Brain Tumors, Glioma and Metastatic

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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. 

Advantages:

  • 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.

Clinical Trials

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

The following ongoing studies are recruiting patients with brain tumors for focused ultrasound treatment:

Blood-Brain Barrier Disruption Using Transcranial MRI-Guided Focused Ultrasound 
Purpose: Evaluate the safety of blood-brain barrier disruption using transcranial MRI-guided focused ultrasound in conjunction with a microbubble contrast agent to increase the delivery of chemotherapy to brain tumors

  • Sunnybrook Health Sciences Centre - Toronto, Canada
  • Contact: Allison Bethune at

A Feasibility Safety Study of Benign Centrally-Located Intracranial Tumors in Pediatric and Young Adult Subjects
Purpose: 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.

  • Miami Children's Research Institute, Nicklaus Children's Hospital - Miami, Florida
  • Contacts: Coraly Diaz (305-496-4188 or ); Tami Quintero (305-496-4188 or )

See here for a list of treatment sites >
See here for a list of clinical trials sites >
See here for 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

Pre-clinical 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

FUS for Glioblastoma Workshop PDF - November 9-10, 2015

Hersh DS, Kim AJ, Winkles JA, Eisenberg HM, Woodworth GF, Frenkel V. Emerging Applications of Therapeutic Ultrasound in Neuro-oncology: Moving Beyond Tumor Ablation. Neurosurgery. 2016 Nov;79(5):643-654.

Alkins R, Burgess A, Kerbel R, Wels WS, Hynynen K. Early treatment of HER2-amplified brain tumors with targeted NK-92 cells and focused ultrasound improves survival. 

Neuro Oncol. 2016 Jan 26. pii: nov318.

Mead BP, Mastorakos P, Suk JS, Klibanov AL, Hanes J, Price RJ. Targeted gene transfer to the brain via the delivery of brain-penetrating DNA nanoparticles with focused ultrasound. J Control Release. 2016 Feb 10;223:109-17. doi: 10.1016/j.jconrel.2015.12.034. Epub 2015 Dec 28.

Timbie KF, Mead BP, Price RJ. Drug and gene delivery across the blood-brain barrier with focused ultrasound. J Control Release. 2015 Dec 10;219:61-75. doi: 10.1016/j.jconrel.2015.08.059. Epub 2015 Sep 8.

Werner B, Martin E. Transcranial focused ultrasound: Neurological applications of magnetic resonance-guided high-intensity focused ultrasound. Radiologe. 2015 Nov;55(11):976-80, 982-3. doi: 10.1007/s00117-015-0026-1. German. 

Endo S, Kudo N, Yamaguchi S, Sumiyoshi K, Motegi H, Kobayashi H, Terasaka S, Houkin K. Porphyrin derivatives-mediated sonodynamic therapy for malignant gliomas in vitro. Ultrasound Med Biol. 2015 Sep;41(9):2458-65. doi: 10.1016/j.ultrasmedbio.2015.05.007. Epub 2015 Jun 10.

Ghanouni P, Pauly KB, Elias WJ, Henderson J, Sheehan J, Monteith S, Wintermark M. Transcranial MRI-Guided Focused Ultrasound: A Review of the Technologic and Neurologic Applications. AJR Am J Roentgenol. 2015 Jul;205(1):150-9. doi: 10.2214/AJR.14.13632.

Kovacs Z, Werner B, Rassi A, Sass JO, Martin-Fiori E, Bernasconi M. Prolonged survival upon ultrasound-enhanced doxorubicin delivery in two syngenic glioblastoma mouse models. J Control Release. 2014 May 27. pii: S0168-3659(14)00336-8. doi: 10.1016/j.jconrel.2014.05.033.

McDannold N, Arvanitis CD, Vykhodtseva N, Livingstone MS. Temporary disruption of the blood-brain barrier by use of ultrasound and microbubbles: safety and efficacy evaluation in rhesus macaques. Cancer Res. 2012 Jul 15;72(14):3652-63

McDannold N, Clement GT, Black P, Jolesz F, Hynynen K. Transcranial magnetic resonance imaging- guided focused ultrasound surgery of brain tumors: initial findings in 3 patients. Neurosurgery 66:323-332; discussion 332, 2010

Click here for additional references from PubMed.


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