MR-HIFU for treatment of painful bone metastases

Abstract

Purpose: Bone metastases are the most common cause of pain in cancer patients. Palliative radiotherapy is effective in relieving pain in bone metastases and has been the standard of care for decades. Nevertheless, an increasing amount of patients is insufficiently palliated by radiotherapy alone. MRI-guided High Intensity Focused Ultrasound (MR-HIFU) has recently been proposed as a novel noninvasive ablative treatment option for metastatic bone pain. To translate MR-HIFU for painful bone metastases to the clinic, several steps have to be taken. First, a reference value for a new treatment modality needs to be established as in clinical practice patients with unrelieved metastatic bone pain after radiotherapy commonly receive repeat radiotherapy (reirradiation), although its effectiveness is unknown. Then, early evaluation of MR-HIFU on safety, feasibility and effectiveness may provide rationale for larger studies, needed to determine the clinical value of MR-HIFU for treatment of patients with painful bone metastases.

Materials and Methods: In part I, we conducted a meta-analysis (7 studies, n=527) and a 10-year retrospective cohort study (n=247) to determine the effectiveness of reirradiation for painful bone metastases and to identify predictors for response. Also, a matched case-control study (n=114) was conducted to investigate the association between spinal instability and radiotherapy outcome. In part II, a literature review on MR-HIFU in oncology is described. A feasibility study (n=11) on MR-HIFU for patients with painful bone metastases was conducted in pain response and complications were evaluated. Lastly, an international evidence-based consensus on MR-HIFU for painful bone metastases was established among experts in the field to determine current treatment goals, indications and research priorities.

Results: In the meta-analysis an overall pain response rate of 58% of reirradiated patients was found. In the retrospective cohort-study an overall response rate of 43% in an intention-to-treat analysis and 66% in a per-protocol analysis was observed. Patients who showed beneficial response to initial radiation were more likely to respond well to reirradiation. Patients previously treated with systemic therapy were less likely to respond to reirradiation. The matched case-control study showed that patients with increased spinal instability were more likely to be retreated after radiotherapy. In the feasibility study on MR-HIFU for painful bone metastases, no major adverse events were observed and pain response was noted in 67% of patients. The main statements of the consensus were that MR-HIFU is currently a secondary palliative treatment option, and its role in primary treatment of bone metastases as a stand-alone treatment or in combination with radiotherapy needs to be investigated in a three-armed randomized controlled trial.

Conclusions: Overall, the work is this thesis shows there is a clinical need for additional palliative treatments for metastatic bone pain beyond radiotherapy and early results indicate MR-HIFU may be a beneficial treatment option for selected patients. Comparative studies will be needed to establish the exact clinical value of MR-HIFU for patients with painful bone metastases.