Charlottesville, Va., October 13, 2021 – In a first-in-world clinical trial, researchers at Sunnybrook Health Sciences Centre in Toronto, Canada, have demonstrated that magnetic resonance (MR)-guided focused ultrasound can be used to safely deliver antibody therapy to breast cancer that has metastasized to the brain.
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The 2021 American Urological Association (AUA) Annual Meeting was held September 10-13, 2021.
On September 7-10, 2021, iTRUSST held its 2nd Focused Ultrasound Neuromodulation (FUN) Symposium as an online conference originating from the University of Oxford, UK.
The IEEE International Ultrasonics Symposium (IUS) 2021 was held as a virtual meeting September 11-16, 2021.
The Cardiovascular and Interventional Radiology Society of Europe (CIRSE) 2021 Summit was held virtually September 25-28, 2021.
Parkinson’s Disease (PD) is a neurodegenerative brain disease that is progressively debilitating and leads to motor dysfunction and cognitive decline. PD affects more than 10 million people worldwide and nearly 1 million in the US. Healthcare costs in the US alone related to PD are estimated at $52 billion per year.
The first patient has been treated in a new phase I/II clinical trialfor patients with recurrent glioblastoma (GBM). Researchers at Northwestern University in Chicago will recruit up to 39 patients to have CarThera’s SonoCloud-9 implanted after surgical removal of the tumor, as it will be used to temporarily open the blood-brain barrier (BBB) prior to the administration of chemotherapy.
A complicated process like using focused ultrasound plus microbubbles to modulate the permeability of the blood-brain barrier (BBB) is not easy to describe. Now, with the availability of advanced digital tools and technologies, the biomedical visualization field is allowing talented young artists with an interest in medicine and an understanding of cellular and molecular biology in addition to anatomy to develop new visual communication tools to help scientists graphically share their discoveries.
Elisa Konofagou, PhD, the Robert and Margaret Hariri Professor of Biomedical Engineering and Radiology at Columbia University, and her research team recently treated the first patient in their clinical trial to open the blood-brain barrier (BBB) in patients with Alzheimer’s disease.
β-Amyloid Plaque Reduction in the Hippocampus After Focused Ultrasound-Induced Blood–Brain Barrier Opening in Alzheimer’s DiseaseA collaborative research group from West Virginia University, Vanderbilt University, and Weill Cornell Medical College measured the beta-amyloid plaque changes in six patients with Alzheimer’s disease who underwent multiple sessions of focused ultrasound—based blood brain barrier (BBB) opening.
The focused ultrasound research community is actively pursuing the treatment of various stages of breast cancer in nine ongoing clinical trials worldwide.
Researchers in Switzerland have developed a novel neuromodulation sequence for aggregating and uncaging drug carriers at a circuit-specific location in the brain.
On September 15, 2020, the Focused Ultrasound Foundation helped sponsor the Breast Cancer Alliance’s annual Medical Symposium: Hot Topics in Breast Cancer.
The IEEE International Ultrasonics Symposium (IUS) took place virtually September 6–11, 2020. The international group of more than 1,900 ultrasound experts and researchers watched live lectures and prerecorded abstract presentations, attended interactive poster sessions, and enrolled in a wide variety of virtual webinars and workshops.
A new undergraduate seminar course in the Biomedical Engineering department at the University of Virginia will introduce students to focused ultrasound therapy.
On July 14, graduate student Natasha Sheybani successfully defended her dissertation to earn a PhD from the Department of Biomedical Engineering in the University of Virginia (UVA) School of Engineering & Applied Science. “Leveraging Focused Ultrasound to Potentiate Immunotherapy for Primary and Disseminated Solid Tumors” was the accumulation of five years spent studying the use of focused ultrasound for cancer immunotherapy.
Denmark-based TOOsonix recently announced the publication of two peer-reviewed studies. One paper found the company’s novel device to be successful in treating skin lesions, including cancer; the other announced results for tattoo ink removal in problematic cases. Read on to learn how TOOsonix is able to use focused ultrasound to treat various depths in the skin without thermal injury to the adjacent, non-target tissue.
The 42nd Annual International Conference of the IEEE Engineering in Medicine and Biology (EMBC) Society and the 43rd Annual Conference of the Canadian Medical and Biological Engineering Society were held July 20–24, 2020.
On July 23, the International Society for Therapeutic Ultrasound (ISTU) broadcasted the next installment in its new series of “ISTU On Air’ webinars.
Neurologist Prof. José Obeso has built a large research and clinical practice centered on using focused ultrasound to halt the progression of Parkinson’s and other brain diseases.
Dr. Craig Slingluff is a University of Virginia Professor of Surgery who is conducting a clinical trial to study the effects of focused ultrasound with or without a cancer immunotherapy drug (pembrolizumab or imiquimod) to treat advanced solid tumors.
The Foundation established a dedicated Cancer Immunotherapy Program in 2015, with a mission to explore the potential of focused ultrasound in the cancer immunotherapy field. As part of this program, the Foundation invites funding applications for collaborative projects that address key questions driving the field.
New and ongoing clinical and preclinical research is examining the use of focused ultrasound in initiating an anti-tumor immune response – either alone or in combination with immunotherapies – to treat cancer.
The Foundation thanks Joan Vidal-Jové, MD, PhD, of the Interventional and Surgical Oncology department at the Comprehensive Tumor Center Barcelonain Barcelona, Spain, for providing this case report.
In November 2013, a 67-year-old male with stage 4 colon cancer underwent surgical resection of a part of his colon containing cancer. During the operation, he was noted to have hepatic metastases. After recovery from his colon surgery, the patient was started on chemotherapy. In 2014 and 2015, he underwent two separate open surgeries to remove liver masses, and chemotherapy was continued. From 2015 to 2018, his cancer was in remission, and he was maintained on adjuvant chemotherapy. In May 2018, during routine follow-up, the patient showed marked progression of his liver tumors in addition to new lung masses. Due to these findings, he was started on a different chemotherapy regimen plus an immunotherapy drug. In July 2018, three of the patient’s liver masses were treated with thermal ablation by ultrasound-guided, high-intensity focused ultrasound (HIFU). He had a partial response to this treatment, but, unfortunately, his disease continued to progress, and he was maintained on the chemotherapy plus immunotherapy regimen. In April 2019, an MRI of the patient’s abdomen revealed countless liver masses that had increased in number and size since his last evaluation (Figure 1). The patient received an evaluation by the Tumor Board at Comprehensive Tumor Center Barcelona, and his inclusion in a clinical trial – the THERESA study – was approved. The THERESA studyis a first-in-human clinical trial sponsored by HistoSonics, Inc. to establish the safety and efficacy of their histotripsy device to treat liver tumors. The patient was not considered a candidate for other surgical or locoregional therapies.On May 13, 2019, the patient underwent histotripsy-mediated ablation of a 1.2 cm x 1 cm lesion in his liver. No adverse events occurred during or after the procedure, including no pain. In the weeks following the procedure, lab tests revealed a significant decrease in the value of the tumor marker CEA (Figure 2), and the patient continued to feel well with no pain. Follow up MRI scans at one, four, and eight weeks showed a decrease in size of the targeted, treated lesion as well as a decrease in size of numerous other, non-treated lesions throughout the liver (Figure 3). Immune assessment (CD3, CD4, CD8, IL6, Complement) was equivocal. Following the advice of the patient’s oncologist, a new chemotherapy regime was initiated five weeks after the ablation procedure. After this, both tumor marker levels and the size of the liver lesions continued to decrease. In December 2019, there was progression of the liver metastases and appearance of a new tumor in the colon. New treatment options and clinical trials are still being explored. At present, one year after his treatment with histotripsy and evidence of an abscopal effect, the patient has slow progression of his disease.
Surgical resection is the established first-line treatment for primary and metastatic liver cancer. However, surgical removal with curative intent is only feasible for a minority of patients with liver metastases (10-25 percent) since only a small proportion of patients have tumors that are entirely resectable at presentation.1 Despite the survival advantage of hepatic resection on colorectal cancer liver metastases, relapse is common following curative resection.2 In addition, surgery is an invasive procedure associated with high rates of morbidity and mortality.3Ablation techniques are promising alternatives for those patients who are not eligible for surgical resection or who have failed other therapies. Current ablation methods include non-thermal ablation methods (e.g., percutaneous ethanol injection [PEI] and irreversible electroporation [IRE]) and thermal modalities (e.g., radiofrequency ablation [RFA, microwave ablation [MWA], and HIFU.)4Despite the efficacy of some of these local thermal ablation modalities, significant limitations exist due to their mode of action (thermal tissue destruction). Thermal ablation is inconsistent in tissue with non-uniform heat dissipation patterns, which is common in liver tumors.5 It often results in incomplete tumor necrosis in tissue that is located near major vessels.6, 7 Consequently, the shape and the size of the ablation zone may be unpredictable, and the efficacy of thermal ablation may be restricted.8 In addition, thermal ablation methods are often unsuitable for treating tumors larger than three centimeters due to excessive treatment time and practical ultrasound probe sizes.9-11 Most complications associated with RFA and MWA are consequences related to thermal injury.12 Another limitation of these methods is the lack of imaging feedback during treatment. Thus, CT or MRI evaluates the effect of ablation treatment after the application of thermal treatment while no real-time imaging provides monitoring during treatment.13HIFU is a noninvasive, image-guided, thermal ablation method. Unlike percutaneous thermal modalities, HIFU is completely extracorporeal and lacks the risks of bleeding and tumor seeding with the direct puncture of tumors. HIFU can improve upon other thermal ablation modalities due to its noninvasiveness, real-time feedback, and the ability to scan the focal zone over a large volume.13 As with the other thermal-based methods, HIFU is limited by the heat-sink effect, resulting in reduced efficacy in ablating tissue near major vessels and by extended treatment time for larger liver volumes.13 Another major challenge in the noninvasive treatment of liver tumors using HIFU is rib obstruction, which may result in secondary hot spots near the treatment main focal zone, inducing loss of therapeutic precision and collateral damage.14 Moreover, because of the high ultrasound absorption coefficient at the bone-tissue interface, overheating of ribs and surrounding tissue often results in unwanted tissue damage. Skin burns and subcostal edema have been reported with HIFU ablation cases.15, 16Therefore, developing new strategies in which a liver tumor can be ablated noninvasively and avoiding thermal-related collateral damage and inefficacy would be a major clinical advancement. To address this unmet clinical need, cavitation-based, ultrasound-guided treatment (histotripsy) is a promising option to destroy liver tumors and overcome the limitations of currently available ablation modalities.Histotripsy is a treatment technology that mechanically destroys targeted tissue through the precise targeting of acoustic cavitation.17-19 The ablation system is an image-guided device designed to deliver noninvasive, non-thermal histotripsy for local treatment that has the potential to overcome many limitations of other focal liver tumor treatment options.The Histotripsy Group in the Biomedical Engineering Department at University of Michigan invented and pioneered the development of focused ultrasound histotripsy more than 12 years ago. Starting with their earliest work with the use of microbubbles to cause tissue damage, this group developed histotripsy into a highly controlled and predictable tool to remove unwanted tissue with microscopic precision. In 2010, HistoSonics, Inc. entered into a worldwide exclusive license with the University of Michigan for exclusive rights to the entire portfolio of histotripsy patents and patent applications.Favorable characteristics of histotripsy treatment method include:
An additional potential benefit of histotripsy may be as immunogenic ablation20 if it can be used to stimulate tumor-specific immune responses capable of magnifying the impact of checkpoint inhibition immunotherapy. The characteristics of this cavitation-based ablation likely allow cytokines and metabolites – not destroyed in the tumor micro-environment – to become highly immunogenic and contribute to the abscopal effect, where shrinkage of untargeted tumors occurs secondary to an immune response. The abscopal – or “off target” – effect was first described in patients who were receiving radiation therapy that were noted to have regression of tumors that were in a non-irradiated zone. It describes the ability of localized radiation to initiate an antitumor response that kills cancer cells distant to the primary target. Similar to radiation, focused ultrasound has been shown to produce an abscopal effect in both preclinical and human cancers. When combined with immunotherapy, the abscopal effect could produce a durable treatment response to control or eradicate metastatic cancer.
This case report shows clear evidence of an immunologic relationship between histotripsy ablation and the abscopal effect. A patient with progressive and extensive metastatic disease with a short overall survival prognosis had noticeable shrinkage of non-targeted metastases and is still alive and considering new clinical trial options one year after the histotripsy procedure.In addition, this report highlights the differences between two focused ultrasound modalities. Thermal US guided HIFU was performed previously and obtained a substantial volume ablation but no immune effects. Less volume ablation with histotripsy generated a noticeable abscopal effect, and this data will influence future research assumptions.Histotripsy is a disruptive technology. The non-thermal and noninvasive characteristics of histotripsy offer patients the potential for a tumor treatment with fewer clinical complications and adverse events than currently available ablation methods and surgical procedures. The safety of histotripsy has been demonstrated through rigorous testing including benchtop and both acute and chronic disease preclinical studies. Future clinical trials with the objectives to evaluate technical performance, including acute technical success, while collecting safety-related data are forthcoming. In addition, further clinical trials should continue to explore histotripsy-mediated immune effects in detail. The THERESA Study used an investigative histotripsy device that is not yet commercially available. The THERESA Study is currently ongoing; therefore, data is not considered final.
The Foundation is seeking public comments on these guidelines to ensure that they are comprehensive and address challenges faced by the community. The public comment period is open until July 15, 2020.
Submit your Comments Now > Your feedback is essential so please comment by July 15.
The scientific program for the Annual Meeting of the American Society of Clinical Oncology (ASCO)was held virtually from May 29–31, 2020.
The New York Academy of Sciences held “Frontiers in Cancer Immunotherapy 2020” as an online symposium May 11–12, 2020.
CarThera, a French ultrasound company, has announced the start of a new clinical trial in France. The “SoniMel” study has enrolled and treated its first patient diagnosed with brain metastases from a primary melanoma.
The Core Hub for Medical Research of UltraSound (CHORUS) is a focused ultrasound research facility located within the Department of Radiology at Seoul National University Hospital in Korea. The group’s incredibly wide breadth of applications combined with their multifaceted internal and external collaborations has created a highly productive environment for clinical and preclinical research. Importantly, CHORUS scientists recently discovered a potential mechanism for how focused ultrasound treatment clears amyloid plaques in Alzheimer’s disease. We interviewed Jae Young Lee, MD, PhD, to learn more about one of Seoul’s many impressive focused ultrasound centers.
A 15-year-old female diagnosed with a benign brain tumor called a hypothalamic hamartoma (HH) presented to Nicklaus Children’s Hospital in Miami, Florida, in 2019.
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