Periodic Reporting for period 5 - FURTHER (Focused Ultrasound and RadioTHERapy for Noninvasive Palliative Pain Treatment in Patients with Bone Metastasis)
Periodo di rendicontazione: 2024-01-01 al 2024-12-31
Sixty-five percent of patients with advanced cancer develop bone metastases, with pain as a common and devastating consequence. Metastatic bone pain strongly interferes with quality of life and daily functioning of patients and their families. It affects mobility, productivity and independence, creating an extra burden for informal carers. Current standard local treatment of metastatic bone disease consists of external beam radiotherapy, which is effective in only 65% of patients after a median period of 4-6 weeks. Magnetic Resonance Guided High Intensity Focused Ultrasound (MR-HIFU) is a non-invasive local treatment that has the potential to induce faster pain (i.e. within day) in a large proportion of patients, The FURTHER project sets out to investigate whether MR-Hifu is an effective and cost-effective alternative or addition to standard radiotherapy treatment for patients with painful bone metastases. FURTHER also addresses scientific and socio-economic barriers that currently limit widespread adoption of MR-HIFU and aims to raise awareness, and acceptance of MR-HIFU and promote its uptake into medical guidelines for palliative treatment of cancer induced bone pain.
In order to reach these aims, the FURTHER consortium sets out to:
- Generate Level I evidence to demonstrate that short-term pain relief is superior in treatment regimens with MR-HIFU (alone or in combination with External Beam Radiation Therapy) as compared to standard-of-care treatment with External Beam Radiation Therapy (EBRT). A multicentre randomized controlled trial is designed to compare outcomes of EBRT, MR-HIFU in combination with EBRT, and MR-HIFU alone, for palliation in patients that present with painful bone metastases. Primary endpoint of the trial is pain at 14 days after randomization. (WP1, 2,).
- Develop a prediction model for identification of patients who are likely to benefit from MR- HIFU or radiotherapy in order to contribute to the (cost-) effective use of the treatment (WP 2,3).
- Set up a prospective registry of patients treated with MR-HIFU who can’t, or don’t want to be enrolled in the RCT.
- Investigate whether exposing patients to a pain education prior to MR-HIFU treatment will improve their (time to) pain response. (WP 4).
- Determine cost-effectiveness of pain palliation using approaches based on MR-HIFU and EBRT. (WP 2, 3).
- Identify strategies for the adoption of MR-HIFU into standard care, mapping and analysing socio- economic factors that influence uptake and access to MR-HIFU treatment (WP 3, 5).
- Raise awareness and acceptance of MR-HIFU as a treatment option for pain palliation amongst patients, care professionals and informal carers (WP6).
In order to reach these aims, the FURTHER consortium sets out to:
- Generate Level I evidence to demonstrate that short-term pain relief is superior in treatment regimens with MR-HIFU (alone or in combination with External Beam Radiation Therapy) as compared to standard-of-care treatment with External Beam Radiation Therapy (EBRT). A multicentre randomized controlled trial is designed to compare outcomes of EBRT, MR-HIFU in combination with EBRT, and MR-HIFU alone, for palliation in patients that present with painful bone metastases. Primary endpoint of the trial is pain at 14 days after randomization. (WP1, 2,).
- Develop a prediction model for identification of patients who are likely to benefit from MR- HIFU or radiotherapy in order to contribute to the (cost-) effective use of the treatment (WP 2,3).
- Set up a prospective registry of patients treated with MR-HIFU who can’t, or don’t want to be enrolled in the RCT.
- Investigate whether exposing patients to a pain education prior to MR-HIFU treatment will improve their (time to) pain response. (WP 4).
- Determine cost-effectiveness of pain palliation using approaches based on MR-HIFU and EBRT. (WP 2, 3).
- Identify strategies for the adoption of MR-HIFU into standard care, mapping and analysing socio- economic factors that influence uptake and access to MR-HIFU treatment (WP 3, 5).
- Raise awareness and acceptance of MR-HIFU as a treatment option for pain palliation amongst patients, care professionals and informal carers (WP6).
The project encompasses several components: a Randomized Controlled Trial (RCT), a registry study, a cost-effectiveness analysis, and a pain education initiative. Ethical approvals for both the trial and registry have been successfully obtained across all partner institutions.
Significant progress has been made in the FURTHER trial. Preliminary data has been generated, a database established, and all trial-related and patient questionnaires developed and translated. Additionally, a technical expert visited partner institutions to optimize the MR-HIFU workflow, addressing local logistics and refining procedural approaches. Trial monitors conducted initiation visits—either in person or virtually—at all clinical partner institutions.
The impact of COVID-19 caused considerable delays in patient enrollment. By December 31, 2022, only 22 patients had been enrolled over three years, reflecting a much lower accrual rate than initially anticipated. To address this, several measures were implemented to boost recruitment, and by December 2024, 68 patients had been enrolled.
A detailed analysis of the radiotherapy-referred patient population's eligibility for MR-HIFU revealed that only 8% of patients with painful bone metastases referred for radiotherapy met the eligibility criteria for MR-HIFU. These findings were presented at multiple conferences and accepted for publication. Furthermore, the consortium investigated the variability in eligibility assessments among radiologists and radiation oncologists. Substantial variation was identified, prompting a consortium-led expert session to develop consensus guidelines on eligibility criteria.
The cost-effectiveness studies have been completed, including a literature review, identification of observer groups, and determination of parameters for cost analyses. Costing models for MR-HIFU and radiotherapy treatments were constructed, culminating in a publication detailing MR-HIFU costs from a hospital perspective in the German context.
To address practical barriers, a pan-European survey was conducted with clinical and patient stakeholders to identify obstacles to deploying anesthetic services for MR-HIFU treatment. This survey informed the development of an integrated pain management pathway, supported by evidence synthesis. Another European survey, employing Group Concept Mapping, identified barriers to the adoption of MR-HIFU for treating painful bone metastases. Over 40 participants contributed to the brainstorming and sorting phases of this process.
The project also achieved key communication milestones, including the launch of a dedicated project website and the finalization of a comprehensive communication plan. Numerous abstracts, presentations, and manuscripts were published, covering Pre-FURTHER trial results, trial design, and the health economic aspects of MR-HIFU.
The annual consortium meeting was held in Turku in 2024, where recruitment challenges and overall project progress were discussed. As part of these meetings, the consortium invited a representative from the European Association for Palliative Care to conduct an interactive session on strategies for boosting trial enrollment in palliative care patients. A consensus session on MR-HIFU eligibility criteria, leveraging the expertise of consortium members, was also conducted.
Significant progress has been made in the FURTHER trial. Preliminary data has been generated, a database established, and all trial-related and patient questionnaires developed and translated. Additionally, a technical expert visited partner institutions to optimize the MR-HIFU workflow, addressing local logistics and refining procedural approaches. Trial monitors conducted initiation visits—either in person or virtually—at all clinical partner institutions.
The impact of COVID-19 caused considerable delays in patient enrollment. By December 31, 2022, only 22 patients had been enrolled over three years, reflecting a much lower accrual rate than initially anticipated. To address this, several measures were implemented to boost recruitment, and by December 2024, 68 patients had been enrolled.
A detailed analysis of the radiotherapy-referred patient population's eligibility for MR-HIFU revealed that only 8% of patients with painful bone metastases referred for radiotherapy met the eligibility criteria for MR-HIFU. These findings were presented at multiple conferences and accepted for publication. Furthermore, the consortium investigated the variability in eligibility assessments among radiologists and radiation oncologists. Substantial variation was identified, prompting a consortium-led expert session to develop consensus guidelines on eligibility criteria.
The cost-effectiveness studies have been completed, including a literature review, identification of observer groups, and determination of parameters for cost analyses. Costing models for MR-HIFU and radiotherapy treatments were constructed, culminating in a publication detailing MR-HIFU costs from a hospital perspective in the German context.
To address practical barriers, a pan-European survey was conducted with clinical and patient stakeholders to identify obstacles to deploying anesthetic services for MR-HIFU treatment. This survey informed the development of an integrated pain management pathway, supported by evidence synthesis. Another European survey, employing Group Concept Mapping, identified barriers to the adoption of MR-HIFU for treating painful bone metastases. Over 40 participants contributed to the brainstorming and sorting phases of this process.
The project also achieved key communication milestones, including the launch of a dedicated project website and the finalization of a comprehensive communication plan. Numerous abstracts, presentations, and manuscripts were published, covering Pre-FURTHER trial results, trial design, and the health economic aspects of MR-HIFU.
The annual consortium meeting was held in Turku in 2024, where recruitment challenges and overall project progress were discussed. As part of these meetings, the consortium invited a representative from the European Association for Palliative Care to conduct an interactive session on strategies for boosting trial enrollment in palliative care patients. A consensus session on MR-HIFU eligibility criteria, leveraging the expertise of consortium members, was also conducted.
The initial research initiative comprises two Randomized Controlled Trials (RCTs): Unforeseen circumstances led to the termination of the UK partner's participation, pausing ethical approval in the UK. A mitigation strategy, led by the University of Bologna, introduced a registry-based pain education study y for non-RCT1 patients with painful bone metastases treated with High-Intensity Focused. Part of these patients will be exposed to a pain education, and in a before-after analysis, the impact of pain education on pain control will be evaluated.