Brain Tumors, Benign

Background

Clinical KeyTumors of the brain can be malignant (cancerous) or benign. For the cancerous types, please see the Brain Cancer section. There are over 120 types of brain tumors in adults, and meningioma and schwannomas are the most common benign tumors. Benign tumors are more common than malignant ones, with more than 500,000 people in the US living with a non-cancerous tumor.

Common symptoms include headache; balance or coordination issues; trouble with vision, hearing or mental status symptoms; and/or seizures or numbness of the extremities. Many brain tumors are inherently serious and life-threatening — they are invasive and destroy brain tissue, as well as create pressure on brain because of the limited space within the skull.

Not all brain tumors cause symptoms. The most common symptoms that occur could be the result of increased intracranial pressure or damage to/irritation of nerve. Diagnosis is based on clinical evaluation and imaging.

Pediatric Tumors

Pediatric tumors are the most common cause of death for children after automobile accidents. Due to the morbidity of treatment, some small, slow-growing tumors are followed with serial MRI scans with surgical resection being considered if progression occurs. Some tumors can be managed with minimally invasive approaches such as endoscopic surgery and laser thermal ablation, which have lower risks than open craniotomy.

Many non-malignant pediatric tumors will still require intervention simply due to the size of the tumors and the impact on surrounding tissues. The location of the tumors, impacts of growth on motor and sensory pathways, occurrence of developmental delays, seizures and other mechanisms can prompt interventions. Many tumors impact the cerebrospinal fluid (CSF) flow and result in hydrocephalus (accumulation of CSF in the brain), which can lead to injuries or even death if not treated.

Current Treatment

Treatment options for brain tumors include surgical removal or destruction of the tumor using heat, radiotherapy, and chemotherapy, or a combination of two or more of these modalities:

  • Surgery: complete or partial resection of the tumor to remove as much as possible. This has all the risks of open surgery, including bleeding, sensory and motor weakness, and neurologic injury. For malignant tumors, the challenge of tumor recurrence is a major concern.
  • Radiofrequency ablation: the most commonly used nonsurgical treatment for brain tumors. This stereotactic approach typically uses small lesions, which can limit the accuracy of energy delivery and the effectiveness in larger lesions. It also contains all the risks of invasive procedures.
  • Gamma Knife treatment: the use of Gamma Knife’s non-invasive approach to the patient is very attractive, but the drawbacks are significant. Using ionizing radiation is problematic, especially in pediatric patients. There is also a delayed response to treatment, risks to long term cognitive abilities, and oncologic risks.
  • Laser thermal therapy: is an invasive approach where the cranium is opened for placement of the probe via stereotactic techniques. The probe is then heated and ablates the tissue. While this is less invasive than open techniques, it still carries the risks of open interventions.
  • Chemotherapy: seldom used to treat brain tumors, as the blood-brain barrier prevents the drugs from reaching the cancerous cells.

Focused Ultrasound Treatment

Focused ultrasound has tremendous potential to improve the treatment of certain brain tumors. As this modality is non-invasive and accurate, it may be able to ablate only targeted tissue while sparing healthy adjacent tissue. This is especially critical in the brain where any damage to healthy tissue can result in significant loss of function. In addition, focused ultrasound has the potential to reduce the risk for infection and bleeding, lower procedural morbidity by not opening the skull, and avoid the toxicity of radiation.

Currently, focused ultrasound can effectively target small tumors located in the center of the brain, in areas such as the thalamus. In addition, some pediatric tumors in the central part of the brain could also be treatable. The Foundation is collaborating with academia and industry on technical research to expand the area of the brain that can be reached by focused ultrasound.

While research continues for direct treatment of brain tumors with thermal heating of the tumor, additional work has expanded to other treatment options. One is to use focused ultrasound’s ability to temporarily disrupt the blood- brain barrier (BBB), which can allow therapeutic agents (genes, antibiotics, or chemotherapy) that cannot normally enter the brain to gain access via the temporary disruption. Another area is to incorporate the therapeutic agents into microbubbles, which will only release their payload when sonicated. This allows the treatment material to only impact the needed region, as opposed to the entire body.

Preclinical Research

Researchers at the University of Virginia - in collaboration with the Foundation and Insightec - are conducting a pre-clinical study to evaluate the safety and efficacy of using focused ultrasound’s different frequencies and impacts to expand the treatment envelope for clinical use.

Another area of research is to use focused ultrasound to temporarily disrupt the BBB, as mentioned above, to understand how this occurs and investigate inflammation that may occur. There is also a multi-site effort to determine the proper pathway, timing and other important factors for this technique.

Another approach that is being investigated is using focused ultrasound to enable the targeted delivery and/or activation of drugs. The goal is to deliver drugs into the brain tumor in high concentrations while minimizing systemic side-effects. One mechanism to accomplish this is embedding the agents in microbubbles, and releasing the agents via sonification.

Also, non-thermal destruction of tissue with focused ultrasound is being evaluated by several sites. In this method the acoustic energy is used to create non-thermal mechanical effects at the focal point which can damage and destroy tissue.

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:

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 )

Regulatory Approval and Reimbursement

Focused ultrasound is not approved by any regulatory bodies worldwide as a treatment for brain tumors, nor is it reimbursed by medical insurance providers for such.

More Information

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

O'Reilly MA, Hough O, Hynynen K. Blood-Brain Barrier Closure Time After Controlled Ultrasound-Induced Opening Is Independent of Opening Volume. J Ultrasound Med. 2017 Jan 21. doi: 10.7863/ultra.16.02005.

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.

Park J, Aryal M, Vykhodtseva N, Zhang YZ, McDannold N. Evaluation of permeability, doxorubicin delivery, and drug retention in a rat brain tumor model after ultrasound-induced blood-tumor barrier disruption. J Control Release. 2016 Oct 11. pii: S0168-3659(16)30955-5. doi: 10.1016/j.jconrel.2016.10.011.

Ter Haar G. HIFU Tissue Ablation: Concept and Devices. Adv Exp Med Biol. 2016;880:3-20. doi: 10.1007/978-3-319-22536-4_1.

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.

Monteith S, Sheehan J, Medel R, Wintermark M, Eames M, Snell J, Kassell NF, Elias WJ. Potential intracranial applications of magnetic resonance-guided focused ultrasound surgery. J Neurosurg. 2013 Feb;118(2):215-21. doi: 10.3171/2012.10.JNS12449. Epub 2012 Nov 23

Park J, Zhang Y, Vykhodtseva N, Akula JD, McDannold NJ. Targeted and reversible blood-retinal barrier disruption via focused ultrasound and microbubbles. PLoS One. 2012 Aug 13;7(8):e42754 Epub

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.


Video courtesy of InSightec

     

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