Gamma Knife surgery for the management of glomus tumors: a multicenter study.

OBJECT: Glomus tumors are rare skull base neoplasms that frequently involve critical cerebrovascular structures and lower cranial nerves. Complete resection is often difficult and may increase cranial nerve deficits. Stereotactic radiosurgery has gained an increasing role in the management of glomus tumors. The authors of this study examine the outcomes after radiosurgery in a large, multicenter patient population. METHODS: Under the auspices of the North American Gamma Knife Consortium, 8 Gamma Knife surgery centers that treat glomus tumors combined their outcome data retrospectively. One hundred thirty-four patient procedures were included in the study (134 procedures in 132 patients, with each procedure being analyzed separately). Prior resection was performed in 51 patients, and prior fractionated external beam radiotherapy was performed in 6 patients. The patients' median age at the time of radiosurgery was 59 years. Forty percent had pulsatile tinnitus at the time of radiosurgery. The median dose to the tumor margin was 15 Gy. The median duration of follow-up was 50.5 months (range 5-220 months). RESULTS: Overall tumor control was achieved in 93% of patients at last follow-up; actuarial tumor control was 88% at 5 years postradiosurgery. Absence of trigeminal nerve dysfunction at the time of radiosurgery (p = 0.001) and higher number of isocenters (p = 0.005) were statistically associated with tumor progression-free tumor survival. Patients demonstrating new or progressive cranial nerve deficits were also likely to demonstrate tumor progression (p = 0.002). Pulsatile tinnitus improved in 49% of patients who reported it at presentation. New or progressive cranial nerve deficits were noted in 15% of patients; improvement in preexisting cranial nerve deficits was observed in 11% of patients. No patient died as a result of tumor progression. CONCLUSIONS: Gamma Knife surgery was a well-tolerated management strategy that provided a high rate of long-term glomus tumor control. Symptomatic tinnitus improved in almost one-half of the patients. Overall neurological status and cranial nerve function were preserved or improved in the vast majority of patients after radiosurgery.

Impact of endoscopic surgical techniques on efficiency in pituitary surgery.

OBJECTIVE: To assess the impact of the introduction of endoscopic surgical techniques into a neurosurgical practice for pituitary surgery on operative efficiency. STUDY DESIGN: Case series with chart review. SETTING: Tertiary referral center. SUBJECTS AND METHODS: Patients undergoing transsphenoidal pituitary surgery over a 4-year period were identified. The approach over this period evolved from classic transseptal surgery to exclusively endoscopic techniques. Patients were classified as having transseptal surgery, endoscopic approach with microsurgical resection, aborted endoscopic resection with subsequent microsurgery, and exclusive endoscopic techniques. Patient and surgeon demographics, operative times, total operating room times, and room setup time were examined. Univariate analysis and multivariate regression modeling were used to assess outcome measures. RESULTS: One hundred seven patients were identified. The use of the endoscope for either sphenoid exposure alone (n = 41) or for the entire procedure (n = 35) resulted in a significant reduction in operative and room times compared to transseptal approaches (n = 25). Exclusively endoscopic techniques resulted in a significant reduction in operative and room times independent of all other clinical and surgical parameters (P < .001). Progressive use of endoscopic techniques resulted in statistically significant progressive reduction in setup time (P = .001), operative time (P = .04), and total room time (P = .03) over the study period. CONCLUSION: The transition from transseptal transsphenoidal pituitary surgery to endoscopic techniques implies a learning process for both neurosurgeon and otolaryngologist. Despite this, a noteworthy reduction in operative times, operating room times, and room setup times is observed. The impact of endoscopic techniques on efficiency in pituitary surgery is discussed.

Long-term hearing results in gamma knife radiosurgery for acoustic neuromas.

OBJECTIVES: There are many studies that have examined functional outcomes following Gamma Knife treatment; however, few have reported long-term audiometric data. This study analyzed the long-term hearing results of Gamma Knife radiosurgery in the treatment of acoustic neuromas. STUDY DESIGN: Retrospective cohort study. METHODS: Seventeen patients were selected from our acoustic neuroma Gamma Knife registry of 113 patients treated from 1991 to 2005. Pretreatment audiograms were analyzed for pure-tone average and word recognition scores and assigned a Gardner-Robertson classification score (GRC). Either a current audiogram was obtained or the most recent audiogram (if the patient was lost to follow-up) was reviewed from clinic charts and these were compared with the preoperative results. Audiometric data of the pre- and posttreatment normal ear were obtained and used as the patient's own control. RESULTS: The tumor size ranged from 0.5 to 2.8 cm (mean, 1.33 cm) and patients received a range of 12.5-16 Gy (mean, 13.82 Gy) to 50% isodose line. Patient follow-up ranged from 3 to 82 months with a mean of 33.6 months. Pretreatment pure-tone average for the involved side group was 30.6 dB HL with a word recognition score of 74%. Pretreatment mean GRC was 1.76. posttreatment pure-tone average for the group was 59.7 dB HL with a word recognition score of 37%. posttreatment mean GRC was 3.29. Comparing pre- versus post-Gamma Knife radiosurgery results on the treatment ear, means were statistically significantly different for both pure-tone average and word recognition scores, based on a paired-samples t test (P < .001 for both). The group "normal" ear pure-tone average was 14 dB HL and 17.75 dB HL pre- and posttreatment, respectively. Normal ear pre- and posttreatment word recognition score and GRC were 93% and 98%, and 1.13 and 1.31, respectively. CONCLUSION: Gamma Knife radiosurgery remains a noninvasive treatment option for patients with acoustic neuromas; however, they may experience a delayed hearing loss. Of those patients with useful audition pretreatment, 42% maintained useful hearing posttreatment.

Unilateral intraputamenal glial cell line-derived neurotrophic factor in patients with Parkinson disease: response to 1 year of treatment and 1 year of withdrawal.

OBJECT: Glial cell line-derived neurotrophic factor (GDNF) infused unilaterally into the putamen for 6 months has been previously shown to improve significantly motor functions and quality of life measures in 10 patients with Parkinson disease (PD) in a Phase I trial. In the present study the authors report the safety and efficacy of continuous treatment for a minimum of 1 year. After the trial was halted by the drug sponsor, the patients were monitored for an additional 1 year during which the effects of drug withdrawal were evaluated. METHODS: During the extended study period, patients received a 30-microg/day unilateral intraputamenal infusion of GDNF at a basal infusion rate supplemented with pulsed boluses every 6 hours at a convection-enhanced delivery rate to increase tissue penetration of the protein. When the study was stopped, the delivery system was reprogrammed to deliver sterile saline at the basal infusion rate of 2 microl/hour. The Unified Parkinson's Disease Rating Scale (UPDRS) total scores after 1 year of therapy were improved by 42 and 38% in the off- and on-medication states; the motor UPDRS scores were also improved 45 and 39%, respectively. Benefits from treatment were lost by 9 to 12 months after the cessation of GDNF infusion. The UPDRS scores returned to their baseline and the patients required higher levels of conventional antiparkinsonian drugs to treat symptoms. After 11 months of treatment, the delivery system had to be removed in one patient because of risk of infection. Seven patients developed antibodies to GDNF but without evident clinical sequelae. There was no evidence for GDNF-induced cerebellar toxicity, as evaluated by magnetic resonance imaging and clinical testing. CONCLUSIONS: The unilateral administration of GDNF results in significant, sustained bilateral benefits in patients with PD. These improvements are lost within 9 months of drug withdrawal. Safety concerns with GDNF therapy can be closely monitored and managed.

Unilateral intraputaminal glial cell line-derived neurotrophic factor in patients with Parkinson disease: response to 1 year each of treatment and withdrawal.

OBJECT: Glial cell line-derived neurotrophic factor (GDNF) infused unilaterally into the putamen for 6 months was previously shown to improve motor functions and quality of life measures significantly in 10 patients with Parkinson disease (PD) in a Phase I trial. In this study the authors report the safety and efficacy of continuous treatment for 1 year or more. After the trial was halted by the sponsor, the patients were monitored for an additional year to evaluate the effects of drug withdrawal. METHODS: During the extended study, patients received unilateral intraputaminal infusion of 30 mg/day GDNF at a basal infusion rate supplemented with pulsed boluses every 6 hours at a convection-enhanced delivery rate to increase tissue penetration of the protein. When the study was stopped, the delivery system was reprogrammed to deliver sterile saline at the basal infusion rate of 2 ml/hour. The Unified PD Rating Scale (UPDRS) total scores after 1 year of therapy were improved by 42 and 38%, respectively, in the "off" and "on" states. Motor UPDRS scores were also improved: 45 and 39% in the off and on conditions, respectively. Benefits from treatment were lost by 9 to 12 months after GDNF infusion was halted. At that time, the patients had returned to their baseline UPDRS scores and required higher levels of conventional antiparkinsonian drugs to treat symptoms. After 11 months of treatment, the delivery system had to be removed in one patient because of the risk of infection. In seven patients antibodies to GDNF developed, with no evidence of clinical sequelae. There was also no evidence of GDNF-induced cerebellar toxicity, as evaluated using magnetic resonance imaging analysis and clinical testing. CONCLUSIONS: Unilateral administration of GDNF results in significant, sustained bilateral benefits. These improvements are lost within 9 months after drug withdrawal. Safety concerns with GDNF therapy can be closely monitored and managed.

Recursive partitioning analysis classifications I and II: applicability evaluated in a randomized trial for resected single brain metastases.

PURPOSE: Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis (RPA) prognostic classes I and II for patients with brain metastases is derived from a database made up primarily of patients with unresected and multiple metastases. An analysis of a previously published randomized trial was performed to determine the applicability of these RPA prognostic classes in the setting of resection of single metastases to the brain. PATIENTS AND METHODS: Ninety-five patients with single metastases to the brain that were treated with complete surgical resection entered this study. Patients were randomly assigned to treatment with postoperative whole brain radiotherapy (WBRT) (n = 49 patients) or no further brain treatment (n = 46 patients). All patients entered on this study had a Karnofsky performance status of > or =70. Therefore, although the RTOG RPA has 3 classes, only patients with RPA classes I (n = 26) or II (n = 69) were eligible for this study analysis. RESULTS: For RPA class I, the median survival was 10.9 months versus 9.8 months for class II patients (P = 0.45). Multivariate analysis showed that only postoperative WBRT, independent of RPA class I or II, lessened the risk of brain tumor recurrence (P < 0.0001). CONCLUSION: This analysis of a randomized trial evaluating postoperative WBRT in the treatment of single metastases to the brain showed no difference in survival between RPA class I or II patients. In addition, the use of postoperative WBRT after complete surgical resection of single brain metastases results in substantially better control of disease in the brain independent of RPA classes I or II.

Gamma knife stereotactic radiosurgery for synchronous versus metachronous solitary brain metastases from non-small cell lung cancer.

A retrospective study was conducted analyzing the clinical outcome and various prognostic factors in patients treated with gamma knife stereotactic radiosurgery (GK-SRS) for solitary brain metastasis from non-small cell lung carcinoma (NSCLC). A total of 72 patients from June of 1992 to January of 1999 were treated. All patients received GK-SRS to a median dose of 18Gy, with 45 patients receiving additional whole-brain radiation therapy. No one had evidence of extra-cranial metastasis at the time of diagnosis of brain metastases. The median follow-up was 15.7 months for the entire population and 99.5 months for those who were alive at the last follow-up. Univariate and multivariate analyses were used to test the impact of various prognostic factors on survival. The median and 5-year actuarial survivals for the entire cohort were 15.7 months and 10.4%, respectively. The presence of a metachronous versus a synchronous brain metastasis was the only factor significant in the univariate (P=0.045) and multivariate (P=0.002) analyses. Patients with metachronous solitary brain metastases had a significant median survival advantage compared to those with synchronous metastases (33.3 months versus 8.6 months, P=0.001). However, there was no statistically significant difference in median survival from the time of metastasis when treated with GK-SRS in these groups (12.5 months versus 8.4 months, P=0.50). The addition of WBRT did not improve overall survival (12.0 months versus 7.7 months, P=0.73). The 5-year actuarial survival for the metachronous and synchronous groups were 13.2 and 8.1%, respectively. In conclusion, patients presenting with a solitary metachronous brain metastasis from NSCLC achieved longer survivals than those with a synchronous metastasis. The tail in the survival curves demonstrates that a prolonged survival may be attained in patients with solitary metastases from NSCLC. This study adds to the growing body of literature that supports the use of SRS in the management of this patient population.

Clinical trials in head injury.

Traumatic brain injury (TBI) remains a major public health problem globally. In the United States the incidence of closed head injuries admitted to hospitals is conservatively estimated to be 200 per 100,000 population, and the incidence of penetrating head injury is estimated to be 12 per 100,000, the highest of any developed country in the world. This yields an approximate number of 500,000 new cases each year, a sizeable proportion of which demonstrate significant long-term disabilities. Unfortunately, there is a paucity of proven therapies for this disease. For a variety of reasons, clinical trials for this condition have been difficult to design and perform. Despite promising pre-clinical data, most of the trials that have been performed in recent years have failed to demonstrate any significant improvement in outcomes. The reasons for these failures have not always been apparent and any insights gained were not always shared. It was therefore feared that we were running the risk of repeating our mistakes. Recognizing the importance of TBI, the National Institute of Neurological Disorders and Stroke (NINDS) sponsored a workshop that brought together experts from clinical, research, and pharmaceutical backgrounds. This workshop proved to be very informative and yielded many insights into previous and future TBI trials. This paper is an attempt to summarize the key points made at the workshop. It is hoped that these lessons will enhance the planning and design of future efforts in this important field of research.

Risk of symptomatic brain tumor recurrence and neurologic deficit after radiosurgery alone in patients with newly diagnosed brain metastases: results and implications.

PURPOSE: A single-institution experience using primary stereotactic radiosurgery (SRS) alone in the management of newly diagnosed brain metastases was analyzed to identify the risk of symptomatic brain tumor recurrence (BTR) and neurologic deficit associated with such a treatment strategy. METHODS AND MATERIALS: Thirty-six patients were treated for newly diagnosed single/multiple brain metastases using SRS alone followed by planned observation. SRS minimum tumor dose ranged from 8 to 25 Gy (median: 20 Gy). Factors evaluated in analysis of treatment outcome included number of metastases, site of metastasis, primary tumor site, histology, extent of intracranial and extracranial disease, and interval to diagnosis of brain metastasis. RESULTS: Median and 1-year survival for the entire group was 9 months and 36%, respectively. BTR anywhere in the brain occurred in 47% (17/36) of patients. Forty-seven percent of BTR (8/17) recurred at the site of original metastasis; 35% (6/17) recurred at both original [corrected] and distant sites in the brain, and 18% (3/17) recurred at distant only [corrected] brain sites. Seventy-one percent (12/17) of the patients were symptomatic at the time of recurrence, and 59% (10/17) had an associated neurologic deficit. Multivariate analysis found that only the extent of disease was a predictor of BTR. Patients who had disease limited to the brain only had a BTR rate of 80% (8/10) vs. 35% (9/26) who had disease involving the brain, primary site, and/or other extracranial metastatic sites (p = 0.03). CONCLUSIONS: Use of primary SRS alone in this setting is associated with an increasingly significant risk of BTR with increasing survival time. In addition, the majority of such recurrences are symptomatic and associated with a neurologic deficit, a finding not analyzed in recently reported experiences withholding whole brain radiation therapy as part of the primary treatment of brain metastasis.