Focused Ultrasound Therapy
Focused ultrasound is a rapidly evolving, noninvasive therapeutic which is transforming the treatment and quality of life for patients with glioblastoma. 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. Several different approaches are currently in consideration for glioblastoma, and these will be briefly discussed.
Blood-Brain Barrier (BBB) Disruption
The BBB is normally a protective barrier for the brain, preventing adverse agents that may be in the blood stream from gaining unfettered access to the brain. However, in the setting of glioblastoma, the BBB may still be intact, especially around the peripheral regions of the tumor, and preventing therapeutic agents (like chemotherapy) from accessing this area in sufficient quantities for maximal effect. The temporary disruption of the BBB in the targeted area enables enhanced penetration by the therapeutic agent, and following the treatment, the BBB will re-form, typically in about a day.
Sonodynamic Therapy (SDT)
Certain agents that were originally used as visual dyes to help surgeons differentiate between tumor and normal tissue, have been found to be altered after treatment by focused ultrasound, resulting in materials that are toxic to the tumor in the local area. These agents are also accumulated in tumor cells, which maximizes the detrimental effect on the targeted tissue. Clinical trials are using this technique are to provide targeted therapy to certain tumors, including glioblastomas.
Combination with Radiation
The combination of focused ultrasound and radiation has been shown to enhance the effectiveness of radiation. The joint use of these regimens is being used in patients with recurrent glioblastoma.
Thermal ablation is one of the earliest mechanisms of action for focused ultrasound, and it is currently in use for other neurologic indications. While it was in use in some earlier clinical trials for glioblastoma, the recent efforts have shifted to the above mechanisms.
The use of sound sensitive, ultrasound packages that can carry a variety of therapeutic agents throughout the body, and only release them when they encounter focused ultrasound is a very attractive model for treating a wide variety of diseases, including glioblastoma. This mechanism is being studied in body cancers and preclinical brain lesions currently, and it is likely to be used in clinical trials soon.
Current treatments for glioblastoma 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
- Focused ultrasound enables enhanced chemotherapy dose for the target, with less impact to the rest of the patient.
- It can be repeated, if necessary.
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 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.
An Ultrasound-Based Blood Brain Barrier Opening Clinical Trial Using Albumin Bound Paclitaxel to Treat Recurrent Glioblastoma
This invasive procedure that is similar to focused ultrasound uses an implanted device to treat patients with recurrent glioblastoma.
Blood-Brain Barrier Disruption (BBBD) for Liquid Biopsy in Subjects With GlioBlastoma Brain Tumors
A clinical trial for patients with Glioblastoma for liquid biopsy has also begun recruiting patients.
The following study concerns 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 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 study concerns tumors in pediatric patients.
A clinical trial by Carthera is organizing and will be treating recurrent malignant brain tumors in children in France.
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.
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
- Brain Tumor Research
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