Magnetic resonance-guided focused ultrasound for patients with painful bone metastases: phase III trial results

Mark D Hurwitz, Pejman Ghanouni, Sergey V Kanaev, Dmitri Iozeffi, David Gianfelice, Fiona Mary Fennessy, Abraham Kuten, Joshua E Meyer, Suzanne D LeBlang, Ann Roberts, Junsung Choi, James M Larner, Alessandro Napoli, Vladimir G Turkevich, Yael Inbar, Clare Mary C Tempany, Raphael M Pfeffer, Mark D Hurwitz, Pejman Ghanouni, Sergey V Kanaev, Dmitri Iozeffi, David Gianfelice, Fiona Mary Fennessy, Abraham Kuten, Joshua E Meyer, Suzanne D LeBlang, Ann Roberts, Junsung Choi, James M Larner, Alessandro Napoli, Vladimir G Turkevich, Yael Inbar, Clare Mary C Tempany, Raphael M Pfeffer

Abstract

Background: Pain 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.

Methods: Patients 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.

Results: One 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.

Conclusions: This 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.

Trial registration: ClinicalTrials.gov NCT00656305.

© The Author 2014. Published by Oxford University Press.

Figures

Figure 1.
Figure 1.
Day of treatment pre- and post-procedure magnetic resonance (MR) imaging. Axial T1-weighted contrast-enhanced MR images demonstrating a right ischial metastasis (black arrow) before treatment (left) and immediately after magnetic resonance-guided focused ultrasound surgery (MRgFUS) treatment (right). The post-treatment image shows nonenhancement of the lesion, which was targeted from a posterior approach. Each hash mark on the scale bars represents 1cm.
Figure 2.
Figure 2.
CONSORT 2010 flow diagram: magnetic resonance-guided focused ultrasound surgery (MRgFUS) vs placebo for pain palliation of bone metastasis. MRI = magnetic resonance imaging.
Figure 3.
Figure 3.
Treatment response per the primary endpoint. Response is defined as a decrease in Numerical Rating Scale for pain (NRS) score by at least 2 points and morphine equivalent daily dose (MEDD) intake that did not increase by more than 25% from baseline. MRgFUS = magnetic resonance-guided focused ultrasound surgery.
Figure 4.
Figure 4.
Additional response parameters. A) Numerical Rating Scale (NRS) for pain score: mean change in worst NRS for pain score over the 3-month evaluation period is shown. B) Morphine Equivalent Daily Dose (MEDD) intake: change from baseline in MEDD intake over the 3-month evaluation period is shown. C) Brief Pain Inventory–Quality of Life (BPI-QoL): change in BPI-QoL score over the 3-month evaluation period is shown. The 95% confidence intervals are shown in each diagram. MRgFUS = magnetic resonance-guided focused ultrasound surgery.

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