Magnetic Resonance–guided Focused Ultrasound for Palliating Pain from Bone Metastases

Proprietary names: Achieva 1.5 tesla (T) Magnetic Resonance System, Achieva 3.0 T Magnetic Resonance System, EasyWater Degasser, ExAblate®One, ExAblate O.R., ExAblate, ExAblate 2000, ExAblate 2100, ExAblate 2100 Conformal Bone System, Ingenia 1.5T Magnetic Resonance System, Ingenia 3.0T Magnetic Resonance System, Signa 1.5 Tesla Magnetic Resonance System, Intera 1.5 Tesla Magnetic Resonance System, Intera 3.0 Tesla Magnetic Resonance System, Signa 3 Tesla Magnetic Resonance System, Sonalleve MR High-intensity Focused Ultrasound system, Sonalleve MR-HIFU System

Generic names: acoustic surgery, acoustic therapy, focused ultrasound ablation, high-intensity focused ultrasound ablation (HIFUA), high-intensity focused ultrasound surgery (HIFUS), high-intensity focused ultrasound (HIFU) therapy, HIFU-MRI; image-guided acoustic surgery, hyperthermia therapy, image-guided surgery, incisionless surgery, magnetic resonance-guided focused ultrasound ablation (MRgFUA), magnetic resonance (MR)–guided focused ultrasound surgery (MRgFUS), MR-HIFU therapy, MRI-guided high intensity focused ablation, MRI-guided high intensity focused ultrasound (HIFU), magnetic resonance (MR) thermal ablation, therapeutic ultrasound, thermoablative therapy, ultrasound ablation, ultrasound surgery

Interest in minimally invasive local treatment options that target pain from bone metastases has increased because patient longevity and advances in cancer management have led to more people living with bone metastases.1 Magnetic resonance–guided focused ultrasound (MRgFUS)—a noninvasive thermal ablation technique for treating uterine fibroids that has been performed for about 10 years—is being used for palliating pain from bone metastases.

Bones are a common place for metastatic cancer cells to colonize and establish secondary tumor sites. Risk factors for bone metastasis are those associated with the primary cancer that has spread to the bone and include tobacco use, unhealthy diet, sedentary lifestyle, obesity, and alcohol abuse.2 Higher-grade tumors and late diagnoses are also associated with the presence of bone metastasis.2 Metastases can develop in any bone, but certain cancers such as solid tumors (breast, prostate, lung, thyroid, and kidney cancers) are more likely than others to spread to bone,3 and bone metastases occur in late stages of most solid tumor cancers.2

Bone metastases are a common cause of significant morbidity and mortality;4 metastatic lesions can predispose the bone to fractures.5 When metastases form in bone, the cancer cells release substances that can activate nearby bone cells, called osteoclasts and osteoblasts. Osteoclasts dissolve and weaken surrounding bone, which can lead to formation of osteolytic lesions. Osteoblasts stimulate bone formation, causing sclerotic, osteoblastic lesions.2 Both types of bone metastases can cause pain, but osteolytic lesions usually lead to fracture more often than osteoblastic lesions.6

Between 50% and 70% of patients with bone metastases experience severe pain.4 Pain may "originate directly from the bone, from nerve root compression, or from muscle spasms in the lesion areas"7 and can significantly hinder daily functioning and quality of life (QOL).1 Some patients describe the pain as dull and aching, while other patients experience sudden, severe pain originating in the affected area and moving through the body.8 Depending on the bone(s) affected, the pain may worsen at night, with bed rest, or with activity or movement.8 Also, spinal compression from a metastatic lesion may cause urination difficulties, numbness and weakness in the legs, and paralysis.2 Also, an imbalance between bone formation and bone resorption can lead to high blood calcium levels and associated symptoms (i.e., nausea and vomiting, loss of appetite, extreme thirst, frequent urination, constipation, abdominal pain, muscle weakness, muscle and joint pain, confusion, lethargy and fatigue).2

Clinical condition, life expectancy, and impact on quality of life (QOL) guide pain palliation treatment decisions.7 First-line treatment is pain medication with nonsteroidal anti-inflammatory drugs progressing to opioids.9 Increasing opioid doses can result in nausea, sedation, constipation, somnolence, and dependence, which negatively affects a patient's QOL.9 External beam radiation therapy (EBRT) is the standard second-line treatment for pain from bone metastases; however, radiation is effective in only 60% to 65% of patients, and pain relief may not occur in those patients for two to four weeks after treatment.10-14 EBRT is also limited by its cumulative radiation effects to healthy organs, bone, and surrounding tissue. Patients who have previously had EBRT may be unable to tolerate additional EBRT. Furthermore, for patients who experience some relief from EBRT, the relief is only temporary for about 30% because of disease progression.12,15 Furthermore, retreatment of patients who can be re-irradiated is effective in only about 30% of patients. Its effectiveness may be diminished by having to deliver a smaller dose because of concerns about cumulative radiation dose to normal tissues.10,16-18 Other systemic palliative therapies (e.g., chemotherapy, hormonal therapy, radioisotopes, bisphosphonates) are available; however, many patients experience inadequate pain control or unwanted side effects with these options.1,7,19,20 Thus, new options are needed, particularly for patients who are ineligible for EBRT.

More recent options involve methods to ablate the pain-transmitting cells at the boundary of bone tumors, which is believed to inhibit the patient's ability to feel pain.7 Researchers have explored radiofrequency ablation (RFA), cryoablation, microwave ablation, and most recently high-intensity focused ultrasound (HIFU) guided by magnetic resonance (MR) or ultrasound imaging to palliate pain from bone metastases.1,11 Unlike diagnostic ultrasound, which exposes tissue to biologically insignificant acoustic energy levels, HIFU energy acts on bone primarily through thermal effects.1,21 HIFU energy can rapidly heat tissue to the point at which irreversible thermal ablation and coagulative necrosis occurs.21,22 The periosteum (outer covering of the bone) is the target for HIFU energy as the bone tumor itself may be more or less absorptive depending on whether it is osteolytic or osteoblastic (or mixed). Bone is particularly conducive to HIFU ablation because of its higher ultrasound energy absorption, lower thermal conductance, and less susceptibility to penetration of ultrasound waves than soft tissue.1,15,21,23 As a result, the absorption pattern by bones allows wider surface areas of the bone to be treated with each energy pulse.1,15,21

Imaging guidance with ultrasound or MR is essential throughout all stages of HIFU procedures.24 MRgFUS's major advantages...