Background

Key types of brain tumors are:

• Glioma (or astrocytoma) is a type of cancer that starts in the brain or spinal cord. The most common site of gliomas is the brain, and they are the most common type of brain tumor that comes to medical attention.   The average annual incidence of gliomas is 5.9 per 100,000 patients in the US population.  Among primary brain tumors, astrocytomas are the most common in all age groups.  Glioblastoma Multiforme, the most malignant form, is the most common brain tumor in adults and accounts for 50-60% of all primary adult brain tumors. The prognosis for patients with high-grade (grade 3 and 4) gliomas is generally poor. Of 10,000 Americans diagnosed each year with malignant gliomas, about half are alive 1 year after diagnosis, and 25% after two years. Those with anaplastic (grade 3) astrocytoma survive about three years, on average. Most glioblastoma multiforme patients survive about 9-15 months. No definitive treatment exists for gliomas.
• Metastatic brain tumors are tumors which spread from cancer elsewhere in the body.  The most common sources for brain metastases include lung, breast, renal carcinoma and melanoma.  Metastatic brain tumors are the most commonly diagnosed brain tumors.  There are more than 100,000 new cases in the United States each year.  Patients are often diagnosed with multiple metastases at the same time.  Even in cases where only a single tumor is seen on imaging, the presence of radiographically invisible (micrometastatic) disease cannot be ruled out.
• Pituitary macroadenomas are typically benign tumors involving the pituitary gland that measure greater than 10mm (microadenomas, the majority of pituitary tumors, are less then 10mm).  Pituitary macro-adenomas generally cause symptoms due to their size (from compression of the optic nerve) or less commonly by causing hormonal oversecretion. Pituitary macroadenomas typically present with visual difficulties arising from the compression of the optic nerve by the tumor, or on the basis of manifestations of excess hormone secretion: the specifics depend on the type of hormone. These tumors compress the visual pathway at the optic chiasm. Pressure on the chiasm by an adjacent pituitary tumor produces a defect in the temporal visual field on both sides, a condition called bitemporal hemianopia.
• Meningiomas are tumors which arise from the meninges (the covering of the brain and spinal cord). They are the most common primary tumor of the central nervous system. They are almost always benign, but atypical and malignant meningiomas exist. The annual incidence of symptomatic meningiomas is 2 cases per 100,000 people in the United States.  Meningiomas account for 20% of all primary intracranial neoplasms.

Most meningiomas are sporadic, but they also occur in some genetic syndromes. Meningiomas have also been known to develop as a long-term complication of  radiation therapy. Histologically, meningiomas are graded on a scale of 1-4 with grade 1 being the most common (benign) variety.  Grade 3 and 4 tumors (quite rare) are considered malignant.

Small tumors (e.g., < 2.0 cm) are usually incidental findings at autopsy without having caused symptoms. Larger tumors can cause symptoms depending on the size and location. Seizures, focal motor weakness and cranial nerve palsies have been reported for larger tumors. Some tumors may cause elevated intracranial pressure, resulting in sleepiness, nausea, vomiting and headaches.  MRI or CT with contrast is required for the diagnosis.

Current State

In 2002 the FDA granted approval for a feasibility study for the treatment of brain tumors by means of the ExAblate 3000-System. This study was performed in four patients at the Brigham & Women’s Hospital in Boston, who had been diagnosed with a new or relapsed glioma.

The results of these first three patients led to following further developments and changes to the system:

1. The ultrasound transducer was increased from 512 to 1024 elements, allowing for higher precision and a higher sound level density (and thus a higher temperature at the target).
2. The ultrasound frequency was changed from 650kHz to 220kHz with the possibility of “burst sonication” (instead of continuous sonication).

The fourth tumor patient was then treated with this new device configuration. The use of “burst sonication” instead of the “continuous sonication” led to the fact that the brain tumor could be entirely coagulated.  The team is reviewing the results at both frequency ranges, and considering possible continuation of the protocol.

Clinical Trials

Protocols are currently being developed, with possible resumption of clinical trials in 2011.

The following centers are likely: 

1. The University of Virginia Medical Center, Charlottesville, VA, USA
2. Sunnybrook Hospital, Toronto, Ontario, Canada
3. University Hospital and the Kinderspital, Zürich, and the Aarau Cantonal Hospital, Switzerland

Vendors

1. Insightec, Ltd, Tirat Carmel, Israel
2. Supersonic Imagine, Inc., Aix-en-Provence, France

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