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

Abstract 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.

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Magnetic Resonance–Guided High-Intensity-Focused Ultrasound for Palliation of Painful Skeletal Metastases: A Pilot Study

Technology in Cancer Research & Treatment ◽

10.1177/1533034616658576 ◽

2016 ◽

Vol 16 (5) ◽

pp. 570-576 ◽

Cited By ~ 9

Author(s):

Michael Chan ◽

Kristopher Dennis ◽

Yuexi Huang ◽

Charles Mougenot ◽

Edward Chow ◽

...

Keyword(s):

Pilot Study ◽

Magnetic Resonance ◽

Bone Metastases ◽

Focused Ultrasound ◽

Metastatic Cancer ◽

High Intensity Focused Ultrasound ◽

Clinical Indication ◽

Skeletal Metastases ◽

Pain Response ◽

Painful Bone Metastases

Background: Bone is one of the most common sites of metastases, with bone metastases-related pain representing a significant source of morbidity among patients with cancer. Magnetic resonance–guided focused ultrasound is a noninvasive, outpatient modality with the potential for treating painful bone metastases. The aim of this study is to report our initial experience with magnetic resonance–guided focused ultrasound in the treatment of bone metastases and our preliminary analysis of urinary cytokine levels after therapy. Methods: This was a single-center pilot study of 10 patients with metastatic cancer to investigate the feasibility of magnetic resonance–guided focused ultrasound for primary pain control in device-accessible skeletal metastases. Treatments were performed on a clinical magnetic resonance–guided focused ultrasound system using a volumetric ablation technique. Primary efficacy was assessed using Brief Pain Inventory scores and morphine equivalent daily dose intake at 3 time points: before, day 14, and day 30 after the magnetic resonance–guided focused ultrasound treatment. Urine cytokines were measured 3 days before treatment and 2 days after the treatment. Results: Of the 10 patients, 8 were followed up 14 days and 6 were followed up 30 days after the treatment. At day 14, 3 patients (37.5%) exhibited partial pain response and 4 patients (50%) exhibited an indeterminate response, and at day 30 after the treatment, 5 patients (83%) exhibited partial pain response. No treatment-related adverse events were recorded. Of the urine cytokines measured, only Transforming growth factor alpha (TGFα) demonstrated an overall decrease, with a trend toward statistical significance ( P = .078). Conclusion: Our study corroborates magnetic resonance–guided focused ultrasound as a feasible and safe modality as a primary, palliative treatment for painful bone metastases and contributes to the limited body of literature using magnetic resonance–guided focused ultrasound for this clinical indication.

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Comparison of (Cost-)Effectiveness of Magnetic Resonance Image–Guided High-Intensity–Focused Ultrasound With Standard (Minimally) Invasive Fibroid Treatments: Protocol for a Multicenter Randomized Controlled Trial (MYCHOICE) (Preprint)

10.2196/preprints.29467 ◽

2021 ◽

Author(s):

Kimberley J Anneveldt ◽

Ingrid M Nijholt ◽

Joke M Schutte ◽

Jeroen R Dijkstra ◽

Geert W J Frederix ◽

...

Keyword(s):

Cost Effectiveness ◽

Uterine Fibroid ◽

Focused Ultrasound ◽

Controlled Trial ◽

Uterine Fibroids ◽

High Intensity Focused Ultrasound ◽

Hifu Treatment ◽

Image Guided ◽

Randomized Controlled

BACKGROUND Magnetic resonance image–guided high-intensity–focused ultrasound (MR-HIFU) is a rather new, noninvasive option for the treatment of uterine fibroids. It is safe, effective, and has a very short recovery time. However, a lack of prospectively collected data on long-term (cost-)effectiveness of the MR-HIFU treatment compared with standard uterine fibroid care prevents the MR-HIFU treatment from being reimbursed for this indication. Therefore, at this point, when conservative treatment for uterine fibroid symptoms has failed or is not accepted by patients, standard care includes the more invasive treatments hysterectomy, myomectomy, and uterine artery embolization (UAE). Primary outcomes of currently available data on MR-HIFU treatment often consist of technical outcomes, instead of patient-centered outcomes such as quality of life (QoL), and do not include the use of the latest equipment or most up-to-date treatment strategies. Moreover, data on cost-effectiveness are rare and seldom include data on a societal level such as productivity loss or use of painkillers. Because of the lack of reimbursement, broad clinical implementation has not taken place, nor is the proper role of MR-HIFU in uterine fibroid care sufficiently clear. OBJECTIVE The objective of our study is to determine the long-term (cost-)effectiveness of MR-HIFU compared with standard (minimally) invasive fibroid treatments. METHODS The MYCHOICE study is a national, multicenter, open randomized controlled trial with randomization in a 2:1 ratio to MR-HIFU or standard care including hysterectomy, myomectomy, and UAE. The sample size is 240 patients in total. Women are included when they are 18 years or older, in premenopausal stage, diagnosed with symptomatic uterine fibroids, conservative treatment has failed or is not accepted, and eligible for MR-HIFU. Primary outcomes of the study are QoL 24 months after treatment and costs of treatment including direct health care costs, loss of productivity, and patient costs. RESULTS Inclusion for the MYCHOICE study started in November 2020 and enrollment will continue until 2024. Data collection is expected to be completed in 2026. CONCLUSIONS By collecting data on the long-term (cost-)effectiveness of the MR-HIFU treatment in comparison to current standard fibroid care, we provide currently unavailable evidence about the proper place of MR-HIFU in the fibroid treatment spectrum. This will also facilitate reimbursement and inclusion of MR-HIFU in (inter)national uterine fibroid care guidelines. CLINICALTRIAL Netherlands Trial Register NL8863; https://www.trialregister.nl/trial/8863 INTERNATIONAL REGISTERED REPORT DERR1-10.2196/29467

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HIFU for the treatment of gastric cancer with liver metastases with unsuitable indications for hepatectomy and radiofrequency ablation: a prospective and propensity score-matched study

BMC Surgery ◽

10.1186/s12893-021-01307-y ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Bin Zhou ◽

Ning He ◽

Jiaze Hong ◽

Tong Yang ◽

Derry Minyao Ng ◽

...

Keyword(s):

Gastric Cancer ◽

Radiofrequency Ablation ◽

Propensity Score ◽

Adverse Events ◽

Liver Metastases ◽

Hepatic Metastasis ◽

Focused Ultrasound ◽

Progression Free Survival ◽

High Intensity Focused Ultrasound ◽

Entire Cohort

Abstract Background The purpose of this study was to explore the efficacy and safety of high intensity focused ultrasound (HIFU) in gastric cancer with liver metastasis (GCLM) patients who were contraindicated for either hepatectomy or radiofrequency ablation (RFA). Methods This is a prospective, observational study on GCLM patients with 1–3 liver metastases. The primary gastric lesions were thoroughly resected and any case that exhibited extra-hepatic metastasis was excluded. A 1:2:2 propensity score-matching analysis was performed using a logistic regression model on the HIFU group, best supportive care (BSC) group, and palliative chemotherapy (PC) group. The primary endpoints include progression-free survival (PFS) and overall survival (OS). Results Forty patients were finally included, there were 8 cases in HIFU group, 16 cases in BSC group, and 16 cases in PC group. The median follow-up time for the entire cohort was 10 months. The median PFS was 16.5 months in HIFU group, 2 months in BSC group, and 5 months in PC group. The median OS was 27.5 months in the HIFU group, 7 months in the BSC group, and 11.5 months in the PC group. Additionally, no grade 3 or higher adverse events occurred in the HIFU group. Conclusion The results of this study showed that HIFU treatment could improve the long-term prognosis of GCLM patients without a significant increase in the occurrence of adverse events. Compared with PC and BSC, HIFU is the preferred treatment option when GCLM patients without extra-hepatic metastasis are unable to undergo either surgery or RFA.

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High-intensity focused ultrasound therapy as part of combined treatment for inoperable pancreatic cancer

Onkologiya Zhurnal imeni P A Gertsena ◽

10.17116/onkolog2020901150 ◽

2020 ◽

Vol 9 (1) ◽

pp. 50

Author(s):

A. N. Khitrova ◽

L. V. Bolotina ◽

A. L. Kornietskaya ◽

L. I. Moskvicheva

Keyword(s):

Pancreatic Cancer ◽

High Intensity ◽

Focused Ultrasound ◽

Combined Treatment ◽

High Intensity Focused Ultrasound ◽

Ultrasound Therapy

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Feasibility of volumetric MRI-guided high intensity focused ultrasound (MR-HIFU) for painful bone metastases

Journal of Therapeutic Ultrasound ◽

10.1186/2050-5736-2-16 ◽

2014 ◽

Vol 2 (1) ◽

pp. 16 ◽

Cited By ~ 36

Author(s):

Merel Huisman ◽

Mie K Lam ◽

Lambertus W Bartels ◽

Robbert J Nijenhuis ◽

Chrit T Moonen ◽

...

Keyword(s):

Bone Metastases ◽

High Intensity ◽

Focused Ultrasound ◽

High Intensity Focused Ultrasound ◽

Volumetric Mri ◽

Mri Guided ◽

Painful Bone Metastases

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Pain response after stereotactic body radiation therapy versus conventional radiotherapy in patients with bone metastases – a phase II, randomized controlled trial within a prospective cohort

International Journal of Radiation Oncology*Biology*Physics ◽

10.1016/j.ijrobp.2020.11.060 ◽

2020 ◽

Author(s):

Bart J. Pielkenrood ◽

Joanne M. van der Velden ◽

Yvette M. van der Linden ◽

Marcia M T Bartels ◽

Nicolien Kasperts ◽

...

Keyword(s):

Randomized Controlled Trial ◽

Radiation Therapy ◽

Bone Metastases ◽

Phase Ii ◽

Prospective Cohort ◽

Stereotactic Body Radiation Therapy ◽

Controlled Trial ◽

Pain Response ◽

Conventional Radiotherapy ◽

Randomized Controlled

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Clinical and cost-effectiveness of guided internet-based interventions in the indicated prevention of depression in green professions (PROD-A): study protocol of a 36-month follow-up pragmatic randomized controlled trial

BMC Psychiatry ◽

10.1186/s12888-019-2244-y ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 2

Author(s):

Lina Braun ◽

Ingrid Titzler ◽

David Daniel Ebert ◽

Claudia Buntrock ◽

Yannik Terhorst ◽

...

Keyword(s):

Randomized Controlled Trial ◽

Cost Effectiveness ◽

Large Scale ◽

Controlled Trial ◽

Health Economic Evaluation ◽

Depressive Mood ◽

Trial Registration ◽

Depression Prevention ◽

Pragmatic Randomized Controlled Trial ◽

Randomized Controlled

Abstract Background People in green professions are exposed to a variety of risk factors, which could possibly enhance the development of depression. Amongst possible prevention approaches, internet- and mobile-based interventions (IMIs) have been shown to be effective and scalable. However, little is known about the effectiveness in green professions. The aim of the present study is to examine the (cost-)effectiveness of a tailored IMI program for reducing depressive symptoms and preventing the onset of clinical depression compared to enhanced treatment as usual (TAU+). Methods A pragmatic randomized controlled trial (RCT) will be conducted to evaluate a tailored and therapeutically guided preventive IMI program in comparison to TAU+ with follow-ups at post-treatment (9 weeks), 6-, 12-, 24-, and 36-months. Entrepreneurs in green professions, collaborating spouses, family members and pensioners (N = 360) with sufficient insurance status and at least subthreshold depression (PHQ-9 ≥ 5) are eligible for inclusion. Primary outcome is depressive symptom severity (QIDS-SR16). Secondary outcomes include incidence of depression (QIDS-SR16), quality of life (AQoL-8D) and negative treatment effects (INEP). A health-economic evaluation will be conducted from a societal perspective. The IMI program is provided by psychologists of an external service company and consists of six guided IMIs (6–8 modules, duration: 6–8 weeks) targeting different symptoms (depressive mood, depressive mood with comorbid diabetes, perceived stress, insomnia, panic and agoraphobic symptoms or harmful alcohol use). Intervention choice depends on a screening of participants’ symptoms and individual preferences. The intervention phase is followed by a 12-months consolidating phase with monthly contact to the e-coach. Discussion This is the first pragmatic RCT investigating long-term effectiveness of a tailored guided IMI program for depression prevention in green professions. The present trial builds on a large-scale strategy for depression prevention in green professions. The intended implementation of the IMI program with a nationwide rollout has the potential to reduce overall depression burden and associated health care costs in case of given effectiveness. Trial registration German Clinical Trial Registration: DRKS00014000. Registered on 09 April 2018.

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