Douglas Kondziolka

Stereotactic radiosurgery plus whole brain radiotherapy versus radiotherapy alone for patients with multiple brain metastases

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.

A multi-institutional experience with stereotactic radiosurgery for solitary brain metastasis

PURPOSE A multi-institutional experience in radiosurgery for solitary brain metastases was combined to identify factors associated with safety, efficacy, tumor control, and survival. MATERIALS AND METHODS A review of 116 patients with solitary brain metastases who underwent gamma knife stereotactic radiosurgery at five institutions was performed. The median follow-up was 7 months following radiosurgery and 12 months following diagnosis. Minimum tumor doses varied from 8-30 Gy (mean, 17.5 Gy). Forty-five patients failed prior radiotherapy and 71 had no prior brain irradiation. Fifty-one patients had radiosurgery alone and 65 underwent combined radiosurgery with fractionated large-field radiotherapy (mean dose, 33.8 Gy). RESULTS Median survival was 11 months after radiosurgery and 20 months after diagnosis. Follow-up documented local tumor control in 99 patients (85%), tumor recurrence in 17 (15%), and documented radiation necrosis in one (1%). The 2-year actuarial tumor control rate was 67 +/- 8%. Tumor histology affected survival (better for breast cancer, p = .004) and local control (better for melanoma and renal cell, p = .0003) in multivariate analyses. Combined fractionated radiotherapy and radiosurgery improved local control (p = 0.111), but not survival in multivariate testing. CONCLUSION Radiosurgery is effective in controlling solitary brain metastases with low morbidity. Further study is needed to better define optimum treatment parameters for radiosurgery.

Brain metastases in patients with no known primary tumor

The care of patients with a brain metastasis from unknown primary site is controversial. The authors reviewed the results of stereotactic radiosurgery in this group of patients to better define clinical expectations.

Transplantation of cultured human neuronal cells for patients with stroke

Article abstract Transplantation of cultured neuronal cells is safe in animal models and improves motor and cognitive deficits in rats with stroke. The authors studied the safety and feasibility of human neuronal cellular transplantation in patients with basal ganglia stroke and fixed motor deficits, including 12 patients (aged 44 to 75 years) with an infarct 6 months to 6 years previously (stable for at least 2 months). Serial evaluations (12 to 18 months) showed no adverse cell-related serologic or imaging-defined effects. The total European Stroke Scale score improved in six patients (3 to 10 points), with a mean improvement 2.9 points in all patients (p = 0.046). Six of 11 PET scans at 6 months showed improved fluorodeoxyglucose uptake at the implant site. Neuronal transplantation is feasible in patients with motor infarction.

Long-Term Outcomes after Radiosurgery for Acoustic Neuromas

BACKGROUND Stereotactic radiosurgery is the principal alternative to microsurgical resection for acoustic neuromas (vestibular schwannomas). The goals of radiosurgery are the long-term prevention of tumor growth, maintenance of neurologic function, and prevention of new neurologic deficits. Although acceptable short-term outcomes have been reported, long-term outcomes have not been well documented. METHODS We evaluated 162 consecutive patients who underwent radiosurgery for acoustic neuromas between 1987 and 1992 by means of serial imaging tests, clinical evaluations, and a survey between 5 and 10 years after the procedure. The average dose of radiation to the tumor margin was 16 Gy, and the mean transverse diameter of the tumor was 22 mm (range, 8 to 39). Resection had been performed previously in 42 patients (26 percent); in 13 patients the tumor represented a recurrence of disease after a previous total resection. Facial function was normal in 76 percent of the patients before radiosurgery, and 20 percent had useful hearing. RESULTS The rate of tumor control (with no resection required) was 98 percent. One hundred tumors (62 percent) became smaller, 53 (33 percent) remained unchanged in size, and 9 (6 percent) became slightly larger. Resection was performed in four patients (2 percent) within four years after radiosurgery. Normal facial function was preserved in 79 percent of the patients after five years (House-Brackmann grade 1), and normal trigeminal function was preserved in 73 percent. Fifty-one percent of the patients had no change in hearing ability. No new neurologic deficits appeared more than 28 months after radiosurgery. An outcomes questionnaire was returned by 115 patients (77 percent of the 149 patients still living). Fifty-four of these patients (47 percent) were employed at the time of radiosurgery, and 37 (69 percent) remained so. Radiosurgery was believed to have been successful by all 30 patients who had undergone surgery previously and by 81 (95 percent) of the 85 who had not. Thirty-six of the 115 patients (31 percent) described at least one complication, which resolved in 56 percent of those cases. CONCLUSIONS Radiosurgery can provide long-term control of acoustic neuromas while preserving neurologic function.

Recommendations for the Management of Intracranial Arteriovenous Malformations A Statement for Healthcare Professionals From a Special Writing Group of the Stroke Council, American Stroke Association

Intracranial arteriovenous malformations (AVMs) are relatively uncommon but increasingly recognized lesions that can cause serious neurological symptoms or death. Although AVMs can present with hemorrhage or seizure, since the advent of contemporary brain imaging techniques, an increasing number are detected before rupture. Over the last decade, there have been significant developments in the management of intracranial AVMs. There has been an evolution of microsurgical as well as endovascular and radiosurgical techniques to treat these lesions. As the management options have evolved, individual and combined modality treatment protocols have been developed in different institutions for the management of AVMs. A writing group was formed by the Stroke Council of the American Stroke Association to review published data for intracranial AVMs to develop practice recommendations regarding epidemiology, natural history, potential treatment strategies, and outcomes. The reports reviewed for this synthesis were selected on the basis of study design, sample size, and relevance to a particular topic. Each report was graded according to previously defined criteria.1 2 After review of the available literature, recommendations for current practice standards have been made according to 3 separate grades (Table 1⇓). View this table: Table 1. Levels of Evidence in Grading of Recommendations for Treatment of Patients With Subarachnoid Hemorrhage By the design of this type of review, the recommendations in this report represent an overview of existing treatment protocols that may vary considerably. These guidelines were developed to serve as a basis for the development of treatment strategies for AVMs, which overall represent a fairly heterogeneous group of cerebrovascular lesions and which may demonstrate different natural histories. In addition, for brain AVMs, no level I or II data are available in the literature. Because of the heterogeneity of these lesions and their relatively infrequent occurrence, strictly defined subcategories for comparison of the efficacy of various treatment modalities …

Factors associated with successful arteriovenous malformation radiosurgery.

OBJECTIVE To analyze the clinical and angiographic variables that affect the results of arteriovenous malformation (AVM) radiosurgery and to propose a new method of reporting patient outcomes after AVM radiosurgery. This method incorporates both the obliteration status of the AVMs and the postoperative neurological condition of the patient. METHODS Patient outcomes were defined as excellent (nidus obliteration and no new deficits), good (nidus obliteration with a new minor deficit), fair (nidus obliteration with a new major deficit), unchanged (incomplete nidus obliteration without a new deficit), poor (incomplete nidus obliteration with any new deficit), and dead. Two hundred twenty patients who underwent AVM radiosurgery at our center before 1992 were subjected to a multivariate analysis with patient outcomes as the dependent variable. RESULTS Multivariate analysis determined four factors associated with successful AVM radiosurgery: smaller AVM volume (P=0.003), number of draining veins (P=0.001), younger patient age (P=0.0003), and hemispheric AVM location (P=0.002). Preradiosurgical embolization was a negative predictor of successful AVM radiosurgery (P=0.02). CONCLUSION AVM obliteration without new neurological deficits can be achieved in at least 80% of patients with small volume, hemispheric AVMs after single-session AVM radiosurgery. Future studies on AVM radiosurgery should report patient outcomes in a fashion that incorporates all the factors involved in successful AVM radiosurgery.

Radiosurgery of vestibular schwannomas: summary of experience in 829 cases

OBJECT Management options for vestibular schwannomas (VSs) have greatly expanded since the introduction of stereotactic radiosurgery. Optimal outcomes reflect long-term tumor control, preservation of cranial nerve function, and retention of quality of life. The authors review their 15-year experience. METHODS Between 1987 and 2002, some 829 patients with VSs underwent gamma knife surgery (GKS). Dose selection, imaging, and dose planning techniques evolved between 1987 and 1992 but thereafter remained stable for 10 years. The average tumor volume was 2.5 cm3. The median margin dose to the tumor was 13 Gy (range 10-20 Gy). No patient sustained significant perioperative morbidity. The average duration of hospital stay was less than 1 day. Unchanged hearing preservation was possible in 50 to 77% of patients (up to 90% in those with intracanalicular tumors). Facial neuropathy risks were reduced to less than 1%. Trigeminal symptoms were detected in less than 3% of patients whose tumors reached the level of the trigeminal nerve. Tumor control rates at 10 years were 97% (no additional treatment needed). CONCLUSIONS Superior imaging, multiple isocenter volumetric conformal dose planning, and optimal precision and dose delivery contributed to the long-term success of GKS, including in those patients in whom initial microsurgery had failed. Gamma knife surgery provides a low risk, minimally invasive treatment option for patients with newly diagnosed or residual VS. Cranial nerve preservation and quality of life maintenance are possible in long-term follow up.

Development of a model to predict permanent symptomatic postradiosurgery injury for arteriovenous malformation patients

PURPOSE To better predict permanent complications from arteriovenous malformation (AVM) radiosurgery. METHODS AND MATERIALS Data from 85 AVM patients who developed symptomatic complications following gamma knife radiosurgery and 337 control patients with no complications were evaluated as part of a multi-institutional study. Of the 85 patients with complications, 38 patients were classified as having permanent symptomatic sequelae (necrosis). AVM marginal doses varied from 10-35 Gy and treatment volumes from 0.26-47.9 cc. Median follow-up for patients without complications was 45 months (range: 24-92). RESULTS Multivariate analysis of the effects of AVM location and the volume of tissue receiving 12 Gy or more (12-Gy-Volume) allowed construction of a significant postradiosurgery injury expression (SPIE) score. AVM locations in order of increasing risk and SPIE score (from 0-10) were: frontal, temporal, intraventricular, parietal, cerebellar, corpus callosum, occipital, medulla, thalamus, basal ganglia, and pons/midbrain. The final statistical model predicts risks of permanent symptomatic sequelae from SPIE scores and 12-Gy-Volumes. Prior hemorrhage, marginal dose, and Marginal-12-Gy-Volume (target volume excluded) did not significantly improve the risk-prediction model for permanent sequelae (p >/= 0.39). CONCLUSION The risks of developing permanent symptomatic sequelae from AVM radiosurgery vary dramatically with location and, to a lesser extent, volume. These risks can be predicted according to the SPIE location-risk score and the 12-Gy-Volume.

A dose-response analysis of arteriovenous malformation obliteration after radiosurgery

PURPOSE Although radiosurgery is effective in obliterating the pathologic vessels of intracranial arteriovenous malformations (AVM), the relationships of both dose and volume to obliteration have not been well defined. METHODS AND MATERIALS The results of radiosurgery in 197 AVM patients with 3-year angiographic follow-up were analyzed. Volume varied from 0.06-18 cc (median: 4.1 cc), and minimum target dose (Dmin) varied from 12.0-25.6 Gy (median: 20.0 Gy). RESULTS Follow-up angiography revealed complete AVM obliteration in 142 out of 197 patients (72%). The targeted AVM nidus failed to obliterate in 20 patients (10%), but in-field obliteration was complete in the remaining 35 patients (18%) discovered to have residual untargeted AVM nidus. Multivariate logistic regression analysis of in-field obliteration revealed a significant independent correlation with Dmin (p = 0.04), but not with volume or maximum dose. A sigmoid dose-response curve for in-field obliteration was constructed that significantly differed from the dose-volume-response relationships that would have been expected from overall obliteration data. CONCLUSIONS The success rate for in-field obliteration of AVM after radiosurgery depends on Dmin but does not appear to change appreciably with volume or maximum dose. Success rates for complete obliteration additionally are limited by problems defining the complete AVM nidus.