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

doi:10.1093/jnci/dju082

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

J Natl Cancer Inst. 2014 Apr 23;106(5):dju082. doi: 10.1093/jnci/dju082.

Authors

Mark D Hurwitz¹, Pejman Ghanouni², Sergey V Kanaev², Dmitri Iozeffi², David Gianfelice², Fiona Mary Fennessy², Abraham Kuten², Joshua E Meyer², Suzanne D LeBlang², Ann Roberts², Junsung Choi², James M Larner², Alessandro Napoli², Vladimir G Turkevich², Yael Inbar², Clare Mary C Tempany², Raphael M Pfeffer²

Affiliations

¹ Affiliations of authors: Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, PA (MDH); Department of Radiology, Brigham and Women's Hospital, Boston, MA (FMF, CMCT); Department of Radiology, Stanford University Medical Center, Stanford, CA (PG); Department of Radiation Oncology and Radiology, N. N. Petrov Institute of Oncology, St. Petersburg, Russian Federation (SK, VT); Department of MRI and FUS, Rostov State Research Institute of Oncology, Rostov on Don, Russian Federation (DI); Department of Medical Imaging, University Health Network, University of Toronto, Toronto, Canada (DG); Department of Oncology, Rambam Medical Center, Haifa, Israel (AK); Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, PA (JM); University MRI & Diagnositc Imaging Centers, Boca Raton, FL (SDL); Department of Radiology, University of California at San Diego, San Diego, CA (AR); Department of Diagnostic Imaging and Interventional Radiology,H. Lee Moffitt Cancer Center, Tampa, FL (JC); Department of Radiation Oncology, University of Virginia, Charlottesville, VA (JML); Department of Radiological, Oncological, and Pathological Sciences, Sapienza University of Rome, Rome, Italy (AN); Department of Radiation Oncology, Sheba Medical Center, Tel Hashomer, Israel (YI,RMP). mark.hurwitz@jefferson.edu.
² Affiliations of authors: Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, PA (MDH); Department of Radiology, Brigham and Women's Hospital, Boston, MA (FMF, CMCT); Department of Radiology, Stanford University Medical Center, Stanford, CA (PG); Department of Radiation Oncology and Radiology, N. N. Petrov Institute of Oncology, St. Petersburg, Russian Federation (SK, VT); Department of MRI and FUS, Rostov State Research Institute of Oncology, Rostov on Don, Russian Federation (DI); Department of Medical Imaging, University Health Network, University of Toronto, Toronto, Canada (DG); Department of Oncology, Rambam Medical Center, Haifa, Israel (AK); Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, PA (JM); University MRI & Diagnositc Imaging Centers, Boca Raton, FL (SDL); Department of Radiology, University of California at San Diego, San Diego, CA (AR); Department of Diagnostic Imaging and Interventional Radiology,H. Lee Moffitt Cancer Center, Tampa, FL (JC); Department of Radiation Oncology, University of Virginia, Charlottesville, VA (JML); Department of Radiological, Oncological, and Pathological Sciences, Sapienza University of Rome, Rome, Italy (AN); Department of Radiation Oncology, Sheba Medical Center, Tel Hashomer, Israel (YI,RMP).

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.

Publication types

Clinical Trial, Phase III
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Aged, 80 and over
Bone Neoplasms / diagnostic imaging
Bone Neoplasms / secondary*
Bone Neoplasms / therapy*
Female
High-Intensity Focused Ultrasound Ablation / adverse effects
High-Intensity Focused Ultrasound Ablation / methods*
Humans
Magnetic Resonance Imaging / adverse effects
Magnetic Resonance Imaging / methods*
Male
Middle Aged
Neoplasms / diagnostic imaging
Neoplasms / pathology
Neoplasms / therapy
Single-Blind Method
Ultrasonography
Young Adult

Associated data

ClinicalTrials.gov/NCT00656305