The Roles of Magnetic Resonance-Guided Focused Ultrasound in Pain Relief in Patients With Bone Metastases: A Systemic Review and Meta-Analysis

Abstract

ObjectiveCancer pain, the most common skeleton-related event of bone metastases, significantly disturbs patients’ life. MRI-guided focused ultrasound (MRgFUS) is a therapeutic option to relieve pain; however, its efficacy and safety have not been fully explored. Therefore, we aim to conduct a meta-analysis on studies reporting MRgFUS for patients with bone metastases.MethodsRandomized controlled trials (RCT) and non-RCTs on MRgFUS treatment for patients with bone metastases were collected using PubMed, MEDLINE In-Process (US National Library of Medicine), National Institutes of Health (US National Library of Medicine), Embase (Elsevier), Web of Science, CINAHL, and the Cochrane Library between August 2007 and September 2019. Data on quantitative pain assessment before/after MRgFUS, response rate, and complication were extracted and analyzed.ResultsFifteen eligible studies with 362 patients were selected in this meta-analysis. The average pain score was 6.74 (95% CI: 6.30–7.18) at baseline, 4.15 (95% CI: 3.31–4.99) at 0–1 week, 3.09 (95% CI: 2.46–3.72) at 1–5 weeks, and 2.28 (95% CI: 1.37–3.19) at 5–14 weeks. Compared with baseline, the pain improvement at 0–1 week was 2.54 (95% CI: 1.92–3.16, p < 0.01), at 1–5 weeks was 3.56 (95% CI: 3.11–4.02, p < 0.01), and at 5–14 weeks was 4.22 (95% CI: 3.68–4.76, p < 0.01). Change from baseline in OMEDD at 2 weeks after treatment was −15.11 (95% CI: −34.73, 4.50), at 1 month after treatment was −10.87 (95% CI: −26.32, 4.58), and at 3 months after treatment was −5.53 (95% CI: −20.44, 9.38). The overall CR rate was 0.36 (95% CI: 0.24–0.48), PR rate was 0.47 (95% CI: 0.36–0.58), and NR rate was 0.23 (95% CI: 0.13–0.34). Among 14 studies including 352 patients, 93 (26.4%) patients with minor complications and 5 (1.42%) patients with major complications were recorded.ConclusionThis meta-analysis identifies MRgFUS as a reliable therapeutic option to relieve cancer pain for patients with metastatic bone tumors with controllable related complications.

Early economic modeling of magnetic resonance image-guided high intensity focused ultrasound compared to radiotherapy for pain palliation of bone metastases

“…Furthermore, a scenario with MR-HIFU being offered as first-line treatment for all patients increased the ICER (31,048 EUR/QALY), due to a higher increase in costs despite a slight increase in QALYs. Although not considered in our calculations, some case series indicate that patients without prior radiation might respond better to MR-HIFU than those with prior radiation (30,42). The mechanism of action supporting this finding warrants further investigation.…”

“…In contrast, MR-HIFU could be repeated for non-responders since there is theoretically no limit for the accrued acoustic energy (5,30). However, the possibility of repeating MR-HIFU (i.e., MR-HIFU after initial treatment with MR-HIFU) was not considered in this model, because to date there is not sufficient clinical data on the effectiveness and safety of repeating MR-HIFU (30,42). Moreover, long-term outcomes of repeating MR-HIFU such as risk of pathological fracture, duration of pain response, retreatment rates are unknown in this early phase of implementation.…”

High Intensity Focused Ultrasound for Treatment of Bone Malignancies—20 Years of History

“…In a 3-month follow-up period, NRS and VAS pain scores significant decreased from 6.27 ± 1.53 to 2.18 ± 1.04 and from 6.56 ± 2.38 to 1.85 ± 0.96, respectively [18]. A systemic review and meta-analysis, including 15 studies with 362 patients, reported the average pain score at baseline was 6.74 (95% CI: 6.30-7.18), and decreased to 4.15 (95% CI: 3.31-4.99) at 0-1 week, 3.09 (95% CI: 2.46-3.72) at 1-5 weeks, and 2.28 (95% CI: 1.37-3.19) at 5-14 weeks [19]. In a separate systemic review and meta-analysis including 33 studies and 1082 patients, pain response was observed in 79% of patients at 3 months after HIFU treatments, with a mean pain score difference of −3.8 and −4.4 between baseline and 1-month and 3-month follow-up, respectively [20].…”

“…At 90 days post treatment, there was no further increase in MEDD [27]. Based on 2 separate meta-analyses, the change in MEDD after treatments was −15.11 (2 weeks), −10.87 (1 month), and −5.53 (3 months) [19]; meanwhile, on average, 55.8% of patients were able to stop taking pain medication and 33% of patients were able to reduce their analgesic intake [20]. Reducing the need for pain medication would reduce analgesia-related side effects and improve the wellbeing and QoL of patients in palliative settings.…”

Minimally Invasive Interventional Procedures for Metastatic Bone Disease: A Comprehensive Review

“…Pain palliation effect is likely due to local bone denervation, based on the degeneration of nociceptors and primary afferent sensory nerve fibers on the bone surface [ 124 , 125 , 126 , 127 ]. The effectiveness of MRgFUS as a mini-invasive treatment option for metastatic bone pain has been discussed in some literature reviews [ 71 , 120 , 128 , 129 , 130 ] reporting that more than approximately 70% of patients with radiation refractory metastatic bone pain experienced symptom improvement and a reduction of opioid usage after treatment. In addition, pain palliation has proved to be quickly achieved a few days after the procedure, lasting more than 3 months [ 63 ].…”