Focused Ultrasound for Pancreatic Cancer: Trial Results Prove Safety, Initial Efficacy

Published:
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
Read More ...

Symposium 2022 Videos Now Available

Published:
This October, the US based Focused Ultrasound Foundation hosted the 8th International Symposium on Focused Ultrasound. For many, this was one of the first chances to interact with colleagues from around the world in-person since the COVID-19 pandemic began. It was certainly a pleasure to convene again as a community. The Symposium showcased the tremendous progress in the field. Before the meeting began, more than 200 prerecorded scientific presentations were made available to all attendees. In total, over 600 participants from 23 countries joined us in-person or virtually for four days of panel discussions, keynote speakers, and special lectures. This year’s meeting also included an increased spotlight on many commercialization topics, because the field is rapidly moving from laboratory research to standard of care. All presentation videos are now permanently available on the Symposium YouTube channel. Videos of Note for the Hong Kong Community Focused Ultrasound for the Treatment of Thyroid Diseases Brian Hung-Hin Lang, MS, MBBS, FACS, University of Hong Kong, Queen Mary Hospital   Clinical Adoption Award Acceptance Speech Zhibiao Wang, MD, founder and chairman of Chongqing Medical
Read More ...

Investigator Profile: Lei Sun, PhD

Published:
Key Points Lei Sun, PhD, is a Professor in the Department of Biomedical Engineering at Hong Kong Polytechnic University.He shares his research on sonogenetics and nanoparticle-mediated, cell-type-specific ultrasound neuromodulation. Lei Sun, PhD, is a Professor in the Department of Biomedical Engineering at Hong Kong Polytechnic University. He received his bachelor’s degree from the University of Science and Technology of China (USTC) and his PhD from Pennsylvania State University (Penn State). He then conducted postdoctoral research at the University of Southern California (USC). Dr. Sun joined Hong Kong Polytechnic University in 2008 and was promoted to Professor in 2022. Focused Ultrasound Work When and how did you get interested in focused ultrasound?I started my journey with focused ultrasound during my PhD study under the late Professor Nadine Smith at Penn State, where I conducted MR-guided high-intensity focused ultrasound (HIFU) for treating prostate cancer. The recent wave of ultrasound neuromodulation research inspired me mostly, and I began to pursue methodologies for precise and accurate ultrasound neuromodulation. What are your areas of interest in focused ultrasound?Our group studies the biological mechanisms and possible translational strategies of using ultrasound to modulate cellular activities (i.e., neuromodulation or immunotherapy), investigates the potential of using ultrasonic bioeffects for cancer therapy and diabetes, and develops multimodality molecular imaging and theranostics. Specifically, we develop (1) “sonogenetics,” a cell-type-specific and spatiotemporally accurate ultrasound modulation method; and (2) nanoparticle-mediated ultrasound modulation for cell-type-specific and accurate neural circuit activation of targeted neurons for distinct behaviors. Our studies are based on the understanding and identification of responsible molecular mechanisms of ultrasound modulation, especially the role of mechanosensitive ion channels. We also include other ultrasound-responsive cells into our studies, such as immune cells and beta cells. What mechanisms and clinical indications do you study?We primarily focus on the role of mechanosensitive ion channels as a main cellular mechanism to understand how low-intensity ultrasound modulates cells. What is the goal of your work?The ultimate goal of our research is to translate the technologies we develop to disease therapy for clinical use. Our specific objectives include developing therapies to battle Parkinson’s disease, depression, and epilepsy by demonstrating utility in small and large animal models. What are your funding sources?We have received financial support from the Hong Kong government through various funding schemes, including the Innovation Technology Fund (ITF), General Research Fund (GRF), and Health Medical Research Fund. Funding from the mainland China government has been granted through the National Natural Science Foundation of China (NSFC), Guangdong Science and Technology Department, and Shenzhen Municipal Science and Technology Commissioner. Research Details Who are your team members?Our team is multidisciplinary and includes neuroscientists, biologists, biomedical engineers, clinicians, physicists, and nanotechnologists. Who are your internal and external collaborators?We have a long collaboration history with Professors Hairong Zheng and Weibao Qiu at Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, in ultrasound transducers and instrumentation. We also extensively collaborate with Professors Baojun Li and Yao Zhang in optical nanotechnology. Collaboration with Prof. Dawei Wu from Nanjing University of Aeronautics and Astronautics and Prof. Chunlong Fei from Xidan University has been fruitful in understanding the acoustics behind ultrasound neuromodulation. What are your greatest achievements? Any major disappointments?We are proud of our work to understand the mechanosensitive ion channel’s role in ultrasound neuromodulation, which has allowed us to create neuronal manipulation accurately and precisely with sonogenetics and nanotechnology. On the other hand, it has never been a smooth ride for a new research topic. Difficulties are always there; we like to consider them as surprises rather than disappointments. What do you see as impediments to your success?It is still a long journey for ultrasound to be applied clinically and extensively. Although I am confident, there are still obstacles that need to be solved. For instance, understanding the biophysical mechanisms would be a major one for its future utility. What is on your research wish list?We would like to demonstrate the treatment potential of our neuromodulation method for Parkinson’s disease, depression, and epilepsy. Has the US-based Foundation played a role in your work?The Foundation has been an information hub for different kinds of activities in focused ultrasound, from research to clinics. Its biennial meeting and annual [State of the Field] report have been particularly useful in understanding the current situation. Looking Ahead Do you have any follow-up funding opportunities?We are seeking funding support to develop a sonogenetic approach to inhibit a cell instead of exciting one. What comes next?We plan to demonstrate accurate neural circuit manipulation through sonogenetics and nanotechnology for distinct advanced animal behavior. Recent Key Publications Tianyi Liu, Dongmin He, Mi Hyun Choi, Quanxiang Xian, Jiejun Zhu, Xuandi Hou, Jinghui Guo, Kim Butts Pauly, Lei Sun*, Zhihai Qiu* Sonogenetics: Recent Advances and Future Directions. Brain Stimulation (accepted)J Guo†*, Y Wu†, …, Y Li*, Y Zhang*, L Sun*. Photonic nanojet-mediated optogenetics. Advanced Science 20 Feb 2022, DOI: 10.1002/advs.202104140.L Song†, X Hou†, KF Wong, Y Yang, Z Qiu, S Kala, S Hou, Y Wu, C Fei, J Guo, L Sun*. Gas-filled Protein Nanostructures as Cavitation Nuclei for Molecule-Specific Sonodynamic Therapy. Acta Biomaterialia DOI:10.1016/j.actbio.2021.09.010X Hou†, Z Qiu†, Q Xian†, S Kala†, J Jing, KF Wong, J Zhu, J Guo, T Zhu, M Yang, L Sun*. Precise ultrasound neuromodulation in a deep brain region using nanobubble actuators. Advanced Science 2021, Nov, 8 (21):2101934, doi:10.1002/advs.202101934Q Xian†, Z Qiu†, S Kala, KF Wong, J Guo, L Sun*. Behavioral and functional assessment of ultrasound neuromodulation on Caenorhabditis elegans. IEEE Transactions on Ultrasonics Ferroelectrics Frequency Control 2021 68(6) 2150-2154, doi:10.1109/TUFFC.2021.3057873Q Xian†, Z Qiu†, S Kala†, J Guo†, J Zhu, KF Wong, S Guo, T Zhu, X Hou, L Sun*. Protocol for the sonogenetic stimulation of mouse brain by non-invasive ultrasound. STAR Protocol Vol 2, Issue 2, Mar 2021, DOI: 10.1016/j.xpro.2021.100393Z Qiu†, S Kala†, J Guo†, Q Xian†, J Zhu, T Zhu, X Hou, KF Wong, M Yang, H Wang, L Sun*. Targeted neuronal stimulation in mouse brains using non-invasive ultrasound Cell Reports:32(7), 18 August 2020, DOI:10.1016/j.celrep.2020.108033L Song, G Wang, X Hou, S Kala, Z Qiu, KF Wong, F Cao, L Sun*. Biogenic ...
Read More ...

Patient Profile: Focused Ultrasound for Benign Thyroid Nodules

Published:
Key Points Venus Leung, a 52-year-old Hong Kong woman with benign thyroid nodules, was successfully treated with focused ultrasound by Professor Brian Lang.She recalled, “I couldn’t believe that I had undergone a treatment with better results than surgical removal, and I didn’t feel any discomfort.”This profile is written in English and Chinese. After focused ultrasound treatment, Venus’s thyroid nodule has been treated and she does not have any scars on her neck that are associated with traditional surgery. Ms. Venus Leung discovered a lump near her thyroid, and although it was benign, she chose focused ultrasound treatment at Queen Mary Hospital in Hong Kong. Professor Brian Lang performed the procedure. Thyroid nodules are solid or fluid-filled lumps that form within the thyroid gland, and most of them are benign. They are not generally harmful, but they can impede breathing and swallowing if allowed to grow. We spoke with Ms. Leung about her experience and how she is doing today, more than two years after treatment. Tell me a little about yourself. 請簡單介紹一下你自己。My name is Ms. Venus Leung. I am 52 years old and currently employed. 本人梁女士,52歲是一位在職人士 When did your symptoms start? 你的症狀是什麼時候開始的?About four years ago, I unintentionally felt a lump next to my throat on the right side of my neck.大約四年前,有一次無意中摸到右邊頸喉嚨側有仲粒 Tell me about your diagnosis. 請形容您的診斷。After finding out about the lump, I thought there might be a problem with my thyroid gland, but I wasn’t sure whether it was benign or malignant.當發現後也自覺得是可能甲狀腺出現問題,但不知是良性還是惡性 What treatment options did your doctor offer? 您的醫生提供了哪些治療方案?I immediately visited and told my family doctor, who referred me to the specialist outpatient department of Pamela Youde Nethersole Eastern Hospital for further examination, including fine needle aspiration biopsy and ultrasound examination. Turns out the thyroid nodule was benign, and the doctor said that since it was still small, I only had to do regular checkups to see if there were any changes and further treatments needed. 立即去看家庭醫生說這情況,家庭醫生轉介我去東區那打素醫院專科門診作進一步檢查,包括抽針和做超聲波檢查,結果係甲狀線結節良性的,醫生說我個結節暫時還小,只需要定期檢查觀察有否變異,再作進一步治療 When did you first hear about focused ultrasound? 您是什麼時候第一次聽說到聚焦超聲的?About a year later, during a follow-up consultation, the doctor said that if my nodule is too large, surgical removal would be a clean and complete option, but it would leave a scar and compromised thyroid function, and even possibly affect the vocal cords. The doctor said that if I didn’t want a surgery, Queen Mary Hospital had a technology called focused ultrasound ablation that could eliminate nodules without the need for surgery. For the time being, this technology only existed at Queen Mary Hospital [in Hong Kong]. 大約過咗一年後,有一次覆診,醫生說如果我個結節太大開刀切除係一個切底選擇,但會留意疤痕和無左甲狀線的功能,而且有機會影響聲帶,之後醫生說如果唔想開刀,瑪麗醫院有一個叫聚焦消融不用開刀可以消除結節,暫時只有瑪麗醫院有這技術 Why did you decide to take part in a clinical trial?你為什麼決定參加臨床試驗? Beauty is always a priority for ladies. After hearing about not needing a surgery, no scars left, and being able to preserve the thyroid function, I didn’t have to think twice and asked my doctor for a referral to try it out. 女士總是愛美的,聽到不需做手術不留疤痕而且還可以保留甲狀腺功能,想也不想就叫醫生轉介一試 Describe how you felt waking up the morning of treatment. 請描述您在接受治療後那個早上醒來時的感受。After the treatment, I felt very relaxed, and life was wonderful. 治療後感受很輕鬆,生活很美好 What was the treatment itself like? 治療本身是怎麽樣的?您有什麽感覺?Before the treatment, Professor Lang told me not to worry; it would take about 40 minutes and there was no need for general anesthesia. The equipment would be placed at the location of the nodule on the neck to eliminate it with high temperature, and there might be a bit of swelling and discomfort after the treatment. I felt very comfortable with the procedure and was not afraid. 治療前梁教授說,不用擔心,大約四十分鐘左右,不需全身麻醉,只要將儀器放在頸上結節的位置用高溫消死,治療後的位置可能有紅腫不適,我感覺很放心也不害怕 How did you feel going home from treatment? 治療結束後回家那時的感覺如何?The feeling of going home from the treatment was that I couldn’t believe that I had undergone a treatment with better results than surgical removal, and I didn’t have any problems or feel any discomfort. 治療後回家的感覺是,不相信做了一個比切除手術更好功能的治療,身體沒有什麼大礙和不適 Describe your life now. 請描述您現在的生活。Now my life is the same as before having the nodule; everything is normal, and my voice is not affected. Professor [Lang] says I’m doing well every time during checkup, and the shrinkage of the nodule is favorable; this is really what I had hoped for. 現在生活同未發病前沒有不同,一切正常,聲音也沒影響,每次檢查教授都說很好,結節委縮很理想,這就是我想要的 Tell me what you would like to say to your clinical team. 您想對您的臨床團隊說些什麼嗎?Here, I would like to express my heartfelt thanks to Professor Lang and the team of doctors and nurses from Queen Mary Hospital for their contribution to mankind! They make our lives more wonderful and beautiful! I wish the team more success in the future! Thank you very much! 在這裡我衷心多謝瑪麗醫院梁教授等醫生,護士團隊對人們的貢獻!使我們的生活更精彩美好!祝願團隊以後有更多好好的成績!多謝多謝!!!
Read More ...

Physician Profile: Professor Brian Lang

Published:
Key Points Brian Hung-Hin Lang, MS, MBBS, FACS, is an endocrine surgeon and a Clinical Professor in the Department of Surgery at the University of Hong Kong.He is also Chief of the Division of Endocrine Surgery at Queen Mary Hospital in Hong Kong. Dr. Lang and his team have treated more than 600 patients using focused ultrasound, primarily for benign thyroid nodules. Brian Hung-Hin Lang, MS, MBBS, FACS, is a Clinical Professor in the Department of Surgery at the University of Hong Kong and the Chief of the Division of Endocrine Surgery at Queen Mary Hospital in Hong Kong. Over the past seven years, Prof. Lang and his team have treated more than 600 patients using focused ultrasound, primarily for benign thyroid nodules. Because of this vast experience and expertise, Queen Mary Hospital and its associated sites in Hong Kong have become one of the most active areas today using Theraclion’s EchoPulse® device. FUSHK director Carolyn Yeh recently visited Prof. Lang and observed a focused ultrasound treatment. “Attending a benign thyroid nodule treatment led by Prof. Lang was a fascinating experience,” Yeh said. “It was truly remarkable that under Prof. Lang’s expert handling of the device, intersecting beams of ultrasound energy focused precisely on the target achieved what was possible only with surgery traditionally. Prof. Lang and his team are providing qualified patients in Hong Kong with a tremendous opportunity to address their nodules noninvasively and with lower risk of complications compared with the standard of care.” We recently spoke with Prof. Lang to learn about his practice and why he believes focused ultrasound offers so much to these patients. Focused Ultrasound Work When and how did you get interested in focused ultrasound?In 2014, I was approached by one of the founders of Theraclion in Hong Kong. Theraclion had established an echotherapy division to promote its EchoPulse device, which is an ultrasound-guided high-intensity focused ultrasound (HIFU) system designed specifically for the treatment of thyroid nodules and breast fibroadenomas. That December, I visited a hospital in Frankfurt, Germany, and observed HIFU treatments using the EchoPulse device. I learned from that team’s experience; so, after coming back from the trip, I decided to start our own HIFU program in Hong Kong. We performed our first treatment at the end of 2015, and we were the first center to do this treatment in Asia. I believe that our group is among the largest treatment sites in terms of patient volume using the Theraclion system. What are your areas of interest in focused ultrasound?I use focused ultrasound for the thermal ablation of benign thyroid nodules and nontoxic multinodular goiter. How many patients have you treated?We have treated more than 600 patients since the end of 2015 (just over six years). What is the goal of your work?Our main goal is to provide the least invasive and safest treatment for our patients who need surgery but do not necessarily want or are not fit to undergo surgery. HIFU ablation is a good alternative to surgery. To that end, our site mainly focuses on the clinical outcomes of our treatment. Our treatments are performed at three different hospitals or sites in Hong Kong. We are interested in looking at outcomes (such as the extent of swelling or shrinkage over time after single-session HIFU ablation), safety and complications, patient satisfaction, quality of life, and medical cost. What are your funding sources?Our funding comes mainly from the hospital, our department, and some from research grants. Who are your team members?I work with Dr. Matrix Fung, who is also an endocrine surgeon, and three surgical residents. Who are your internal and external collaborators?We have a multidisciplinary team comprised of three endocrinologists, two clinical oncologists, a community health researcher, and two pathologists. I also work closely with a PhD student from China. What are your greatest achievements?I was awarded two competitive research grants recognizing our work in HIFU: “A randomized, open-label, parallel-group study to explore the efficacy of high-intensity focused ultrasound (HIFU) versus fixed-dose radioiodine-131 in the treatment of relapsed Graves’ disease.” Sponsor: Health and Medical Research Fund (HMRF) (#04150716) “A randomized, open-label, parallel-group study to determine the efficacy of sequential high-intensity focused ultrasound (HIFU) ablation versus fixed-dose radioiodine-131 therapy in moderate-sized non-toxic multinodular goiter.”Sponsor: Health and Medical Research Fund (HMRF) (#06171646) Looking Ahead What do you see as impediments to your success?Because it is a good treatment, I would like to continue to make progress toward improving the treatment efficiency (i.e., shortening treatment time) of the EchoPulse treatments. What comes next?It would be nice to compare different ablation techniques. The most common technique globally is still radiofrequency ablation, not HIFU. I am also interested in finding new ways to ablate thyroid nodules more efficiently with HIFU. Recent Key Publications Lang BH, Woo YC, Chiu KW. Single-Session High-Intensity Focused Ultrasound Treatment in Large-Sized Benign Thyroid Nodules. Thyroid. 2017 May;27(5):714-721. doi: 10.1089/thy.2016.0664. Epub 2017 Mar 22. PMID: 28326895.Lang BH, Woo YC, Wong CKH. High-Intensity Focused Ultrasound for Treatment of Symptomatic Benign Thyroid Nodules: A Prospective Study. Radiology. 2017 Sep;284(3):897-906. doi: 10.1148/radiol.2017161640. Epub 2017 Apr 18. PMID:28419814.Lang BH, Wu ALH. High intensity focused ultrasound (HIFU) ablation of benign thyroid nodules – a systematic review. J Ther Ultrasound. 2017 May 17;5:11. doi: 10.1186/s40349-017-0091-1. PMID: 28523127; PMCID: PMC5434558.Lang BHH, Wong CKH, Ma EPM. Single-session high intensity focussed ablation (HIFU) versus open cervical hemithyroidectomy for benign thyroid nodule: analysis on early efficacy, safety and voice quality. Int J Hyperthermia. 2017 Dec;33(8):868-874. doi: 10.1080/02656736.2017.1305127. Epub 2017 Mar 24. PMID: 28540785.Lang BHH, Woo YC, Chiu KW. High-intensity focused ablation (HIFU) of single benign thyroid nodule rarely alters underlying thyroid function. Int J Hyperthermia. 2017 Dec;33(8):875-881. doi: 10.1080/02656736.2017.1318456. Epub 2017 Apr 24. PMID: 28540804.Lang BHH, Woo YC, Chiu KW. Vocal cord paresis following single-session high intensity focused ablation (HIFU) treatment of benign thyroid nodules: incidence and risk factors. Int J Hyperthermia. 2017 Dec;33(8):888-894. doi: 10.1080/02656736.2017.1328130. Epub 2017 Jun 6. PMID: 28540836.Lang BH, Woo YC, Wong IY, Chiu KW. Single-Session High-Intensity Focused Ultrasound Treatment for Persistent or Relapsed Graves ...
Read More ...
Business Strategy: Theraclion Expands Varicose Vein Treatment into Hong Kong Meet the Team: Q&A with FUSHK Leadership New Interactive Map Provides Global Perspective on Focused Ultrasound Foundation-Funded Research Update: Carbon Nanotube Transducers for Blood-Brain Barrier Opening A New Method for Using Ultrasound Neuromodulation in Deep Regions of the Brain