HIFU for Bone Metastases and other Musculoskeletal Applications

Verpalen

Clinical and Translational Radiation Oncology

et al. 2021

Background: Cancer induced bone pain (CIBP) strongly interferes with patient's quality of life. Currently, the standard of care includes external beam radiotherapy (EBRT), resulting in pain relief in approximately 60% of patients. Magnetic Resonance guided High Intensity Focused Ultrasound (MR-HIFU) is a promising treatment modality for CIBP. Methods: A single arm, R-IDEAL stage I/IIa study was conducted. Patients presenting at the department of radiation oncology with symptomatic bone metastases in the appendicular skeleton, as well as in the sacrum and sternum were eligible for inclusion. All participants underwent EBRT, followed by MR-HIFU within 4 days. Safety and feasibility were assessed, and pain scores were monitored for 4 weeks after completing the combined treatment. Results: Six patients were enrolled. Median age was 67 years, median lesion diameter was 56,5 mm. In all patients it was logistically possible to plan and perform the MR-HIFU treatment within 4 days after EBRT. All patients tolerated the combined procedure well. Pain response was reported by 5 out of 6 patients at 7 days after completion of the combined treatment, and stabilized on 60% at 4 weeks follow up. No treatment related serious adverse events occurred. Conclusion: This is the first study to combine EBRT with MR-HIFU. Our results show that combined EBRT and MR-HIFU in first-line treatment of CIBP is safe and feasible, and is well tolerated by patients. Superiority over standard EBRT, in terms of (time to) pain relief and quality of life need to be evaluated in comparative (randomized) study.

Section: Introductionmentioning

confidence: 99%

“…In this study response occurred within three days after MR-HIFU treatment [13] . Secondly, there may be a complimentary effect of MR-HIFU and EBRT, as both treatments have a slightly different mechanism of action [21] . Until now, there is no evidence available on the feasibility or safety of combined EBRT and MR-HIFU treatment.…”

Section: Introductionmentioning

confidence: 99%

Combining radiotherapy and focused ultrasound for pain palliation of cancer induced bone pain; a stage I/IIa study according to the IDEAL framework

Verpalen

Clinical and Translational Radiation Oncology

et al. 2021

“…MRI‐guided high intensity focused ultrasound (MR‐HIFU) allows non‐invasive treatments of various conditions 1 by thermal ablation, and its effectiveness for treatment of patients with painful bone metastases has been clinically demonstrated. 2 Pain reduction in these patients is achieved by ablation of the periosteum in the proximity of the metastases. MRI is a reliable guidance technique for HIFU, due to its excellent soft‐tissue contrast and its capacity to map tissue temperature changes.…”

Section: Introductionmentioning

confidence: 99%

Interleaved water and fat MR thermometry for monitoring high intensity focused ultrasound ablation of bone lesions

Lena

Magnetic Resonance in Med

et al. 2021

Purpose To demonstrate that interleaved MR thermometry can monitor temperature in water and fat with adequate temporal resolution. This is relevant for high intensity focused uUltrasounds (HIFU) treatment of bone lesions, which are often found near aqueous tissues, as muscle, or embedded in adipose tissues, as subcutaneous fat and bone marrow. Methods Proton resonance frequency shift (PRFS)‐based thermometry scans and T1‐based 2D variable flip angle (2D‐VFA) thermometry scans were acquired alternatingly over time. Temperature in water was monitored using PRFS thermometry, and in fat by 2D‐VFA thermometry with slice profile effect correction. The feasibility of interleaved water/fat temperature monitoring was studied ex vivo in porcine bone during MR‐HIFU sonication. Precision and stability of measurements in vivo were evaluated in a healthy volunteer under non‐heating conditions. Results The method allowed observing temperature change over time in muscle and fat, including bone marrow, during MR‐HIFU sonication, with a temporal resolution of 6.1 s. In vivo, the apparent temperature change was stable on the time scale of the experiment: In 7 min the systematic drift was <0.042°C/min in muscle (PRFS after drift correction) and <0.096°C/min in bone marrow (2D‐VFA). The SD of the temperature change averaged over time was 0.98°C (PRFS) and 2.7°C (2D‐VFA). Conclusions Interleaved MR thermometry allows temperature measurements in water and fat with a temporal resolution high enough for monitoring HIFU ablation. Specifically, combined fat and water thermometry provides uninterrupted information on temperature changes in tissue close to the bone cortex.

“…11,12 MR-HIFU is a non-invasive image-guided treatment modality, which can deliver acoustic energy to heat target tissue to ablative temperatures. 11,13 One of many potential applications of MR-HIFU is in palliative pain treatment for CIBP, in which the pain palliation mechanism is hypothesized to be through ablation of periosteal nerves and tumor debulking. Previous studies have shown that pain response may occur within three days after MR-HIFU treatment, and response rates are promising with pain responses ranging from 67-88% of patients.…”

Section: Introductionmentioning

confidence: 99%

Focused Ultrasound and RadioTHERapy for Non-Invasive Palliative Pain Treatment in Patients with Bone Metastasis: A Study Protocol for the Three Armed Randomized Controlled FURTHER-trial

Bos

et al. 2021

Preprint

Self Cite

Background Cancer Induced Bone Pain (CIBP), caused by bone metastases, is a common complication of cancer and strongly impairs quality of life (QoL). External Beam RadioTherapy (EBRT) is the current standard of care for treatment of CIBP. However, approximately 45% of patients have no adequate pain response after EBRT. Magnetic Resonance image guided High Intensity Focused Ultrasound (MR-HIFU) may improve pain palliation in this patient population. Methods/design: The FURTHER trial is an international multicenter, three-armed randomized controlled trial. A total of 216 patients with painful bone metastases will be randomized in a 1:1:1 ratio to receive EBRT only, MR-HIFU only, or combined treatment with EBRT followed by MR-HIFU. During a follow-up period of six months, patients will be contacted at eight time points to retrieve information about their level of pain, QoL and the occurrence of (serious) adverse events. The primary outcome of the trial is pain response at 14 days after completion of treatment. Secondary outcomes include pain response at 14 days after trial enrolment, pain scores (daily until the 21st day, weekly until the 6th week and monthly until the 6th month), toxicity, adverse events, QoL, and survival. Cost-effectiveness and cost-utility analysis will be conducted. Discussion The FURTHER trial aims to evaluate the effectiveness and cost-effectiveness of MR-HIFU – alone or in combination with EBRT – compared to EBRT to relieve CIBP. The trial will be performed in six hospitals in four European countries, all of which are partners in the FURTHER consortium. Trial registration: The FURTHER trial is registered under the Netherlands Trials Register number NL71303.041.19 and ClinicalTrials.gov registration number NCT04307914. Date of trial registration is 13-01-2020.