Ann Maitz

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.

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.

An analysis of the dose-response for arteriovenous malformation radiosurgery and other factors affecting obliteration.

PURPOSE The aim of this study was to better understand arteriovenous malformation (AVM) obliteration rates after radiosurgery. METHODS AND MATERIALS We studied obliteration after Gamma knife radiosurgery in 351 AVM patients with 3-11 years of follow-up imaging. The median marginal dose was 20 Gy (range: 12-30) and median treatment volume was 5.7 cm(3) (range: 0.26-24). Stereotactic targeting was with angiography alone in 250 AVMs, and additional magnetic resonance (MR) imaging in 101 AVMs. RESULTS We documented obliteration by angiography in 193/264 (73%) AVM, and by MR alone in 75/87 (86%) AVM for a 75% corrected obliteration rate. We identified persistent out-of-field nidus in 18% of embolized vs. 5% of non-embolized patients, (P = 0.006). Multivariate analysis correlated in-field obliteration with marginal dose (P < 0.0001) and sex (P < or = 0.026, but not for overall obliteration P = 0.19). A mathematical dose-response model for overall obliteration was constructed to generate a dose-response curve for AVM obliteration with a maximum overall obliteration rate of 88% and minimal improvement above 25 Gy. We could not define the value of alpha/beta for AVM obliteration to a level of statistical significance. CONCLUSION The rate of AVM obliteration from radiosurgery depends on the marginal dose administered with a dose-response curve that reaches a maximum of approximately 88%. The dose-response plateau reflects problems with target definition which is made more difficult by prior embolization.

GAMMA KNIFE RADIOSURGERY OF IMAGING-DIAGNOSED INTRACRANIAL MENINGIOMA

PURPOSE To evaluate tumor control and outcome from radiosurgery of meningiomas diagnosed by imaging without pathologic verification. METHODS AND MATERIALS A total of 219 meningiomas diagnosed by imaging criteria underwent gamma knife radiosurgery to a median marginal tumor dose of 14 Gy (range 8.9-20), a median treatment volume of 5.0 cm(3) (range 0.47-56.5), and a median maximal dose of 28 Gy (range 22-50). The median follow-up was 29 months (range 2-164). RESULTS Tumor progression developed in 7 cases, 2 of which turned out to be different tumors (metastatic nasopharyngeal adenoid cystic carcinoma and chondrosarcoma). One tumor was controlled, but the development of other brain metastases suggested a different diagnosis. The actuarial tumor control rate was 93.2% +/- 2.7% at 5 and 10 years. The actuarial rate of identifying a diagnosis other than meningioma was 2.3% +/- 1.4% at 5 and 10 years. The actuarial rate of developing any postradiosurgical injury reaction was 8.8% +/- 3.0% at 5 and 10 years. No pretreatment variables correlated with tumor control in univariate or multivariate analysis. The risk of postradiosurgery sequelae was lower (5.3% +/- 2.3%) in patients treated after 1991 (with stereotactic MRI and lower doses; p = 0.0104) and tended to increase with treatment volume (p = 0.0537). CONCLUSION Radiosurgery of meningioma diagnosed by imaging without tissue confirmation is associated with a high rate of tumor control and acceptable morbidity but carries a small risk (2.3%) of an incorrect diagnosis.

Patient Outcomes after Stereotactic Radiosurgery for “Operable” Arteriovenous Malformations

: To define the outcomes after stereotactic radiosurgery performed for smaller volume arteriovenous malformations (AVMs) that are potentially suitable for surgical removal, we retrospectively reviewed our 4-year experience in 65 patients who declined microsurgery. All 65 patients had Spetzler-Martin Grade I or II AVMs and a minimum follow-up of 24 months (median, 29 mo). Symptomatic improvement after radiosurgery occurred in 52% of patients with seizures and in 63% of patients with headaches. The annual risk of AVM hemorrhage during the latency interval after radiosurgery was 3.7%. Five patients (7.7%) had a subsequent hemorrhage (all within 8 mo of radiosurgery); two died, and three recovered (one after hematoma evacuation and two with conservative management). Forty-seven patients (72%) returned to their previous employment status or activity level within 1 week of radiosurgery (92% within 1 yr). No patient suffered radiation-related complications. Twenty-seven (84%) of 32 patients evaluated by postradiosurgical angiography had complete AVM obliteration. Radiosurgery is an effective and less invasive management strategy for Grade I or II AVM patients who are either medically unsuitable for or unwilling to undergo surgical removal. The risk of AVM hemorrhage during the latency interval until obliteration occurs appears to be no different than the natural history of untreated AVMs. These results (including hemorrhage prevention and symptom amelioration) indicate that the conservative management of small AVMs can rarely be justified.To define the outcomes after stereotactic radiosurgery performed for smaller volume arteriovenous malformations (AVMs) that are potentially suitable for surgical removal, we retrospectively reviewed our 4-year experience in 65 patients who declined microsurgery. All 65 patients had Spetzler-Martin Grade I or II AVMs and a minimum follow-up of 24 months (median, 29 mo). Symptomatic improvement after radiosurgery occurred in 52% of patients with seizures and in 63% of patients with headaches. The annual risk of AVM hemorrhage during the latency interval after radiosurgery was 3.7%. Five patients (7.7%) had a subsequent hemorrhage (all within 8 mo of radiosurgery); two died, and three recovered (one after hematoma evacuation and two with conservative management). Forty-seven patients (72%) returned to their previous employment status or activity level within 1 week of radiosurgery (92% within 1 yr). No patient suffered radiation-related complications. Twenty-seven (84%) of 32 patients evaluated by postradiosurgical angiography had complete AVM obliteration. Radiosurgery is an effective and less invasive management strategy for Grade I or II AVM patients who are either medically unsuitable for or unwilling to undergo surgical removal. The risk of AVM hemorrhage during the latency interval until obliteration occurs appears to be no different than the natural history of untreated AVMs. These results (including hemorrhage prevention and symptom amelioration) indicate that the conservative management of small AVMs can rarely be justified.

Radiosurgery and brain tolerance: An analysis of neurodiagnostic imaging changes after gamma knife radiosurgery for arteriovenous malformations

In order to analyze complications and the factors responsible for the development of serial imaging changes after stereotactic radiosurgery for intracranial arteriovenous malformations, we reviewed serial post-treatment magnetic resonance imaging scans in 72 patients. Median follow-up was 23 months (range 12 to 35 months). Twenty patients developed post-radiosurgical imaging changes consisting of new regions of increased T2 signal on magnetic resonance imaging in brain surrounding the arteriovenous malformation (two year actuarial incidence of 31%). Imaging changes were associated with headache or new neurological deficits in nine of these 20 (45%) and remained asymptomatic in 11 (55%). Symptoms developed in three of 13 patients with imaging changes in the cerebral cortex or cerebellum, in contrast to six of seven patients who had symptoms with imaging changes in the brainstem (p = .028). The onset of imaging changes varied from five to 18 months after radiosurgery (median, 12 months). Serial follow-up scans four to 25 months after the onset of imaging changes were available for review in 16 patients. Post-radiosurgical imaging changes completely resolved within 4 to 19 months in ten patients and have not yet completely resolved after 6 to 25 months in six patients. The projected actuarial rate for resolution of imaging changes was 88%, 19 months after onset; the median time for resolution was 14 months. Univariate analysis revealed that the development of imaging changes was significantly associated with treatment volume (p = .025), the risk predicted from the integrated logistic formula (p = .042), and the number of isocenters treated (p = .042). In multivariate analysis, volume was the only factor significantly associated with the development of imaging changes.

Analysis of neurological sequelae from radiosurgery of arteriovenous malformations: how location affects outcome.

PURPOSE/OBJECTIVE To elucidate how the risks of developing temporary and permanent neurological sequelae from radiosurgery for arteriovenous malformations (AVM) are related to AVM location, the addition of stereotactic magnetic resonance (MR) imaging to angiographic targeting, and prior hemorrhage or neurological deficits. MATERIALS AND METHODS We evaluated follow-up imaging and clinical data in 332 AVM patients who received gamma knife radiosurgery at the University of Pittsburgh between 1987 and 1994. All patients had regular clinical or imaging follow-up for a minimum of 2 years (range: 24-96 months, median = 45 months). There were 83 patients with MR-assisted planning, 187 with prior hemorrhages, and 143 with prior neurological deficits. RESULTS Symptomatic postradiosurgery sequelae (any neurological problem including headache) developed in 30 (9%) of 332 patients. Symptoms resolved in 58% of patients within 27 months with a significantly greater proportion (p = 0.006) resolving in patients with Dmin < 20 Gy vs. > or = 20 Gy (89 vs. 36%). The 7-year actuarial rate for developing persistent symptomatic sequelae was 3.8%. We first evaluated the relative risks for different locations to construct a postradiosurgery injury expression (PIE) score for AVM location. Multivariate logistic regression analysis of symptomatic postradiosurgery sequelae identified independent significant correlations with PIE location score (p = 0.0007) and 12 Gy volume (p = 0.008), but with none of the other factors tested (p > 0.3), including the addition of MR targeting, average radiation dose in 20 cc, prior hemorrhage, or neurological deficit. We used these results to construct a risk prediction model for symptomatic postradiosurgery sequelae. The risk of radiation necrosis was significantly correlated with PIE score (p < 0.048), but not with 12-Gy volume. CONCLUSION The risks of developing complications from AVM radiosurgery can be predicted according to location with the PIE score, in conjunction with the 12-Gy treatment volume. Further study of factors affecting persistence of these sequelae (progression to radiation necrosis) is needed.

Treatment planning for gamma knife radiosurgery with multiple isocenters

Many arteriovenous malformations and tumors suitable for radiosurgical treatment have non-spherical or irregular shapes. Forty-eight percent of the first 156 patients treated with the gamma unit at the University of Pittsburgh required treatment with two or more isocenters to optimize dose distributions. Dose distributions for combining gamma knife treatments to two or more isocenters were systematically investigated. High speed computerized dosimetry was performed using specially developed software and dose distributions were confirmed with film densitometry. We have developed guidelines for treatment to two or more isocenters which help reduce treatment planning time, and facilitate selection of treatment doses and optimum dose distributions. These guidelines include maintaining an account of the distances between all isocenters, using a catalogue of sample two-isocenter isodose plans, comparing dose volume histograms, and calculating complication probabilities using the integrated logistic formula.

Prospective staged volume radiosurgery for large arteriovenous malformations: indications and outcomes in otherwise untreatable patients.

OBJECTIVE The obliteration response of an arteriovenous malformation (AVM) to radiosurgery is strongly dependent on dose and volume. For larger volumes, the dose must be reduced for safety, but this compromises obliteration. In 1992, we prospectively began to stage anatomic components in order to deliver higher single doses to symptomatic AVMs > 15 ml in volume. METHODS During a 17-year interval at the University of Pittsburgh, 1040 patients underwent radiosurgery for a brain AVM. Out of 135 patients who had multiple procedures, 37 patients underwent prospectively staged volume radiosurgery for symptomatic otherwise unmanageable larger malformations. Twenty-eight patients who were managed before 2002 were included in this study to achieve sufficient follow-up in assessing the outcomes. The median age was 37 years (range, 13-57 yr). Thirteen patients had previous hemorrhages and 13 patients had attempted embolization. Separate anatomic volumes were irradiated at 3 to 8 months (median, 5 mo) intervals. The median initial AVM volume was 24.9 ml (range, 10.2-57.7 ml). Twenty-six patients had two stages and two had three-stage radiosurgery. Seven patients had repeat radiosurgery after a median interval of 63 months. The median target volume was 12.3 ml. (range, 4.2-20.8 ml.) at Stage I and 11.5 ml. (range, 2.8-22 ml.) at Stage II. The median margin dose was 16 Gy at both stages. Median follow-up after the last stage of radiosurgery was 50 months (range, 3-159 mo). RESULTS Four patients (14%) sustained a hemorrhage after radiosurgery; two died and two patients recovered with mild permanent neurological deficits. Worsened neurological deficits developed in one patient. Seizure control was improved in three patients, was stable in eight patients and worsened in two. Magnetic resonance imaging showed T2 prolongation in four patients (14%). Out of 28 patients, 21 had follow-up more than 36 months. Out of 21 patients, seven underwent repeat radiosurgery and none of them had enough follow- up. Of 14 patients followed for more than 36 months, seven (50%) had total, four (29%) near total, and three (21%) had moderate AVM obliteration. CONCLUSIONS Prospective staged volume radiosurgery provided imaging defined volumetric reduction or closure in a series of large AVMs unsuitable for any other therapy. After 5 years, this early experience suggests that AVM related symptoms can be stabilized and anticipated bleed rates can be reduced.