Bone metastasis

A system with very stiff electrode pins has been developed for the treatment of bone metastases. In this system, a bone metastasis is defined, and pins positioned according to a treatment planning system, in and on all sides of the lesion. After pulse delivery the pins are removed and treatment completed. Extensive preclinical data have been obtained [32] and the first phase 1 chnical trial has commenced. 

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Strontium-89 chloride is a calcium analogue that rapidly clears from the blood and is taken up into bone mineral, particularly in areas of active osteogenesis, as weU as primary bone tumors and metastases. It is used for reHef of bone pain in patients having painful skeleton bone metastases. It is suppHed in an injectable solution. 

As endothelins mediate potent vasoconstrictor effects, ECE inhibitors and endothelin receptor antagonists were developed for the treatment of cardiovascular diseases, such as acute and chronic heart failure, pulmonary hypertension and subarachnoid haemorrhage. As ETa recqrtors have potent mitogenic responses and may promote progression of ovarian and prostate cancer and bone metastases ETA receptors are also considered as a potential targets for anti-tumour activity. 

Various pain states (e.g. headache, toothache and migraine), primarily pathophysiological inflammatory pain, e.g. rheumatic pain and pain caused by bone metastases... 

Warning associated with the administration of estrogen include an increased risk of endometrial cancer, gallbladder disease, hypertension, hepatic adenoma (a benign tumor of the liver), cardiovascular disease, increased risk of thromboembolic disease and hypercalcemia in those with breast cancer and bone metastases. 

Tamoxifen can be used in both premenopausal and postmenopausal women with metastatic breast cancer who have tumors that are hormone-receptor-positive. The toxicities of tamoxifen are described in the section on adjuvant endocrine therapy. The only additional toxicity that one might expect to find in the setting of metastatic breast cancer (specifically bone metastases) is a tumor flare or hypercalcemia, which occurs in approximately 5% of patients following the initiation of any SERM therapy and is not an indication to discontinue SERM therapy. It is generally accepted that this is a positive indication that the patient will respond to endocrine therapy. 

Radiation is an important modality in the treatment of symptomatic metastatic disease. The most common indication for treatment with radiation therapy is painful bone metastases or other localized sites of disease refractory to systemic therapy. Radiation therapy gives significant pain relief to approximately 90% of patients who are treated for painful bone metastases. Radiation is also an important modality in the palliative treatment of metastatic brain lesions and spinal cord lesions, which respond poorly to systemic therapy, as well as eye or orbit lesions and other sites where significant accumulation of tumor cells occurs. Skin and/or lymph node metastases confined to the chest wall area also may be treated with radiation therapy for palliation (e.g., open wounds or painful lesions). 

The delicate balance maintained by these factors is altered in patients with cancer by two principal mechanisms tumor production of humoral factors that alter calcium metabolism (humoral hypercalcemia) and local osteolytic activity from bone metastases.27 Humoral hypercalcemia causes around 80% of all hypercalcemia cases and is mediated primarily by systemic secretion of parathyroid hormone-related protein... 

The need for and ethics of cancer therapy with radiopharmaceuticals are now being carefully discussed. The success in diagnosis of cancer using "Tc has provoked interest in the possibility of cancer therapy with radiorhenium. Even if complete recovery from the disease has not yet been achieved, positive changes in the quality of life (in about 80% of all patients) were reported by rhenium treatment for bone metastases. 

Figure 5. Gamma camera image of a prostate cancer patient with widespread bone metastases, showing uptake of Re-188-DMSA in bone metas-tases. Left to right anterior, 3 h posterior, 3 h anterior, 24 h posterior, 24 h. 

The combination of an opioid and nonopioid oral analgesic often results in analgesia superior to monotherapy and may allow for lower doses of each agent. An NSAID with a scheduled opioid dose is often effective for painful bone metastases. 

Radiation is commonly used to treat painful bone metastases or other localized sites of disease including brain and spinal cord lesions. Pain relief is seen in approximately 90% of patients who receive RT. 

Disseminated disease can cause neurologic deficits from CNS metastases, bone pain or pathologic fractures secondary to bone metastases, or liver dysfunction from hepatic involvement. 

Metastatic bone disease (MBD) is characterized by very high levels of bone turnover in regions proximal to the tumour [33]. Bone resorption inhibitors such as bisphosphonates represent the current standard of care for the treatment of bone metastases primarily due to breast or prostate cancer and multiple myeloma. It has been proposed that other strong anti-resorptives such as a Cat K inhibitor could be useful in the treatment of bone metastases. Evidence for this has been presented in the form of a preclinical MBD model in which human breast cancer cells are implanted into nude mice. Treatment with a Cat K inhibitor gave a significantly lower area of breast cancer-mediated osteolytic lesions in the tibia [34]. In a separate study, the efficacy of a Cat K inhibitor in the reduction in tumour-induced osteolysis was found to be enhanced in the presence of the bisphosphonate zolendronic acid [35,36]. When prostate cancer cells were injected into the tibia of SCID mice, treatment with a Cat K inhibitor both prevented and diminished the progression of cancer growth in bone [37]. 

Radiotherapy is a local treatment aiming to achieve local control or cure of locally confined tumours. It cannot treat metastases. Radiotherapy may be administered as external beam radiotherapy with X-rays or gamma rays, in sealed radioactive sources (e.g. prostate brachytherapy), or unsealed sources (e.g. orally administered radioiodine for thyroid cancer, intravenous strontium-89 for bone metastases). In external beam radiotherapy, the X-ray or gamma ray beams are targeted at the tumour to damage and kill the tumour cells. Inevitably, surrounding normal tissues are also affected resulting in the early and late side effects of radiotherapy. 

Hypercalcemia Estrogens may lead to severe hypercalcemia in patients with breast cancer and bone metastases. If this occurs, discontinue the drug and take appropriate measures to reduce the serum calcium level. 

Hypercalcemia of malignancy (HCM) For the treatment of FICM (zoledronic acid) in conjunction with adequate hydration for the treatment of moderate or severe hypercalcemia associated with malignancy, with or without bone metastases (pamidronate patients with epidermoid or nonepidermoid tumors respond to pamidronate) for FICM that persists after adequate hydration has been restored (zoledronic acid). 

Breast cancer/Multiple myeloma (pamidronate) In conjunction with standard antineoplastic therapy for the treatment of osteolytic bone metastases of breast... 

Multiple myeloma and bone metastases of solid tumors (zoledronic acid) For the treatment of multiple myeloma and bone metastases from solid tumors, in conjunction with standard antineoplastic therapy. 

Osteolytic bone metastases of breast cancer- 90 mg administered over a 2-hour infusion every 3 to 4 weeks. 

Renal function impairment- In patients receiving pamidronate for bone metastases who show evidence of deterioration in renal function, withhold treatment until renal function returns to baseline. In a clinical study, renal deterioration was defined as follows for patients with normal baseline creatinine, an increase of 0.5 mg/dL for patients with abnormal baseline creatinine, an increase of 1 mg/dL. In this clinical study, pamidronate treatment was resumed only when the creatinine returned to within 10% of the baseline value. In other indications, clinical judgment should determine whether the potential benefit outweighs the potential risk in such patients. 

Zoledronic acid- Single doses of zoledronic acid should not exceed 4 mg and the duration of infusion should be no less than 15 minutes. Zoledronic acid treatment is not recommended in patients with bone metastases with severe renal impairment. Patients who receive zoledronic acid should have serum creatinine assessed prior to each treatment. 

Teriparatide (Forteo) [Antiosteoporotic/Parathyroid Hormono] WARNING T Osteosarcoma risk in animals, therefore only use in pts for whom the potential benefits outweigh risks Uses Severe/refractory osteoporosis Action PTH (recombinant) Dose 20 meg SQ daily in thigh or abd Caution [C, /-] Contra w/ Paget Dz, prior radiation, bone metastases, T Ca caution in urolithiasis Disp Inj SE Orthostatic X BP on administration, N/D, T... 

Nausea, vomiting, and hot flashes may accompany tamoxifen administration. Tamoxifen may cause a transient flare of tumor growth and increased pain due to bone metastases. These reactions are thought to be due to an initial estrogenic action of this drug. Mild or tran-... 

F]-Fluoride-PET Imaging of bone metastases [ F]FET-PET Imaging with amino acids [ F]Fluorodopa-PET Imaging with amino precursors Acknowledgments References Note from the Editors... 

Schirrmeister et al. prospectively evaluated the clinical value of planar bone scans, SPECT and [ F]-labeled sodium fluoride in 53 patients with newly diagnosed lung cancer [193], Twelve of the 53 patients turned out to have bone metas-tases. [ F]-fluoride-PET detected all patients with bone metastases, whereas bone scan and SPECT produced false-negative results (6 vs. 1). An area under the curve analysis (ROC) proved p F]-fluoride-PET to be the most accurate whole-body imaging modality for screening of bone metastases in this study. 

According to Langsteger et al. [ F]-fluoride seems to better visualize bone metastases in [ F]-FDG negative tumors, such as renal cell and thyroid carcinoma and in [ F]-FDG avid tumors under therapy [196]. 

G.J. Cook, I. Fogelman, The role of positron emission tomography in the management of bone metastases. Cancer 88(12 Suppl.) (2000) 2927-2933. 

E. Even-Sapir, U. Metser, E. Mishani, G. Lievshitz, H. Lerman, I. Leibovitch, The detection of bone metastases in patients with high-risk prostate cancer 99mTc-MDP planar bone scintigraphy, single- and multi-field-of-view SPECT, F-fluoride PET, and F-fluoride PET/CT, J. Nucl. Med. 47(2) (2006) 287-297. 

Unlabeled Uses Prevention of bone metastases from breast, prostate cancer, treatment of bone diseases... 

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