
Radioisotope treatment of brain cancer is done by brachytherapy, by placing the radioisotope [the source of the radiation] directly in or around the tumor or tumor cavity.  It is often done by packaging the radioisotope so that it can be easily physically placed in the cavity where the tumor has ben surgically removed.  In the case if Iodine-131, the radioisotope is inside plastic tubing, which allows removal of the pellets.   The GlialSite system uses a catheter that has a ballon on it, and the balloon is filled with the radioisotope in solution.  At the end of treatment, the liquid from the balloon is removed, deflating the balloon, and the catheter removed.  Sometimes radioisotopes are permanently implanted in the surgical cavity. 

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Further Information:

1. News Release 16 MAY 2001 
Wake Forest University Baptist Medical Center. </b>

WINSTON-SALEM, N.C. - Physicians at Wake Forest University Baptist Medical Center are the first in the world to treat a brain tumor patient with the newly FDA-approved GliaSite" Radiation Therapy System (RTS). The GliaSite RTS delivers site-specific, internal radiation to malignant brain tumors, treating the target area while minimizing exposure to healthy tissue. 

Stephen B. Tatter, M.D., Ph.D., assistant professor of neurosurgery at Wake Forest University School of Medicine, said "GliaSite represents an important new treatment option for malignant brain tumors. Until now, treatment for patients with recurrent brain tumors has been extremely limited. Radiation combined with surgery is the single most effective treatment, and the GliaSite RTS will enable these patients to receive additional radiation, while minimizing the risks associated with external beam radiation." 

The device is a balloon catheter that is inserted into the cavity created by surgical removal of the malignant brain tumor and filled with liquid radiation. Over a course of three to seven days, GliaSite delivers radiation directly to the tissue surrounding the cavity, where tumors are most likely to recur. ,,,
Traditionally, patients are first treated with external beam radiation therapy, in which the radiation travels from outside the body to the tumor site, passing through healthy brain tissue. While this treatment is proven to delay tumor regrowth, a second course of external beam radiation is rarely an option due to the high risk of damage to healthy tissue. 

"It's a significant advancement to be able to offer an improved therapy that delivers radiation directly to the site of the cancer, while maintaining the quality of life for patients by completing the treatment in just one week," said Tatter. In addition, study results suggest that the survival rate of these patients is favorable in comparison to the next best secondary treatment, which is surgery plus chemotherapy wafers. 

Safety and performance of the device were demonstrated in a National Cancer Institute (NCI)-sponsored, multi-centered study. Tatter was the principal investigator for the national study, which involved patients with recurrent brain tumors. All of the patients had undergone previous surgery and radiation therapy, and more than half had received chemotherapy. The median survival rate of the patients is currently 14 months, with patients still being followed, a substantial improvement over the results historically seen with other treatments. 

Additionally, GliaSite has the potential to be used in combination with external beam radiation when treating newly diagnosed tumors, and there is substantial interest in using the device in combination with surgical removal of metastatic brain tumors. The GliaSite RTS was developed by Proxima Therapeutics Inc., a Georgia-based developer and marketer of site-specific cancer treatments. 


2. Int J Oncol. 2002 Oct;21(4):817-23. 
<b>Results of interstitial brachytherapy for malignant brain tumors. </b>
Mayr MT, Crocker IR, Butker EK, Williams H, Cotsonis GA, Olson JJ. 
Department of Neurosurgery, Naval Medical Center Portsmouth, Portsmouth, VA 23708, USA. 

We evaluated the efficacy of brachytherapy in patients with malignant brain tumors and assessed the factors associated with longer disease control after treatment. From June 1989 to October 1995, 73 patients were treated with stereotactic brachytherapy with temporary placement of iodine-125 implants. ... <b>Eleven patients (16%) developed radiation necrosis. Nine patients (13%) developed other complications.</b> Age and histologic diagnosis were significant predictors of survival from diagnosis. Age and KPS were independent predictors of time to failure after implant. Certain characteristics, specifically younger age (<55), and a higher KPS (</=70), appear to be associated with longer survival after brachytherapy. <b>Complications, some of which are life-threatening, can and do occur.</b> 
&&url PMID: 12239621  


3: Neurol Neurochir Pol. 2001;35 Suppl 5:5-11. 
<b>[Stereotactic biopsy and brachytherapy in the diagnostics and treatment of brain tumors--preliminary report]
[Article in Polish] </b>
Radek A, Grochal M, Gasinski P, Zielinski K, Kopczynski J, Sobotkowski J, Grzelak M, Lyczak P, Blaszczyk B. 
Kliniki Neurochirurgii Szpitala Klinicznego Wojskowcj Akademii Medycznej, Lodzi. 

Promising results have been obtained using brachytherapy in the treatment of brain tumors. Between November 99 and August 2000, 28 patients with brain tumors ... underwent implantation of temporary iridium 192 sources with stereotactic technique. This group received external beam radiation therapy (45 Gy) following implantation. Patients were followed-up with CT scans every 3 months. Serious complications occurred in two patients (postradiation brain oedema)... 
&&url PMID: 11935681  


4. Int J Radiat Oncol Biol Phys. 2000 Oct 1;48(3):831-6. 
<b>Extraneural metastatic glioblastoma after interstitial brachytherapy. </b>
Houston SC, Crocker IR, Brat DJ, Olson JJ. 
Department of Neurosurgery, Emory University School of Medicine, Atlanta, GA, USA. 

This is a report of 3 cases of extraneural metastasis of glioblastoma after interstitial radiation and assessment of pertinent literature addressing concern over an increased risk of these events with this therapy. ... In a series of 82 patients treated with (125)I brachytherapy for primary malignant brain tumors over a 7-year interval, 3 cases of extraneural glioblastoma were identified. The multicatheter technique for delivery of (125)I sources was utilized in all. Extraneural metastases were documented by imaging studies or biopsy. Over the same period, 310 patients with primary malignant brain tumors were treated without brachytherapy. ...<b>Biopsy-proven scalp and skull metastases occurred in 2 patients, at 3 and 8 months following brachytherapy. Each developed radiographic evidence of systemic metastases at 7 and 14 months postbrachytherapy,</b> respectively. The third patient developed biopsy-proven cervical node involvement 4 months after brachytherapy. No patients with malignant gliomas undergoing craniotomy or stereotactic biopsy, but not brachytherapy, during the same time period developed extraneural metastases. Incidence in previously reported series commenting on this otherwise rare process range from 0% to 4.3%. The incidence of extraneural metastases in this series is 3.7% (3/82) and is comparable to those reports. <b>CONCLUSIONS: Percutaneous catheter-delivered brachytherapy may be associated with an increased incidence of extraneural metastatic glioma. [what this means, actually, is that tumor might track along the catheter or incision lines used for the brachytherapy, AND that there might be tumor made metastatic by the procedure.  Be Warned. ed.]</b> 
&&url PMID: 11020581  


5. J Neurooncol. 1997 Jul;33(3):213-21. 
<b>Permanent low-activity iodine-125 implants for cerebral metastases. </b>
Schulder M, Black PM, Shrieve DC, Alexander E 3rd, Loeffler JS. 
Brain Tumor Center, Brigham and Women's Hospital, Dana Farber Cancer Institute, Boston, MA, USA. schulder@umdnj.edu 

<b>Beginning in 1987, selected patients with metastatic brain tumors were treated with permanent implants of low-activity radioactive iodine-125(125I) seeds. These patients underwent craniotomy, gross total resection of the metastatic lesion, and placement of the seeds. In general, criteria for treatment included the presence of a recurrent tumor with a volume too large to permit radiosurgery, and a Karnofsky Performance Score of 70 or higher.</b> Thirteen patients underwent 14 implant procedures; all received external whole-brain radiotherapy. Implant dose ranged from 43 Gy to 132 Gy, with a mean of 83 Gy. Survival after implantation ranged from 2 weeks to almost 9 years, with a median of 9 months. Clinical and radiographic local control was obtained in 9 patients. Two patients died of acute, postoperative complications within a month of implantation, so no information regarding tumor control is available for them. Late complications included a bone flap infection in one patient and a CSF leak in another; both were treated without further sequelae. <b>These results demonstrate that permanent 125I implants can results in good survival and quality of life, and occasionally can yield long-term survival. Potentially, it is a cost-effective treatment in that a separate procedure for stereotactic implantation or radiosurgery is not needed, as is the case with the use of temporary high-activity seeds. The permanent implantation itself adds less than 10 minutes to the craniotomy, and the risk of symptomatic radiation necrosis is low. We recommend consideration of this procedure in patients harboring large, recurrent metastatic tumors that require further surgery. </b>  
&&url PMID: 9195493  


6. Am J Clin Oncol. 1996 Aug;19(4):351-5. 
<b>Late onset of isolated central nervous system metastasis of liposarcoma--a case report. </b>
Arepally G, Kenyon LC, Lavi E. 
Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia 19104, USA. 

Metastatic soft-tissue sarcoma of the central nervous system (CNS) is exceedingly rare. We report a case of a 56-year-old male treated for a right lower extremity liposarcoma at the age of 30 years, whose first recurrence was an intracerebral metastasis occurring 26 years after resection of the primary tumor. Initial treatment of the metastasis with surgical resection and adjuvant radiotherapy was followed rapidly by CNS recurrence in 3 months. Further debulking and interstitial brachytherapy were unsuccessful in controlling disease progression. <b>Clinical presentation and treatment of brain metastases in soft-tissue sarcoma are discussed.</b> 
&&url PMID: 8677903  


7. Neurosurg Clin N Am. 1996 Jul;7(3):485-95.  
<b>Interstitial brachytherapy for intracranial metastases. </b>
McDermott MW, Cosgrove GR, Larson DA, Sneed PK, Gutin PH. 
Department of Neurosurgery, University of California at San Francisco, USA. 

In large medical centers, the availability of radiosurgery has relegated brachytherapy to a lesser role in the treatment of newly diagnosed solitary brain metastases. However, the treatment planning in radiosurgery is complex, and in some case the hardware is prohibitively expensive; low or high dose rate brachytherapy requires only a stereotactic frame, commercially available software, and encapsulated radionuclides or newer tiny linear accelerators. Interstitial brachytherapy also remains an option for the treatment of recurrent solitary metastases when other forms of treatment have failed. This article reviews the radiobiology of low and high dose rate interstitial brachytherapy, the University of California San Francisco (UCSF) results using iodine-125 implants, and early experience with the photon radiosurgery system (PRS) at Massachusetts General Hospital for the treatment of brain metastases. 
&&url PMID: 8823776  


8. Can J Neurol Sci. 1995 Feb;22(1):13-6. 
<b>Brachytherapy for recurrent single brain metastasis. </b>
Bernstein M, Cabantog A, Laperriere N, Leung P, Thomason C. 
Division of Neurosurgery, Toronto Hospital, Ontario, Canada. 

Of 112 stereotactic high-activity iodine-125 implants for malignant brain tumors done as of July 1, 1994, ten have been done for recurrent single brain metastasis and constitute the study group described herein. All patients had initially undergone craniotomy for tumor resection followed by fractionated external beam whole brain radiation and recurred at the same site in the brain. The interval between initial cancer therapy and occurrence of the brain metastasis was 13-156 weeks (median: 63 weeks). The interval between initial treatment of the brain metastasis and its recurrence treated with brachytherapy was 13-69 weeks (median: 35 weeks). Minimum brachytherapy dose administered was 70 Gy at a median dose rate of 67 cGy/hour. Eight patients have died. Two died suddenly at 2 and 13 weeks post-implant of presumed pulmonary embolus. Five died of recurrence of the brain metastasis at 20, 39, 52, 103, and 143 weeks post-implant, and one died of systemic metastases at 40 weeks post-implant. Two patients remain alive 183 and 324 weeks post-implant. High-activity iodine-125 brachytherapy appears to be of benefit for selected patients with recurrent single brain metastasis but larger, and preferably randomized studies are needed. 
&&url PMID: 7750066  


9. Acta Neurochir Suppl (Wien). 1995;63:29-34. 
<b>Interstitial irradiation of brain metastases. </b>
Alesch F, Hawliczek R, Koos WT. 
Neurochirurgische Universitatsklinik, Wien, Austria. 

<b>Randomized studies have shown that survival in patients with single brain metastases is significantly higher after the combined treatment of surgical removal and whole-brain irradiation than after whole-brain radiation therapy alone. </b>In patients with deep-seated lesions or those located in critical sites of the brain, as well as in cases in which the patient's general condition makes general anaesthesia difficult or impossible microsurgical resection usually cannot be performed or only with an increased surgical risk. Stereotactic radiosurgery, which can be done by means of convergent beam irradiation or by the implantation of highly loaded 125I seeds, provides an alternative to open procedures. In the following we report on our results using a stereotactic radiosurgical technique. A series of 20 treatments is presented, in which biopsy was performed and 125I seeds were implanted, both under stereotactic conditions in the same session. The 125I seeds were sealed in a teflon catheter, were left indwelling temporarily, and then removed after application of the prescribed radiation dose (6,000cGy at the tumour margin). There was only one recurrence in our series, complications occurred in only one patient by temporary aggravation of a pre-existing hemiparesis. Our results indicate that interstitial irradiation of brain metastases is a valuable, less stressful alternative to both open microsurgery as well as to stereotactic radiosurgical convergent beam irradiation. 
&&url PMID: 7502724  


10. Br J Neurosurg. 1995;9(5):593-603.
Comment in: Br J Neurosurg. 1996 Apr;10(2):229. 
<b>Interstitial iodine-125 radiosurgery for cerebral metastases. </b>
Ostertag CB, Kreth FW. 
Abteilung Stereotaktische Neurochirurgie, Neurochirurgische Universitatsklinik Freiburg, Germany. 

The current study evaluates the efficacy of interstitial 125-iodine radiosurgery (brachytherapy) in 93 patients with circumscribed, spherical, mostly solitary metastases. In all patients the histological diagnosis was established by stereotactic biopsy. The treatment results of three therapeutic regimens have been examined retrospectively: Group A (38 patients) had interstitial radiosurgery with a reference tumour dose of 60 Gy in combination with percutaneous radiotherapy (40 Gy). Group B (34 patients) was treated by interstitial radiosurgery alone (reference dose 60 Gy). Group C (21 patients with recurrent metastases after previous radiotherapy/surgery) was treated by interstitial radiosurgery alone (reference dose 60 Gy). Median survival after interstitial radiosurgery was 17 months in group A, 15 months in group B, 6 months in group C. Favourable prognostic factors were a Karnofsky performance rating > or = 70, solitary metastasis, absence of disseminated disease, and a time interval > 1 year between diagnosis of the primary tumour and diagnosis of the cerebral metastases. Interstitial radiosurgery plus percutaneous radiotherapy did not prove to be superior to interstitial radiosurgery alone. No patient died of a locally irradiated metastasis. We conclude that interstitial radiosurgery achieves control of the growth of solitary spherical cerebral metastases in any location without radiation toxicity.<b> [This may not be true of sarcomas. Ed.] </b> 
&&url PMID: 8561931  
