Magnetic Resonance–Guided Focused Ultrasound for Patients With Painful Bone Metastases: Phase III Trial Results

Abstract

BackgroundPain due to bone metastases is a common cause of cancer-related morbidity, with few options available for patients refractory to medical therapies and who do not respond to radiation therapy. This study assessed the safety and efficacy of magnetic resonance-guided focused ultrasound surgery (MRgFUS), a noninvasive method of thermal tissue ablation for palliation of pain due to bone metastases.MethodsPatients with painful bone metastases were randomly assigned 3:1 to receive MRgFUS sonication or placebo. The primary endpoint was improvement in self-reported pain score without increase of pain medication 3 months after treatment and was analyzed by Fisher’s exact test. Components of the response composite, Numerical Rating Scale for pain (NRS) and morphine equivalent daily dose intake, were analyzed by t test and Wilcoxon rank-sum test, respectively. Brief Pain Inventory (BPI-QoL), a measure of functional interference of pain on quality of life, was compared between MRgFUS and placebo by t test. Statistical tests were two-sided.ResultsOne hundred forty-seven subjects were enrolled, with 112 and 35 randomly assigned to MRgFUS and placebo treatments, respectively. Response rate for the primary endpoint was 64.3% in the MRgFUS arm and 20.0% in the placebo arm (P < .001). MRgFUS was also superior to placebo at 3 months on the secondary endpoints assessing worst score NRS (P < .001) and the BPI-QoL (P < .001). The most common treatment-related adverse event (AE) was sonication pain, which occurred in 32.1% of MRgFUS patients. Two patients had pathological fractures, one patient had third-degree skin burn, and one patient suffered from neuropathy. Overall 60.3% of all AEs resolved on the treatment day.ConclusionsThis multicenter phase III trial demonstrated that MRgFUS is a safe and effective, noninvasive treatment for alleviating pain resulting from bone metastases in patients that have failed standard treatments.

Focused ultrasound for treatment of bone tumours

“…In order to quantify its use, a morphine equivalent daily dose (MEDD) intake form was used in some studies [43]. In the case of metastatic tumors, both pain scales and MEDD followed the standards published by the International Bone Metastases Consensus Working Party (IBMCWP) [44].…”

Evaluation of CT Image Guided Radiofrequency Ablation in the Management of Painful Bone Metastases Originating from NSCLC

“…Prospective, single-arm multicenter trials have shown RFA and cryoablation to be safe and highly effective for treatment of symptomatic skeletal metastases [12][13][14][15][16]. A large randomized, controlled, multicenter phase III trial has shown Focused Ultrasound (FUS) to be effective in the treatment of painful bone metastases [17], confirming results of earlier retrospective reports [18]. Small case series also support benefit from other percutaneous methods of image-guided ablation, including microwave ablation, laser ablation, and irreversible electroporation to treat skeletal metastases, although the data are more limited [19][20][21][22][23][24][25][26].…”

MRI-guided focused ultrasound surgery in musculoskeletal diseases: the hot topics

“…75 MRgFUS has been first proposed with a potential in pain palliation of bone metastases, for its good results in patients non-responding to radiotherapy while applying acoustic energy on the bone surface resulting in bone cortex heating, and indirectly ablating the adjacent periosteum-the most innervated component of mature bone tissue, and tumour tissue, and a major source of pain. 11,76 The bone is a common site for metastasis. The primary cancers that most frequently metastasize to bone are breast and prostate cancers (post-mortem incidence of bone metastases: breast 73%, prostate 68%, thyroid 42%, lung 36%, renal 35%), and these are among the most incident and curable worldwide.…”

“…This study demonstrated that MRgFUS is a non-invasive and safe treatment in painful bone metastases for patients in whom standard treatments have failed. 11 Recently, an article published by an international consensus held at the Focused Ultrasound Therapy Second European Symposium in Rome (2013), Italy, focused on the point about current treatment goals, current indications, technical considerations, future directions including research priorities, and economic and logistical considerations. 84 A…”