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.

Histology-stratified tumor control and patient survival following stereotactic radiosurgery for pineal region tumors: a report from the International Gamma Knife Research Foundation
Iorio-Morin C, Kano H, Huang M, Lunsford LD, Simonová G Liscak R, Cohen-Inbar O, Sheehan J, Lee CC, Wu HM, Mathieu D. World Neurosurg. 2017 Jul 24
PMID: 28751141

Abstract

OBJECT:
Pineal region tumors represent a rare and histologically diverse group of lesions. Few studies are available to guide management and the outcomes following stereotactic radiosurgery (SRS) are unknown for many histologies.

METHODS:
Patients who underwent SRS for a pineal region tumor and for whom at least 6 months of imaging follow-up was available were retrospectively assessed in five centers. Data was collected from the medical record and histology-level analyses were performed, including actuarial tumor control and survival analyses.

RESULTS:
70 patients were treated between 1989 and 2014 with a median follow-up of 47 months. Diagnoses were pineocytoma (37%), pineoblastoma (19%), pineal parenchymal tumor of intermediate differentiation (PPTID) (10%), papillary tumor of the pineal region (PTPR) (9%), germinoma (7%), teratoma (3%), embryonal carcinoma (1%) and unknown (14%). Median prescription dose was 15 Gy at the 50% isodose line. Actuarial local control and survival rates were: 81% and 76% at 20 years for pineocytoma, 50% and 56% at 5 years for PPTID, 27% and 48% at 5 years for pineoblastoma, 33% and 100% at 5 years for PTPR, 80% and 80% at 20 years for germinoma, and 61% and 67% at 5 years for tumors of unknown histology. New focal neurological deficit, Parinaud’s syndrome and hydrocephalus occurred in 9%, 7% and 3% of cases respectively.

CONCLUSIONS:
SRS is a safe modality for the management of pineal region tumors. Its specific role is highly dependent on tumor histology. As such, all efforts should be made to obtain a reliable histological diagnosis.

The emerging role of gamma knife radiosurgery in the management of glossopharyngeal neuralgia
Spina A, Boari N, Gagliardi F, Bailo M, Morselli C, Iannaccone S, Mortini P. Neurosurg Rev. 2017 Jul 26.
PMID: 28748271

Abstract

Glossopharyngeal neuralgia (GPN) represents a rare craniofacial disorder accounting for about 1% of all craniofacial pain syndromes. GPN shares several pathophysiologic and clinical features with the more common trigeminal neuralgia. Medical therapy and microvascular decompression, in case of vascular nerve compression, represented the mainstay of GPN management. Other ablative therapies have been reported to date; however, few data are available because of the rarity of this pain syndrome. Among the ablative procedures, gamma knife radiosurgery (GKRS) has been recently introduced in the management of GPN with good pain control and low complication rates. Authors performed a systematic review of the published literature about GKRS in the management of GPN. Radiosurgical treatment data, pain control and recurrence rate have been analysed and compared. GKRS represented a valuable and effective treatment option for the management of GPN. Pain control and complication rates are better than those reported by other ablative procedures and microvascular decompression; however, future studies should be focused on the long-term efficacy of GKRS.

Cumulative Intracranial Tumor Volume and Number of Brain Metastasis as Predictors of Developing New Lesions after Stereotactic Radiosurgery for Brain Metastasis
Sharma M, Jia X, Ahluwalia M, Barnett GH, Vogelbaum MA, Chao ST, Suh JH, Murphy ES, Yu JS, Angelov L, Mohammadi AM. World Neurosurg. 2017 Jul 19.
PMID: 28735139

Abstract

INTRODUCTION

The aim of our study was to identify risk factors associated with early distant radiographic progression in patients undergoing stereotactic radiosurgery (SRS) for brain metastases (BM).

METHODS

Following IRB approval, data of 1427 patients (4283 BM lesions) who were treated using SRS at Cleveland Clinic from 2000-2012 were collected. Local tumor progression (LTP), distant tumor progression (DTP) and radiographic radiation necrosis (RN) were the primary end points. Patient, imaging, radiosurgery, and tumor variables and follow-up data were collected.

RESULTS

The median number of targets was 2 (range 1-17) with 45% of patients having a single lesion. DTP was observed in 10% and 19% at 3 and 6 months, respectively. Patients with 5-10 target lesions for SRS were more likely to develop new lesions at both 3 and 6 months compared to those with 2-4 lesions (OR: 0.83, CI: 0.40-0.85 and OR:0.85, CI: 0.45-0.86 respectively, p<0.05). Younger age (<65 years) [p<0.001], higher number of lesions (>1) [p <0.001], cumulative intracranial tumor volume (CITV) (< 2.75 cc) [p=0.023], type of SRS (upfront and salvage vs boost) [p <0.001] and tumor pathology (radiosensitive) [p <0.001], were independent predictors of early distant tumor progression following SRS.

CONCLUSION

Number of target lesions and low CITV are both independent predictors of early DTP following SRS for BM. Radiosensitive tumor histology, younger patients (<65 years of age) and SRS without prior WBRT (upfront or salvage) are also predictors of early DTP.

Survival patterns of 5750 SRS-treated brain metastasis patients as a function of the number of lesions
Ali MA, Hirshman BR, Wilson B, Carroll KT, Proudfoot JA, Goetsch SJ, Alksne JF, Ott K, Aiyama H, Nagano O, Carter BS, Fogarty G, Hong A, Serizawa T, Yamamoto M, Chen CC. World Neurosurg. 2017 Jul 19.
PMID: 28735121

Abstract

BACKGROUND:

The number of brain metastases (BM) plays an important role in the decision between stereotactic radiosurgery (SRS) and whole brain radiation therapy (WBRT).

METHODS:

We analyzed the survival of 5750 SRS-treated BM patients as a function of BM number. Survival analyses were performed using Kaplan-Meier analysis as well as univariate and multivariate Cox proportional hazards models.

RESULTS:

BM patients were first categorized as those with 1, 2-4, and 5-10 BM based on the scheme proposed by Yamamoto et al (Lancet Oncology 2014). Median overall survival for patients with 1 BM was superior to those with 2-4 BMs (7.1 mo v. 6.4 mo, p=0.009), and survival of patients with 2-4 BMs did not differ from those with 5-10 BMs (6.4 mo v. 6.3 mo, p=0.170). The median survival of patients with >10 BMs was lower than those with 2-10 BMs (6.3 mo v. 5.5 mo, p=0.025). In a multivariate model that accounted for age, Karnofsky Performance Score (KPS), systemic disease status, tumor histology, and cumulative intracranial tumor volume (CITV), we observed a ∼10% increase in hazard of death when comparing patients with 1 versus 2-10 BM (p<0.001) or 10 versus >10 BM (p<0.001). When BM number was modeled as a continuous variable rather than using the Yamamoto classification, we observed a step-wise 5% increase in the hazard of death for every increment of 5-6 BM (p<0.001).

CONCLUSIONS:

The contribution of BM number to overall survival is modest, and should be considered as one of the many variables considered in the decision between SRS and WBRT.

Stereotactic Radiosurgery for Trigeminal Neuralgia Improves Patient-Reported Quality of Life and Reduces Depression
Kotecha R, Miller JA, Modugula S, Barnett GH, Murphy ES, Reddy CA, Suh JH, Neyman G, Machado A, Nagel S, Chao ST. Int J Radiat Oncol Biol Phys. 2017 Aug 1;98(5):1078-1086.
PMID:28721891

Abstract

PURPOSE

To characterize quality-of-life (QOL) outcomes after stereotactic radiosurgery (SRS) for trigeminal neuralgia (TN).

METHODS AND MATERIALS

The EuroQOL 5 Dimensions (EQ-5D) and Patient Health Questionnaire 9 (PHQ-9) were prospectively collected before and after SRS for 50 patients with TN. Pain response and treatment-related facial numbness were classified by Barrow Neurological Institute (BNI) scales. Differences in pooled QOL outcomes were tested with paired t tests and sign tests. The Kaplan-Meier method was used to estimate time-dependent improvements in the EQ-5D index, EQ-5D perceived health status (PHS), PHQ-9 score, and freedom from pain failure (BNI class IV-V) or facial numbness (BNI class III-IV).

RESULTS

Following SRS, the 12-month rate of freedom from pain failure was 92% (95% confidence interval [CI], 77%-97%) while the 12-month rate of freedom from facial numbness was 89% (95% CI, 66%-97%). Significant improvements in the EQ-5D index (P<.01), PHS (P=.01), and PHQ-9 (P=.03) were observed, driven by the EQ-5D subscores for self-care and for pain and/or discomfort (P=.02 and P<.01, respectively). At 12 months after SRS, the actuarial rates of improvement in the EQ-5D, PHS, and PHQ-9 were 55% (95% CI, 40%-70%), 59% (95% CI, 40%-76%), and 59% (95% CI, 39%-76%), respectively. The median time to improvement in each of the QOL measures was 9 months (95% CI, 3-36 months) for the EQ-5D index, 5 months (95% CI, 3-36 months) for PHS, and 9 months (95% CI, 3-18 months) for the PHQ-9. On multivariate analysis, only higher prescription dose (86 Gy vs ≤82 Gy) was associated with improvement in the EQ-5D index (hazard ratio, 5.73; 95% CI, 1.85-22.33; P<.01).

CONCLUSIONS

Patients with TN treated with SRS reported significant improvements in multiple QOL measures, with the therapeutic benefit strongly driven by improvements in pain and/or discomfort and in self-care, along with lower rates of depression. In this analysis, there appears to be a correlation between prescription dose and treatment response as measured by the EQ-5D.

Gamma Knife radiosurgery for large vestibular schwannomas greater than 3 cm in diameter
Huang CW, Tu HT, Chuang CY, Chang CS, Chou HH, Lee MT, Huang CF. J Neurosurg. 2017 Jul 14:1-8.
PMID:28707997

Abstract

OBJECTIVE
Stereotactic radiosurgery (SRS) is an important alternative management option for patients with small- and medium-sized vestibular schwannomas (VSs). Its use in the treatment of large tumors, however, is still being debated. The authors reviewed their recent experience to assess the potential role of SRS in larger-sized VSs. METHODS Between 2000 and 2014, 35 patients with large VSs, defined as having both a single dimension > 3 cm and a volume > 10 cm3, underwent Gamma Knife radiosurgery (GKRS). Nine patients (25.7%) had previously undergone resection. The median total volume covered in this group of patients was 14.8 cm3 (range 10.3-24.5 cm3). The median tumor margin dose was 11 Gy (range 10-12 Gy).

RESULTS
The median follow-up duration was 48 months (range 6-156 months). All 35 patients had regular MRI follow-up examinations. Twenty tumors (57.1%) had a volume reduction of greater than 50%, 5 (14.3%) had a volume reduction of 15%-50%, 5 (14.3%) were stable in size (volume change < 15%), and 5 (14.3%) had larger volumes (all of these lesions were eventually resected). Four patients (11.4%) underwent resection within 9 months to 6 years because of progressive symptoms. One patient (2.9%) had open surgery for new-onset intractable trigeminal neuralgia at 48 months after GKRS. Two patients (5.7%) who developed a symptomatic cyst underwent placement of a cystoperitoneal shunt. Eight (66%) of 12 patients with pre-GKRS trigeminal sensory dysfunction had hypoesthesia relief. One hemifacial spasm completely resolved 3 years after treatment. Seven patients with facial weakness experienced no deterioration after GKRS. Two of 3 patients with serviceable hearing before GKRS deteriorated while 1 patient retained the same level of hearing. Two patients improved from severe hearing loss to pure tone audiometry less than 50 dB. The authors found borderline statistical significance for post-GKRS tumor enlargement for later resection (p = 0.05, HR 9.97, CI 0.99-100.00). A tumor volume ≥ 15 cm3 was a significant factor predictive of GKRS failure (p = 0.005). No difference in outcome was observed based on indication for GKRS (p = 0.0761).

CONCLUSIONS
Although microsurgical resection remains the primary management choice in patients with VSs, most VSs that are defined as having both a single dimension > 3 cm and a volume > 10 cm3 and tolerable mass effect can be managed satisfactorily with GKRS. Tumor volume ≥ 15 cm3 is a significant factor predicting poor tumor control following GKRS.

Postoperative stereotactic radiosurgery compared with whole brain radiotherapy for resected metastatic brain disease (NCCTG N107C/CEC·3): a multicentre, randomised, controlled, phase 3 trial
Brown PD, Ballman KV, Cerhan JH, Anderson SK, Carrero XW, Whitton AC, Greenspoon J, Parney IF, Laack NNI, Ashman JB, Bahary JP, Hadjipanayis CG, Urbanic JJ, Barker FG 2nd, Farace E, Khuntia D, Giannini C, Buckner JC, Galanis E, Roberge D. Lancet Oncol. 2017 Aug;18(8):1049-1060.
PMID:28687377

Abstract

BACKGROUND
Whole brain radiotherapy (WBRT) is the standard of care to improve intracranial control following resection of brain metastasis. However, stereotactic radiosurgery (SRS) to the surgical cavity is widely used in an attempt to reduce cognitive toxicity, despite the absence of high-level comparative data substantiating efficacy in the postoperative setting. We aimed to establish the effect of SRS on survival and cognitive outcomes compared with WBRT in patients with resected brain metastasis.

METHODS
In this randomised, controlled, phase 3 trial, adult patients (aged 18 years or older) from 48 institutions in the USA and Canada with one resected brain metastasis and a resection cavity less than 5•0 cm in maximal extent were randomly assigned (1:1) to either postoperative SRS (12-20 Gy single fraction with dose determined by surgical cavity volume) or WBRT (30 Gy in ten daily fractions or 37•5 Gy in 15 daily fractions of 2•5 Gy; fractionation schedule predetermined for all patients at treating centre). We randomised patients using a dynamic allocation strategy with stratification factors of age, duration of extracranial disease control, number of brain metastases, histology, maximal resection cavity diameter, and treatment centre. Patients and investigators were not masked to treatment allocation. The co-primary endpoints were cognitive-deterioration-free survival and overall survival, and analyses were done by intention to treat. We report the final analysis. This trial is registered with ClinicalTrials.gov, number NCT01372774.

FINDINGS
Between Nov 10, 2011, and Nov 16, 2015, 194 patients were enrolled and randomly assigned to SRS (98 patients) or WBRT (96 patients). Median follow-up was 11•1 months (IQR 5•1-18•0). Cognitive-deterioration-free survival was longer in patients assigned to SRS (median 3•7 months [95% CI 3•45-5•06], 93 events) than in patients assigned to WBRT (median 3•0 months [2•86-3•25], 93 events; hazard ratio [HR] 0•47 [95% CI 0•35-0•63]; p<0•0001), and cognitive deterioration at 6 months was less frequent in patients who received SRS than those who received WBRT (28 [52%] of 54 evaluable patients assigned to SRS vs 41 [85%] of 48 evaluable patients assigned to WBRT; difference -33•6% [95% CI -45•3 to -21•8], p<0•00031). Median overall survival was 12•2 months (95% CI 9•7-16•0, 69 deaths) for SRS and 11•6 months (9•9-18•0, 67 deaths) for WBRT (HR 1•07 [95% CI 0•76-1•50]; p=0•70). The most common grade 3 or 4 adverse events reported with a relative frequency greater than 4% were hearing impairment (three [3%] of 93 patients in the SRS group vs eight [9%] of 92 patients in the WBRT group) and cognitive disturbance (three [3%] vs five [5%]). There were no treatment-related deaths.

INTERPRETATION
Decline in cognitive function was more frequent with WBRT than with SRS and there was no difference in overall survival between the treatment groups. After resection of a brain metastasis, SRS radiosurgery should be considered one of the standards of care as a less toxic alternative to WBRT for this patient population.

Dejerine-Roussy syndrome from thalamic metastasis treated with stereotactic radiosurgery
Patel RA, Chandler JP, Jain S, Gopalakrishnan M, Sachdev S. J Clin Neurosci. 2017 Jul 3.
PMID:28684151

Abstract

Dejerine-Roussy syndrome (central thalamic pain) is associated with damage to the ventral posterior sensory nuclei of the thalamus. We report a patient with breast cancer who developed contralateral hemibody paresthesias and dysesthesias. MR imaging revealed limited volume intracranial metastatic disease including a right posterior thalamic lesion. Stereotactic radiosurgery was utilized to selectively treat the lesion while preserving the remaining thalamus. Two months following treatment, the patient reported vastly improved to complete resolution of her sensory symptoms. This is the first reported case of thalamic tumor directed radiosurgical treatment leading to resolution of central neuropathic pain.

Comparison of WBRT alone, SRS alone, and their combination in the treatment of one or more brain metastases: Review and meta-analysis
Khan M, Lin J, Liao G, Li R, Wang B, Xie G, Zheng J, Yuan Y. Tumour Biol. 2017 Jul;39(7)
PMID:28675121

Abstract

Whole brain radiotherapy has been a standard treatment of brain metastases. Stereotactic radiosurgery provides more focal and aggressive radiation and normal tissue sparing but worse local and distant control. This meta-analysis was performed to assess and compare the effectiveness of whole brain radiotherapy alone, stereotactic radiosurgery alone, and their combination in the treatment of brain metastases based on randomized controlled trial studies. Electronic databases (PubMed, MEDLINE, Embase, and Cochrane Library) were searched to identify randomized controlled trial studies that compared treatment outcome of whole brain radiotherapy and stereotactic radiosurgery. This meta-analysis was performed using the Review Manager (RevMan) software (version 5.2) that is provided by the Cochrane Collaboration. The data used were hazard ratios with 95% confidence intervals calculated for time-to-event data extracted from survival curves and local tumor control rate curves. Odds ratio with 95% confidence intervals were calculated for dichotomous data, while mean differences with 95% confidence intervals were calculated for continuous data. Fixed-effects or random-effects models were adopted according to heterogeneity. Five studies (n = 763) were included in this meta-analysis meeting the inclusion criteria. All the included studies were randomized controlled trials. The sample size ranged from 27 to 331. In total 202 (26%) patients with whole brain radiotherapy alone, 196 (26%) patients receiving stereotactic radiosurgery alone, and 365 (48%) patients were in whole brain radiotherapy plus stereotactic radiosurgery group. No significant survival benefit was observed for any treatment approach; hazard ratio was 1.19 (95% confidence interval: 0.96-1.43, p = 0.12) based on three randomized controlled trials for whole brain radiotherapy only compared to whole brain radiotherapy plus stereotactic radiosurgery and hazard ratio was 1.03 (95% confidence interval: 0.82-1.29, p = 0.81) for stereotactic radiosurgery only compared to combined approach. Local control was best achieved when whole brain radiotherapy was combined with stereotactic radiosurgery. Hazard ratio 2.05 (95% confidence interval: 1.36-3.09, p = 0.0006) and hazard ratio 1.84 (95% confidence interval: 1.26-2.70, p = 0.002) were obtained from comparing whole brain radiotherapy only and stereotactic radiosurgery only to whole brain radiotherapy + stereotactic radiosurgery, respectively. No difference in adverse events for treatment difference; odds ratio 1.16 (95% confidence interval: 0.77-1.76, p = 0.48) and odds ratio 0.92 (95% confidence interval: 0.59-1.42, p = 71) for whole brain radiotherapy + stereotactic radiosurgery versus whole brain radiotherapy only and whole brain radiotherapy + stereotactic radiosurgery versus stereotactic radiosurgery only, respectively. Adding stereotactic radiosurgery to whole brain radiotherapy provides better local control as compared to whole brain radiotherapy only and stereotactic radiosurgery only with no difference in radiation related toxicities.

Postoperative stereotactic radiosurgery for resected brain metastases: A comparison of outcomes for large resection cavities
Zhong J, Ferris MJ, Switchenko J, Press RH, Buchwald Z, Olson JJ, Eaton BR, Curran WJ, Shu HG, Crocker IR, Patel KR. Pract Radiat Oncol. 2017 Apr 26.
PMID:28668668

Abstract

PURPOSE
Although historical trials have established the role of surgical resection followed by whole brain irradiation (WBRT) for brain metastases, WBRT has recently been shown to cause significant neurocognitive decline. Many practitioners have employed postoperative stereotactic radiosurgery (SRS) to tumor resection cavities to increase local control without causing significant neurocognitive sequelae. However, studies analyzing outcomes of large brain metastases treated with resection and postoperative SRS are lacking. Here we compare outcomes in patients with large brain metastases >4 cm to those with smaller metastases ≤4 cm treated with surgical resection followed by SRS to the resection cavity.

METHODS AND MATERIALS
Consecutive patients with brain metastases treated at our institution with surgical resection and postoperative SRS were retrospectively reviewed. Patients were stratified into ≤4 cm and >4 cm cohorts based on preoperative maximal tumor dimension. Cumulative incidence of local failure, radiation necrosis, and death were analyzed for the 2 cohorts using a competing-risk model, defined as the time from SRS treatment date to the measured event, death, or last follow-up.

RESULTS
A total of 117 consecutive cases were identified. Of these patients, 90 (77%) had preoperative tumors ≤4 cm, and 27 (23%) >4 cm in greatest dimension. The only significant baseline difference between the 2 groups was a higher proportion of patients who underwent gross total resection in the ≤4 cm compared with the >4 cm cohort, 76% versus 48%, respectively (P <.01). The 1-year rates of local failure, radiation necrosis, and overall survival for the ≤4 cm and >4 cm cohorts were 12.3% and 16.0%, 26.9% and 28.4%, and 80.6% and 67.6%, respectively (all P >.05). The rates of local failure and radiation necrosis were not statistically different on multivariable analysis based on tumor size.

CONCLUSIONS
Brain metastases >4 cm in largest dimension managed by resection and radiosurgery to the tumor cavity have promising local control rates without a significant increase in radiation necrosis on our retrospective review.

Stereotactic radiosurgery for medically refractory multiple sclerosis-related tremor
Raju SS, Niranjan A, Monaco EA 3rd, Flickinger JC, Lunsford LD. J Neurosurg. 2017 Jun 30:1-8.
PMID:28665251

Abstract

OBJECTIVE
Multiple sclerosis (MS) is a neurodegenerative disease that can lead to severe intention tremor in some patients. In several case reports, conventional radiotherapy has been reported to possibly exacerbate MS. Radiosurgery dramatically limits normal tissue irradiation to potentially avoid such a problem. Gamma Knife thalamotomy (GKT) has been established as a minimally invasive technique that is effective in treating essential tremor and Parkinson’s disease-related tremor. The goal in this study was to analyze the outcomes of GKT in patients suffering from medically refractory MS-related tremor.

METHODS
The authors retrospectively studied the outcomes of 15 patients (mean age 46.5 years) who had undergone GKT over a 15-year period (1998-2012). Fourteen patients underwent GKT at a median maximum dose of 140 Gy (range 130-150 Gy) using a single 4-mm isocenter. One patient underwent GKT at a dose of 140 Gy delivered via two 4-mm isocenters (3 mm apart). The posteroinferior region of the nucleus ventralis intermedius (VIM) was the target for all GKTs. The Fahn-Tolosa-Marin clinical tremor rating scale was used to evaluate tremor, handwriting, drawing, and drinking. The median time to the last follow-up was 39 months.

RESULTS
After GKT, 13 patients experienced tremor improvement on the side contralateral to surgery. Four patients noted tremor arrest at a median of 4.5 months post-GKT. Seven patients had excellent tremor improvement and 6 had good tremor improvement. Four patients noted excellent functional improvement, 8 noted good functional improvement, and 1 noted satisfactory functional improvement. Three patients experienced diminished tremor relief at a median of 18 months after radiosurgery. Two patients experienced temporary adverse radiation effects. Another patient developed a large thalamic cyst 60 months after GKT, which was successfully managed with Ommaya reservoir placement.

CONCLUSIONS
Gamma Knife thalamotomy was found to be a minimally invasive and beneficial procedure for medically refractory MS tremor.