Gamma Knife surgery for metastatic brain tumors

Object The authors compared results of Gamma Knife surgery (GKS) for brain metastases obtained at 2 institutions in Japan. Methods They analyzed a consecutive series of 2390 patients with brain metastases who underwent GKS from 1998 through 2005 in 2 institutes (1181 patients in Chiba; 1209 in Mito). In the 2 facilities, 1 neurosurgeon each was responsible for diagnosis, patient selection, GKS procedures, and follow-up (T.S. in Chiba, M.Y. in Mito). Even if tumor numbers exceeded 4, all visible lesions were irradiated with a total skull integral dose (TSID) of ≤ 10–12 J. No prophylactic whole-brain radiotherapy (WBRT) was applied. If new distant lesions were detected, salvage GKS was appropriately performed. Results The distributions of patient and treatment factors did not differ between institutes. The most common primary tumors were lung cancer (1572 patients), followed by gastrointestinal tract (316), breast (211), kidney (113), and other cancers (159). The median survival periods were 7.7 months in Chiba and 7.0 months in Mito (p = 0.0635). The significant poor prognostic factors for overall survival were active extracranial disease status, male sex, and low initial Karnofsky Performance Scale score on multivariate analysis (all p < 0.0001). The neurological survival rates at 1 year were 86.6% in Chiba and 84.2% in Mito (p = 0.3310). Conclusions This 2-institute study demonstrated no significant institutional differences in any of the treatment result items. Gamma Knife surgery for brain metastases without prophylactic WBRT prevents neurological death and allows a patient to maintain good brain condition. However, there is 1 important patient selection criterion: regardless of how many tumors there are, all lesions can be irradiated with a TSID of ≤12 J.

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Gamma Knife surgery as sole treatment for multiple brain metastases: 2-center retrospective review of 1508 cases meeting the inclusion criteria of the JLGK0901 multi-institutional prospective study

Journal of Neurosurgery ◽

10.3171/2010.8.gks10838 ◽

2010 ◽

Vol 113 (Special_Supplement) ◽

pp. 48-52 ◽

Cited By ~ 37

Author(s):

Toru Serizawa ◽

Masaaki Yamamoto ◽

Yasunori Sato ◽

Yoshinori Higuchi ◽

Osamu Nagano ◽

...

Keyword(s):

Brain Metastases ◽

Gamma Knife ◽

Class Ii ◽

Hazard Ratio ◽

Gamma Knife Surgery ◽

Inclusion Criteria ◽

Primary Tumors ◽

Poor Prognostic Factor ◽

Group A ◽

Group B

Object The authors retrospectively reviewed the results of Gamma Knife surgery (GKS) used as the sole treatment for brain metastases in patients who met the eligibility criteria for the ongoing JLGK0901 multi-institutional prospective trial. They also discuss the anticipated results of the JLGK0901 study. Methods Data from 1508 consecutive cases were analyzed. All of the patients were treated at the Gamma Knife House of Chiba Cardiovascular Center or the Mito Gamma House of Katsuta Hospital between 1998 and 2007 and met the following JLGK0901 inclusion criteria: 1) newly diagnosed brain metastases, 2) 1–10 brain lesions, 3) less than 10 cm3 volume of the largest tumor, 4) no more than 15 cm3 total tumor volume, 5) no findings of CSF dissemination, and 6) no impairment of activities of daily living (Karnofsky Performance Scale score < 70) due to extracranial disease. At the initial treatment, all visible lesions were irradiated with GKS without upfront whole-brain radiation therapy. Thereafter, gadolinium-enhanced MR imaging was performed every 2–3 months, and new distant lesions were appropriately retreated with GKS. Patients were divided into groups according to numbers of tumors: Group A, single lesions (565 cases); Group B, 2–4 tumors (577 cases); and Group C, 5–10 tumors (366 cases). The differences in overall survival (OS) were compared between groups. Results The median age of the patients was 66 years (range 19–96 years). There were 963 men and 545 women. The primary tumors were in the lung in 1114 patients, gastrointestinal tract in 179, breast in 105, urinary tract in 66, and other sites in 44. The overall mean survival time was 0.78 years (0.99 years for Group A, 0.68 years for Group B, and 0.62 years for Group C). The differences between Groups A and B (p < 0.0001) and between Groups B and C (p = 0.0312) were statistically significant. Multivariate analysis revealed significant prognostic factors for OS to be sex (poor prognostic factor: male, p < 0.0001), recursive partitioning analysis class (Class I vs Class II and Class II vs III, both p < 0.0001), primary site (lung vs breast, p = 0.0047), and number of tumors (Group A vs Group B, p < 0.0001). However, no statistically difference was detected between Groups B and C (p = 0.1027, hazard ratio 1.124, 95% CI 0.999–1.265). Conclusions The results of this retrospective analysis revealed an upper CI of 1.265 for the hazard ratio, which was lower than the 1.3 initially set by the JLGK0901 study. The JLGK0901 study is anticipated to show noninferiority of GKS as sole treatment for patients with 5–10 brain metastases compared with those with 2–4 in terms of OS.

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Role of Gamma Knife surgery in patients with 5 or more brain metastases

Journal of Neurosurgery ◽

10.3171/2012.8.gks12983 ◽

2012 ◽

Vol 117 (Special_Suppl) ◽

pp. 5-12 ◽

Cited By ~ 23

Author(s):

Alireza Mohammad Mohammadi ◽

Pablo F. Recinos ◽

Gene H. Barnett ◽

Robert J. Weil ◽

Michael A. Vogelbaum ◽

...

Keyword(s):

Overall Survival ◽

Prognostic Factors ◽

Brain Metastases ◽

Gamma Knife ◽

Cleveland Clinic ◽

Salvage Treatment ◽

Gamma Knife Surgery ◽

Karnofsky Performance Scale ◽

Related Factors ◽

Extracranial Metastases

Object The authors evaluated overall survival and factors predicting outcome in patients with ≥ 5 brain metastases who were treated with Gamma Knife surgery (GKS). Methods Medical records from patients with ≥ 5 brain metastases treated with GKS between 1997 and 2010 at the Cleveland Clinic Gamma Knife Center were retrospectively reviewed. Patient demographics, tumor characteristics, treatment-related factors, and outcome data were evaluated. Results One hundred seventy patients were identified, with a median age of 58 years. The female/male ratio was 1.2:1. Gamma Knife surgery was used as an upfront treatment in 35% of patients and as salvage treatment in 65% of patients with multiple brain metastases. The median overall survival after GKS was 6.7 months (95% CI 5.5–8.1). At the time of GKS, 128 patients (75%) had concurrent extracranial metastases, and in 69 patients (41%) multiple extracranial sites were involved. Ninety-two patients (54%) had a history of whole-brain radiation therapy, and 158 patients (93%) had a Karnofsky Performance Scale (KPS) score ≥ 70. The median total intracranial disease volume was 3.2 cm3 (range 0.2–37.2 cm3). A total intracranial tumor volume ≥ 10 cm3 was observed in 32 patients (19%). Lower KPS score at the time of treatment (p < 0.0001), patient age > 60 years (p = 0.004), multiple extracranial metastases (p = 0.0001), and greater intracranial burden of disease (p = 0.03) were prognostic factors for poor outcome in the univariate and multivariate analyses. Conclusions In this study, GKS was safe and effective for upfront and salvage treatment in patients with ≥ 5 brain metastases. Gamma Knife surgery should be considered as an additional treatment modality for these patients, especially in the subset of patients with favorable prognostic factors.

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Clinical impact of magnetic resonance imaging on Gamma Knife surgery for brain metastases

Journal of Neurosurgery ◽

10.3171/sup.2006.105.7.69 ◽

2006 ◽

Vol 105 (Supplement) ◽

pp. 69-74 ◽

Cited By ~ 1

Author(s):

Julian R. Perks ◽

Tianxiao Liu ◽

William H. Hall ◽

Allan Y. Chen

Keyword(s):

Magnetic Resonance ◽

Mr Imaging ◽

Brain Metastases ◽

Thin Section ◽

Gamma Knife ◽

Medical Center ◽

Systemic Disease ◽

Gamma Knife Surgery ◽

Karnofsky Performance Scale ◽

Time Interval

ObjectStereotactic radiosurgery is beneficial for patients with a limited number of small brain metastases. Increased numbers of brain metastases, not infrequently at unreachable locations, are identified using thin-section magnetic resonance (MR) imaging on the day of Gamma Knife surgery (GKS). To improve patient selection and design better treatment strategies, a retrospective study was conducted to determine factors that may contribute to detecting additional brain metastases on the day of GKS.MethodsA total of 100 patients with brain metastases who underwent GKS between October 2003 and May 2006 at the University of California Davis Medical Center were included in the present study. Patients were categorized by age, sex, Karnofsky Performance Scale score, status of systemic disease, histological characteristics of the primary tumor, and whether they received previous whole-brain radiotherapy (WBRT). The number of lesions identified by diagnostic MR imaging at referral, by thin-section double-contrast MR imaging on the day of GKS, and the actual lesions treated by GKS were recorded. The diagnostic MR images were categorized in terms of section thickness and time interval before GKS.Conclusions The characteristics of this patient population match well with the general GKS practice. Fifty-six had been treated with WBRT. On average, patients presented with 2.2 ± 1.7 lesions, a number based on their original diagnostic MR imaging, had 3.6 ± 3.4 lesions identified on the thin-section treatment MR imaging (p < 0.05), and underwent treatment of 3.1 ± 2.6 lesions on the day of GKS. Significantly, treatment was compromised in 21 patients, in whom not all additional lesions could be treated with the initial headframe placement. Analysis shows that a significantly greater number of lesions were detected using thin-section MR imaging on the day of GKS in patients who had undergone thick-section diagnostic MR imaging, did not receive WBRT, and had progressive systemic disease. To optimize treatment planning and minimize additional treatment, the number of metastases needs to be determined accurately before frame placement, ideally by performing thin-section MR imaging, as used on the day of GKS.

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Do Recent Advances in MR Technologies Contribute to Better Gamma Knife Radiosurgery Treatment Results for Brain Metastases?

The Neuroradiology Journal ◽

10.1177/197140090702000501 ◽

2007 ◽

Vol 20 (5) ◽

pp. 481-490 ◽

Cited By ~ 3

Author(s):

M. Hayashi ◽

M. Yamamoto ◽

C. Nishimura ◽

H Satoh

Keyword(s):

Mr Imaging ◽

Brain Metastases ◽

Gamma Knife ◽

Gamma Knife Radiosurgery ◽

Lesion Size ◽

Neurological Deficits ◽

Consecutive Series ◽

Slice Thickness ◽

Treatment Results ◽

Primary Tumors

The detection of intracerebral lesions has improved greatly with advancements in MR imaging, especially the greater sensitivity of the 1.5 Tesla unit versus the older 1.0 Tesla unit. We aimed to determine whether improvements in MR imaging have actually improved diagnostic capabilities and treatment outcomes in gamma knife radiosurgery (GKRS) for brain metastases (METs). Ours was a retrospective study of a consecutive series of 1179 patients (441 females, 738 males, mean age: 63 years, range: 19–92 years) with brain METs who underwent GKRS from 1998 to 2004. Our treatment policy was to irradiate all lesions visible on MR images during a single GKRS session. Mean and median tumor numbers were seven and three (range; 1–74). The 1179 patients were divided into two groups: a 1.0 T-group of 660 patients examined using a 1.0 Tesla MR unit before August, 2002, and a 1.5 T-group of 519 examined using a 1.5 Tesla MR unit after September 2002. In the 1.5 T-group, lesion volumes as small as 0.004 cc were detected with a 5 mm slice thickness. The corresponding lesion size was 0.013 cc in the 1.0 T-group. One or more lesions invisible on a 5 mm slice study were additionally detected on a 2 mm slice study in 47.8% of patients in the 1.0 T-group and 25.2% in the 1.5 T-group (p<.0001). The median survival time (MST) in the 1.5 T-group was significantly longer than that in the 1.0 T-group (8.4 vs. 6.3 months, p=.0004). Due to biases in patient numbers between the two groups, we analyzed subgroups with KPS of 80% or better, no neurological deficits, stable primary tumors, lung cancer, tumor numbers of four or less and tumor volumes of 10.0 cc or smaller. In every subgroup analysis, the MSTs of the 1.5-Tesla group were significantly longer than those of the 1.0-Tesla group. The prognosis of a cancer patient is undoubtedly influenced by multiple factors. Nevertheless, we conclude that application of the 1.5 Tesla MR unit has had a favorable impact on diagnosis and GKRS treatment results in patients with brain METs.

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Gamma Knife surgery for multiple brain metastases from a malignant schwannoma of the penis

Journal of Neurosurgery ◽

10.3171/sup.2006.105.7.238 ◽

2006 ◽

Vol 105 (Supplement) ◽

pp. 238-240 ◽

Cited By ~ 4

Author(s):

Albertus T. C. J. van Eck ◽

Gerhard A. Horstmann

Keyword(s):

Brain Metastasis ◽

Brain Metastases ◽

Gamma Knife ◽

De Novo ◽

Tumor Resection ◽

Gamma Knife Surgery ◽

Malignant Schwannoma ◽

Efficacy And Safety ◽

Single Brain Metastasis ◽

Therapy Option

✓The occurrence of brain metastases from a malignant schwannoma of the penis is extremely rare. In patients with a single brain metastasis, microsurgical extirpation is the treatment of choice and verifies the diagnosis. In cases of multiple or recurrent metastases, radiosurgery is an effective and safe therapy option. Gamma Knife surgery was performed in a patient who had previously undergone tumor resection and who presented with recurrence of the lesion and three de novo brain metastases. This first report on brain metastasis from a malignant penile schwannoma illustrates the efficacy and safety of radiosurgical treatment for these tumors.

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Tumor recurrence and survival following gamma knife surgery for brain metastases

Journal of Neurosurgery ◽

10.3171/sup.2005.102.s_supplement.0287 ◽

2005 ◽

Vol 102 (Special_Supplement) ◽

pp. 287-288 ◽

Cited By ~ 2

Author(s):

Thomas Mindermann

Keyword(s):

Brain Metastasis ◽

Brain Metastases ◽

Gamma Knife ◽

Tumor Recurrence ◽

Patient Survival ◽

Gamma Knife Surgery ◽

Recurrence Rates ◽

Term Survival ◽

Content Type ◽

Fine Print

Object. The authors evaluated prognostic factors for tumor recurrence and patient survival following gamma knife surgery (GKS) for brain metastasis. Methods. A retrospective review of 101 patient charts was undertaken for those patients treated with GKS for brain metastases from 1994 to 2001. Recurrence rates of brain metastasis following GKS depended on the duration of patient survival. Long-term survival was associated with a higher risk of tumor recurrence and shorter-term survival was associated with a lower risk. The duration of survival following GKS for brain metastases seems to be characteristic of the primary disease rather than the cerebral disease. Conclusions. Recurrence rates of brain metastasis following GKS are related to duration of survival, which is in turn mostly dependent on the nature and course of the primary tumor.

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Prolonged survival in a subgroup of patients with brain metastases treated by gamma knife surgery

Journal of Neurosurgery ◽

10.3171/sup.2005.102.s_supplement.0262 ◽

2005 ◽

Vol 102 (Special_Supplement) ◽

pp. 262-265

Author(s):

C. P. Yu ◽

Joel Y. C. Cheung ◽

Josie F. K. Chan ◽

Samuel C. L. Leung ◽

Robert T. K. Ho

Keyword(s):

Brain Metastases ◽

Gamma Knife ◽

Patient Survival ◽

Gamma Knife Surgery ◽

Prolonged Survival ◽

Organ Involvement ◽

Lesion Volume ◽

Content Type ◽

The Mean ◽

Fine Print

Object. The authors analyzed the factors involved in determining prolonged survival (≥ 24 months) in patients with brain metastases treated by gamma knife surgery (GKS). Methods. Between 1995 and 2003, a total of 116 patients underwent 167 GKS procedures for brain metastases. There was no special case selection. Smaller and larger lesions were treated with different protocols. The mean patient age was 56.9 years, the mean number of initial lesions was 3.15, and the mean lesion volume was 10.45 cm.3 The mean follow-up time was 9.2 months. The median patient survival was 8.68 months. One-, 2-, 3-, 4-, and 5-year actuarial survival rates were 31.8%, 19.8%, 14.6%, 7.7%, and 6.9%, respectively. Patient age, number of lesions at presentation, and lesion volume had no influence on patient survival. Twenty-three (19.8%) patients survived for 24 months or more. Certain factors were associated with increased survival time. These were stable primary disease (21 of 23 patients), a long latency between diagnosis of the primary tumor and the occurrence of brain metastases (mean 28.4 months, median 16 months), absence of third-organ involvement, and repeated local procedures. Ten patients underwent repeated GKS (mean 3.4 per patient). Seven patients required open surgery for local treatment failures (recurrence or radiation necrosis). Two patients had both. Fifteen patients underwent repeated procedures. Conclusions. Aggressive local therapy with GKS, repeated GKS, and GKS plus surgery can achieve increased survival in a subgroup of patients with stable primary disease, no third-organ involvement, and long primary-brain secondary intervals.

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Incidence, timing, and treatment of new brain metastases after Gamma Knife surgery for limited brain disease: the case for reducing the use of whole-brain radiation therapy

Journal of Neurosurgery ◽

10.3171/2011.2.jns101724 ◽

2011 ◽

Vol 115 (1) ◽

pp. 37-48 ◽

Cited By ~ 9

Author(s):

Stephen Rush ◽

Robert E. Elliott ◽

Amr Morsi ◽

Nisha Mehta ◽

Jeri Spriet ◽

...

Keyword(s):

Radiation Therapy ◽

Brain Metastases ◽

Gamma Knife ◽

Gamma Knife Surgery ◽

Whole Brain Radiation Therapy ◽

Leptomeningeal Disease ◽

Whole Brain ◽

Whole Brain Radiation ◽

Brain Radiation

Object In this paper, the authors' goal was to analyze the incidence, timing, and treatment of new metastases following initial treatment with 20-Gy Gamma Knife surgery (GKS) alone in patients with limited brain metastases without whole-brain radiation therapy (WBRT). Methods A retrospective analysis of 114 consecutive adults (75 women and 34 men; median age 61 years) with KPS scores of 60 or higher who received GKS for 1–3 brain metastases ≤ 2 cm was performed (median lesion volume 0.35 cm3). Five patients lacking follow-up data were excluded from analysis. After treatment, patients underwent MR imaging at 6 weeks and every 3 months thereafter. New metastases were preferentially treated with additional GKS. Indications for WBRT included development of numerous metastases, leptomeningeal disease, or diffuse surgical-site recurrence. Results The median overall survival from GKS was 13.8 months. Excluding the 3 patients who died before follow-up imaging, 12 patients (11.3%) experienced local failure at a median of 7.4 months. Fifty-three patients (50%) developed new metastases at a median of 5 months. Six (7%) of 86 instances of new lesions were symptomatic. Most patients (67%) with distant failures were successfully treated using salvage GKS alone. Whole-brain radiotherapy was indicated in 20 patients (18.3%). Thirteen patients (11.9%) died of neurological disease. Conclusions For patients with limited brain metastases and functional independence, 20-Gy GKS provides excellent disease control and high-functioning survival with minimal morbidity. New metastases developed in almost 50% of patients, but additional GKS was extremely effective in controlling disease. Using our algorithm, fewer than 20% of patients required WBRT, and only 12% died of progressive intracranial disease.

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Neurological complications and symptom resolution following Gamma Knife surgery for brain metastases 2 cm or smaller in relation to eloquent cortices

Journal of Neurosurgery ◽

10.3171/2010.7.gks101047 ◽

2010 ◽

Vol 113 (Special_Supplement) ◽

pp. 53-64 ◽

Cited By ~ 6

Author(s):

Robert E. Elliott ◽

Stephen Rush ◽

Amr Morsi ◽

Nisha Mehta ◽

Jeri Spriet ◽

...

Keyword(s):

Brain Metastases ◽

Gamma Knife ◽

Neurological Complications ◽

Gamma Knife Surgery ◽

Neurological Deterioration ◽

Neurological Deficits ◽

Lesion Volume ◽

Symptom Resolution ◽

Grade Ii ◽

Grade Iii

Object Reports on resection of tumors in or near eloquent cortices have noted neurological complications in up to 30% of patients. This paper contains an analysis of symptom resolution and neurological morbidity following 20-Gy Gamma Knife surgery (GKS) for supratentorial brain metastases ≤ 2 cm in greatest diameter. Methods The authors performed a retrospective analysis of 98 consecutively treated adults (33 men and 65 women with a median age of 61.4 years at the time of GKS) with Karnofsky Performance Scale score ≥ 60, who underwent GKS for supratentorial brain metastases ≤ 2 cm in diameter. Lesion location was classified as noneloquent (Grade I), near eloquent (Grade II), or eloquent (Grade III), in accordance with the grading system developed by the group at M. D. Anderson Cancer Center. Following treatment, the patients underwent MR imaging and clinical examinations at 6 weeks and every 3 months thereafter. Results Ninety-eight patients underwent 20-Gy GKS for 131 metastases at initial presentation and 31 patients underwent salvage 20-Gy GKS for 76 new lesions, for a total of 207 lesions (mean lesion volume 0.44 cm3). Lesions were classified as follows: Grade I, 96 (46.4%); Grade II, 51 (24.6%); and Grade III, 60 (29%). Fifteen patients (2 with Grade II and 13 with Grade III lesions) presented with deficits referable to their lesions, yielding pre-GKS deficit rates of 7.2% per lesion and 15.3% per patient. The pre-GKS deficits improved or resolved in 10 patients (66.7%) at a median time of 2.8 months and remained stable in 3 patients (20%). Two patients (13.3%) experienced worsened neurological deficits. One patient who was neurologically intact prior to treatment developed a new hemiparesis (1 of 83 patients [1.2%]). The rates of permanent neurological deterioration following GKS for Grades I, II, and III lesions were 0% (0 of 96 tumors), 2% (1 of 51), and 3.3% (2 of 60), respectively. The pre-GKS neurological deficits and larger lesions were the most significant risk factors for post-GKS neurological deterioration. Conclusions Gamma Knife surgery performed using a 20-Gy dose provides amelioration of neurological deficits from brain metastases that are ≤ 2 cm in diameter and located in or near eloquent cortices in nearly two-thirds of patients with a low incidence of morbidity. Consistent with the surgical literature, higher rates of neurological complications were observed as proximity to eloquent regions and lesion size increased. There was no neurological deterioration in patients harboring metastases in noneloquent areas.

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