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Meeting Report: Society of Neuro-Oncology (SNO) Annual Meeting and Education Day

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Key Points SNO held its 27th annual meeting and education day November 16-20, 2022. Investigators presented abstracts on using focused ultrasound to treat brain metastases and recurrent glioblastoma. Focused ultrasound—enhanced liquid biopsy was discussed with other researchers in the liquid biopsy session. Devices from Insightec, Carthera, and Cordance Medical were represented. SNO held its 27th Annual Meeting and Education Day in Tampa Bay, Florida, from November 16–20, 2022. With an in-person attendance of 2,500, the conference broke its previous attendance record. Along with the Foundation, many other nonprofits and patient advocacy organizations that support brain tumor research were represented, which created productive networking and collaboration opportunities. Suzanne LeBlang, MD, the Foundation’s Director of Clinical Relationships, attended many sessions at SNO and said, “Overall, I was impressed by the number of studies presented by focused ultrasound researchers. New research efforts clearly show the potential of this incisionless technology to combat brain tumors with numerous mechanisms of action.” At the liquid biopsy meeting, Dr. LeBlang presented an update on the state of the field of focused ultrasound–enhanced liquid biopsy for brain tumors and how focused ultrasound blood-brain barrier opening in and around a brain tumor could enhance the quantity and perhaps quality of analytes detected in the peripheral blood. Investigators presented abstracts and posters on using focused ultrasound to treat glioblastoma, primary brain tumors, and brain metastases with blood-brain barrier opening as well as sonodynamic therapy as the mechanisms of action. Focused ultrasound—enhanced liquid biopsy, a mechanism of action that has the potential to make a big impact in brain cancer diagnosis and treatment, and drug delivery approaches were also presented. Hideho Okada, MD, PhD, from the University of California, San Francisco, presented “Immunotherapy for Patients with IDH-Mutant LGG,” a keynote lecture and mentioned that focused ultrasound has the potential to enhance chimeric antigen receptor (CAR) T cell delivery. Each abstract is listed below. The full text for each abstract can be found by searching the ID number on SNO’s program website. CTNI-10 – Randomized pivotal study of blood-brain barrier (BBB) disruption using Exablate Model 4000 with standard of care (SOC) therapy in non-small cell lung cancer (NSCLC) brain metastases: LIMITLESS trial (Multiple medical centers, Insightec) poster presented by Manmeet S. Ahluwalia CTNI-13 – A first-in-human phase 0/1 trial of 5-Aminolevulinic Acid Sonodynamic Therapy (5-ALA SDT) in recurrent glioblastoma (Barrow Neurological Institute and Ivy Brain Tumor Center) oral abstract presented by Nader Sanai CTNI-20 – Results of a phase 1/2 clinical trial of blood-brain barrier (BBB) opening with the SonoCloud-9 implantable ultrasound device in recurrent glioblastoma patients receiving IV carboplatin (Multiple medical centers, Carthera) poster presented by Michael Canney CTNI-37 – Repeated opening of the blood-brain barrier with the skull-implantable SonoCloud-9 (SC9) device: Phase 1 trial of nab-paclitaxel and SC9 in recurrent glioblastoma (multiple medical centers, Carthera) oral abstract presented by Adam Sonabend CTNI-46 – Pivotal study to evaluate safety and efficacy of Exablate model 4000 using microbubble resonators to temporarily mediate blood-brain barrier disruption for liquid biopsy in glioblastoma (LIBERATE) (Multiple medical centers, Insightec) poster presented by Manmeet S. Ahluwalia CTNI-64 – Focused ultrasound mediated blood-brain barrier penetrance to enable cell-free DNA (cfDNA) as a liquid biopsy in recurrent primary brain tumors (Memorial Sloan Kettering Cancer Center and Cordance Medical) – poster presented by Ryan Dittamore DDEL-10 – Ultrasound-enhanced drug delivery in humans alters endothelial phenotype and perturbs the ultrastructure of the blood-brain barrier (Northwestern University, Carthera) poster presented by Andrew Gould DDEL-13 – Ultrasound-enhanced delivery of liposomal doxorubicin across the blood brain barrier induces an IFN-g phenotype in microglia, macrophages, and T cells and improves response to PD-1 blockade in gliomas (Northwestern University, IIT Research Institute, Carthera) poster presented by Victor A. Arrieta See the Meeting Website >
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Focused Ultrasound for Pancreatic Cancer: Trial Results Prove Safety, Initial Efficacy

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Key Points The data from an initial clinical trial in Korea were critical for establishing safety, preliminary efficacy, and the protocol parameters for a larger study. Jae Young Lee, MD, PhD, used the ultrasound-guided Alpinion focused ultrasound device plus standard-of-care chemotherapy to decrease tumor size in patients with pancreatic cancer. A phase II clinical trial is now underway in Korea and nearing its enrollment goal. Early, proof-of-concept safety data and the protocol parameters from a pancreatic cancer focused ultrasound plus chemotherapy clinical trial have now been published. This small, 9-participant clinical trial, which completed enrollment in 2019, was critical for establishing safety, preliminary efficacy, and the protocol parameters for the phase II clinical trial that is now underway. All participants were pathologically diagnosed with unresectable pancreatic cancer. Jae Young Lee, MD, PhD, professor of Radiology and president at Seoul National University Medical Research Center in Korea, is the principal investigator for both (phase I and II) studies. He and his team are using the ultrasound-guided Alpinion focused ultrasound device and standard-of-care chemotherapy regimens to address pancreatic cancer that is unresectable (which is the case in about 80% of patients with pancreatic cancer). “Pancreatic cancer typically presents with a dense fibrous stroma and low vascularity, which limits drug delivery and efficacy,” said Dr. Lee in the publication. “Therefore, there is an urgent need to develop new treatment options to enhance drug delivery.” Dr. Lee hypothesizes that focused ultrasound can weaken the tumor’s dense stroma to allow chemotherapy to penetrate the cancer cells. As published in European Radiology, the nine participants in the phase I study were assigned to one of three predefined treatment intensity groups (low, intermediate, or high) for six combined treatments of focused ultrasound plus nab-paclitaxel plus gemcitabine chemotherapy. Although it was primarily a safety study, after treatment, the team also measured changes in tumor size, tumor response, tumor marker levels, patient-reported outcomes, and survival. The treatments were safe, and participants experienced no adverse effects. Tumor size decreased more than 15% in seven of the nine participants at both the immediate and 3-month follow-up computed tomography scans. Tumor marker levels decreased in all participants. The intermediate intensity treatment was the most effective, with this group showing the largest decreases in tumor size (more than 30%) and tumor markers plus a significant improvement in survival (p < 0.05). “A key point of the proof-of-concept study is that the Seoul National team showed that they were able to access the patients’ tumors and treat them without complications,” said Tim Meakem, MD, the Foundation’s Chief Medical Officer. “This was not a small issue to solve, because accessing the pancreas with focused ultrasound has been challenging. Some efforts to treat similar patients using MRI guidance have been difficult, simply due to the size and access limitations of the MRI. Dr. Lee used ultrasound guidance for this procedure, which avoided these issues. The safety and initial efficacy of this project were well received by his colleagues, and almost all of the participants for the phase II study have already been enrolled.” The phase II, 60-participant study is being funded by the Focused Ultrasound Foundation. For phase II, the team is using a FOLFIRINOX regimen of chemotherapy. Dr. Lee presented interim phase II results at the 8th International Symposium on Focused Ultrasound. See the Video > See European Radiology > Related StoriesPancreatic Cancer Clinical Trial Begins in Korea October 2021 Research Awards Update: 15 Projects Initiated in the First Six Months of 2021 September 2021
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Call for Manuscripts: Special Collection on Histotripsy

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Key Points The International Journal of Hyperthermia is seeking manuscripts for an upcoming special collection on histotripsy.Suzanne LeBlang, MD, the Foundation’s director of clinical relationships, is one of the guest advisors for the collection.The deadline to submit a manuscript is March 10, 2023. The International Journal of Hyperthermia is requesting manuscripts for an upcoming special collection, “The Art of Histotripsy: A Focused Ultrasound Application that has the Potential to Treat from Head to Toe!” Histotripsy is a non-thermal method of using focused ultrasound to mechanically destroy target tissue. The goal of the collection is to solicit the contribution and submission of articles that describe the current state of the field with respect to understanding the following: Describe the technical aspects of histotripsyProvide a technical description of the mechanisms of action of histotripsy and its subtypes (boiling and nonboiling)Describe approaches to provide imaging guidance for histotripsy treatmentsDetail technical considerations on bypassing the skullDescribe preclinical histotripsy ablation research for varied clinical applicationsDescribe preclinical studies researching the immune response with histotripsyPresent early clinical data with liver ablation and optimal clinical trial designPresent current veterinary applications with histotripsy Suzanne LeBlang, MD, the Foundation’s director of clinical relationships, and Timothy J. Ziemlewicz, MD, associate professor of radiology at the University of Wisconsin, are serving as guest advisors for the collection. “Histotripsy is a rapidly developing area of focused ultrasound with the potential to impact many challenging diseases,” said Dr. Leblang. “At this stage, it is imperative that the field promotes early research and supports a collaborative environment for researchers in this space. We hope this special collection will both increase awareness of this modality and also encourage further studies.” To submit a manuscript, please visit the special collection page on the International Journal of Hyperthermia website. For any pre-submission enquiries, please contact Dr. LeBlang or Dr. Ziemlewicz. The submission deadline is March 10, 2023. Learn More about the Collection >
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Meeting Report: International Bubble Conference 2022

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The 37th Advances in Contrast Ultrasound International Bubble Conference took place from August 31 through September 2, 2022, in Chicago. Touted as “the world’s premier meeting dedicated to the science, research, and practice of cross-specialty contrast-enhanced ultrasound (CEUS),” its two-day agenda included worldwide uses, clinical studies, sonothrombolysis, educational outreach, advanced applications, and expert case presentations. The meeting audience includes clinicians, physiologists, engineers, and scientists working in the fields of cardiology, radiology, vascular medicine, gynecology, gastroenterology, and body imaging. Representing the focused ultrasound community, Kullervo Hynynen, PhD, from Sunnybrook Research Institute and the University of Toronto, presented “Brain Cancer Therapy,” and John Eisenbrey, PhD, from Thomas Jefferson University in Philadelphia, presented “Microbubble Cavitation Augmentation of Radiotherapy.” Both were members of the meeting’s impressive list of faculty. “The 37th annual bubble conference provided an excellent showcase of emerging therapeutic ultrasound-based technologies,” said Dr. Eisenbrey. “It was encouraging to see the wide variety of microbubble-based focused ultrasound therapies now in clinical trials including augmentation of chemotherapy in patients with pancreatic cancer,  opening of the blood-brain barrier for the treatment of brain cancers, and sonothrombolysis for the treatment of myocardial infarction.”
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Meeting Report: European Society for Hyperthermic Oncology (ESHO) 2022 Cleveland Clinic’s Comprehensive Review of Focused Ultrasound Brain Treatments Meeting Report: European Association of Neuro-Oncology (EANO) 2022 Standardization of Focused Ultrasound–Induced Blood-Brain Barrier (BBB) Opening: A Systematic Review of Protocols, Efficacy, and Safety Outcomes Interim Report: Focused Ultrasound for Twin-Twin Transfusion Syndrome