Initial Gamma Knife Radiosurgery Research Articles

Recurrence of pediatric cerebral arteriovenous malformation after obliteration by radiosurgery: a case report

The rupture of a cerebral arteriovenous malformation is the most common cause of cerebral hemorrhage in children, with recurrence rates reported to be higher than that in adults. Herein, we present the case of a 4-year-old child who initially demonstrated obliteration of a ruptured brain arteriovenous malformation after initial Gamma Knife radiosurgery, but subsequently experienced delayed recurrence, ultimately necessitating a second Gamma Knife radiosurgery procedure. By reviewing this case, we aim to explore considerations regarding the recurrence, treatment, and follow-up strategies for pediatric arteriovenous malformations.

Gamma Knife radiosurgery for metastatic brain tumors from ovarian cancer: histopathological analysis of survival and local control. A Japanese multi-institutional cooperative and retrospective cohort study.

Brain metastasis is rare in ovarian cancer patients. The results of Gamma Knife radiosurgery (GKRS) for the treatment of patients with brain metastases from ovarian cancer were retrospectively analyzed to derive the efficacy and prognostic factors for survival and local tumor control. Further histopathological analysis was also performed. The authors retrospectively reviewed the medical records of 118 patients with 566 tumors who had undergone GKRS at the 10 GKRS institutions in Japan. After the initial GKRS, the median overall survival time was 18.1 months. Multivariate analysis showed that uncontrolled primary cancer (p = 0.003) and multiple intracranial metastases (p = 0.034) were significant unfavorable factors. Ten patients died of uncontrolled brain metastases at a median of 17.1 months. The 6-, 12-, and 24-month neurological death rates were 3.2%, 4.6%, and 11.9%, respectively. The 6-, 12-, and 24-month neurological deterioration rates were 7.2%, 13.5%, and 31.4%, respectively. The 6-, 12-, and 24-month distant brain control failure rates were 20.6%, 40.2%, and 42.3%, respectively. Median tumor volume was 1.6 cm3 and marginal dose was 20 Gy. The 6-, 12-, and 24-month local tumor control rates were 97.6%, 95.2%, and 88.0%, respectively. Peritumoral edema (p = 0.043), more than 7-cm3 volume (p = 0.021), and prescription dose less than 18 Gy (p = 0.014) were factors that were significantly correlated in local tumor control failure. Eight patients had symptomatic radiation injury. The 6-, 12-, and 24-month GKRS-related complication rates were 3.3%, 7.8%, and 12.2%, respectively. Primary ovarian cancer was histopathologically diagnosed for 313 tumors in 69 patients. Serous adenocarcinoma was found in 37 patients and other types in 32 patients. Median survival times were 32.3 months for the serous type and 17.4 months for other types after initial GKRS. Patients with serous-type tumors survived significantly longer than patients with other types (p = 0.039). The 6-, 12-, and 24-month local tumor control rates were 100%, 98.8%, and 98.8%, respectively. Serous-type tumors were a significantly good prognosis factor for local tumor control after GKRS (p = 0.005). This study established a relationship between the efficacy of GKRS treatment for brain metastases and the histological type of primary ovarian cancer. GKRS for ovarian cancer brain metastasis can provide satisfactory survival and local control, especially in cases of serous adenocarcinoma.

Gamma Knife Radiosurgery for Trigeminal Neuralgia : Review and Update.

Accurate diagnosis of trigeminal neuralgia (TN) is the starting point for optimal treatment. Gamma knife radiosurgery (GKRS) is currently regarded as one of the first-line treatment options for medically refractory TN. GKRS is a less invasive treatment with a low risk of complications than other surgical procedures that provides a favorable pain control (BNI I–IIIb) rate of >75% at short-term follow-up. Drawbacks of GKRS include the latency period before pain relief and higher recurrence rate compared with microvascular decompression. Therefore, repeat treatment is necessary if the initial GKRS was effective but followed by recurrence. The concept of dose rate and the biologically effective dose of radiation has been actively studied in radiation oncology and is also applied in GKRS for TN to achieve high safety and efficacy by prescribing the optimal dose. Recent progress in functional imaging, such as diffusion tensor imaging, enables us to understand the pathophysiology of TN and predict the clinical outcome after GKRS. Here, we review TN, GKRS, and recent updates, especially in the concepts of radiation dose, diffusion tensor imaging studies, and repeat treatment in GKRS for TN.

Clinical outcomes of patients with multiple courses of radiosurgery for brain metastases from non-small cell lung cancer

We investigated the long-term clinical outcomes of patients who underwent multiple courses (≥ 5) of gamma knife radiosurgery (GKRS) due to recurrent brain metastases (BM) from non-small cell lung cancer (NSCLC). Between December 2001 and July 2019, consecutive 2571 patients underwent GKRS for BM from NSCLC. Clinical and radiological outcomes were investigated in 76 patients who underwent GKRS ≥ 5 times. The median follow-up period after the diagnosis of NSCLC was 54.6 months (range 14.5–159.1 months). The median number of GKRS procedures per patient was six (range 5–15). Actuarial post-GKRS survival rates at 1, 2, 3, 4, and 5 years following initial GKRS were 88.1%, 79.5%, 65.3%, 51.4%, and 37.3%, respectively. No significant difference in overall survival was observed between patients (n = 22) with whole-brain radiotherapy (WBRT) and patients (n = 54) without WBRT (p = 0.076). The incidence of radiation-induced leukoencephalopathy was 64% and 18% in patients with and without WBRT, respectively (p < 0.0001). Multiple courses of SRS are a tolerable and effective treatment option for recurrent BM from NSCLC. Repeat SRS may be an alternative treatment option to avoid or delay WBRT.

Neurofibromatosis type 2-associated meningiomas: an international multicenter study of outcomes after Gamma Knife stereotactic radiosurgery.

The management of neurofibromatosis type 2 (NF2)-associated meningiomas is challenging. The role of Gamma Knife radiosurgery (GKRS) in the treatment of these tumors remains to be fully defined. In this study, the authors aimed to examine the role of GKRS in the treatment of NF2-associated meningiomas and to evaluate the outcomes and complications after treatment. Seven international medical centers contributed data for this retrospective cohort. Tumor progression was defined as a ≥ 20% increase from the baseline value. The clinical features, treatment details, outcomes, and complications were studied. The median follow-up was 8.5 years (range 0.6-25.5 years) from the time of initial GKRS. Shared frailty Cox regression was used for analysis. A total of 204 meningiomas in 39 patients treated with GKRS were analyzed. Cox regression analysis showed that increasing the maximum dose (p = 0.02; HR 12.2, 95% CI 1.287-116.7) and a lower number of meningiomas at presentation (p = 0.03; HR 0.9, 95% CI 0.821-0.990) were predictive of better tumor control in both univariable and multivariable settings. Age at onset, sex, margin dose, location, and presence of neurological deficit were not predictive of tumor progression. The cumulative 10-year progression-free survival was 94.8%. Radiation-induced adverse effects were noted in 4 patients (10%); these were transient and managed medically. No post-GKRS malignant transformation was noted in 287 person-years of follow-up. GKRS achieved effective tumor control with a low and generally acceptable rate of complications in NF2-associated meningiomas. There did not appear to be an appreciable risk of post-GKRS-induced malignancy in patients with NF2-treated meningiomas.

Outcomes of Gamma Knife Radiosurgery for Brain Metastases From Anaplastic Lymphoma Kinase Rearrangement-Positive and EGFR Mutation-Positive Non-Small Cell Lung Cancer.

IntroductionThe outcomes after gamma knife radiosurgery (GKRS) were retrospectively analysed in patients with brain metastases from anaplastic lymphoma kinase (ALK) rearrangement-positive and epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC) to evaluate the efficacy, safety and difference for overall survival and local tumor control.MethodsThe medical records were retrospectively reviewed of 607 patients (25 ALK-positive, 171 EGFR-positive, and 411 wild type) with 2959 tumors who had undergone GKRS.ResultsThe median overall survival time after initial GKRS was 14 months. Driver gene mutation-positive patients had significantly longer overall survival than wild type patients (p < 0.0001), and ALK-positive patients survived significantly longer than EGFR-positive patients (p = 0.04). Multivariate analysis showed the unfavorable factors significantly affecting overall survival outcomes were older age, lower Karnofsky Performance Status score, multiple intracranial metastases, uncontrolled primary cancer, uncontrolled extracranial metastases, no administration of immune checkpoint inhibitors, and driver gene mutation-negative cases. Seventy-three patients died of uncontrolled brain metastases at a median of 12 months. Driver gene mutations had no influence (p = 0.33), and ALK-positive and EGFR-positive patients showed no significant difference in neurological survival (p = 0.83). A total of 174 patients demonstrated distant brain control failure at a median of 15 months. ALK-positive type was significant compared with EGFR-positive type (p = 0.047), but driver gene mutation-positive and -negative types showed no significant difference in the development of new brain metastases (p = 0.2). The median tumor volume was 1.06 cm3 in the driver gene mutation-positive type and 1.85 cm3 in wild type. The median marginal dose was 20 Gy in both types. The 6-, 12-, and 24-month local tumor control rates were 97.3%, 96.1%, and 95.9%, respectively. Driver gene mutations had a significantly positive impact on local tumor control (p = 0.001), and ALK-positive and EGFR-positive types showed no significant difference (p = 0.95). A total of 193 tumors had radiation injury at a median of 12 months after GKRS. The 6-, 12-, and 24-month GKRS-related complication rates were 3.3%, 8.1%, and 8.7%, respectively. Driver gene mutations significantly induced radiation damage (p = 0.021), and the ALK-positive type was affected more than the EGFR-positive type (p = 0.02).ConclusionsALK rearrangement-positive NSCLC patients tended to have significantly longer survival, but had higher incidence of new intracranial metastases due to long-term survival after GKRS, compared with EGFR mutation-negative and driver gene mutation-negative NSCLC patients. GKRS induced significantly satisfactory local tumor control in driver gene mutation-positive tumors but GKRS-related complication frequency was higher, especially in ALK-positive NSCLC patients. Therefore, more careful imaging follow-up is necessary after GKRS for patients with driver gene mutation-positive NSCLC.

Gamma Knife radiosurgery as the initial treatment for elderly patients with nonfunctioning pituitary adenomas.

The aim of this study was to investigate the efficacy and safety of initial Gamma Knife radiosurgery (GKRS) for elderly patients with nonfunctioning pituitary adenomas (NFPAs). We retrospectively reviewed 45 elderly patients underwent GKRS as the initial treatment for NFPAs at our institution between December 2007 and December 2017. Patients' radiographic and clinical data were collected. The median age of patients at the time of GKRS was 71years (range 65-82years). The median tumor volume was 2.6 cm3 (range 0.3-21.8 cm3). The median marginal dose was 13Gy (range 6-23Gy). The median maximum dose to the optic apparatus was 6.5Gy (range 2.3-10.3Gy). Thirty-five patients (77.8%) achieved tumor regression, 6 patients (13.3%) had tumor stable and 4 patients (8.9%) occurred tumor progression during a median radiological follow-up time of 51.4months (range 11.1-158.7months). The crude tumor control rate was 91.1%. The actuarial tumor control rates were 100%, 95.0%, 87.6%, and 87.6%, at 1, 3, 5, and 10years after initial GKRS, respectively. New-onset hypopituitarism occurred in 6 patients. Two patients with pre-GKRS visual dysfunction developed further deterioration of visual function. No other radiation-induced complications were noted. Initial GKRS can provide a high tumor control rate as well as low risk of postradiosurgical complications for elderly patients with NFPAs. Attention should be paid to avoid radiation-related adverse effects including hypopituitarism, optic neuropathy and cranial neuropathy in elderly patients.

Skull Base Meningiomas in Patients with Neurofibromatosis Type 2: An International Multicenter Study Evaluating Stereotactic Radiosurgery.

Objective Meningiomas are the second most common tumors in neurofibromatosis type 2 (NF-2). Microsurgery is challenging in NF-2 patients presenting with skull base meningiomas due to the intrinsic risks and need for multiple interventions over time. We analyzed treatment outcomes and complications after primary Gamma Knife radiosurgery (GKRS) to delineate its role in the management of these tumors. Methods An international multicenter retrospective study approved by the International Radiosurgery Research Foundation was performed. NF-2 patients with at least one growing and/or symptomatic skull base meningioma and 6-month follow-up after primary GKRS were included. Clinical and radiosurgical parameters were recorded for analysis. Results In total, 22 NF-2 patients with 54 skull base meningiomas receiving GKRS as primary treatment met inclusion criteria. Median age at GKRS was 38 years (10-79 years). Most lesions were located in the posterior fossa (55.6%). Actuarial progression free survival (PFS) rates were 98.1% at 2 years and 90.0% at 5 and 10 years. The median follow-up time after initial GKRS was 5.0 years (0.6-25.5 years). Tumor volume at GKRS was a predictor of tumor control. Lesions >5.5 cc presented higher chances to progress after radiosurgery ( p = 0.043). Three patients (13.64%) developed adverse radiation effects. No malignant transformation or death due to meningioma or radiosurgery was reported. Conclusions GKRS is effective and safe in the management of skull base meningiomas in NF-2 patients. Tumor volume deserve greater relevance during clinical decision-making regarding the most appropriate time to treat. GKRS offers a minimally invasive approach of particular interest in this specific group of patients.

Radiosurgery for unruptured brain arteriovenous malformations in the pre-ARUBA era: long-term obliteration rate, risk of hemorrhage and functional outcomes

The management of non-hemorrhagic arteriovenous malformations (AVMs) remains a subject of debate, even more since the ARUBA trial. Here, we report the obliteration rate, the risk of hemorrhage and the functional outcomes after Gamma Knife radiosurgery (GKRS) as first-line treatment for non-hemorrhagic AVMs treated before the ARUBA publication, in a reference university center with multimodal AVM treatments available. We retrospectively analyzed data from a continuous series of 172 patients harboring unruptured AVMs treated by GKRS as first-line treatment in our Lille University Hospital, France, between April 2004 and December 2013. The primary outcome was obliteration rate. Secondary outcomes were the hemorrhage rate, the modified Rankin Scale (mRS), morbidity and epilepsy control at last follow-up. The minimal follow-up period was of 3 years. Median age at presentation was 40 years (IQR 28; 51). Median follow-up was 8.8 years (IQR 6.8; 11.3). Median target volume was 1.9 cm3 (IQR 0.8–3.3 cm3), median Spetzler-Martin grade: 2 (IQR 1–2), median Pollock-Flickinger score: 1.07 (IQR 0.82–2.94), median Virginia score: 1 (IQR 1–2). Median treatment dose was 24 Gy at 50% isodose line. Twenty-three patients underwent a second GKRS after a median time of 58 months after first GKRS. The overall obliteration rate was of 76%, based primarily on cerebral angiography and/or rarely only upon MRI. Hemorrhage during the post-treatment follow-up was reported in 18 (10%) patients (annual risk of 1.1%). Transient post-GKRS morbidity was reported in 14 cases (8%) and persistent neurological deficit in 8 (4.6%) of patients. At last follow-up, 86% of patients had a mRS ≤ 1. Concerning patients with pretherapeutic epilepsy, 84.6% of them were seizure-free at last follow-up. GKRS as first-line therapeutic option for unruptured cerebral AVMs achieves high obliteration rates (76%) while maintaining a high-level patient’s autonomy. All hemorrhagic events occurred during the first 4 years after the initial GKRS. In cases with epilepsy, there was 84.6% seizure free at last follow-up. Permanent morbidity was reported in only 4.6%.

Initial Gamma Knife Radiosurgery for Large or Documented Growth Asymptomatic Meningiomas: Long-Term Results From a 27-Year Experience.

ObjectiveThe aims of this study were to investigate the long-term outcomes of initial Gamma Knife radiosurgery (GKRS) for large (≥20 mm) or documented growth asymptomatic meningiomas.Design and MethodsThis was a single-center retrospective study. Fifty-nine patients with large (≥20 mm) or documented growth asymptomatic meningiomas undergoing initial GKRS were enrolled. The median age was 56 (range, 27–83) years. The median time of follow-up was 66.8 (range, 24.6–245.6) months, and the median tumor margin dose was 13.0 Gy (range, 11.6–22.0 Gy).ResultsTumors shrunk in 35 patients (59.3%) and remained stable in 23 (39.0%). One patient (1.7%) experienced radiological progression at 54 months after GKRS. The PFS was 100%, 97%, and 97% at 3, 5, and 10 years, respectively. Nine patients (15.3%) occurred new neurological symptoms or signs at a median time of 8.1 (range, 3.0–81.6) months. The symptom PFS was 90% and 78% at 5 and 10 years, respectively. Fifteen patients (25.4%) occurred peritumoral edema (PTE) at a median time of 7.2 (range, 2.0–81.6) months. One patient underwent surgical resection for severe PTE. In univariate and multivariate analysis, Only tumor size (≥25 mm) and maximum dose (≥34 Gy) were significantly associated with PTE [hazard ratio (HR)= 3.461, 95% confidence interval (CI)=1.157-10.356, p=0.026 and HR=3.067, 95% CI=1.068-8.809, P=0.037, respectively].ConclusionsIn this study, initial GKRS can provide a high tumor control rate as well as an acceptable rate of complications in large or documented growth asymptomatic meningiomas. GKRS may be an alternative initial treatment for asymptomatic meningiomas.

Convexity Meningiomas in Patients with Neurofibromatosis Type 2: Long-Term Outcomes After Gamma Knife Radiosurgery

Convexity meningiomas are common tumors requiring treatment in patients with neurofibromatosis type 2 (NF2). Although different therapeutic options are described for sporadic convexity meningioma, much less is known about these lesions in patients with NF2 despite their distinct biology and need for multiple treatments. We analyzed the value of Gamma Knife radiosurgery (GKRS) as definitive treatment for convexity meningiomas in patients with NF2. This international multicenter retrospective study was approved by the International Radiosurgery Research Foundation. Patients with NF2 with at least 1 convexity meningioma and 6-month follow-up after primary GKRS were included. Inclusion criteria were met by 18 patients with NF2. A total of 120 convexity meningiomas (median treatment volume, 0.66 cm3 [range, 0.10-21.20 cm3]) were analyzed. Median follow-up after initial GKRS was 15.6 years (range, 0.6-25.5 years). Median age at GKRS was 32.5 years (range, 16-53 years). Median number of meningiomas per patient was 13 (range, 1-27), and median number of convexity lesions receiving GKRS per patient was 3.5 (range, 1-27). One case of tumor progression was reported 24 years after GKRS, leading to actuarial progression-free survival rates of 100% at 2, 5, and 10 years. No malignant transformation or death due to meningioma or radiosurgery was recorded. GKRS is safe and effective as definitive treatment of small to medium-sized convexity meningiomas in patients with NF2. Despite concerns about the particular mutational burden of these tumors, no malignant transformation manifested after treatment. GKRS represents a minimally invasive option that offers long-term tumor control to this specific group of patients.

Initial Gamma Knife radiosurgery for nonfunctioning pituitary adenomas: results from a 26-year experience.

The aim of this study was to evaluate the long-term outcomes of initial Gamma Knife radiosurgery (GKRS) for patients with nonfunctioning pituitary adenomas (NFPAs). This was a single-center retrospective study. Eighty-one patients with NFPAs undergoing initial GKRS were enrolled. The median age was 44.9 years (range, 7.2-75.5 years). The median tumor volume was 2.3 cm3 (range, 0.1-31.3 cm3), and the median tumor margin dose was 13.0 Gy (range, 8-22 Gy). Tumor shrunk in 63 patients (77.8%), remained stable in 9 (11.1%), treatment failure in 9 (11.1%) during a median follow-up of 67.1 months (range, 11.5-263.9 months). The tumor control rates were 100%, 99%, 95%, and 84%, at 1, 3, 5, and 10 years, respectively. In multivariate analysis, tumor volume (≥4 cm3) and margin dose (<12 Gy) were associated with treatment failure (hazard ratio (HR) = 7.093, 95% confidence interval (CI) = 1.098-45.083, p = 0.040, and HR = 9.643, 95% CI = 1.108-83.927, p = 0.040, respectively). New apoplexy occurred in seven patients (8.6%) after GKRS with a median time of 39.9 months (range, 11.9-166.8 months). In multivariate analysis, tumor volume (≥10 cm3) was a significant risk factor (HR = 10.642, 95% CI = 2.121-53.398, p = 0.004). New hypopituitarism occurred in 14 patients (17.3%). No factors were associated with new hypopituitarism. Four patients (4.9%) developed new or worsening visual dysfunction. No new cranial neuropathy was noted. In this study, initial GKRS can provide a high tumor control rate, as well as a low incidence rate of complications in NFPAs. GKRS may be an alternative initial treatment for selected NFPAs.

Gamma Knife radiosurgery for bilateral trigeminal neuralgia

OBJECTIVEA small subset of patients with trigeminal neuralgia (TN) will experience bilateral symptoms. Treatment in these patients is controversial because the population is heterogeneous and patients may have nonvascular etiologies of their pain. This study reports treatment outcomes in the largest cohort of patients with bilateral TN who have undergone Gamma Knife radiosurgery (GKRS) to date.METHODSA retrospective chart review identified 51 individual nerves in 34 patients with bilateral TN who were treated with GKRS at the authors’ institution between 2001 and 2015, with 12 nerves in 11 patients undergoing repeat GKRS for recurrent or persistent symptoms. Long-term follow-up was obtained by telephone interview. Pain outcomes were measured using the Barrow Neurological Institute (BNI) pain scale, with BNI IIIb or better considered a successful treatment.RESULTSThere was sufficient follow-up to determine treatment outcomes for 48 individual nerves in 33 patients. Of these nerves, 42 (88%) achieved at least BNI IIIb pain relief. The median duration of pain relief was 1.9 years, and 1-, 3-, and 5-year pain relief rates were 64%, 44%, and 44%, respectively. No patients experienced bothersome facial numbness, and 1 case of anesthesia dolorosa and 2 cases of corneal dryness were reported. Patients with a history of definite or possible multiple sclerosis were significantly more likely to experience BNI IV–V relapse. There was no statistically significant difference in treatment outcomes between patients in this series versus a large cohort of patients with unilateral TN treated at the authors’ institution. There was sufficient follow-up to determine treatment outcomes for 11 individual nerves in 10 patients treated with repeat GKRS. Ten nerves (91%) improved to at least BNI IIIb after treatment. The median duration of pain relief was 2.8 years, with 1-, 3-, and 5-year rates of pain relief of 79%, 53%, and 53%, respectively. There was no statistically significant difference in outcomes between initial and repeat GKRS. One case of bothersome facial numbness and 1 case of corneal dryness were reported, with no patients developing anesthesia dolorosa with retreatment.CONCLUSIONSGKRS is a safe, well-tolerated treatment for patients with medically refractory bilateral TN. Efficacy of treatment appears similar to that in patients with unilateral TN. GKRS can be safely repeated in this population if necessary.

Gamma Knife Radiosurgery for Metastatic Brain Tumors from Cancer of Unknown Primary

We retrospectively analyzed treatment efficacy and identified prognostic factors impacting tumor control and survival in patients with brain metastases from cancer of unknown primary (CUP) treated with gamma knife radiosurgery (GKRS). We retrospectively reviewed the medical records of 87 patients with 520 tumors who underwent GKRS for brain metastases from CUP. The median overall survival time after initial GKRS was 6 months. The 6- and 12-month overall survival rates were 79.3% and 14.9%, respectively. Older age (P=0.002), lower Karnofsky Performance Status Index score (P= 0.026), extracranial metastases (P= 0.013), and multiple brain metastases (P= 0.007) were significantly correlated with shorter survival periods. The 6- and 12-month neurologic death rates were 25.3% and 32.2%, respectively. The 6- and 12-month neurologic deterioration rates were 24.1% and 27.6%, respectively. The 6- and 12-month distant brain control failure rates were 21.8% and 24.1%, respectively. The median tumor volume was 1.7 cm3. The median marginal prescription dose was 18 Gy. The 6- and 12-month tumor recurrence rates were 5.1% and 15.7%, respectively. Larger tumor volume (P < 0.0001) and lower prescription dose (P= 0.001) were significantly correlated with local tumor control failure. Seven patients had symptomatic radiation injury. The 6- and 12-month GKRS-related complication rates were both 6.9%. Our findings suggest that GKRS is a relatively effective and safe treatment for control of tumor progression in patients with brain metastases from CUP. Overall and neurologic survivals were short, but we recommend GKRS treatment to prevent early neurologic dysfunction and death in patients with CUP.

Repeat Gamma Knife radiosurgery versus microvascular decompression following failure of GKRS in trigeminal neuralgia: a systematic review and meta-analysis.

Gamma Knife radiosurgery (GKRS) has emerged as a promising treatment modality for patients with classical trigeminal neuralgia (TN); however, considering that almost half of the patients experience post-GKRS failure or lesion recurrence, a repeat treatment is typically necessary. The existing literature does not offer clear evidence to establish which treatment modality, repeat GKRS or microvascular decompression (MVD), is superior. The present study aimed to compare the overall outcome of patients who have undergone either repeat GKRS or MVD after failure of their primary GKRS; the authors do so by conducting a systematic review and meta-analysis of the literature and analysis of data from their own institution. The authors conducted a systematic review and meta-analysis of the PubMed, Cochrane Library, Web of Science, and CINAHL databases to identify studies describing patients who underwent either repeat GKRS or MVD after initial failed GKRS for TN. The primary outcomes were complete pain relief (CPR) and adequate pain relief (APR) at 1 year. The secondary outcomes were rate of postoperative facial numbness and the retreatment rate. The pooled data were analyzed with R software. Bias and heterogeneity were assessed using funnel plots and I2 tests, respectively. A retrospective analysis of a series of patients treated by the authors who underwent repeat GKRS or MVD after post-GKRS failure or relapse is presented. A total of 22 studies met the selection criteria and were included for final data retrieval and meta-analysis. The search did not identify any study that had directly compared outcomes between patients who had undergone repeat GKRS versus those who had undergone MVD. Therefore, the authors' final analysis included two groups: studies describing outcome after repeat GKRS (n = 17) and studies describing outcome after MVD (n = 5). The authors' institutional study was the only study with direct comparison of the two cohorts. The pooled estimates of primary outcomes were APR in 83% of patients who underwent repeat GKRS and 88% of those who underwent MVD (p = 0.49), and CPR in 46% of patients who underwent repeat GKRS and 72% of those who underwent MVD (p = 0.02). The pooled estimates of secondary outcomes were facial numbness in 32% of patients who underwent repeat GKRS and 22% of those who underwent MVD (p = 0.11); the retreatment rate was 19% in patients who underwent repeat GKRS and 13% in those who underwent MVD (p = 0.74). The authors' institutional study included 42 patients (repeat GKRS in 15 and MVD in 27), and the outcomes 1 year after retreatment were APR in 80% of those who underwent repeat GKRS and 81% in those who underwent MVD (p = 1.0); CPR was achieved in 47% of those who underwent repeat GKRS and 44% in those who underwent MVD (p = 1.0). There was no difference in the rate of postoperative facial numbness or retreatment. The current meta-analysis failed to identify any superiority of one treatment over the other with comparable outcomes in terms of APR, postoperative facial numbness, and retreatment rates. However, MVD was shown to provide a better chance of CPR compared with repeat GKRS.

Gamma Knife Radiosurgery for Metastatic Brain Tumors from Malignant Melanomas: A Japanese Multi-Institutional Cooperative and Retrospective Cohort Study (JLGK1501)

Background: The incidences of metastatic brain tumors from malignant melanomas have increased and survival has been prolonged by novel molecular targeted agents and immunotherapy. However, malignant melanomas are uncommon in Asian populations. Objectives: We retrospectively analyzed treatment efficacy and identified prognostic factors impacting tumor control and survival in Japanese melanoma patients with brain metastases treated with gamma knife radiosurgery (GKRS). Methods: We retrospectively reviewed the medical records of 177 patients with 1,500 tumors who underwent GKRS for brain metastases from malignant melanomas. This study was conducted by the Japanese Leksell Gamma Knife Society (JLGK1501). Results: Six and 12 months after GKRS, the cumulative incidences of local tumor recurrence were 9.2 and 13.8%. Intratumoral hemorrhage (p < 0.0001) and larger tumor volume (p = 0.001) in GKRS were associated with significantly poorer local control outcomes. The use of immune checkpoint inhibitors before GKRS was significantly associated with symptomatic adverse events (p = 0.037). The median overall survival time after the initial GKRS was 7.3 months. Lower Karnofsky performance status scores (p = 0.016), uncontrolled primary cancer (p < 0.0001), and multiple brain metastases (p = 0.014) significantly influenced unfavorable overall survival outcomes. The cumulative incidences of neurological death 6 and 12 months after GKRS were 9.7 and 17.4%, those of neurological deterioration were 14.2 and 19.6%, and those of new tumor appearance were 34.5 and 40.5%. Conclusions: The results of the present multicenter study suggest that GKRS is a relatively effective and safe modality for control of tumor progression in Japanese patients with brain metastases from malignant melanomas.

Progression of vestibular schawnnoma after GammaKnife radiosurgery: A challenge for microsurgical resection

ObjectiveWe aimed to evaluate the outcome of patients who underwent salvage microsurgery for vestibular schwannoma (VS) that failed primary Gammaknife radiosurgery (GKS). Patients and MethodsAmong the 1098 patients who received GKS for the treatment of VS in our center between January 2004 and December 2012, the follow-up was organized in our institution for 290 patients who lived in our recruitment area. Tumor progression was noted in 23 patients. A salvage microsurgical resection was performed in 11 patients, who were included in our study. Grading of facial function was done according to the House & Brackman scale. ResultsThe mean age at diagnosis was 50.2 years (19–68 years) and the mean follow-up was 9.4 years (4–13 years). The mean dose was 11.8 Gy (11–12 Gy) and the mean volume was 922 mm3 (208–2500 mm3). The mean period between GKS and diagnosis of tumor progression was 32 months (18–72 months). Concerning salvage microsurgery, complete resection was obtained in 8 patients. Small residual tumor on the facial nerve was deliberately left in 3 patients and no tumor progression was noted with a mean follow-up of 26 months. At last follow-up, facial nerve function was grade 1 in 4 patients, grade 2 in 3 patients, grade 3 in 1 patient and grade 4 in 3 patients. ConclusionSalvage surgery of recurrent vestibular schwannoma after failed initial GKS remains a good treatment. However, facial nerve preservation is more challenging in this case and small tumor remnant could be sometimes deliberately left.

Stereotactic Radiosurgery for Multiple Sclerosis Associated Trigeminal Neuralgia

Trigeminal neuralgia in the setting of multiple sclerosis (MS-TN) is a challenging condition to manage and frequently does not respond as well to medications or surgical intervention when compared with classic TN. Gamma Knife radiosurgery (GKRS) is a commonly used treatment modality for these patients, however, data regarding the efficacy of this treatment is limited. Here we report a large single institution retrospective analysis for MS-TN treated with GKRS. A retrospective review of our GKRS database was performed to identify patients with MS-TN treated with GKRS between 2001 and 2016. Seventy-seven cases of unilateral MS-TN (UMSTN) in 74 patients were treated with GKRS at our institution between 2001 and 2016. Background medical history, treatment outcomes and complications, and dosimetric data were obtained by retrospective chart reviews and telephone interviews. Time-to-failure outcomes were estimated using the Kaplan-Meier method. Cox proportional hazards methods were used to estimate the hazard ratios (HR) associated with patient and treatment-related variables for time-to-failure outcomes. Seventy-four of 77 cases of UMSTN had sufficient follow up to determine BNI pain score outcomes. Three patients had both nerves treated. Sixty-one out of 74 cases (82%) of UMSTN achieved BNI IIIb or better pain relief following initial GKRS, with 18 cases (24%) achieving BNI I pain relief. Median time to BNI IIIb pain relief was 1.8 weeks. At a median follow up of 2.5 years, the estimated median duration of BNI IIIb pain relief after initial GKRS was 1.1 years. Estimated rates of pain relief at 1, 3 and 5 years were 51%, 37%, and 27% respectively. Three cases (4.1%) developed bothersome numbness and three cases (4.1%) developed ipsilateral corneal anesthesia, although none experienced vision loss. No patients experienced anesthesia dolorosa. Thirty-seven of the original 77 cases of UMSTN were treated with repeat GKRS after initial treatment failure. Of 35 patients with sufficient follow up to determine pain outcomes, 30 (86%) achieved BNI IIIb or better pain relief, with 12 (34%) achieving BNI I following repeat GKRS. Median time to BNI IIIb pain relief was 4.5 weeks. At a median follow up of 2.3 years from repeat GKRS, the median duration of BNI IIIb pain relief after repeat GKRS was 2.8 years. Estimated rates of pain relief at 1 and 3 years were 67% and 49% respectively. One case (2.9%) developed bothersome numbness after repeat GKRS, and three cases (8.6%) developed new ipsilateral corneal anesthesia, but none reported vision loss. No patients developed anesthesia dolorosa. Patients with episodic pain were more likely to achieve a good pain outcome after repeat GKRS than those with atypical symptoms (HR 10.51, p = 0.03). GKRS is a viable, well tolerated treatment option for patients with MS-TN. More durable relief is often achieved with a second application of GKRS. Patients with episodic pain are more likely to have successful second procedure.

203 Treatment Options Following Failed Gamma Knife Radiosurgery in Trigeminal Neuralgia

Abstract INTRODUCTION Primary treatment of trigeminal neuralgia with gamma knife radiosurgery (GKRS) is an accepted and effective modality, but is associated with a significant failure rate. Many of the patients ultimately require additional treatment for adequate pain relief. The present paper discusses the long term outcome of this group of patients who are treated with either repeat GKRS or microvascular decompression (MVD) as a secondary procedure. METHODS Using the retrospective database, the clinical data was analyzed of the patients who underwent GKRS at our institute between January 2000 and June 2016. The initial GKRS plan included median prescription dose of 80 Gy at a single iso-center using 4 mm collimator. The patients who did not improve after initial therapy and maximal medication dosage were offered either repeat radiosurgery or MVD. Repeat radiosurgery included a similar plan but a reduced median prescription dose of 40 Gy. Long term pain relief was measured using Marseille's score. Multiple factors including demographic factors, the type of pain, post GKRS facial numbness, treatment interval were analyzed to predict association with the final outcome. RESULTS &gt;In the study preriod, a total of 198 patients underwent GKRS for trigeminal neuralgias. Among these patients 42 (21.2%) patients had treatment failure and required additional treatment. The median interval of subsequent interventions was 16 months (range 2 months to 154 months). Six patients (14.2%) required repeat treatment after 5 years of initial treatment. Out of 42 failed GKRS patients, 15 (35.7%) underwent repeat radiosurgery and 27 (64.3%) underwent MVD. The mean follow up duration was 4.3 years. Overall, 34 patients (81%) improved and had adequate pain relief (Marseille's score III or better) after the second procedure. The rate of adequate pain relief after repeat GKRS and microvascular decompression were 86.6% and 77.7% respectively (P = 0.68). Univariate analysis failed to reveal any significant predictor for pain relief after second treatment. CONCLUSION Repeat GKRS and MVD both are valid treatment options after failed initial radiosurgery, with no difference in long term outcome. Unless specifically indicated, repeat GKRS being noninvasive, may be considered over microvascular decompression.

Treating intracranial dural arteriovenous fistulas with gamma knife radiosurgery: A single-center experience.

Objective:We evaluated the effectiveness and safety of gamma knife radiosurgery (GKRS) for the treatment of intracranial dural arteriovenous fistulas (dural AVFs) over the past 10 years.Materials and Methods:The records of 21 patients diagnosed with dural AVFs between 2004 and 2014 and treated with GKRS were reviewed retrospectively. Complete obliteration (CO) was defined as total symptom relief plus confirmation through magnetic resonance imaging or conventional angiography.Results:The median follow-up was 70.5 months (range 3–136 months). Five patients underwent embolization (2 after GKRS). One patient underwent GKRS twice. The CO rate was 47%, and partial to CO rate was 88%. The complete symptom resolution rate was 77%, and all patients achieved partial to complete symptom resolution. The CO rates for Borden Type I and Type II/III dural AVFs were 66.7% and 25% (P = 0.153), respectively, and complete symptom-free rates were 76.9% and 75.0% (P = 1.000%), respectively. The median duration between initial GKRS and complete symptom resolution was 14.3 months. The median treatment to image-free durations for Borden Type I and Type II/III dural AVFs were 25.9 and 60.4 months (P = 0.028), respectively, and treatment to symptom-free durations were 10.6 and 36.7 months (P = 0.103), respectively. One patient had a recurrent hemorrhage. Two patients experienced brain edema after stereotactic radiosurgery and one patient experienced cystic formation after GKRS. The morbidity rate was 19% (four patients) and there was no mortality.Conclusion:Treatment with GKRS for dural AVFs offers a favorable rate of obliteration. Patients with dural AVFs that are refractory or not amenable to endovascular or surgical therapy may be safely and effectively treated using GKRS.