MR-guided focused ultrasound therapy of extra-abdominal desmoid tumors: a multicenter retrospective study of 105 patients.

OBJECTIVE: To assess the safety and efficacy of magnetic resonance-guided focused ultrasound (MRgFUS) for the treatment extra-abdominal desmoids. METHODS: A total of 105 patients with desmoid fibromatosis (79 females, 26 males; 35 ± 14 years) were treated with MRgFUS between 2011 and 2021 in three centers. Total and viable tumors were evaluated per patient at last follow-up after treatment. Response and progression-free survival (PFS) were assessed with (modified) response evaluation criteria in solid tumors (RECIST v.1.1 and mRECIST). Change in Numerical Rating Scale (NRS) pain and 36-item Short Form Health Survey (SF-36) scores were compared. Treatment-related adverse events were recorded. RESULTS: The median initial tumor volume was 114 mL (IQR 314 mL). After MRgFUS, median total and viable tumor volume decreased to 51 mL (95% CI: 30-71 mL, n = 101, p < 0.0001) and 29 mL (95% CI: 17-57 mL, n = 88, p < 0.0001), respectively, at last follow-up (median: 15 months, 95% CI: 11-20 months). Based on total tumor measurements (RECIST), 86% (95% CI: 75-93%) had at least stable disease or better at last follow-up, but 50% (95% CI: 38-62%) of remaining viable nodules (mRECIST) progressed within the tumor. Median PFS was reached at 17 and 13 months for total and viable tumors, respectively. NRS decreased from 6 (IQR 3) to 3 (IQR 4) (p < 0.001). SF-36 scores improved (physical health (41 (IQR 15) to 46 (IQR 12); p = 0.05, and mental health (49 (IQR 17) to 53 (IQR 9); p = 0.02)). Complications occurred in 36%, most commonly 1st/2nd degree skin burns. CONCLUSION: MRgFUS reduced tumor volume, reduced pain, and improved quality of life in this series of 105 patients with extra-abdominal desmoid fibromatosis. CLINICAL RELEVANCE STATEMENT: Imaging-guided ablation is being increasingly used as an alternative to surgery, radiation, and medical therapy for the treatment of desmoid fibromatosis. MR-guided high-intensity focused ultrasound is an incisionless ablation technique that can be used to reduce tumor burden effectively and safely. KEY POINTS: • Desmoid fibromatosis was treated with MR-guided high-intensity focused ultrasound in 105 patients. • MR-guided focused ultrasound ablation reduced tumor volume and pain and improved quality of life. • MR-guided focused ultrasound is a treatment option for patients with extra-abdominal desmoid tumors.

Design and evaluation of an open-source, conformable skin-cooling system for body magnetic resonance guided focused ultrasound treatments.

PURPOSE: Magnetic resonance guided focused ultrasound (MRgFUS) treatment of tumors uses inter-sonication delays to allow heat to dissipate from the skin and other near-field tissues. Despite inter-sonication delays, treatment of tumors close to the skin risks skin burns. This work has designed and evaluated an open-source, conformable, skin-cooling system for body MRgFUS treatments to reduce skin burns and enable ablation closer to the skin. METHODS: A MR-compatible skin cooling system is described that features a conformable skin-cooling pad assembly with feedback control allowing continuous flow and pressure maintenance during the procedure. System performance was evaluated with hydrophone, phantom and in vivo porcine studies. Sonications were performed 10 and 5 mm from the skin surface under both control and forced convective skin-cooling conditions. 3D MR temperature imaging was acquired in real time and the accumulated thermal dose volume was measured. Gross analysis of the skin post-sonication was further performed. Device conformability was demonstrated at several body locations. RESULTS: Hydrophone studies demonstrated no beam aberration, but a 5-12% reduction of the peak pressure due to the presence of the skin-cooling pad assembly in the acoustic near field. Phantom evaluation demonstrated there is no MR temperature imaging precision reduction or any other artifacts present due to the coolant flow during MRgFUS sonication. The porcine studies demonstrated skin burns were reduced in size or eliminated when compared to the control condition. CONCLUSION: An open-source design of an MRgFUS active skin cooling system demonstrates device conformability with a reduction of skin burns while ablating superficial tissues.

A rapid beam simulation framework for transcranial focused ultrasound.

Transcranial focused ultrasound is a non-invasive therapeutic modality that can be used to treat essential tremor. Beams of energy are focused into a small spot in the thalamus, resulting in tissue heating and ablation. Here, we report on a rapid 3D numeric simulation framework that can be used to predict focal spot characteristics prior to the application of ultrasound. By comparing with magnetic resonance proton resonance frequency shift thermometry (MR thermometry) data acquired during treatments of essential tremor, we verified that our simulation framework can be used to predict focal spot position, and with patient-specific calibration, predict focal spot temperature rise. Preliminary data suggests that lateral smearing of the focal spot can be simulated. The framework may also be relevant for other therapeutic ultrasound applications such as blood brain barrier opening and neuromodulation.

Treatment of Low-Flow Vascular Malformations of the Extremities Using MR-Guided High Intensity Focused Ultrasound: Preliminary Experience.

Five patients with painful vascular malformations of the extremities that were refractory to standard treatment and were confirmed as low-flow malformations on dynamic contrast-enhanced magnetic resonance (MR) imaging were treated with MR imaging-guided high intensity focused ultrasound. Daily maximum numeric rating scale scores for pain improved from 8.4 ± 1.5 to 1.6 ± 2.2 (P = .004) at a median follow-up of 9 months (range, 4-36 mo). The size of the vascular malformations decreased on follow-up MR imaging (median enhancing volume, 8.2 mL [0.7-10.1 mL] before treatment; 0 mL [0-2.3 mL] after treatment; P = .018) at a median follow-up of 5 months (range, 3-36 mo). No complications occurred.

A meta-analysis of palliative treatment of pancreatic cancer with high intensity focused ultrasound.

BACKGROUND: Pancreatic adenocarcinoma is currently the fourth-leading cause of cancer-related death. Up to 60-90% of patients with advanced disease suffer cancer-related pain, severely impacting their quality of life. Current management involves primarily pharmacotherapy with opioid narcotics and celiac plexus neurolysis; unfortunately, both approaches offer transient relief and cause undesired side-effects. High intensity focused ultrasound (HIFU) is a non-invasive thermal ablation technique that has been used to treat pancreatic cancer. This meta-analysis aims to evaluate the role of HIFU in pain palliation of advanced unresectable pancreatic adenocarcinoma. METHODS: An electronic search was performed in PubMed Medline database up to the end of July 2016, for unresectable pancreatic cancer pain palliation with HIFU. Pertinent studies were identified through the PubMed search engine using the following keywords: HIFU, pancreas, pancreatic cancer, pain and palliation. Additional studies were included after manual search of the selected bibliographies. Pain palliation results reported in each study were analyzed using a logit-transformed random-effects model using the inverse variance method, with the DerSimonian-Laird estimator for τ2, and Cochran's Q test for heterogeneity among studies. The I2 was calculated to assess the percentage of the total variability in the different effect size estimates that can be attributed to heterogeneity among the true effects. A rank correlation test of funnel plot asymmetry was done to assess possible publication bias. RESULTS: The meta-analysis includes a total number of 23 studies with 865 patients, 729 with pancreatic cancer. The population enrolled ranges from 3 patients in the smallest series, up to 61 in the largest study. τ2 (variance among studies) was 0.195, and I2 (percentage of variation among studies) was 40% (95% CI: 1-64%); the Q test p-value was 0.026, indicating significant heterogeneity among studies. Among 639 patients treated with HIFU, 567 complained of pancreatic pain before the treatment and 459 patients experienced partial or complete pain relief after treatment. The random effects estimate of the proportion of patients with pain reduction was 0.81 (95% CI: 0.76-86). CONCLUSIONS: HIFU appears to be an effective tool for pain palliation in advanced pancreatic cancer. Studies assessing treatment in patients with pancreatic adenocarcinoma are limited by factors such as small sample sizes and heterogeneity in clinical definitions and assessments. Prospective randomized and standardized studies are necessary to confirm the effectiveness of HIFU in relieving pain, and to evaluate for any potential impact on tumor control and patient survival.

Magnetic resonance-guided focused ultrasound treatment of extra-abdominal desmoid tumors: a retrospective multicenter study.

OBJECTIVES: To assess the feasibility, safety and preliminary efficacy of magnetic resonance-guided focused ultrasound (MRgFUS) for the treatment of extra-abdominal desmoid tumours. METHODS: Fifteen patients with desmoid fibromatosis (six males, nine females; age range, 7-66 years) were treated with MRgFUS, with seven patients requiring multiple treatments (25 total treatments). Changes in viable and total tumour volumes were measured after treatment. Efficacy was evaluated using an exact one-sided Wilcoxon test to determine if the median reduction in viable tumour measured immediately after initial treatment exceeded a threshold of 50 % of the targeted volume. Median decrease after treatment of at least two points in numerical rating scale (NRS) worst and average pain scores was tested with an exact one-sided Wilcoxon test. Adverse events were recorded. RESULTS: After initial MRgFUS treatment, median viable targeted tumour volume decreased 63 %, significantly beyond our efficacy threshold (P = 0.0013). Median viable total tumour volume decreased (105 mL [interquartile range {IQR}, 217 mL] to 54 mL [IQR, 92 mL]) and pain improved (worst scores, 7.5 ± 1.9 vs 2.7 ± 2.6, P = 0.027; average scores, 6 ± 2.3 vs 1.3 ± 2, P = 0.021). Skin burn was the most common complication. CONCLUSIONS: MRgFUS significantly and durably reduced viable tumour volume and pain in this series of 15 patients with extra-abdominal desmoid fibromatosis. KEY POINTS: • Retrospective four-centre study shows MRgFUS safely and effectively treats extra-abdominal desmoid tumours • This non-invasive procedure can eradicate viable tumour in some cases • Alternatively, MRgFUS can provide durable control of tumour growth through repeated treatments • Compared to surgery or radiation, MRgFUS has relatively mild side effects.

Correcting heat-induced chemical shift distortions in proton resonance frequency-shift thermometry.

PURPOSE: To reconstruct proton resonance frequency-shift temperature maps free of chemical shift distortions. THEORY AND METHODS: Tissue heating created by thermal therapies such as focused ultrasound surgery results in a change in proton resonance frequency that causes geometric distortions in the image and calculated temperature maps, in the same manner as other chemical shift and off-resonance distortions if left uncorrected. We propose an online-compatible algorithm to correct these distortions in 2DFT and echo-planar imaging acquisitions, which is based on a k-space signal model that accounts for proton resonance frequency change-induced phase shifts both up to and during the readout. The method was evaluated with simulations, gel phantoms, and in vivo temperature maps from brain, soft tissue tumor, and uterine fibroid focused ultrasound surgery treatments. RESULTS: Without chemical shift correction, peak temperature and thermal dose measurements were spatially offset by approximately 1 mm in vivo. Spatial shifts increased as readout bandwidth decreased, as shown by up to 4-fold greater temperature hot spot asymmetry in uncorrected temperature maps. In most cases, the computation times to correct maps at peak heat were less than 10 ms, without parallelization. CONCLUSION: Heat-induced proton resonance frequency changes create chemical shift distortions in temperature maps resulting from MR-guided focused ultrasound surgery ablations, but the distortions can be corrected using an online-compatible algorithm. Magn Reson Med 76:172-182, 2016. © 2015 Wiley Periodicals, Inc.

Is MR-guided High-intensity Focused Ultrasound a Feasible Treatment Modality for Desmoid Tumors?

BACKGROUND: MR-guided high-intensity focused ultrasound is a noninvasive treatment modality that uses focused ultrasound waves to thermally ablate tumors within the human body while minimizing side effects to surrounding healthy tissues. This technology is FDA-approved for certain tumors and has potential to be a noninvasive treatment option for extremity soft tissue tumors. Development of treatment modalities that achieve tumor control, decrease morbidity, or both might be of great benefit for patients. We wanted to assess the potential use of this technology in the treatment of extremity desmoid tumors. QUESTIONS/PURPOSES: (1) Can we use MR-guided high-intensity focused ultrasound to accurately ablate a predetermined target volume within a human cadaver extremity? (2) Does MR-guided high-intensity focused ultrasound treatment stop progression and/or cause regression of extremity desmoid tumors? METHODS: Simulated tumor volumes in four human cadavers, created by using plastic markers, were ablated using a commercially available focused ultrasound system. Accuracy was determined in accordance with the International Organization of Standards location error by measuring the farthest distance between the ablated tissue and the plane corresponding to the target. Between 2012 and 2014, we treated nine patients with desmoid tumors using focused ultrasound ablation. Indications for this were tumor-related symptoms or failure of conventional treatment. Of those, five of them were available for MRI followup at 12 months or longer (mean, 18.2 months; range, 12-23 months). The radiographic and clinical outcomes of five patients who had desmoid tumors treated with focused ultrasound were prospectively recorded. Patients were assessed preoperatively with MRI and followed at routine intervals after treatment with MRI scans and clinical examination. RESULTS: The ablation accuracy for the four cadaver extremities was 5 mm, 3 mm, 8 mm, and 8 mm. Four patients' tumors became smaller after treatment and one patient has slight progression at the time of last followup. The mean decrease in tumor size determined by MRI measurements was 36% (95% confidence interval, 7%-66%). No patient has received additional adjuvant systemic or local treatment. Treatment-related adverse events included first- and second-degree skin burns occurring in four patients, which were managed successfully without further surgery. CONCLUSIONS: This preliminary investigation provides some evidence that MR-guided high-intensity focused ultrasound may be a feasible treatment for desmoid tumors. It may also be of use for other soft tissue neoplasms in situations in which there are limited traditional treatment options such as recurrent sarcomas. Further investigation is necessary to better define the indications, efficacy, role, and long-term oncologic outcomes of focused ultrasound treatment. LEVEL OF EVIDENCE: Level IV, therapeutic study.