Amgad Matter

Permanent I-125 brain stem implants in children

Abstract Between 1988 and 1997, 28 children have had iodine-125 implants for CNS tumors performed in our institution. Ten had stereotactic implantation in the brain stem region, and nine had the diagnosis of brain stem glioma (8 diffuse pontine, 1 midbrain tumor). Their ages ranged from 1.8 to 12 years. All patients had histological confirmation of malignancy (7 high-grade glioma, 2 low-grade glioma, 1 PNET). Diffuse pontine glioma patients received external beam radiation (50 Gy) followed by a fractionated stereotactic boost of 3 Gy×4 fractions. After 4–6 weeks, patients were reevaluated for stereotactic interstitial I-125 therapy. The planned implant dose was 82.9 Gy to the enhancing tumor (4 cGy per h). Preliminary results indicated that no surgical complications were associated with the catheter placement. Four patients have died (7–9 months from diagnosis) and four patients remain alive (5–38 months from diagnosis, median 10 months). Two autopsies confirmed the presence of progressive glioblastoma multiforme and intralesional necrosis. In one patient who received an implant alone for midbrain LGA, necrosis without tumor was found on biopsy after 36 months. He was successfully treated with hyperbaric oxygen therapy. The implementation of permanent I-125 implants appears to have a role in the management of pediatric CNS malignancy. This study confirms the results of previous reports regarding the safety of stereotactic interstitial brachytherapy in the brain stem. Tumor control for patients with high-grade brain stem glioma remains poor even with high focal radiation doses.

Radiosurgery for Cerebral Arteriovenous Malformations

From September 1991 to May 1997, a total of 59 patients diagnosed with cerebral arteriovenous malformations were treated using radiosurgery. There were 29 men and 30 women, with an age range of 5 to 75 years (mean 36). Of these patients, 39 patients were treated using a LINAC-based system (group 1) and 20 using the Leksell γ-knife unit (group 2). Tumor volume ranged from 0.38 to 35 cc, and the number of isocenters varied from 1 to 3 in group 1 and from 2 to 15 in group 2. Lesion location was as follows: 14 temporal, 8 basal ganglionic, 8 frontal, 6 parietal, 6 thalamic, 5 intraventricular, 5 cerebellar, 3 brain stem, 3 occipital, and 1 corpus callosal. Seven patients underwent prior embolization and three patients had prior surgery with incomplete resection of their lesions. The marginal radiation dose ranged between 1500 and 2000 cGy with a mean of 1800 cGy. Twelve patients had concomitant embolization done on the morning of radiosurgery. Follow-up ranged from 1 month to 4 years. Thirty-six patients have been followed for more than 1 year. Thirty had an angiography during the follow-up period that showed complete obliteration of the lesion in 28 patients. The rate of obliteration was estimated to be 47.1% at 1 year, 82.3% at 2 years and 88.2% at 3 years.

Interactive Image-Guided Resection of Cerebral Cavernous Malformations

Between July 1992, and February 1997, 15 patients with cavernous malformations underwent interactive image-guided resection of their lesions. There were eight women and seven men in the group, ranging in age from 6 years to 62 years (mean 34 years). Clinical presentations included seizures (n = 7), headache (n = 4), and hemorrhage (n = 4). Prior conventional subtotal resection had been performed in one patient, and a history of prior hemorrhage was found for two patients. Diagnosis was made using magnetic resonance imaging and digital substraction angiography. Locations of the lesions were temporal (n = 9), frontal (n = 3), thalamus (n = 1), basal ganglia (n = 1), and pons (n = 1). Size ranged from 9 to 20 mm (mean 12 mm). For those lesions located near or within eloquent areas (n = 7), an awake craniotomy with functional cortical and subcortical mapping was performed. An infrared system was used intraoperatively to confirm the location and the extent of the resection of these lesions in real time. In 1996 we started using a robotic microscope to aid in localization and resection. Clinical follow-up ranged from 2 to 54 months (mean 27 months). In all 15 patients, complete surgical resection was achieved as demonstrated by postoperative magnetic resonance imaging studies. Two patients had postoperative transient neurological deficits (13.3%) that cleared over a 6-month period. One of them had a lesion in the pons, with multiple cranial nerve deficits postoperatively that gradually improved. There was no associated mortality. Histological diagnosis was consistent with cavernous angioma in all cases. Clinical follow-up revealed that 13 patients experienced complete recovery from preoperative symptoms and two patients with seizures showed marked improvement. We conclude that interactive image-guided surgery for deep-seated cavernous malformations represents a very accurate and safe approach.

Interactive Image-Guided Surgical Resection of Intracranial Arteriovenous Malformations

Surgical excision is the only treatment method that immediately prevents increased morbidity or mortality as a result of hemorrhage from arteriovenous malformations (AVMs). For those lesions located deep within the cerebral hemispheres or near eloquent areas, conventional surgical resection may be associated with an unacceptable degree of morbidity and mortality. Herein we report our experience in the resection of these lesions using interactive image guidance. There were five women and five men in the patient group. Their age ranged from 16 to 73 years (mean = 41). Clinical presentation included hemorrhage (n = 7), headaches (n = 2), and seizures (n = 1). All lesions were classified using the Spetzler-Martin grading system as follows: grade I (n = 4), grade II (n = 5), and grade III (n = 1). The locations of the lesions were supratentorial (9) and infratentorial (1). Surgical planning was carried out using the Neurological Surgery Planning System software developed at Wayne State University. An infrared-based system was used to locate and define the lesion intraoperatively. For those lesions located near or within eloquent areas, an awake craniotomy with functional mapping was carried out. Clinical follow-up ranged from 3 to 62 months (mean = 34). Complete surgical excision was achieved in all patients, which was demonstrated postoperatively by digital substraction angiography. The preoperative neurological status remained unchanged in seven patients and improved in three. There was no associated morbidity and mortality with this technique. Image-guided surgical resection of arteriovenous malformations represents a valuable technique, especially in small deep-seated lesions and in those near eloquent areas.

Radiosurgical Treatment of Meningiomas

From January 1992 to November 1996, 17 patients with the diagnosis of intracranial meningioma underwent radiosurgical treatment. Of these, 7 patients were treated using a Linac-based system (group 1), and 10 using the Leksell Gamma Knife unit (group 2). The follow-up ranged between 12 and 48 (median 33) months for group 1 and between 1 and 11 (median 5) months for group 2, consisting of clinical and MRI assessments every 3 months during the first year, and every 6 months thereafter. There were 14 women and 3 men. The mean age was 42 years. Prior to radiosurgery, 15 patients underwent surgical procedures. Histological diagnosis was consistent with benign meningioma, except in 2 patients (malignant meningioma). In 15 patients with benign meningiomas there was no evidence of tumor growth as demonstrated by clinical and radiological evaluation, in 2 patients with a malignant histological type there was tumor progression.

Permanent Iodine-125 Implants in the Treatment of Low-Grade Gliomas

We report a retrospective study on the use of the permanent iodine-125 (125I) implants in the management of low-grade gliomas. From July 1988 to July 1997, 16 patients with low-grade gliomas underwent permanent 125I implants in the management of their lesions. There were 7 males and 9 females ranging in age from 4 to 48 years (mean 19). The location was in the cerebral hemisphere in 7 patients, brainstem in 5 patients and thalamus/basal ganglia in 4 patients. Prior to brachytherapy, 9 patients underwent surgical resection and 7 patients underwent stereotactic biopsy procedures. Fourteen patients were treated as part of the initial management and 2 were recurrent. The histological diagnosis was: 9 WHO grade II astrocytomas, 3 oligodendrogliomas, 2 gemistocytic astrocytomas, 1 pilocytic astrocytoma, and 1 ependymoma. The tumor volume ranged from 0.7 to 33.4 cc (mean 8.4). Stereotactic treatment planning was used to encompass the contrast-enhancing rim of the tumor visualized by computerized tomography with an initial dose rate of 0.05 Gy/hour with 125I. The total activity ranged from 0.8 to 20.5 mCi. With a median follow-up period of 35 months (range, 4–105 months), the 2- and 5-year survival rates were 93.7% and 87.5%, respectively. Three patients underwent reoperation after implants, two of three had recurrent disease, and one had radiation necrosis. Permanent 125I implants appear to be safe and effective as a part of the multimodality management of low-grade gliomas.

Permanent I Interstitial Radiation Therapy in the Treatment of Non-GBM High-Grade Gliomas

This study evaluates prognostic factors influencing survival outcomes for 50 patients with permanent125 iodine-125 implants in the primary treatment of non-GBM high-grade gliomas. Stereotactic treatment planning aimed to encompass the contrast-enhancing rim of the tumor visualized by CT, with an initial dose rate of 0.05 Gy/hour with 125I, delivering 100 Gy at 1 year and 103.68 Gy at infinity. Survival was evaluated using the Kaplan–Meier method for unvariate analysis and the Cox regressional method for multivariate analysis. In addition to the implant, 31 patients received external radiation therapy (5000 to 6000 cGy) before the implant; 10 patients were implanted without additional external beam radiation, and 9 patients underwent external radiation therapy before implant placement. With a mean follow-up of 40.76 months (range 3.47–87 months); 1−, 3−, and 5-year survival were 78.5% (± .05%), 58.7% (± .07%), and 56.2% (± .07%) respectively. Since 56.2% of the patients were alive at 5 years, median survival has not been reached yet. Second surgery was performed following the implant in 19 patients. Findings were tumor recurrence in 11 patients (22.5%), radiation necrosis in 7 patients (14.3%), and brain abcess in 1 patient (2%). Age, sex, tumor location, side of brain, tumor volume, Karnofsky, and neurological status were correlated with survival outcome. Favorable prognostic factors were age younger than 45 years, superficial tumor location, and preoperative Karnofsky greater than 70. Surgical treatment of patients with non-GBM high grade gliomas combined with external beam radiation and permanent 125I implants represent a valuable alternative for the treatment of patients with malignant gliomas, allowing patients good quality of life and long survival.