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1.  Clinical Outcome in Gamma Knife Radiosurgery for Metastatic Brain Tumors from the Primary Breast Cancer : Prognostic Factors in Local Treatment Failure and Survival 
Brain metastases in primary breast cancer patients are considerable sources of morbidity and mortality. Gamma knife radiosurgery (GKRS) has gained popularity as an up-front therapy in treating such metastases over traditional radiation therapy due to better neurocognitive function preservation. The aim of this study was to clarify the prognostic factors for local tumor control and survival in radiosurgery for brain metastases from primary breast cancer.
From March 2001 to May 2011, 124 women with metastatic brain lesions originating from a primary breast cancer underwent GKRS at a tertiary medical center in Seoul, Korea. All patients had radiosurgery as a primary treatment or salvage therapy. We retrospectively reviewed their clinical outcomes and radiological responses. The end point of this study was the date of patient's death or the last follow-up examination.
In total, 106 patients (268 lesions) were available for follow-up imaging. The median follow-up time was 7.5 months. The mean treated tumor volume at the time of GKRS was 6273 mm3 (range, 4.5-27745 mm3) and the median dose delivered to the tumor margin was 22 Gy (range, 20-25 Gy). Local recurrence was assessed in 86 patients (216 lesions) and found to have occurred in 36 patients (83 lesions, 38.6%) with a median time of 6 months (range, 4-16 months). A treated tumor volume >5000 mm3 was significantly correlated with poor local tumor control through a multivariate analysis (hazard risk=7.091, p=0.01). Overall survival was 79.9%, 48.3%, and 15.3% at 6, 12, and 24 months, respectively. The median overall survival was 11 months after GKRS (range, 6 days-113 months). Multivariate analysis showed that the pre-GKRS Karnofsky performance status, leptomeningeal seeding prior to initial GKRS, and multiple metastatic lesions were significant prognostic factors for reduced overall survival (hazard risk=1.94, p=0.001, hazard risk=7.13, p<0.001, and hazard risk=1.46, p=0.046, respectively).
GKRS has shown to be an effective and safe treatment modality for treating brain metastases of primary breast cancer. Most metastatic brain lesions initially respond to GKRS, though, many patients have further CNS progression in subsequent periods. Patients with poor Karnofsky performance status and multiple metastatic lesions are at risk of CNS progression and poor survival, and a more frequent and strict surveillance protocol is suggested in such high-risk groups.
PMCID: PMC3841276  PMID: 24294457
Breast cancer; Metastases; Gamma knife radiosurgery; Prognosis
2.  The Role of Radiosurgery in Patients with Brain Metastasis from Small Cell Lung Carcinoma 
The purpose of this retrospective study was to evaluate the outcome of gamma knife radiosurgery (GKRS) and/or whole brain radiation therapy (WBRT) for the treatment of small cell lung carcinoma (SCLC) metastasis to the brain.
From 2000 to 2010, 50 patients underwent GKRS for metastatic brain lesions originating from SCLC. Among these patients, 11 received prophylactic cranial irradiation (PCI) before the development of metastatic lesions (PCI group), and GKRS was performed as an initial treatment for newly diagnosed lesions in 12 patients who had not received PCI (primary GKRS group). In addition, GKRS was performed as a salvage treatment for progressive lesions after WBRT in 27 patients (salvage GKRS group). The medical records and imaging data of all patients were retrospectively analyzed.
The overall survival of the 50 patients was 20.8 months (range 1-53) after the diagnosis of primary tumor and 12.0 months (range 1-47) after the development of cerebral metastasis. Median survival after GKRS was 4.8 months (range 1-15) in the PCI group, 4.6 months (range 0-18) in the primary GKRS group, and 7.6 months (range 0-33) in the salvage GKRS group. Further treatment for progressive lesions after GKRS was necessary in 15 patients, after a mean interval of 3.8 months. Causes of death were systemic organ failure in 15 patients, deterioration of neurological state in 13 patients, and unknown or combined causes in 16 patients. The local control rate of the lesions treated with GKRS was 76.4% (decreased in 13 patients and stable in 16 patients at the final imaging follow-up (mean 5.60 months).
GKRS is an effective local treatment for brain metastasis from SCLC both as an initial treatment for newly diagnosed lesions after PCI and as a salvage treatment for recurrent or progressive lesions. However, the survival benefit is not significant because most patients die of systemic multi-organ failure with a short life expectancy.
PMCID: PMC3206286  PMID: 22053227
Small cell lung carcinoma; Radiosurgery; Gamma knife; Metastasis
3.  Gamma Knife Radiosurgery for Brainstem Metastasis 
Brainstem metastases are rarely operable and generally unresponsive to conventional radiation therapy or chemotherapy. Recently, Gamma Knife Radiosurgery (GKRS) was used as feasible treatment option for brainstem metastasis. The present study evaluated our experience of brainstem metastasis which was treated with GKRS.
Between November 1992 and June 2010, 32 patients (23 men and 9 women, mean age 56.1 years, range 39-73) were treated with GKRS for brainstem metastases. There were metastatic lesions in pons in 23, the midbrain in 6, and the medulla oblongata in 3 patients, respectively. The primary tumor site was lung in 21, breast in 3, kidney in 2 and other locations in 6 patients. The mean tumor volume was 1,517 mm3 (range, 9-6,000), and the mean marginal dose was 15.9 Gy (range, 6-23). Magnetic Resonance Imaging (MRI) was obtained every 2-3 months following GKRS. Follow-up MRI was possible in 24 patients at a mean follow-up duration of 12.0 months (range, 1-45). Kaplan-Meier survival analysis was used to evaluate the prognostic factors.
Follow-up MRI showed tumor disappearance in 6, tumor shrinkage in 14, no change in tumor size in 1, and tumor growth in 3 patients, which translated into a local tumor control rate of 87.5% (21 of 24 tumors). The mean progression free survival was 12.2 months (range, 2-45) after GKRS. Nine patients were alive at the completion of the study, and the overall mean survival time after GKRS was 7.7 months (range, 1-22). One patient with metastatic melanoma experienced intratumoral hemorrhage during the follow-up period. Survival was found to be associated with score of more than 70 on Karnofsky performance status and low recursive partitioning analysis class (class 1 or 2), in terms of favorable prognostic factors.
GKRS was found to be safe and effective for management of brainstem metastasis. The integral clinical status of patient seems to be important in determining the overall survival time.
PMCID: PMC3243831  PMID: 22200010
Brainstem tumor; Gamma knife radiosurgery; Metastasis; Stereotactic radiosurgery
4.  Gamma knife radiosurgery for elderly patients with brain metastases: evaluation of scoring systems that predict survival 
BMC Cancer  2015;15:54.
Gamma knife radiosurgery (GKRS) has been increasingly employed for the treatment of elderly patients with brain metastases, mainly due to its demonstrated effectiveness and low complication rate. However, only a few studies have investigated the prognostic factors that influence the survival of elderly patients after GKRS. The purpose of this study was to identify a scoring system that is able to predict the survival of elderly patients undergoing GKRS using data obtained at the time of diagnosis for brain metastases.
Between 2004 and 2011, death was confirmed in 147 patients aged 70 years and older who had been treated with GKRS for brain metastases. Median age at the time of GKRS was 75.7 years (range, 70–86 years). The median tumor volume was 5.1 cm3 (range, 0.05–59.9 cm3). The median marginal prescription dose was 21.4 Gy (range, 14–25 Gy).
The median survival was 167 days. Overall survival rates at 6 months and 1 year were 60.4% and 29.4%, respectively. Among the patient characteristics pertaining to systemic cancer and brain metastasis for which data were obtained preoperatively, a multivariate analysis showed that low Karnofsky performance status (KPS ≤ 80, P = 0.047) and the presence of extracranial metastases (P = 0.014) detected at the time of brain metastasis diagnosis were independent prognostic factors for short survival. A high score index for radiosurgery (SIR score ≥ 4, P = 0.024) and a high graded prognostic assessment (GPA score ≥ 2, P = 0.004) were associated with longer survival. A multivariate analysis of the important characteristics of systemic cancer, and the scoring system evaluating survival duration showed that a low GPA score was the most powerful independent factor for predicting short survival (hazard ratio 1.756, 95% confidence interval 1.252–2.456, P = 0.001).
GKRS is a safe approach to treat brain metastases in patients age 70 years and older. In this group, our study identified GPA score at the time of GKRS as a powerful prognostic factor for survival.
PMCID: PMC4333254
Brain metastasis; Elderly; Gamma knife radiosurgery; Prognosis; Survival
5.  Therapeutic Effect of Gamma Knife Radiosurgery for Multiple Brain Metastases 
The aim of this study is to evaluate the therapeutic effects of gamma knife radiosurgery (GKRS) in patients with multiple brain metastases and to investigate prognostic factors related to treatment outcome.
We retrospectively reviewed clinico-radiological and dosimetric data of 36 patients with 4-14 brain metastases who underwent GKRS for 264 lesions between August 2008 and April 2011. The most common primary tumor site was the lung (n=22), followed by breast (n=7). At GKRS, the median Karnofsky performance scale score was 90 and the mean tumor volume was 1.2 cc (0.002-12.6). The mean prescription dose of 17.8 Gy was delivered to the mean 61.1% isodose line. Among 264 metastases, 175 lesions were assessed for treatment response by at least one imaging follow-up.
The overall median survival after GKRS was 9.1±1.7 months. Among various factors, primary tumor control was a significant prognostic factor (11.1±1.3 months vs. 3.3±2.4 months, p=0.031). The calculated local tumor control rate at 6 and 9 months after GKRS were 87.9% and 84.2%, respectively. Paddick's conformity index (>0.75) was significantly related to local tumor control. The actuarial peritumoral edema reduction rate was 22.4% at 6 months.
According to our results, GKRS can provide beneficial effect for the patients with multiple (4 or more) brain metastases, when systemic cancer is controlled. And, careful dosimetry is essential for local tumor control. Therefore, GKRS can be considered as one of the treatment modalities for multiple brain metastase.
PMCID: PMC3218174  PMID: 22102945
Gamma knife radiosurgery; Metastases; Cerebral edema
6.  Gamma Knife Treatment of Brainstem Metastases 
The management of brainstem metastases is challenging. Surgical treatment is usually not an option, and chemotherapy is of limited utility. Stereotactic radiosurgery has emerged as a promising palliative treatment modality in these cases. The goal of this study is to assess our single institution experience treating brainstem metastases with Gamma Knife radiosurgery (GKRS). This retrospective chart review studied 41 patients with brainstem metastases treated with GKRS. The most common primary tumors were lung, breast, renal cell carcinoma, and melanoma. Median age at initial treatment was 59 years. Nineteen (46%) of the patients received whole brain radiation therapy (WBRT) prior to or concurrent with GKRS treatment. Thirty (73%) of the patients had a single brainstem metastasis. The average GKRS dose was 17 Gy. Post-GKRS overall survival at six months was 42%, at 12 months was 22%, and at 24 months was 13%. Local tumor control was achieved in 91% of patients, and there was one patient who had a fatal brain hemorrhage after treatment. Karnofsky performance score (KPS) >80 and the absence of prior WBRT were predictors for improved survival on multivariate analysis (HR 0.60 (p = 0.02), and HR 0.28 (p = 0.02), respectively). GKRS was an effective treatment for brainstem metastases, with excellent local tumor control.
PMCID: PMC4100118  PMID: 24886816
brainstem metastases; Gamma Knife; radiosurgery
7.  The Usefulness of Stereotactic Radiosurgery for Radioresistant Brain Metastases 
We investigated the effectiveness of stereotactic gamma knife Radiosurgery (GKR) for radioresistant brain metastases with the impact upon histology.
Between April 2004 and May 2011, a total of 23 patients underwent GKR for 67 metastatic brain tumors from 12 renal cell cancers, 5 sarcomas and 6 melanomas. The mean age was 56 years (range, 18 to 79 years). Most of the patients were classified as the Radiation Therapy Oncology Group recursive partitioning analysis class II (91.3%). The synchronous metastasis was found in 6 patients (26.1%) and metachronous metastasis in 17 patients (73.9%). We analyzed the local control rate, intracranial progression-free survival (PFS) and overall survival (OS).
The mean tumor volume for GKR was 2.24 cc and the mean prescription dose was 19.4 Gy (range, 10 to 24) to the tumor margin. Out of metachronous metastases, the median duration to intracranial metastasis was 3.3 years in renal cell cancer (RCC), 2.4 years in melanoma and 1.1 years in sarcoma (p=0.012). The total local control rate was 89.6% during the mean 12.4 months follow-up. The six-month and one-year local control rate was 90.2% and 83% respectively. Depending on the pathology, the control rate of RCC was 95.7%, sarcoma 91.3% and melanoma 80.5% during the follow-up. The common cause of local failure was the tumor bleeding in melanoma. The median PFS and OS were 5.2 and 8.4 months in RCC patients, 6.5 and 9.8 months in sarcoma, and 3.8 and 5.1 months in melanoma.
The GKR can be one of the effective management options for the intracranial metastatic tumors from the radioresistant tumors. The melanoma showed a poor local control rate compared to other pathologies because of the hemorrhage.
PMCID: PMC3809435  PMID: 24175024
Intracranial; Metastasis; Radioresistant; Renal cell cancer; Sarcoma; Melanoma
8.  Breast cancer subtype affects patterns of failure of brain metastases after treatment with stereotactic radiosurgery 
Journal of neuro-oncology  2012;110(3):10.1007/s11060-012-0976-3.
We investigate the variance in patterns of failure after Gamma Knife™ radiosurgery (GKRS) for patients with brain metastases based on the subtype of the primary breast cancer. Between 2000 and 2010, 154 breast cancer patients were treated with GKRS for brain metastases. Tumor subtypes were approximated based on hormone receptor (HR) and HER2 status of the primary cancer: Luminal A/B (HR+/HER2(−)); HER2 (HER2+/ HR(−)); Luminal HER2 (HR+/HER2+), Basal (HR(−)/ HER2(−)), and then based on HER2 status alone. The median follow-up period was 54 months. Kaplan–Meier method was used to estimate survival times. Multivariable analysis was performed using Cox regression models. Median number of lesions treated was two (range 1–15) with a median dose of 20 Gy (range 9–24 Gy). Median overall survival (OS) was 7, 9, 11 and 22 months for Basal, Luminal A/B, HER2, and Luminal HER2, respectively (p = 0.001), and was 17 and 8 months for HER2+ and HER(−) patients, respectively (p <0.001). Breast cancer subtype did not predict time to local failure (p = 0.554), but did predict distant brain failure rate (76, 47, 47, 36 % at 1 year for Basal, Luminal A/B, HER2, and Luminal HER2 respectively, p <0.001). An increased proportion of HER2+ patients experienced neurologic death (46 vs 31 %, p = 0.066). Multivariate analysis revealed that HER2+ patients (p = 0.007) independently predicted for improved survival. Women with basal subtype have high rates of distant brain failure and worsened survival. Our data suggest that differences in biologic behavior of brain metastasis occur across breast cancer subtypes.
PMCID: PMC3852435  PMID: 23001361
Radiosurgery; Brain metastases; Breast cancer; Failure
9.  Tumor Histology Predicts Patterns of Failure and Survival in Patients With Brain Metastases From Lung Cancer Treated With Gamma Knife Radiosurgery 
Neurosurgery  2013;73(4):10.1227/NEU.0000000000000072.
We review our experience with lung cancer patients with newly diagnosed brain metastases treated with Gamma Knife radiosurgery (GKRS).
To determine whether tumor histology predicts patient outcomes.
Between July 1, 2000, and December 31, 2010, 271 patients with brain metastases from primary lung cancer were treated with GKRS at our institution. Included in our study were 44 squamous cell carcinoma (SCC), 31 small cell carcinoma (SCLC), and 138 adenocarcinoma (ACA) patients; 47 patients with insufficient pathology to determine subtype were excluded. No non-small cell lung cancer (NSCLC) patients received whole-brain radiation therapy (WBRT) before their GKRS, and SCLC patients were allowed to have prophylactic cranial irradiation, but no previously known brain metastases. A median of 2 lesions were treated per patient with median marginal dose of 20 Gy.
Median survival was 10.2 months for ACA, 5.9 months for SCLC, and 5.3 months for SCC patients (P = .008). The 1-year local control rates were 86%, 86%, and 54% for ACA, SCC, and SCLC, respectively (P = .027). The 1-year distant failure rates were 35%, 63%, and 65% for ACA, SCC, and SCLC, respectively (P = .057). The likelihood of dying of neurological death was 29%, 36%, and 55% for ACA, SCC, and SCLC, respectively (P = .027). The median time to WBRT was 11 months for SCC and 24 months for ACA patients (P = .04). Multivariate analysis confirmed SCLC histology as a significant predictor of worsened local control (hazard ratio [HR]: 6.46, P = .025) and distant failure (HR: 3.32, P = .0027). For NSCLC histologies, SCC predicted for earlier time to salvage WBRT (HR: 2.552, P = .01) and worsened overall survival (HR: 1.77, P < .0121).
Histological subtype of lung cancer appears to predict outcomes. Future trials and prognostic indices should take these histology-specific patterns into account.
PMCID: PMC3880778  PMID: 23842552
Cranial metastases; Lung cancer; Stereotactic radiosurgery
10.  Local control and toxicity outcomes in brainstem metastases treated with single fraction radiosurgery: is there a volume threshold for toxicity? 
Journal of neuro-oncology  2014;117(1):167-174.
Gamma Knife Radiosurgery (GKRS) has been reported in the treatment of brainstem metastases while dose volume toxicity thresholds remain mostly undefined. A retrospective review of 52 brainstem metastases in 44 patients treated with GKRS was completed. A median dose of 18 Gy (range 10–22 Gy) was prescribed to the tumor margin (median 50 % isodose). 25 patients had undergone previous whole brain radiation therapy. Toxicity was graded by the LENT-SOMA scale. Mean and median follow-up was 10 and 6 months. Only 3 of the 44 patients are living. Multiple brain metastases were treated in 75 % of patients. Median size of lesions was 0.134 cc, (range 0.013–6.600 cc). Overall survival rate at 1 year was 32 % (95 % CI 51.0–20.1 %) with a median survival time of 6 months (95 % CI 5.0–16.5). Local control rate at 6 months and 1 year was 88 % (95 % CI 70–95 %) and 74 % (95 % CI 52–87 %). Cause of death was neurologic in 17 patients, non-neurologic in 20 patients, and unknown in four. Four patients experienced treatment related toxicities. Univariate analysis of tumor volume revealed that volume greater than 1.0 cc predicted for toxicity. A strategy of using lower marginal doses with GKRS to brain stem metastases appears to lead to a lower local control rate than seen with lesions treated within the standard dose range in other locations. Tumor size greater than 1.0 cc predicted for treatment-related toxicity.
PMCID: PMC4019212  PMID: 24504497
Gamma Knife; Brainstem; Metastasis; Toxicity; Radiosurgery
11.  Gamma knife radiosurgery for typical trigeminal neuralgia: An institutional review of 108 patients 
In this study, we present the previously unreported pain relief outcomes of 108 patients treated at Gamma Knife of Spokane for typical trigeminal neuralgia (TN) between 2002 and 2011.
Pain relief outcomes were measured using the Barrow Neurological Institute (BNI) pain intensity scale. In addition, the effects gender, age at treatment, pain laterality, previous surgical treatment, repeat Gamma Knife radiosurgery (GKRS), and maximum radiosurgery dose have on patient pain relief outcomes were retrospectively analyzed. Statistical analysis was performed using Andersen 95% confidence intervals, approximate confidence intervals for log hazard ratios, and multivariate Cox proportional hazard models.
All 108 patients included in this study were grouped into BNI class IV or V prior to GKRS. The median clinical follow-up time was determined to be 15 months. Following the first GKRS procedure, 71% of patients were grouped into BNI class I-IIIb (I = 31%; II = 3%; IIIa = 19%; IIIb = 18%) and the median duration of pain relief for those patients was determined to be 11.8 months. New facial numbness was reported in 19% of patients and new facial paresthesias were reported in 7% of patients after the first GKRS procedure. A total of 19 repeat procedures were performed on the 108 patients included in this study. Following the second GKRS procedure, 73% of patients were grouped into BNI class I-IIIb (I = 44%; II = 6%; IIIa = 17%, IIIb = 6%) and the median duration of pain relief for those patients was determined to be 4.9 months. For repeat procedures, new facial numbness was reported in 22% of patients and new facial paresthesias were reported in 6% of patients.
GKRS is a safe and effective management approach for patients diagnosed with typical TN. However, further studies and supporting research is needed on the effects previous surgical treatment, number of radiosurgery procedures, and maximum radiosurgery dose have on GKRS clinical outcomes.
PMCID: PMC3740613  PMID: 23956935
Barrow Neurological Institute pain intensity scale; gamma knife radiosurgery; trigeminal neuralgia
12.  Long-term outcome of gamma knife radiosurgery for metastatic brain tumors originating from lung cancer 
Surgical Neurology International  2014;5(Suppl 8):S396-S403.
Gamma knife radiosurgery (GKRS) has emerged as an important treatment option for metastasis brain tumors (MBTs). However, the long-term outcome of GKRS on MBTs originating from lung carcinoma is not well understood. The treatment of MBTs derived from lung cancer with GKRS at our institution is reviewed.
We performed a retrospective review (2000-2013) of 173 patients with MBTs from lung cancer who received GKRS. Out of 173 patients, 38 patients had recurrent tumors after microsurgical resection and whole brain radiotherapy (WBT).
GKRS in MBTs metastasized from lung carcinoma showed significant variations in tumor growth control (decreased in 79 [45.7%] patients, arrested growth in 54 [31.2%] patients, and increased tumor size in 40 [23.1%] patients). The median survival in the study population was 14 months. Overall survival after 3 years was 25%, whereas progression-free survival after 3 years was 45%. The predictive factors for improving survival in the patients with MBTs were recursive partitioning analysis (RPA) class I (P = 0.005), absence of hydrocephalus (P = 0.001), Karnofsky performance scale (KPS) >70 (P = 0.007), age ≤65 (P = 0.041), tumor size ≤3 cm (P = 0.023), controlled primary tumor (P = 0.049), and single number of MBTS (P = 0.044).
Long-term follow-up revealed that GKRS offers a high rate of tumor control and good overall survival period in both new and recurrent patients with MBTs originating from lung carcinoma. Thus, GKRS is an effective treatment option for new patients with MBTs from lung cancer, as well as an adjuvant therapy in patients with recurrent MBTs derived from lung cancer.
PMCID: PMC4173307  PMID: 25289169
Gamma knife radiosurgery; lung cancer; long-term outcome; metastatic brain tumors; predictive factors
13.  The Treatment Outcome of Elderly Patients with Idiopathic Trigeminal Neuralgia : Micro-Vascular Decompression versus Gamma Knife Radiosurgery 
This study was designed to compare the efficacy of micro-vascular decompression (MVD) and Gamma knife radiosurgery (GKRS) for elderly idiopathic trigeminal neuralgia patients by analyzing the clinical outcome.
In the past 10 years, 27 elderly patients were treated with MVD while 18 patients were treated with GKRS (>65-years-old). We reviewed their clinical characteristics and clinical courses after treatment as well as the treatment outcomes. For patients who were treated with MVD, additional treatment methods such as rhizotomy were combined in some areas. In GKRS, we radiated the root entry zone (REZ) with the mean maximum dose of 77.8 (70-84.3) Gy and one 4 mm collimator.
The mean age was 68.1 years for MVD, and 71.1 years for GKS group. The average time interval between first presenting symptom and surgery was 84.1 (1-361) months, and 51.4 (1-120) months, respectively. The mean follow-up period after the surgery was 35.9 months for MVD, and 33.1 months for GKRS. According to Pain Intensity Scale, MVD group showed better prognosis with 17 (63%) cases in grade I-II versus 10 (55.6%) cases in GKRS group after the treatment. The pain recurrence rate during follow up did not show much difference with 3 (11.1%) in MVD, and 2 (11.1%) in GKRS. After the treatment, 2 cases of facial numbness, and 1 case each of herpes zoster, cerebrospinal fluid (CSF) leakage, hearing disturbance, and subdural hematoma occurred in MVD Group. In GKRS, there was 1 (5.6%) case of dysesthesia but was not permanent. Three cases were retreated by GKRS but the prognosis was not as good as when the surgery was used as primary treatment, with 1 case of grade I-II, and 1 case of recurrence. The maximal relieve of pain was seen just after surgery in MVD group, and 1 year after treatment in GKRS group.
For trigeminal neuralgia patients with advanced age, MVD showed advantages in immediately relieving the pain. However, in overall, GKRS was preferable, despite the delayed pain relief, due to the lower rate of surgical complications that arise owing to the old age.
PMCID: PMC2588323  PMID: 19096677
Elderly patient; Idiopathic trigeminal neuralgia; Micro-vascular decompression; Gamma knife radiosurgery
14.  Radiation-Induced Intratumoral Necrosis and Peritumoral Edema after Gamma Knife Radiosurgery for Intracranial Meningiomas 
To study the clinical significance and relevant factors of radiation-induced intratumoral necrosis (RIN) and peritumoral edema (PTE) after Gamma knife radiosurgery (GKRS) for intracranial meningiomas.
We retrospectively analyzed the data of 64 patients who underwent GKRS for intracranial meningioma. The mean lesion volume was 4.9 cc (range, 0.3-20), and the mean prescription dose of 13.4 Gy (range, 11-18) was delivered to the mean 49.9% (range, 45-50) isodose line. RIN was defined as newly developed or enlarged intratumoral necrosis after GKRS.
RIN and new development or aggravation of PTE were observed in 21 (32.8%) and 18 (28.1%) cases of meningioma, respectively during the median follow-up duration of 19.9±1.0 months. Among various factors, maximum dose (>25 Gy) and target volume (>4.5 cc) were significantly related to RIN, and RIN and maximum dose (>24 Gy) were significantly related to the development or aggravation of PTE. In 21 meningiomas with development of RIN after GKRS, there was no significant change of the tumor volume itself between the times of GKRS and RIN. However, the PTE volume increased significantly compared to that at the time of GKRS (p=0.013). The median interval to RIN after GKRS was 6.5±0.4 months and the median interval to new or aggravated PTE was 7.0±0.7 months.
A close observation is required for meningiomas treated with a maximum dose >24 Gy and showing RIN after GKRS, since following or accompanying PTE may deteriorate neurological conditions especially when the location involves adjacent critical structures.
PMCID: PMC3467383  PMID: 23091666
Gamma knife radiosurgery; Intracranial meningioma; Peritumoral edema; Radiation necrosis
15.  Gamma knife radiosurgery of meningiomas involving the foramen magnum 
Foramen magnum meningiomas represent a challenging clinical entity. Although resection is performed for those with a mass effect, complete resection is not always feasible. For some patients, stereotactic radiosurgery may be used as the primary treatment modality. We evaluatedthe long-term outcome of Gamma Knife radiosurgery (GKRS) for the treatment of patientswith a foramen magnum meningioma.
Materials and Methods:
Between 1991 and 2005, 222 patients with a meningioma in the posterior fossa were treated with GKRS at the University of Virginia. Of these patients, 5 had meningiomas involving the foramen magnum. At the time of GKRS, the median age of the patients was 60 years (range, 51–78). Three patients were treated with radiosurgery following an initial resection and 2 were treated with upfront radiosurgery. The patients were assessed clinically and radiologically at routine intervals following GKRS.
The median tumor volume was 6.8 cc (range 1.9–17 cc). The GKRS tumor received a marginal dose of 12 Gy (range 10–15), and the median number of isocenters was 5 (range 3–19). The mean follow-up was 6 years (range 4–13). One lesion increased in size following GKRS requiring a second treatment, resulting in size stabilization. At the time of the last follow-up, all meningiomas had either demonstrated no growth (n = 4) or reduction in size (n = 1). No patients experienced post-radiotherapy complications.
GKRS affords a high rate of tumor control and preservation of neurologic function for patients with foramen magnum meningiomas. Further study of its role in the neurosurgical management of such patients seems warranted.
PMCID: PMC2944857  PMID: 20890411
Foramen magnum; gamma knife; meningioma; microsurgery; outcome; radiosurgery; recurrence; skull base
16.  Clinical Outcomes of Gamma Knife Radiosurgery in the Treatment of Patients with Trigeminal Neuralgia 
Since its introduction by Leksell, Gamma Knife radiosurgery (GKRS) has become increasingly popular as a management approach for patients diagnosed with trigeminal neuralgia (TN). For this reason, we performed a modern review of the literature analyzing the efficacy of GKRS in the treatment of patients who suffer from TN. For patients with medically refractory forms of the condition, GKRS has proven to be an effective initial and repeat treatment option. Cumulative research suggests that patients treated a single time with GKRS exhibit similar levels of facial pain control when compared to patients treated multiple times with GKRS. However, patients treated on multiple occasions with GKRS are more likely to experience facial numbness and other facial sensory changes when compared to patients treated once with GKRS. Although numerous articles have reported MVD to be superior to GKRS in achieving facial pain relief, the findings of these comparison studies are weakened by the vast differences in patient age and comorbidities between the two studied groups and cannot be considered conclusive. Questions remain regarding optimal GKRS dosing and targeting strategies, which warrants further investigation into this controversial matter.
PMCID: PMC3202097  PMID: 22229034
17.  MASEP gamma knife radiosurgery for secretory pituitary adenomas: experience in 347 consecutive cases 
Secretory pituitary adenomas are very common brain tumors. Historically, the treatment armamentarium for secretory pituitary adenomas included neurosurgery, medical management, and fractionated radiotherapy. In recent years, MASEP gamma knife radiosurgery (MASEP GKRS) has emerged as an important treatment modality in the management of secretory pituitary adenomas. The goal of this research is to define accurately the efficacy, safety, complications, and role of MASEP GKRS for treatment of secretory pituitary adenomas.
Between 1997 and 2007 a total of 347 patients with secretory pituitary adenomas treated with MASEP GKRS and with at least 60 months of follow-up data were identified. In 47 of these patients some form of prior treatment such as transsphenoidal resection, or craniotomy and resection had been conducted. The others were deemed ineligible for microsurgery because of body health or private choice, and MASEP GKRS served as the primary treatment modality. Endocrinological, ophthalmological, and neuroradiological responses were evaluated.
MASEP GKRS was tolerated well in these patients under the follow-up period ranged from 60 to 90 months; acute radioreaction was rare and 17 patients had transient headaches with no clinical significance. Late radioreaction was noted in 1 patient and consisted of consistent headache. Of the 68 patients with adrenocorticotropic hormone-secreting(ACTH) adenomas, 89.7% showed tumor volume decrease or remain unchanged and 27.9% experienced normalization of hormone level. Of the 176 patients with prolactinomas, 23.3% had normalization of hormone level and 90.3% showed tumor volume decrease or remain unchanged. Of the 103 patients with growth hormone-secreting(GH) adenomas, 95.1% experienced tumor volume decrease or remain unchanged and 36.9% showed normalization of hormone level.
MASEP GKRS is safe and effective in treating secretory pituitary adenomas. None of the patients in our study experienced injury to the optic apparatus or had other neuropathies related with gamma knife. MASEP GKRS may serve as a primary treatment method in some or as a salvage treatment in the others. However, treatment must be tailored to meet the patient's symptoms, tumor location, tumor morphometry, and overall health. Longer follow-up is required for a more complete assessment of late radioreaction and treatment efficacy.
PMCID: PMC2660297  PMID: 19284583
18.  Gamma Knife Radiosurgery after Stereotactic Aspiration for Large Cystic Brain Metastases 
Several treatment options have proven effective for metastatic brain tumors, including surgery and stereotactic radiosurgery. Tumors with cystic components, however, are difficult to treat using a single method. We retrospectively assessed the outcome and efficacy of gamma knife radiosurgery (GKRS) for cystic brain metastases after stereotactic aspiration of cystic components to decrease the tumor volume.
The study population consisted of 24 patients (13 males, 11 females; mean age, 58.3 years) with cystic metastatic brain tumors treated from January 2002 to August 2008. Non-small cell lung cancer was the most common primary origin. After Leksell stereotactic frame was positioned on each patient, magnetic resonance images (MRI)-guided stereotactic cyst aspiration and GKRS were performed (mean prescription dose : 20.2 Gy). After treatment, patients were evaluated by MRI every 3 or 4 months.
After treatment, 13 patients (54.2%) demonstrated tumor control, 5 patients (20.8%) showed local tumor progression, and 6 patients (25.0%) showed remote progression. Mean follow-up duration was 13.1 months. During this period, 10 patients (41.7%) died, but only 1 patient (4.2%) died from brain metastases. The overall median survival after these procedures was 17.8 months.
These results support the usefulness of GKRS after stereotactic cyst aspiration in patients with large cystic brain metastases. This method is especially effective for the patients whose general condition is very poor for general anesthesia and those with metastatic brain tumors located in eloquent areas.
PMCID: PMC2773395  PMID: 19893727
Cystic brain metastases; Gamma knife radiosurgery; Stereotactic cyst aspiration
19.  Long-Term Survival in a Patient with Multiple Brain Metastases from Small-Cell Lung Cancer Treated with Gamma Knife Radiosurgery on Four Occasions: A Case Report 
Brain metastases are the most common cancerous neoplasm in the brain. The treatment of these lesions is challenging and often includes a multimodality management approach with whole-brain radiation therapy, stereotactic radiosurgery, and neurosurgery options. Although advances in biomedical imaging technologies and the treatment of extracranial cancer have led to the overall increase in the survival of brain metastases patients, the finding that select patients survive several years remains puzzling. For this reason, we present the case of a 70-year-old patient who was diagnosed with multiple brain metastases from small-cell lung cancer five years ago and is currently alive following treatment with chemotherapy for the primary cancer and whole-brain radiation therapy and Gamma Knife radiosurgery on four separate occasions for the neurological cancer. Since the diagnosis of brain metastases five years ago, the patient's primary cancer has remained controlled. Furthermore, multiple repeat GKRS procedures provided this patient with high levels of local tumor control, which in combination with a stable primary cancer led to an extended period of survival and a highly functional life. Further analysis and clinical research will be valuable in assessing the durability of multiple GKRS for brain metastases patients who experience long-term survival.
PMCID: PMC3471406  PMID: 23091748
20.  Clinical outcomes following salvage Gamma Knife radiosurgery for recurrent glioblastoma 
Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor with a survival prognosis of 14-16 mo for the highest functioning patients. Despite aggressive, multimodal upfront therapies, the majority of GBMs will recur in approximately six months. Salvage therapy options for recurrent GBM (rGBM) are an area of intense research. This study compares recent survival and quality of life outcomes following Gamma Knife radiosurgery (GKRS) salvage therapy. Following a PubMed search for studies using GKRS as salvage therapy for malignant gliomas, nine articles from 2005 to July 2013 were identified which evaluated rGBM treatment. In this review, we compare Overall survival following diagnosis, Overall survival following salvage treatment, Progression-free survival, Time to recurrence, Local tumor control, and adverse radiation effects. This report discusses results for rGBM patient populations alone, not for mixed populations with other tumor histology grades. All nine studies reported median overall survival rates (from diagnosis, range: 16.7-33.2 mo; from salvage, range: 9-17.9 mo). Three studies identified median progression-free survival (range: 4.6-14.9 mo). Two showed median time to recurrence of GBM. Two discussed local tumor control. Six studies reported adverse radiation effects (range: 0%-46% of patients). The greatest survival advantages were seen in patients who received GKRS salvage along with other treatments, like resection or bevacizumab, suggesting that appropriately tailored multimodal therapy should be considered with each rGBM patient. However, there needs to be a randomized clinical trial to test GKRS for rGBM before the possibility of selection bias can be dismissed.
PMCID: PMC4014786  PMID: 24829861
Gamma Knife radiosurgery; Malignant glioma; Glioblastoma; Salvage therapy; Stereotactic radiosurgery; Multimodal treatment
21.  Survival following gamma knife radiosurgery for brain metastasis from breast cancer 
Breast cancer is the second most common cause of brain metastases in the United States. Although breast cancer induced brain metastases represent an incurable condition, some patients experience prolonged survival. In this retrospective study, we examine a cohort of patients with brain metastases from breast cancer treated with Gamma Knife stereotactic radiosurgery to identify factors that predict better outcomes.
A retrospective database of 100 patients treated for brain metastases due to breast cancer via Gamma Knife radiosurgery (GKS) from July 1998 through March 2009 was reviewed. Patients who received radiosurgery as sole treatment, as a planned boost after whole brain radiotherapy or surgical resection, or as salvage after prior whole brain radiation therapy (WBRT) or surgical resection were included. Prognostic factors identified to be significant for survival in previous brain metastasis studies were analyzed for significance by univariate and multivariate Cox analysis.
Overall, the median brain progression-free survival time was 7.1 months and the median survival time was 12.3 months. No prognostic variables were significant for brain progression-free survival. For patients treated with a planned GKS after WBRT, GKS as sole treatment, GKS salvage after WBRT, GKS boost after surgery, or GKS for surgical salvage the median survival times (MSTs) were as follows: 12.2 months, 12.4 months, 9.5 months, 27.6 months and 33.4 months respectively. Differences between the groups were not significant (p = 0.06); however, GKS boost after surgery and GKS for salvage after surgery did have a trend toward better overall survival.
The MST for patients of age <65 years was 14.5 months, compared to age ≥65 which was 7.7 months (p = 0.06) and remained a significant prognostic factor for overall survival on multivariate analysis. The MST for patients with a single lesion was 16.9 months, not significantly different than the MST of 14.5 months for patients with 2–3 lesions. However patients with >3 lesions had a MST of 5.9 months, which was significantly worse. Breast cancer subtype as approximated by biomarkers and KPS were not significant predictors of overall survival and stage at initial diagnosis was inversely associated with survival.
Stereotactic radiosurgery offers good local control and prolonged survival in selected patients. Age and number of lesions are strong predictors of overall survival.
PMCID: PMC3698070  PMID: 23718256
Gamma knife; Stereotactic radiosurgery; GKS; Breast cancer; Brain metastasis
22.  Salvage Gamma Knife Radiosurgery after failed management of bilateral trigeminal neuralgia 
The incidence of bilateral trigeminal neuralgia (TN) is 1-6% of total number of TN cases. Gamma Knife Radiosurgery (GKRS) is effective in treating unilateral TN; however, outcomes of bilateral TN treated by GKRS have not been well evaluated. The purpose of this study is to evaluate the long-term GKRS outcomes of bilateral TN at our institution and compare with our published treatment outcomes of unilateral TN.
Between 2000 and 2006, eight patients with bilateral TN were treated with GKRS. Data available on seven patients were collected. Facial pain outcomes were defined using the Barrow Neurological Institute pain intensity scale. Outcomes and toxicities were compared to published outcomes of unilateral TN patients treated with GKRS at our institution.
The incidence of bilateral TN in our series is 2.3%. Treatment outcomes were excellent in 5/14, good in 1/14, and poor in 8/14. Median follow-up time was 58 months. Median time-to-failure was 38 months. Pain control rate was 80% at 12 months and 65% at 36 months. Bothersome side effects were seen in 4/14 nerves treated. Compared with our long-term unilateral TN cohort, there was no statistically significant difference in outcome, time-to-failure, or rate of toxicity.
Bilateral TN is rare, and effective treatment is crucial to improve the quality of life of those afflicted. Salvage GKRS is a reasonable treatment modality for individuals with bilateral TN.
PMCID: PMC4258705  PMID: 25525553
Bilateral; Gamma Knife surgery; stereotactic radiosurgery; trigeminal neuralgia
23.  Fractionated Gamma Knife Radiosurgery for Benign Perioptic Tumors: Outcomes of 38 Patients in a Single Institute 
This study was performed to evaluate the efficacy and safety of fractionated Gamma Knife radiosurgery (GKRS) for perioptic lesions.
Thirty-eight patients with perioptic tumors were treated at our institute from May 2004 to December 2008. All patients had a lesion in close contact with the optic apparatus. Twenty-four of these patients had undergone surgical resection before fractionated GKRS. Radiation was delivered in four sessions with 12 hours intervals between sessions. The mean target volume was 3,851 mm3 and the median cumulative marginal dose was 20 Gy. The median follow-up was 38.2 months. Visual acuity and visual fields were analyzed according to visual impairment score using the German Ophthalmological Society guidelines.
Tumor control was achieved in 35 (94.6%) of the 37 patients with available follow-up images. Progressive tumor growth was observed in two craniopharyngioma patients (5.4%). Favorable visual outcomes in the postoperative period were achieved in 94.7% of cases (36/38). Sixteen patients showed visual function after fractionated GKRS, twenty cases were stationary, and two patients showed visual function deterioration after GKRS.
GKRS is a safe and effective alternative to either surgery or fractionated radiotherapy for selected benign lesions that are adjacent to the optic apparatus.
PMCID: PMC4231616  PMID: 25408926
Gamma Knife radiosurgery; Fractionated radiosurgery; Stereotactic radiosurgery; Tumor control; Visual outcome
24.  Cavity-directed radiosurgery as adjuvant therapy after resection of a brain metastasis 
Journal of neurosurgery  2010;114(6):1585-1591.
As a strategy to delay or avoid whole-brain radiotherapy (WBRT) after resection of a brain metastasis, the authors used high-resolution MR imaging and cavity-directed radiosurgery for the detection and treatment of further metastases.
Between April 2001 and October 2009, 112 resection cavities in 106 patients with no prior WBRT were treated using radiosurgery directed to the tumor cavity and for any synchronous brain metastases detected on high-resolution MR imaging at the time of radiosurgical planning. A median dose of 17 Gy to the 50% isodose line as the rim of enhancement around was prescribed to the gross tumor volume, defined the resection cavity. Patients were followed up via serial imaging, and new brain metastases were generally treated using additional radiosurgery, with salvage WBRT typically reserved for local treatment failure at a resection cavity, numerous failures, or failures occurring at short time intervals. Local and distant treatment failures were determined based on imaging results. Kaplan-Meier curves were generated to estimate local and distant treatment failure rates, overall survival, neurological cause–specific survival, and time delay to salvage WBRT.
Radiosurgery was delivered to the resection cavity alone in 57.5% of patients, whereas 24.5% of patients also received treatment for 1 synchronous metastasis, 11.3% also received treatment for 2 synchronous metastases, and 6.6% also received treatment for 3–10 additional lesions. The median overall survival was 10.9 months. Overall survival at 1 year was 46.8%. The local tumor control rate at 1 year was 80.3%. The disease control rate in distant regions of the brain at 1 year was 35.4%, with a median time of 6.9 months to distant failure. Thirty-nine of 106 patients eventually received salvage WBRT, and the median time to salvage WBRT was 12.6 months. Kaplan-Meier estimates showed that the rate of requisite WBRT at 1 year was 45.9%. Neurological cause–specific survival at 1 year was 50.1%. Leptomeningeal failure occurred in 8 patients. One patient had treatment failure within the resection tract. Seven patients required reoperation: 2 for resection cavity recurrence, 3 for radiation necrosis, 1 for hydrocephalus, and 1 for a CSF cutaneous fistula. On multivariate analysis, a preoperative tumor diameter > 3 cm was predictive of local treatment failure.
Cavity-directed radiosurgery combined with high-resolution MR imaging detection and radiosurgical treatment of synchronous brain metastases is an effective strategy for delaying and even foregoing WBRT in most patients. This technique provides acceptable local disease control, although distant treatment failure remains significant.
PMCID: PMC3789371  PMID: 21166567
resection cavity; stereotactic radiosurgery; brain metastasis
25.  Long term experience of gamma knife radiosurgery for benign skull base meningiomas 
Objectives: As most reports on the gamma knife have related only to short or mid-term results, we decided to evaluate the effectiveness and toxicity of radiosurgical treatment for benign skull base meningiomas in 200 patients with a follow up of 5–12 years to define the role of gamma knife radiosurgery (GKRS) for basal meningiomas and to provide further data for comparison with other treatment options.
Methods: In total, 99 patients were treated with a combination of microsurgical resection and GKRS. In 101 patients, GKRS was performed as the sole treatment option. Tumour volumes ranged from 0.38 to 89.8 cm3 (median 6.5 cm3), and doses of 7–25 Gy (median 12 Gy) were given to the tumour borders at covering isodose volume curves (range 20–80%, median 45%).
Results: The actuarial progression free survival rate was 98.5% at 5 years and 97.2% at 10 years. Passing radiation induced oedema occurred in two patients (1%). The neurological status improved in 83 cases (41.5%), remained unaltered in 108 (54%), and deteriorated in 9 (4.5%). Worsening was transient in seven patients (3.5%) and unrelated to tumour or treatment in one (0.5%). Repeated microsurgical resection was performed in five patients following GKRS (2.5%).
Conclusions: GKRS has proved to be an effective alternative to microsurgical resection, radiotherapy, and Linac based radiosurgery for adjunctive and primary treatment of selected patients with basal meningiomas. Because of the excellent long term tumour control rate and low morbidity associated with GKRS, this treatment option should be used more frequently in the therapeutic management of benign skull base meningiomas.
PMCID: PMC1739368  PMID: 16170090

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