Focused Ultrasound Therapy
Focused ultrasound is an early stage, noninvasive therapeutic technology with the potential to improve the quality of life and decrease the cost of care for patients with brain tumors. This novel technology focuses beams of ultrasonic energy precisely and accurately on targets deep in the brain without damaging surrounding normal tissue. Where the beams converge, the ultrasound produces a variety of therapeutic effects enabling treatment without incisions or radiation.
Current treatments for brain tumors include surgery, radiation therapy, and chemotherapy, all of which have limitations and side effects. Focused ultrasound has the potential to provide an alternative to invasive surgery or to replace or augment radiosurgery for treatment of tumors in the brain. There are no incisions, no ionizing radiation and no damage to surrounding healthy tissue. Focused ultrasound may also be able to enhance delivery of chemotherapy or immunotherapy, reducing toxicity and side-effects, and/or promote anti-tumor immune responses.
- Focused ultrasound is non-invasive – no incisions, holes in the skull, electrodes in the brain – and therefore has reduced risk for infection, blood clots, and mechanical tissue damage.
- Precise targeting minimizes damage to non-targeted healthy brain.
- Treatment can be a complement to drug therapy, enabling enhanced delivery of chemotherapy or immunotherapy into the brain via temporary opening of the blood-brain barrier and/or enhanced permeability of the blood-tumor barrier.
- Focused ultrasound may potentially induce an anti-tumor immune response.
The following studies are recruiting patients with brain tumors for focused ultrasound treatment:
Safety and efficacy of opening the blood brain barrier (BBB) with the SonoCloud-9 in patients with Glioblastoma
This clinical trial is opening the BBB in patients with recurrent glioblastoma and is designed to help enhance the penetration of chemotherapy. This study began in France and has extended to include US sites.
Exablate Blood Brain Barrier Disruption (BBBD) for Planned Surgery in Glioblastoma
This clinical trial is a feasibility study that will open blood brain barrier prior to surgery in patients with glioblastoma.
A Feasibility Safety Study of Benign Centrally-Located Intracranial Tumors in Pediatric and Young Adult Subjects
Centrally located intracranial benign tumors that require intervention in pediatric and young adult patients. Click here for a list of tumors treated in this study.
Exablate Blood-Brain Barrier Disruption for Glioblastoma in Patients Undergoing Standard Chemotherapy
A clinical trial at Severance Hospital, a part of Yonsei University Health System, in Seoul, Korea, is investigating the use of focused ultrasound to open the blood-brain barrier (BBB) and allow chemotherapeutic agents to more efficiently reach the tumors of patients with glioblastoma.
Exablate Blood-Brain Barrier Disruption for Patients with Glioblastoma Undergoing Standard Chemotherapy
This US clinical trial is investigating the use of focused ultrasound to open the BBB to allow chemotherapeutic agents to more efficiently reach the tumors of patients with glioblastoma.
The following studies concern treatment of tumors from the body that have metastasized to the brain.
A clinical trial for patients with breast cancer that has metastasized to their brain is enrolling patients in Canada. The team will us focused ultrasound to open the blood-brain barrier to allow therapeutic medications to more effectively reach the tumor in their brain. This study is only open to Canadian citizens.
For a full list of known brain tumor clinical trials, please see here.
Regulatory Approval and Reimbursement
Focused ultrasound is not approved by any regulatory bodies worldwide as a treatment for brain tumors, nor is the treatment reimbursed by medical insurance providers.
Preclinical Laboratory Studies
Preclinical studies are underway to investigate the use of various mechanisms of focused ultrasound in the treatment of brain tumors. Examples of these studies include:
- Focused ultrasound to temporarily disrupt the BBB and deliver a variety of chemotherapy or immunotherapy drugs, including the dosing and timing (e.g. frequency) of drug administration.
- Focused ultrasound to induce an immune response, including a multi-site study investigating the type of immune response elicited by different “modes” of energy delivery.
- Focused ultrasound to enable targeted delivery and/or activation of drugs via carrier vehicles (e.g. microbubbles, nanoparticles, liposomes) to enable delivery of high concentrations in the tumor with minimal systemic side effects.
- Non-thermal mechanical destruction of tumor using a type of focused ultrasound called histotripsy.
There are many government bodies and patient groups dedicated to brain tumors, including the following:
- Medline Plus: A service of the U.S. National Library of Medicine and NIH
- National Cancer Institute's Brain Tumor Page
- American Brain Tumor Association
- National Brain Tumor Society
Suggested Reading: Focused Ultrasound for Glioblastoma (PDF), June 2019.
Zhu L, Nazeri A, Pacia CP, Yue Y, Chen H. Focused ultrasound for safe and effective release of brain tumor biomarkers into the peripheral circulation. PLoS One. 2020 Jun 3;15(6):e0234182. doi: 10.1371/journal.pone.0234182. eCollection 2020.
Prada F, Sheybani S, Franzini A, Moore D, Cordeiro D, Sheehan J, Timbie K, Xu Z. Fluorescein mediated sonodynamic therapy in a rat glioma model. Journal of Neuro-Oncology, Received: 11 December 2019 / Accepted: 12 May 2020
Sheehan K, Sheehan D, Sulaiman M, Padilla F, Moore D, Sheehan J, Xu Z. Investigation of the tumoricidal effects of sonodynamic therapy in malignant glioblastoma brain tumors. J Neurooncol. 2020 May 2. doi: 10.1007/s11060-020-03504-w.
Beccaria K, Sabbagh A, de Groot J, Canney M, Carpentier A, Heimberger A. Blood-brain Barrier Opening With Low Intensity Pulsed Ultrasound for Immune Modulation and Immune Therapeutic Delivery to CNS Tumors. J Neurooncol 2020 Feb 28. doi: 10.1007/s11060-020-03425-8.
Park SH, Kim MJ, Jung HH, Chang WS, Choi HS, Rachmilevitch I, Zadicario E, Chang JW. Safety and feasibility of multiple blood-brain barrier disruptions for the treatment of glioblastoma in patients undergoing standard adjuvant chemotherapy. J Neurosurg. 2020 Jan 3:1-9. doi: 10.3171/2019.10.JNS192206.
Daniel Y. Zhang, Crismita Dmello, Li Chen, Victor A. Arrieta, Edgar Gonzalez-Buendia, J. Robert Kane, Lisa P. Magnusson, Aneta Baran, C. David James, Craig Horbinski, Alexandre Carpentier, Carole Desseaux, Michael Canney, Miguel Muzzio, Roger Stupp and Adam M. Sonabend Ultrasound-mediated Delivery of Paclitaxel for Glioma: A Comparative Study of Distribution, Toxicity, and Efficacy of Albumin-bound Versus Cremophor Formulations. Clin Cancer Res 2019. DOI: 10.1158/1078-0432.CCR-19-2182 Published January 2020
Bunevicius A, McDannold NJ, Golby AJ. Focused Ultrasound Strategies for Brain Tumor Therapy. Oper Neurosurg (Hagerstown). 2019 Dec 19. pii: opz374. doi:10.1093/ons/opz374.
Kuzan-Fischer CM, Souweidane MM. The intersect of neurosurgery with diffuse intrinsic pontine glioma. J Neurosurg Pediatr. 2019 Dec 1;24(6):611-621. doi: 10.3171/2019.5.PEDS18376. Review.
McDannold N, Zhang Y, Supko JG, Power C, Sun T, Peng C, Vykhodtseva N, Golby AJ, Reardon DA. Acoustic feedback enables safe and reliable carboplatin delivery across the blood-brain barrier with a clinical focused ultrasound system and improves survival in a rat glioma model. Theranostics. 2019 Aug 14;9(21):6284-6299. doi: 10.7150/thno.35892. eCollection 2019.
Park TY, Pahk KJ, Kim H. Method to optimize the placement of a single-element transducer for transcranial focused ultrasound. Comput Methods Programs Biomed. 2019 Oct;179:104982. doi: 10.1016/j.cmpb.2019.104982. Epub 2019 Jul 9.
Schneider CS, Woodworth GF, Vujaskovic Z, Mishra MV. Radiosensitization of high-grade gliomas through induced hyperthermia: Review of clinical experience and the potential role of MR-guided focused ultrasound. Radiother Oncol. 2019 Aug 17. pii: S0167-8140(19)33010-5. doi: 10.1016/j.radonc.2019.07.017.
Wu SK, Santos MA, Marcus SL, Hynynen K. Brain Tumor GLioma MR-guided Focused Ultrasound Facilitates Sonodynamic Therapy with 5-Aminolevulinic Acid in a Rat Glioma Model. Sci Rep. 2019 Jul 18;9(1):10465. doi: 10.1038/s41598-019-46832-2.
Idbaih A, Canney M, Belin L, Desseaux C, Vignot A, Bouchoux G, Asquier N, Law-Ye B, Leclercq D, Bissery A, De Rycke Y, Trosch C, Capelle L, Sanson M, Hoang-Xuan K, Dehais C, Houillier C, Laigle-Donadey F, Mathon B, André A, Lafon C, Chapelon JY, Delattre JY, Carpentier A. Safety and Feasibility of Repeated and Transient Blood-Brain Barrier Disruption by Pulsed Ultrasound in Patients with Recurrent Glioblastoma. Clin Cancer Res. 2019 Jul 1;25(13):3793-3801. doi: 10.1158/1078-0432.CCR-18-3643. Epub 2019 Mar 19.
Borasi G, Nahum A, Paulides MM, Powathil G, Russo G, Fariselli L, Lamia D, Cirincione R, Forte GI, Borrazzo C, Caccia B, di Castro E, Pozzi S, Gilardi MC. Fast and high temperature hyperthermia coupled with radiotherapy as a possible new treatment for glioblastoma. J Ther Ultrasound. 2016 Dec 8;4:32. eCollection 2016.
Yoshida M, Kobayashi H, Terasaka S, Endo S, Yamaguchi S, Motegi H, Itay R, Suzuki S, Brokman O, Shapira Y, Moriyama K, Kawase Y, Akahane T, Kato Y, Kamada H, Houkin K. Sonodynamic Therapy for Malignant Glioma Using 220-kHz Transcranial Magnetic Resonance Imaging-Guided Focused Ultrasound and 5-Aminolevulinic acid. Ultrasound Med Biol. 2019 Feb;45(2):526-538. doi: 10.1016/j.ultrasmedbio.2018.10.016. Epub 2018 Dec 4 PMID:
Papachristodoulou A, Signorell RD, Werner B, Brambilla D, Luciani P, Cavusoglu M, Grandjean J, Silginer M, Rudin M, Martin E, Weller M, Roth P, Leroux JC. Chemotherapy sensitization of glioblastoma by focused ultrasound-mediated delivery of therapeutic liposomes. J Control Release. 2018 Dec 8;295:130-139. doi: 10.1016/j.jconrel.2018.12.009.
Dong Q, He L, Chen L, Deng Q. Opening the Blood-Brain Barrier and Improving the Efficacy of Temozolomide Treatments of Glioblastoma Using Pulsed, Focused Ultrasound with a Microbubble Contrast Agent. Biomed Res Int. 2018 Nov 11;2018:6501508. doi: 10.1155/2018/6501508. eCollection 2018.
Prada F, Kalani MYS, Yagmurlu K, Norat P, Del Bene M, DiMeco F, Kassell NF. Applications of Focused Ultrasound in Cerebrovascular Diseases and Brain Tumors. Neurotherapeutics. 2018 Nov 7. doi: 10.1007/s13311-018-00683-3.
Goutal S, Gerstenmayer M, Auvity S, Caillé F, Mériaux S, Buvat I, Larrat B, Tournier N. Physical blood-brain barrier disruption induced by focused ultrasound does not overcome the transporter-mediated efflux of erlotinib. J Control Release. 2018 Nov 8;292:210-220. doi: 10.1016/j.jconrel.2018.11.009.
Pi Z, Huang Y, Shen Y, Zeng X, Hu Y, Chen T, Li C, Yu H, Chen S, Chen X. Sonodynamic Therapy on Intracranial Glioblastoma Xenografts Using Sinoporphyrin Sodium Delivered by Ultrasound with Microbubbles. Ann Biomed Eng. 2018 Oct 12. doi: 10.1007/s10439-018-02141-9.
Arvanitis CD, Askoxylakis V, Guo Y, Datta M, Kloepper J, Ferraro GB, Bernabeu MO, Fukumura D, McDannold N, Jain RK. Mechanisms of enhanced drug delivery in brain metastases with focused ultrasound-induced blood-tumor barrier disruption. Proc Natl Acad Sci U S A. 2018 Sep 11;115(37):E8717-E8726. doi: 10.1073/pnas.1807105115. Epub 2018 Aug 27.
Meng Y, Suppiah S, Surendrakumar S, Bigioni L, Lipsman N. Low-Intensity MR-Guided Focused Ultrasound Mediated Disruption of the Blood-Brain Barrier for Intracranial Metastatic Diseases. Front Oncol. 2018 Aug 28;8:338. doi: 10.3389/fonc.2018.00338. eCollection 2018. Review.
O'Reilly MA, Hynynen K. Ultrasound and Microbubble-Mediated Blood-Brain Barrier Disruption for Targeted Delivery of Therapeutics to the Brain. Methods Mol Biol. 2018;1831:111-119. doi: 10.1007/978-1-4939-8661-3_9.
Lipsman N, Meng Y, Bethune AJ, Huang Y, Lam B, Masellis M, Herrmann N, Heyn C, Aubert I, Boutet A, Smith GS, Hynynen K, Black SE. Blood-brain barrier opening in Alzheimer's disease using MR-guided focused ultrasound. Nat Commun. 2018 Jul 25;9(1):2336. doi: 10.1038/s41467-018-04529-6.
Click here for additional references from PubMed.
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