Periodic Reporting for period 4 - FURTHER (Focused Ultrasound and RadioTHERapy for Noninvasive Palliative Pain Treatment in Patients with Bone Metastasis)
Berichtszeitraum: 2023-01-01 bis 2023-12-31
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:
o 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,).
o 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).
o Set up a prospective registry of patients treated with MR-HIFU who can’t, or don’t want to be enrolled in the RCT.
o Investigate whether exposing patients to a pain education prior to MR-HIFU treatment will improve their (time to) pain response. (WP 4).
o Determine cost-effectiveness of pain palliation using approaches based on MR-HIFU and EBRT. (WP 2, 3).
o 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).
o Raise awareness and acceptance of MR-HIFU as a treatment option for pain palliation amongst patients, care professionals and informal carers (WP6).
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:
o 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,).
o 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).
o Set up a prospective registry of patients treated with MR-HIFU who can’t, or don’t want to be enrolled in the RCT.
o Investigate whether exposing patients to a pain education prior to MR-HIFU treatment will improve their (time to) pain response. (WP 4).
o Determine cost-effectiveness of pain palliation using approaches based on MR-HIFU and EBRT. (WP 2, 3).
o 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).
o Raise awareness and acceptance of MR-HIFU as a treatment option for pain palliation amongst patients, care professionals and informal carers (WP6).
The project involves a Randomized Controlled Trial (RCT), a registry study, a cost-effectiveness study and a pain education study. During the first period, ethical approval for Randomized Controlled Trial was obtained in the Netherlands and Italy. In the second period, the RCT protocol was approved in Germany and Finland.
Ethical approval for the registry has been secured in all partner institutions. Meanwhile, the FURTHER trial has made progress, with preliminary data generated, a database created, and all necessary trial and patient questionnaires developed and translated. A technical expert visited partner institutions to optimize the MR-HIFU workflow, addressing local logistics and approaches.
Trial monitors conducted initiation visits, either physically or virtually, at all clinical partner institutions. The impact of COVID-19 on clinical trial treatments led to a substantial delay in inclusions, with 22 patients enrolled 3 years into the project (December 31, 2022). The accrual rate was lower than initially expected, prompting a detailed analysis of the eligibility of the radiotherapy-referred patient population for MR-HIFU. This work was presented at several conferences and is currently under review in a peer-reviewed journal. Several other measures were taken at by December 2023, 43 patients had been enrolled.
Cost studies is completed, as well as a literature review, identification of observer groups, and parameter identification for cost-effectiveness analyses. Costing models for MR-HIFU and radiotherapy treatments were constructed, resulting in a publication on MR-HIFU costs from a hospital perspective in the German context.
A pan-European survey was conducted to identify barriers to the deployment of anesthetic services for MR-HIFU treatment. This involved clinical and patient stakeholders and informed the development of an integrated pain pathway following an evidence synthesis exercise.
Another European survey, using a Group Concept Mapping approach, identified barriers to the adoption of MR-HIFU treatment for painful bone metastases. Over 40 participants were involved in the brainstorming and sorting phases of the process.
The project achieved communication milestones with the launch of a project website and finalization of a communication plan. Several abstracts, presentations, and manuscripts have been published, covering Pre-FURTHER trial results, trial design, and the health economic aspects of HIFU.
Consortium meetings were held in Cologne in March 2023 and Zwolle in November 2023, signaling not only significant progress in clinical studies and collaboration, but achievements such as completion of WP3, switching towards tailored recruiting approaches for each center; ongoing development of registry and pain education Initiatives
Ethical approval for the registry has been secured in all partner institutions. Meanwhile, the FURTHER trial has made progress, with preliminary data generated, a database created, and all necessary trial and patient questionnaires developed and translated. A technical expert visited partner institutions to optimize the MR-HIFU workflow, addressing local logistics and approaches.
Trial monitors conducted initiation visits, either physically or virtually, at all clinical partner institutions. The impact of COVID-19 on clinical trial treatments led to a substantial delay in inclusions, with 22 patients enrolled 3 years into the project (December 31, 2022). The accrual rate was lower than initially expected, prompting a detailed analysis of the eligibility of the radiotherapy-referred patient population for MR-HIFU. This work was presented at several conferences and is currently under review in a peer-reviewed journal. Several other measures were taken at by December 2023, 43 patients had been enrolled.
Cost studies is completed, as well as a literature review, identification of observer groups, and parameter identification for cost-effectiveness analyses. Costing models for MR-HIFU and radiotherapy treatments were constructed, resulting in a publication on MR-HIFU costs from a hospital perspective in the German context.
A pan-European survey was conducted to identify barriers to the deployment of anesthetic services for MR-HIFU treatment. This involved clinical and patient stakeholders and informed the development of an integrated pain pathway following an evidence synthesis exercise.
Another European survey, using a Group Concept Mapping approach, identified barriers to the adoption of MR-HIFU treatment for painful bone metastases. Over 40 participants were involved in the brainstorming and sorting phases of the process.
The project achieved communication milestones with the launch of a project website and finalization of a communication plan. Several abstracts, presentations, and manuscripts have been published, covering Pre-FURTHER trial results, trial design, and the health economic aspects of HIFU.
Consortium meetings were held in Cologne in March 2023 and Zwolle in November 2023, signaling not only significant progress in clinical studies and collaboration, but achievements such as completion of WP3, switching towards tailored recruiting approaches for each center; ongoing development of registry and pain education Initiatives
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.