Neoplasms

Symptoms and General Pathology

All Conditions

Musculoskeletal Diseases

Neoplasm Metastasis

Pain

Bone Neoplasms

Neoplastic Processes

Bone Diseases

Patients with bone metastasis causing pain.

HIFU is the use of focused ultrasound energy to penetrate through soft tissue and causes localized high temperatures (55°C to 70°C) for a few seconds within the target producing well defined regions of protein and nerve denaturation, irreversible cell damage, and coagulative necrosis.

High Intensity Focused Ultrasound

Hervé Trillaud, Professor

This study is to confirm the safety and technical of MRI guided High Intensity Focused Ultrasound (HIFU) for Palliation for Pain of Skeletal Metastases.

MRI guided high intensity focused ultrasound uses ultrasound to heat and thermally ablate tissue. The MRI system identifies the ultrasound path and monitors heat rise in the tissue. The goal of the study is to show treatment safety and effectiveness. MR-guided HIFU will be performed in patients who pass inclusion/exclusion criteria.

Bone is the third most common site of metastases spread after the liver and the lungs, with a great incidence in breast, prostate, lung, kidney and thyroid cancers. For example, 90% of patients dying from breast cancer and most of patients with advanced prostate cancer suffer from bone metastases, which are frequently responsible of chronic pain and lead to an increase in morbidity and mortality with pathological fractures, compression syndrome and hypercalcemia..Moreover, the increasing longevity of patients with cancer resulting from the improvement of the effectiveness of the treatments leads to a higher incidence and prevalence of metastating bone lesions.

Palliative treatment with management of pain and improvement of quality of life remains the first goal of therapy. Current treatments options include systemic drug therapy (chemotherapy, hormonal therapy, analgesics and bi-phosphonates), local invasive treatment (surgery), local mini-invasive treatment with interventional radiological techniques (cimentoplasty, cryotherapy and radiofrequency ablation) and radiation therapy.

External-beam radiation therapy remains the current standard of care for patients with bone metastases in first intention. However, up to 20-30 % of patients treated do not experience pain relief and recurrence of pain appear in 27 % after treatment. Moreover radiation treatment is limited due to accumulation of dose. Since few years, cryotherapy and percutaneous radiofrequency ablation have shown good results in management of pain with bone metastases, however these techniques are still invasive.

In MRI-guided High Intensity Focused Ultrasound (HIFU), the ultrasound generated by the transducer is focused into a small focal tissue volume at specific target locations. During treatment, the beam of focused ultrasound energy penetrates through soft tissue and causes localized temperatures elevation up 55-70°C for a few seconds within the target producing well defined regions of irreversible protein denaturation, cell damage, and coagulative necrosis. A single exposure of focused ultrasound energy is called a "sonication." Multiple sonications are necessary to ablate the targeted tissue. Tight focusing is designed to limit the ablation to the targeted location.

Applying HIFU energy to a patient's lesion requires treatment planning, targeting of the ultrasound (US) beam to desired locations and monitoring of the energy delivery. In some applications this can be performed using diagnostic ultrasound imaging in combination with the HIFU. While diagnostic US provides some anatomical details and helps with procedure planning and treatment targeting, it does not provide 3D planning, means of measuring the temperature increase generated by HIFU, or metrics for quantifying the energy/dose delivered to the treatment zone. Currently, only MR imaging can provide a validated non-invasive temperature measurement and thermal dose quantification in the treated tissue. Furthermore, these real-time MR temperature measurements can be used to control the HIFU system to deliver optimal temperatures to the target locations. The Philips MR-guided focused ultrasound system will provide real-time tissue temperature mapping in multiple planes and control of the temperature delivering dose to the target location. Recent advances in MR temperature mapping make it possible to achieve temperature accuracy of 1°C in stationary soft tissues.

Pilot Study for Palliation of Pain in Bone Metastases by MR-HIFU

Pilot Study for the Treatment of Bone Metastases by High Intensity Focused Ultrasound Guided by MRI to Perform Pain Palliation

Technical efficacy of HIFU for treatment of bone metastasis as assessed by a change in the medication and pain scores

Safety of HIFU for treatment of the bone metastasis as determined by adverse event reporting

Safety of HIFU for treatment of the bone metastasis as determined by formation of intended lesions.

Philips Healthcare

All patients undergoing thermal ablation and cementoplasty procedure for one or more painful bone lesion

Percutaneous thermal ablation with subsequent cementoplasty in a single procedure

Ablation and Cementoplasty

Jason K Wong

Stefan Przybojewski

Stefan Przybojewski, MD

The aim of this research study is to assess the effectiveness of combined ablation and cementoplasty in the treatment of spinal, pelvic, and extraspinal lesions causing pain resistant to conventional treatment at our centre. In particular, the investigator seek to verify the safety and efficacy for multiple primary tumor types and benign lesions as well as encompass multiple measurements of outcome, including visual analog scale (VAS) for pain, opioid and analgesic use, and overall performance scales, combined with cross-sectional imaging follow-up to assess tumor burden, to ascertain a comprehensive Canadian single-centre experience that has been lacking in previous studies.

Research Question \& Objectives

1. To conduct a prospective, single-centre study of combined ablation and cementoplasty treatment for painful spinal and extraspinal osseous lesions.
2. Report the technical outcome and safety of percutaneous ablation prior to image-guided cementoplasty in a single treatment session.
3. Review the effectiveness and durability of pain control, local tumor control, and the impact on QoL using ablation and cementoplasty in treating spinal/extraspinal osseous tumors.
4. Assess the feasibility and efficacy of ablation and cementoplasty treatment for different primary tumor types and benign lesions.

Research Design

The investigators will conduct a single-centre, single-arm, cohort analysis of all patients who undergo cementoplasty for osseous disease in the department of interventional radiology over a two-year period. This will be a prospective paired comparison study with patients serving as their own controls. Technical success and procedural complications will be monitored and recorded for all patients. All patients will be followed until death or 3 months post-procedure.

The investigators aim to enroll a minimum of 40 patients referred for symptomatic osseous lesions. Bipolar radiofrequency ablation (Osteocool RFA system, Medtronic) or cryoablation (Visual Ice Cryoablation, Boston Scientific) will be performed under CT, ultrasound, or fluoroscopic guidance at the discretion of the treating radiologist, and immediately followed by cement injection. Radiological outcomes, including local tumor control and disease progression, will be assessed by CT imaging immediately post-procedure as well as 3-month follow-up. Clinical outcomes will be evaluated by VAS, analgesic use, and QoL assessment using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) prior to procedure and immediately post-procedure, as well at 1-week, 1-month, and 3-month intervals post-procedure.

Single-arm prospective study of pain and quality of life before and after ablation/cementoplasty procedure

Ablation and Cementoplasty for Painful Bone Lesions

Percutaneous Ablation and Cementoplasty for Painful Bone Lesions: A Canadian Single-Centre Experience

Visual Analog Scale; values 0-10 with 0 being no pain and 10 being the worst pain imaginable.

European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). The QLQ-C30 is composed of 3 multi-item scales including a functional scale, a global health status/quality of life scale, and a symptom scale. Each scale ranges in score from 0-100 with a higher scale score representing a high/healthy level of functioning, quality of life, and symptomatology/problems, respectively.

Tumor burden as assessed by CT scan following procedure as compared to pre-procedure scan

University of Calgary

Interventional Radiologist; Clinical Associate Professor, University of Calgary

Skin and Connective Tissue Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Respiratory Tract (Lung and Bronchial) Diseases

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

Rare Diseases

Breast Neoplasms

Prostatic Neoplasms

Osteosarcoma

Lung Neoplasms

Multiple Myeloma

Neoplasms, Plasma Cell

Cancer Pain

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Neoplasms, Bone Tissue

Neoplasms, Connective Tissue

Neoplasms, Connective and Soft Tissue

Sarcoma

Soft Tissue Sarcoma

Exablate treatment

Radiation

The goal of this study is to collect comparative data on safety and efficacy of MR Guided Focused Ultrasound and External Beam Radiation for treatment of metastatic bone tumors or multiple myeloma.

Bone is the third most common organ involved by metastatic disease behind lung and liver \[6\]. In breast cancer, bone is the second most common site of metastatic spread, and 90% of patients dying of breast cancer have bone metastasis. Breast and prostate cancer metastasize to bone most frequently, which reflects the high incidence of both these tumors, as well as their prolonged clinical courses. Post-cancer survival has increased with improvement in early detection and treatments. As a consequence, the number of patients developing metastatic bone disease during their lifetime has also increased.

Current treatments for patients with bone metastases are primarily palliative and include localized therapies (radiation and surgery), systemic therapies (chemotherapy, hormonal therapy, radiopharmaceutical, and bisphosphonates although the primary goal of the use of these therapies are often to address the disease itself), and analgesics (opioids and non-steroidal anti-inflammatory drugs). Recently, radiofrequency ablation has been tested as a treatment option for bone metastases \[8\]. Currently, an off label use of Cryoablation techniques are being tested as another alternative for bone Mets palliation. The main goals of these treatments are improvement of quality of life and functional level. These goals can be further described:

* Pain relief
* Preservation and restoration of function
* Local tumor control
* Skeletal stabilization

Treatment with external beam radiation therapy (EBRT) is the standard of care for patients with localized bone pain, and results in the palliation of pain for many of these patients. Twenty to 30% of patients treated with radiation therapy do not experience pain relief \[9-13\]. Re-treatment rates are generally reported in the range of 10-25%. Many patients with relapsed pain or poor response to initial radiation may be lost to follow up or may not be referred back to oncologists for consideration of re-radiation. In addition to relapse and re-treatment, there is an increased risk of pathologic fracture in the peri-radiation period. The fracture rate reported in radiation studies is generally in the range of 1% to 8%. The hyperemic response weakens the adjacent bone and increases the risk of spontaneous fracture. Furthermore, patients who have recurrent pain at a site previously irradiated may not be eligible for further radiation therapy secondary to limitations in normal tissue tolerance. Hesitation on the part of physicians to use a larger dose may be related to increased long-term toxicity. Larger radiation dose produces a greater risk of complications such as fibrosis of normal soft tissue, which can cause a decrement in the quality of life in cases of life expectancy longer than 6 months. There may also be a greater incidence of acute side effects of nausea and vomiting if the treatment field includes the stomach. The percent of patients experiencing vomiting following EBRT ranges from about 5% to 30%.

A palliative treatment for painful bone metastases that is non-invasive, without long-term toxicity and having minimal complications would be a useful tool for treating physicians and also a beneficial option for patients suffering from painful bone metastases. Results of preliminary studies indicate that ExAblate treatment of painful bone metastases may be a beneficial treatment option \[14, 15\]. The ExAblate system is a non-invasive thermal ablation device used in the coagulation of various types of soft tissue. The ExAblate system has the potential to achieve the first three of the four previously mentioned goals in the treatment of bone tumors; namely pain relief, preservation and restoration of functional levels and local tumor control \[11\].

This study will compare the safety and effectiveness of MR Guided Focused Ultrasound and External Beam Radiation for treatment of metastatic bone tumors or multiple myeloma.

Study Comparing the Safety and Effectiveness of Magnetic Resonance Guided Focused Ultrasound (MRgFUS) and External Beam Radiation (EBRT) for Treatment of Metastatic Bone Tumors and Multiple Myeloma

Phase IIIA Study Comparing the Safety and Effectiveness of MR Guided Focused Ultrasound and External Beam Radiation for Treatment of Metastatic Bone Tumors and Multiple Myeloma

Incidence and severity of adverse events associated with the ExAblate MRgFUS bone system used in the palliation of pain due to metastatic bone tumors or multiple myeloma to that of EBRT

Effect of treatment with MRgFUS ExAblate Bone System (BS) of painful bone tumors or multiple myeloma

Improved quality of life (measured by questionnaires)

InSightec

ExAblate 2100 ablation for the treatment of painful bone metastases.

ExAblate 2100

A study to evaluate the safety and initial effectiveness of the ExAblate 2100 Conformal Bone System in the treatment of pain resulting from metastatic bone tumors.

Bone is the third most common organ involved by metastatic disease behind lung and liver \[6\]. In breast cancer, bone is the second most common site of metastatic spread, and 90% of patients dying of breast cancer have bone metastasis. Breast and prostate cancer metastasize to bone most frequently, which reflects the high incidence of both these tumors, as well as their prolonged clinical courses. Post-cancer survival has increased with improvement in early detection and treatments. As a consequence, the number of patients developing metastatic bone disease during their lifetime has also increased.

Current treatments for patients with bone metastases are primarily palliative and include localized therapies (radiation and surgery), systemic therapies (chemotherapy, hormonal therapy, radiopharmaceutical, and bisphosphonates although the primary goal of the use of these therapies are often to address the disease itself), and analgesics (opioids and non-steroidal anti-inflammatory drugs). Recently, radiofrequency ablation has been tested as a treatment option for bone metastases \[8\]. Currently, an off label use of Cryoablation techniques are being tested as another alternative for bone Mets palliation. The main goals of these treatments are improvement of quality of life and functional level. These goals can be further described:

1. Pain relief
2. Preservation and restoration of function
3. Local tumor control
4. Skeletal stabilization

Treatment with external beam radiation therapy (EBRT) is the standard of care for patients with localized bone pain, and results in the palliation of pain for many of these patients. Twenty to 30% of patients treated with radiation therapy do not experience pain relief \[9-13\]. Re-treatment rates are generally reported in the range of 10-25%. Many patients with relapsed pain or poor response to initial radiation may be lost to follow up or may not be referred back to oncologists for consideration of re-radiation. In addition to relapse and re-treatment, there is an increased risk of pathologic fracture in the peri-radiation period. The fracture rate reported in radiation studies is generally in the range of 1% to 8%. The hyperemic response weakens the adjacent bone and increases the risk of spontaneous fracture. Furthermore, patients who have recurrent pain at a site previously irradiated may not be eligible for further radiation therapy secondary to limitations in normal tissue tolerance. Hesitation on the part of physicians to use a larger dose may be related to increased long-term toxicity. Larger radiation dose produces a greater risk of complications such as fibrosis of normal soft tissue, which can cause a decrement in the quality of life in cases of life expectancy longer than 6 months. There may also be a greater incidence of acute side effects of nausea and vomiting if the treatment field includes the stomach. The percent of patients experiencing vomiting following EBRT ranges from about 5% to 30%.

A palliative treatment for painful bone metastases that is non-invasive, without long-term toxicity and having minimal complications would be a useful tool for treating physicians and also a beneficial option for patients suffering from painful bone metastases. Results of preliminary studies indicate that ExAblate treatment of painful bone metastases may be a beneficial treatment option \[14, 15\]. The ExAblate system is a non-invasive thermal ablation device used in the coagulation of various types of soft tissue. The ExAblate system has the potential to achieve the first three of the four previously mentioned goals in the treatment of bone tumors; namely pain relief, preservation and restoration of functional levels and local tumor control \[11\]. The ExAblate system used in the present study is a technological advance over the ExAblate 2000 fixed transducer system in terms of flexibility of use and reduction of positioning related pain to the patients. The ExAblate system used in this study conforms to the patient's body shape at the location of the bone mets location.

ExAblate Conformal Bone System Treatment of Metastatic Bone Tumors for the Palliation of Pain

A Feasibility Study to Evaluate the Safety and Initial Effectiveness of ExAblate MR Guided Focused Ultrasound Surgery in the Treatment of Pain Resulting From Metastatic Bone Tumors With the ExAblate 2100 Conformal Bone System

Adverse effects outcomes are reported in the adverse events module.

Efficacy was evaluated by change in Numerical Rating Scale (NRS) pain scores at 3 months post treatment The NRS is an 11 point scale (0-10) with 0 as no pain and 10 as the worst pain. Larger numbers in score change from baseline indicate improvement (decrease) in pain. Two points improvement has been reported as a clinically meaningful.

Quality of life was evaluated using average change from baseline at 3 Months using the Pain Interference section of the Brief Pain Inventory (BPI-Pain Interference). Larger change from Baseline numbers indicate improved function. Pain Interference is the mean of seven questions scored on an 11-point scale of 0 (does not interfere) to 10 (completely interferes). A positive change from Baseline (higher values) at the 3 Month visit indicates improvement or a reduction in pain interference

ExAblate 2100 ablation for the treatment of painful bone metastases.

ExAblate 2100: Conformal Bone System

ExAblate 2100 Treatment

Age, Continuous

Sex: Female, Male

Hispanic

Black

White

Asian

Pacific Islander

The baseline characteristics were tabulated for the treated subjects.

Race/Ethnicity, Customized

United States

Region of Enrollment

The study was terminated early leading to small numbers of subjects analyzed. The study was designed to enroll 50 subjects. Enrollment was terminated after enrolling 17 subjects.

Nadir Alikacem

Number of Adverse Device Effects

Change in NRS Pain Scores From Baseline at 3 Months

Change Brief Pain Inventory - Pain Interference From Baseline at 3 Months

Overall Study

Behaviors and Mental Disorders

Neoplasms, Second Primary

Bone Marrow Diseases

Quality of Life

Analgesics

All Drugs and Chemicals

Combination of focused ultrasound and external beam radiotherapy

Following standard EBRT (single or multiple fraction), patients will receive one MR-HIFU treatment with the Profound Sonalleve MR-HIFU device on the most painful of their bone metastases. This treatment will take place in a short time frame of 3 hours to maximum 4 days. Patients will be followed up until 4 weeks after treatment. During follow-up they will be phoned around day 3, 7, 14, 21 and 28 to retrieve pain scores, pain medication and (serious) adverse events. At day 3 the patient's experience with the combined treatment will also be inquired.

combined radiotherapy and MR-HIFU

Helena M Verkooijen, MD, PhD

The PRE-FURTHER study aims to evaluate the feasibility of the combined treatment with radiotherapy and focussed ultrasound for pain palliation in patients with painful bone metastases, and to optimize the combined treatment logistics. Six to ten patients will be included according to in- and exclusion criteria.

Rationale: Metastatic bone pain strongly interferes with quality of life and daily functioning of patients with advanced cancer. Pain palliation may be improved by including magnetic resonance image guided high intensity focused ultrasound (MR-HIFU) in addition to External Beam Radiotherapy (EBRT). For this purpose, feasibility and optimal logistics of the combined treatment need to be evaluated.

Objective: The PRE-FURTHER project aims to evaluate the feasibility of the combined EBRT and MR-HIFU treatment for relief of metastatic bone pain, and to optimize the combined treatment logistics.

Study design: The PRE-FURTHER study is a prospective case series, stage I and IIA study according to the Innovation, Development, Evaluation, Assessment and Long term evaluation (IDEAL) recommendations. 6-10 patients will receive MR-HIFU treatment following standard EBRT.

Endpoints: The main outcome of this study is the feasibility of the procedure, in terms of planability as well as patient-tolerability of the combined treatment within a short time frame (3 hours - 4 days interval). In addition, pain relief and safety of the combined procedure will be monitored.

Prospective case series (n = 6 - 10), stage I and IIA study according to the Innovation, Development, Evaluation, Assessment and Long term evaluation (IDEAL) recommendations. The study will be performed in male and female adult (≥ 18 years) cancer patients capable of giving informed consent and referred for EBRT of painful bone metastases (Numerical Rating Scale (NRS) ≥ 4).

Feasibility of Combined Focused Ultrasound and Radiotherapy Treatment in Patients With Painful Bone Metastasis

Feasibility of Combined Focused Ultrasound and Radiotherapy Treatment in Patients With Painful Bone Metastasis - the PRE-FURTHER Study -

The main outcome of this study is the feasibility of the combined procedure in terms of patient tolerance and hospital logistics. Patient tolerance will be assessed using a Patient Reported Experience Measure questionnaire.

The main outcome of this study is the feasibility of the combined procedure in terms of patient tolerance and hospital logistics. Hospital logistics will be assessed by analysing comments of the treating physicians and research staff on the problems that occurred during treatment planning, and whether extra hospital visits that were needed.

Patient reported pain scores will be based on a Numeric Rating Scale (from 0 to 10 with 0 being no pain and 10 being the worst pain imaginable) from the Brief Pain Inventory (BPI) questionnaire \[Cleeland 1994\].

Toxicity/safety of the combined treatment will be assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0

Isala

UMC Utrecht

Principal Investigator

High intensity focused ultrasound energy, delivered under the guidance of the MR images (MgFUS) allows for a predefined amount of energy to be delivered in the desired target (Metastasis). Bone readily absorbs focused ultrasound energy resulting in a thermo-related neurolysis of the periostium with consequent pain palliation. The amount of energy delivered can be modulated with the objective to penetrate cortical space and obtain necrosis of the metastasis thus preventing local recurrence.

Focused ultrasound energy is accumulated into the target tissue (skeletal metastasis) thanks to the real time guidance of the MR images.

MRgFUS

Alessandro Napoli, MD, PhD

Magnetic Resonance guided Focused Ultrasound (MRgFUS) has demonstrated to be effective for pain control through thermally-induced cell death and periosteal denervation caused by cortical heating relative to acoustic energy absorption. There is also evidence that a high intensity focused ultrasound beam can penetrate through the cortical bone to the medullary space, producing thermal necrosis of cancer tissue. However, little is known about the potential effects of MRgFUS as first line therapeutic modality for pain palliation in skeletal metastases.

Our hypothesis sought to assess the clinical performance of MRgFUS primary treatment of painful bone metastases and determine the potential of this technique for local tumor control.

Unlike previous studies, in which patients were enrolled for MRgFUS treatment because of the failure of other therapies, our study will be conducted in patients not previously treated with EBRT to the targeted lesion.

This is an important new feature, especially given the advantages of MRgFUS, such as lack of ionizing radiation, the ability to conduct treatment on an outpatient basis and the possibility to repeat the treatment as necessary.

Primary Pain Palliation in Bone Metastases Treated With Magnetic Resonance-guided Focused Ultrasound

Primary Pain Palliation and Local Tumor Control in Bone Metastases Treated With Magnetic Resonance-guided Focused Ultrasound

Patients will be monitored for major or minor adverse events

necrosis of the actual lesion will be analyzed according to area on non-perfused volume at the end of the procedure

University of Roma La Sapienza

MD, PhD

The goal of this prospective, non-randomized, single-arm, phase 2 study is to evaluate the safety and effectiveness of this treatment using this ExAblate conformal system in the treatment of pain resulting from metastatic bone tumors Up to Fifty (50) patients will be recruited in this feasibility study. The treated patients will be followed for 3-Months post their last treatment, patients with the standard contraindications to MRI examination, such as implanted metal devices (pacemakers, etc.), will be excluded.

Bone is the third most common organ involved by metastatic disease behind lung and liver \[6\]. In breast cancer, bone is the second most common site of metastatic spread, and 90% of patients dying of breast cancer have bone metastasis. Breast and prostate cancer metastasize to bone most frequently, which reflects the high incidence of both these tumors, as well as their prolonged clinical courses. Post-cancer survival has increased with improvement in early detection and treatments. As a consequence, the number of patients developing metastatic bone disease during their lifetime has also increased.

Current treatments for patients with bone metastases are primarily palliative and include localized therapies (radiation and surgery), systemic therapies (chemotherapy, hormonal therapy, radiopharmaceutical, and bisphosphonates although the primary goal of the use of these therapies are often to address the disease itself), and analgesics (opioids and non-steroidal anti-inflammatory drugs). Recently, radiofrequency ablation has been tested as a treatment option for bone metastases \[8\]. Currently, an off label use of Cryoablation techniques are being tested as another alternative for bone Mets palliation. The main goals of these treatments are improvement of quality of life and functional level. These goals can be further described:

1. Pain relief
2. Preservation and restoration of function
3. Local tumor control
4. Skeletal stabilization

Treatment with external beam radiation therapy (EBRT) is the standard of care for patients with localized bone pain, and results in the palliation of pain for many of these patients. Twenty to 30% of patients treated with radiation therapy do not experience pain relief \[9-13\]. Re-treatment rates are generally reported in the range of 10-25%. Many patients with relapsed pain or poor response to initial radiation may be lost to follow up or may not be referred back to oncologists for consideration of re-radiation. In addition to relapse and re-treatment, there is an increased risk of pathologic fracture in the peri-radiation period. The fracture rate reported in radiation studies is generally in the range of 1% to 8%. The hyperemic response weakens the adjacent bone and increases the risk of spontaneous fracture. Furthermore, patients who have recurrent pain at a site previously irradiated may not be eligible for further radiation therapy secondary to limitations in normal tissue tolerance. Hesitation on the part of physicians to use a larger dose may be related to increased long-term toxicity. Larger radiation dose produces a greater risk of complications such as fibrosis of normal soft tissue, which can cause a decrement in the quality of life in cases of life expectancy longer than 6 months. There may also be a greater incidence of acute side effects of nausea and vomiting if the treatment field includes the stomach. The percent of patients experiencing vomiting following EBRT ranges from about 5% to 30%.

A palliative treatment for painful bone metastases that is non-invasive, without long-term toxicity and having minimal complications would be a useful tool for treating physicians and also a beneficial option for patients suffering from painful bone metastases. Results of preliminary studies indicate that ExAblate treatment of painful bone metastases may be a beneficial treatment option \[14, 15\]. The ExAblate system is a non-invasive thermal ablation device used in the coagulation of various types of soft tissue. The ExAblate system has the potential to achieve the first three of the four previously mentioned goals in the treatment of bone tumors; namely pain relief, preservation and restoration of functional levels and local tumor control \[11\]. The ExAblate system used in the present study is a technological advance over the ExAblate 2000 fixed transducer system in terms of flexibility of use and reduction of positioning related pain to the patients. The ExAblate system used in this study conforms to the patient's body shape at the location of the bone mets location

Focused Ultrasound Surgery in the Treatment of Pain Resulting From Metastatic Bone Tumors With the ExAblate 2100 Conformal Bone System

Phase II Study to Evaluate the Safety and Effectiveness of ExAblate MR Guided Focused Ultrasound Surgery in the Treatment of Pain Resulting From Metastatic Bone Tumors With the ExAblate 2100 Conformal Bone System

Evaluate incidence and severity of adverse events associated with ExAblate MRgFUS ExAblate Conformal system used in the palliation of pain due to metastatic bone tumors

Level of pain relief (measured by Pain Scale)

Improved quality of life (measured by questionnaire)

ExAblate MRfFUS

Sham

A Pivotal Study to Evaluate the Effectiveness and Safety of ExAblate Treatment of Metastatic Bone and Multiple Myeloma Tumors for the Palliation of Pain in Patients Who are not Candidates for Radiation Therapy

ExAblate (MRgFUS) Treatment of Metastatic Bone Tumors for the Palliation of Pain

A Pivotal Study to Evaluate the Effectiveness and Safety of ExAblate Treatment of Metastatic and Multiple Myeloma Bone Tumors for the Palliation of Pain in Patients Who Are Not Candidates for Radiation Therapy

Using the Numerical Rating Score (NRS) for pain (0 being no pain and 10 being worst imaginable pain), each subject was rated as a Responder or Non-responder. A responder is defined as a subject with a reduction in NRS worst score from baseline of two (2) or more points, and no increase in pain medication use.

Medication Use change reported from baseline until of study. Medication use is quantified by "morphine equivalent usage" (measured separately from Responder/Non-responder definition for the primary endpoint)

The BPI-QOL questionnaire is designed to show the severity and interference of pain in the lives of patients. This is a 7-item questionnaire that asks respondents the extent to which pain interferes with their general activity, mood, walking ability, normal work, relations with other people, sleep and enjoyment of life using a 0-10 numerical rating scale in which 0 represents 'does not interfere' and 10 indicates 'completely interferes'. Responses to the 7 items are averaged to form the pain interference scale score. Lower scores are better, showing less interference in daily activities while higher scores show more interference and hence worse outcomes.

ExAblate 2000: MR guided focused ultrasound

ExAblate Treatment Arm

ExAblate 2000: MR guided focused ultrasound sham

ExAblate Sham Control Arm

Total

Race (NIH/OMB)

Canada

Italy

Israel

Russia

115 subjects were underwent treatment. Of these, 4 subjects terminated treatment prior to full completion. These 4 subjects are excluded from the efficacy analysis. An additional 4 subjects were found to have been enrolled in the study more than once. In a pre-PMA meeting with FDA, it was agreed upon to exclude these 4 subjects from the analysis.

Number of Responders

Only 26 of the 81 subjects in ExAblate treatment arm and 6 of 26 in the sham arm were taking non-opioid medication at baseline.

Number of Participants With a Change in Medication Use

Quality of Life (QOL) as Measured by Change in Bodily Pain Inventory (BPI) From Baseline

Focused Ultrasound Surgery - FUS delivered by ExAblate for the palliation of pain due to bone metastases.

ExAblate MRgFUS (Magnetic Resonance guided Focused Ultrasound Surgery)

The purpose of this enhanced surveillance study ("ESS") is to collect information regarding chronic adverse events that are possibly related to the ExAblate® System ("ExAblate") that are received by InSightec ("InSightec") following PMA approval. This study will examine adverse events reported in patients undergoing the device procedure for the first two years of commercial experience. Other relevant data may be collected as well.

This proposed Registry will be performed in full compliance with all HIPAA rules and their implementations at potential participating sites. All patients planned to undergo the ExAblate procedure in a commercial setting after PMA approval will be offered a consent so they can be included in the ESS. Non-consenting patients will not be included in the ESS. However, information regarding the total number of subjects treated at each participating site with the device will also be collected.

InSightec will set up a (password protected) EDC database for the sites to enter the information of participating subjects treated with the ExAblate device from all U.S. sites using the ExAblate procedure for the bone metastases indication. This will occur for a total duration of 2 years following device approval. It should be noted that any adverse event that meets the Medical Device Report ("MDR") definition will be reported as an MDR as well.

There will be no control group. Reporting to FDA will occur at six-month intervals for the first two-years after PMA approval.

ExAblate Treatment of Metastatic Bone Tumors for the Palliation of Pain

A Post Approval Registry: ExAblate Treatment of Metastatic Bone Tumors for the Palliation of Pain

This study is designed to collect safety data during the first two years of commercial use of ExAblate MRgFUS treatment for palliation of pain resulting from bone metastases.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Pilot Study for Palliation of Pain in Bone Metastases by MR-HIFU	NCT01117246	Secondary Malig...	High Intensity ...	18 Years - 80 Years	Philips Healthcare
Ablation and Cementoplasty for Painful Bone Lesions	NCT04635137	Bone Lesion Bone Metastases Spine Metastase...	Ablation and Ce...	18 Years -	University of Calgary
Study Comparing the Safety and Effectiveness of Magnetic Resonance Guided Focused Ultrasound (MRgFUS) and External Beam Radiation (EBRT) for Treatment of Metastatic Bone Tumors and Multiple Myeloma	NCT01091883	Bone Cancer Bone Metastases Pain	Exablate treatm... Radiation	18 Years -	InSightec
ExAblate Conformal Bone System Treatment of Metastatic Bone Tumors for the Palliation of Pain	NCT00981578	Bone Metastases	ExAblate 2100	18 Years -	InSightec
Feasibility of Combined Focused Ultrasound and Radiotherapy Treatment in Patients With Painful Bone Metastasis	NCT04310410	Bone Metastases Bone Neoplasm Bone Lesion Bone Cancer Pain Cancer Induced ... Radiation Toxic... Quality of Life Tumor Neoplasm Metast...	combined radiot...	18 Years -	UMC Utrecht
Primary Pain Palliation in Bone Metastases Treated With Magnetic Resonance-guided Focused Ultrasound	NCT01693770	Secondary Malig...	MRgFUS	18 Years - 90 Years	University of Roma La Sapienza
Primary Pain Palliation in Bone Metastases Treated With Magnetic Resonance-guided Focused Ultrasound	NCT01693770	Secondary Malig...	MRgFUS	18 Years - 90 Years	University of Roma La Sapienza
Focused Ultrasound Surgery in the Treatment of Pain Resulting From Metastatic Bone Tumors With the ExAblate 2100 Conformal Bone System	NCT01085565	Bone Cancer Bone Metastases Pain	ExAblate 2100	18 Years -	InSightec
Study Comparing the Safety and Effectiveness of Magnetic Resonance Guided Focused Ultrasound (MRgFUS) and External Beam Radiation (EBRT) for Treatment of Metastatic Bone Tumors and Multiple Myeloma	NCT01091883	Bone Cancer Bone Metastases Pain	Exablate treatm... Radiation	18 Years -	InSightec
ExAblate (MRgFUS) Treatment of Metastatic Bone Tumors for the Palliation of Pain	NCT00656305	Bone Metastases Multiple Myelom...	ExAblate MRfFUS Sham	18 Years - 100 Years	InSightec
ExAblate Treatment of Metastatic Bone Tumors for the Palliation of Pain	NCT01834937	Pain Resulting ...	ExAblate MRgFUS...	18 Years -	InSightec

Spots Global Cancer Trial Database for pain palliation