Faculty Bibliography

BACKGROUND: The diagnosis of leptomeningeal dissemination of malignant glioma (meningeal gliomatosis) is associated with poor survival. Intrathecal (IT) chemotherapeutic agents used to achieve tumor control and improve survival include methotrexate, cytosine arabinoside (ara-C), thiotriethylenephosphoramide (thio-TEPA), neocarzinostatin, and 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1-nitros ourea hydrochloride (ACNU). Little information exists about survival following administration of IT chemotherapy. The authors report survival data from a series of patients with supratentorial anaplastic astrocytoma (AA) or glioblastoma multiforme (GBM) treated for ependymal or leptomeningeal gliomatosis with IT thio-TEPA. METHODS: The authors reviewed the records of 14 patients treated between 1991 and 1997 (GBM: n = 9; AA: n = 5). All patients were diagnosed with ependymal (n = 8) or leptomeningeal (n = 6) dissemination of tumor on the basis of clinical signs and symptoms, ependymal or leptomeningeal contrast enhancement on magnetic resonance imaging (MRI), and/or cerebrospinal fluid analysis. All 14 patients underwent placement of a ventricular reservoir system and subsequent instillation of IT thio-TEPA on a weekly basis for 6-12 weeks. Response to treatment was evaluated clinically and by MRI at intervals of 1-3 months and 3-6 months from the initiation of IT thio-TEPA. Data on survival from the time of diagnosis of dissemination was assessed. RESULTS: The median survival, from the time of diagnosis of ependymal or leptomeningeal dissemination, of patients who received IT thio-TEPA was 10 months (AA = 19 months; GBM = 10 months). Five of 14 patients had a radiographic response to treatment within 6 months. The median survival of patients with a radiographic response was 15.5 months, compared with 10 months for nonresponders. No significant neurotoxicity or myelopathy was observed. CONCLUSIONS: Early treatment with IT thio-TEPA may result in improved survival with minimal morbidity. Radiographic response may predict prolonged survival.

OBJECTIVE: To assess the potential for long-term serviceable hearing preservation in intracanalicular acoustic tumor patients who underwent stereotactic radiosurgery. METHODS: Between August 1987 and December 1997, 29 patients with intracanalicular acoustic tumors underwent stereotactic radiosurgery at our center using the Leksell gamma knife (Elekta Instruments, Inc., Atlanta, GA). Fifteen assessable patients had serviceable preradiosurgery hearing (pure tone average, < or = 50 dB; speech discrimination score, > or = 50%). We retrospectively analyzed our hearing results and compared hearing preservation in patients who received a minimal tumor dose of 14 Gy or less versus those who received more than 14 Gy to the tumor margin. RESULTS: No perioperative patient morbidity or mortality was observed. Serviceable hearing was preserved in 11 (73%) of 15 assessable patients (actuarial rate, 65%). Long-term follow-up demonstrated serviceable hearing preservation in 10 (100%) of 10 patients who received marginal tumor doses of 14 Gy or less but in only one of five patients who received more than 14 Gy. Preradiosurgery Gardner-Robertson class was preserved in 49%, and testable hearing was present in 68% of patients who had any testable hearing at presentation. Five patients demonstrated improvement in hearing (three had serviceable and two had nonserviceable hearing before radiosurgery). No patient developed a facial or trigeminal neuropathy. Seven of 13 patients with preoperative tinnitus continued to experience tinnitus in follow-up. Episodic vertigo continued in 3 of the 11 patients who presented with vertigo. CONCLUSION: Gamma knife radiosurgery (using conformal dose planning, small-beam geometry, and < or = 14 Gy to the margin) prevents tumor growth and achieves excellent hearing preservation rates.

Historically, neurosurgery has improved the environment of the nervous system to promote maximal spontaneous recovery of function. The population of patients whom we treat at present is a small portion of those who suffer from disabling neurological illnesses. Based on a combination of new technology, and advances in neuroscience, restorative neurosurgery is advancing the frontiers of our specialty, and providing the potential to restore lost function. Significant advancements in gene therapy, the discovery and delivery of neurotrophic factors, and cell transplantation now require neurosurgeons to broaden the scope of our practice so that it includes the restoration of function in an enormous number of patients with acquired, degenerative and idiopathic neurological diseases. In order to meet the present challenge, neurosurgeons must broaden our vision, our role, and our future educational goals. In this review, we summarize the landmark advances in the basic and clinical neurosciences and the results of clinical trials that are driving our evolution from passive reaction to disease to active attempts to restore lost central nervous system function.

OBJECT: Brainstem metastases portend a dismal prognosis. Surgical resection is not part of routine management and radiation therapy has offered little clinical benefit. Radiosurgery provides a safe and effective treatment for many patients with brain metastasis, but its role in the brainstem has not been evaluated. In this study the authors examine the role of radiosurgery in the treatment of brainstem metastases. METHODS: The authors reviewed the outcomes after stereotactic radiosurgery in 26 patients with 27 brainstem metastases. Tumor locations included the pons (21 tumors) and midbrain (six tumors): 14 patients had additional tumors in other locations. Twenty patients presented with brainstem signs. The median dose to the tumor margin was 16 Gy (range 12-20 Gy). Twenty-four patients received fractionated whole-brain radiation therapy (WBRT) and 12 underwent additional chemotherapy or immunotherapy. The median follow-up time in these patients was 9.5 months (range 1-43 months). After radiosurgery, the local control rate in brainstem tumors was 95%. In one patient in whom the tumor initially decreased in size, tumor enlargement was seen 7 months later. The median survival time was 11 months after diagnosis and 9 months after radiosurgery. Thirteen patients improved, 10 were stable, and three deteriorated. Eventually, 22 patients died, 18 of progression of their extracranial disease, three of new tumor growth (including one hemorrhage into a new brain metastasis), and one of extracranial disease plus new brain tumor growth. CONCLUSIONS: Although they have slightly lower than the expected survival rates of patients with nonbrainstem tumors, patients with brainstem metastases may achieve effective palliation after stereotactic radiosurgery and WBRT.

PURPOSE: Multiple brain metastases are a common health problem, frequently diagnosed in patients with cancer. The prognosis, even after treatment with whole brain radiation therapy (WBRT), is poor with average expected survivals less than 6 months. Retrospective series of stereotactic radiosurgery have shown local control and survival benefits in case series of patients with solitary brain metastases. We hypothesized that radiosurgery plus WBRT would provide improved local brain tumor control over WBRT alone in patients with two to four brain metastases. METHODS: Patients with two to four brain metastases (all < or =25 mm diameter and known primary tumor type) were randomized to initial brain tumor management with WBRT alone (30 Gy in 12 fractions) or WBRT plus radiosurgery. Extent of extracranial cancer, tumor diameters on MRI scan, and functional status were recorded before and after initial care. RESULTS: The study was stopped at an interim evaluation at 60% accrual. Twenty-seven patients were randomized (14 to WBRT alone and 13 to WBRT plus radiosurgery). The groups were well matched to age, sex, tumor type, number of tumors, and extent of extracranial disease. The rate of local failure at 1 year was 100% after WBRT alone but only 8% in patients who had boost radiosurgery. The median time to local failure was 6 months after WBRT alone (95% confidence interval [CI], 3.5-8.5) in comparison to 36 months (95% CI, 15.6-57) after WBRT plus radiosurgery (p = 0.0005). The median time to any brain failure was improved in the radiosurgery group (p = 0.002). Tumor control did not depend on histology (p = 0.85), number of initial brain metastases (p = 0.25), or extent of extracranial disease (p = 0.26). Patients who received WBRT alone lived a median of 7.5 months, while those who received WBRT plus radiosurgery lived 11 months (p = 0.22). Survival did not depend on histology or number of tumors, but was related to extent of extracranial disease (p = 0.02). There was no neurologic or systemic morbidity related to stereotactic radiosurgery. CONCLUSIONS: Combined WBRT and radiosurgery for patients with two to four brain metastases significantly improves control of brain disease. WBRT alone does not provide lasting and effective care for most patients.

BACKGROUND: Jugular foramen schwannomas pose difficult management problems because of the surgical risk of lower cranial neuropathy. The indications and results of stereotactic radiosurgery are not well documented. METHODS: We reviewed our 10-year experience in the management of 17 patients who had jugular foramen schwannomas managed with the gamma knife. Thirteen patients previously had undergone surgery (range, 1-6 resections). Four patients had multiple cranial nerve deficits before microsurgical resection; 12 developed multiple lower cranial nerve palsies after resection. Four patients underwent radiosurgery based on imaging criteria alone. Conformal dose planning (tumor margin dose of 12-18 Gy) successfully encompassed the irregular tumor volumes in all patients. RESULTS: Follow-up varied from 6 to 74 months. Tumor size decreased in eight patients, remained stable in eight, and increased in one patient during the average follow-up interval of 3.5 years. Six patients improved and 10 others retained their preradiosurgery clinical status. One patient had an increase in tumor size and clinical deterioration 6 months after radiosurgery and underwent microsurgical resection. No patient developed new cranial nerve or other neurological deficits after radiosurgery. CONCLUSIONS: We believe that gamma knife radiosurgery is an effective alternative to microsurgical resection for patients who have small tumors and intact lower cranial nerve function. It is also effective for patients who have residual or recurrent tumors after microsurgical resection.

The indications for stereotactic radiosurgery for patients with cavernous malformations of the brain are discussed. Specific reference is made to technique and dose selection and to the results and potential complications of this approach. Radiosurgery is an alternative to microsurgical resection for some patients with malformations in high-risk brain locations.

OBJECTIVE: To determine the risks and survival benefit associated with implantation of an absorbable, 1,3-bis(2chloroethyl)-1-nitrosourea-impregnated polymer wafer, we prospectively studied patients with recurrent glioblastoma multiforme and compared them with a demographically matched cohort group. METHODS: Over a 29-month period, 62 patients underwent operations. All had tumor growth despite standard treatment, a Karnofsky performance score of > or =70, and histopathological confirmation of glioblastoma. Seventeen patients underwent gross total resection with placement of 1,3-bis(2-chloroethyl)-1-nitrosourea wafers (wafer group) at a median 44 weeks from diagnosis (6 women, 11 men; median age, 56 years). A cohort group of 45 patients undergoing surgery for recurrent glioblastoma during the same time period, but not receiving wafers, was identified. Surgery was performed at a median 47 weeks from diagnosis (14 women, 31 men; median age, 54 years). RESULTS: Within 6 weeks of surgery, 13 complications were identified in 8 patients in the wafer group. In the cohort group, 6 patients sustained 8 complications. We were unable to identify any survival advantage using Kaplan-Meier analysis. In the wafer group, median survival was 58 weeks from diagnosis and 14 weeks from wafer implantation. In the cohort group, median survival was 97 weeks from diagnosis and 50 weeks from operation. CONCLUSION: 1,3-bis(2-chloroethyl)-1-Nitrosourea wafer implantation for recurrent glioblastoma was associated with a higher risk of postoperative complications, particularly those related to infection and wound healing. No clear survival benefit associated with wafer implantation was identified.