Embolization and radiosurgery for AVMs.
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Embolization, Therapeutic↗
Biomedical subjects
J C Flickinger
Publications and source records attributed to J C Flickinger.
Gamma knife radiosurgery for trigeminal neuralgia.
Radiosurgery is one of the surgical treatments of trigeminal neuralgia. Through precise irradiation of the proximal trigeminal nerve identified on high-resolution imaging, pain relief can be achieved after a short latency interval. This image-guided approach has been useful for both patients with persistent pain after other surgeries, and as a primary surgical option. A minimum dose of 70 Gy delivered with the gamma knife has been associated with low risk for facial numbness, and no other morbidity. Management of trigeminal neuralgia without an incision, transfacial needle placement or nerve section may prove useful to increasing numbers of patients.
Humans↗
Gamma knife for glioma: selection factors and survival.
PURPOSE: To determine factors associated with survival differences in patients treated with radiosurgery for glioma. METHODS AND MATERIALS: We analyzed 189 patients treated with Gamma Knife radiosurgery for primary or recurrent glioma World Health Organization (WHO) Grades 1-4. RESULTS CONCLUSION: The median minimum tumor dose was 16 Gy (8-30 Gy) and the median tumor volume was 5.9 cc (1.3-52 cc). Brachytherapy selection criteria were satisfied in 65% of patients. Median follow-up of all surviving patients was 65 weeks after radiosurgery. For primary glioblastoma patients, median survival from the date of pathologic diagnosis was 86 weeks if brachytherapy criteria were satisfied and 40 weeks if they were not (p = 0.01), indicating that selection factors strongly influence survival. Multivariate analysis showed that increased survival was associated with five variables: lower pathologic grade, younger age, increased Karnofsky performance status (KPS), smaller tumor volume, and unifocal tumor. Survival was not found to be significantly related to radiosurgical technical parameters (dose, number of isocenters, prescription isodose percent, inhomogeneity) or extent of preradiosurgery surgery. We developed a hazard ratio model that is independent of the technical details of radiosurgery and applied it to reported radiosurgery and brachytherapy series, demonstrating a significant correlation between survival and hazard ratio. CONCLUSIONS: Survival after radiosurgery for glioma is strongly related to five selection variables. Much of the variation in survival reported in previous series can be attributed to differences in distributions of these variables. These variables should be considered in selecting patients for radiosurgery and in the design of future studies.
Adolescent↗
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.
Analysis of Variance↗
Evolution in technique for vestibular schwannoma radiosurgery and effect on outcome.
PURPOSE: To define changes in treatment technique for vestibular schwannoma radiosurgery and to relate them to changes in outcome, a large single institution experience was reviewed. METHODS AND MATERIALS: Two hundred seventy-three patients with unilateral vestibular schwannomas underwent Gamma knife radiosurgery: 118 with computed tomography (CT) treatment planning during 1987-1991, and 155 with magnetic resonance imaging (MR) treatment planning in 1991-1994. Mean treatment parameters differed between the CT and MR groups: minimum tumor dose (D(min)) was 17 vs. 14 Gy, number of isocenters was 3.4 vs. 5.8, and volume was 3.5 vs 2.7 cc., respectively. RESULTS: The actuarial 7-year clinical tumor control rate (no requirement for surgical intervention) for the entire series was 96.4 +/- 2.3%, with a radiographic tumor control rate of 91.0 +/- 3.4%; these rates were similar for the CT and MR groups. Significantly lower rates of postradiosurgery facial, trigeminal, and auditory neuropathy were observed in the MR group compared to the CT group. Multivariate analyses found significant independent correlations of increasing rates of facial and trigeminal neuropathy with increasing transverse tumor diameter and D(min), as well as with CT treatment planning (compared to MR). Decreased hearing was similarly correlated with diameter and CT planning but not with D(min). CONCLUSIONS: Changes in radiosurgery technique and the use of lower doses improved the outcome after vestibular schwannoma radiosurgery by decreasing cranial neuropathy rates. MR-based treatment planning appears to have significantly contributed to this improvement. Despite decreases in radiation dose, no change in the high rate of tumor control has yet been observed.
Actuarial Analysis↗
Radiosurgery for hemangioblastoma: results of a multiinstitutional experience.
PURPOSE: Between June 1988 and June 1994. 38 hemangioblastomas were treated with stereotactic radiosurgery (SR) at three SR centers to evaluate the efficacy and potential toxicity of this therapeutic modality as an adjuvant or alternative treatment to surgical resection. METHODS AND MATERIALS: SR was performed using either a 201-cobalt source unit or a dedicated SR linear accelerator. Of the 18 primary tumors treated, 16 had no prior history of surgical resection and were treated definitively with SR and two primary lesions were subtotally resected and subsequently treated with SR. Twenty lesions were treated with SR after prior surgical failure (17 tumors) or failure after prior surgery and conventional radiotherapy (three tumors). Eight patients were treated with SR for multifocal disease (total, 24 known tumors). SR tumor volumes measured 0.05 to 12 cc (median: 0.97 cc). Minimum tumor doses ranged from 12 to 20 Gy (median: 15.5 Gy). RESULTS: Median follow-up from the time of SR was 24.5 months (range: 6-77 months). The 2-year actuarial over-all survival was 88 +/- 15% (95% confidence interval). Two-year actuarial freedom from progression was 86 +/- 12% (95% confidence interval). The median tumor volume of the lesions that failed to be controlled by SR was 7.85 cc (range: 3.20-10.53 cc) compared to 0.67 cc (range: 0.05-12 cc) for controlled lesions (p - 0.0023). The lesions that failed to be controlled by SR received a median minimum tumor dose of 14 Gy (range: 13-17 Gy) compared to 16 Gy (range: 12-20 Gy) for controlled lesions (p = 0.0239). Seventy-eight percent of the surviving patients remained neurologically stable or clinically improved. There were no significant permanent complications directly attributable to SR. CONCLUSIONS: This report documents the largest experience in the literature of the use of SR in the treatment of hemangioblastoma. We conclude that SR: (a) controls the majority of primary and recurrent hemangioblastomas; (b) offers the ability to treat multiple lesions in a single treatment session, which is particularly important for patients with Von Hippel-Lindau Syndrome; and that (c) better control rates are associated with higher doses and smaller tumor volumes.
Adrenal Cortex Hormones↗
Radiosurgery instead of resection for solitary brain metastasis: the gold standard redefined.
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Brain Neoplasms↗
Dose and diameter relationships for facial, trigeminal, and acoustic neuropathies following acoustic neuroma radiosurgery.
PURPOSE AND OBJECTIVE: To define the relationships between dose and tumor diameter for the risks of developing trigeminal, facial, and acoustic neuropathies after acoustic neuroma radiosurgery, a large single-institution experience was analyzed. MATERIALS AND METHODS: Two hundred and thirty-eight patients with unilateral acoustic neuromas who underwent Gamma knife radiosurgery between 1987-1994 with 6-91 months of follow-up (median 30 months) were studied. Minimum tumor doses were 12-20 Gy (median 15 Gy). Transverse tumor diameter varied from 0.3-5.5 cm (median 2.1 cm). The relationships of dose and diameter to the development of cranial neuropathies were delineated by multivariate logistic regression. RESULTS: The development of post-radiosurgery neuropathies affecting cranial nerves V, VII, and VIII were correlated with minimum tumor dose and transverse tumor diameter (P < 0.01 for all except Dmin for VIII where P = 0.10). A comparison of the dose-diameter response curves showed the acoustic nerve to be the most sensitive to doses of 12-16 Gy and the facial nerve to be the least sensitive. CONCLUSION: The risks of developing trigeminal, facial, and acoustic neuropathies following acoustic neuroma radiosurgery can be predicted from the transverse tumor diameter and the minimum tumor dose using models constructed from data presently available.
Cranial Nerve Diseases↗
Repeat stereotactic radiosurgery of arteriovenous malformations: factors associated with incomplete obliteration.
Second stereotactic radiosurgery procedures were required in 45 patients with arteriovenous malformations (AVMs) who initially had incomplete obliteration. Repeat radiosurgery was performed at a median of 39 months (range, 24-71 mo) after the first stage. The median AVM volume at the first procedure was 6.0 ml (range, 0.2-18.0 ml). Thirty-seven patients (82%) had AVMs of Spetzler-Martin Grades III through VI. A retrospective analysis revealed definite causes for incomplete obliteration after the first procedure in 33 patients (73%). Incomplete angiographic definition of the nidus was the most frequent factor (57%) associated with failed radiosurgery. Three patients (7%) had recanalization of the AVM nidus after prior embolization; four patients (9%) had incomplete nidus recognition, because AVM vessels were not visualized in the presence of a hematoma. "Radiobiological resistance" was another potential factor associated with failed radiosurgery in 17 patients (38%). Our current technique for volume determination and dose planning includes stereotactic magnetic resonance angiography, magnetic resonance imaging, and complete cerebral angiography (including superselective and external carotid artery injections, as indicated). Integrated multiplanar high-resolution imaging will likely increase the rate of AVM obliteration after stereotactic radiosurgery.
Adolescent↗
Use of magnetic resonance imaging in stereotactic surgery. A survey of members of the American Society of Stereotactic and Functional Neurosurgery.
Members of the American Society of Stereotactic Functional Neurosurgery were surveyed to determine the current use of magnetic resonance imaging (MRI) for stereotactic coordinate determination. Of 137 respondents, 48% used MRI as the sole technique for some biopsy procedures. Of those performing functional surgery, more surgeons use MRI alone than CT alone for localization. Of those surgeons who used MRI alone for stereotactic surgery, 98.6% were satisfied with this method. Significant factors related to the use of MRI amongst individual surgeons included the performance of > or = 2 stereotactic surgeries per week, the performance of radiosurgery, and being in an academic practice (p < 0.0004). The increasing use of MRI in stereotactic surgery must be coupled with quality assurance testing from frame manufacturers, imaging manufacturers, and surgeons.
Biopsy↗
Trigeminal neuralgia radiosurgery: the University of Pittsburgh experience.
The results of Gamma Knife stereotactic radiosurgery in the management of 51 patients who had typical trigeminal neuralgia were evaluated at the University of Pittsburgh. In all cases, a 4-mm isocenter was targeted at the proximal nerve at the root entry zone. The target dose varied from 60 to 90 Gy. Forty-four patients (86%) had undergone prior surgery. The mean follow-up after radiosurgery was 9.6 months (range, 2-29 months). The initial response rate was 86%. At the last follow-up, 19 patients (37%) had excellent control (pain free), 21 (41%) had good control (50-90% relief), and 11 (21%) had failed treatment. No patient developed further sensory loss or deafferentation pain. A maximum radiosurgery dose > or = 70 Gy was associated with a significantly greater chance for complete pain relief. Using magnetic resonance imaging stereotactic targeting, the proximal trigeminal nerve is an appropriate anatomic target for radiosurgery. Gamma Knife radiosurgery is a useful additional surgical approach in the management of medically or surgically refractory trigeminal neuralgia.
Adult↗
Seizure outcome in children treated for arteriovenous malformations using gamma knife radiosurgery.
Seizures are the second most common presenting symptom of arteriovenous malformations (AVMs) in children. Although radiosurgery has been found to be a safe and effective alternative treatment, the outcome of seizure control in children after radiosurgery for AVMs is unknown. Between 1987 and 1994, 72 children under the age of 18 years were treated with gamma knife radiosurgery for AVMs at our institution. Fifteen patients (21%) had seizures as part of their clinical course. There were 11 boys and 4 girls with ages varying from 2 to 17 years (median 16 years). Seizures included: generalized tonic-clonic (n = 8); focal motor or sensory (n = 4); partial complex (n = 2), and a combination of generalized and partial complex (n = 1). Nine lesions were in cortical locations; six were subcortical. Spetzler-Martin grades included: II (n = 7); III (n = 4); IV (n = 2), and VI (n = 2). During follow-up after radiosurgical treatment, 11 of 13 patients (85%) were seizure free and off anticonvulsant therapy (mean follow-up 47 months). Two patients had a significant improvement in their seizures but continue on medication. Two of the 72 patients (3%) developed seizures after treatment and remain on medication. Seizure outcome was not associated with the location or complete obliteration of the lesion. We conclude that stereotactic radiosurgery, as a non-invasive alternative, is associated with a good outcome for the AVM as well as AVM-related seizures in children.
Adolescent↗
Early outcomes after stereotactic radiosurgery for growing pilocytic astrocytomas in children.
To examine the role of stereotactic radiosurgery in the adjuvant management of children with growing and unresectable deep-seated pilocytic astrocytomas, we reviewed our experience in 9 patients. The tumors were located in the dorsolateral pons (n = 2), midbrain (n = 1, cerebellar peduncle (n = 2), thalamus (n = 1), temporal lobe (n = 1), hypothalamus (n = 1), and caudate nucleus (n = 1). The mean tumor diameter was 16 mm (range, 11-25 mm). Seven patients had prior partial tumor resection, and 2 had a stereotactic biopsy. Two patients had failed fractionated radiotherapy and 7 were considered at risk for adverse radiation effects because of their age. The mean dose to the tumor margin at radiosurgery was 15 Gy (range, 12-18). During mean follow-up of 19 months (range 13-41 months), there was a marked decrease in tumor size in 5 patients; 4 patients had no further growth. No early or delayed morbidity was associated with radiosurgery. Gamma knife radiosurgery proved a safe and effective therapeutic tool in the management of children with deep, small volume pilocytic astrocytomas. Because this tumor often appears well-delineated on contrast-enhanced neuroimaging, we believe that conformal radiosurgical targeting accurately irradiates tumor cells. For small tumor volumes it can be used in place of fractionated larger-field radiotherapy. The ability to treat the tumor yet spare surrounding brain may reduce the surgical morbidity associated with attempted radical resection and the potential cognitive and endocrine disabilities associated with fractionated radiation therapy.
Adolescent↗
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.
Adult↗
Stereotactic radiosurgery for postgeniculate visual pathway arteriovenous malformations.
Arteriovenous malformations (AVMs) that are located within the postgeniculate optic radiations or striate cortex are difficult to resect without creating postoperative visual defects. To reduce the risk of an AVM hemorrhage and to enhance the possibility of preserving visual function, the authors performed stereotactic radiosurgery in 34 patients with newly diagnosed or residual AVMs of the visual pathways. The mean AVM volume was 4.7 ml, and the average radiation dose to the AVM margin was 21 Gy. The median follow up was 47 months (range 16-83 months). Two (6%) of 34 patients had documented new visual field defects (central scotoma in one, and partial hemianopsia in one) after single-stage radiosurgery, but no patient developed a new permanent homonymous hemianopsia. Angiography was performed in all patients at a median of 26 months after radiosurgery: 22 (65%) had complete obliteration, 10 (29%) had a significant decrease in AVM volume, one (3%) had only a persistent early draining vein without residual nidus, and one (3%) had no change in the AVM. Thirteen (81%) of 16 patients with AVMs less of than 4 ml had complete obliteration. Five patients had second-stage stereotactic radiosurgery after angiography revealed a persistent AVM nidus; two patients eligible for follow-up angiography had complete obliteration, thereby increasing the overall series obliteration rate to 71%. The calculated annual risk of AVM bleeding (before radiographic evidence of obliteration) was 2.4%. No patient bled after angiographically confirmed obliteration. In most patients stereotactic radiosurgery obliterates visual pathway AVMs and also preserves preoperative visual function. Multimodality management (embolization, microsurgery, or staged radiosurgery) enhances AVM obliteration and visual preservation rates.
Adolescent↗
Stereotactic radiosurgery for trigeminal neuralgia: a multiinstitutional study using the gamma unit.
A multiinstitutional study was conducted to evaluate the technique, dose-selection parameters, and results of gamma knife stereotactic radiosurgery in the management of trigeminal neuralgia. Fifty patients at five centers underwent radio-surgery performed with a single 4-mm isocenter targeted at the nerve root entry zone. Thirty-two patients had undergone prior surgery, and the mean number of procedures that had been performed was 2.8 (range 1-7). The target dose of the radiosurgery used in the current study varied from 60 to 90 Gy. The median follow-up period after radiosurgery was 18 months (range 11-36 months). Twenty-nine patients (58%) responded with excellent control (pain free), 18 (36%) obtained good control (50%-90% relief), and three (6%) experienced treatment failure. The median time to pain relief was 1 month (range 1 day-6.7 months). Responses remained consistent for up to 3 years postradiosurgery in all cases except three (6%) in which the patients had pain recurrence at 5, 7, and 10 months. At 2 years, 54% of patients were pain free and 88% had 50% to 100% relief. A maximum radiosurgical dose of 70 Gy or greater was associated with a significantly greater chance of complete pain relief (72% vs. 9%, p = 0.0003). Three patients (6%) developed increased facial paresthesia after radiosurgery, which resolved totally in one case and improved in another. No patient developed other deficits or deafferentation pain. The proximal trigeminal nerve and root entry zone, which is well defined on magnetic resonance imaging, is an appropriate anatomical target for radiosurgery. Radiosurgery using the gamma unit is an additional effective surgical approach for the management of medically or surgically refractory trigeminal neuralgia. A longer-term follow-up review is warranted.
Adult↗
Radiosurgery and fractionated radiation therapy: comparison of different techniques in an in vivo rat glioma model.
To identify histological changes and effects on survival in rats harboring C6 gliomas, the authors compared radiosurgery to different fractionated radiation therapy regimens including doses of calculated biological equivalence. Rats were randomized to control (54 animals) or treatment groups after implantation of C6 glioma cells into the right frontal brain region. At 14 days, treated rats underwent stereotactic radiosurgery (35 Gy to tumor margin; 22 animals), whole-brain radiation therapy (WBRT) (20 Gy in five fractions; 18 animals), radiosurgery plus WBRT (13 animals), hemibrain radiation therapy (85 Gy in 10 fractions; 16 animals) or single-fraction hemibrain irradiation (35 Gy; 10 animals). When compared to the control group (median survival 22 days), prolonged survival was identified after radiosurgery (p < 0.0001), radiosurgery plus WBRT (p < 0.0001), WBRT alone (p = 0.0002), hemibrain radiation therapy to 85 Gy (p < 0.0001), and 35-Gy hemibrain single-fraction irradiation (p = 0.004). Compared to the control group (mean tumor diameter, 6.8 mm), the tumor size was reduced in all treatment groups except WBRT alone. Reduced tumor cell density was exhibited in rats that underwent radiosurgery (p = 0.006) and radiosurgery plus WBRT (p = 0.009) when compared with rats in the control group, a finding not observed after any fractionated regimen. Increased intratumoral edema was identified after radiosurgery (p = 0.03) and combined treatment (p = 0.05), but not after fractionated radiation therapy or 35-Gy single-fraction hemibrain irradiation. In this animal model, the addition of radiosurgery significantly increased tumor cytotoxicity, potentially at the expense of radiation effects to regional brain. We found no difference in survival benefit or tumor diameter in animals that underwent radiosurgery compared to the calculated biologically equivalent regimen of 10-fraction radiation therapy to 85 Gy. The histological responses after radiosurgery were generally greater than those achieved with biologically equivalent doses of fractionated radiation therapy.
Animals↗
Magnetic resonance imaging: an accurate method to evaluate arteriovenous malformations after stereotactic radiosurgery.
To determine the accuracy of magnetic resonance (MR) imaging in comparison to cerebral angiography after radiosurgery for an arteriovenous malformation (AVM), the authors reviewed the records of patients who underwent radiosurgery at the University of Pittsburgh Medical Center before 1992. All patients in the analysis had AVMs in which the flow-void signal was visible on preradiosurgical MR imaging. One hundred sixty-four postradiosurgical angiograms were obtained in 140 patients at a median of 2 months after postradiosurgical MR imaging (median 24 months after radiosurgery). Magnetic resonance imaging correctly predicted patency in 64 of 80 patients in whom patent AVMs were seen on follow-up angiography (sensitivity 80%) and angiographic obliteration in 84 of 84 patients (specificity 100%). Overall, 84 of 100 AVMs in which evidence of obliteration was seen on MR images displayed angiographic obliteration (negative predictive value, 84%). Ten of the 16 patients with false-negative MR images underwent follow-up angiography: in seven the lesions progressed to complete angiographic obliteration without further treatment. Exclusion of these seven patients from the false-negative MR imaging group increases the predictive value of a negative postradiosurgical MR image from 84% to 91%. No AVM hemorrhage was observed in clinical follow up of 135 patients after evidence of obliteration on MR imaging (median follow-up interval 35 months; range 2-96 months; total follow up 382 patient-years). Magnetic resonance imaging proved to be an accurate, noninvasive method for evaluating the patency of AVMs that were identifiable on MR imaging after stereotactic radiosurgery. This imaging modality is less expensive, more acceptable to patients, and does not have the potential for neurological complications that may be associated with cerebral angiography. The risk associated with follow-up cerebral angiography may no longer justify its role in the assessment of radiosurgical results in the treatment of AVMs.
Humans↗