New Approaches to Management of Bone Lesions
Dr. Matthew Callstrom, Professor of Radiology at the Mayo Clinic College of Medicine and a specialist in radiofrequency ablation and cryoablation, talks with Dr. Tony Nimeh of PracticeUpdate about ablation techniques used for palliation and treatment of painful metastases involving bone.
Dr. Nimeh: Dr. Callstrom, what are the most common cancers that metastasize to the bone, and approximately how many patients per year would you say are suffering from this problem?
Dr. Callstrom: Overall, about a million people develop cancer in the United States every year, and, ultimately, about 200,000 end up with bone metastases. Of those, a significant portion ends up with metastases that are either limited in number or cause significant pain. Most of these patients are ultimately treated with radiation therapy. Of those who are treated with radiation therapy for painful metastases, about 80% do pretty well. Between 20% and 30% end up with painful metastases that don’t respond, and those patients are the ones who typically are treated with different ablative techniques, which are helpful in terms of symptom treatment.
Dr. Nimeh: What is the main goal of the treatment? Pain control, cancer control, or both?
Dr. Callstrom: The majority of patients with metastases that go to the bony skeleton are treated for palliation, meaning that they are treated for pain, or to prevent progression that would lead to significant morbidity, such as a fracture. A smaller number of patients have limited metastatic disease—also called oligometastatic disease—and these patients can be treated with radiation therapy, surgery if it’s reasonable, or with ablative techniques.
Dr. Nimeh: What ablative options are available, and how do you decide which patient needs which therapeutic modality?
Dr. Callstrom: Multiple ablative technologies are available. The first that was used for palliation was radiofrequency ablation, a heat-based technique that works very well. Other heat-based techniques including microwave ablation and, most recently, MR-guided focused ultrasound, heat up the tissue and destroy cancer growth, which typically leads to the effective reduction or elimination of pain.
Cryoablation is a method of freezing the tissue, with the same goal of destroying the tissue and roughly the same outcomes as is achieved with all of these different ablative techniques.
Deciding which technique to use in an individual patient gets into the technical aspects of treatment. If the cancer is in a difficult location, meaning near neural structures or adjacent to bowel or bladder, then we feel that visibility is very important. In this situation, using cryoablation is advantageous because you can see the ablation zone as you perform the procedure. You can also monitor neural function with cryoablation and, in that way, avoid injury.
The most recently introduced approach is MR-guided focused ultrasound, which also has some important advantages. You can use the focused ultrasound and ablate across normal tissue as long as it isn’t in the zone of heat. It can also be used in more difficult areas.
Dr. Nimeh: What are the inclusion and exclusion criteria for these treatments?
Dr. Callstrom: The typical patient considered for palliation treatment is someone with metastatic disease involving bone or soft tissue that causes pain. The patient can have multiple metastatic lesions, but only one, two, or maybe three, might be painful. When you examine the patient, the painful area correlates with an abnormality on imaging toward which you can direct your therapy.
Osteolytic metastatic disease or metastatic disease with a soft tissue component is typically amenable to treatment; osteoblastic or sclerotic lesions are also possible to treat, but they tend to be more multifocal and it is harder to determine the exact location of the source of pain. As long as you have a physical finding that correlates with an imaging finding, you can direct the therapy.
Patients excluded from treatment include those who have widespread, painful, multifocal disease. Cancers that involve the cord or important motor nerves in a way that cannot be treated effectively are really not amenable to treatment.
The focus of the treatment effort is really to improve quality of life. Patients who have mild pain—a pain score of around 1 to 3—typically do pretty well with oral medication. A pain score higher than about 4 indicates moderate to severe pain. You can certainly use oral medications in those patients, and you’d typically transition to narcotic or opioid medications for those types of symptoms, but many patients say that the pain negatively impacts their quality of life and would prefer to eliminate or reduce it, if possible. In those situations, radiation therapy would be the first-line, gold-standard treatment. If patients respond to external beam radiation therapy, that’s fantastic; if they don’t, or if they have recurrent pain, you could certainly reconsider radiation, but, if that doesn’t work for the patient, then you transition to using focal therapies, such as ablation.
Dr. Nimeh: Are there any risks, such as fractures, associated with these treatments?
Dr. Callstrom: The risks depend on the circumstances of the situation. If you’re dealing with a small, painful metastatic lesion, the typical risk profile is the same as for any other intervention—bleeding and infection, which are relatively small risks in approximately 1% of patients.
If patients have significant bony destruction, where the bone or the structure is already at risk for fracture, then it’s hard to know whether or not they would eventually fracture anyway or whether the intervention itself increases that risk. We don’t really think that the intervention increases the risk so long as the ablation is performed in a way that that does not further weaken the bone. In a few special situations, such as structural locations in the spine or near the hip joint, we know that, if the patient progresses, or sometimes even in his or her current state, the patient is at risk for fracture. In those situations, we will typically ablate those areas and then try to provide further support for that structure with bone cement to reduce the risk for fracture. Over the past 5 years or so, we have been finding that this approach does seem to provide some protection against fracture.
Dr. Nimeh: Have there been any important trials on these treatments?
Dr. Callstrom: Multiple phase I/II clinical trials have been performed in the past 5 to 10 years, including trials for radiofrequency ablation that worked well. We saw significant numbers of patients who did very well following treatment. A trial with cryoablation showed good clinical outcomes, and, more recently, a trial evaluating MR-guided focused ultrasound was concluded.1 In this trial, the researchers found that the placebo effect was relatively small, and, in patients who experienced the placebo effect, it was short-lived, and their pain returned close to their initial pain scores in a short period of time. I think that the trial demonstrated that the focal therapy approach for patients with a few painful metastases is an effective treatment.
It is important to recognize that the different types of ablative technologies are effective in the hands of experienced professionals. A person who is well-versed in the use of the various approaches is likely to see the same outcomes, irrespective of the type of ablative technology being used. When you transition to local control—meaning that you eradicate the entire tumor—you start to see differences based on the technologies that are used. This becomes important for patients with limited metastatic disease and patients who will live a long time with their disease. For example, patients with renal cancer will often have a long survival after their initial diagnosis, even with metastatic disease. Therefore, it is important to try to achieve local control so that you do not have to go back and retreat areas, which can cause the patient further morbidity associated with repeated treatments.
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