive result due to poor accrual. A review of barriers to trial accrual identified several factors that affect study recruitment in this difficult disease area.
Asunto(s)
Antineoplásicos/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/radioterapia , Melanoma/tratamiento farmacológico , Melanoma/radioterapia , Piperidinas/uso terapéutico , Quinazolinas/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Encéfalo/efectos de los fármacos , Encéfalo/patología , Encéfalo/efectos de la radiación , Neoplasias Encefálicas/patología , Terapia Combinada/métodos , Supervivencia sin Enfermedad , Método Doble Ciego , Femenino , Humanos , Masculino , Melanoma/patología , Persona de Mediana Edad , Fármacos Sensibilizantes a Radiaciones/uso terapéutico , Radioterapia/métodosRESUMEN
PURPOSE: The aromatase inhibitor anastrozole is a highly effective well-tolerated treatment for postmenopausal endocrine-responsive breast cancer. However, its use is associated with accelerated bone loss and an increase in fracture risk. The ARIBON trial is a double-blind, randomized, placebo-controlled study designed to evaluate the impact of bisphosphonate treatment on bone mineral density (BMD) in women taking anastrozole. EXPERIMENTAL DESIGN: BMD was assessed in 131 postmenopausal, surgically treated women with early breast cancer at two U.K. centers. Of these, 50 patients had osteopenia (T score -1.0 to -2.5) at either the hip or lumbar spine. All patients were treated with anastrozole 1 mg once a day and calcium and vitamin D supplementation. In addition, osteopenic patients were randomized to receive either treatment with ibandronate 150 mg orally every month or placebo. RESULTS: After 2 years, osteopenic patients treated with ibandronate gained +2.98% (range -8.9, +19.9) and +0.60% (range -9.0, +6.9) at the lumbar spine and hip, respectively. Patients treated with placebo, however, lost -3.22% (range -16.0, +4.3) at the lumbar spine and -3.90% (range -12.3, +7.2) at the hip. The differences between the two treatment arms were statistically significant at both sites (P < 0.01). At 12 months, urinary n-telopeptide, serum c-telopeptide, and serum bone-specific alkaline phosphatase levels declined in patients receiving ibandronate (30.9%, 26.3%, and 22.8%, respectively) and increased in those taking placebo (40.3%, 34.9%, and 37.0%, respectively). CONCLUSIONS: Monthly oral ibandronate improves bone density and normalizes bone turnover in patients treated with anastrozole.
Asunto(s)
Inhibidores de la Aromatasa/farmacología , Enfermedades Óseas/inducido químicamente , Enfermedades Óseas/complicaciones , Neoplasias de la Mama/complicaciones , Neoplasias de la Mama/tratamiento farmacológico , Difosfonatos/administración & dosificación , Nitrilos/efectos adversos , Triazoles/efectos adversos , Anciano , Anastrozol , Antineoplásicos Hormonales/efectos adversos , Densidad Ósea , Conservadores de la Densidad Ósea/efectos adversos , Método Doble Ciego , Femenino , Fracturas Óseas/inducido químicamente , Fracturas Óseas/complicaciones , Humanos , Ácido Ibandrónico , Vértebras Lumbares/efectos de los fármacos , Vértebras Lumbares/patología , Persona de Mediana Edad , PlacebosRESUMEN
PURPOSE: Bisphosphonates play a central role in the management of bone loss due to a range of disorders, including metastatic bone disease, cancer treatment-induced bone loss, and postmenopausal osteoporosis. With potent bisphosphonates, such as zoledronic acid, it may be possible to maintain efficacy with relatively infrequent administration. EXPERIMENTAL DESIGN: Sixty-six patients who were osteopenic at >1 year following curative cancer therapy received a single i.v. 4 mg dose of the bisphosphonate zoledronic acid. Bone mineral density (BMD) was measured using double-beam X-ray absorptiometry scan and the bone resorption marker N-telopeptide of type II collagen was determined using a chemiluminescence ELISA assay. RESULTS: The single dose of zoledronic acid induced mean increases in bone BMD at the lumbar spine of 3.1%, 5.2%, and 5.3% and at the total hip of 2.7%, 3.5%, and 4.3% after 12, 24, and 36 months of follow-up, respectively (P < 0.001 at all time points). By 36 months, 84% of patients had achieved increase in BMD at the spine and 90% at the hip. The mean percentage decrease in the bone resorption marker N-telopeptide was approximately 58% at 6 weeks and 42%, 33%, and 31% at 12, 24, and 36 months, respectively (P < 0.001). CONCLUSIONS: A single dose of zoledronic acid in patients with low BMD results in a sustained increase in BMD and a corresponding decrease in bone resorption. Very infrequent administration of zoledronic acid may have clinical benefits in terms of convenience, reduced toxicity, improved compliance, and cost.
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Conservadores de la Densidad Ósea/administración & dosificación , Enfermedades Óseas Metabólicas/tratamiento farmacológico , Difosfonatos/administración & dosificación , Imidazoles/administración & dosificación , Neoplasias/complicaciones , Absorciometría de Fotón , Adulto , Anciano , Densidad Ósea , Enfermedades Óseas Metabólicas/diagnóstico por imagen , Enfermedades Óseas Metabólicas/etiología , Huesos/diagnóstico por imagen , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ácido ZoledrónicoAsunto(s)
Imagen por Resonancia Magnética/efectos adversos , Imagen por Resonancia Magnética/normas , Guías de Práctica Clínica como Asunto , Pautas de la Práctica en Medicina/normas , Traumatismos por Radiación/prevención & control , Administración de la Seguridad/organización & administración , Humanos , Estados UnidosRESUMEN
Bisphosphonates will become increasingly important in the management of patients with breast cancer. Currently, bisphosphonates are used to treat bone metastasis because they effectively relieve pain, prevent pathological fractures and treat hypercalcaemia of malignancy. Recent advances in systemic adjuvant therapies for breast cancer are improving survival but many treatments are detrimental to bone and can increase the risk of fracture. The monitoring of breast cancer patients at risk of developing osteoporosis will become increasingly important as survival times improve and more potent treatments are developed. Bisphosphonates may also play a role as an adjuvant therapy for the prevention of bone metastasis in high-risk breast cancer patients.
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Neoplasias de la Mama/tratamiento farmacológico , Difosfonatos/administración & dosificación , Osteoporosis Posmenopáusica/prevención & control , Antineoplásicos/efectos adversos , Femenino , Humanos , Osteoporosis Posmenopáusica/inducido químicamenteRESUMEN
Despite an increasing incidence, the outlook for women with early breast cancer has improved considerably over recent years with a steady fall in the death rate in most western countries. This is due, at least in part, to the widespread use of adjuvant systemic therapy. However, some of these treatments have adverse effects on bone metabolism with increased bone loss which may result in osteoporosis and associated fractures. Most of the effects on bone are mediated by endocrine changes, either induction of an early menopause by chemotherapy and ovarian ablation, or further suppression of postmenopausal circulating oestrogens by aromatase inhibitors. There may also be direct effects of chemotherapy on bone cell function. The pathophysiology of osteoporosis in breast cancer patients, the methods of assessment and treatment options are reviewed. Bone health is a highly topical issue in breast cancer with the emergence of data supporting the use of several years of treatment with aromatase inhibitors. Guidelines on who and how to screen for bone loss, and simple, safe strategies for treatment to prevent osteoporosis are presented.