Radiosurgery for Arteriovenous Malformations and the Impact on Headaches.

BACKGROUND: Arteriovenous malformations (AVMs) can underlie many diverse neurological signs and symptoms. Headaches are a common presentation that can have a significant impact on quality of life. OBJECTIVE: The authors investigated Gamma Knife® stereotactic radiosurgery (SRS) outcomes in patients with AVMs and associated headaches. METHODS: This retrospective study analyzed 102 patients with AVMs who underwent SRS between 1995 and 2013. The patient's headache symptoms led to their AVM diagnosis or developed post hemorrhage of their AVM. Information regarding headache characteristics was obtained from the patient's medical records and at follow-up using a scripted clinical interview. The median imaging follow-up was 61.7 months and clinical follow-up was 89.7 months. The median treatment volume at SRS was 4.1 cm3 and the median marginal dose was 20 Gy. RESULTS: The actuarial AVM obliteration rate was 60% at 5 years and 78% at 10 years. Patients reported that their overall headache severity decreased by -43.6% and their headache frequency was reduced by -53.4%. Headache reduction was reported in 49.1% of patients at 1 year and 69.5% at 5 years. The median time until improvement was 6.5 months. After SRS, headache medication usage decreased in 29% of patients. Permanent adverse radiation effects after SRS occurred in 3% of patients. Until obliteration was complete, the annual risk of a hemorrhage after SRS was 0.4% per year. CONCLUSION: Although recall bias related to a retrospective analysis can impact outcomes, headache symptoms associated with AVMs may potentially be decreased or eliminated in a subset of patients treated with Gamma Knife radiosurgery.

White matter changes in breast cancer brain metastases patients who undergo radiosurgery alone compared to whole brain radiation therapy plus radiosurgery.

Delayed toxicity after whole brain radiation therapy (WBRT) is of increasing concern in patients who survive more than one year with brain metastases from breast cancer. Radiation-related white matter toxicity is detected by magnetic resonance imaging (MRI) and has been correlated with neurocognitive dysfunction. This study assessed the risk of developing white matter changes (WMC) in breast cancer patients who underwent either WBRT plus stereotactic radiosurgery (SRS) or SRS alone. We retrospectively compared 35 patients with breast cancer brain metastases who received WBRT and SRS to 30 patients who only received SRS. All patients had evaluable imaging at a median of one year after their initial management. The development of white matter T2 prolongation as detected by T2 or FLAIR imaging was graded: grade 1 = little or no white matter T2 hyperintensity; grade 2 = limited periventricular hyperintensity; and grade 3 = diffuse white matter hyperintensity. After WBRT plus SRS, patients demonstrated a significantly higher incidence of WMC (p < 0.0001). After one year, 71.5 % of patients whose treatment included WBRT demonstrated WMC (42.9 % grade 2; 28.6 % grade 3). Only one patient receiving only SRS developed WMC. In long-term survivors of breast cancer, the risk of WMC was significantly reduced when SRS alone was used for management. Further prospective studies are necessary to determine how these findings correlate with neurocognitive toxicity. WBRT usage as initial management of limited brain disease should be replaced by SRS alone to reduce the risk of delayed white matter toxicity.

Post-radiosurgical edema associated with parasagittal and parafalcine meningiomas: a multicenter study.

Stereotactic radiosurgery (SRS) offers a high degree of tumor control for benign meningiomas. However, radiosurgery can occasionally incite edema or exacerbate pre-existing peri-tumoral edema. The current study investigates the incidence, timing, and extent of edema around parasagittal or parafalcine meningiomas following SRS. A retrospective multicenter review was undertaken through participating centers in the International Gamma Knife Research Foundation (previously the North American Gamma Knife Consortium or NAGKC). All included patients had a parafalcine or parasagittal meningioma and a minimum of 6 months follow up. The median follow up was 19.6 months (6-158 months). Extent of new or worsening edema was quantitatively analyzed using volumetric analysis; edema indices were longitudinally computed following radiosurgery. Analysis was performed to identify prognostic factors for new or worsening edema. A cohort of 212 patients comprised of 51.9 % (n = 110) females, 40.1 % upfront SRS and 59.9 % underwent adjuvant SRS for post-surgical residual tumor. The median tumor volume at SRS was 5.2 ml. Venous sinus compression or invasion was demonstrated in 25 % (n = 53). The median marginal dose was 14 Gy (8-20 Gy). Tumor volume control was determined in 77.4 % (n = 164 out of 212 patients). Tumor edema progressed and then regressed in 33 % (n = 70), was stable or regressed in 52.8 % (n = 112), and progressively worsened in 5.2 % (n = 11). Tumor location, tumor volume, venous sinus invasion, margin, and maximal dose were found to be significantly related to post-SRS edema in multivariate analysis. SRS affords a high degree of tumor control for patients with parasagittal or parafalcine meningiomas. Nevertheless, SRS can lead to worsening peritumoral edema in a subset of patients such as those with larger tumors (>10 cc) and venous sinus invasion/compression. Long-term follow up is required to detect and appropriately manage post-SRS edema.

Stereotactic radiosurgery for trigeminal schwannoma: tumor control and functional preservation Clinical article.

OBJECT: To evaluate outcome predictors after stereotactic radiosurgery (SRS) in patients with trigeminal schwannomas, the authors compared tumor control, functional preservation, and complications with tumor grade, tumor volume, patient age, and tumor imaging characteristics. METHODS: The records of 33 consecutive patients with trigeminal schwannoma treated via Gamma Knife surgery were retrospectively reviewed. The median patient age was 49.5 years (range 15.1-82.5 years). Eleven patients had undergone prior tumor resection. Two patients had neurofibromatosis Type 2. Lesions were classified as root type (6 tumors), ganglion type (17 tumors), and dumbbell type (10 tumors) based on their location. The median radiosurgery target volume was 4.2 cm3 (range 0.5-18.0 cm3), and the median dose to the tumor margin was 15.0 Gy (range 12-20 Gy). RESULTS: At an average of 6 years (range 7.2-147.9 months), the rate of progression-free survival (PFS) at 1, 5, and 10 years after SRS was 97.0, 82.0, and 82.0%, respectively. Factors associated with improved PFS included female sex, smaller tumor volume, and a root or ganglion tumor type. Neurological symptoms or signs improved in 11 (33.3%) of 33 patients and were unchanged in 19 (57.6%). Three patients (9.1%) had symptomatic disease progression. Patients who had not undergone a prior tumor resection were significantly more likely to show improvement in neurological symptoms or signs. CONCLUSIONS: Stereotactic radiosurgery is an effective and minimally invasive management option in patients with residual or newly diagnosed trigeminal schwannomas. Predictors of a better treatment response included female sex, smaller tumor volume, root or ganglion tumor type, and the application of SRS as the primary treatment.

A proposed plan for personalized radiosurgery in patients with trigeminal neuralgia.

OBJECTIVE During the last 25 years, more than 100,000 patients worldwide with trigeminal neuralgia (TN) have undergone stereotactic radiosurgery (SRS) with a standard dose of radiation. However, the radiobiological effect of radiation is determined by the amount of energy delivered to the tissue (integral dose [ID] = mean dose × target volume) and is directly associated with the nerve volume. Although the trigeminal nerve volume varies among patients with TN, the clinical impact of this variation in delivered energy is unknown. The objective of this study was to evaluate the effect of delivered ID on the outcome of TN radiosurgery. METHODS The authors evaluated 155 patients with unilateral TN who had undergone SRS as their initial surgical management over a 13-year period. The authors measured the postganglionic ID within the SRS target and retrospectively stratified patients into 3 groups: low (< 1.4 mJ), medium (1.4-2.7 mJ), and high (> 2.7 mJ) ID. Clinical outcomes, which included pain status (scored using the Barrow Neurological Institute Pain Scale) and sensory dysfunction (scored using the Barrow Neurological Institute Numbness Scale), were evaluated at a median follow-up of 71 months. RESULTS Patients who were treated with a medium ID had superior pain relief either with or without medications (p = 0.006). In the medium ID group, the rates of complete pain relief without medications at 1, 3, and 6 years after SRS were 67%, 54%, and 33%, respectively, while the rates in the rest of the cohort were 55%, 36%, and 19%, respectively. Patients given a high ID had a higher rate of post-SRS trigeminal sensory deterioration (p < 0.0001). At 1, 3, and 6 years after SRS, the high ID group had an estimated rate for developing sensory dysfunction of 35%, 45%, and 50%, respectively, while the rates in patients receiving low and medium IDs were 3%, 4%, and 9%, respectively. The optimal clinical outcome (maximum pain relief and minimal trigeminal sensory dysfunction) was obtained in patients who had received a medium ID. CONCLUSIONS With current dose selection methods, nerve volume affects long-term clinical outcomes in patients with TN who have undergone SRS. This study suggests that the prescribed SRS dose should be customized for each TN patient based on the nerve volume.

International multicenter cohort study of pediatric brain arteriovenous malformations. Part 2: Outcomes after stereotactic radiosurgery.

OBJECTIVE Pediatric patients (age < 18 years) harboring brain arteriovenous malformations (AVMs) are burdened with a considerably higher cumulative lifetime risk of hemorrhage than adults. Additionally, the pediatric population was excluded from recent prospective comparisons of intervention versus conservative management for unruptured AVMs. The aims of this multicenter, retrospective cohort study are to analyze the outcomes after stereotactic radiosurgery for unruptured and ruptured pediatric AVMs. METHODS We analyzed and pooled AVM radiosurgery data from 7 participating in the International Gamma Knife Research Foundation. Patients younger than 18 years of age who had at least 12 months of follow-up were included in the study cohort. Favorable outcome was defined as AVM obliteration, no post-radiosurgical hemorrhage, and no permanently symptomatic radiation-induced changes (RIC). The post-radiosurgery outcomes of unruptured versus ruptured pediatric AVMs were compared, and statistical analyses were performed to identify predictive factors. RESULTS The overall pediatric AVM cohort comprised 357 patients with a mean age of 12.6 years (range 2.8-17.9 years). AVMs were previously treated with embolization, resection, and fractionated external beam radiation therapy in 22%, 6%, and 13% of patients, respectively. The mean nidus volume was 3.5 cm3, 77% of AVMs were located in eloquent brain areas, and the Spetzler-Martin grade was III or higher in 59%. The mean radiosurgical margin dose was 21 Gy (range 5-35 Gy), and the mean follow-up was 92 months (range 12-266 months). AVM obliteration was achieved in 63%. During a cumulative latency period of 2748 years, the annual post-radiosurgery hemorrhage rate was 1.4%. Symptomatic and permanent radiation-induced changes occurred in 8% and 3%, respectively. Favorable outcome was achieved in 59%. In the multivariate logistic regression analysis, the absence of prior AVM embolization (p = 0.001) and higher margin dose (p < 0.001) were found to be independent predictors of a favorable outcome. The rates of favorable outcome for patients treated with a margin dose ≥ 22 Gy vs < 22 Gy were 78% (110/141 patients) and 47% (101/216 patients), respectively. A margin dose ≥ 22 Gy yielded a significantly higher probability of a favorable outcome (p < 0.001). The unruptured and ruptured pediatric AVM cohorts included 112 and 245 patients, respectively. Ruptured AVMs had significantly higher rates of obliteration (68% vs 53%, p = 0.005) and favorable outcome (63% vs 51%, p = 0.033), with a trend toward a higher incidence of post-radiosurgery hemorrhage (10% vs 4%, p = 0.07). The annual post-radiosurgery hemorrhage rates were 0.8% for unruptured and 1.6% for ruptured AVMs. CONCLUSIONS Radiosurgery is a reasonable treatment option for pediatric AVMs. Obliteration and favorable outcomes are achieved in the majority of patients. The annual rate of latency period hemorrhage after radiosurgery for both ruptured and unruptured pediatric AVM patients conveys a significant risk until the nidus is obliterated.

International multicenter cohort study of pediatric brain arteriovenous malformations. Part 1: Predictors of hemorrhagic presentation.

OBJECTIVE Brain arteriovenous malformations (AVMs) are the most common cause of spontaneous intracranial hemorrhage in pediatric patients (age < 18 years). Since the cumulative lifetime risk of AVM hemorrhage is considerable in children, an improved understanding of the risk factors influencing hemorrhagic presentation may aid in the management of pediatric AVMs. The aims of this first of a 2-part multicenter, retrospective cohort study are to evaluate the incidence and determine the predictors of hemorrhagic presentation in pediatric AVM patients. METHODS The authors analyzed pooled AVM radiosurgery data from 7 institutions participating in the International Gamma Knife Research Foundation (IGKRF). Patients younger than 18 years at the time of radiosurgery and who had at least 12 months of follow-up were included in the study cohort. Patient and AVM characteristics were compared between unruptured and ruptured pediatric AVMs. RESULTS A total of 357 pediatric patients were eligible for analysis, including 112 patients in the unruptured and 245 patients in the ruptured AVM cohorts (69% incidence of hemorrhagic presentation). The annual hemorrhage rate prior to radiosurgery was 6.3%. Hemorrhagic presentation was significantly more common in deep locations (basal ganglia, thalamus, and brainstem) than in cortical locations (frontal, temporal, parietal, and occipital lobes) (76% vs 62%, p = 0.006). Among the factors found to be significantly associated with hemorrhagic presentation in the multivariate logistic regression analysis, deep venous drainage (OR 3.2, p < 0.001) was the strongest independent predictor, followed by female sex (OR 1.7, p = 0.042) and smaller AVM volume (OR 1.1, p < 0.001). CONCLUSIONS Unruptured and ruptured pediatric AVMs have significantly different patient and nidal features. Pediatric AVM patients who possess 1 or more of these high-risk features may be candidates for relatively more aggressive management strategies.

Worldwide variance in the potential utilization of Gamma Knife radiosurgery.

OBJECTIVE The role of Gamma Knife radiosurgery (GKRS) has expanded worldwide during the past 3 decades. The authors sought to evaluate whether experienced users vary in their estimate of its potential use. METHODS Sixty-six current Gamma Knife users from 24 countries responded to an electronic survey. They estimated the potential role of GKRS for benign and malignant tumors, vascular malformations, and functional disorders. These estimates were compared with published disease epidemiological statistics and the 2014 use reports provided by the Leksell Gamma Knife Society (16,750 cases). RESULTS Respondents reported no significant variation in the estimated use in many conditions for which GKRS is performed: meningiomas, vestibular schwannomas, and arteriovenous malformations. Significant variance in the estimated use of GKRS was noted for pituitary tumors, craniopharyngiomas, and cavernous malformations. For many current indications, the authors found significant variance in GKRS users based in the Americas, Europe, and Asia. Experts estimated that GKRS was used in only 8.5% of the 196,000 eligible cases in 2014. CONCLUSIONS Although there was a general worldwide consensus regarding many major indications for GKRS, significant variability was noted for several more controversial roles. This expert opinion survey also suggested that GKRS is significantly underutilized for many current diagnoses, especially in the Americas. Future studies should be conducted to investigate health care barriers to GKRS for many patients.

Hearing subclassification may predict long-term auditory outcomes after radiosurgery for vestibular schwannoma patients with good hearing.

OBJECTIVE In the era of MRI, vestibular schwannomas are often recognized when patients still have excellent hearing. Besides success in tumor control rate, hearing preservation is a main goal in any procedure for management of this population. The authors evaluated whether modified auditory subclassification prior to radiosurgery could predict long-term hearing outcome in this population. METHODS The authors reviewed a quality assessment registry that included the records of 1134 vestibular schwannoma patients who had undergone stereotactic radiosurgery during a 15-year period (1997-2011). The authors identified 166 patients who had Gardner-Robertson Class I hearing prior to stereotactic radiosurgery. Fifty-three patients were classified as having Class I-A (no subjective hearing loss) and 113 patients as Class I-B (subjective hearing loss). Class I-B patients were further stratified into Class I-B1 (pure tone average ≤ 10 dB in comparison with the contralateral ear; 56 patients), and I-B2 (> 10 dB compared with the normal ear; 57 patients). At a median follow-up of 65 months, the authors evaluated patients' hearing outcomes and tumor control. RESULTS The median pure tone average elevations after stereotactic radiosurgery were 5 dB, 13.5 dB, and 28 dB in Classes I-A, I-B1, and I-B2, respectively. The median declines in speech discrimination scores after stereotactic radiosurgery were 0% for Class I-A (p = 0.33), 8% for Class I-B1 (p < 0.0001), and 40% for Class I-B2 (p < 0.0001). Serviceable hearing preservation rates were 98%, 73%, and 33% for Classes I-A, I-B1, and I-B2, respectively. Gardner-Robertson Class I hearing was preserved in 87%, 43%, and 5% of patients in Classes I-A, I-B1, and I-B2, respectively. CONCLUSIONS Long-term hearing preservation was significantly better if radiosurgery was performed prior to subjective hearing loss. In patients with subjective hearing loss, the difference in pure tone average between the affected ear and the unaffected ear was an important factor in long-term hearing preservation.

Clinical research in stereotactic radiosurgery: lessons learned from over 10,000 cases.

Stereotactic radiosurgery is used for many neoplastic, vascular, and functional disorders of the nervous system. The expanded use of this technique over the past two decades is based mainly on the spectrum of clinical research performed for these disorders. From case series to randomized trials, the safety and efficacy of radiosurgery is well documented. In this report, we discuss the key indications for radiosurgery and the kinds of research performed in this field.