Treatment Of Metastatic Bone Pain Research Articles

Europium radionuclides in samarium-153-Ethylene Diamine Tetramethylene phosphonic acid (153Sm-EDTMP) radiopharmaceutical waste

153Sm-EDTMP is widely used as a palliative radiopharmaceutical for treatment of metastatic bone pain. It is produced by neutron activation of enriched 152Sm targets in a nuclear reactor. The long-lived europium radionuclides are co-produced along with production of 153Sm and it give rise to radioactive waste in 153Sm-EDTMP production. The gamma radiation dose rate was found significant on the radioactive waste generated during the production of 153Sm-EDTMP. Residual activity in six waste samples generated in different batches of 153Sm-EDTMP production were analysed for percentage contributions of 152,154,155Eu using gamma-ray spectrometry. 154Eu was a major contributor with around 62%, and the other radioisotopes, viz. 152Eu &155Eu contribution were ∼29% & ∼9% respectively. The activity concentration of these long-lived europium radionuclides in samarium radiopharmaceutical production waste may be utilised for the dose rate estimation, and vice versa.

Radiofrequency thermoablation (RFA) and radiotherapy (RT) combined treatment for bone metastases: a systematic review.

Approximately 50% of cancer patients develop bone metastases in their natural disease history. The management of metastatic bone disease requires a multidisciplinary approach. Both radiofrequency ablation (RFA) and radiation therapy (RT) were safe and effective in the management of painful metastases, even if they rely on totally different action mechanisms. A synergistic combination of RT and RFA seems to result in a better pain control. A systematic review was performed to describe the feasibility and effectiveness of the association between RFA and RT in the treatment of metastatic bone pain in oligo-metastatic patients, evaluating its role in alleviating bone pain, reducing the risk of fractures, and consequently ensuring a better quality of life. A systematic database search was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. This systematic review included studies that reported populations meeting the following inclusion criteria: (I) confirmed bone metastases in adult patients; (II)active bone metastases pain; (III) patients treated with combined RFA-RT; (IV) Original studies. Three papers that evaluated the combined treatment with doses ranging from moderately hypofractionated three-dimensional conformal RT (3D-CRT) and stereotactic body radiation therapy (SBRT) schedules were selected. The RFA-RT combined strategy appears to be promising in terms of efficiency and safety with adequate pain control and quality of life improvement. Positive effects on time to local failure and overall survival increase were also observed.Further prospective studies are needed to better delineate RFA-RT treatment benefits.

Effects of Curcumin on Biological Behavior and NF-κB/TNF-α Pathway in Mice with Metastatic Bone Pain of Breast Cancer Induced by Walker 256 Cells

Background. The active ingredient curcumin of traditional Chinese medicine was selected as the research object to investigate the possible mechanism of breast cancer metastatic bone pain in mouse walker 256 cells and the effect of curcumin on the NF-κB/TNF-α pathway in order to provide a new idea for clinical treatment of breast cancer metastatic bone pain. Methods. By establishing an animal model of breast cancer bone metastasis in walker 256 cells, the biological behavior of nude mice was observed on the 8th day after successful modeling. Meanwhile, the low dose group, middle dose group and high dose group of mice were given 15 mg/kg, 25 mg/kg, 50 mg/kg of curcumin solution intraperitoneally in 21 days, and the right cavity bone and spinal cord distended in mice (L4-L6) tissues were used to detect related factors, Immunohistochemical method was used to detect c-fos in spinal cord. Expression levels of RANK, NF-κB and TNF-α were detected by RT-PCR and Western blot. Meanwhile, serum levels of Cox2, il-6, leukotriene and PGE2 were detected. Results. Observing the biological behavior index of nude mice, we found that the mechanical pain and thermal pain threshold decreased (p Conclusions. On the 8th day after the success of the animal model of breast cancer bone metastasis in Walker 256 cells, abnormal biological behaviors such as heat pain, cold pain sensation and spontaneous hyperalgesia were observed. Further studies have found that the increased expression of rank on osteoclasts induced up-regulated expression of NF-κB and c-fos, induced expression of TNF-α gene, and could induce synthesis and release of leukotriene, PGE2 through direct activation of cyclooxygenase, inflammatory media IL-6 cascade reaction, resulting in pathological pain and hypersensitivity. Traditional Chinese medicine active ingredient curcumin could reduce RANK expression of osteoclast, inhibit cell NF-κB and spinal cord c-fos activity, reduce TNF-α expression, inhibit Cox2 activity, and reduce the synthesis and release of inflammatory factors leukotriene and PGE2, thus exerting its analgesic effect, which provides new ideas and methods for clinical treatment of metastatic bone pain in breast cancer.

The history of cancer pain and bone-targeted agents: 10 most commonly asked questions.

The prevalence of pain and skeletal complications of metastatic bone disease is high and an important factor, which contributes to decreased quality of life and low survival rate. Bone-targeted agents are well-established therapies to reduce the skeletal-related events in patients with bone metastasis. However, the analgesic effect of these medications is still controversial. The objective of this review is to summarize the existing evidence about the use of bone-targeted agents in the treatment of metastatic bone pain, trying to answer to the 10 most commonly asked questions in this matter. To achieve this goal, authors did a research of reviews published between January 2001 and January 2018, using the terms MeSH: “cancer pain” and bisphosphonates. The source used was the PubMed (NLM) database. The search yielded 36 reviews, but only 16 met the inclusion criteria. Even with the introduction of a new class of drugs, bisphosphonates and specially zoledronic acid are the most commonly used drugs in most oncology centers. Bisphosphonates and denosumab appear to be beneficial in preventing skeletal morbidity but their analgesic role and impact on quality of life and survival are not so well established.

Ibandronate: The loading dose concept in the treatment of metastatic bone pain

Background/AimSevere bone pain is experienced by 60–80% of patients with metastatic bone disease, and has a profound impact on quality of life. Therefore, effective pain relief is an important goal in managing metastatic bone disease. Orthopedic surgeons are often challenged with patients presenting with newly diagnosed bone metastases and severe and disabling bone pain. It is important to provide fast and sufficient analgesia. Clinical trials have demonstrated that bisphosphonates reduce effectively and sustained bone pain by approved standard dosage over time. Open label prospective trials have shown that short time high dose i.v. Ibandronate is effective in rapid pain relief in different primary tumors. Patients and methodsIn 33 patients with metastatic bone pain from newly diagnosed skeletal metastases we utilized the loading-dose concept for intravenous ibandronate (6mg infused over 1h on 3 consecutive days). ResultsIn 33 patients loading-dose ibandronate therapy significantly reduced bone pain within the first 5–7 days (VAS day 0: 6–8 vs. day 7: 3–4). Only 3 patients showed no response concerning a distinct pain reduction within the first days of therapy. There was no increase in pain medication. ConclusionThis clinical observational study in selected patients with severe metastatic bone pain undergoing an intensive high dosed ibandronate-therapy for a short period demonstrated that loading-dose ibandronate (6mg i.v., 3 consecutive days) resulted in a reduction of pain within days.

3D MR neurography targeted peripheral nerve ablation with MR-guided high intensity focused ultrasound (MR-HIFU): initial results of a feasibility study in a swine model

MR-guided HIFU is an effective treatment for metastatic bone pain through periosteal nerve ablation,[1] and is being investigated for treating back pain through facet joint denervation.[2] For peripheral neuropathy, ultrasound-guided HIFU has been investigated preclinically as a means of achieving either an irreversible conduction block to treat severe spasticity,[3] or a reversible partial conduction block to alleviate chronic pain.[4] However, ultrasound offers limited visualization of deeply situated pelvic nerves [5] and lacks the ability to measure thermal dose, which predicts the extent of changes in peripheral nerve histology and function.[6] Recently developed diffusion-prepared 3D MR neurography imaging techniques with fat suppression and nerve-selective T2-weighting [7] could improve targeting accuracy over ultrasound guidance. We present initial investigations into the use of MRI to guide HIFU ablation of peripheral nerves in a swine model. The objectives were 1) to evaluate the feasibility of identifying peripheral nerves using MR neurography on the clinical MR-HIFU system, 2) to monitor HIFU ablation of peripheral nerves using MR thermometry, and 3) to evaluate the ability to measure thermal lesions in peripheral nerves using contrast-enhanced T1-weighted images and thermal dose maps calculated from MR thermometry.

Radiopharmaceuticals and their Therapeutic Applications in Health Care System

Radiopharmaceuticals, as the name suggests, are pharmaceutical formulations consisting of radioactive substances (radioisotopes and molecules labelled with radioisotopes), which are intended for use either in diagnosis or therapy or diagnosis. Recently, however, there has been a significant growth of this branch of nuclear medicine with the introduction of a number of new radionuclides and radiopharmaceuticals for the treatment of metastatic bone pain, neuroendocrine and other tumours. This review focused on the production of radiopharmaceuticals, their applications, labelling, packaging and storage.

Therapeutic radionuclides in nuclear medicine: current and future prospects.

The potential use of radionuclides in therapy has been recognized for many decades. A number of radionuclides, such as iodine-131 ((131)I), phosphorous-32 ((32)P), strontium-90 ((90)Sr), and yttrium-90 ((90)Y), have been used successfully for the treatment of many benign and malignant disorders. Recently, the rapid growth of this branch of nuclear medicine has been stimulated by the introduction of a number of new radionuclides and radiopharmaceuticals for the treatment of metastatic bone pain and neuroendocrine and other malignant or non-malignant tumours. Today, the field of radionuclide therapy is enjoying an exciting phase and is poised for greater growth and development in the coming years. For example, in Asia, the high prevalence of thyroid and liver diseases has prompted many novel developments and clinical trials using targeted radionuclide therapy. This paper reviews the characteristics and clinical applications of the commonly available therapeutic radionuclides, as well as the problems and issues involved in translating novel radionuclides into clinical therapies.

Phase 2 Study of a High Dose of 186Re-HEDP for Bone Pain Palliation in Patients with Widespread Skeletal Metastases

(186)Re-1-hydroxyethylidene-1,1-diphosphonate (HEDP) is an attractive radiopharmaceutical for the treatment of bone pain arising from skeletal metastatic lesions. Currently, (186)Re-HEDP is most commonly used in European countries. The aim of this study was to investigate the palliative efficacy and adverse effects of (186)Re-HEDP in patients with different types of cancers and skeletal bone pain. Nineteen (8 male, 11 female) patients with various cancers (breast, prostate, renal cell carcinoma, colon, and neuroendocrine tumors) and painful bone metastases were included in the study. A dose of 1,480-3,330 MBq (40-90 mCi) of (186)Re-HEDP was administered intravenously. The patients' level of pain relief was assessed by the Visual Analog Scale for 8 wk after treatment and by a weekly blood cell count to evaluate for hematologic toxicity. The overall response rate was 89.5%, and the mean pain score assessed by the Visual Analog Scale was reduced from 9.1 to 5.3 after 1 wk (P = 0.003). No adverse effects were reported by patients during intravenous administration or for up to 24 h after administration. A flare reaction was seen in 63.2% of patients, mainly during days 1-3, and lasted for 2-4 d. There was no significant correlation between the response to therapy and the flare reactions (P > 0.05). The nadir of platelet reduction occurred at the fourth or fifth week and led to platelet infusion in only 4 patients with a low baseline platelet count and diffuse skeletal metastases. Bone marrow suppression occurred in patients receiving higher doses, but no clinical problems were seen except in 2 patients who required packed cell transfusion similar to their prior transfusions. (186)Re-HEDP is an effective radiopharmaceutical for the palliative treatment of metastatic bone pain and has minimal adverse effects.

Samarium-153–Lexidronam Therapy for Metastatic Bone Pain

ABSTRACTMultidisciplinary management may offer alternative therapeutic strategies in patients. Bone-seeking radiopharmaceuticals offered alongside traditional approaches to analgesia may be useful in the treatment of metastatic bone pain. A case of metastatic bone pain in which 153Sm-lexidronam therapy was used is presented. Minimal side effects, as well as a reduction in opioid use (via patient-controlled analgesia), were observed in this case.

The Role of Palliative External Beam Radiation Therapy in Boney Metastases Pain Management

ABSTRACTBone is the third most common organ affected by neoplastic metastases, and about 70% of patients with breast cancer or prostate cancer that develop metastases will have osseous involvement. As part of a multi-pronged approach to pain management in these patients, external beam radio therapy (EBRT) continues to be a mainstay of treatment for metastatic bone pain. This article reviews the role of radiation therapy in palliative management strategies for patients with bone metastases, including the clinical and cost-effectiveness of single fraction (SFRT) versus multiple fraction (MFRT) EBRT in pain relief. Studies indicate that SFRT is more cost-effective than MFRT, yet both are clinically effective in pain management. Therefore, EBRT use retains an important place among analgesia, bone modifying agents, chemotherapy, and hormone therapy in improving quality of life (QoL) and reducing morbidity from metastatic bone pain.

1424P - Comparison of 8GY Single Fraction Radiotherapy Versus 20GY in Five Fractions or 30GY in 10 Fractions for the Treatment of Metastatic Bone Pain

ABSTRACT Introduction In 1974 the Radiation Therapy Oncology Group (RTOG) initiated a randomized clinical trial comparing various dose-fractionation schedules in the palliation of cancer metastatic to bone. The trial was closed in February of 1980 and results have been published in 1982, with the conclusion that: “low-dose short schedules are as effective as more aggressive protracted programs. Since that time, different radiotherapy schedules had been employed for palliation of bone metastasis: 40 Gy in 20 fractions, 30 Gy in 10 fractions and single fractions of 8 Gy, 6 Gy or 4 Gy. Several randomized prospective trials and meta-analyses have been reported showing the same results in pain relief when comparing single doses vs protracted treatments. Objectives The aim of this study was to compare the most common fractionation used in oncology to treat bone metastases which are 8Gy single fraction, 20Gy in five fractions and 30Gy in 10 fractions. Method A total dose of 120 patients who is known to have stage VI cancer with bone metastasis at King Hussein Medical Center between January 2007 and December 2009, were allocated to receive either 8Gy single fraction, 20Gy in five fractions or 30Gy in 10 fractions for the treatment of their pain. Patient recorded pain severity and analgesic requirements on questionnaire which was filled by the main investigator before treatment, at 2 weeks and at 1,2,3,4,5,6,8,10, and 12 months after radiotherapy. Pain relief was the primary endpoint of treatment benefit. Results There was no difference in the time to first improvement in pain, time to complete pain relief or in time to first increase in pain at any time up to 12 months after randomization, nor in the class of analgesic used. Retreatment was twice as common after 8Gy than after multifraction radiotherapy, although retreatment for residual or recurrent pain did not reflect a difference between the three groups in the probability of pain relief. Conclusion A single fraction of 8 Gy when used for the treatment of bone metastasis is as safe and effective as a multifraction regimen for the palliation of metastatic bone pain for at least 12 months. This may make it suitable alternative to the multifraction radiotherapy regimens. Keywords: Bone metastases; Radiotherapy; Pain relief; Palliation Disclosure All authors have declared no conflicts of interest.

Bone Metastatic Disease: Taking Aim at New Therapeutic Targets

Conventional treatment for metastatic bone pain requires a multidisciplinary approach (medical therapy, surgery, and radiation), but is primarily palliative. Biphosphonates introduced the concept of disease-modifying therapy, by effectively reducing bone pain and skeletal related events in patients suffering from bone metastatic cancer. In the past decade, the growing knowledge of bone biology and our understanding of the molecular mechanisms at the basis of the interaction between cancer cells and bone matrix led to the identification of new therapeutic targets for innovative "smart drugs". The most investigated is the RANK/RANKL/OPG pathway, and denosumab, among novel targeted therapies, is the molecule that is in the most advanced development phase. Additional targets have been identified and potential novel therapeutic interventions, classified as inhibitors of bone resorption or stimulators of bone formation, are under preclinical and clinical evaluation. These promising targets include cathepsin K, the Src tyrosine kinases, integrins, chloride channels, the parathyroid hormone-related peptide, endotelin-1, sclerostin, and TGF-beta. Other pathways or molecules expressed by bone cells and cancer cells, such as CXCR4, GPNMB, EGF-family ligands, Wnt/DKK1, and MIP-1 alpha have recently emerged as potential targets. The aim of this review is to discuss the molecular mechanisms behind these emerging therapeutic targets in bone metastases and to give an overview of results from those in advanced clinical phases.

Emerging therapies in metastatic bone pain

Introduction: Current treatment for metastatic bone pain is mainly palliative. Recent insights into the molecular mechanisms involved in bone metastases have led to the identification of promising therapeutic targets. This review offers an update of preclinical and clinical data on new drugs for metastatic bone pain.Areas covered: Biphosphonates are the gold standard of bone-targeted therapy in bone metastases, for their anti-resorptive and analgesic effects. New drugs aim at breaking the ‘vicious cycle’ of bone metastatic disease, due to the bidirectional interaction between cancer cells and bone microenvironment. Osteoprotegerin, RANK/RANKL interaction, cathepsin K, the Wnt/beta-catenin pathway and sclerostin are emerging targets for modulation of cancer-induced bone desorption. Other promising targets are those expressed in cancer cells that metastasize to bone, including Src, nerve growth factor, endothelin A, TGF-beta and CXCR4. Interesting therapeutic options include targets on nociceptors that innervate the bone, such as TPRV1, Trk and cannabinoid receptors.Expert opinion: Emerging therapies promise, in the next 10 years, a significant expansion in the array of therapeutic options for bone metastases. Most of these drugs are still in an early phase of development. Further clinical trials are needed to support the evidence of their efficacy and tolerability profile.

Bisphosphonate treatment and radiotherapy in metastatic breast cancer

Patients with advanced breast cancer frequently develop metastasis to bone. Bone metastasis results in intractable pain and high risk of pathologic fractures due to osteolysis. The treatment of breast cancer patients with bone metastases requires a multidisciplinary approach. Radiotherapy is an established treatment for metastatic bone pain. It may be delivered either as a localized low dose treatment for localized bone pain or systemically for more widespread symptoms. Bisphosphonates have been shown to reduce morbidity and bone pain from bone metastases when given to patients with metastatic bone disease. In vivo studies indicate that early bisphosphonates administration in combination with radiotherapy improves remineralization and restabilization of osteolytic bone metastases in animal tumor models. This review focused on a brief discussion about biology of bone metastases, the effects of radiotherapy and bisphosphonate therapy, and possible mechanisms of combination therapy in metastatic breast cancer patients.

The role of electron-emitting radiopharmaceuticals in the palliative treatment of metastatic bone pain and for radiosynovectomy: applications of conversion electron emitter Tin-117m

A variety of radionuclides continue to be investigated and/or clinically used for different therapeutic applications in nuclear medicine. The choice of a particular radionuclide with regard to appropriate emissions, linear energy transfer (LET), and physical half-life, etc., is dictated to a large extent by the character of the disease (e.g., solid tumor or metastatic disease), and by the carrier to selectively transport the radionuclide to the desired site. An impressive body of information has appeared in the recent literature that addresses many of these considerations. This article summarizes and discusses the role of high-LET electron emitters and their advantage in the treatment of cancer or for other disorders in specific situations. Areas such as bone pain palliation, bone malignancy therapy, and radiation synovectomy are covered in greater detail. Projections are made as to the future directions and progress in these areas. A discussion of the various issues related to the selection criteria that are useful for choosing the appropriate radionuclide for a particular application is included. Use of high-LET electron emitters is discussed in greater detail, with particular emphasis on the use of conversion electron emitter tin-117m for various therapeutic applications.

Ibandronate: An effective treatment for metastatic bone pain

Increasing evidence suggests that ibandronate, a single-nitrogen, non-cyclic bisphosphonate, provides relief of metastatic bone pain (MBP). In phase III trials, both intravenous and oral formulations of ibandronate significantly reduced MBP below baseline for up to 2 years, with concurrent improvements in patient functioning and quality of life compared with placebo. Phase II studies in patients with severe or opioid-resistant MBP suggest that loading-dose ibandronate (intravenous ibandronate 6 mg administered daily for 3 consecutive days) can provide rapid and substantial pain relief within a few days. These findings have been confirmed in clinical pilot studies. Ibandronate is the only intravenous bisphosphonate with a renal safety profile that allows loading-dose treatment. The efficacy of ibandronate in MBP should be considered when choosing a bisphosphonate treatment for metastatic bone disease.

A review of calcitonin and its use in the treatment of acute pain

Summary Calcitonin is a 32 amino acid peptide hormone which regulates calcium homeostasis in vertebrates. It also has analgesic properties, primarily through receptor mediated modulation of serotonergic pain pathways in the central nervous system. Salmon calcitonin has greater physiological and analgesic potency than mammalian forms of the hormone and is therefore reproduced as a synthetic drug for clinical use. A meta-analysis concluded that calcitonin was effective in the treatment of complex regional pain syndrome and systematic reviews reported benefit in the treatment of acute vertebral fracture pain. A randomized controlled trial (RCT) showed calcitonin was effective in the treatment of acute phantom limb pain, however a Cochrane review did not support its use in the treatment of metastatic bone pain although individual RCTs suggested benefit.

Bisphosphonates and radiation therapy for palliation of metastatic bone disease

Radiotherapy is an established treatment for metastatic bone pain. It may be delivered as a localised low dose treatment for localised bone pain or systemically for more widespread symptoms using hemibody external beam radiotherapy or intravenous bone-seeking radioisotopes. Bisphosphonates have been shown to reduce morbidity from bone metastases when given to patients with asymptomatic disease from myeloma and primary breast and prostate cancers. They also reduce metastatic bone pain in these sites. In the absence of randomised data comparing radiotherapy with bisphosphonates in the same clinical setting, comparison of the response rates from individual trials of the two modalities suggests that the overall pain response in all tumour types from radiotherapy is around 80% compared to a similar rate in myeloma with bisphosphonates but only 40% in solid tumours. Optimal use of the two modalities requires further investigation but since they have different dose limiting toxicities their incorporation in a combined modality approach to metastatic bone pain is rational using the concepts of additive effect and spatial co-operation in which bisphosphonates provide background control alongside acute pain relief using radiotherapy. They are also an important alternative for bone pain where radiation tolerance has been reached or radiotherapy is not readily available.

Six gray single dose radiotherapy in the treatment of metastatic bone pain.

Bone metastases are observed in approximately 50% of patients with cancer and these are essential to influence the quality of life. As one of the most effective means of therapy for patients with bone metastases, radiotherapy can be applied as fractional and single dose. In this prospective study, we analyzed the pain relief after 6 Gy single dose irradiation in 62 patients with painful bone metastases. This was assessed by an 11-point scale questionnaire. In 88.7% of the treatments response was obtained after the single-dose radiotherapy (37.1% complete response, 51.6% partial response, 11.3% no response). In approximately 53% of the treatments the response initiated within one week. We concluded that a single dose of 6 Gy was very effective in the palliation of painful bone metastases.