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      Feasibility of volumetric MRI-guided high intensity focused ultrasound (MR-HIFU) for painful bone metastases

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          Abstract

          Background

          Magnetic resonance-guided high intensity focused ultrasound (MR-HIFU) has recently emerged as an effective treatment option for painful bone metastases. We describe here the first experience with volumetric MR-HIFU for palliative treatment of painful bone metastases and evaluate the technique on three levels: technical feasibility, safety, and initial effectiveness.

          Methods

          In this observational cohort study, 11 consecutive patients (7 male and 4 female; median age, 60 years; age range, 53–86 years) underwent 13 treatments for 12 bone metastases. All patients exhibited persistent metastatic bone pain refractory to the standard of care. Patients were asked to rate their worst pain on an 11-point pain scale before treatment, 3 days after treatment, and 1 month after treatment. Complications were monitored. All data were prospectively recorded in the context of routine clinical care. Response was defined as a ≥2-point decrease in pain at the treated site without increase in analgesic intake. Baseline pain scores were compared to pain scores at 3 days and 1 month using the Wilcoxon signed-rank test. For reporting, the STROBE guidelines were followed.

          Results

          No treatment-related major adverse events were observed. At 3 days after volumetric MR-HIFU ablation, pain scores decreased significantly ( p = 0.045) and response was observed in a 6/11 (55%) patients. At 1-month follow-up, which was available for nine patients, pain scores decreased significantly compared to baseline ( p = 0.028) and 6/9 patients obtained pain response (overall response rate 67% (95% confidence interval (CI) 35%–88%)).

          Conclusions

          This is the first study reporting on the volumetric MR-HIFU ablation for painful bone metastases. No major treatment-related adverse events were observed during follow-up. The results of our study showed that volumetric MR-HIFU ablation for painful bone metastases is technically feasible and can induce pain relief in patients with metastatic bone pain refractory to the standard of care. Future research should be aimed at standardization of the treatment procedures and treatment of larger numbers of patients to assess treatment effectiveness and comparison to the standard of care.

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          Most cited references 27

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               S Mercadante (1996)
              The presence of bone metastases predicts the presence of pain and is the most common cause of cancer-related pain. Although bone metastases do not involve vital organs, they may determine deleterious effects in patients with prolonged survival. Bone fractures, hypercalcaemia, neurologic deficits and reduced activity associated with bone metastases result in an overall compromise in the patient's quality of life. A metastasis is a consequence of a cascade of events including a progressive growth at the primary site, vascularization phase, invasion, detachment, embolization, survival in the circulation, arrest at the site of a metastasis, extravasion, evasion of host defense and progressive growth. Once cancer cells establish in the bone, the normal process of bone turnover is disturbed. The different mechanisms responsible for osteoclast activation correspond to typical radiologic features showing lytic, sclerotic or mixed metastases, according to the primary tumor. The release of chemical mediators, the increased pressure within the bone, microfractures, the stretching of periosteum, reactive muscle spasm, nerve root infiltration and compression of nerves by the collapse of vertebrae are the possible mechanisms of malignant bone pain. Pain is often disproportionate to the size or degree of bone involvement. A comprehensive assessment including a trusting relationship with the patient, taking a careful history of the pain complaint, the characteristics of the pain, the evaluation of the psychological status of the patient, neurological examination, the reviewing of diagnostic studies and laboratory findings, and individualization of the therapeutic approach, should precede any treatment. Radiotherapy is the cornerstone of the treatment. Low doses given in a single session are safe and effective, and reduce distress and inconvenience associated with repeated session. Radioisotopes are more imprecise in delivering specific doses of radiation, but have less toxicity and easy administration as well as effectiveness in subclinical sites of metastases, although storage, dispensing and administration should be under strict control. Chemotherapy and endocrine therapy are difficult to measure in terms of pain relief. Prophylactic fixation surgery can lead to improved survival and quality of life of patients with bone metastases. Surgical treatment should be undertaken when fracture occurs. Careful selection of patients for surgical spinal decompression is required. The potential benefits of surgical interventions have to be tempered with patient survival. The use of analgesics according to the WHO ladder is recommended. There is no clear evidence that non-steroidal anti-inflammatory drugs (NSAIDs) have a specific efficacy in malignant bone pain. The difficulty with incident pain is not a lack of response to systemic opioids, but rather that the doses required to control the incidental pain produce unacceptable side-effects at rest. Alternative measures are often required. The inhibition of bone resorption and hypercalcaemia can be reduced by the use of bisphosphonates. This class of drugs potentiate the effects of analgesics in improving metastatic bone pain. Invasive techniques are rarely indicated, but may provide analgesia in the treatment of pain resistant to the other modalities. Neural blockade should never be used as the sole modality for malignant bone pain, but should be considered as a helpful in specific pain situations. Careful appraisal and the application of a correct approach should enable the patient with bone metastases to obtain an acceptable pain relief despite the advanced nature of their malignant disease.
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                Author and article information

                Contributors
                Journal
                J Ther Ultrasound
                J Ther Ultrasound
                Journal of Therapeutic Ultrasound
                BioMed Central
                2050-5736
                2014
                10 October 2014
                : 2
                : 16
                Affiliations
                [1 ]Department of Radiology, University Medical Center Utrecht, Heidelberglaan 100, 3508 GA Utrecht, The Netherlands
                [2 ]Image Sciences Institute, University Medical Center Utrecht, 3508 GA Utrecht, The Netherlands
                [3 ]Department of Radiation Oncology, University Medical Center Utrecht, 3508 GA Utrecht, The Netherlands
                Article
                2050-5736-2-16
                10.1186/2050-5736-2-16
                4193684
                Copyright © 2014 Huisman et al.; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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