Magnetic Resonance–Guided Focused Ultrasound Reduces Pain From Bone Metastases
Few options are available to treat pain from bone metastases in patients refractory to drug and radiation therapy. In a phase III study reported in the Journal of the National Cancer Institute, Hurwitz et al found significant pain relief using magnetic resonance–guided focused ultrasound surgery—a noninvasive method of thermal tissue ablation—in patients in whom other treatments had failed.
Focused ultrasound is a noninvasive technique that delivers acoustic energy to focally heat lesions to ablative temperatures. The combination of focused ultrasound and magnetic resonance imaging permits precise localized tumor tissue ablation and real-time temperature monitoring.
Study Details
In the study, 147 patients with painful bone metastases were randomly assigned 3:1 to receive magnetic resonance–guided focused ultrasound surgery sonication (n = 112) or placebo (n = 35). The primary endpoint was improvement in Numerical Rating Scale self-reported pain score (0-10 scale) without increase of pain medication (morphine equivalent daily dose intake) 3 months after treatment; patients whose worst pain score decreased by ≥ 2 and whose morphine equivalent daily dose intake did not increase > 25% from baseline to 3 months were considered responders. The Brief Pain Inventory (BPI-QoL) was used to measure functional interference of pain on quality of life.
For the magnetic resonance–guided focused ultrasound surgery and placebo groups: median age was 62 and 60 years; 55% and 80% were female (P = .009); median Karnofsky performance score was 80 in both; worst pain score was 7 in both; median morphine equivalent daily dose was 0.80 vs 0.48; primary tumor was breast in 30% and 54%, prostate in 13% and 6%, and lung in 15% and 11%; target lesion was osteolytic in 53% and 60%; target lesion location was pelvis in 63% and 54%; number of distinguishable painful lesions was 1 in 80% and 74%; and 44% and 26% had received prior radiotherapy (P = .03), 21% and 29% had received chemotherapy, 14% and 11% had received hormone therapy, and 41% and 54% had received bisphosphonate treatment.
Response Rates
Response was achieved in 64.3% of patients in the magnetic resonance–guided focused ultrasound surgery group and in 20.0% of the placebo group (P < .001). Complete response (worst pain = 0 by study end) occurred in 23.2% of magnetic resonance–guided focused ultrasound surgery patients vs 5.7% of placebo patients. Pain relief was significantly greater in the magnetic resonance–guided focused ultrasound surgery group by day 3 (P = .02) and remained so thereafter. Mean reduction in pain scores were 3.6 vs 0.7 (P< .001). There was trend toward a significant reduction in change in medication use from baseline (morphine equivalent daily dose = +3.7% vs +15.3%); 27% vs 14% of responders discontinued medication, and 17% and 0% reduced medication use.
The changes in BPI-QoL from baseline at 3 months with magnetic resonance–guided focused ultrasound surgery was 2.4 points better than that with placebo (P < .001). Improvement in BPI-QoL was significantly better in the magnetic resonance–guided focused ultrasound surgery group by day 3 (P = .03) and remained so thereafter.
Analyses of covariance for sex and prior radiotherapy separately for response, pain alone, medication use alone, and BPI-QoL showed no significance of interaction terms. Results with magnetic resonance–guided focused ultrasound surgery were better than placebo for all endpoints for both men and women and for patients with or without prior radiation therapy to target or nontarget lesions.
Adverse Events
The most common treatment-related adverse event was sonication pain, which occurred in 32.1% of magnetic resonance–guided focused ultrasound surgery patients (0% of placebo patients), followed by position pain (8.0% vs 2.9%) and postprocedure pain (4.5% vs 0%). Two patients had pathologic fractures, one had third-degree skin burn, and one patient suffered from neuropathy. Overall, 60.3% of all adverse events resolved on the day of treatment.
The investigators concluded, “This multicenter phase III trial demonstrated that [magnetic resonance–guided focused ultrasound surgery] is a safe and effective, noninvasive treatment for alleviating pain resulting from bone metastases in patients that have failed standard treatments.”
Mark D. Hurwitz, MD, of Jefferson University, is the corresponding author for the Journal of the National Cancer Institute article.
The study was supported by InSightec Ltd, Tirat Carmel, Israel.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
