An approach using heat to alleviate the pain commonly associated with bone metastases has proven to be safe and effective in a multicenter phase III clinical trial, yielding a 64% response rate based on self-reported pain scores among patients receiving the noninvasive intervention.
Mark Hurwitz, MD
An approach using heat to alleviate the pain commonly associated with bone metastases has proven to be safe and effective in a multicenter phase III clinical trial, yielding a 64% response rate based on self-reported pain scores among patients receiving the noninvasive intervention. The study was published online ahead of print April 23, 2014 in the Journal of the National Cancer Institute.
“This is the first phase III study to use this technology in the treatment of cancer,” said lead study author Mark Hurwitz, MD, director of Thermal Oncology in the Department of Radiation Oncology at Thomas Jefferson University in Philadelphia. “It’s clear that for many of these patients, pain has a major impact on their everyday lives. This approach offers a new way to help alleviate that pain via an outpatient, noninvasive procedure.”
For this international study, 147 patients receiving treatment at 17 centers were randomized 3:1 to receive MRI-guided focused ultrasound (MRg- FUS; n = 112) or placebo (n = 35). To be eligible for the study, patients had ≤5 painful lesions and a life expectancy of ≥3 months. In addition, eligible participants were either experiencing painful bone metastases despite previous treatment with radiation (RT), were inappropriate to receive further RT, or had refused RT.
MRgFUS was performed on a device-accessible targeted tumor (eg, in the ribs, extremities [excluding joints], pelvis, shoulders, or spinal vertebra), with the ultrasound used to heat the tumor tissue to between 65ËšC and 85ËšC during the ablation phase. MRI was deployed to target the correct tumor and thus spare surrounding normal tissue and organs. Time inside the scanner was an average of 176 ± 57 minutes, and average sonication time (both low-energy subtherapeutic and ablative) was 83 ± 43 minutes.
Patients in the placebo arm had the same procedure, but the ultrasound device was not activated— an approach that researchers said made the blinding of placebo patients very effective.
Composite change in self-reported pain scores without an increase in pain medication was the study’s primary endpoint, based on assessments at baseline and 3 months, using the Numerical Rating Scale for pain (NRS) and Morphine Equivalent Daily Dose (MEDD) measure. Patients experiencing at least a two-point decrease in worst NRS and whose MEDD did not go up >25% were considered responders for the purposes of the study.
Seventy-two patients in the treatment arm (64.3%) were responders, compared with 20% of patients receiving placebo treatment at 3 months (P <.001). Of responders in the MRgFUS arm, 23.2% achieved complete response by the conclusion of the trial, reporting a worst NRS pain score of 0, versus 5.7% of patients in the placebo arm. Patients who did not respond to placebo in ≤2 weeks could be unblinded to the MRgFUS intervention, and 70.7% of placebo crossover patients had a statistically significant pain response.
Notably, said the researchers, most patients receiving MRgFUS experienced pain relief and improved functioning within several days of treatment, and many were able to reduce or stop use of opioid medications.
Statistically significant differences between the two arms were sustained at each subsequent timepoint throughout the trial.
The most common adverse event (AE) reported with the MRgFUS approach was pain during the procedure experienced by approximately onethird of patients in the experimental arm who reported pain that was either mild (6.2%), moderate (10.7%), or severe (15.2%).
Study authors noted that 60.3% of all adverse events (AEs) resolved on the day of treatment. Two patients had fractures, a rate that compares favorably with the fracture risk associated with RT.
Hurwitz said that the next steps for this research will be to refine the treatment technique to get an even better response rate and to apply radiation and thermal therapy in combination to treat bone metastases, noting that the combination has demonstrated clinical benefits for treating other malignant conditions.
David Leos, RN, MBA, OCN
Clinical Research Nurse Supervisor
Department of Radiation OncologyUT MD Anderson Cancer CenterHouston, TX
The announcement of this new potential and noninvasive treatment should be welcome news to those familiar with the limitations of currently available treatments for patients suffering due to bone metastasis. While radiation therapy is a mainstay for such cases, the described MRgFUS approach seems to offer desirable and fairly rapid results when radiation is, for whatever reason, not an option.
The preparation and implementation time seems to offer an advantage over the treatment planning required for radiation, and its integrated use of MRI allows for conformal treatment fields that spare surrounding normal tissue which mimics conformal techniques used in radiation therapy. Not mentioned in the article is whether retreatment, if needed with this technique, is possible versus the typical limitations of radiation in having to avoid prior treatment fields.
One dilemma with using radiation for bone metastasis is the question of what is optimal fractionation for palliation. The literature varies on this. Prior work has investigated using a single dose versus the standard multiple fractions. In this and other studies, effective palliation of pain has been achieved; however, the retreatment rate has been reported to be higher.
Utilizing the MRgFUS technique is reported to hold other advantages over ablative treatments in that the results in pain control were rapid and durable and significantly reduced the use of pain medications. As evidenced by the patientreported outcomes, quality of life—and specifically, functional interference from pain—was positively impacted. Additionally, the procedure was generally welltolerated and adverse events few and quite short-lived.
Of note, the rather lengthy average treatment time for MRgFUS may exclude those patients with claustrophobic concerns related to MR imaging, but this Phase III study serves as a proof of concept for the technology as a cancer treatment option.