Single-fraction Gamma Knife Radiosurgery Research Articles

Promising outcome of patients with recurrent glioblastoma after Gamma Knife-based hypofractionated radiotherapy

BackgroundThe role of Gamma Knife radiosurgery (GKRS) in recurrent glioblastoma remains unclear. The purpose of this study is to evaluate the effects of GKRS in a group of patients with recurrent glioblastoma, focusing on survival and safety. MethodsPatients undergoing GKRS for recurrent glioblastoma between September 2014 and April 2019 were included in this study. Relevant clinical and radiosurgical data, including GKRS-related complications, were recorded and analyzed. Overall survival (OS), local progression free survival (LPFS) and prognostic factors for outcome were thoroughly evaluated. ResultsFifty-three patients were analyzed (24 female, 29 male). The median age was 50 years (range, 19–78 years). The median GKRS treatment volume was 35.01 cm3 (range, 2.38-115.57 cm3). Twenty patients (38%) were treated with single fraction GKRS, while 33 (62%) were treated with GKRS-based hypofractionated stereotactic radiotherapy (HSRT). The median prescription dose for single fraction GKRS, 3-fractions HSRT and 5-fractions HSRT were 16 Gy (range, 10−20 Gy), 27 Gy (range, 18−33 Gy) and 25 Gy (range, 25−30 Gy), respectively. The median LPFS and OS times were 8.1 months and 11.4 months after GKRS, respectively. HSRT and Bevacizumab were associated with improved LPFS, while HSRT alone was associated with longer OS. ConclusionOur findings suggested that HRST would likely improve LPFS and OS in definite settings; the addition of Bevacizumab to GKRS was associated with increased rates of local control. No major complications were reported. Further prospective studies are warranted to confirm our findings.

Development of an RPA for Prediction of Radiation Necrosis Following Single Fraction Gamma Knife Radiosurgery for Brain Metastases

Radiation necrosis (RN) is a potential complication following treatment of brain metastases with stereotactic radiosurgery (SRS). Several risk factors for RN have been reported, but to our knowledge there are no recursive partitioning analysis (RPA) models to identify patients at highest risk for RN. We therefore sought to develop a predictive tool to identify patients at highest risk for the development of RN following single fraction SRS. Patients who underwent single fraction SRS for brain metastases from 2017-2021 were identified from a single institutional IRB-approved database. Patients with concern for RN were discussed in a multi-disciplinary setting and a diagnosis of RN was made based on pathologic or radiographic findings. Cox proportional hazards regression was done to identify factors associated with RN. RPA was performed to categorize patients into distinct risk groups for RN. Variables with p<0.1 on univariate analysis from the Cox regression analysis were included in the RPA. Patients with staged SRS, incomplete treatment records, or < 3 months radiographic follow-up were excluded from the analysis. The study population comprised 1,011 lesions from 283 patients with a median follow-up of 9.7 months. The majority of lesions had non-small cell lung cancer (NSCLC) (49%) as the primary site followed by breast (12%) and melanoma (11%). The median prescription dose was 24 Gy (range: 12-24 Gy). RN was diagnosed in 12.2% of lesions, of which 28% (35/123) were symptomatic RN. The median time to RN was 4.9 months. Variables identified for inclusion in the RPA included primary tumor site, use of targeted therapy, tumor location, pre-SRS hemorrhage, post-SRS hemorrhage, prior SRS to other lesions, number of SRS targets, maximum dose, maximum lesion diameter, 70% isodose line, heterogeneity index, conformality index, and gradient index. RPA identified four distinct groups. Group 1 was defined as maximum lesion diameter (MLD) <0.8 cm with primary tumor site other than breast, colorectal (CRC) or NSCLC (n = 174); group 2 was MLD <0.8 cm with breast, CRC, or NSCLC (n = 372). Group 3 was defined as MLD ≥ 0.8 cm without post-SRS hemorrhage (n = 336) and group 4 was MLD ≥0.8 cm with post-SRS hemorrhage (n = 129). Two-year RN free survival for all lesions was 82%, 100% for group 1, 89% for group 2, 76% for group 3, and 58% for group 4. We created the first RPA predictive model for RN following single fraction SRS and identified a subgroup of patients at highest risk. This RPA can help guide clinicians when educating patients on RN risk for brain metastases.

Clinically Driven Alpha/Beta Ratios for Melanoma Brain Metastases and Investigation of Biologically Effective Dose as a Predictor for Local Control After Radiosurgery: A Proof of Concept in a Retrospective Longitudinal Series of 274 Consecutive Lesions.

Brain metastases (BM) develop in nearly half of the patients with advanced melanoma. The aim of this retrospective historical cohort study was to analyze radiological response of melanoma BM to single-fraction Gamma Knife radiosurgery (GKRS), in relation to biologically effective dose (BED) for various alpha/beta ratios. Included in the study were 274 lesions. Primary outcome was local control (LC). Mean marginal dose was 21.6 Gy (median 22, range 15-25). Biologically effective dose was calculated for an alpha/beta ratio of 3 (Gy 3 ), 5 (Gy 10 ), 10 (Gy 10 ), and 15 (Gy 15 ). Receiver operating characteristic value for LC and BED was 85% (most statistically significant odds ratio 1.14 for BED Gy 15 , P = .006), while for LC and physical dose was 79% ( P = .02). When comparing equality of 2 receiver operating characteristic areas, this was statistically significant ( P = .02 and .03). Fractional polynomial regression revealed BED (Gy 10 and Gy 15 ) as statistically significant ( P = .05) with BED of more than 63 Gy 10 or 49 Gy 15 as relevant, also for higher probability of quick decrease in volume first month after GKRS and lower probability of radiation necrosis. Shorter irradiation time was associated with better LC ( P = .001), particularly less than 40 minutes (LC below 90%, P = .05). BED Gy 10 and particularly Gy 15 were more statistically significant than physical dose for LC after GKRS for radioresistant melanoma BM. Irradiation time (per lesion) longer than 40 minutes was predictive for lower rates of LC. Such results need to be validated in larger cohorts.

On the stability of Leksell Vantage stereotactic head frame fixation in Gamma Knife radiosurgery: a study based on cone-beam computed tomography imaging and the High Definition Motion Management system.

The authors' objective was to investigate the stability of the newly introduced Vantage stereotactic frame fixation in single-fraction Gamma Knife radiosurgery. A total of 255 patients were included in this work and treated with the Vantage frame and Leksell Gamma Knife (LGK) Icon equipped with cone-beam computed tomography (CBCT) imaging. After the frame was mounted on the patient's head, a CT scan was acquired. After the patient was positioned on the couch of LGK, CBCT was acquired to verify the target position before treatment delivery. A second CBCT examination was acquired after treatment delivery to assess intrafractional motion. During treatment delivery, the High Definition Motion Management (HDMM) system was enabled to track a marker on the nose tip of the patient as a surrogate of intracranial motion. The stability of the Vantage frame was deconstructed into two parts: 1) motion between CT and the first CBCT prior to treatment delivery (CT-CBCT1), and 2) motion between CBCT procedures during treatment delivery (CBCT1-CBCT2). Transformation between CT and CBCT1 was given by Leksell GammaPlan, whereas transformation between CBCT1 and CBCT2 required mathematical processing of the transformation and coregistration matrices in the source files. The average CT-CBCT1 displacement vector was 0.31 mm, with a range as great as 1.09 mm, and 89% and 97% of cases were within 0.5 mm and 0.7 mm, respectively. The CBCT1-CBCT2 displacement vectors averaged at 0.09 mm, with 97% of cases being within 0.2 mm. Spatial shift in the posterior direction was evident, with 94% of cases demonstrating this trend and averaging 0.05 mm. This was attributed to increased pressure on the posterior fixation pins. The HDMM displacement vectors presented larger values with an average of 0.4 mm and a range as great as 1.6 mm, and 98% of cases were within 1.0 mm. The correlation between CBCT1-CBCT2 and HDMM displacements was weak, which was attributed to the high stability of the Vantage frame and consequently small target displacements coupled with the sensitivity of HDMM to face mimics. This work demonstrated that the Vantage frame possess the same degree of submillimeter stability as the well-established Leksell Coordinate Frame G (G-frame). Displacements between CT and CBCT1 were 3 times higher than between CBCT1 and CBCT2. A suggested HDMM threshold of 1.2 mm ensures a target accuracy within 0.2 mm in Vantage frame treatments.

Comparing Fractionated and Single-Fraction Gamma Knife Radiosurgery for Brain Metastases From Non-Small-Cell Lung Cancer With a Focus on Driver Alterations.

Background As the overall survival in non-small-cell lung cancer has increased, safer, long-term treatments for brain metastases are increasingly needed. This study aimed to analyze the outcomes of fractionated and single-fraction gamma knife radiosurgery for brain metastases from non-small-cell lung cancer, focusing on driver alteration status. Methodology Patients who underwent gamma knife radiosurgery as their first local treatment for brain metastases from non-small-cell lung cancer between May 2018 and December 2021 at our institution were retrospectively enrolled. Results Among the 98 patients (287 lesions), 45 (130 lesions) harbored driver alterations, includingepidermal growth factor receptor mutations in 35 patients and anaplastic lymphoma kinase or ROS1 rearrangement in 10 patients. Overall, 64 and 34 patients underwent single-fraction and fractionated radiosurgery (3-15 fractions), respectively. Large tumor size was a risk factor for recurrence, while fractionated radiosurgery (subdistribution hazard ratio (sHR) = 16.47; confidence interval (CI) = 3.58-75.77; p < 0.001) and small tumor size (sHR = 1.15; CI = 1.04-1.28; p = 0.008) independently protected against radiation necrosis. In the case-matched analyses, the cumulative radiation necrosis rates were significantly lower in the fractionated group than in the single-fraction group among all lesions (p = 0.017) and among those with driver alterations (p = 0.046),whereas no significant difference was confirmed among wild-type lesions (p = 0.382). Conclusions Fractionated gamma knife radiosurgery may be an alternative therapeutic approach for reducing the risk of radiation necrosis, particularly for patients with driver alterations, even when the tumors are small. Further research is necessary to determine the optimal indications for fractionated gamma knife radiosurgery and fractionation methods.

The role of single fraction Gamma Knife radiosurgery for intraventricular central neurocytomas and the utility of F-18 fluroethyltyrosine: two case reports

BackgroundPrimary treatment of central neurocytomas is surgical resection. Gamma Knife surgery is considered a valuable therapeutic option in case of residual (after subtotal resection) or recurrent central neurocytomas. Here, we focused on the role of F-18 fluroethyltyrosine as a marker to document tumor progression after initial resection, in the context of an atypical central neurocytoma. We also describe MIB-1’s role in evaluating therapeutic decision-making.Case presentationTwo patients with central neurocytomas were treated by Gamma Knife surgery in our center. The first case (31-year-old Caucasian male) had atypical central neurocytoma. Four and a half years after surgical resection, magnetic resonance imaging and F-18 fluroethyltyrosine documented clear progression of residual central neurocytoma, further treated by Gamma Knife surgery (18 Gy at 50%, target volume 1.4 cc, and prescription isodose volume 1.8 cc). The initial post-Gamma Knife surgery clinical course was uneventful, with progressive volumetric reduction of residual tumor up to 4.5 years, when out-of-field recurrence was suspected and confirmed by local F-18 fluroethyltyrosine hyperactivity. Second single-fraction Gamma Knife surgery was performed (18 Gy at 50%, target volume 0.49 cc, prescription isodose volume 0.72 cc). The second (32-year-old Caucasian female) had previous subtotal resection and typical central neurocytoma. Seven years later, she had residual tumor progression. Single-fraction Gamma Knife surgery was performed (16 Gy at 50% isodose line, target volume 1.7 cc, and prescription isodose volume 2.5 cc). Last follow-up showed tumor volume reduction. Follow-up magnetic resonance imaging showed important volumetric reduction of both treated lesions.ConclusionsIn atypical central neurocytomas, F-18 fluroethyltyrosine could be used as postoperative examination to detect small tumor remnants, follow-up evaluation following the Gamma Knife surgery or, in select cases, following surgical resection. The role of MIB-1 is important in therapeutic decision-making, as tumors with MIB-1 exceeding 2% are characterized by more aggressive clinical course. Single-fraction Gamma Knife surgery remains a valuable therapeutic option for postoperative residual atypical central neurocytomas and central neurocytoma recurrences.

Gamma Knife radiosurgery as salvage therapy for gangliogliomas after initial microsurgical resection

IntroductionGangliogliomas (GG) are considered WHO grade I rare tumors. While they commonly manifest as temporal lobe epilepsy, they can be located anywhere in the brain. Primary treatment is complete microsurgical resection. Remnant or recurrent GG can benefit from radiation therapy. Here, we present a series of GG who received Gamma Knife radiosurgery (GKR) after initial microsurgery. MethodsBetween October 2009 and February 2020, four patients benefitted from such approach. The median age at surgery was 16 years (mean 17, 11–25) and at the time of GKR was 22.5 years (mean 23, 19–28). Initial clinical symptom was epilepsy in 3 cases and incidental in one. Biopsy was firstly performed in one case. One patient had stereotactic electroencephalography. The respective anatomical locations were right parieto-occipital, sylvian, left paraventricular and left inferior parietal. ResultsGamma Knife radiosurgery was performed after a median time of 3.5 years after initial gross total microsurgical resection (GTR). The median follow-up after GKR was 54 months (mean 58.5, 6–120). The median marginal dose was 18 Gy (mean 17.5, 16–18). The median target volume was 0.5 mL (mean 0.904, 0.228–2.3). The median prescription isodose volume was 0.6 mL (mean 0.9, 0.3–2.4). At last follow-up, GG majorly decreased in 3 patients, remained stable in one. ConclusionGamma Knife radiosurgery is safe and effective for remnant GG after GTR. Primary treatment remains microsurgical resection, especially in cases with symptomatic mass effect or with epilepsy. Single fraction GKR can be a valuable option for remnant or recurrent tumors after initial resection.

Prognostic Factors for Patients With Brain Metastases Treated With Single-fraction Gamma Knife Radiosurgery.

The aim of this study was to identify prognostic factors for brain metastases treated with Gamma knife radiosurgery. Multivariate Cox proportional hazards regression analyses were conducted for patients who received treatment between June 2013 and March 2018. A total of 131 consecutive patients were included. The median follow-up period was 16.0 months (range=1.5-61.5 months). Brain metastases [hazard ratio (HR)=0.42, 95%CI=0.27-0.67, p<0.001], history of systemic therapy (HR=2.23, 95%CI=1.28-3.89, p=0.005), and active extracranial disease (HR=2.49, 95%CI=1.30-4.76, p=0.006) were independent predictors of overall survival. Number of brain metastases (HR=0.39, 95%CI=0.26-0.59, p<0.001) and history of systemic therapy (HR=1.90, 95%CI=1.17-3.08, p=0.005) were independent predictors of intracranial progression-free survival. The number of brain metastases and the history of systemic therapy are associated with patient overall survival and intracranial progression-free survival.

Long-term results of gamma knife radiosurgery for foramen magnum meningiomas.

Outcomes of 37 patients of foramen magnum meningioma (FMM) were evaluated, and the related literature was reviewed to determine the efficacy of Gamma Knife radiosurgery (GKRS) for treating patients with FMM. We present the largest series reported from a single institution with the longest follow-up to date. The database of patients who underwent GKRS for FMM between 2007 and 2019 was evaluated retrospectively. A total of 37 patients with radiological and pathological features consistent with FMM were included in this series. Thirty-three patients were female, and 4 were male. The median age was 58years (range, 23-74years). The most common symptom at diagnosis was headache (64.9%). Twelve patients had a history of microsurgical resection. The median duration from the initial onset of symptoms to GKRS was 12months (range 1-140months). Among the 37 tumors, eight (21.6%) were located ventrally, 24 (64.9%) laterally, and five (13.5%) dorsally. The median target volume was 3.30cm3 (range, 0.6-17.6cm3). Thirty-five patients (95%) were treated with single fraction GKRS, and two patients (5%) were treated with hypofractionated GKRS. The median clinical follow-up was 80months (range, 18-151months), while the median radiological follow-up was 84months (range, 18-144months). At the last clinical follow-up after GKRS, 27 patients (73%) had improved symptoms, and none had worsened pre-GKRS symptoms. At the last radiological follow-up after GKRS, 23 tumors (62.2%) remained stable, 13 (35.1%) decreased in size, and 1 (2.7%) increased in size. Tumor control, including stable and regressed tumors, was achieved in 97.3% of patients. Our cohort demonstrates that GKRS is an effective and safe treatment for patients with either primary or recurrent/residual FMM.

Stereotactic Gamma Knife Radiosurgery for Extracranial Arteriovenous Malformations

Introduction: Head and neck extracranial arteriovenous malformations (AVMs) are rare pathological conditions which pose diagnostic and reconstruction challenges. Stereotactic radiosurgery (SRS) is nowadays an established treatment method for brain AVMs, with high obliteration and low complication rates. Here we describe the first report of head extracranial AVMs successfully treated by Gamma Knife (GK) as a retrospective historical cohort. Methods: Over a 9-year period, 2 cases of extracranial AVMs were treated by GK Perfexion (Elekta Instruments AB, Stockholm, Sweden) at a single institution. A stereotactic frame and multimodal imaging, including digital subtraction angiography (DSA), were used. The prescribed dose was 24 Gy at the 50% isodose line. Results: The first case was of a patient with pulsating tinnitus and left superficial parotido-condylian AVM. Embolization achieved partial obliteration. Tinnitus disappeared during the following 6 months after GK. The second case was a patient with repetitive gingival hemorrhages and right superior maxillary AVM, fed by the right internal maxillary and facial arteries. Embolization achieved partial obliteration with recurrence of symptoms. GK was further performed. DSA confirmed complete obliteration in both patients. Conclusions: Single-fraction GK radiosurgery appears to be safe and effective for extracranial AVMs. We recommend prescribing doses that are comparable to the ones used for brain AVMs (i.e., 24 Gy). A stereotactic frame is an important tool to ensure higher accuracy in the context of these particular locations. However, in selected cases, a mask could be applied either for single fraction purposes (if in a non-mobile location) or for hypofractionation, in case of larger volumes. These findings should be validated in larger cohorts, inclusively in terms of dose prescription.

Metastatic renal cell carcinoma to the brain: optimizing patient selection for gamma knife radiosurgery.

The effects of single-fraction gamma knife radiosurgery (sf-GKRS) on patients with renal cell carcinoma (RCC) brain metastases (BM) in the era of targeted agents (TA) and immune checkpoint inhibitors (ICI) are insufficiently studied. Clear cell metastatic RCC patients treated with sf-GKRS due to BM in 2005-2014 at three European centres were retrospectively analysed (n = 43). Median follow-up was 56 months. Ninety-five percent had prior nephrectomy, 53% synchronous metastasis and 86% extracranial disease at first sf-GKRS. Karnofsky performance status (KPS) ranged from 60 to 100%. Outcome measures were overall survival (OS), local control (LC) and adverse radiation effects (ARE). One hundred and ninety-four targets were irradiated. The median number of targets at first sf-GKRS was two. The median prescription dose was 22.0 Gy. Thirty-seven percent had repeated sf-GKRS. Eighty-eight percent received TA. LC rates at 12 and 18 months were 97% and 90%. Median OS from the first sf-GKRS was 15.7 months. Low serum albumin (HR for death 5.3), corticosteroid use pre-sf-GKRS (HR for death 5.8) and KPS < 80 (HR for death 9.1) were independently associated with worse OS. No further prognostic information was gleaned from MSKCC risk group, synchronous metastasis, age, number of BM or extracranial metastases. Other prognostic scores for BM radiosurgery, including DS-GPA, renal-GPA, LLV-SIR and CITV-SIR, again, did not add further prognostic value. ARE were seldom symptomatic and were associated with tumour volume, 10-Gy volume and pre-treatment perifocal oedema. ARE were less common among patients treated with TA within 1 month of sf-GKRS. We identified albumin, corticosteroid use and KPS as independent prognostic factors for sf-GKRS of clear cell RCC BM. Studies focusing on the prognostic significance of albumin in sf-GKRS are rare. Further studies with a larger number of patients are warranted to confirm the above analytical outcome. Also, in keeping with previous studies, our data showed optimal rates of local tumour control and limited toxicity post radiosurgery, rendering GKRS the tool of choice in the management of RCC BM.

Clinical and radiographic adverse events after Gamma Knife radiosurgery for brainstem lesions: A dosimetric analysis

ObjectivesTo analyze the association between dosvolume relationships and adverse events in brainstem lesions treated with Gamma Knife radiosurgery (GKRS). MethodsTreatment plans were generated on BrainLab Elements and GammaPlan software. Dosimetric data were analyzed as continuous variables for patients who received GKRS to brain metastases or arteriovenous malformations (AVM) within or abutting the brainstem. Adverse events were classified as clinical and/or radiographic. Logistic and cox regression were used to assess the relationship between dosimetric variables and adverse events. ResultsSixty-one patients who underwent single fraction GKRS for brain metastases or AVM were retrospectively analyzed. Median age was 62 years (range: 12–92 years) and the median prescription dose was 18 Gy (range: 13–25 Gy). Median follow-up was 6months. Clinical and radiographic complications were seen in ten (16.4%) and 17 (27.9%) patients, respectively. On logistic regression, increasing D05% was found to be associated with an increased probability of developing a clinical complication post-GKRS (OR: 1.18; 95% CI: 1.01–1.39; p = 0.04). Furthermore, mean brainstem dose (HR: 1.43; 95% CI: 1.05–1.94; p < 0.02), D05% (HR: 1.09; 95% CI: 1.01–1.18; p = 0.03), and D95% (HR: 2.37; 95% CI: 0.99–5.67; p = 0.05) were associated with an increased hazard of experiencing post-GKRS complications over time. ConclusionsIncreasing D05% to the brainstem is associated with an increased risk of developing clinical complications. Clinicians may consider this parameter in addition to fractionated stereotactic radiation therapy when well-established dose constraints are not met in this patient population. Additional data are needed to further validate these findings.

One-Day Two-Fraction Radiosurgery for Brain Metastases Using Gamma Knife.

Objective: We aimed to evaluate the feasibility of a one-day two-fraction Gamma Knife radiosurgery (GKRS) for brain metastases.Cases and methods: Ten cases with ten brain metastases (four cases of lung adenocarcinoma, one small cell lung carcinoma (SCLC), two renal cell carcinoma, one breast cancer, one esophageal carcinoma, and one bile duct carcinoma) were treated by one-day two-fraction (with an interval of more than six hours) GKRS under rigid skull frame fixation. Of the ten brain metastases, five lesions were in the frontal lobe, one in temporal, one in occipital, and three in the cerebellar hemisphere. The mean planning target volume (PTV) of the ten brain tumors was 7.8 ml (median, 8.0; range, 3.8 - 11.8). The ten targets of the mean prescription isodose volume (PIV) of 10.1 ml (median, 10.1; range, 4.4 - 15.9) were treated with a mean margin dose of 20.4 Gy (median, 20.5; range, 16.4 - 22) in two fractions. In five cases, other small brain metastases (one to seven tumors) were also treated simultaneously in a single fraction GKRS. The indication of two-fraction radiosurgery was large lesion size in eight, retreatment in three, the proximity of the motor area in three, and pre-existing perifocal edema symptom of dysarthria in two, nausea and vomiting in one, and dementia in one.Results: Eight cases were alive at the end of the follow-up period of one to nine months (median, 6). One patient with SCLC died four and a half months after GKRS, from aggressive regrowth of the treated frontal lesion after transient marked shrinkage. Another patient died four months after GKRS due to the progression of other brain tumors treated by single fraction GKRS at the same time. In nine of 10 cases, the size of the treated tumors was controlled until the end of the follow-up period or the patient’s death. In two cases, an additional GKRS was performed for newly developed brain metastases at distant locations at six months and five months after one-day two-fraction GKRS, respectively, and controlled at the end of the follow-up period.Conclusions: A relatively high dose may be safely delivered to large lesions, to those close to the important structures, or those with perifocal edema by one-day two-fraction radiosurgery. Local control was good except for a relapsed SCLC metastasis case. Evaluation in more cases with a longer follow-up period is necessary to determine definite indications and optimal prescription doses.

Gamma Knife radiosurgery for the treatment of Nelson's syndrome: a multicenter, international study.

Nelson's syndrome is a rare and challenging neuroendocrine disorder, and it is associated with elevated adrenocorticotrophic hormone (ACTH) level, skin hyperpigmentation, and pituitary adenoma growth. Management options including resection and medical therapy are traditional approaches. Ionizing radiation in the form of Gamma Knife radiosurgery (GKRS) is also being utilized to treat Nelson's syndrome. In the current study the authors sought to better define the therapeutic role of stereotactic radiosurgery (SRS) in Nelson's syndrome. Study patients with Nelson's syndrome were treated with single-fraction GKRS (median margin dose of 25 Gy) at 6 different centers as part of an International Radiosurgery Research Foundation (IRRF) investigation. Data including neurological function, endocrine response, and radiological tumor response were collected and sent to the study-coordinating center for review. Fifty-one patients with median endocrine and radiological follow-ups of 91 and 80.5 months from GKRS, respectively, were analyzed for endocrine remission, tumor control, and neurological outcome. Statistical methods were used to identify prognostic factors for these endpoints. At last follow-up, radiological tumor control was achieved in 92.15% of patients. Endocrine remission off medical management and reduction in pre-SRS ACTH level were achieved in 29.4% and 62.7% of patients, respectively. Improved remission rates were associated with a shorter time interval between resection and GKRS (p = 0.039). Hypopituitarism was seen in 21.6% and new visual deficits were demonstrated in 15.7% of patients. GKRS affords a high rate of pituitary adenoma control and improvement in ACTH level for the majority of Nelson's syndrome patients. Hypopituitarism is the most common adverse effect from GKRS in Nelson's syndrome patients and warrants longitudinal follow-up for detection and endocrine replacement.

Single fraction and multisession Gamma Knife radiosurgery for craniopharyngioma.

The optimal management of residual or recurring craniopharyngioma is still a matter of debate even though adjuvant radiation therapy plays a crucial role. Aim of our study is to report the results of single fraction or multisession Gamma Knife radiosurgery (GKRS) in patients with craniopharyngioma. We included 50 consecutive patients treated from 1994 to 2016. All patients had at least one post GKRS magnetic resonance imaging reviewed at our center. Vital status of all patients was assessed at the end of 2016. There were 29 males (58.0%) and 21 females (42.0%). Mean age was 41.5 ± 2.8year. Single session GKRS was delivered in 29 patients (58.0%). The mean tumor volume was 2.15 ± 0.3cm3 and the mean prescription dose to the tumor margin was 14.3 ± 0.3Gy. During a mean follow-up of 74.6 ± 8.4months, seven patients (14.0%) had recurrence of disease. The 5- and 10-year recurrence-free survivals were 90.3% (95% CI, 81.0-99.6%) and 78.4% (95% CI, 59.9-96.9%), respectively. Multisession GKRS was not less effective than single fraction GKRS. Eighteen of the 28 patients (64.3%) had a tumor volume decrease of at least 10%. No serious side effects occurred after GKRS treatment, except for one case of mild visual worsening. GKRS was effective for controlling the growth of residual or recurrent craniopharyngioma. Serious side effects were uncommon. Multisession GKRS seems a very promising tool to allow performing GKRS even in patients with large residual or recurrent craniopharyngioma.

Safety and efficacy of single-fraction gamma knife radiosurgery for benign confined cavernous sinus tumors: our experience and literature review.

Gamma knife radiosurgery (GKRS) has emerged as a suitable primary treatment option for confined cavernous sinus tumors (CSTs) and residual/recurrent benign tumors extending from the surrounding neighborhood. The aim of this review was to further investigate the safety and efficacy of single-fraction GKRS for primary confined CSTs (hemangioma, meningioma, and schwannoma). This was a retrospective analysis of 16 patients of CSTs, primarily treated with GKRS between 2009 and 2017. The patients underwent follow-up clinical and radiological evaluation at a regular interval. Data on clinical and imaging parameters were analyzed. The published literature on GKRS for CSTs was reviewed. There were total 16 patients (eight meningiomas, seven hemangiomas, and one schwannoma). Patients presented with a headache (56.3%), ptosis (50%), and/or restricted extraocular movements (50%). There was 46.6% tumor volume (TV) reduction after single-fraction GKRS. Hemangiomas showed best TV reduction (64% reduction at > 3-year follow-up) followed by schwannoma (41.5%) and meningioma (25.4%). 56.3% of patients developed transient hypoesthesia in trigeminal nerve distribution. 44.4% of patients became completely pain-free. Among cranial nerves, the superior division of the oculomotor nerve showed best outcome (ptosis 62.5%) followed by an improved range of EOM. There was no adverse event in the form of new-onset deficit, vascular complication, or malignant transformation except for one out of the field failures. Among available treatment options, GKRS is the most suitable option by virtue of its minimally invasive nature, optimal long-term tumor control, improvement in cranial neuropathies, cost-effectiveness, favorable risk-benefit ratio, and minimal long-term complications.

Emerging Indications for Fractionated Gamma Knife Radiosurgery.

Gamma Knife radiosurgery (GKRS) allows for the treatment of intracranial tumors with a high degree of dose conformality and precision. There are, however, certain situations wherein the dose conformality of GKRS is desired, but single session treatment is contraindicated. In these situations, a traditional pin-based GKRS head frame cannot be used, as it precludes fractionated treatment. To report our experience in treating patients with fractionated GKRS using a relocatable, noninvasive immobilization system. Patients were considered candidates for fractionated GKRS if they had one or more of the following indications: a benign tumor >10 cc in volume or abutting the optic pathway, a vestibular schwannoma with the intent of hearing preservation, or a tumor previously irradiated with single fraction GKRS. The immobilization device used for all patients was the Extend system (Leksell Gamma Knife Perfexion, Elekta, Kungstensgatan, Stockholm). We identified 34 patients treated with fractionated GKRS between August 2013 and February 2015. There were a total of 37 tumors treated including 15 meningiomas, 11 pituitary adenomas, 6 brain metastases, 4 vestibular schwannomas, and 1 hemangioma. At last follow-up, all 21 patients treated for perioptic tumors had stable or improved vision and all 4 patients treated for vestibular schwannoma maintained serviceable hearing. No severe adverse events were reported. Fractionated GKRS was well-tolerated in the treatment of large meningiomas, perioptic tumors, vestibular schwannomas with intent of hearing preservation, and in reirradiation of previously treated tumors.

Gamma Knife radiosurgery for neurofibromatosis type 2-associated meningiomas: a 22-year patient series.

Neurofibromatosis type 2 (NF2) is a debilitating genetic condition with potential development of multiple meningiomas. We report our experience treating a series of NF2-associated intracranial meningiomas with Gamma Knife radiosurgery (GKRS). Between 1992 and 2013, 15 consecutive patients (age 20-54 years) with 62 intracranial meningiomas were treated with single-fraction GKRS. Fifty-five percent of tumors involved the convexity or parasagittal/falx. The median prescription dose was 16Gy (range 13-20Gy). The median tumor diameter was 2.1cm (range 0.7-4.5cm). The median radiographic and clinical follow-up periods were 103 and 111 months, respectively. The 5-year and 10-year local controls were both 96 %. The disease specific survival was 93 % at 5 years and 68 % at 10 years. Fifty-three percent of patients had multiple meningiomas and received multiple GKRS treatments (range 1-7) for new or enlarging intracranial meningiomas. 11 (73 %) patients were alive at last follow-up, with 60 (97 %) tumors controlled (smaller or unchanged in size). There were 2 in-field failures, one at 1year and the other at 3.5 years. There were no marginal failures. Major Complications after GKRS included: 1 case of radiation necrosis, 1 case of post treatment edema, and 1 case of a presumed radiation induced cavernous malformation 5 years after GKRS. GK is an effective treatment for enlarging NF2-associated meningiomas. No cases of malignant transformation or secondary malignancies were seen during the follow-up period.

357 Gamma Knife Stereotactic Radiosurgery in the Management of Large Cerebral Arteriovenous Malformations

Abstract Large brain arteriovenous malformations (AVMs) pose management challenge in neurosurgical practice. Management remains conservative unless these AVMs bleed or present with neurological deficits. For patients who require treatment, options are limited with very high treatment-related morbidity. Gamma knife radiosurgery remains an excellent noninvasive option for such AVMs. This is a retrospective study of 74 patients with large AVMs who were treated with gamma knife radiosurgery over 16 years. Sixty-five patients were treated with single-fraction and 9 patients were treated with volume-staged gamma knife radiosurgery. Average follow-up was 4.2 years. In the single-fraction group, 90% patients had SM grade 3 and 4 AVMs while 10% patients had SM grade 5 AVMs. Mean marginal radiation dose was 23.66 Gy. Overall obliteration rate of 66% was observed. Four percent of patients rebled in this group. Postradiation edema was observed in 18% of patient who presented with headache, new-onset seizures, and motor deficits. The symptoms improved with steroid therapy in most patients. Delayed cyst formations were seen in 2 patients. Interestingly, 41% patients showed seizure control after gamma knife radiosurgery. In volume-staging group, 60% patients had SM grade 4 AVMs and 40% patients has SM grade 5 AVMs. All patients were treated in 2 sittings. Average marginal dose used was 23 Gy. These patients showed nearly 80% reduction in the nidus volume at follow-up. No new-onset deficit was observed in this group, and all patients tolerated the treatment very well. Large-volume AVMs can be managed with gamma knife radiosurgery with acceptable risks. Single-fraction gamma knife radiosurgery should be considered for moderate-size AVMs away from critical structures. Large-volume lesions should be treated with volume-staged gamma knife radiosurgery.

Biochemical and clinical responses after treatment of a catecholamine‐secreting glomus jugulare tumor with gamma knife radiosurgery

Functional glomus jugulare tumors (GJTs) are commonly managed with resection. Although primary radiation therapy of functional GJT can provide durable control of tumor growth, little is known of its ability to ablate functional capacity. We describe a case of a 47-year-old man with a symptomatic norepinephrine-hypersecreting GJT treated with definitive single-fraction gamma knife radiosurgery and pharmacologic catecholamine blockade. At a 32-month follow-up, he has experienced significant symptomatic improvement, excellent control of local tumor growth, minimal treatment-related morbidity, and near normalization of catecholamine levels. Radiosurgery was safe and effective in significantly reducing the functional capacity of a paraganglioma. Care must be taken to avoid inducing a hypertensive crisis during and following treatment, and longer follow-up will help determine whether and when pharmacologic blockade can be discontinued.