Double balloon GliaSite in the management of recurrent glioblastoma multiforme.

To the Editor: Glioblastoma multiforme (GBM) is the most common and aggressive of the malignant adult primary brain tumors. (1) Despite significant advances over the last several years in imaging capability, neurosurgical techniques, and radiation treatments, the prognosis for individuals diagnosed with malignant primary brain tumors remains poor. The median survival for patients with GBM is 10 to 12 months after conventional treatment. (2) The initial therapy for GBM is resection/debulking followed by external beam radiotherapy delivered in a shrinking field manner. These tumors frequently recur in or adjacent to the area of resection due to their tendency for extensive infiltration of the brain parenchyma. In fact, the majority of recurrences are within 1 to 2 cm from the margin of the original tumor location. (2)

At recurrence, treatment options are limited as patients are not candidates for further conventional external beam radiation due to the possibility of treatment-related toxicities such as radiation necrosis and other late radiation effects. (3) Many patients proceed with a second debulking surgery with postoperative therapies that include stereotactic radiosurgery, brachytherapy implants, immunotherapy, intracavitary chemotherapy, and conventional IV chemotherapy. Until recently, brachytherapy techniques involved the permanent placement of low activity I-125 seeds around the tumor bed or temporary implants with percutaneous external catheters for placement of high activity temporary sources. (4) These brachytherapy methods have produced inhomogeneous dose distributions around the resection cavity. (5) The Glia-Site Radiation Therapy System (Proxima Therapeutics. Alpharetta, GA) is a relatively new approach to intracavitary brachytherapy for brain tumor treatment. This system utilizes an inflatable balloon inserted in the tumor bed following debulking surgery. Several days later, this balloon is temporarily filled with a proprietary I-125 solution to treat the tumor bed margins and any residual enhancing disease. The balloon design allows close conformity between the resection cavity and the balloon surface and eliminates dose inhomogeneities that are seen with other brachytherapy methods. (5)

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The GliaSite Radiotherapy System consists of a thick walled multilumen silicone catheter with an infusion port pre-attached at the proximal end and an inflatable double-walled balloon at the distal end. The infusion port is placed sub-cutaneously during debulking surgery and can then be accessed in a manner similar to a Port-A-Cath. An appropriatesized balloon (2 cm, 3 cm, or 4 cm diameter) is placed in the tumor cavity at the time of craniotomy. Balloon diameters correspond to maximum fill volumes of 5, 15, and 35 cc respectively. The radiation dose is usually prescribed from 0.5 to 1.0 cm from the surface of the filled balloon. At the time of treatment, an aqueous solution of I-125 and saline is injected. This I-125 solution emits low energy photons in the range of 27 to 35 KeV and demonstrates rapid falloff beyond the normal prescription distances. The wall of the resection cavity conforms to the surface of the filled balloon, which then provides a spherically uniform dose distribution around the surrounding tumor bed while minimizing exposure to healthy brain tissue outside this treatment area. The dwell time is determined based on the prescribed dose and dose rate from the I-125 solution, but is typically delivered over a 72 to 144 hour period.

We used this system to implant two brachytherapy balloons in a patient diagnosed with two abutting GBM lesions. She had been previously treated with debulking surgery and external beam radiotherapy. At time of recurrence, she elected re-resection. Afterwards the two resection cavities were joined, forming a large, complex cavity, which could not be readily treated with a single brachytherapy balloon.

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Two brachytherapy balloons were placed to adequately fill the large resection cavity. The catheters connected to the balloons were brought out through the dural opening, and the ports were anchored to the skull. The double balloon configuration delivered 240 Gy at the surface of the balloon, 120 Gy at 5 mm, and 60 Gy at a depth of 12 mm. The isodose curves demonstrated a highly conformal dose distribution that closely matched the surface contour of the balloon-filled resection cavity without generating unacceptable hot spots. Treatment time was 98 hours, after which the I-125 and saline solution was removed.

The use of multiple balloons allowed treatment of a large, odd-shaped, nonspherical cavity that would have been extremely difficult to treat with stereotactic radiosurgery or other brachytherapy techniques. The dosimetry derived from the tandem balloon implants was gratifying, in that the isodose lines closely paralleled the corresponding surgical cavity/balloon surface. This brachytherapy system maximizes the radiation dose to the tissue at greatest risk of relapse while minimizing the dose to healthy brain tissue.

James T. Payne, MD

William H. St. Clair, MD, PHD

Curtis A. Given II, MD

Byron Young, MD

Ali Meigooni, PHD

Departments of Radiation Medicine.

Neuroradiology, and Neurosurgery 

University of Kentucky Medical Center

Lexington, KY

References

1. Shapiro WR, Shapiro JR, Walker RW. Central Nervous System, In: Abeloff MD, Armitage JO, Lichter AS, Niederhuber JE, eds. Clinical Oncology. Churchill Livingstone, Philadelphia, ed 2, pp 1103-1192.

2. Algan O, Nelson DF, Dinapoli RP, et al High Grade Gliomas. In: Gunderson LL, Tepper JE, eds. Clinical Oncology. Churchill Livingstone, Philadelphia, pp 355-378.

3. Halligan JB, Stelzer KJ, Rostomily RC, et al. Operation and permanent low activity [.sup.125]I brachytherapy for recurrent high grade astrocytomas. Int J Radiat Oncol Biol Phys 1996;35:541-547.

4. Patel S, Breneman JC, Warnick RE, et al. Permanent iodine-125 interstitial implants for the treatment of recurrent glioblastoma multi-forme. Neurosurgery 2000;46:1123-1130.

5. Dempsey JF, Williams JA, Stubbs JB, et al. Dosimetric properties of a novel brachytherapy balloon applicator for the treatment of malignant brain-tumor resection-cavity margins. Int J Radiat Oncol Biol Phys 1998;42:421-429.