Bruce E. Pollock

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.

Meningioma radiosurgery: tumor control, outcomes, and complications among 190 consecutive patients.

OBJECTIVETo determine local control (LC) and complication rates for patients with intracranial meningiomas who underwent radiosurgery. METHODSOne hundred ninety consecutive patients with 206 meningiomas underwent radiosurgery between 1990 and 1998. One hundred forty-seven tumors (77%) involved the cranial base. The median age at the time of radiosurgery was 58 years (range, 20–90 yr). There were 126 female patients (66%). One hundred twelve patients (59%) had undergone one or more previous operations (median, 1; range, 1–5). Twenty-two patients (12%) had either atypical (n = 13) or malignant (n = 9) tumors. The median prescription isodose volume was 8.2 cm3 (range, 0.5–50.5 cm3), and the median tumor margin dose was 16 Gy (range, 12–36 Gy). The median imaging and clinical follow-up periods were 40 and 47 months, respectively. RESULTSOverall survival rates for the entire cohort at 5 and 7 years were 82 and 82%, respectively; cause-specific survival rates at 5 and 7 years were 94 and 92%, respectively. The cause-specific survival rates at 5 years for patients with benign, atypical, and malignant tumors were 100, 76, and 0%, respectively (P < 0.0001). The 5-year LC rate was 89%, with 114 tumors (56%) decreasing in size. LC rates were correlated with tumor histological features (P < 0.0001); patients with benign tumors exhibited a 5-year LC rate of 93%, compared with 68 and 0% for patients with atypical or malignant meningiomas, respectively. No correlation was observed between radiation dose and LC rate. Twenty-four patients (13%) experienced treatment-related complications, including cranial nerve deficits (8%), symptomatic parenchymal changes (3%), internal carotid artery stenosis (1%), and symptomatic cyst formation (1%). Only six patients (3%) exhibited decreases in functional status that were directly related to radiosurgery. Tumor volume, tumor margin dose, or previous radiotherapy was not associated with the development of radiation-related complications. CONCLUSIONRadiosurgery is an effective management strategy for many patients with meningiomas. Patients with atypical or malignant tumors exhibit high recurrence rates despite the use of radiosurgery, and these patients continue to exhibit worse cause-specific survival rates despite aggressive treatment, including surgery, external-beam radiotherapy, and radiosurgery. Further study is needed to determine the tumor control and complication rates 10 years or more after meningioma radiosurgery.

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.

A study on the radiation tolerance of the optic nerves and chiasm after stereotactic radiosurgery

PURPOSE To evaluate the risk of clinically significant radiation optic neuropathy (RON) for patients having stereotactic radiosurgery of benign tumors adjacent to the optic apparatus. METHODS AND MATERIALS We reviewed the dose plans and clinical outcomes of 218 gamma knife procedures (215 patients) for tumors of the sellar and parasellar region (meningiomas, n = 122; pituitary adenomas, n = 89; craniopharyngiomas, n = 7 patients). Previous surgery or radiation therapy was performed in 156 (66%) and 24 (11%) patients, respectively. Median follow-up was 40 months (range 4-115). RESULTS The median maximum radiation dose to the optic nerve was 10 Gy (range 0.4-16.0). Four patients (1.9%) developed RON at a median of 48 months after radiosurgery. All had prior surgery, and 3 of 4 had external beam radiotherapy (EBRT) in their management either before (n = 2) or adjuvantly (n = 1). The risk of developing a clinically significant RON was 1.1% for patients receiving 12 Gy or less. Patients receiving prior or concurrent EBRT had a greater risk of developing RON after radiosurgery (p = 0.004). CONCLUSION RON occurred in less than 2% of our patients, despite the majority (73%) receiving more than 8 Gy to a short segment of the optic apparatus. Knowledge of the dose tolerance of these structures permits physicians to be more aggressive in treating patients with sellar or parasellar tumors, especially those with hormone-producing pituitary adenomas that appear to require higher doses to achieve biochemical remission.

Factors That Predict the Bleeding Risk of Cerebral Arteriovenous Malformations

BACKGROUND AND PURPOSE Arteriovenous malformations (AVMs) have an overall 2% to 4% annual risk of hemorrhage. The purpose of this study was to determine whether specific clinical and radiographic factors predispose AVMs to bleed and to predict the bleeding risk for individual AVM patients. METHODS We reviewed the clinical histories and cerebral angiograms of 315 AVM patients who underwent stereotactic radiosurgery at our center. One half of the patient data (analysis cohort) was used to determine risk factors for bleeding and to construct AVM hemorrhage risk groups. These risk groups were then tested with the second half of the patient data (test cohort). RESULTS The mean AVM volume was 4.0 +/- 3.4 mL (approximate maximum diameter of 2 cm). One hundred ninety-six initial hemorrhages occurred in 10,348 patient-years for an annual initial bleed rate of 1.89%; 44 of these 196 patients had a repeat bleed in 591 patient-years for an annual rebleed rate of 7.45%. The overall crude annual hemorrhage rate was 2.40%. Multivariate analysis revealed three factors associated with hemorrhage: history of a prior bleed (relative risk [RR], 9.09; 95% confidence interval [CI], 5.44 to 15.19; P < .001), a single draining vein (RR, 1.66; 95% CI, 1.13 to 2.38; P < .01), and a diffuse AVM morphology (RR, 1.64; 95% CI, 1.12 to 2.46; P < .01). Four AVM hemorrhage risk groups were constructed on the basis of the significant factors. The annual rate of bleeding was 0.99% for low-risk AVMs, 2.22% for intermediate-low-risk AVMs, 3.72% for intermediate-high-risk AVMs, and 8.94% for high-risk AVMs. CONCLUSIONS Analysis of a large group of AVM patients who underwent stereotactic radiosurgery demonstrated that small AVMs have an annual hemorrhage risk similar to that of the general AVM population. AVM patients have a wide variability of bleeding risk that can be predicted from their clinical presentation and the angiographic characteristics of the AVM. The management of AVM patients should be based not only on the morbidity of the proposed treatment but also those factors that predispose individual patients to either a low or high hemorrhage risk.

A comparison of surgical resection and stereotactic radiosurgery in the treatment of solitary brain metastases

PURPOSE To determine whether neurosurgery (NS) or stereotactic radiosurgery (RS) provided better local tumor control and enhanced patient survival. METHODS AND MATERIALS Retrospective review of all solitary brain metastases (SBM) patients newly diagnosed at Mayo Clinic Rochester between 1991 and 1999. Eligible patients satisfied tumor size and SBM site criteria to qualify for both NS and RS. RESULTS There were no significant differences between 74 NS and 23 RS patients in terms of baseline characteristics (age, gender, systemic disease type, systemic disease status, signs/symptoms at SBM presentation) or percent of patients who received whole brain radiotherapy. Median follow-up for alive patients was 20 months (range 0-106 months). There was no significant difference in patient survival (p = 0.15); the 1-year survival rate was 56% for the RS patients and 62% for the NS patients. Multivariate Cox regression analysis found that a significant prognostic factor for survival was a performance score of 0 or 1. There was a significant (p = 0.020) difference in local tumor control between NS and RS for solitary brain metastasis; none of the RS group had local recurrence compared to 19 (58%) of the NS group. CONCLUSION The need for a Phase III study comparing these two techniques appears to be supported by the data from this study.

Patient Outcomes After Vestibular Schwannoma Management: a Prospective Comparison of Microsurgical Resection and Stereotactic Radiosurgery

OBJECTIVE The best management for patients with small- to medium-sized vestibular schwannomas (VS) is controversial. METHODS : A prospective cohort study of 82 patients with unilateral, unoperated VS less than 3 cm undergoing surgical resection (n = 36) or radiosurgery (n = 46). Patients undergoing resection were younger (48.2 yr versus 53.9 yr, P = 0.03). The groups were similar with regard to hearing loss, associated symptoms, and tumor size. The mean follow-up period was 42 months (range, 12-62 mo). RESULTS Normal facial movement and preservation of serviceable hearing was more frequent in the radiosurgical group at 3 months (P < 0.001), 1 year (P < 0.001), and at the last follow-up examination (P < 0.01) compared with the surgical resection group. Patients undergoing surgical resection had a significant decline in the following subscales of the Health Status Questionnaire 3 months after surgery: physical functioning (P = 0.006), role-physical (P < 0.001), energy/fatigue (P = 0.02), and overall physical component (P = 0.004). Patients in the surgical resection group continued to have a significant decline in the physical functioning (P = 0.04) and bodily pain (P = 0.04) subscales at 1 year and in bodily pain (P = 0.02) at the last follow-up examination. The radiosurgical group had no decline on any component of the Health Status Questionnaire after the procedure. The radiosurgical group had lower mean Dizziness Handicap Inventory scores (16.5 versus 8.4, P = 0.02) at the last follow-up examination. There was no difference in tumor control (100 versus 96%, P = 0.50). CONCLUSION Early outcomes were better for VS patients undergoing stereotactic radiosurgery compared with surgical resection (Level 2 evidence). Unless long-term follow-up evaluation shows frequent tumor progression at currently used radiation doses, radiosurgery should be considered the best management strategy for the majority of VS patients.

Effect of Radiosurgery Alone vs Radiosurgery With Whole Brain Radiation Therapy on Cognitive Function in Patients With 1 to 3 Brain Metastases: A Randomized Clinical Trial

IMPORTANCE Whole brain radiotherapy (WBRT) significantly improves tumor control in the brain after stereotactic radiosurgery (SRS), yet because of its association with cognitive decline, its role in the treatment of patients with brain metastases remains controversial. OBJECTIVE To determine whether there is less cognitive deterioration at 3 months after SRS alone vs SRS plus WBRT. DESIGN, SETTING, AND PARTICIPANTS At 34 institutions in North America, patients with 1 to 3 brain metastases were randomized to receive SRS or SRS plus WBRT between February 2002 and December 2013. INTERVENTIONS The WBRT dose schedule was 30 Gy in 12 fractions; the SRS dose was 18 to 22 Gy in the SRS plus WBRT group and 20 to 24 Gy for SRS alone. MAIN OUTCOMES AND MEASURES The primary end point was cognitive deterioration (decline >1 SD from baseline on at least 1 cognitive test at 3 months) in participants who completed the baseline and 3-month assessments. Secondary end points included time to intracranial failure, quality of life, functional independence, long-term cognitive status, and overall survival. RESULTS There were 213 randomized participants (SRS alone, n = 111; SRS plus WBRT, n = 102) with a mean age of 60.6 years (SD, 10.5 years); 103 (48%) were women. There was less cognitive deterioration at 3 months after SRS alone (40/63 patients [63.5%]) than when combined with WBRT (44/48 patients [91.7%]; difference, -28.2%; 90% CI, -41.9% to -14.4%; P < .001). Quality of life was higher at 3 months with SRS alone, including overall quality of life (mean change from baseline, -0.1 vs -12.0 points; mean difference, 11.9; 95% CI, 4.8-19.0 points; P = .001). Time to intracranial failure was significantly shorter for SRS alone compared with SRS plus WBRT (hazard ratio, 3.6; 95% CI, 2.2-5.9; P < .001). There was no significant difference in functional independence at 3 months between the treatment groups (mean change from baseline, -1.5 points for SRS alone vs -4.2 points for SRS plus WBRT; mean difference, 2.7 points; 95% CI, -2.0 to 7.4 points; P = .26). Median overall survival was 10.4 months for SRS alone and 7.4 months for SRS plus WBRT (hazard ratio, 1.02; 95% CI, 0.75-1.38; P = .92). For long-term survivors, the incidence of cognitive deterioration was less after SRS alone at 3 months (5/11 [45.5%] vs 16/17 [94.1%]; difference, -48.7%; 95% CI, -87.6% to -9.7%; P = .007) and at 12 months (6/10 [60%] vs 17/18 [94.4%]; difference, -34.4%; 95% CI, -74.4% to 5.5%; P = .04). CONCLUSIONS AND RELEVANCE Among patients with 1 to 3 brain metastases, the use of SRS alone, compared with SRS combined with WBRT, resulted in less cognitive deterioration at 3 months. In the absence of a difference in overall survival, these findings suggest that for patients with 1 to 3 brain metastases amenable to radiosurgery, SRS alone may be a preferred strategy. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00377156.

Complications from arteriovenous malformation radiosurgery: Multivariate analysis and risk modeling

PURPOSE/OBJECTIVE To assess the relationships of radiosurgery treatment parameters to the development of complications from radiosurgery for arteriovenous malformations (AVM). METHODS AND MATERIALS We evaluated follow-up imaging and clinical data in 307 AVM patients who received gamma knife radiosurgery at the University of Pittsburgh between 1987 and 1993. All patients had regular clinical or imaging follow up for a minimum of 2 years (range: 24-96 months, median = 44 months). RESULTS Post-radiosurgical imaging (PRI) changes developed in 30.5% of patients with regular follow-up magnetic resonance imaging, and were symptomatic in 10.7% of all patients at 7 years. PRI changes resolved within 3 years developed significantly less often (p = 0.0274) in patients with symptoms (52.8%) compared to asymptomatic patients (94.8%). The 7-year actuarial rate for developing persistent symptomatic PRI changes was 5.05%. Multivariate logistic regression modeling found that the 12 Gy volume was the only independent variable that correlated significantly with PRI changes (p < 0.0001) while symptomatic PRI changes were correlated with both 12 Gy volume (p = 0.0013) and AVM location (p = 0.0066). CONCLUSION Complications from AVM radiosurgery can be predicted with a statistical model relating the risks of developing symptomatic post-radiosurgical imaging changes to 12 Gy treatment volume and location.