Focused ultrasound is a non-invasive tissue ablation technique that uses acoustic energy to heat lesions to ablative temperatures of more than 65 °C. Adding MR guidance confers additional advantages, including high-resolution imaging of the targeted tumour and surrounding anatomy, real-time MR thermometry during treatment to ensure adequate ablation temperatures while respecting normal tissue tolerances, and immediate post-treatment validation of the extent of ablation.

MRgFUS has previously been used to treat thousands of women with uterine fibroids, with excellent safety and efficacy profiles. This latest work represents the first completed phase III study to use the technology for cancer treatment, says principal investigator Mark Hurwitz from Thomas Jefferson University. Hurwitz and colleagues performed the randomized controlled trial to evaluate the safety and efficacy of MRgFUS for palliation of pain due to bone metastases (J. Natl. Cancer. Inst. 106 dju082).

Blinded trial

The phase III study included 147 patients from 17 centres in the USA, Canada, Israel, Italy and Russia. Participants had bone metastases that were painful despite previous radiotherapy, or were not candidates for or declined radiotherapy. The patients were randomly assigned to receive MRgFUS (112 subjects) or placebo treatments (35 subjects).

The researchers created treatment plans for each patient, to precisely target ultrasound to their bone tumours while avoiding damage to non-targeted tissue. After verifying correct positioning using low-energy sonications, they used the ExAblate MRgFUS system from InSightec to heat lesions to ablative temperatures of between 65 and 85 °C. Patients randomized to placebo underwent the same procedure but without ultrasound energy deposition.

The study's primary endpoint was improvement in self-reported pain score, without an increase in pain medication, three months after treatment. Specifically, a patient whose highest numerical rating scale (NRS) for pain decreased by at least two points and whose morphine equivalent daily dose did not increase by more than 25% was considered a responder; otherwise, they were considered a non-responder.

The study met its primary endpoint, with 64.3% of patients in the MRgFUS arm designated as responders, compared with 20.0% in the placebo arm. In the MRgFUS group, 23.2% of participants had a complete response (worst NRS of zero by trial end), while 5.7% in the placebo arm had a complete response. Response to MRgFUS was typically rapid, with about two-thirds of patients experiencing pain relief within days of treatment.

The researchers also observed a statistically significant difference in change from baseline in the worst NRS, with a mean reduction of 3.6 ± 3.1 points in the MRgFUS group and 0.7 ± 2.4 points in the placebo group. Additionally, 47% of patients treated by MRgFUS reduced (21%) or completely stopped (26%) their pain medication.

The most common treatment-related adverse event was sonication pain, which occurred in 32.1% of sonicated patients. In addition, two patients had pathological fractures, one had third-degree skin burn and one suffered from neuropathy. Overall, 60.3% of all adverse events resolved on the treatment day, with an additional 14.3% resolving within one week.

The authors concluded that their study results support previous findings, with MRgFUS providing durable pain relief and improved function in patients who had failed, or were not candidates for, radiation therapy. They note that MRgFUS should be considered a viable treatment option for painful bone metastases and that further studies are required to assess its role as a first-line therapy.

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