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Does Focused Ultrasound for Bone Mets Spark Wider Antitumor Activity?

If cancer spreads from the primary tumor (e.g. breast cancer, prostate cancer, etc.) to the bone, it can do a lot of damage. Metastasis to the bone—or bone mets—can weaken the bone, making it vulnerable to a fracture that’s difficult to repair. Even more frightening, bone mets cause fierce pain for 50-75% of patients. For them, the two conditions severely diminish their quality of life.
Fortunately, the local bone pain and the bone tumor’s damage can be blocked by ablating (destroying) the bony lesion. This is called a local treatment because it targets just the lesion, though it does not cure the disease. In 2012, the FDA approved the use of a noninvasive treatment for pain relief due to bone mets. It is called MRI-guided Focused Ultrasound (MRgFUS), though some studies refer to it as High Intensity Focused Ultrasound (HIFU). When it is used to stop bone pain, it is referred to as palliation.

MRgFUS for bone mets

While there are other approaches to palliative ablation for bone mets (e.g. cryotherapy, radiofrequency ablation) they are invasive so there is a risk of infection and some possible post-treatment discomfort. Another approach uses radiation, but unlike ablation, it takes weeks to bring pain to its lowest level.

On the other hand, MRgFUS involves no surgical entry or radiation. It is an outpatient procedure, often done with light sedation to relax the patient and a nerve block to deaden pain during treatment. It uses beams of ultrasound that pass harmlessly and painlessly through the skin. The beams are aimed at the bone lesion. When they meet at the target, they create enough heat to destroy the bone tumor as well as its blood vessels and nearby nerves. When the nerves are inactivated, the pain signals to the brain stop. When the heat destroys the lesion and its blood vessel, it stops the tumor’s activity and may reduce the size of the tumor, easing pressure on nerves. Best of all, pain relief occurs very rapidly, usually within a day or two.

Thanks to MRgFUS, patients quickly resume normal activities, and quality of life is much improved. Although local treatment is not expected to impact the total cancer burden in the patient’s body, a Canadian research study suggests there may be a broader effect of bone mets ablation by MRgFUS.

Possible wider anti-tumor activity after MRgFUS

A Canadian research team explored the possibility that MRgFUS destruction of a bony lesion affects the cancer cells’ release of cytokines designed to block the immune system’s antitumor action. Cytokines are molecules that are released by both healthy and cancerous cells, and among other things, they help intercellular communication. According to the article,

Cytokines play a significant role in pain initiation and maintenance. Cytokines may be either pro-inflammatory [increase pain] or anti-inflammatory [reduce pain] …Cytokines are mainly involved in the processes of angiogenesis [building new blood vessels], inflammation, wound healing and tumorigenesis [build new tumors]. They can down-regulate and inhibit the immune system of the host, contributing to the growth and progression of tumor.i

The researchers hypothesized that MRgFUS treatment reduces the immunosuppressing cytokine release by tumor cells, thus helping the immune system renew its antitumor activity after treatment. This would occur not only at the local treatment site, which would help control further metastasis from that lesion, but also potentially communicate with the immune system more widely since cytokines circulate in bodily fluid, including urine. In fact, their presence can be measured in urine samples.

Thus, the authors sought to measure levels of inflammatory and anti-inflammatory cytokines and chemokines in urine, both before and after MRgFUS for palliation of bone mets pain, and also to compare the results with patients whose bone mets pain was treated with radiation therapy. All 15 MRgFUS patients in the study gave urine specimens 3 days before and 2 days after MRgFUS.

Study results

The authors identified measure 42 different cytokines potentially in patient urine. They observed that nine specific cytokines were significantly decreased after MRgFUS. When compared with the records of 28 bone mets patients who had radiation, the patterns of higher or lower cytokine levels varied between the two treatments. One treatment difference between the two groups was the absence of pain flare among the MRgFUS group, whereas some of the radiation group had reported post-treatment pain flare. The team discovered that the radiation patients who reported pain flare had lower levels of certain cytokines and higher levels of others than the MRgFUS group, while radiation patients who did not report pain flare had significantly lower levels of other cytokines than the MRgFUS group.

Since the aim of the study was to evaluate cytokine levels in urine after MRgFUS, the authors were able to identify a decrease in nine particular cytokines. While the team could not comment on the exact clinical effect of the cytokines (more research is needed) the implication that MRgFUS may indeed have a wider influence in the immune system as well as local pain control is very encouraging.

If you have been diagnosed with a painful primary bone cancer or bone mets, visit our website for more information. Contact us for a consultation to learn if you are a candidate for MRgFUS.

iBushehri A, Czarnota G, Zhang L, Hynyen K et al. Urinary cytokines/chemokines after magnetic resonance-guided high intensity focused ultrasound for palliative treatment of painful bone metastases. Ann Palliat Med. 2017 Jan;6(1):36-54.

Bone mets