Brain Tumors, Glioma and Metastatic

Last Updated:

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.

How it Works
Where the beams converge, the ultrasound produces a variety of therapeutic effects enabling treatment without incisions or radiation. These include temporary opening of the blood-brain barrier, designed to improve levels in the brain of therapeutic agents; thermal ablation; activation of sono-sensitive agents at the target; and combining with radiation therapy for a more pronounce effect. There is also a study using focused ultrasound prior to surgery to help mark the extend of the tumor extension.

Advantages
Current treatments for brain tumors include surgery, radiation therapy, and chemotherapy, all of which have limitations and side effects.

Focused ultrasound, used alone or in combination with conventional therapies, has the potential for several advantages.

  • Focused ultrasound is non-invasive, so it does not carry added concerns like surgical wound healing or infection.
  • Focused ultrasound can reach the desired target without damaging surrounding tissue.
  • Focused ultrasound does not include the use of ionizing radiation
  • Enhanced chemotherapy dose for the target, with less impact to the rest of the patient.
  • It can be repeated, if necessary.

Clinical Trials

The following clinical trials are recruiting patients with brain tumors for focused ultrasound treatment:

Exablate Blood-Brain Barrier Disruption for Glioblastoma in Patients Undergoing Standard Chemotherapy
A clinical trial in Milan, Italy 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 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 in patients with glioblastoma.

A study using focused ultrasound and bevacizumide in Taiwan is treating recurrent glioblastoma
This study uses neuronavigation to guide temporary opening of the blood-brain barrier, which is aimed at allowing increased drug penetration to patients with recurrent glioblastoma.

Exablate Blood-Brain Barrier Disruption With Carboplatin for the Treatment of rGBM
New clinical trials have opened in the United States, Canada, and Korea that use focused ultrasound to temporarily open the blood brain barrier (BBB) prior to carboplatin therapy for patients with recurrent glioblastoma.

Exablate Blood Brain Barrier Disruption (BBBD) for Planned Surgery in Glioblastoma
This clinical trial is a planned continuation of a prior study that will open blood-brain barrier prior to surgery in patients with glioblastoma.

The following studies concern focused ultrasound combined with radiation therapy.
A study combining focused ultrasound and radiation therapy in patients with glioblastoma
This study uses neuronavigation combined with radiation therapy and is looking for an increase effectiveness from the combination.

The following studies concern focused ultrasound and sonodynamic therapy.
A study of sonodynamic therapy for patient with high grade glioma
A new clinical trial in the US is using sound activated drugs to treat patients with recurrent high grade glioma, including glioblastoma.

A study of sonodynamic therapy in patients with newly diagnosed glioblastoma
This study will use low frequency focused ultrasound to activate drugs in patients with newly diagnosed glioblastoma.

The following studies concern pediatric tumors.
Non-invasive Focused Ultrasound with Oral Pabinostat in Children with Diffuse Midline Gliomas
This clinical trial is recruiting patents and using focused ultrasound to help achieve greater chemotherapy penetration to the targeted regions.

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.

A clinical trial by Carthera is organizing and will be treating recurrent malignant brain tumors in children in France.

The following studies concern treatment of tumors from the body that have metastasized to the brain.
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. A summary of the first four patients has been published.

The following study concerns a wide variety of brain tumors.
This clinical trial is for a wide variety of brain tumors that are planned to be biopsied. This study is only open to Canadian citizens.

For a full list of known brain tumor clinical trials, please see here.

See a list of treatment sites >
See a list of clinical trials sites >
See a list of laboratory research sites >

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.

Additional Resources

There are many government bodies and patient groups dedicated to brain tumors, including the following:

Notable Papers

Suggested Reading: Focused Ultrasound for Glioblastoma (PDF), June 2021.

Roberts JW, Powlovich L, Sheybani N, LeBlang S. Focused ultrasound for the treatment of glioblastoma. J Neurooncol. 2022 Mar 10. doi: 10.1007/s11060-022-03974-0. Online ahead of print. PMID: 35267132

Brighi C, Salimova E, de Veer M, Puttick S, Egan G. Translation of focused ultrasound for blood-brain barrier opening in glioma. J Control Release. 2022 Mar 23;345:443-463. doi: 10.1016/j.jconrel.2022.03.035.

Ngamcherdtrakul W, Bejan DS, Cruz-Muñoz W, Reda M, Zaidan HY, Siriwon N, Marshall S, Wang R, Nelson MA, Rehwaldt JPC, Gray JW, Hynynen K, Yantasee W. Targeted Nanoparticle for Co-delivery of HER2 siRNA and a Taxane to Mirror the Standard Treatment of HER2+ Breast Cancer: Efficacy in Breast Tumor and Brain Metastasis. Small. 2022 Mar;18(11):e2107550. doi: 10.1002/smll.202107550. Epub 2022 Jan 27.

Tierney TS, Alavian KN, Altman N, Bhatia S, Duchowny M, Hyslop A, Jayakar P, Resnick T, Wang S, Miller I, Ragheb J. Initial experience with magnetic resonance-guided focused ultrasound stereotactic surgery for central brain lesions in young adults. J Neurosurg. 2022 Jan 14:1-8. doi: 10.3171/2021.10.JNS21416.

Mathew EN, Berry BC, Yang HW, Carroll RS, Johnson MD. Delivering Therapeutics to Glioblastoma: Overcoming Biological Constraints. Int J Mol Sci. 2022 Feb 2;23(3):1711. doi: 10.3390/ijms23031711.

Ngamcherdtrakul W, Bejan DS, Cruz-Muñoz W, Reda M, Zaidan HY, Siriwon N, Marshall S, Wang R, Nelson MA, Rehwaldt JPC, Gray JW, Hynynen K, Yantasee W. Targeted Nanoparticle for Co-delivery of HER2 siRNA and a Taxane to Mirror the Standard Treatment of HER2+ Breast Cancer: Efficacy in Breast Tumor and Brain Metastasis. Small. 2022 Jan 27:e2107550. doi: 10.1002/smll.202107550.

Gould A, Zhang D, Arrieta VA, Stupp R, Sonabend AM. Delivering albumin-bound paclitaxel across the blood-brain barrier for gliomas. Oncotarget. 2021 Dec 7;12(25):2474-2475. doi: 10.18632/oncotarget.28018. eCollection 2021 Dec 7.

Samuel N, Vetkas A, Pancholi A, Sarica C, Loh A, Germann J, Harmsen IE, Tasserie J, Milano V, Yamamoto K, Kalia SK, Kongkham PN, Lozano AM. A Network-Based Approach to Glioma Surgery: Insights from Functional Neurosurgery. Cancers (Basel). 2021 Dec 5;13(23):6127. doi: 10.3390/cancers13236127. 

Paun L, Moiraghi A, Jannelli G, Nouri A, DiMeco F, Pallud J, Meling TR, Momjian S, Schaller K, Prada F, Migliorini D. From Focused Ultrasound Tumor Ablation to Brain Blood Barrier Opening for High Grade Glioma: A Systematic Review. Cancers (Basel). 2021 Nov 10;13(22):5614. doi: 10.3390/cancers13225614. 

Schoen S Jr, Kilinc MS, Lee H, Guo Y, Degertekin FL, Woodworth GF, Arvanitis C. Towards controlled drug delivery in brain tumors with microbubble-enhanced focused ultrasound. Adv Drug Deliv Rev. 2021 Nov 18;180:114043. doi: 10.1016/j.addr.2021.114043. 

Sheybani ND, Witter AR, Garrison WJ, Miller GW, Price RJ, Bullock TNJ. Profiling of the immune landscape in murine glioblastoma following blood brain/tumor barrier disruption with MR image-guided focused ultrasound. J Neurooncol. 2021 Nov 3. doi: 10.1007/s11060-021-03887-4. 

Serra R, Zhao T, Huq S, Gorelick NL, Casaos J, Cecia A, Mangraviti A, Eberhart C, Bai R, Olivi A, Brem H, Jackson EM, Tyler B. Disulfiram and copper combination therapy targets NPL4, cancer stem cells and extends survival in a medulloblastoma model. PLoS One. 2021 Nov 3;16(11):e0251957. doi: 10.1371/journal.pone.0251957. eCollection 2021.

Wei HJ, Pouliopoulos A, Yoh N, Tazhibi M, McQuillan N, Zhang X, Szalontay L, Gartrell R, Jovana P, Zhang Z, Feldstein N, Zacharoulis S, Konofagou EE, Wu CC. Focused Ultrasound-Mediated Blood-Brain Barrier Opening Enhances Panobinostat Efficacy in a Murine Diffuse Intrinsic Pontine Glioma Model. Int J Radiat Oncol Biol Phys. 2021 Nov 1;111(3S):e177. doi: 10.1016/j.ijrobp.2021.07.666.

Batts AJ, Ji R, Kline-Schoder AR, Noel RL, Konofagou EE. Transcranial Theranostic Ultrasound for Pre-Planning and Blood-Brain Barrier Opening: A Feasibility Study Using an Imaging Phased Array In Vitro and In Vivo. IEEE Trans Biomed Eng. 2021 Oct 19;PP. doi: 10.1109/TBME.2021.3120919.

Meng Y, Pople CB, Budiansky D, Li D, Suppiah S, Lim-Fat MJ, Perry J, Sahgal A, Lipsman N. Current state of therapeutic focused ultrasound applications in neuro-oncology. J Neurooncol. 2021 Oct 18. doi: 10.1007/s11060-021-03861-0.

Meng Y, Reilly R, Pezo R, Trudeau M, Sahgal A, Singnurkar A, Perry J, Myrehaug S, Pople C, Davidson B, Llinas M, Hyen C, Huang Y, Hamani C, Suppiah S, Hynynen K, and Lipsman N. MR-guided focused ultrasound enhances delivery of trastuzumab to Her2-positive brain metastases. Science Translational Medicine 13 Oct 2021 Vol 13, Issue 615 DOI: 10.1126/scitranslmed.abj4011

Lu N, Gupta D, Daou BJ, Fox A, Choi D, Sukovich JR, Hall TL, Camelo-Piragua S, Chaudhary N, Snell J, Pandey AS, Noll DC, Xu Z. Transcranial Magnetic Resonance-Guided Histotripsy for Brain Surgery: Pre-clinical Investigation. Ultrasound Med Biol. 2021 Oct 4:S0301-5629(21)00404-X. doi: 10.1016/j.ultrasmedbio.2021.09.008.

Rincon-Torroella J, Khela H, Bettegowda A, Bettegowda C. Biomarkers and focused ultrasound: the future of liquid biopsy for brain tumor patients. J Neurooncol. 2021 Oct 6. doi: 10.1007/s11060-021-03837-0.

Tydings C, Yarmolenko P, Bornhorst M, Dombi E, Myseros J, Keating R, Bost J, Sharma K, Kim A. Feasibility of magnetic resonance-guided high-intensity focused ultrasound treatment targeting distinct nodular lesions in neurofibromatosis type 1. Neurooncol Adv. 2021 Aug 18;3(1):vdab116. doi: 10.1093/noajnl/vdab116. eCollection 2021 Jan-Dec.

Wang F, Dong L, Wei X, Wang Y, Chang L, Wu H, Liu S, Chang Y, Yin Y, Luo X, Jia X, Yan F, Li N. Effect of Gambogic Acid-Loaded Porous-Lipid/PLGA Microbubbles in Combination With Ultrasound-Triggered Microbubble Destruction on Human Glioma. Front Bioeng Biotechnol. 2021 Sep 15;9:711787. doi: 10.3389/fbioe.2021.711787. eCollection 2021. PMID: 34604184

Jimenez-Gambin S, Jimenez N, Pouliopoulos A, Benlloch JM, Konofagou EE, Camarena F. Acoustic holograms for bilateral blood-brain barrier opening in a mouse model. IEEE Trans Biomed Eng. 2021 Sep 27;PP. doi: 10.1109/TBME.2021.3115553.

Anastasiadis P, Gandhi D, Guo Y, Ahmed AK, Bentzen SM, Arvanitis C, Woodworth GF. Localized blood-brain barrier opening in infiltrating gliomas with MRI-guided acoustic emissions-controlled focused ultrasound. Proc Natl Acad Sci U S A. 2021 Sep 14;118(37):e2103280118. doi: 10.1073/pnas.2103280118.

Liu S , Zhang W , Chen Q , Hou J , Wang J , Zhong Y , Wang X , Jiang W , Ran H , Guo D. Multifunctional nanozyme for multimodal imaging-guided enhanced sonodynamic therapy by regulating the tumor microenvironment. Nanoscale. 2021 Sep 7;13(33):14049-14066. doi: 10.1039/d1nr01449h. Epub 2021 Jul 23.

Zhang X, Ye D, Yang L, Yue Y, Sultan D, Pacia CP, Pang H, Detering L, Heo GS, Luehmann H, Choksi A, Sethi A, Limbrick DD, Becher OJ, Tai YC, Rubin JB, Chen H, Liu Y. Magnetic Resonance Imaging-Guided Focused Ultrasound-Based Delivery of Radiolabeled Copper Nanoclusters to Diffuse Intrinsic Pontine Glioma. ACS Appl Nano Mater. 2020 Nov 25;3(11):11129-11134. doi: 10.1021/acsanm.0c02297. Epub 2020 Oct 29.

Liao WH, Hsiao MY, Kung Y, Huang AP, Chen WS. Investigation of the Therapeutic Effect of Doxorubicin Combined With Focused Shockwave on Glioblastoma. Front Oncol. 2021 Jul 28;11:711088. doi: 10.3389/fonc.2021.711088. eCollection 2021.

Bunevicius A, Pikis S, Padilla F, Prada F, Sheehan J. Sonodynamic therapy for gliomas. J Neurooncol. 2021 Jul 12. doi: 10.1007/s11060-021-03807-6.

Kim C, Guo Y, Velalopoulou A, Leisen J, Motamarry A, Ramajayam K, Aryal M, Haemmerich D, Arvanitis CD. Closed-loop trans-skull ultrasound hyperthermia leads to improved drug delivery from thermosensitive drugs and promotes changes in vascular transport dynamics in brain tumors. Theranostics. 2021 May 24;11(15):7276-7293. doi: 10.7150/thno.54630. eCollection 2021.

Raspagliesi L, D’Ammando A, Gionso M, Sheybani ND, Lopes MB, Moore D, Allen S, Gatesman J, Porto E, Timbie K, Franzini A, Di Meco F, Sheehan J, Xu Z, Prada F. Intracranial Sonodynamic Therapy With 5-Aminolevulinic Acid and Sodium Fluorescein: Safety Study in a Porcine Model. Front Oncol. 2021 Jun 21;11:679989. doi: 10.3389/fonc.2021.679989. eCollection 2021.

Click here for additional references from PubMed.


Video courtesy of Insightec

Clinical Trials