Selected Latest Publications

In this section we highlight selected recent publications for Gamma Knife based research. This is updated periodically and therefore we hope by bookmarking this page it will provide you with an easy reference source to keep up to date with latest developments. You can click on the PMID which will provide links to access the full articles.

The NASSAU (New ASSessment of cerebral Arteriovenous Malformations yet Unruptured) Analysis: Are the Results From The ARUBA Trial Also Applicable to Unruptured Arteriovenous Malformations Deemed Suitable for Gamma Knife Surgery?

Karlsson BJokura HYang HC3Yamamoto MMartinez RKawagishi JGuo WYBeute GPan DHCAiyama HChung WYSöderman MYeo TT. Neurosurgery. 2018 Oct 8. PMID:30295870



The optimal management of unruptured brain arteriovenous malformations (AVMs) is controversial after the ARUBA trial.


To confirm or repudiate the ARUBA conclusion that “medical management only is superior to medical management with interventional therapy for unruptured brain arteriovenous malformations.”


Data were collected from 1351 patients treated with Gamma Knife Surgery (GKS; Elekta AB, Stockholm, Sweden) for unruptured and untreated AVMs The follow-up was 8817 yr (median 5.0 and mean 6.5). The results of the analyses were compared to that found in patients randomized to medical management only in the ARUBA trial and extrapolated to a 10-yr time period. Our data were also compared to the natural course in a virtual AVM population for a 25-yr time period.


The incidence of stroke was similar among ARUBA and our patients for the first 5 yr. Thereafter, the longer the follow-up, the relatively better outcome following treatment. Both the mortality rate and the incidence of permanent deficits in patients with small AVMs were the same as in untreated patients for the first 2 to 3 yr after GKS, after which GKS patients did better. Patients with large AVMs had a higher incidence of neurological deficits in the first 3 yr following GKS. The difference decreased thereafter, but the time until break even depended on the analysis method used and the assumed risk for hemorrhage in patent AVMs.


The ARUBA trial conclusion that medical management is superior to medical management with interventional therapy for all unruptured AVMs could be repudiated.


Treatment of brain metastases with stereotactic radiosurgery and immune checkpoint inhibitors: An international meta-analysis of individual patient data.

Lehrer EJ, Peterson J, Brown PD, Sheehan JP, Quiñones-Hinojosa A, Zaorsky NG, Trifiletti DM. Radiother Oncol. 2018 Sep 18.
PMID: 30241791




While the combination of stereotactic radiosurgery (SRS) and immune checkpoint inhibitors (ICI) is becoming more widely used in the treatment of brain metastases (BM), there is a paucity of prospective data to validate both the safety and efficacy, as well as the optimal timing of these two therapies relative to one another.


A PICOS/PRISMA/MOOSE selection protocol was used to identify 17 studies across 15 institutions in 3 countries. Inclusion criteria were patients: diagnosed with BMs; treated with SRS/ICI, either concurrently or non-concurrently; with at least one of the primary or secondary outcomes measures reported. Weighted random effects meta-analyses using the DerSimonian and Laird method was performed. The primary outcome was 1-year overall survival (OS). Secondary outcomes were 1-year local control (LC), 1-year regional brain control (RBC), and radionecrosis incidence.


A total of 534 patients with 1570 BM were included. The 1-year OS was 64.6% and 51.6% for concurrent and non-concurrent therapy, respectively (p < 0.001). Local control at 1-year was 89.2% and 67.8% for concurrent and non-concurrent therapy, respectively (p = 0.09). The RBC at 1-year was 38.1% and 12.3% for concurrent and ICI administration prior to SRS, respectively (p = 0.049). The overall incidence of radionecrosis for all studies was 5.3%.


Concurrent administration of SRS/ICI may be associated with improved safety and efficacy versus sequential therapy. These findings, however, are hypothesis-generating and require further validation by ongoing and planned prospective trials.


Results of Gamma Knife anterior capsulotomy for refractory obsessive-compulsive disorder: results in a series of 10 consecutive patients.

Spatola G, Martinez-Alvarez R, Martínez-Moreno N, Rey G, Linera J, Rios-Lago M, Sanz M, Gutiérrez J, Vidal P, Richieri R, Régis J. J Neurosurg. 2018 Sep 14:1-8. PMID:30215566



OBJECTIVE Obsessive-compulsive disorder (OCD) is a severe psychiatric condition. The authors present their experience with Gamma Knife radiosurgery (GKRS) in the treatment of patients with OCD resistant to any medical therapy. METHODS Patients with severe OCD resistant to all pharmacological and psychiatric treatments who were treated with anterior GKRS capsulotomy were retrospectively reviewed. These patients were submitted to a physical, neurological, and neuropsychological examination together with structural and functional MRI before and after GKRS treatment. Strict study inclusion criteria were applied. Radiosurgical capsulotomy was performed using two 4-mm isocenters targeted at the midputaminal point of the anterior limb of the capsule. A maximal dose of 120 Gy was prescribed for each side. Clinical global changes were assessed using the Clinical Global Impression (CGI) scale, Global Assessment of Functioning (GAF) scale, EQ-5D, Beck Depression Inventory (BDI), and State-Trait Anxiety Inventory (STAI). OCD symptoms were determined by the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). RESULTS Ten patients with medically refractory OCD (5 women and 5 men) treated between 2006 and 2015 were included in this study. Median age at diagnosis was 22 years, median duration of illness at the time of radiosurgery was 14.5 years, and median age at treatment was 38.8 years. Before GKRS, the median Y-BOCS score was 34.5 with a median obsession score of 18 and compulsion score of 17. Seven (70%) of 10 patients achieved a full response at their last follow-up, 2 patients were nonresponders, and 1 patient was a partial responder. Evaluation of the Y-BOCS, BDI, STAI-Trait, STAI-State, GAF, and EQ-5D showed statistically significant improvement at the last follow-up after GKRS. Neurological examinations were normal in all patients at each visit. At last follow-up, none of the patients had experienced any significant adverse neuropsychological effects or personality changes. CONCLUSIONS GKRS anterior capsulotomy is effective and well tolerated with a maximal dose of 120 Gy. It reduces both obsessions and compulsions, improves quality of life, and diminishes depression and anxiety.


The Changing Paradigm for the Surgical Treatment of Large Vestibular Schwannomas.

Daniel RT, Tuleasca C, Rocca A, George M, Pralong E, Schiappacasse L, Zeverino M, Maire R, Messerer M, Levivier M. J Neurol Surg B Skull Base. 2018 Oct;79(Suppl 4): PMID: 30210991




Planned subtotal resection followed by Gamma Knife surgery (GKS) in patients with large vestibular schwannoma (VS) has emerged during the past decade, with the aim of a better functional outcome for facial and cochlear function.


We prospectively collected patient data, surgical, and dosimetric parameters of a consecutive series of patients treated by this method at Lausanne University Hospital during the past 8 years.


A consecutive series of 47 patients were treated between July 2010 and January 2018. The mean follow-up after surgery was 37.5 months (median: 36, range: 0.5-96). Mean presurgical tumor volume was 11.8 mL (1.47-34.9). Postoperative status showed normal facial nerve function (House-Brackmann I) in all patients. In a subgroup of 28 patients, with serviceable hearing before surgery and in which cochlear nerve preservation was attempted at surgery, 26 (92.8%) retained serviceable hearing. Nineteen had good or excellent hearing (Gardner-Robertson class 1) before surgery, and 16 (84.2%) retained it after surgery. Mean duration between surgery and GKS was 6 months (median: 5, range: 3-13.9). Mean residual volume as compared with the preoperative one at GKS was 31%. Mean marginal dose was 12 Gy (11-12). Mean follow-up after GKS was 34.4 months (6-84).


Our data show excellent results in large VS management with a combined approach of microsurgical subtotal resection and GKS on the residual tumor, with regard to the functional outcome and tumor control. Longer term follow-up is necessary to fully evaluate this approach, especially regarding tumor control.


Comparison of treatment results between 3- and 2-stage Gamma Knife radiosurgery for large brain metastases: a retrospective multi-institutional study.

Serizawa T, Higuchi Y, Yamamoto M, Matsunaga S, Nagano O, Sato Y, Aoyagi K, Yomo S, Koiso T, Hasegawa T, Nakazaki K, Moriki A, Kondoh T, Nagatomo Y, Okamoto H, Kohda Y, Kawai H, Shidoh S, Shibazaki T, Onoue S, Kenai H, Inoue A, Mori H. J Neurosurg. 2018 Sep 7:1-11. PMID: 30192195



OBJECTIVE In order to obtain better local tumor control for large (i.e., > 3 cm in diameter or > 10 cm3 in volume) brain metastases (BMs), 3-stage and 2-stage Gamma Knife surgery (GKS) procedures, rather than a palliative dose of stereotactic radiosurgery, have been proposed. Here, authors conducted a retrospective multi-institutional study to compare treatment results between 3-stage and 2-stage GKS for large BMs. METHODS This retrospective multi-institutional study involved 335 patients from 19 Gamma Knife facilities in Japan. Major inclusion criteria were 1) newly diagnosed BMs, 2) largest tumor volume of 10.0-33.5 cm3, 3) cumulative intracranial tumor volume ≤ 50 cm3, 4) no leptomeningeal dissemination, 5) no more than 10 tumors, and 6) Karnofsky Performance Status 70% or better. Prescription doses were restricted to between 9.0 and 11.0 Gy in 3-stage GKS and between 11.8 and 14.2 Gy in 2-stage GKS. The total treatment interval had to be within 6 weeks, with at least 12 days between procedures. There were 114 cases in the 3-stage group and 221 in the 2-stage group. Because of the disproportion in patient numbers and the pre-GKS clinical factors between these two GKS groups, a case-matched study was performed using the propensity score matching method. Ultimately, 212 patients (106 from each group) were selected for the case-matched study. Overall survival, tumor progression, neurological death, and radiation-related adverse events were analyzed. RESULTS In the case-matched cohort, post-GKS median survival time tended to be longer in the 3-stage group (15.9 months) than in the 2-stage group (11.7 months), but the difference was not statistically significant (p = 0.65). The cumulative incidences of tumor progression (21.6% vs 16.7% at 1 year, p = 0.31), neurological death (5.1% vs 6.0% at 1 year, p = 0.58), or serious radiation-related adverse events (3.0% vs 4.0% at 1 year, p = 0.49) did not differ significantly. CONCLUSIONS This retrospective multi-institutional study showed no differences between 3-stage and 2-stage GKS in terms of overall survival, tumor progression, neurological death, and radiation-related adverse events. Both 3-stage and 2-stage GKS performed according to the aforementioned protocols are good treatment options in selected patients with large BMs.


Neoadjuvant Stereotactic Radiosurgery Before Surgical Resection of Cerebral Metastases.

Patel AR, Nedzi L, Lau S, Barnett SL, Mickey BE, Moore W, Bindal S, Wardak Z, Dan T, Timmerman R, Patel TR. World Neurosurg. 2018 Aug 24. (18) 31890-4. PMID: 30149167




Stereotactic radiosurgery (SRS) has redefined the treatment paradigm for cerebral metastases. The benefits of SRS after surgical resection of a metastatic brain tumor have been well-defined. However, it is unclear whether preoperative SRS can improve the outcomes in select patients. The present study examined the safety and efficacy of preoperative neoadjuvant SRS (NaSRS) for the treatment of cerebral metastases.


We performed a retrospective review of 12 patients treated at The University of Texas Southwestern Medical Center. All patients underwent NaSRS, followed by surgical resection of a cerebral metastasis, from 2011 to 2015. Recurrence and overall survival were characterized using Kaplan-Meier and log-rank analyses.


The mean age was 57.5 years (range, 39-69). The median follow-up period was 13 months (range, 1-22.6). The median maximum tumor diameter was 3.66 cm (range, 2.19-4.85). The 6- and 12-month local control rates were 81.8% and 49.1%, respectively. The distant disease control rates were 72.7% and 14.5% at 6 and 12 months, respectively. Overall survival was 83.3% and 74.1% at 6 and 12 months, respectively. Two patients developed leptomeningeal disease at a mean of 11.3 months. A trend toward increased local failure was seen with larger tumor volumes and diameters (P = 0.06).


NaSRS is a promising new approach for the treatment of select cerebral metastases that require surgical intervention. The approach is safe and effective at achieving local control. Further randomized studies with larger patient cohorts are necessary to determine whether the long-term outcomes are improved.

Copyright © 2018 Elsevier Inc. All rights reserved.